Evolved female brain
This page describes the organizational forces that limit change.  It explains how to overcome them when necessary. 

Power& tradition holding back progress
This page uses an example to illustrate how:
  • A business can gain focus from targeting key customers,
  • Business planning activities performed by the whole organization can build awareness, empowerment and coherence. 
  • A program approach can ensure strategic alignment. 
Be responsive to market dynamics
This page uses the example of HP's printer organization freeing itself from its organizational constraints to sell a printer targeted at the IBM pc user. 
The constraints are described. 
The techniques to overcome them are implied. 
Overcome reactionaries
Primary Navigation

Evolved female brain



Summary
The stages of development of the human female, including how her brain changes and the impacts of this on her 'reality' across a full life span: conception, infantile puberty is a period of 9 months in young boys and 24 months in girls, starting around 6 months after birth, where hormone surges prompt the development of ovaries and testes, as well as reproductive adjustments in their brains.  In girls, the ovaries start producing large quantities of estrogen, which induces growth of neural circuits for observation, communication, gut feelings, tending and caring.  Blocking estrogen during this period in primates inhibits development of the female's typical interest in infants. 
, girlhood, juvenile pause is a developmental phase in girls, following on from infantile puberty, initiated when the ovaries temporarily stop generating estrogen. 
, adolescence, dating years, motherhood, post-menopause; are described.  Brizendine notes the significant difference in how emotions are processed by women compared to men. 

Complex adaptive system (CAS) theory associates the stages with the evolutionary under-pinning, psychological implications and behavioral CAS. 

The Female Brain
In Louann Brizendine's book 'The Female Brain' she uses the experiences of her medical practice and research on female brain neuroscience to associate key behaviors with neuronal and endocrine changes over a life span. 

What Makes Us Women
Brizendine was intrigued by the two-to-one ratio in major depression is a debilitating episodic state of extreme sadness, typically beginning in late teens or early twenties. This is accompanied by a lack of energy and emotion, which is facilitated by genetic predisposition - for example genes coding for relatively low serotonin levels, estrogen sensitive CREB-1 gene which increases women's incidence of depression at puberty; and an accumulation of traumatic events.  There is a significant risk of suicide: depression is involved in 50% of the 43,000 suicides in the US, and 15% of people with depression commit suicide.  Depression is the primary cause of disability with about 20 million Americans impacted by depression at any time.  There is evidence of shifts in the sleep/wake cycle in affected individuals (Dec 2015).  The affected person will experience a pathological sense of loss of control, prolonged sadness with feelings of hopelessness, helplessness & worthlessness, irritability, sleep disturbances, loss of appetite, and inability to experience pleasure.  Michael Pollan concludes depression is fear of the past.  It affects 12% of men and 20% of women.  It appears to be associated with androgen deprivation therapy treatment for prostate cancer (Apr 2016).  Chronic stress depletes the nucleus accumbens of dopamine, biasing humans towards depression.  Depression easily leads to following unhealthy pathways: drinking, overeating; which increase the risk of heart disease.   It has been associated with an aging related B12 deficiency (Sep 2016).  During depression, stress mediates inhibition of dopamine signalling.  Both depression and stress activate the adrenal glands' release of cortisol, which will, over the long term, impact the PFC.  There is an association between depression and additional brain regions: Enlarged & more active amygdala, Hippocampal dendrite and spine number reductions & in longer bouts hippocampal volume reductions and memory problems, Dorsal raphe nucleus linked to loneliness, Defective functioning of the hypothalamus undermining appetite and sex drive, Abnormalities of the ACC.  Mayberg notes ACC area 25: serotonin transporters are particularly active in depressed people and lower the serotonin in area 25 impacting the emotion circuit it hubs, inducing bodily sensations that patients can't place or consciously do anything about; and right anterior insula: which normally generates emotions from internal feelings instead feel dead inside; are critical in depression.  Childhood adversity can increase depression risk by linking recollections of uncontrollable situations to overgeneralizations that life will always be terrible and uncontrollable.  Sufferers of mild autism often develop depression.  Treatments include: CBT which works well for cases with below average activity of the right anterior insula (mild and moderate depression), UMHS depression management, deep-brain stimulation of the anterior insula to slow firing of area 25.  Drug treatments are required for cases with above average activity of the right anterior insula.  As of 2010 drug treatments: SSRIs (Prozac), MAO, monoamine reuptake inhibitors; take weeks to facilitate a response & many patients do not respond to the first drug applied, often prolonging the agony.  By 2018, Kandel notes, Ketamine is being tested as a short term treatment, as it acts much faster, reversing the effect of cortisol in stimulating glutamate signalling, and because it reverses the atrophy induced by chronic stress.   Genomic predictions of which treatment will be effective have not been possible because: Not all clinical depressions are the same, a standard definition of drug response is difficult; rates for women compared to men globally (across cultures is how we do and think about things, transmitted by non-genetic means as defined by Frans de Waal.  CAS theory views cultures as operating via memetic schemata evolved by memetic operators to support a cultural superorganism.  Evolutionary psychology asserts that human culture reflects adaptations generated while hunting and gathering.  Dehaene views culture as essentially human, shaped by exaptations and reading, transmitted with support of the neuronal workspace and stabilized by neuronal recycling.  Damasio notes prokaryotes and social insects have developed cultural social behaviors.  Sapolsky argues that parents must show children how to transform their genetically derived capabilities into a culturally effective toolset.  He is interested in the broad differences across cultures of: Life expectancy, GDP, Death in childbirth, Violence, Chronic bullying, Gender equality, Happiness, Response to cheating, Individualist or collectivist, Enforcing honor, Approach to hierarchy; illustrating how different a person's life will be depending on the culture where they are raised.  Culture:
  • Is deployed during pregnancy & childhood, with parental mediation.  Nutrients, immune messages and hormones all affect the prenatal brain.  Hormones: Testosterone with anti-Mullerian hormone masculinizes the brain by entering target cells and after conversion to estrogen binding to intracellular estrogen receptors; have organizational effects producing lifelong changes.  Parenting style typically produces adults who adopt the same approach.  And mothering style can alter gene regulation in the fetus in ways that transfer epigenetically to future generations!  PMS symptoms vary by culture. 
  • Is also significantly transmitted to children by their peers during play.  So parents try to control their children's peer group.  
  • Is transmitted to children by their neighborhoods, tribes, nations etc. 
  • Influences the parenting style that is considered appropriate. 
  • Can transform dominance into honor.  There are ecological correlates of adopting honor cultures.  Parents in honor cultures are typically authoritarian. 
  • Is strongly adapted across a meta-ethnic frontier according to Turchin.  
  • Across Europe was shaped by the Carolingian empire. 
  • Can provide varying levels of support for innovation.  Damasio suggests culture is influenced by feelings: 
    • As motives for intellectual creation: prompting detection and diagnosis of homeostatic deficiencies, identifying desirable states worthy of creative effort.
    • As monitors of the success and failure of cultural instruments and practices
    • As participants in the negotiation of adjustments required by the cultural process over time 
  • Produces consciousness according to Dennet. 
).  And the divergence started only at puberty.  But she notes, researchers have been averse to including females in scientific behavioral studies, because the monthly hormone transitions make interpreting the results difficult.  As a psychiatrist Brizendine took women's hormonal state into account in her evaluations and concluded:
She responded by founding the Women's Mood and Hormone Clinic in the Department of Psychiatry at UCSF.  Hormonal 'states' were inducing different neurological connections that supported new thoughts is the ability to orchestrate thought and action in accordance with internal goals according to Princeton's Jonathan Cohen. 
, emotions are low level fast unconscious agents distributed across the brain and body which associate, via the amygdala and rich club hubs, important environmental signals with encoded high speed sensors, and distributed programs of action to model: predict, prioritize guidance signals, select and respond effectively, coherently and rapidly to the initial signal.  The majority of emotion centered brain regions interface to the midbrain through the hypothalamus.  The cerebellum and basal ganglia support the integration of emotion and motor functions, rewarding rhythmic movement.  The most accessible signs of emotions are the hard to control and universal facial expressions.  Emotions provide prioritization for conscious access given that an animal has only one body, but possibly many cells, with which to achieve its highest level goals.  Because of this emotions clash with group goals and are disparaged by the powerful.  Evolutionary psychology argues evolution shaped human emotions during the long period of hunter-gatherer existence in the African savanna.  Human emotions are universal and include: Anger, Appreciation of natural beauty, Disgust, Fear, Gratitude, Grief, Guilt, Happiness, Honor, Jealousy, Liking, Love, Rage, Romantic love, Lust for revenge, Passion, Sadness, Self-control, Shame, Sympathy, Surprise; and the sham emotions and distrust induced by reciprocal altruism. 
and interests.  Women's neurological reality is not as stable as is men's. 

With the latest probes: PET is positron emission tomography which uses a radioactive tracer (Nuclear medicine) to look for disease processes.  The tracer is intravenously deployed through the blood stream where it collects in organs and tissues.  A whole body scanner is then used to count the indirect gamma ray emissions and a computer builds a 3 dimensional representation.  If the tracer is an analog of glucose such as fluorodeoxyglucose the concentrations of tracer imaged will indicate tissue metabolic activity (glucose uptake).  This can be used to explore for early signs of cancer (unusually active cells) metastasis. 
, fMRI is functional magnetic resonance imaging.  Seiji Ogawa leveraged the coupling of neuronal circuit activity and blood flow through the associated glial cells to build a 3 dimensional picture of brain cell activity.  As haemoglobin gives up its oxygen to support the neural activity it becomes magnetic and acts as a signal detected by the fMRI.  fMRI easily visualizes the state of activity in the living human brain at millimeter resolution, up to several times a second but it cannot track the time course of neural firing so it is augmented with EEG.  ; the brain can be observed operating.  These probe scenarios show men and women's brains differ: structurally, chemically, genetically, hormonally, and functionally; and they respond differently to: stress is a multi-faceted condition reflecting high cortisol levels.  Dr. Robert Sapolsky's studies of baboons indicate that stress helps build readiness for fight or flight.  As these actions occur the levels of cortisol return to the baseline rate.  A stressor is anything that disrupts the regular homeostatic balance.  The stress response is the array of neural and endocrine changes that occur to respond effectively to the crisis and reestablish homeostasis. 
  • The short term response to the stressor
    • activates the amygdala which: Stimulates the brain stem resulting in inhibition of the parasympathetic nervous system and activation of the sympathetic nervous system with the hormones epinephrine and norepinephrine deployed around the body, Activates the PVN which generates a cascade resulting in glucocorticoid secretion to: get energy to the muscles with increased blood pressure for a powerful response.  The brain's acuity and cognition are stimulated.  The immune system is stimulated with beta-endorphin and repair activities curtail.  But when the stressor is
  • long term: loneliness, debt; and no action is necessary, or possible, long term damage ensues.  Damage from such stress may only occur in specific situations: Nuclear families coping with parents moving in.  Sustained stress provides an evolved amplifier of a position of dominance and status.  It is a strategy in female aggression used to limit reproductive competition.  Sustained stress:
    • Stops the frontal cortex from ensuring we do the harder thing, instead substituting amplification of the individual's propensity for risk-taking and impairing risk assessment! 
    • Activates the integration between the thalamus and amygdala. 
      • Acts differently on the amygdala in comparison to the frontal cortex and hippocampus: Stress strengthens the integration between the Amygdala and the hippocampus, making the hippocampus fearful. 
      • BLA & BNST respond with increased BDNF levels and expanded dendrites persistently increasing anxiety and fear conditioning. 
    • Makes it easier to learn a fear association and to consolidate it into long-term memory.  Sustained stress makes it harder to unlearn fear by making the prefrontal cortex inhibit the BLA from learning to break the fear association and weakening the prefrontal cortex's hold over the amygdala.  And glucocorticoids decrease activation of the medial prefrontal cortex during processing of emotional faces.  Accuracy of assessing emotions from faces suffers.  A terrified rat generating lots of glucocorticoids will cause dendrites in the hippocampus to atrophy but when it generates the same amount from excitement of running on a wheel the dendrites expand.  The activation of the amygdala seems to determine how the hippocampus responds. 
    • Depletes the nucleus accumbens of dopamine biasing rats toward social subordination and biasing humans toward depression. 
    • Disrupts working memory by amplifying norepinephrine signalling in the prefrontal cortex and amygdala to prefrontal cortex signalling until they become destructive.  It also desynchronizes activation in different frontal lobe regions impacting shifting of attention.  
    • Increases the risk of autoimmune disease (Jan 2017) 
  • During depression, stress inhibits dopamine signalling.  
  • Strategies for stress reduction include: Mindfulness. 
and conflict.  They use different areas to solve problems, process language, and experience and store the same powerful emotion. 

Women's hippocampus is a part of the medial temporal lobe of the brain involved in the temporary storage or coding of long-term episodic memory.  It includes the dentate gyrus.  Memory formation in the cells of the hippocampus uses the MAP kinase signalling network which is impacted by sleep deprivation.  The hippocampus dependent memory system is directly affected by cholinergic changes throughout the wake-sleep cycle.  Increased acetylcholine during REM sleep promotes information attained during wakefulness to be stored in the hippocampus by suppressing previous excitatory connections while facilitating encoding without interference from previously stored information.  During slow-wave sleep low levels of acetylcholine cause the release of the suppression and allow for spontaneous recovery of hippocampal neurons resulting in memory consolidation.  It was initially associated with memory formation by McGill University's Dr. Brenda Milner, via studies of 'HM' Henry Molaison, whose medial temporal lobes had been surgically destroyed leaving him unable to create new explicit memories.  The size of neurons' dendritic trees expands and contracts over a female rat's ovulatory cycle, with the peak in size and cognitive skills at the estrogen high point.  Adult neurogenesis occurs in the hippocampus (3% of neurons are replaced each month) where the new neurons integrate into preexisting circuits.  It is enhanced by learning, exercise, estrogen, antidepressants, environmental enrichment, and brain injury and inhibited by various stressors explains Sapolsky.  Prolonged stress makes the hippocampus atrophy.  He notes the new neurons are essential for integrating new information into preexisting schemas -- learning that two things you thought were the same are actually different.  Specific cells within the hippocampus and its gateway, the entorhinal cortex, are compromised by Alzheimer's disease.  It directly signals area 25. 
is relatively larger, helping them to detect, remember and express emotions in a different, more nuanced way than men can. 

Women are far more sensitive to and focused on communication.  Adolescent in humans supports the transition from a juvenile configuration, dependent on parents and structured to learn & logistically transform, to adult optimized to the proximate environment.  And it is staged encouraging male adolescents to escape the hierarchy they grew up in and enter other groups where they may bring in: fresh ideas, risk taking; and alter the existing hierarchy: Steve Jobs & Steve Wozniak, Bill Gates & Paul Allen; while females become highly focused on friendships and communications.  It marks the beginning of Piaget's formal operational stage of cognitive development.  The limbic, autonomic and hormone networks are already deployed and functioning effectively.  The frontal cortex has to be pruned: winning neurons move to their final highly connected positions, and are myelinated over time.  The rest dissolve.  So the frontal lobe does not obtain its adult configuration and networked integration until the mid-twenties when prefrontal cortex control becomes optimal.  The evolutionarily oldest areas of the frontal cortex mature first.  The PFC must be iteratively customized by experience to do the right thing as an adult.  Adolescents:
  • Don't detect irony effectively.  They depend on the DMPFC to do this, unlike adults who leverage the fusiform face area.  
  • Regulate emotions with the ventral striatum while the prefrontal cortex is still being setup.  Dopamine projection density and signalling increase from the ventral tegmentum catalyzing increased interest in dopamine based rewards.  Novelty seeking allows for creative exploration which was necessary to move beyond the familial pack.  Criticisms do not get incorporated into learning models by adolescents leaving their risk assessments very poor.  The target of the dopamine networks, the adolescent accumbens, responds to rewards like a gyrating top - hugely to large rewards, and negatively to small rewards.  Eventually as the frontal regions increase in contribution there are steady improvements in: working memory, flexible rule use, executive organization and task shifting.  And adolescents start to see other people's perspective. 
  • Drive the cellular transformations with post-pubescent high levels of testosterone in males, and high but fluctuating estrogen & progesterone levels in females.  Blood flow to the frontal cortex is also diverted on occasion to the groin.  
  • Peer pressure is exceptionally influential in adolescents.  Admired peer comments reduce vmPFC activity and enhance ventral striatal activity.  Adults modulate the mental impact of socially mean treatment: the initial activation of the PAG, anterior cingulate, amygdala, insula cortex; which generate feelings of pain, anger, and disgust, with the VLPFC but that does not occur in adolescents.  
  • Feel empathy intensely, supported by their rampant emotions, interest in novelty, ego.  But feeling the pain of others can induce self-oriented avoidance of the situations. 
girls get the same type of dopamine is a synaptic signal supporting generalized goal-directed behavior & anticipation of reward.  Its significance is that the receptors that detect the signal are of the slow acting type and are used to alter (modulate) the response of fast acting dopaminergic neural circuits in which the receptors are deployed (LTP).  The signal detects significant changes including predictions of models and actual results which differ unexpectedly.  Dopamine is released primarily by neurons of the ventral tegmental area and the substantia nigra.  The dopamine network architecture is designed to signal the possibility of any type of reward: Norm violation punishment, Winning a lottery, & Misfortune of an envied competitor.  Dopamine signalling:
  • Rescales continuously to accommodate the range of intensity offered by different stimuli.  So dopamine's responses to any reward habituate.  GABA is released by some tegmental neurons to induce habituation.  This allows addictions to develop. 
  • Reflects the anticipation of reward.  It supports establishment of a relationship between a signal, working for a reward and obtaining the reward, but subsequently dopamine is mainly released encouraging the work, right after the signal supporting anticipation of the reward.  Anticipation requires learning and is reflected in hippocampus activity.  That explains context dependent cravings.  And the learning architecture means reliable cues become rewarding.  The accumbens supports willpower.  And dopamine
  • Promotes goal-oriented behavior needed to obtain & likely to achieve the reward - through the dopamine projections to the prefrontal cortex.  That makes dopamine central to:
    • Motivation.  This binding fails in depression - due to stress and in anxiety - due to signals from the amygdala.  
    • The prefrontal cortex's mesocortically stimulated support for willpower to act to delay rewards.  To sustain work for delayed rewards additional dopamine is released based on the length of the delay and the rewards uncertainty (modelled in the dorsolateral prefrontal cortex - which promotes the long term and the ventromedial prefrontal cortex - which promotes the short term) and the anticipated size of the reward (modelled in the accumbens).  Impulsiveness in ADHD is reflected in abnormal dopamine processing.  Addictive drugs bias the dopamine network towards impulsiveness.  
  • Is lowered by certain gene variants which induce: less dopamine in the synapse, fewer receptors, lower responsiveness of receptors; associated with (as tiny effects in hugely varying social scenarios): sensation seeking, risk taking, attentional problems, extroversion; where:
    • The receptor D4's gene shows high variability.  The D47R form is relatively unresponsive to dopamine.  
    • Dopamine is degraded by COMT.  The COMT gene includes a variant which is highly efficient reducing dopamine signalling but with complicating gene/environment interactions.  
    • Dopamine is removed from the synapse by a reuptake transporter DAT. 
thrill from friendship and talking as boys do from 'scoring.'

Men have a far larger amount of brain structure dedicated to sex drive - ensuring they are always monitoring for opportunities for sex, aligned with men's
This page describes the consequences of the asymmetries caused by eggs having to include resources required for the development of sexually reproduced organisms while sperms do not.   
The impact of this asymmetry is to force alternative strategies on males and females.  The strategies are outlined. 
asymmetric
role in sex, while women's brains aren't setup to constantly think about sex. 

Men have more neural infrastructure, in the amygdala contains > 12 distinct areas: Central, Lateral.  It receives simple signals from the lower parts of the brain: pain from the PAG; and abstract complex information from the highest areas: Disgust from the insula cortex, allowing it to orchestrate emotion.  It sends signals to almost every other part of the brain, including to the decision making circuitry of the frontal lobes.  It has high levels of D(1) dopamine receptors.  During extreme fear the amygdala drives the hippocampus into fear learning.  It outputs directly to subcortical reflexive motor pathways when speed is required.  Its central nucleus projects to the BNST.  It signals the locus ceruleus.  It directly signals area 25.  The amygdala:
  • Promotes aggression.  Stimulating the amygdala promotes rage.  It converts anger into aggression and when impaired it impacts the ability to detect angry facial expressions.  
  • Participates in disgust
  • Perceives fear promoting stimuli.  In PTSD sufferers the Amygdala overreacts to mildly fearful stimuli and is slow to calm down and the amygdala expands in size over a period of months.  Fear is processed by the lateral nucleus which serves as the input from various senses, and the central nucleus which outputs to the brain stem (central grey - freezing, lateral hypothalamus - blood pressure, activates paraventricular hypothalamus => crf -> hormone adjustments). 
  • Has lots of receptors for and is highly sensitive to glucocorticoids.  Stress inhibits the GABA interneurons in the basolateral amygdala (BLA) allowing the excitatory glutamate releasing neurons to excite more. 
  • Is sensitive to unsettling/uncertain social situations where it promotes anxiety.  It is also interested in uncertain but potentially painful situations.  The amygdala contributes to social and emotional decision making where the BLA supports rejecting an unacceptable offer, as allowed in the Ultimatum Game, by injecting implicit mistrust and vigilance, generating an anger driven rejection that is used as punishment.  The amygdala is very rapidly excited by subliminal signals from the thalamus of outgroup skin color.  The amygdala subsequently tips social emotions against outgroups unless restrained by the frontal lobe or influenced by subliminal priming to prioritize inclusion.  The fast path from the thalamus rapidly but inaccurately signals its identified a weapon. 
  • Promotes male, but not female, sexual motivation when it is an uncertain potential pleasure. 
  • Responds to the longing for uncertain potential pleasures and fear that the reward will not be worth it if it happens.  The amygdala turns off during orgasm. 
  • Uses but is not directly involved in vision.  
, dedicated to registering fear is an emotion which prepares the body for time sensitive action: Blood is sent to the muscles from the gut and skin, Adrenalin is released stimulating: Fuel to be released from the liver, Blood is encouraged to clot, and Face is wide-eyed and fearful.  The short-term high priority goal, experienced as a sense of urgency, is to flee, fight or deflect the danger.  There are both 'innate' - really high priority learning - which are mediated by the central amydala and learned fears which are mediated by the BLA which learns to fear a stimulus and then signals the central amygdala. 
and triggering aggression.  But Brizendine notes that women are more impacted by the stress of conflict.  She concludes that physical and social threats were very dangerous for women in the cognitive niche is Tooby & DeVore's theory that reflects a flexible competitive strategy, described by Steven Pinker, which leverages the power and flexibility of intelligence to defeat the capabilities of genetically evolved specialists focused on specific niches.  , but modern living associates those fears with juggling demands for: home, kids, work; without enough support.  A few unpaid bills can be perceived as life threatening. 

Brizendine asserts that understanding that
Computational theory of the mind and evolutionary psychology provide Steven Pinker with a framework on which to develop his psychological arguments about the mind and its relationship to the brain.  Humans captured a cognitive niche by natural selection 'building out' specialized aspects of their bodies and brains resulting in a system of mental organs we call the mind. 

He garnishes and defends the framework with findings from psychology regarding: The visual system - an example of natural selections solutions to the sensory challenges of inverse modeling of our environment; Intensions - where he highlights the challenges of hunter gatherers - making sense of the objects they perceive and predicting what they imply and natural selections powerful solutions; Emotions - which Pinker argues are essential to human prioritizing and decision making; Relationships - natural selection's strategies for coping with the most dangerous competitors, other people.  He helps us understand marriage, friendships and war. 

These conclusions allow him to understand the development and maintenance of higher callings: Art, Music, Literature, Humor, Religion, & Philosophy; and develop a position on the meaning of life. 

Complex adaptive system (CAS) modeling allows RSS to frame Pinker's arguments within humanity's current situation, induced by powerful evolved amplifiers: Globalization, Cliodynamics, The green revolution and resource bottlenecks; melding his powerful predictions of the drivers of human behavior with system wide constraints.  The implications are discussed. 

biological brain states
guide our impulses, allows awareness to manage how you respond to situations and emotions.  Intelligence enables the achievement of goals in the face of obstacles.  The goals are sub-goals of genes' survival and reproduction and include:
  • Obtaining and eating food
  • Sex
  • Finding and maintaining shelter
  • Fighting for resources - in the preferred hunter gatherer environment loss of resources was critical while possession was often transient. 
  • Understanding the proximate environment
  • Securing the cooperation of others 
and determination can change the effects of sex hormones on brain structure,
The complexity of behavior is explored through Sapolsky developing scenarios of our best and worst behaviors across time spans, and scientific subjects including: anthropology, psychology, neuroscience, sociology.  The rich network of adaptive flows he outlines provides insights and highlight challenges for scientific research on behavior. 

Complex adaptive system (CAS) theory builds on Sapolsky's details highlighting the strategies that evolution has captured to successfully enter niches we now occupy. 

behavior
, reality, creativity--and destiny. 

The Birth of the Female Brain
Girls are born with their brains already structured differently to boys, ensuring they have different impulses, values and experience a different reality. 

Brizendine asserts the brain affects how we conceptualize the world.  Eating a treat can make the world seem better as the chemicals consumed change the brain.  With genetically determined different structures, throughout the organism, boys and girls will be expected to experience and relate to the world differently. 

Girls are setup to differentially build friendships, process and signal, is an emergent capability which is used by cooperating agents to support coordination & rival agents to support control and dominance.  In eukaryotic cells signalling is used extensively.  A signal interacts with the exposed region of a receptor molecule inducing it to change shape to an activated form.  Chains of enzymes interact with the activated receptor relaying, amplifying and responding to the signal to change the state of the cell.  Many of the signalling pathways pass through the nuclear membrane and interact with the DNA to change its state.  Enzymes sensitive to the changes induced in the DNA then start to operate generating actions including sending further signals.  Cell signalling is reviewed by Helmreich.  Signalling is a fundamental aspect of CAS theory and is discussed from the abstract CAS perspective in signals and sensors.  In AWF the eukaryotic signalling architecture has been abstracted in a codelet based implementation.  To be credible signals must be hard to fake.  To be effective they must be easily detected by the target recipient.  To be efficient they are low cost to produce and destroy. 
emotions are low level fast unconscious agents distributed across the brain and body which associate, via the amygdala and rich club hubs, important environmental signals with encoded high speed sensors, and distributed programs of action to model: predict, prioritize guidance signals, select and respond effectively, coherently and rapidly to the initial signal.  The majority of emotion centered brain regions interface to the midbrain through the hypothalamus.  The cerebellum and basal ganglia support the integration of emotion and motor functions, rewarding rhythmic movement.  The most accessible signs of emotions are the hard to control and universal facial expressions.  Emotions provide prioritization for conscious access given that an animal has only one body, but possibly many cells, with which to achieve its highest level goals.  Because of this emotions clash with group goals and are disparaged by the powerful.  Evolutionary psychology argues evolution shaped human emotions during the long period of hunter-gatherer existence in the African savanna.  Human emotions are universal and include: Anger, Appreciation of natural beauty, Disgust, Fear, Gratitude, Grief, Guilt, Happiness, Honor, Jealousy, Liking, Love, Rage, Romantic love, Lust for revenge, Passion, Sadness, Self-control, Shame, Sympathy, Surprise; and the sham emotions and distrust induced by reciprocal altruism. 
, in the first 18 weeks of embryonic development by gene driven hormone are signalling molecules: ACTH, TRH, Melanocyte stimulating hormone, Testosterone, Oxytocin, Vasopressin, Insulin, Growth hormone, Estrogen, Progesterone, Angiotensin II, Asprosin, EPO, Irisin, Leptin, FGF21 hormone, Prostaglandins, TSH, Thyroxine, Glococorticoids; that are transported by the circulatory system to interact with target organs having appropriate receptors.  The levels of hormones can fluctuate massively, as in pregnancy. 
signals.  In boys a huge testosterone is a hormone secreted by the testes, ovaries, and adrenal glands, in response to stimulation from the hypothalamic/pituitary/testicular cascade, that makes humans more willing to do what it takes to attain and maintain status, according to Sapolsky.  That means players of the Ultimatum Game, if previously given testosterone can become more generous.  High testosterone in a fetus masculinizes the brain.  Males generate 10 times the amount.  It is the trigger for sexual desire in males and females, stimulating the hypothalamus.  Testosterone's effect is highly socially contextual so it may encourage acts of kindness or aggression (when challenged).  The level of testosterone does not predict which individuals will be aggressive in: Birds, Fish, Mammals including primates.  Genes impact the potency of testosterone by altering the enzymes that: Construct it, Convert it to estrogen, code the androgen receptor.   This androgen receptor includes a variable polyglutamine repeat which alters the sensitivity to the testosterone signal.  The more potent form is associated with boys showing more dramatic 'masculinization' of the cortex.  But the detected genetic influences are small.  Testosterone decreases activity in the prefrontal cortex and its functional coupling to the amygdala while increasing the coupling between the amygdala & the thalamus.  Testosterone shortens the refactory period of amygdaloid & amygdaloid target neurons.  This results in impulsive risk taking and more focus on unfamiliar faces and distrust of them.  Testosterone increases activity in the ventral tegmentum projecting dopamine to enhance place preference.  Winners of fights become more willing to fight in part due to testosterone increasing confidence and optimism and reducing fear and anxiety.  And winning at: Chess, Athletics, Stock trades; induces the BNST to add testosterone receptors increasing its sensitivity to the hormone.  People become overconfident and overly optimistic. 
surge begins in the eighth week, to transform the developing default female brain structure into male ones: killing off cells in the communications nodes and growing more cells in the sex and aggression centers.  Without the additional testosterone a female brain builds more communication and emotion neurons.  The fetal girl will grow up to use more forms of communication than a boy will, and it will give her a female perspective on the world.  Girls with CAH is either:
  • Critical access hospital, a CMS designation to certain rural hospitals, authorized by Congress (BBA) to limit further closures.  
  • Congenital adrenal hyperplasia, which results in abnormally high testosterone levels about 8 weeks after conception, and causes girls brains to be deploy male attributes: making them identify as boys, and act like them - showing reduced eye contact, nurturing, and empathy and good spatial awareness; but they still like dresses and being treated like a girl.  It affects 1 in 10,000 infants in the US. 
respond more like boys. 

Baby female brains are driven to study faces.  Brizendine notes that in comparison, baby boys look everywhere else, contrary to prior teaching which did not focus on the sex of the babies being studied.  Girls leverage their more developed communication and emotion networks to develop mother-infant bonds.  Girls build skills in eye contact, and mutual facial gazing.  Brizendine writes it does not mean they are needier than boys. 

Girls develop
The agents in complex adaptive systems (CAS) must model their environment to respond effectively to it.  Samuel modeling is described as an approach. 
models
of themselves is dorsomedial prefrontal cortex which is:
  • A major agent of the sense of self and theory of mind in human adults. 
  • It participates in altruism.  
based on reactions from people they signal, is an emergent capability which is used by cooperating agents to support coordination & rival agents to support control and dominance.  In eukaryotic cells signalling is used extensively.  A signal interacts with the exposed region of a receptor molecule inducing it to change shape to an activated form.  Chains of enzymes interact with the activated receptor relaying, amplifying and responding to the signal to change the state of the cell.  Many of the signalling pathways pass through the nuclear membrane and interact with the DNA to change its state.  Enzymes sensitive to the changes induced in the DNA then start to operate generating actions including sending further signals.  Cell signalling is reviewed by Helmreich.  Signalling is a fundamental aspect of CAS theory and is discussed from the abstract CAS perspective in signals and sensors.  In AWF the eukaryotic signalling architecture has been abstracted in a codelet based implementation.  To be credible signals must be hard to fake.  To be effective they must be easily detected by the target recipient.  To be efficient they are low cost to produce and destroy. 
.  They are concerned if they don't get a response, and will doggedly persist.  They decide if they are worthy, lovable or annoying.  This means a depressed is a debilitating episodic state of extreme sadness, typically beginning in late teens or early twenties. This is accompanied by a lack of energy and emotion, which is facilitated by genetic predisposition - for example genes coding for relatively low serotonin levels, estrogen sensitive CREB-1 gene which increases women's incidence of depression at puberty; and an accumulation of traumatic events.  There is a significant risk of suicide: depression is involved in 50% of the 43,000 suicides in the US, and 15% of people with depression commit suicide.  Depression is the primary cause of disability with about 20 million Americans impacted by depression at any time.  There is evidence of shifts in the sleep/wake cycle in affected individuals (Dec 2015).  The affected person will experience a pathological sense of loss of control, prolonged sadness with feelings of hopelessness, helplessness & worthlessness, irritability, sleep disturbances, loss of appetite, and inability to experience pleasure.  Michael Pollan concludes depression is fear of the past.  It affects 12% of men and 20% of women.  It appears to be associated with androgen deprivation therapy treatment for prostate cancer (Apr 2016).  Chronic stress depletes the nucleus accumbens of dopamine, biasing humans towards depression.  Depression easily leads to following unhealthy pathways: drinking, overeating; which increase the risk of heart disease.   It has been associated with an aging related B12 deficiency (Sep 2016).  During depression, stress mediates inhibition of dopamine signalling.  Both depression and stress activate the adrenal glands' release of cortisol, which will, over the long term, impact the PFC.  There is an association between depression and additional brain regions: Enlarged & more active amygdala, Hippocampal dendrite and spine number reductions & in longer bouts hippocampal volume reductions and memory problems, Dorsal raphe nucleus linked to loneliness, Defective functioning of the hypothalamus undermining appetite and sex drive, Abnormalities of the ACC.  Mayberg notes ACC area 25: serotonin transporters are particularly active in depressed people and lower the serotonin in area 25 impacting the emotion circuit it hubs, inducing bodily sensations that patients can't place or consciously do anything about; and right anterior insula: which normally generates emotions from internal feelings instead feel dead inside; are critical in depression.  Childhood adversity can increase depression risk by linking recollections of uncontrollable situations to overgeneralizations that life will always be terrible and uncontrollable.  Sufferers of mild autism often develop depression.  Treatments include: CBT which works well for cases with below average activity of the right anterior insula (mild and moderate depression), UMHS depression management, deep-brain stimulation of the anterior insula to slow firing of area 25.  Drug treatments are required for cases with above average activity of the right anterior insula.  As of 2010 drug treatments: SSRIs (Prozac), MAO, monoamine reuptake inhibitors; take weeks to facilitate a response & many patients do not respond to the first drug applied, often prolonging the agony.  By 2018, Kandel notes, Ketamine is being tested as a short term treatment, as it acts much faster, reversing the effect of cortisol in stimulating glutamate signalling, and because it reverses the atrophy induced by chronic stress.   Genomic predictions of which treatment will be effective have not been possible because: Not all clinical depressions are the same, a standard definition of drug response is difficult; mother, whose expression will be deadened, will be a problem for a baby girl.  She will decide she is not liked and will shift to other faces that are more responsive. 

Girls are monitoring and adapting to visual and vocal social cues from an early age.  Boys don't monitor the cues often, or respond to them, doing what they please.  Brizendine stresses the iterative nature of these interactions and that it results in
This page reviews the inhibiting effect of the value delivery system on the expression of new phenotypic effects within an agent. 
phenotypic alignment
on gender and cultural is how we do and think about things, transmitted by non-genetic means as defined by Frans de Waal.  CAS theory views cultures as operating via memetic schemata evolved by memetic operators to support a cultural superorganism.  Evolutionary psychology asserts that human culture reflects adaptations generated while hunting and gathering.  Dehaene views culture as essentially human, shaped by exaptations and reading, transmitted with support of the neuronal workspace and stabilized by neuronal recycling.  Damasio notes prokaryotes and social insects have developed cultural social behaviors.  Sapolsky argues that parents must show children how to transform their genetically derived capabilities into a culturally effective toolset.  He is interested in the broad differences across cultures of: Life expectancy, GDP, Death in childbirth, Violence, Chronic bullying, Gender equality, Happiness, Response to cheating, Individualist or collectivist, Enforcing honor, Approach to hierarchy; illustrating how different a person's life will be depending on the culture where they are raised.  Culture:
  • Is deployed during pregnancy & childhood, with parental mediation.  Nutrients, immune messages and hormones all affect the prenatal brain.  Hormones: Testosterone with anti-Mullerian hormone masculinizes the brain by entering target cells and after conversion to estrogen binding to intracellular estrogen receptors; have organizational effects producing lifelong changes.  Parenting style typically produces adults who adopt the same approach.  And mothering style can alter gene regulation in the fetus in ways that transfer epigenetically to future generations!  PMS symptoms vary by culture. 
  • Is also significantly transmitted to children by their peers during play.  So parents try to control their children's peer group.  
  • Is transmitted to children by their neighborhoods, tribes, nations etc. 
  • Influences the parenting style that is considered appropriate. 
  • Can transform dominance into honor.  There are ecological correlates of adopting honor cultures.  Parents in honor cultures are typically authoritarian. 
  • Is strongly adapted across a meta-ethnic frontier according to Turchin.  
  • Across Europe was shaped by the Carolingian empire. 
  • Can provide varying levels of support for innovation.  Damasio suggests culture is influenced by feelings: 
    • As motives for intellectual creation: prompting detection and diagnosis of homeostatic deficiencies, identifying desirable states worthy of creative effort.
    • As monitors of the success and failure of cultural instruments and practices
    • As participants in the negotiation of adjustments required by the cultural process over time 
  • Produces consciousness according to Dennet. 
lines reflected in strengthening of used neural circuits, a network of interconnected neurons which perform signalling, modeling and control functions.  In Cajal's basic neural circuits the signalling is unidirectional.  He identified three classes of neurons in the circuits:
  • Sensory, Interneurons, Motor; which are biochemically distinct and suffer different disease states. 
.  But Brizendine suggests boys don't have the neural networks that support these social activities in similarly aged girls: 

Young girls, eighteen months old, monitor if they are being listened to by adults.  They use eye contact to gain attention and agreement, even if the words they say are not understood by the adults.  It supports their development of sense of self.  This allows them to develop empathy is the capability to relate to another person from their perspective.  It is implemented by spindle neurons.  It is context dependently mediated by estrogen.  It develops over time: Piaget's preoperational stage includes rudimentary empathy, Theory of mind supports the development; initially feeling someone's pain as one integrated being, then for them and eventually as them.  In adults, when someone else is hurt the anterior cingulate cortex, amygdala & insula activates projecting [scapegoating] to the vmPFC.  If the pain is physical the PAG activates and motor neurons for the area where the other person was injured.  The intertwining of the ACC amygdala & insula in adults results in attribution of fault even when there is none which can make it hard to step in and actually help.  But in seven-year-olds the activation is concrete: PAG and sensory & motor cortexes with minimal coupling to the rudimentary vmPFC.  In older children the vmPFC is coupled to limbic structures.  Ten to twelve year olds abstract empathy to classes of people.  Brizendine asserts young girls develop empathy earlier than boys, because their evolved greater neuronal investment in communication and emotion networks.  Year old girls are much more responsive to the distress of other people than boys are.  At 18 months girls are experiencing infantile puberty.  By adolescence the vmPFC is coupled to theory of mind regions and intentional harm induces disgust via the amygdala.  Sapolsky explains adolescent boys are utilitarian and tend to accept inequality more than girls do.  But both sexes accept inequality as the way it is.  Sociopaths do not develop empathy.  , while interacting with their mothers, at a younger age than boys.  This is helped by girl's longer infantile puberty is a period of 9 months in young boys and 24 months in girls, starting around 6 months after birth, where hormone surges prompt the development of ovaries and testes, as well as reproductive adjustments in their brains.  In girls, the ovaries start producing large quantities of estrogen, which induces growth of neural circuits for observation, communication, gut feelings, tending and caring.  Blocking estrogen during this period in primates inhibits development of the female's typical interest in infants. 


Depending on the environment they grow up in, during pregnancy and the first two years after birth, and especially the relationship with their mother, girls will develop differently.  If the situation includes a lot of stress is a multi-faceted condition reflecting high cortisol levels.  Dr. Robert Sapolsky's studies of baboons indicate that stress helps build readiness for fight or flight.  As these actions occur the levels of cortisol return to the baseline rate.  A stressor is anything that disrupts the regular homeostatic balance.  The stress response is the array of neural and endocrine changes that occur to respond effectively to the crisis and reestablish homeostasis. 
  • The short term response to the stressor
    • activates the amygdala which: Stimulates the brain stem resulting in inhibition of the parasympathetic nervous system and activation of the sympathetic nervous system with the hormones epinephrine and norepinephrine deployed around the body, Activates the PVN which generates a cascade resulting in glucocorticoid secretion to: get energy to the muscles with increased blood pressure for a powerful response.  The brain's acuity and cognition are stimulated.  The immune system is stimulated with beta-endorphin and repair activities curtail.  But when the stressor is
  • long term: loneliness, debt; and no action is necessary, or possible, long term damage ensues.  Damage from such stress may only occur in specific situations: Nuclear families coping with parents moving in.  Sustained stress provides an evolved amplifier of a position of dominance and status.  It is a strategy in female aggression used to limit reproductive competition.  Sustained stress:
    • Stops the frontal cortex from ensuring we do the harder thing, instead substituting amplification of the individual's propensity for risk-taking and impairing risk assessment! 
    • Activates the integration between the thalamus and amygdala. 
      • Acts differently on the amygdala in comparison to the frontal cortex and hippocampus: Stress strengthens the integration between the Amygdala and the hippocampus, making the hippocampus fearful. 
      • BLA & BNST respond with increased BDNF levels and expanded dendrites persistently increasing anxiety and fear conditioning. 
    • Makes it easier to learn a fear association and to consolidate it into long-term memory.  Sustained stress makes it harder to unlearn fear by making the prefrontal cortex inhibit the BLA from learning to break the fear association and weakening the prefrontal cortex's hold over the amygdala.  And glucocorticoids decrease activation of the medial prefrontal cortex during processing of emotional faces.  Accuracy of assessing emotions from faces suffers.  A terrified rat generating lots of glucocorticoids will cause dendrites in the hippocampus to atrophy but when it generates the same amount from excitement of running on a wheel the dendrites expand.  The activation of the amygdala seems to determine how the hippocampus responds. 
    • Depletes the nucleus accumbens of dopamine biasing rats toward social subordination and biasing humans toward depression. 
    • Disrupts working memory by amplifying norepinephrine signalling in the prefrontal cortex and amygdala to prefrontal cortex signalling until they become destructive.  It also desynchronizes activation in different frontal lobe regions impacting shifting of attention.  
    • Increases the risk of autoimmune disease (Jan 2017) 
  • During depression, stress inhibits dopamine signalling.  
  • Strategies for stress reduction include: Mindfulness. 
this will be reflected in the attitudes and personality describes the operation of the mind from the perspective of psychological models and tests based on them.  Early 'Western' models of personality resulted in a simple segmentation noting the tension between: individual desires and group needs, and developing models and performing actions.  Dualistic 'Eastern' philosophies promote the legitimacy of an essence which Riso & Hudson argue is hidden within a shell of personality types and is only reached by developing presence.  The logic of a coherent essence is in conflict with the evolved nature of emotions outlined by Pinker.  Current psychiatric models highlight at least five key aspects:
  • Extroversion-introversion - whether the person gains energy from socializing or retiring
  • Neuroticism-stability - does a person worry or are they calm and self-satisfied
  • Agreeableness-antagonism - is a person courteous & trusting or rude and suspicious
  • Conscientiousness-un-directedness - is a person careful or careless
  • Openness-non-openness - are they daring or conforming
deployed during development is a phase during the operation of a CAS agent.  It allows for schematic strategies to be iteratively blended with environmental signals to solve the logistical issues of migrating newly built and transformed sub-agents.  That is needed to achieve the adult configuration of the agent and optimize it for the proximate environment.  Smiley includes examples of the developmental phase agents required in an emergent CAS.  In situations where parents invest in the growth and memetic learning of their offspring the schematic grab bag can support optimizations to develop models, structures and actions to construct an adept adult.  In humans, adolescence leverages neural plasticity, elder sibling advice and adult coaching to help prepare the deploying neuronal network and body to successfully compete. 
.  And due to epigenetic imprinting, it can be passed on through further generations. 

The transition to the juvenile pause is a developmental phase in girls, following on from infantile puberty, initiated when the ovaries temporarily stop generating estrogen. 
results in a more stable hormone environment for young girls aged from two and a half years until the onset of puberty.  Levels of estrogen is a generic term for a number of related steroid hormones each of which works differently.  Estrogen:
  • Is generated in the ovaries.  It supports the generation of oxytocin, and so is associated with attachment, nurturing and other affiliative behaviors. 
  • Supports verbal memory.  Removal of ovaries without immediate estrogen replacement therapy degrades verbal memory performance.  The HT reduces age-related shrinkage of the PFC, parietal cortex, and temporal lobe in women, and made them less depressed and angry. 
  • Supports mitochondrial operation in the blood vessels of the brain. 
  • Contributes to maternal aggression but it can reduce aggression and enhance empathy, depending on brain state.  There are two different estrogen receptor types which mediate these conflicting effects.  The level of each type of receptor is independently regulated.  Different receptor variants are associated with:
    • Higher rates of anxiety among women
    • Higher rates of antisocial behavior and conduct disorder in men
  • Is essential for vaginal lubrication
and testosterone become very low, but girls still have 8 times the estrogen of boys.  Girls enjoy playing with their best girlfriend - building a one-on-one relationship, and don't like boys and their rough play, boys - who are more focused on: the game, toy, social rank, power, defense of territory, and physical strength

Girls in the juvenile pause use their well-developed emotional intelligence to get what they want.  That is usually to:
  • Forge connections
  • Create community
  • Organize her world so she is at the center; which results in the need for aggression
That can be challenging since overt use of aggression can drive people out of her community.  It is a delicate balance that will become much more challenging when her hormonal state destabilizes during the pubescent teen years

Teen Girl Brain
Brizendine explains the teen girl's brain is: developing, reorganizing, and pruning; neural circuits, a network of interconnected neurons which perform signalling, modeling and control functions.  In Cajal's basic neural circuits the signalling is unidirectional.  He identified three classes of neurons in the circuits:
  • Sensory, Interneurons, Motor; which are biochemically distinct and suffer different disease states. 
, initially deployed when she was a fetus, that drive the way she now responds: thinks, feels, and
Plans are interpreted and implemented by agents.  This page discusses the properties of agents in a complex adaptive system (CAS). 
It then presents examples of agents in different CAS.  The examples include a computer program where modeling and actions are performed by software agents.  These software agents are aggregates. 
The participation of agents in flows is introduced and some implications of this are outlined. 
acts
; causing her to obsess about her looks.  She is encouraged, by
Plans emerge in complex adaptive systems (CAS) to provide the instructions that agents use to perform actions.  The component architecture and structure of the plans is reviewed. 
gene
driven monthly hormonal are signalling molecules: ACTH, TRH, Melanocyte stimulating hormone, Testosterone, Oxytocin, Vasopressin, Insulin, Growth hormone, Estrogen, Progesterone, Angiotensin II, Asprosin, EPO, Irisin, Leptin, FGF21 hormone, Prostaglandins, TSH, Thyroxine, Glococorticoids; that are transported by the circulatory system to interact with target organs having appropriate receptors.  The levels of hormones can fluctuate massively, as in pregnancy. 
cycles linked to the newly activated pituitary is a protrusion off the bottom of the hypothalamus.  The anterior lobe regulates stress, growth, reproduction and lactation.  The intermediate lobe synthesizes and secretes melanocyte stimulating hormone.  The posterior lobe is functionally connected to the hypothalamus by the pituitary stalk. 
and rampant hypothalamus is essential to many instinctive operations of the body.  It can be viewed as the executor of emotion: happiness, sadness, aggression, eroticism and mating, relaying the amygdala's responses to low level sensory signals.  It has many small sub-regions whose main functions are to regulate hunger, thirst, temperature, sexual behavior, parenting, heart rate, blood pressure, sleep cycles, and similar body operations.  Kandel notes it includes a nucleus containing two distinct populations of neurons: one that regulates aggression and one that regulates sex and mating.  At the intersection neurons are active in both.  Depending on the intensity of the stimulus applied to these neurons mating (weak) or aggression (danger) is activated.  This probably contributes to sexual rage and is why some couples derive extra pleasure from sexual experiences following an argument.  The hypothalamus's (paraventricular nucleus) is closely connected to the pituitary which secrets hormones into the bloodstream ( => acth -> adrenal cortex => cortisol (+)->  amygdala & (-)-> hippocampus).  It directly signals area 25. 
: estrogen is a generic term for a number of related steroid hormones each of which works differently.  Estrogen:
  • Is generated in the ovaries.  It supports the generation of oxytocin, and so is associated with attachment, nurturing and other affiliative behaviors. 
  • Supports verbal memory.  Removal of ovaries without immediate estrogen replacement therapy degrades verbal memory performance.  The HT reduces age-related shrinkage of the PFC, parietal cortex, and temporal lobe in women, and made them less depressed and angry. 
  • Supports mitochondrial operation in the blood vessels of the brain. 
  • Contributes to maternal aggression but it can reduce aggression and enhance empathy, depending on brain state.  There are two different estrogen receptor types which mediate these conflicting effects.  The level of each type of receptor is independently regulated.  Different receptor variants are associated with:
    • Higher rates of anxiety among women
    • Higher rates of antisocial behavior and conduct disorder in men
  • Is essential for vaginal lubrication
surges twice a month, testosterone is a hormone secreted by the testes, ovaries, and adrenal glands, in response to stimulation from the hypothalamic/pituitary/testicular cascade, that makes humans more willing to do what it takes to attain and maintain status, according to Sapolsky.  That means players of the Ultimatum Game, if previously given testosterone can become more generous.  High testosterone in a fetus masculinizes the brain.  Males generate 10 times the amount.  It is the trigger for sexual desire in males and females, stimulating the hypothalamus.  Testosterone's effect is highly socially contextual so it may encourage acts of kindness or aggression (when challenged).  The level of testosterone does not predict which individuals will be aggressive in: Birds, Fish, Mammals including primates.  Genes impact the potency of testosterone by altering the enzymes that: Construct it, Convert it to estrogen, code the androgen receptor.   This androgen receptor includes a variable polyglutamine repeat which alters the sensitivity to the testosterone signal.  The more potent form is associated with boys showing more dramatic 'masculinization' of the cortex.  But the detected genetic influences are small.  Testosterone decreases activity in the prefrontal cortex and its functional coupling to the amygdala while increasing the coupling between the amygdala & the thalamus.  Testosterone shortens the refactory period of amygdaloid & amygdaloid target neurons.  This results in impulsive risk taking and more focus on unfamiliar faces and distrust of them.  Testosterone increases activity in the ventral tegmentum projecting dopamine to enhance place preference.  Winners of fights become more willing to fight in part due to testosterone increasing confidence and optimism and reducing fear and anxiety.  And winning at: Chess, Athletics, Stock trades; induces the BNST to add testosterone receptors increasing its sensitivity to the hormone.  People become overconfident and overly optimistic. 
peaks at ovulation, progesterone is a steroid hormone.  It:
  • Rarely directly effects areas of the brain.  Instead it is converted into other sterioids which have different actions in different brain areas. 
  • Increases maternal aggression in concert with estrogen by increasing oxytocin release in certain brain regions.  However, on its own progresterone decreases aggression and anxiety.  It decreases anxiety by entering neurons where it is converted to allopregnanolone which binds to GABA receptors increasing their sensitivity to GABA.  
  • Decreases female sex drive during the second half of the menstrual cycle. 
is low during the first estrogen wave but rises with the second smaller one; to make herself sexually desirable, judging herself relative to her peers and signals of attractive females from the media.  The hormonal surges result in weekly changes in sensitivity to stress is a multi-faceted condition reflecting high cortisol levels.  Dr. Robert Sapolsky's studies of baboons indicate that stress helps build readiness for fight or flight.  As these actions occur the levels of cortisol return to the baseline rate.  A stressor is anything that disrupts the regular homeostatic balance.  The stress response is the array of neural and endocrine changes that occur to respond effectively to the crisis and reestablish homeostasis. 
  • The short term response to the stressor
    • activates the amygdala which: Stimulates the brain stem resulting in inhibition of the parasympathetic nervous system and activation of the sympathetic nervous system with the hormones epinephrine and norepinephrine deployed around the body, Activates the PVN which generates a cascade resulting in glucocorticoid secretion to: get energy to the muscles with increased blood pressure for a powerful response.  The brain's acuity and cognition are stimulated.  The immune system is stimulated with beta-endorphin and repair activities curtail.  But when the stressor is
  • long term: loneliness, debt; and no action is necessary, or possible, long term damage ensues.  Damage from such stress may only occur in specific situations: Nuclear families coping with parents moving in.  Sustained stress provides an evolved amplifier of a position of dominance and status.  It is a strategy in female aggression used to limit reproductive competition.  Sustained stress:
    • Stops the frontal cortex from ensuring we do the harder thing, instead substituting amplification of the individual's propensity for risk-taking and impairing risk assessment! 
    • Activates the integration between the thalamus and amygdala. 
      • Acts differently on the amygdala in comparison to the frontal cortex and hippocampus: Stress strengthens the integration between the Amygdala and the hippocampus, making the hippocampus fearful. 
      • BLA & BNST respond with increased BDNF levels and expanded dendrites persistently increasing anxiety and fear conditioning. 
    • Makes it easier to learn a fear association and to consolidate it into long-term memory.  Sustained stress makes it harder to unlearn fear by making the prefrontal cortex inhibit the BLA from learning to break the fear association and weakening the prefrontal cortex's hold over the amygdala.  And glucocorticoids decrease activation of the medial prefrontal cortex during processing of emotional faces.  Accuracy of assessing emotions from faces suffers.  A terrified rat generating lots of glucocorticoids will cause dendrites in the hippocampus to atrophy but when it generates the same amount from excitement of running on a wheel the dendrites expand.  The activation of the amygdala seems to determine how the hippocampus responds. 
    • Depletes the nucleus accumbens of dopamine biasing rats toward social subordination and biasing humans toward depression. 
    • Disrupts working memory by amplifying norepinephrine signalling in the prefrontal cortex and amygdala to prefrontal cortex signalling until they become destructive.  It also desynchronizes activation in different frontal lobe regions impacting shifting of attention.  
    • Increases the risk of autoimmune disease (Jan 2017) 
  • During depression, stress inhibits dopamine signalling.  
  • Strategies for stress reduction include: Mindfulness. 
, especially in the hippocampus is a part of the medial temporal lobe of the brain involved in the temporary storage or coding of long-term episodic memory.  It includes the dentate gyrus.  Memory formation in the cells of the hippocampus uses the MAP kinase signalling network which is impacted by sleep deprivation.  The hippocampus dependent memory system is directly affected by cholinergic changes throughout the wake-sleep cycle.  Increased acetylcholine during REM sleep promotes information attained during wakefulness to be stored in the hippocampus by suppressing previous excitatory connections while facilitating encoding without interference from previously stored information.  During slow-wave sleep low levels of acetylcholine cause the release of the suppression and allow for spontaneous recovery of hippocampal neurons resulting in memory consolidation.  It was initially associated with memory formation by McGill University's Dr. Brenda Milner, via studies of 'HM' Henry Molaison, whose medial temporal lobes had been surgically destroyed leaving him unable to create new explicit memories.  The size of neurons' dendritic trees expands and contracts over a female rat's ovulatory cycle, with the peak in size and cognitive skills at the estrogen high point.  Adult neurogenesis occurs in the hippocampus (3% of neurons are replaced each month) where the new neurons integrate into preexisting circuits.  It is enhanced by learning, exercise, estrogen, antidepressants, environmental enrichment, and brain injury and inhibited by various stressors explains Sapolsky.  Prolonged stress makes the hippocampus atrophy.  He notes the new neurons are essential for integrating new information into preexisting schemas -- learning that two things you thought were the same are actually different.  Specific cells within the hippocampus and its gateway, the entorhinal cortex, are compromised by Alzheimer's disease.  It directly signals area 25. 
, and pain emerged as a mental experience, Damasio asserts, constructed by the mind using mapping structures and events provided by nervous systems.  But feeling pain is supported by older biological functions that support homeostasis.  These capabilities reflect the organism's underlying emotive processes that respond to wounds: antibacterial and analgesic chemical deployment, flinching and evading actions; that occur in organisms without nervous systems.  Later in evolution, after organisms with nervous systems were able to map non-neural events, the components of this complex response were 'imageable'.  Today, a wound induced by an internal disease is reported by old, unmyelinated C nerve fibers.  A wound created by an external cut is signalled by evolutionarily recent myelinated fibers that result in a sharp well-localized report, that initially flows to the dorsal root ganglia, then to the spinal cord, where the signals are mixed within the dorsal and ventral horns, and then are transmitted to the brain stem nuclei, thalamus and cerebral cortex.  The pain of a cut is located, but it is also felt through an emotive response that stops us in our tracks.  Pain amplifies the aggression response of people by interoceptive signalling of brain regions providing social emotions including the PAG projecting to the amygdala; making aggressive people more so and less aggressive people less so.  Fear of pain is a significant contributor to female anxiety.  Pain is the main reason people visit the ED in the US.  Pain is mediated by the thalamus and nucleus accumbens, unless undermined by sleep deprivation. 
.  Boys sensitivity to cortisol is a glucocorticoid produced in the adrenal cortex of the adrenal glands.  It:
  • Stimulates
    • Gluconeogenesis to increase production of blood sugar
    • Metabolism of fats, proteins and carbohydrates
  • Suppresses the immune system.  
  • Decreases bone formation
  • In excessive concentrations destroy synaptic connections in the: hippocampus, and prefrontal cortex; leading to flattened emotions and impaired memory. 
reduces while for girls it increases.  Different types of stress impact boys and girls after puberty.  For boys: challenges to their authority - their position in the hierarchy; and for girls: relationships - they need to be liked and are stressed by rejection; are influential. 

Female specific brain regions become more aware of emotional nuance: approval, disapproval, acceptance, rejection; but are not sure how to interpret the increased attention to her body.  And the interpretation depends on what phase of the sex hormone cycle is current.  Stress has more impact when progesterone is high and estrogen is lower.  These hormone waves are significantly affecting the hippocampus is a part of the medial temporal lobe of the brain involved in the temporary storage or coding of long-term episodic memory.  It includes the dentate gyrus.  Memory formation in the cells of the hippocampus uses the MAP kinase signalling network which is impacted by sleep deprivation.  The hippocampus dependent memory system is directly affected by cholinergic changes throughout the wake-sleep cycle.  Increased acetylcholine during REM sleep promotes information attained during wakefulness to be stored in the hippocampus by suppressing previous excitatory connections while facilitating encoding without interference from previously stored information.  During slow-wave sleep low levels of acetylcholine cause the release of the suppression and allow for spontaneous recovery of hippocampal neurons resulting in memory consolidation.  It was initially associated with memory formation by McGill University's Dr. Brenda Milner, via studies of 'HM' Henry Molaison, whose medial temporal lobes had been surgically destroyed leaving him unable to create new explicit memories.  The size of neurons' dendritic trees expands and contracts over a female rat's ovulatory cycle, with the peak in size and cognitive skills at the estrogen high point.  Adult neurogenesis occurs in the hippocampus (3% of neurons are replaced each month) where the new neurons integrate into preexisting circuits.  It is enhanced by learning, exercise, estrogen, antidepressants, environmental enrichment, and brain injury and inhibited by various stressors explains Sapolsky.  Prolonged stress makes the hippocampus atrophy.  He notes the new neurons are essential for integrating new information into preexisting schemas -- learning that two things you thought were the same are actually different.  Specific cells within the hippocampus and its gateway, the entorhinal cortex, are compromised by Alzheimer's disease.  It directly signals area 25. 
, hypothalamus is essential to many instinctive operations of the body.  It can be viewed as the executor of emotion: happiness, sadness, aggression, eroticism and mating, relaying the amygdala's responses to low level sensory signals.  It has many small sub-regions whose main functions are to regulate hunger, thirst, temperature, sexual behavior, parenting, heart rate, blood pressure, sleep cycles, and similar body operations.  Kandel notes it includes a nucleus containing two distinct populations of neurons: one that regulates aggression and one that regulates sex and mating.  At the intersection neurons are active in both.  Depending on the intensity of the stimulus applied to these neurons mating (weak) or aggression (danger) is activated.  This probably contributes to sexual rage and is why some couples derive extra pleasure from sexual experiences following an argument.  The hypothalamus's (paraventricular nucleus) is closely connected to the pituitary which secrets hormones into the bloodstream ( => acth -> adrenal cortex => cortisol (+)->  amygdala & (-)-> hippocampus).  It directly signals area 25. 
and amygdala contains > 12 distinct areas: Central, Lateral.  It receives simple signals from the lower parts of the brain: pain from the PAG; and abstract complex information from the highest areas: Disgust from the insula cortex, allowing it to orchestrate emotion.  It sends signals to almost every other part of the brain, including to the decision making circuitry of the frontal lobes.  It has high levels of D(1) dopamine receptors.  During extreme fear the amygdala drives the hippocampus into fear learning.  It outputs directly to subcortical reflexive motor pathways when speed is required.  Its central nucleus projects to the BNST.  It signals the locus ceruleus.  It directly signals area 25.  The amygdala:
  • Promotes aggression.  Stimulating the amygdala promotes rage.  It converts anger into aggression and when impaired it impacts the ability to detect angry facial expressions.  
  • Participates in disgust
  • Perceives fear promoting stimuli.  In PTSD sufferers the Amygdala overreacts to mildly fearful stimuli and is slow to calm down and the amygdala expands in size over a period of months.  Fear is processed by the lateral nucleus which serves as the input from various senses, and the central nucleus which outputs to the brain stem (central grey - freezing, lateral hypothalamus - blood pressure, activates paraventricular hypothalamus => crf -> hormone adjustments). 
  • Has lots of receptors for and is highly sensitive to glucocorticoids.  Stress inhibits the GABA interneurons in the basolateral amygdala (BLA) allowing the excitatory glutamate releasing neurons to excite more. 
  • Is sensitive to unsettling/uncertain social situations where it promotes anxiety.  It is also interested in uncertain but potentially painful situations.  The amygdala contributes to social and emotional decision making where the BLA supports rejecting an unacceptable offer, as allowed in the Ultimatum Game, by injecting implicit mistrust and vigilance, generating an anger driven rejection that is used as punishment.  The amygdala is very rapidly excited by subliminal signals from the thalamus of outgroup skin color.  The amygdala subsequently tips social emotions against outgroups unless restrained by the frontal lobe or influenced by subliminal priming to prioritize inclusion.  The fast path from the thalamus rapidly but inaccurately signals its identified a weapon. 
  • Promotes male, but not female, sexual motivation when it is an uncertain potential pleasure. 
  • Responds to the longing for uncertain potential pleasures and fear that the reward will not be worth it if it happens.  The amygdala turns off during orgasm. 
  • Uses but is not directly involved in vision.  
: building critical thinking skills and emotional capabilities.  By late puberty these brain structures have stabilized into their adult configuration. 

The flood of estrogen is a generic term for a number of related steroid hormones each of which works differently.  Estrogen:
  • Is generated in the ovaries.  It supports the generation of oxytocin, and so is associated with attachment, nurturing and other affiliative behaviors. 
  • Supports verbal memory.  Removal of ovaries without immediate estrogen replacement therapy degrades verbal memory performance.  The HT reduces age-related shrinkage of the PFC, parietal cortex, and temporal lobe in women, and made them less depressed and angry. 
  • Supports mitochondrial operation in the blood vessels of the brain. 
  • Contributes to maternal aggression but it can reduce aggression and enhance empathy, depending on brain state.  There are two different estrogen receptor types which mediate these conflicting effects.  The level of each type of receptor is independently regulated.  Different receptor variants are associated with:
    • Higher rates of anxiety among women
    • Higher rates of antisocial behavior and conduct disorder in men
  • Is essential for vaginal lubrication
in teen girls activates oxytocin is a peptide hormone which makes humans more prosocial to and socially competent in their in-group and more antisocial to everyone else.  The effects are contingent; changing during stress and in the presence of a threatening out-group.  Oxytocin makes people look at eyes longer, encouraging improved accuracy at perceiving emotions.  It enhances activity in the TPJ supporting modeling of other people's thinking.  Dogs and their owners secrete oxytocin increasing the amount of eye contact between them.  It is associated with pair bonding.  Brizendine explains that oxytocin and dopamine production are stimulated by ovarian estrogen at the onset of puberty, encouraging girls to connect and bond with their girlfriends, reducing stress, and exclude the out-group.  It is central to female mammals wanting to nurse, nursing, and remembering their child.  Its effects are context dependent and so is the regulation of the genes that control oxytocin.  Variants of a gene CD38 which facilitates oxytocin secretion from neurons are associated with differing levels of activation of the fusiform face area when looking at faces.  Sapolsky describes an oxytocin receptor gene variant that is associated with children showing: Extreme aggression, A callous unemotional style; foreshadowing adult psychopathy.  And another receptor gene variant is associated with childhood social disconnection and unstable adult relationships.  Gene/environment interactions complicate the interpretation of the presence of particular gene variants.  Hypothalamic neurons send projections to: ventral tegmentum which also becomes more receptive during child birth, nucleus accumbens, hippocampus, amygdala where it inhibits the central amygdala suppressing fear & anxiety consistently in men while still allowing women to respond to threats to their infants, frontal cortex, olfactory network where it helps new rat mums to learn the smell of their offspring; where oxytocin prepares the brain for in-group bonding, out-grouping, birth and maternal behavior.  Outside the brain hypothalamic neurons in females send oxytocin to the posterior pituitary where it enters the blood stream stimulating uterine contraction during labor & supporting milk production for weaning.  Disorders associated with oxytocin abnormalities include ASD. 
and sex-focused female neural circuits for: talking, flirting and socializing; encouraging girls to hangout together and gossip: trading secrets to build connections and intimacy through language.  So women talk, and listen, a lot more than men and it relieves their stress and gives them a huge dopamine is a synaptic signal supporting generalized goal-directed behavior & anticipation of reward.  Its significance is that the receptors that detect the signal are of the slow acting type and are used to alter (modulate) the response of fast acting dopaminergic neural circuits in which the receptors are deployed (LTP).  The signal detects significant changes including predictions of models and actual results which differ unexpectedly.  Dopamine is released primarily by neurons of the ventral tegmental area and the substantia nigra.  The dopamine network architecture is designed to signal the possibility of any type of reward: Norm violation punishment, Winning a lottery, & Misfortune of an envied competitor.  Dopamine signalling:
  • Rescales continuously to accommodate the range of intensity offered by different stimuli.  So dopamine's responses to any reward habituate.  GABA is released by some tegmental neurons to induce habituation.  This allows addictions to develop. 
  • Reflects the anticipation of reward.  It supports establishment of a relationship between a signal, working for a reward and obtaining the reward, but subsequently dopamine is mainly released encouraging the work, right after the signal supporting anticipation of the reward.  Anticipation requires learning and is reflected in hippocampus activity.  That explains context dependent cravings.  And the learning architecture means reliable cues become rewarding.  The accumbens supports willpower.  And dopamine
  • Promotes goal-oriented behavior needed to obtain & likely to achieve the reward - through the dopamine projections to the prefrontal cortex.  That makes dopamine central to:
    • Motivation.  This binding fails in depression - due to stress and in anxiety - due to signals from the amygdala.  
    • The prefrontal cortex's mesocortically stimulated support for willpower to act to delay rewards.  To sustain work for delayed rewards additional dopamine is released based on the length of the delay and the rewards uncertainty (modelled in the dorsolateral prefrontal cortex - which promotes the long term and the ventromedial prefrontal cortex - which promotes the short term) and the anticipated size of the reward (modelled in the accumbens).  Impulsiveness in ADHD is reflected in abnormal dopamine processing.  Addictive drugs bias the dopamine network towards impulsiveness.  
  • Is lowered by certain gene variants which induce: less dopamine in the synapse, fewer receptors, lower responsiveness of receptors; associated with (as tiny effects in hugely varying social scenarios): sensation seeking, risk taking, attentional problems, extroversion; where:
    • The receptor D4's gene shows high variability.  The D47R form is relatively unresponsive to dopamine.  
    • Dopamine is degraded by COMT.  The COMT gene includes a variant which is highly efficient reducing dopamine signalling but with complicating gene/environment interactions.  
    • Dopamine is removed from the synapse by a reuptake transporter DAT. 
and oxytocin is a peptide hormone which makes humans more prosocial to and socially competent in their in-group and more antisocial to everyone else.  The effects are contingent; changing during stress and in the presence of a threatening out-group.  Oxytocin makes people look at eyes longer, encouraging improved accuracy at perceiving emotions.  It enhances activity in the TPJ supporting modeling of other people's thinking.  Dogs and their owners secrete oxytocin increasing the amount of eye contact between them.  It is associated with pair bonding.  Brizendine explains that oxytocin and dopamine production are stimulated by ovarian estrogen at the onset of puberty, encouraging girls to connect and bond with their girlfriends, reducing stress, and exclude the out-group.  It is central to female mammals wanting to nurse, nursing, and remembering their child.  Its effects are context dependent and so is the regulation of the genes that control oxytocin.  Variants of a gene CD38 which facilitates oxytocin secretion from neurons are associated with differing levels of activation of the fusiform face area when looking at faces.  Sapolsky describes an oxytocin receptor gene variant that is associated with children showing: Extreme aggression, A callous unemotional style; foreshadowing adult psychopathy.  And another receptor gene variant is associated with childhood social disconnection and unstable adult relationships.  Gene/environment interactions complicate the interpretation of the presence of particular gene variants.  Hypothalamic neurons send projections to: ventral tegmentum which also becomes more receptive during child birth, nucleus accumbens, hippocampus, amygdala where it inhibits the central amygdala suppressing fear & anxiety consistently in men while still allowing women to respond to threats to their infants, frontal cortex, olfactory network where it helps new rat mums to learn the smell of their offspring; where oxytocin prepares the brain for in-group bonding, out-grouping, birth and maternal behavior.  Outside the brain hypothalamic neurons in females send oxytocin to the posterior pituitary where it enters the blood stream stimulating uterine contraction during labor & supporting milk production for weaning.  Disorders associated with oxytocin abnormalities include ASD. 
reward.  And they have some verbal brain areas that are relatively larger.  While boys eventually have equivalent vocabularies, they never match girls in speed or ability to overlap speech. 

Brizendine contrasts the reality for pubescent boys:
The goal of the pubescent girl is to maintain relationships.  Their neurology encourages them to ease or prevent social conflict.  Otherwise they feel anxious.  Unlike men, who often enjoy competition and interpersonal conflict, they have a strong negative alert reaction to relationship conflict and rejection: feelings of stress is a multi-faceted condition reflecting high cortisol levels.  Dr. Robert Sapolsky's studies of baboons indicate that stress helps build readiness for fight or flight.  As these actions occur the levels of cortisol return to the baseline rate.  A stressor is anything that disrupts the regular homeostatic balance.  The stress response is the array of neural and endocrine changes that occur to respond effectively to the crisis and reestablish homeostasis. 
  • The short term response to the stressor
    • activates the amygdala which: Stimulates the brain stem resulting in inhibition of the parasympathetic nervous system and activation of the sympathetic nervous system with the hormones epinephrine and norepinephrine deployed around the body, Activates the PVN which generates a cascade resulting in glucocorticoid secretion to: get energy to the muscles with increased blood pressure for a powerful response.  The brain's acuity and cognition are stimulated.  The immune system is stimulated with beta-endorphin and repair activities curtail.  But when the stressor is
  • long term: loneliness, debt; and no action is necessary, or possible, long term damage ensues.  Damage from such stress may only occur in specific situations: Nuclear families coping with parents moving in.  Sustained stress provides an evolved amplifier of a position of dominance and status.  It is a strategy in female aggression used to limit reproductive competition.  Sustained stress:
    • Stops the frontal cortex from ensuring we do the harder thing, instead substituting amplification of the individual's propensity for risk-taking and impairing risk assessment! 
    • Activates the integration between the thalamus and amygdala. 
      • Acts differently on the amygdala in comparison to the frontal cortex and hippocampus: Stress strengthens the integration between the Amygdala and the hippocampus, making the hippocampus fearful. 
      • BLA & BNST respond with increased BDNF levels and expanded dendrites persistently increasing anxiety and fear conditioning. 
    • Makes it easier to learn a fear association and to consolidate it into long-term memory.  Sustained stress makes it harder to unlearn fear by making the prefrontal cortex inhibit the BLA from learning to break the fear association and weakening the prefrontal cortex's hold over the amygdala.  And glucocorticoids decrease activation of the medial prefrontal cortex during processing of emotional faces.  Accuracy of assessing emotions from faces suffers.  A terrified rat generating lots of glucocorticoids will cause dendrites in the hippocampus to atrophy but when it generates the same amount from excitement of running on a wheel the dendrites expand.  The activation of the amygdala seems to determine how the hippocampus responds. 
    • Depletes the nucleus accumbens of dopamine biasing rats toward social subordination and biasing humans toward depression. 
    • Disrupts working memory by amplifying norepinephrine signalling in the prefrontal cortex and amygdala to prefrontal cortex signalling until they become destructive.  It also desynchronizes activation in different frontal lobe regions impacting shifting of attention.  
    • Increases the risk of autoimmune disease (Jan 2017) 
  • During depression, stress inhibits dopamine signalling.  
  • Strategies for stress reduction include: Mindfulness. 
, fear is an emotion which prepares the body for time sensitive action: Blood is sent to the muscles from the gut and skin, Adrenalin is released stimulating: Fuel to be released from the liver, Blood is encouraged to clot, and Face is wide-eyed and fearful.  The short-term high priority goal, experienced as a sense of urgency, is to flee, fight or deflect the danger.  There are both 'innate' - really high priority learning - which are mediated by the central amydala and learned fears which are mediated by the BLA which learns to fear a stimulus and then signals the central amygdala. 
; with cortisol is a glucocorticoid produced in the adrenal cortex of the adrenal glands.  It:
  • Stimulates
    • Gluconeogenesis to increase production of blood sugar
    • Metabolism of fats, proteins and carbohydrates
  • Suppresses the immune system.  
  • Decreases bone formation
  • In excessive concentrations destroy synaptic connections in the: hippocampus, and prefrontal cortex; leading to flattened emotions and impaired memory. 
taking the place of oxytocin, serotonin is a neurotransmitter.  it is:
  • Inversely associated with: human impulsive, cricket, mollusk, crustacean; aggression.  Low levels of serotonin are associated with impulsive aggression ranging from psychological measures of hostility to overt violence and cognitive impulsivity and impulsive suicide. 
  • Nearly all synthesized in the Raphe nucleus.  Tryptophan hydroxylase makes serotonin from the amino-acid tryptophan.  Monoamine oxidase degrades serotonin.  The serotonin receptor binds serotonin to initiate cross membrane signalling.  The serotonin transporter actively removes serotonin from synapses.  Serotonin levels can be increased with: exercise, high light levels, consumption of chickpeas and traditional lime boiled corn tortillas.  Reuptake is inhibited by SSRIs.  Variants of the genes coding for these various enzymes alter the strength of their effects. 
  • Increasing serotonin signalling does not lessen impulsiveness in normal subjects but did in those prone to impulsivity.  However, such experiments are fraught with complexity:
    • Transient changes induced by drugs may adjust the immediate levels of serotonin but may not demonstrate structural effects. 
    • Gene variants likely produce structural changes in the developing brain.  
    • Effects monitored in experiments are often tiny.  
    • Behavioral changes: Violence, Arson, Exhibitionism; seen in different test subjects may be difficult to compare.  
    • Monoamine oxidase has high gene/environment interactions undermining heritability estimates.  Its gene promotor is regulated by stress and glucocorticoids.  So non genetic factors such as childhood adversity and adult provocation appear to be significant.  
& dopamine is a synaptic signal supporting generalized goal-directed behavior & anticipation of reward.  Its significance is that the receptors that detect the signal are of the slow acting type and are used to alter (modulate) the response of fast acting dopaminergic neural circuits in which the receptors are deployed (LTP).  The signal detects significant changes including predictions of models and actual results which differ unexpectedly.  Dopamine is released primarily by neurons of the ventral tegmental area and the substantia nigra.  The dopamine network architecture is designed to signal the possibility of any type of reward: Norm violation punishment, Winning a lottery, & Misfortune of an envied competitor.  Dopamine signalling:
  • Rescales continuously to accommodate the range of intensity offered by different stimuli.  So dopamine's responses to any reward habituate.  GABA is released by some tegmental neurons to induce habituation.  This allows addictions to develop. 
  • Reflects the anticipation of reward.  It supports establishment of a relationship between a signal, working for a reward and obtaining the reward, but subsequently dopamine is mainly released encouraging the work, right after the signal supporting anticipation of the reward.  Anticipation requires learning and is reflected in hippocampus activity.  That explains context dependent cravings.  And the learning architecture means reliable cues become rewarding.  The accumbens supports willpower.  And dopamine
  • Promotes goal-oriented behavior needed to obtain & likely to achieve the reward - through the dopamine projections to the prefrontal cortex.  That makes dopamine central to:
    • Motivation.  This binding fails in depression - due to stress and in anxiety - due to signals from the amygdala.  
    • The prefrontal cortex's mesocortically stimulated support for willpower to act to delay rewards.  To sustain work for delayed rewards additional dopamine is released based on the length of the delay and the rewards uncertainty (modelled in the dorsolateral prefrontal cortex - which promotes the long term and the ventromedial prefrontal cortex - which promotes the short term) and the anticipated size of the reward (modelled in the accumbens).  Impulsiveness in ADHD is reflected in abnormal dopamine processing.  Addictive drugs bias the dopamine network towards impulsiveness.  
  • Is lowered by certain gene variants which induce: less dopamine in the synapse, fewer receptors, lower responsiveness of receptors; associated with (as tiny effects in hugely varying social scenarios): sensation seeking, risk taking, attentional problems, extroversion; where:
    • The receptor D4's gene shows high variability.  The D47R form is relatively unresponsive to dopamine.  
    • Dopamine is degraded by COMT.  The COMT gene includes a variant which is highly efficient reducing dopamine signalling but with complicating gene/environment interactions.  
    • Dopamine is removed from the synapse by a reuptake transporter DAT. 
.  Brizendine notes women's response to threats may not be 'fight or flight,' but rather 'tend and befriend.'  Aggression by males during our hunter-gatherer past likely generated push-back by the threatened female's social network, to protect the young. 

Estrogen surges, at puberty, alter the operation of the suprachiasmatic nucleus is a cluster of cells, in the hypothalamus, that coordinate daily, monthly and annual rhythms of the body including: hormones, body temperature, sleep and mood. 
.  It turns on a uniquely female sleep facilitates salient memory formation and removal of non-salient memories.  The five different stages of the nightly sleep cycles support different aspects of memory formation.  The sleep stages follow Pre-sleep and include: Stage one characterized by light sleep and lasting 10 minutes, Stage two where theta waves and sleep spindles occur, Stage three and Stage four together represent deep slow-wave sleep (SWS) with delta waves, Stage five is REM sleep; sleep cycles last between 90-110 minutes each and as the night progresses SWS times reduce and REM times increase.   Sleep includes the operation of synapse synthesis and maintenance through DNA based activity including membrane trafficking, synaptic vesicle recycling, myelin structural protein formation and cholesterol and protein synthesis.  Sleep also controls inflammation (Jan 2019)  Sleep deprivation undermines the thalamus & nucleus accumbens management of pain. 
cycle and generates growth hormone.  Males and females rhythms become very different.  At eight to ten for girls, sleep facilitates salient memory formation and removal of non-salient memories.  The five different stages of the nightly sleep cycles support different aspects of memory formation.  The sleep stages follow Pre-sleep and include: Stage one characterized by light sleep and lasting 10 minutes, Stage two where theta waves and sleep spindles occur, Stage three and Stage four together represent deep slow-wave sleep (SWS) with delta waves, Stage five is REM sleep; sleep cycles last between 90-110 minutes each and as the night progresses SWS times reduce and REM times increase.   Sleep includes the operation of synapse synthesis and maintenance through DNA based activity including membrane trafficking, synaptic vesicle recycling, myelin structural protein formation and cholesterol and protein synthesis.  Sleep also controls inflammation (Jan 2019)  Sleep deprivation undermines the thalamus & nucleus accumbens management of pain. 
times change leading to later bedtimes, later wake-up times, and more sleep overall.  And the brain waves during sleep, become different to boys.  Females have a tendency to go to sleep earlier than males and wake earlier, until menopause

Estrogen controls the menstrual cycle:
Teen girls are shocked at their sudden instability and shift in needs.  Ovaries that make the most estrogen and progesterone keep their brains resistant to stress.  Women with low estrogen and progesterone are more sensitive to stress, and have fewer serotonin neurons.  They can suffer from PMDD is premenstrual dysphoric disorder, where the ovaries send out relatively low levels of estrogen and progesterone, which affects 2 to 5% of women impairing their normal functioning so they feel: hostility, hopeless depression, suicidal, panic attacks, fear, rage; and the PFC becomes undermined allowing unconstrained emotions to penetrate from the unconscious.  It is treated with: the continuous birth control pill, which keeps the estrogen and progesterone levels moderately high and inhibits the ovaries from sending out the hormones with large fluctuations, and, if necessary, an SSRI. 
and feel: hostility, hopeless depression is a debilitating episodic state of extreme sadness, typically beginning in late teens or early twenties. This is accompanied by a lack of energy and emotion, which is facilitated by genetic predisposition - for example genes coding for relatively low serotonin levels, estrogen sensitive CREB-1 gene which increases women's incidence of depression at puberty; and an accumulation of traumatic events.  There is a significant risk of suicide: depression is involved in 50% of the 43,000 suicides in the US, and 15% of people with depression commit suicide.  Depression is the primary cause of disability with about 20 million Americans impacted by depression at any time.  There is evidence of shifts in the sleep/wake cycle in affected individuals (Dec 2015).  The affected person will experience a pathological sense of loss of control, prolonged sadness with feelings of hopelessness, helplessness & worthlessness, irritability, sleep disturbances, loss of appetite, and inability to experience pleasure.  Michael Pollan concludes depression is fear of the past.  It affects 12% of men and 20% of women.  It appears to be associated with androgen deprivation therapy treatment for prostate cancer (Apr 2016).  Chronic stress depletes the nucleus accumbens of dopamine, biasing humans towards depression.  Depression easily leads to following unhealthy pathways: drinking, overeating; which increase the risk of heart disease.   It has been associated with an aging related B12 deficiency (Sep 2016).  During depression, stress mediates inhibition of dopamine signalling.  Both depression and stress activate the adrenal glands' release of cortisol, which will, over the long term, impact the PFC.  There is an association between depression and additional brain regions: Enlarged & more active amygdala, Hippocampal dendrite and spine number reductions & in longer bouts hippocampal volume reductions and memory problems, Dorsal raphe nucleus linked to loneliness, Defective functioning of the hypothalamus undermining appetite and sex drive, Abnormalities of the ACC.  Mayberg notes ACC area 25: serotonin transporters are particularly active in depressed people and lower the serotonin in area 25 impacting the emotion circuit it hubs, inducing bodily sensations that patients can't place or consciously do anything about; and right anterior insula: which normally generates emotions from internal feelings instead feel dead inside; are critical in depression.  Childhood adversity can increase depression risk by linking recollections of uncontrollable situations to overgeneralizations that life will always be terrible and uncontrollable.  Sufferers of mild autism often develop depression.  Treatments include: CBT which works well for cases with below average activity of the right anterior insula (mild and moderate depression), UMHS depression management, deep-brain stimulation of the anterior insula to slow firing of area 25.  Drug treatments are required for cases with above average activity of the right anterior insula.  As of 2010 drug treatments: SSRIs (Prozac), MAO, monoamine reuptake inhibitors; take weeks to facilitate a response & many patients do not respond to the first drug applied, often prolonging the agony.  By 2018, Kandel notes, Ketamine is being tested as a short term treatment, as it acts much faster, reversing the effect of cortisol in stimulating glutamate signalling, and because it reverses the atrophy induced by chronic stress.   Genomic predictions of which treatment will be effective have not been possible because: Not all clinical depressions are the same, a standard definition of drug response is difficult;, suicidal, panic attacks, fear is an emotion which prepares the body for time sensitive action: Blood is sent to the muscles from the gut and skin, Adrenalin is released stimulating: Fuel to be released from the liver, Blood is encouraged to clot, and Face is wide-eyed and fearful.  The short-term high priority goal, experienced as a sense of urgency, is to flee, fight or deflect the danger.  There are both 'innate' - really high priority learning - which are mediated by the central amydala and learned fears which are mediated by the BLA which learns to fear a stimulus and then signals the central amygdala. 
, rage is a doomsday machine emotion of uncontrollable righteous anger.  ; with the PFC is prefrontal cortex which is:
  • The front part of the frontal lobe of the cerebral cortex.  It evolved most recently.  During adolescence when the PFC is still deploying, older brain agents provide equivalent strategies: ventral striatum.  The PFC has been implicated in planning, working memory: dorsolateral; decision making: Orbitofrontal cortex; and social behavior.  It regulates feelings.  Different PFC circuits track internal reward driven strategies and externally signalled advice.  The PFC chooses between conflicting options, letting go or restraint, especially between cognition and emotions.  It imposes an overarching strategy for managing working memory.  It is essential for thinking about multiple items with different labels.  It includes neurons that are interested in particular sub-categories: Dog, Cat.  Once it has made a decision it signals the rest of the frontal lobe just behind it.  Glucocorticoids decrease excitability of the PFC.  
undermined allowing uncontrolled emotions are low level fast unconscious agents distributed across the brain and body which associate, via the amygdala and rich club hubs, important environmental signals with encoded high speed sensors, and distributed programs of action to model: predict, prioritize guidance signals, select and respond effectively, coherently and rapidly to the initial signal.  The majority of emotion centered brain regions interface to the midbrain through the hypothalamus.  The cerebellum and basal ganglia support the integration of emotion and motor functions, rewarding rhythmic movement.  The most accessible signs of emotions are the hard to control and universal facial expressions.  Emotions provide prioritization for conscious access given that an animal has only one body, but possibly many cells, with which to achieve its highest level goals.  Because of this emotions clash with group goals and are disparaged by the powerful.  Evolutionary psychology argues evolution shaped human emotions during the long period of hunter-gatherer existence in the African savanna.  Human emotions are universal and include: Anger, Appreciation of natural beauty, Disgust, Fear, Gratitude, Grief, Guilt, Happiness, Honor, Jealousy, Liking, Love, Rage, Romantic love, Lust for revenge, Passion, Sadness, Self-control, Shame, Sympathy, Surprise; and the sham emotions and distrust induced by reciprocal altruism. 
to push through from the subconscious. 

The PFC develops late in adolescence in humans supports the transition from a juvenile configuration, dependent on parents and structured to learn & logistically transform, to adult optimized to the proximate environment.  And it is staged encouraging male adolescents to escape the hierarchy they grew up in and enter other groups where they may bring in: fresh ideas, risk taking; and alter the existing hierarchy: Steve Jobs & Steve Wozniak, Bill Gates & Paul Allen; while females become highly focused on friendships and communications.  It marks the beginning of Piaget's formal operational stage of cognitive development.  The limbic, autonomic and hormone networks are already deployed and functioning effectively.  The frontal cortex has to be pruned: winning neurons move to their final highly connected positions, and are myelinated over time.  The rest dissolve.  So the frontal lobe does not obtain its adult configuration and networked integration until the mid-twenties when prefrontal cortex control becomes optimal.  The evolutionarily oldest areas of the frontal cortex mature first.  The PFC must be iteratively customized by experience to do the right thing as an adult.  Adolescents:
  • Don't detect irony effectively.  They depend on the DMPFC to do this, unlike adults who leverage the fusiform face area.  
  • Regulate emotions with the ventral striatum while the prefrontal cortex is still being setup.  Dopamine projection density and signalling increase from the ventral tegmentum catalyzing increased interest in dopamine based rewards.  Novelty seeking allows for creative exploration which was necessary to move beyond the familial pack.  Criticisms do not get incorporated into learning models by adolescents leaving their risk assessments very poor.  The target of the dopamine networks, the adolescent accumbens, responds to rewards like a gyrating top - hugely to large rewards, and negatively to small rewards.  Eventually as the frontal regions increase in contribution there are steady improvements in: working memory, flexible rule use, executive organization and task shifting.  And adolescents start to see other people's perspective. 
  • Drive the cellular transformations with post-pubescent high levels of testosterone in males, and high but fluctuating estrogen & progesterone levels in females.  Blood flow to the frontal cortex is also diverted on occasion to the groin.  
  • Peer pressure is exceptionally influential in adolescents.  Admired peer comments reduce vmPFC activity and enhance ventral striatal activity.  Adults modulate the mental impact of socially mean treatment: the initial activation of the PAG, anterior cingulate, amygdala, insula cortex; which generate feelings of pain, anger, and disgust, with the VLPFC but that does not occur in adolescents.  
  • Feel empathy intensely, supported by their rampant emotions, interest in novelty, ego.  But feeling the pain of others can induce self-oriented avoidance of the situations. 
, and is left unmyelinated is the fatty insulating material deployed by Schwann cells & oligodendrocytes, both types of glial cells, around axons to improve their conduction rate.  In humans it is still occurring 25 years after birth.  It has great impact on long axons, in neurons that project over long distances, where it helps brain inter-region signalling.  The long development time of myelination allows for the later myelinated brain regions to be particularly shaped by the proximate environment. 
while it is customized to the particular environment.  Blasts from the amygdala contains > 12 distinct areas: Central, Lateral.  It receives simple signals from the lower parts of the brain: pain from the PAG; and abstract complex information from the highest areas: Disgust from the insula cortex, allowing it to orchestrate emotion.  It sends signals to almost every other part of the brain, including to the decision making circuitry of the frontal lobes.  It has high levels of D(1) dopamine receptors.  During extreme fear the amygdala drives the hippocampus into fear learning.  It outputs directly to subcortical reflexive motor pathways when speed is required.  Its central nucleus projects to the BNST.  It signals the locus ceruleus.  It directly signals area 25.  The amygdala:
  • Promotes aggression.  Stimulating the amygdala promotes rage.  It converts anger into aggression and when impaired it impacts the ability to detect angry facial expressions.  
  • Participates in disgust
  • Perceives fear promoting stimuli.  In PTSD sufferers the Amygdala overreacts to mildly fearful stimuli and is slow to calm down and the amygdala expands in size over a period of months.  Fear is processed by the lateral nucleus which serves as the input from various senses, and the central nucleus which outputs to the brain stem (central grey - freezing, lateral hypothalamus - blood pressure, activates paraventricular hypothalamus => crf -> hormone adjustments). 
  • Has lots of receptors for and is highly sensitive to glucocorticoids.  Stress inhibits the GABA interneurons in the basolateral amygdala (BLA) allowing the excitatory glutamate releasing neurons to excite more. 
  • Is sensitive to unsettling/uncertain social situations where it promotes anxiety.  It is also interested in uncertain but potentially painful situations.  The amygdala contributes to social and emotional decision making where the BLA supports rejecting an unacceptable offer, as allowed in the Ultimatum Game, by injecting implicit mistrust and vigilance, generating an anger driven rejection that is used as punishment.  The amygdala is very rapidly excited by subliminal signals from the thalamus of outgroup skin color.  The amygdala subsequently tips social emotions against outgroups unless restrained by the frontal lobe or influenced by subliminal priming to prioritize inclusion.  The fast path from the thalamus rapidly but inaccurately signals its identified a weapon. 
  • Promotes male, but not female, sexual motivation when it is an uncertain potential pleasure. 
  • Responds to the longing for uncertain potential pleasures and fear that the reward will not be worth it if it happens.  The amygdala turns off during orgasm. 
  • Uses but is not directly involved in vision.  
, during the pubescent girl's mood swings, overwhelm the PFC, leaving the adolescent without adult logical constraints.  

By age fifteen, girls are twice as likely to suffer from depression than boys.  It can be treated with cognitive therapy and antidepressants. 

During weeks two and three of the menstrual cycle there are higher levels of androgens are a class of steroid hormones including testosterone, androstenedione and dihydrotestosterone.  They are precursors of estrogens. 
.  These support estrogen in making girls prone to aggression, as they become interested in asserting power over boys and other girls. 

Love and Trust
In short-term couplings, men chase and women choose.  But a long-term partnership is complex: it can be pair-bonding is an increase in the strength of relationship between parents and parents and children in some species: prairie voles, bonobos - not monogamous, and humans.  NIMH's Thomas Insel, Emory's Larry Young & Illinois's Sue Carter's research highlighted prairie voles, where pair-bonding is enabled by a genetic difference from montane voles in the operon controlling generation of the vasopressin receptor.  Oxytocin is associated with pair bonding.  There are: Higher levels of receptors in males (vasopressin) having lots of sex and in females (oxytocin) performing grooming & physical contact, Sex releases oxytocin in the nucleus accumbens of female prairie voles.  Such pair-bonded males are less interested in other females. Insel, Young & Carter engineered: (1) Male mice brains to express the prairie vole version of the vasopressin receptor in their brains resulting in grooming and huddling with familiar females.  (2) Male montane vole brains to add vasopressin receptors to the nucleus accumbens resulting in their being more socially affiliative with individual females.   - but not necessarily, it does reflect our hunter gatherer past on the African savanna is the environment where hunter-gatherers primarily evolved.  Its grassland supported large herbivores that could be hunted easily across the plains.  Clumps of Acacia trees: with short trunks, and broad bows; & rocks supported places to hide from large carnivores.  Streams, especially important in times of drought, and paths add to the signals enabling orientation. 
.  Brizendine stresses that a girl's brain drives the transformation to them being in love is a passionate emotion reflecting the risky agreement to commit resources to the long term activity of raising children. The genes ensure that once a person has chosen, the critical-thinking pathways shut down.  That is especially necessary for women to ignore the uncertainty - they become more passionately in love than men.  For both partners initial separations remove the oxytocin (and vasopressin in men) and dopamine rewards from touching & hugging, generating withdrawal driving the couple closer.  The same circuits, driven again by oxytocin signalling, encourage a mother to fall in love with her newborn baby. 
Signals, is an emergent capability which is used by cooperating agents to support coordination & rival agents to support control and dominance.  In eukaryotic cells signalling is used extensively.  A signal interacts with the exposed region of a receptor molecule inducing it to change shape to an activated form.  Chains of enzymes interact with the activated receptor relaying, amplifying and responding to the signal to change the state of the cell.  Many of the signalling pathways pass through the nuclear membrane and interact with the DNA to change its state.  Enzymes sensitive to the changes induced in the DNA then start to operate generating actions including sending further signals.  Cell signalling is reviewed by Helmreich.  Signalling is a fundamental aspect of CAS theory and is discussed from the abstract CAS perspective in signals and sensors.  In AWF the eukaryotic signalling architecture has been abstracted in a codelet based implementation.  To be credible signals must be hard to fake.  To be effective they must be easily detected by the target recipient.  To be efficient they are low cost to produce and destroy. 
from a potential partner:
This page reviews the implications of selection, variation and heredity in a complex adaptive system (CAS).  The mechanism and its emergence are discussed. 
Evolution
has captured these
The agents in complex adaptive systems (CAS) must model their environment to respond effectively to it.  Samuel modeling is described as an approach. 
models
and we still use them. 

Over time the state of romantic love shifts to long-term coupling as the dopamine is a synaptic signal supporting generalized goal-directed behavior & anticipation of reward.  Its significance is that the receptors that detect the signal are of the slow acting type and are used to alter (modulate) the response of fast acting dopaminergic neural circuits in which the receptors are deployed (LTP).  The signal detects significant changes including predictions of models and actual results which differ unexpectedly.  Dopamine is released primarily by neurons of the ventral tegmental area and the substantia nigra.  The dopamine network architecture is designed to signal the possibility of any type of reward: Norm violation punishment, Winning a lottery, & Misfortune of an envied competitor.  Dopamine signalling:
  • Rescales continuously to accommodate the range of intensity offered by different stimuli.  So dopamine's responses to any reward habituate.  GABA is released by some tegmental neurons to induce habituation.  This allows addictions to develop. 
  • Reflects the anticipation of reward.  It supports establishment of a relationship between a signal, working for a reward and obtaining the reward, but subsequently dopamine is mainly released encouraging the work, right after the signal supporting anticipation of the reward.  Anticipation requires learning and is reflected in hippocampus activity.  That explains context dependent cravings.  And the learning architecture means reliable cues become rewarding.  The accumbens supports willpower.  And dopamine
  • Promotes goal-oriented behavior needed to obtain & likely to achieve the reward - through the dopamine projections to the prefrontal cortex.  That makes dopamine central to:
    • Motivation.  This binding fails in depression - due to stress and in anxiety - due to signals from the amygdala.  
    • The prefrontal cortex's mesocortically stimulated support for willpower to act to delay rewards.  To sustain work for delayed rewards additional dopamine is released based on the length of the delay and the rewards uncertainty (modelled in the dorsolateral prefrontal cortex - which promotes the long term and the ventromedial prefrontal cortex - which promotes the short term) and the anticipated size of the reward (modelled in the accumbens).  Impulsiveness in ADHD is reflected in abnormal dopamine processing.  Addictive drugs bias the dopamine network towards impulsiveness.  
  • Is lowered by certain gene variants which induce: less dopamine in the synapse, fewer receptors, lower responsiveness of receptors; associated with (as tiny effects in hugely varying social scenarios): sensation seeking, risk taking, attentional problems, extroversion; where:
    • The receptor D4's gene shows high variability.  The D47R form is relatively unresponsive to dopamine.  
    • Dopamine is degraded by COMT.  The COMT gene includes a variant which is highly efficient reducing dopamine signalling but with complicating gene/environment interactions.  
    • Dopamine is removed from the synapse by a reuptake transporter DAT. 
driven reward circuit activity reduces and attachment supports a stable sense of connection & calm to another person who provides load sharing, using the 'attachment network': pituitary, hypothalamus, adrenal glands, ACC, VTA, nucleus accumbens, PFC; initially generated in babies by norepinephrine from the locus ceruleus as long as corticosteroid levels are low, which deploys & responds to oxytocin (nucleus accumbens, VTA, amygdala, hippocampus), to maintain critical judgement about our partners, once dopamine from the VTA has reinforced the initial interest of the nucleus accumbens. 
circuits activate and are reinforced by mutually pleasurable and positive experiences that generate oxytocin is a peptide hormone which makes humans more prosocial to and socially competent in their in-group and more antisocial to everyone else.  The effects are contingent; changing during stress and in the presence of a threatening out-group.  Oxytocin makes people look at eyes longer, encouraging improved accuracy at perceiving emotions.  It enhances activity in the TPJ supporting modeling of other people's thinking.  Dogs and their owners secrete oxytocin increasing the amount of eye contact between them.  It is associated with pair bonding.  Brizendine explains that oxytocin and dopamine production are stimulated by ovarian estrogen at the onset of puberty, encouraging girls to connect and bond with their girlfriends, reducing stress, and exclude the out-group.  It is central to female mammals wanting to nurse, nursing, and remembering their child.  Its effects are context dependent and so is the regulation of the genes that control oxytocin.  Variants of a gene CD38 which facilitates oxytocin secretion from neurons are associated with differing levels of activation of the fusiform face area when looking at faces.  Sapolsky describes an oxytocin receptor gene variant that is associated with children showing: Extreme aggression, A callous unemotional style; foreshadowing adult psychopathy.  And another receptor gene variant is associated with childhood social disconnection and unstable adult relationships.  Gene/environment interactions complicate the interpretation of the presence of particular gene variants.  Hypothalamic neurons send projections to: ventral tegmentum which also becomes more receptive during child birth, nucleus accumbens, hippocampus, amygdala where it inhibits the central amygdala suppressing fear & anxiety consistently in men while still allowing women to respond to threats to their infants, frontal cortex, olfactory network where it helps new rat mums to learn the smell of their offspring; where oxytocin prepares the brain for in-group bonding, out-grouping, birth and maternal behavior.  Outside the brain hypothalamic neurons in females send oxytocin to the posterior pituitary where it enters the blood stream stimulating uterine contraction during labor & supporting milk production for weaning.  Disorders associated with oxytocin abnormalities include ASD. 


Brizendine uses prairie vole studies to
The agents in complex adaptive systems (CAS) must model their environment to respond effectively to it.  Samuel modeling is described as an approach. 
model
:
Brizendine notes that breaking up during a love affair alters the brain state from the rewards of romantic love is a passionate emotion reflecting the risky agreement to commit resources to the long term activity of raising children. The genes ensure that once a person has chosen, the critical-thinking pathways shut down.  That is especially necessary for women to ignore the uncertainty - they become more passionately in love than men.  For both partners initial separations remove the oxytocin (and vasopressin in men) and dopamine rewards from touching & hugging, generating withdrawal driving the couple closer.  The same circuits, driven again by oxytocin signalling, encourage a mother to fall in love with her newborn baby. 
to the emotional are low level fast unconscious agents distributed across the brain and body which associate, via the amygdala and rich club hubs, important environmental signals with encoded high speed sensors, and distributed programs of action to model: predict, prioritize guidance signals, select and respond effectively, coherently and rapidly to the initial signal.  The majority of emotion centered brain regions interface to the midbrain through the hypothalamus.  The cerebellum and basal ganglia support the integration of emotion and motor functions, rewarding rhythmic movement.  The most accessible signs of emotions are the hard to control and universal facial expressions.  Emotions provide prioritization for conscious access given that an animal has only one body, but possibly many cells, with which to achieve its highest level goals.  Because of this emotions clash with group goals and are disparaged by the powerful.  Evolutionary psychology argues evolution shaped human emotions during the long period of hunter-gatherer existence in the African savanna.  Human emotions are universal and include: Anger, Appreciation of natural beauty, Disgust, Fear, Gratitude, Grief, Guilt, Happiness, Honor, Jealousy, Liking, Love, Rage, Romantic love, Lust for revenge, Passion, Sadness, Self-control, Shame, Sympathy, Surprise; and the sham emotions and distrust induced by reciprocal altruism. 
state of grief is an emotion which devastates those who have lost a loved one.  Pinker suggests it is an internal Doomsday Machine. 
.  The genes encourage us to find a new partner where sex will induce more dopamine and oxytocin based highs. 

Sex: The Brain Below the Belt
It takes three to ten times longer for a female than a male to reach orgasm, in women, is likely an adaptation to ensure the most fit partner's sperm are the ones that reach and fertilize her egg.  Women have more orgasm's with their most symmetric partners.  Use of contraception and romantic passion did not increase the number of orgasms.  The orgasm also increases the attachment between the partners. 
.  The nerves in the tip of the clitoris are connected directly to the sexual pleasure centers of the brain.   Females can only trigger an orgasm when the amygdala contains > 12 distinct areas: Central, Lateral.  It receives simple signals from the lower parts of the brain: pain from the PAG; and abstract complex information from the highest areas: Disgust from the insula cortex, allowing it to orchestrate emotion.  It sends signals to almost every other part of the brain, including to the decision making circuitry of the frontal lobes.  It has high levels of D(1) dopamine receptors.  During extreme fear the amygdala drives the hippocampus into fear learning.  It outputs directly to subcortical reflexive motor pathways when speed is required.  Its central nucleus projects to the BNST.  It signals the locus ceruleus.  It directly signals area 25.  The amygdala:
  • Promotes aggression.  Stimulating the amygdala promotes rage.  It converts anger into aggression and when impaired it impacts the ability to detect angry facial expressions.  
  • Participates in disgust
  • Perceives fear promoting stimuli.  In PTSD sufferers the Amygdala overreacts to mildly fearful stimuli and is slow to calm down and the amygdala expands in size over a period of months.  Fear is processed by the lateral nucleus which serves as the input from various senses, and the central nucleus which outputs to the brain stem (central grey - freezing, lateral hypothalamus - blood pressure, activates paraventricular hypothalamus => crf -> hormone adjustments). 
  • Has lots of receptors for and is highly sensitive to glucocorticoids.  Stress inhibits the GABA interneurons in the basolateral amygdala (BLA) allowing the excitatory glutamate releasing neurons to excite more. 
  • Is sensitive to unsettling/uncertain social situations where it promotes anxiety.  It is also interested in uncertain but potentially painful situations.  The amygdala contributes to social and emotional decision making where the BLA supports rejecting an unacceptable offer, as allowed in the Ultimatum Game, by injecting implicit mistrust and vigilance, generating an anger driven rejection that is used as punishment.  The amygdala is very rapidly excited by subliminal signals from the thalamus of outgroup skin color.  The amygdala subsequently tips social emotions against outgroups unless restrained by the frontal lobe or influenced by subliminal priming to prioritize inclusion.  The fast path from the thalamus rapidly but inaccurately signals its identified a weapon. 
  • Promotes male, but not female, sexual motivation when it is an uncertain potential pleasure. 
  • Responds to the longing for uncertain potential pleasures and fear that the reward will not be worth it if it happens.  The amygdala turns off during orgasm. 
  • Uses but is not directly involved in vision.  
has deactivated.  Prior to that any worry can undermine the process.  Women need to be comfortable and have their feet kept warm to feel like engaging in sex.  A partner who they don't yet trust could induce worry.  Alcohol, a hot bath, a vacation, can reduce the possibility of worry.  When the threshold is reached dopamine is a synaptic signal supporting generalized goal-directed behavior & anticipation of reward.  Its significance is that the receptors that detect the signal are of the slow acting type and are used to alter (modulate) the response of fast acting dopaminergic neural circuits in which the receptors are deployed (LTP).  The signal detects significant changes including predictions of models and actual results which differ unexpectedly.  Dopamine is released primarily by neurons of the ventral tegmental area and the substantia nigra.  The dopamine network architecture is designed to signal the possibility of any type of reward: Norm violation punishment, Winning a lottery, & Misfortune of an envied competitor.  Dopamine signalling:
  • Rescales continuously to accommodate the range of intensity offered by different stimuli.  So dopamine's responses to any reward habituate.  GABA is released by some tegmental neurons to induce habituation.  This allows addictions to develop. 
  • Reflects the anticipation of reward.  It supports establishment of a relationship between a signal, working for a reward and obtaining the reward, but subsequently dopamine is mainly released encouraging the work, right after the signal supporting anticipation of the reward.  Anticipation requires learning and is reflected in hippocampus activity.  That explains context dependent cravings.  And the learning architecture means reliable cues become rewarding.  The accumbens supports willpower.  And dopamine
  • Promotes goal-oriented behavior needed to obtain & likely to achieve the reward - through the dopamine projections to the prefrontal cortex.  That makes dopamine central to:
    • Motivation.  This binding fails in depression - due to stress and in anxiety - due to signals from the amygdala.  
    • The prefrontal cortex's mesocortically stimulated support for willpower to act to delay rewards.  To sustain work for delayed rewards additional dopamine is released based on the length of the delay and the rewards uncertainty (modelled in the dorsolateral prefrontal cortex - which promotes the long term and the ventromedial prefrontal cortex - which promotes the short term) and the anticipated size of the reward (modelled in the accumbens).  Impulsiveness in ADHD is reflected in abnormal dopamine processing.  Addictive drugs bias the dopamine network towards impulsiveness.  
  • Is lowered by certain gene variants which induce: less dopamine in the synapse, fewer receptors, lower responsiveness of receptors; associated with (as tiny effects in hugely varying social scenarios): sensation seeking, risk taking, attentional problems, extroversion; where:
    • The receptor D4's gene shows high variability.  The D47R form is relatively unresponsive to dopamine.  
    • Dopamine is degraded by COMT.  The COMT gene includes a variant which is highly efficient reducing dopamine signalling but with complicating gene/environment interactions.  
    • Dopamine is removed from the synapse by a reuptake transporter DAT. 
, oxytocin is a peptide hormone which makes humans more prosocial to and socially competent in their in-group and more antisocial to everyone else.  The effects are contingent; changing during stress and in the presence of a threatening out-group.  Oxytocin makes people look at eyes longer, encouraging improved accuracy at perceiving emotions.  It enhances activity in the TPJ supporting modeling of other people's thinking.  Dogs and their owners secrete oxytocin increasing the amount of eye contact between them.  It is associated with pair bonding.  Brizendine explains that oxytocin and dopamine production are stimulated by ovarian estrogen at the onset of puberty, encouraging girls to connect and bond with their girlfriends, reducing stress, and exclude the out-group.  It is central to female mammals wanting to nurse, nursing, and remembering their child.  Its effects are context dependent and so is the regulation of the genes that control oxytocin.  Variants of a gene CD38 which facilitates oxytocin secretion from neurons are associated with differing levels of activation of the fusiform face area when looking at faces.  Sapolsky describes an oxytocin receptor gene variant that is associated with children showing: Extreme aggression, A callous unemotional style; foreshadowing adult psychopathy.  And another receptor gene variant is associated with childhood social disconnection and unstable adult relationships.  Gene/environment interactions complicate the interpretation of the presence of particular gene variants.  Hypothalamic neurons send projections to: ventral tegmentum which also becomes more receptive during child birth, nucleus accumbens, hippocampus, amygdala where it inhibits the central amygdala suppressing fear & anxiety consistently in men while still allowing women to respond to threats to their infants, frontal cortex, olfactory network where it helps new rat mums to learn the smell of their offspring; where oxytocin prepares the brain for in-group bonding, out-grouping, birth and maternal behavior.  Outside the brain hypothalamic neurons in females send oxytocin to the posterior pituitary where it enters the blood stream stimulating uterine contraction during labor & supporting milk production for weaning.  Disorders associated with oxytocin abnormalities include ASD. 
& endorphins are released.  As the orgasm subsides waves of oxytocin cause the chest and face to flush, and she is enveloped by contentment.  Men are unlikely to detect these signals.  And they struggle to relate to the interconnection of the psychological and physiological aspects.  For men, orgasms are simpler. 

For the 4 out of 10 unfortunate females who have had bad prior experiences with sex, recollections can reactivate the amygdala undermining progress towards orgasm.  And that is also true of job stress or other worries. 

Women respond to male pheromones differently over the menstrual cycle.  Their brains and noses are more sensitive when the estrogen is a generic term for a number of related steroid hormones each of which works differently.  Estrogen:
  • Is generated in the ovaries.  It supports the generation of oxytocin, and so is associated with attachment, nurturing and other affiliative behaviors. 
  • Supports verbal memory.  Removal of ovaries without immediate estrogen replacement therapy degrades verbal memory performance.  The HT reduces age-related shrinkage of the PFC, parietal cortex, and temporal lobe in women, and made them less depressed and angry. 
  • Supports mitochondrial operation in the blood vessels of the brain. 
  • Contributes to maternal aggression but it can reduce aggression and enhance empathy, depending on brain state.  There are two different estrogen receptor types which mediate these conflicting effects.  The level of each type of receptor is independently regulated.  Different receptor variants are associated with:
    • Higher rates of anxiety among women
    • Higher rates of antisocial behavior and conduct disorder in men
  • Is essential for vaginal lubrication
level surges, just prior to ovulation.  And those with partners prefer the smell of, other, more dominant males signals the power to hurt a rival.  Maynard Smith & Parker explain that in group situations females compete for food and males compete for females.  Maleness is a huge factor for violence.  Fighting to the death is costly for all participants so instead they indicate:
  • Size and weapons to demonstrate who will win.  Males who are, or look like, better fighters: Large heads, Big men, Height; gain in dominance. 
  • Political acumen to demonstrate they won't be pushed around and have the support of other powerful groups.  Dominant males push other rivals aside and gain interest of females, enabling themselves to replicate more.  Being a signal its authenticity can be challenged and so must be defended to remain credible.  Hotheads leverage the doomsday machine to constrain rational challenges.  Bands and cultures leverage honor.  Youth and lack of resources reduce the power of rivals' political constraints. 
, while single women showed no preference.  Women practicing infidelity are more likely to fake orgasm with their regular partner.  10% of fathers are not genetically related to their supposed offspring. 

Testosterone is a hormone secreted by the testes, ovaries, and adrenal glands, in response to stimulation from the hypothalamic/pituitary/testicular cascade, that makes humans more willing to do what it takes to attain and maintain status, according to Sapolsky.  That means players of the Ultimatum Game, if previously given testosterone can become more generous.  High testosterone in a fetus masculinizes the brain.  Males generate 10 times the amount.  It is the trigger for sexual desire in males and females, stimulating the hypothalamus.  Testosterone's effect is highly socially contextual so it may encourage acts of kindness or aggression (when challenged).  The level of testosterone does not predict which individuals will be aggressive in: Birds, Fish, Mammals including primates.  Genes impact the potency of testosterone by altering the enzymes that: Construct it, Convert it to estrogen, code the androgen receptor.   This androgen receptor includes a variable polyglutamine repeat which alters the sensitivity to the testosterone signal.  The more potent form is associated with boys showing more dramatic 'masculinization' of the cortex.  But the detected genetic influences are small.  Testosterone decreases activity in the prefrontal cortex and its functional coupling to the amygdala while increasing the coupling between the amygdala & the thalamus.  Testosterone shortens the refactory period of amygdaloid & amygdaloid target neurons.  This results in impulsive risk taking and more focus on unfamiliar faces and distrust of them.  Testosterone increases activity in the ventral tegmentum projecting dopamine to enhance place preference.  Winners of fights become more willing to fight in part due to testosterone increasing confidence and optimism and reducing fear and anxiety.  And winning at: Chess, Athletics, Stock trades; induces the BNST to add testosterone receptors increasing its sensitivity to the hormone.  People become overconfident and overly optimistic. 
is the trigger for sexual desire in both men and women.  It stimulates the hypothalamus is essential to many instinctive operations of the body.  It can be viewed as the executor of emotion: happiness, sadness, aggression, eroticism and mating, relaying the amygdala's responses to low level sensory signals.  It has many small sub-regions whose main functions are to regulate hunger, thirst, temperature, sexual behavior, parenting, heart rate, blood pressure, sleep cycles, and similar body operations.  Kandel notes it includes a nucleus containing two distinct populations of neurons: one that regulates aggression and one that regulates sex and mating.  At the intersection neurons are active in both.  Depending on the intensity of the stimulus applied to these neurons mating (weak) or aggression (danger) is activated.  This probably contributes to sexual rage and is why some couples derive extra pleasure from sexual experiences following an argument.  The hypothalamus's (paraventricular nucleus) is closely connected to the pituitary which secrets hormones into the bloodstream ( => acth -> adrenal cortex => cortisol (+)->  amygdala & (-)-> hippocampus).  It directly signals area 25. 
, igniting erotic feelings and arousing sexual fantasies and physical sensations in the erogenous zones.  Rising testosterone is a predictor of first intercourse.  Progesterone is a steroid hormone.  It:
  • Rarely directly effects areas of the brain.  Instead it is converted into other sterioids which have different actions in different brain areas. 
  • Increases maternal aggression in concert with estrogen by increasing oxytocin release in certain brain regions.  However, on its own progresterone decreases aggression and anxiety.  It decreases anxiety by entering neurons where it is converted to allopregnanolone which binds to GABA receptors increasing their sensitivity to GABA.  
  • Decreases female sex drive during the second half of the menstrual cycle. 
undermines the stimulating effect of testosterone.  Estrogen makes females receptive to sex and is required for vaginal lubrication. 

Men have more neurons dedicated to sex than women do.  They think about it far more often.  They have to initiate sexual activity.  They also generate far higher testosterone levels.  Women's sexual interest also varies over the menstrual cycle.  And the stress of work also reduces women's interest in having sex.  But male partners of work stressed women can feel unloved, rejected and jealous is an emotion driven by the large investment by parents in their children's development combined with a human sexual asymmetry: fertilization occurs inside the female's body, so a male can't be sure it is supporting its own ofspring. 
.  That is often a surprise to the women in the relationship. 

The Mommy Brain
Motherhood results in an attachment is John Bowlby's model of mother infant bonding.  He argued that infants need: love, warmth, affection, responsiveness, stimulation, consistency, reliability; or they become anxious, depressed, and/or poorly attached adults.  Evolutionarily, sociopaths may be highly successful as managers and leaders but they are probably anxious.  Sapolsky notes the powerful association between murder rates and stopping pregnant girls from terminating unwanted pregnancies.  Typical mothers also provide training on social conventions and their children's position in the group hierarchy.  Children raised without a mother's support fail to understand social constraints and when to use social behaviors.  And in the presence of unsupportive mothers newborns attach to negative stimuli.  This response is explained by the SHRP.  Abused children subsequently seek out abusive relationships as adults.  And a percentage of infants abused by their mothers become abusive mothers. 
between mother and child.  And it alters the mother's brain irreversibly.  Hormones are signalling molecules: ACTH, TRH, Melanocyte stimulating hormone, Testosterone, Oxytocin, Vasopressin, Insulin, Growth hormone, Estrogen, Progesterone, Angiotensin II, Asprosin, EPO, Irisin, Leptin, FGF21 hormone, Prostaglandins, TSH, Thyroxine, Glococorticoids; that are transported by the circulatory system to interact with target organs having appropriate receptors.  The levels of hormones can fluctuate massively, as in pregnancy. 
: Oxytocin is a peptide hormone which makes humans more prosocial to and socially competent in their in-group and more antisocial to everyone else.  The effects are contingent; changing during stress and in the presence of a threatening out-group.  Oxytocin makes people look at eyes longer, encouraging improved accuracy at perceiving emotions.  It enhances activity in the TPJ supporting modeling of other people's thinking.  Dogs and their owners secrete oxytocin increasing the amount of eye contact between them.  It is associated with pair bonding.  Brizendine explains that oxytocin and dopamine production are stimulated by ovarian estrogen at the onset of puberty, encouraging girls to connect and bond with their girlfriends, reducing stress, and exclude the out-group.  It is central to female mammals wanting to nurse, nursing, and remembering their child.  Its effects are context dependent and so is the regulation of the genes that control oxytocin.  Variants of a gene CD38 which facilitates oxytocin secretion from neurons are associated with differing levels of activation of the fusiform face area when looking at faces.  Sapolsky describes an oxytocin receptor gene variant that is associated with children showing: Extreme aggression, A callous unemotional style; foreshadowing adult psychopathy.  And another receptor gene variant is associated with childhood social disconnection and unstable adult relationships.  Gene/environment interactions complicate the interpretation of the presence of particular gene variants.  Hypothalamic neurons send projections to: ventral tegmentum which also becomes more receptive during child birth, nucleus accumbens, hippocampus, amygdala where it inhibits the central amygdala suppressing fear & anxiety consistently in men while still allowing women to respond to threats to their infants, frontal cortex, olfactory network where it helps new rat mums to learn the smell of their offspring; where oxytocin prepares the brain for in-group bonding, out-grouping, birth and maternal behavior.  Outside the brain hypothalamic neurons in females send oxytocin to the posterior pituitary where it enters the blood stream stimulating uterine contraction during labor & supporting milk production for weaning.  Disorders associated with oxytocin abnormalities include ASD. 
; generated during the pregnancy, the acts of childbirth, suckling, and close contact between the mother and baby induce the transformation.  The mother becomes motivated, highly attentive, and aggressively protective of the baby. 

Allocating time to work, self and family is a huge conflict for mothers.  Genes aim to shift the balance towards reproduction. 

The feel & smell of a newborn baby will stimulate 'Baby lust' in a female after cradling the baby.  The infant's head carries pheromones that stimulate the female brain to produce oxytocin, setting up
The agents in complex adaptive systems (CAS) must model their environment to respond effectively to it.  Samuel modeling is described as an approach. 
model
's of reality that encourage wanting babies. 

During pregnancy the fetus and placenta generate hormonal signals, is an emergent capability which is used by cooperating agents to support coordination & rival agents to support control and dominance.  In eukaryotic cells signalling is used extensively.  A signal interacts with the exposed region of a receptor molecule inducing it to change shape to an activated form.  Chains of enzymes interact with the activated receptor relaying, amplifying and responding to the signal to change the state of the cell.  Many of the signalling pathways pass through the nuclear membrane and interact with the DNA to change its state.  Enzymes sensitive to the changes induced in the DNA then start to operate generating actions including sending further signals.  Cell signalling is reviewed by Helmreich.  Signalling is a fundamental aspect of CAS theory and is discussed from the abstract CAS perspective in signals and sensors.  In AWF the eukaryotic signalling architecture has been abstracted in a codelet based implementation.  To be credible signals must be hard to fake.  To be effective they must be easily detected by the target recipient.  To be efficient they are low cost to produce and destroy. 
which enter the shared blood supply and modify the mother's body and brain: thirst & hunger centers are activated, the nose becomes sensitive to chemicals in certain plants that can disrupt development of the fetus.  By the fifth month she can detect the baby's movements.  The mother's brain's smell, hunger and thirst networks have enlarged, while the hypothalamus is essential to many instinctive operations of the body.  It can be viewed as the executor of emotion: happiness, sadness, aggression, eroticism and mating, relaying the amygdala's responses to low level sensory signals.  It has many small sub-regions whose main functions are to regulate hunger, thirst, temperature, sexual behavior, parenting, heart rate, blood pressure, sleep cycles, and similar body operations.  Kandel notes it includes a nucleus containing two distinct populations of neurons: one that regulates aggression and one that regulates sex and mating.  At the intersection neurons are active in both.  Depending on the intensity of the stimulus applied to these neurons mating (weak) or aggression (danger) is activated.  This probably contributes to sexual rage and is why some couples derive extra pleasure from sexual experiences following an argument.  The hypothalamus's (paraventricular nucleus) is closely connected to the pituitary which secrets hormones into the bloodstream ( => acth -> adrenal cortex => cortisol (+)->  amygdala & (-)-> hippocampus).  It directly signals area 25. 
is no longer triggering menstruationProgesterone is a steroid hormone.  It:
  • Rarely directly effects areas of the brain.  Instead it is converted into other sterioids which have different actions in different brain areas. 
  • Increases maternal aggression in concert with estrogen by increasing oxytocin release in certain brain regions.  However, on its own progresterone decreases aggression and anxiety.  It decreases anxiety by entering neurons where it is converted to allopregnanolone which binds to GABA receptors increasing their sensitivity to GABA.  
  • Decreases female sex drive during the second half of the menstrual cycle. 
and estrogen is a generic term for a number of related steroid hormones each of which works differently.  Estrogen:
  • Is generated in the ovaries.  It supports the generation of oxytocin, and so is associated with attachment, nurturing and other affiliative behaviors. 
  • Supports verbal memory.  Removal of ovaries without immediate estrogen replacement therapy degrades verbal memory performance.  The HT reduces age-related shrinkage of the PFC, parietal cortex, and temporal lobe in women, and made them less depressed and angry. 
  • Supports mitochondrial operation in the blood vessels of the brain. 
  • Contributes to maternal aggression but it can reduce aggression and enhance empathy, depending on brain state.  There are two different estrogen receptor types which mediate these conflicting effects.  The level of each type of receptor is independently regulated.  Different receptor variants are associated with:
    • Higher rates of anxiety among women
    • Higher rates of antisocial behavior and conduct disorder in men
  • Is essential for vaginal lubrication
levels rise protecting the mother from the very high levels of stress is a multi-faceted condition reflecting high cortisol levels.  Dr. Robert Sapolsky's studies of baboons indicate that stress helps build readiness for fight or flight.  As these actions occur the levels of cortisol return to the baseline rate.  A stressor is anything that disrupts the regular homeostatic balance.  The stress response is the array of neural and endocrine changes that occur to respond effectively to the crisis and reestablish homeostasis. 
  • The short term response to the stressor
    • activates the amygdala which: Stimulates the brain stem resulting in inhibition of the parasympathetic nervous system and activation of the sympathetic nervous system with the hormones epinephrine and norepinephrine deployed around the body, Activates the PVN which generates a cascade resulting in glucocorticoid secretion to: get energy to the muscles with increased blood pressure for a powerful response.  The brain's acuity and cognition are stimulated.  The immune system is stimulated with beta-endorphin and repair activities curtail.  But when the stressor is
  • long term: loneliness, debt; and no action is necessary, or possible, long term damage ensues.  Damage from such stress may only occur in specific situations: Nuclear families coping with parents moving in.  Sustained stress provides an evolved amplifier of a position of dominance and status.  It is a strategy in female aggression used to limit reproductive competition.  Sustained stress:
    • Stops the frontal cortex from ensuring we do the harder thing, instead substituting amplification of the individual's propensity for risk-taking and impairing risk assessment! 
    • Activates the integration between the thalamus and amygdala. 
      • Acts differently on the amygdala in comparison to the frontal cortex and hippocampus: Stress strengthens the integration between the Amygdala and the hippocampus, making the hippocampus fearful. 
      • BLA & BNST respond with increased BDNF levels and expanded dendrites persistently increasing anxiety and fear conditioning. 
    • Makes it easier to learn a fear association and to consolidate it into long-term memory.  Sustained stress makes it harder to unlearn fear by making the prefrontal cortex inhibit the BLA from learning to break the fear association and weakening the prefrontal cortex's hold over the amygdala.  And glucocorticoids decrease activation of the medial prefrontal cortex during processing of emotional faces.  Accuracy of assessing emotions from faces suffers.  A terrified rat generating lots of glucocorticoids will cause dendrites in the hippocampus to atrophy but when it generates the same amount from excitement of running on a wheel the dendrites expand.  The activation of the amygdala seems to determine how the hippocampus responds. 
    • Depletes the nucleus accumbens of dopamine biasing rats toward social subordination and biasing humans toward depression. 
    • Disrupts working memory by amplifying norepinephrine signalling in the prefrontal cortex and amygdala to prefrontal cortex signalling until they become destructive.  It also desynchronizes activation in different frontal lobe regions impacting shifting of attention.  
    • Increases the risk of autoimmune disease (Jan 2017) 
  • During depression, stress inhibits dopamine signalling.  
  • Strategies for stress reduction include: Mindfulness. 
hormones generated by the fetus and placenta.  She does not feel stressed.  The stress hormones ensure the pregnant woman remains vigilant about her safety, nutrition and surroundings, although she is also forgetful, distracted and preoccupied. 

Between six months and the end of pregnancy the woman's brain shrinks, although the cortex includes the paleocortex a thin sheet of cells that mostly process smell, archicortex and the neocortex.  The cerebral cortex is a pair of large folded sheets of brain tissue, one on either side of the top of the head connected by the corpus callosum.  It includes the occipital, parietal, temporal and frontal lobes. 
expands.  In the final two weeks of pregnancy the brain begins expanding again, deploying maternal circuits. 

At birth a cascade of oxytocin signals the 'mommy brain' to start.  The fully developed fetus signals that it is ready to be born, and the mother responds with a collapse of progesterone.  The oxytocin causes the uterus to contract.  As the baby's head moves through the birth canal, it stimulates more oxytocin signals in the mother's brain, causing lots of new connections between neurons.  The mother's sense of smell, hearing, touch and sight are heightened.  Dopamine is a synaptic signal supporting generalized goal-directed behavior & anticipation of reward.  Its significance is that the receptors that detect the signal are of the slow acting type and are used to alter (modulate) the response of fast acting dopaminergic neural circuits in which the receptors are deployed (LTP).  The signal detects significant changes including predictions of models and actual results which differ unexpectedly.  Dopamine is released primarily by neurons of the ventral tegmental area and the substantia nigra.  The dopamine network architecture is designed to signal the possibility of any type of reward: Norm violation punishment, Winning a lottery, & Misfortune of an envied competitor.  Dopamine signalling:
  • Rescales continuously to accommodate the range of intensity offered by different stimuli.  So dopamine's responses to any reward habituate.  GABA is released by some tegmental neurons to induce habituation.  This allows addictions to develop. 
  • Reflects the anticipation of reward.  It supports establishment of a relationship between a signal, working for a reward and obtaining the reward, but subsequently dopamine is mainly released encouraging the work, right after the signal supporting anticipation of the reward.  Anticipation requires learning and is reflected in hippocampus activity.  That explains context dependent cravings.  And the learning architecture means reliable cues become rewarding.  The accumbens supports willpower.  And dopamine
  • Promotes goal-oriented behavior needed to obtain & likely to achieve the reward - through the dopamine projections to the prefrontal cortex.  That makes dopamine central to:
    • Motivation.  This binding fails in depression - due to stress and in anxiety - due to signals from the amygdala.  
    • The prefrontal cortex's mesocortically stimulated support for willpower to act to delay rewards.  To sustain work for delayed rewards additional dopamine is released based on the length of the delay and the rewards uncertainty (modelled in the dorsolateral prefrontal cortex - which promotes the long term and the ventromedial prefrontal cortex - which promotes the short term) and the anticipated size of the reward (modelled in the accumbens).  Impulsiveness in ADHD is reflected in abnormal dopamine processing.  Addictive drugs bias the dopamine network towards impulsiveness.  
  • Is lowered by certain gene variants which induce: less dopamine in the synapse, fewer receptors, lower responsiveness of receptors; associated with (as tiny effects in hugely varying social scenarios): sensation seeking, risk taking, attentional problems, extroversion; where:
    • The receptor D4's gene shows high variability.  The D47R form is relatively unresponsive to dopamine.  
    • Dopamine is degraded by COMT.  The COMT gene includes a variant which is highly efficient reducing dopamine signalling but with complicating gene/environment interactions.  
    • Dopamine is removed from the synapse by a reuptake transporter DAT. 
and oxytocin can generate a feeling of euphoria in the mother.  The brain is forever altered. 

The mother will assimilate the key details of her newborn baby.  Soon the mother will attach supports a stable sense of connection & calm to another person who provides load sharing, using the 'attachment network': pituitary, hypothalamus, adrenal glands, ACC, VTA, nucleus accumbens, PFC; initially generated in babies by norepinephrine from the locus ceruleus as long as corticosteroid levels are low, which deploys & responds to oxytocin (nucleus accumbens, VTA, amygdala, hippocampus), to maintain critical judgement about our partners, once dopamine from the VTA has reinforced the initial interest of the nucleus accumbens. 
to the baby and maternal aggression supports protection of newborns especially in breeds with high risks of infanticide.  During late pregnancy, estrogen and progesterone increase maternal aggression by increasing oxytocin release in the brain.  This outcome reflects the specific late pregnancy brain state and presence of both estrogen and progesterone. 
will begin.  She will develop relatively improved spatial memory is generated by hippocampal ensembles and the memory is altered and consolidated by reactivation during slow-wave sleep. 
, and be more
To benefit from shifts in the environment agents must be flexible.  Being sensitive to environmental signals agents who adjust strategic priorities can constrain their competitors. 
flexible
, adaptive and courageous.  She falls romantically in love is a passionate emotion reflecting the risky agreement to commit resources to the long term activity of raising children. The genes ensure that once a person has chosen, the critical-thinking pathways shut down.  That is especially necessary for women to ignore the uncertainty - they become more passionately in love than men.  For both partners initial separations remove the oxytocin (and vasopressin in men) and dopamine rewards from touching & hugging, generating withdrawal driving the couple closer.  The same circuits, driven again by oxytocin signalling, encourage a mother to fall in love with her newborn baby. 
with the baby.  Oxytocin is released as the babies breast feed, reducing the pain and generating feelings of pleasure.  These changes will be maintained while the mother remains in physical contact with the child.  The changes caused by breast feeding induce fuzzy mellow thinking, which reverts to normal after weaning.  Often this new love impacts the mother's desire for her partner.  Sex isn't important or needed.  When mothers wean they are advised to do it gradually so they don't suffer from withdrawal. 

Fathers also experience brain and hormonal changes during the pregnancy.  Pheromones, produced by the mother, make the father's prolactin levels rise in the weeks before birth, and cortisol is a glucocorticoid produced in the adrenal cortex of the adrenal glands.  It:
  • Stimulates
    • Gluconeogenesis to increase production of blood sugar
    • Metabolism of fats, proteins and carbohydrates
  • Suppresses the immune system.  
  • Decreases bone formation
  • In excessive concentrations destroy synaptic connections in the: hippocampus, and prefrontal cortex; leading to flattened emotions and impaired memory. 
levels double.  In the first weeks after the birth the father's testosterone is a hormone secreted by the testes, ovaries, and adrenal glands, in response to stimulation from the hypothalamic/pituitary/testicular cascade, that makes humans more willing to do what it takes to attain and maintain status, according to Sapolsky.  That means players of the Ultimatum Game, if previously given testosterone can become more generous.  High testosterone in a fetus masculinizes the brain.  Males generate 10 times the amount.  It is the trigger for sexual desire in males and females, stimulating the hypothalamus.  Testosterone's effect is highly socially contextual so it may encourage acts of kindness or aggression (when challenged).  The level of testosterone does not predict which individuals will be aggressive in: Birds, Fish, Mammals including primates.  Genes impact the potency of testosterone by altering the enzymes that: Construct it, Convert it to estrogen, code the androgen receptor.   This androgen receptor includes a variable polyglutamine repeat which alters the sensitivity to the testosterone signal.  The more potent form is associated with boys showing more dramatic 'masculinization' of the cortex.  But the detected genetic influences are small.  Testosterone decreases activity in the prefrontal cortex and its functional coupling to the amygdala while increasing the coupling between the amygdala & the thalamus.  Testosterone shortens the refactory period of amygdaloid & amygdaloid target neurons.  This results in impulsive risk taking and more focus on unfamiliar faces and distrust of them.  Testosterone increases activity in the ventral tegmentum projecting dopamine to enhance place preference.  Winners of fights become more willing to fight in part due to testosterone increasing confidence and optimism and reducing fear and anxiety.  And winning at: Chess, Athletics, Stock trades; induces the BNST to add testosterone receptors increasing its sensitivity to the hormone.  People become overconfident and overly optimistic. 
levels drop by a third, and estrogen levels rise, to prepare the father for bonding with the newborn.  And the changes lower the father's sex drive. 

When mothers are placed under stress they can fail to attach properly is John Bowlby's model of mother infant bonding.  He argued that infants need: love, warmth, affection, responsiveness, stimulation, consistency, reliability; or they become anxious, depressed, and/or poorly attached adults.  Evolutionarily, sociopaths may be highly successful as managers and leaders but they are probably anxious.  Sapolsky notes the powerful association between murder rates and stopping pregnant girls from terminating unwanted pregnancies.  Typical mothers also provide training on social conventions and their children's position in the group hierarchy.  Children raised without a mother's support fail to understand social constraints and when to use social behaviors.  And in the presence of unsupportive mothers newborns attach to negative stimuli.  This response is explained by the SHRP.  Abused children subsequently seek out abusive relationships as adults.  And a percentage of infants abused by their mothers become abusive mothers. 
to their baby which can impact the trust and distrust are evolved responses to sham emotions.  During a friendship where no sham emotions have been detected trust will build up. 
and security circuits of the children.  And through epi-genetic represent state surfaces within cells and eggs which can be operationally modified so as to provide a heritable structure.  DNA, histones and other stable structures provide surfaces where these states may be setup.  Egg carriers are in a particularly powerful position to induce epi-genetic changes.  Sapolsky notes [childhood] events which persistently alter brain structure and behavior via epi-genetic mechanisms including: pair-bonding in prairie voles, as they first mate, is supported by changes in oxytocin & vasopressin receptor gene regulation in the nucleus accumbens. 
effects, more generations can be impacted.  If nurturing grandparents are present, they can break the cycle of trust and attachment issues.  Similarly other people are able to provide the nurturing that children need, without impacting the children, which can reduce the stress on the mother. 

Brizendine notes that resource predictability is essential for good mothering.  When the environment is unpredictable, stress increases, oxytocin decreases, mothers struggle to nurture and become fearful is an emotion which prepares the body for time sensitive action: Blood is sent to the muscles from the gut and skin, Adrenalin is released stimulating: Fuel to be released from the liver, Blood is encouraged to clot, and Face is wide-eyed and fearful.  The short-term high priority goal, experienced as a sense of urgency, is to flee, fight or deflect the danger.  There are both 'innate' - really high priority learning - which are mediated by the central amydala and learned fears which are mediated by the BLA which learns to fear a stimulus and then signals the central amygdala. 
and their babies show signs of depression is a debilitating episodic state of extreme sadness, typically beginning in late teens or early twenties. This is accompanied by a lack of energy and emotion, which is facilitated by genetic predisposition - for example genes coding for relatively low serotonin levels, estrogen sensitive CREB-1 gene which increases women's incidence of depression at puberty; and an accumulation of traumatic events.  There is a significant risk of suicide: depression is involved in 50% of the 43,000 suicides in the US, and 15% of people with depression commit suicide.  Depression is the primary cause of disability with about 20 million Americans impacted by depression at any time.  There is evidence of shifts in the sleep/wake cycle in affected individuals (Dec 2015).  The affected person will experience a pathological sense of loss of control, prolonged sadness with feelings of hopelessness, helplessness & worthlessness, irritability, sleep disturbances, loss of appetite, and inability to experience pleasure.  Michael Pollan concludes depression is fear of the past.  It affects 12% of men and 20% of women.  It appears to be associated with androgen deprivation therapy treatment for prostate cancer (Apr 2016).  Chronic stress depletes the nucleus accumbens of dopamine, biasing humans towards depression.  Depression easily leads to following unhealthy pathways: drinking, overeating; which increase the risk of heart disease.   It has been associated with an aging related B12 deficiency (Sep 2016).  During depression, stress mediates inhibition of dopamine signalling.  Both depression and stress activate the adrenal glands' release of cortisol, which will, over the long term, impact the PFC.  There is an association between depression and additional brain regions: Enlarged & more active amygdala, Hippocampal dendrite and spine number reductions & in longer bouts hippocampal volume reductions and memory problems, Dorsal raphe nucleus linked to loneliness, Defective functioning of the hypothalamus undermining appetite and sex drive, Abnormalities of the ACC.  Mayberg notes ACC area 25: serotonin transporters are particularly active in depressed people and lower the serotonin in area 25 impacting the emotion circuit it hubs, inducing bodily sensations that patients can't place or consciously do anything about; and right anterior insula: which normally generates emotions from internal feelings instead feel dead inside; are critical in depression.  Childhood adversity can increase depression risk by linking recollections of uncontrollable situations to overgeneralizations that life will always be terrible and uncontrollable.  Sufferers of mild autism often develop depression.  Treatments include: CBT which works well for cases with below average activity of the right anterior insula (mild and moderate depression), UMHS depression management, deep-brain stimulation of the anterior insula to slow firing of area 25.  Drug treatments are required for cases with above average activity of the right anterior insula.  As of 2010 drug treatments: SSRIs (Prozac), MAO, monoamine reuptake inhibitors; take weeks to facilitate a response & many patients do not respond to the first drug applied, often prolonging the agony.  By 2018, Kandel notes, Ketamine is being tested as a short term treatment, as it acts much faster, reversing the effect of cortisol in stimulating glutamate signalling, and because it reverses the atrophy induced by chronic stress.   Genomic predictions of which treatment will be effective have not been possible because: Not all clinical depressions are the same, a standard definition of drug response is difficult; and become less outgoing and positive in adolescence in humans supports the transition from a juvenile configuration, dependent on parents and structured to learn & logistically transform, to adult optimized to the proximate environment.  And it is staged encouraging male adolescents to escape the hierarchy they grew up in and enter other groups where they may bring in: fresh ideas, risk taking; and alter the existing hierarchy: Steve Jobs & Steve Wozniak, Bill Gates & Paul Allen; while females become highly focused on friendships and communications.  It marks the beginning of Piaget's formal operational stage of cognitive development.  The limbic, autonomic and hormone networks are already deployed and functioning effectively.  The frontal cortex has to be pruned: winning neurons move to their final highly connected positions, and are myelinated over time.  The rest dissolve.  So the frontal lobe does not obtain its adult configuration and networked integration until the mid-twenties when prefrontal cortex control becomes optimal.  The evolutionarily oldest areas of the frontal cortex mature first.  The PFC must be iteratively customized by experience to do the right thing as an adult.  Adolescents:
  • Don't detect irony effectively.  They depend on the DMPFC to do this, unlike adults who leverage the fusiform face area.  
  • Regulate emotions with the ventral striatum while the prefrontal cortex is still being setup.  Dopamine projection density and signalling increase from the ventral tegmentum catalyzing increased interest in dopamine based rewards.  Novelty seeking allows for creative exploration which was necessary to move beyond the familial pack.  Criticisms do not get incorporated into learning models by adolescents leaving their risk assessments very poor.  The target of the dopamine networks, the adolescent accumbens, responds to rewards like a gyrating top - hugely to large rewards, and negatively to small rewards.  Eventually as the frontal regions increase in contribution there are steady improvements in: working memory, flexible rule use, executive organization and task shifting.  And adolescents start to see other people's perspective. 
  • Drive the cellular transformations with post-pubescent high levels of testosterone in males, and high but fluctuating estrogen & progesterone levels in females.  Blood flow to the frontal cortex is also diverted on occasion to the groin.  
  • Peer pressure is exceptionally influential in adolescents.  Admired peer comments reduce vmPFC activity and enhance ventral striatal activity.  Adults modulate the mental impact of socially mean treatment: the initial activation of the PAG, anterior cingulate, amygdala, insula cortex; which generate feelings of pain, anger, and disgust, with the VLPFC but that does not occur in adolescents.  
  • Feel empathy intensely, supported by their rampant emotions, interest in novelty, ego.  But feeling the pain of others can induce self-oriented avoidance of the situations. 
and adulthood.  Mothers, become focused on their children - able to assess their children's emotions from non-verbal cues, but this concentration means they need considerable support from their partner, parents and friends to sustain a predictable environment. 

Emotion: The Feeling Brain
Women are much better adapted to sensing emotions are low level fast unconscious agents distributed across the brain and body which associate, via the amygdala and rich club hubs, important environmental signals with encoded high speed sensors, and distributed programs of action to model: predict, prioritize guidance signals, select and respond effectively, coherently and rapidly to the initial signal.  The majority of emotion centered brain regions interface to the midbrain through the hypothalamus.  The cerebellum and basal ganglia support the integration of emotion and motor functions, rewarding rhythmic movement.  The most accessible signs of emotions are the hard to control and universal facial expressions.  Emotions provide prioritization for conscious access given that an animal has only one body, but possibly many cells, with which to achieve its highest level goals.  Because of this emotions clash with group goals and are disparaged by the powerful.  Evolutionary psychology argues evolution shaped human emotions during the long period of hunter-gatherer existence in the African savanna.  Human emotions are universal and include: Anger, Appreciation of natural beauty, Disgust, Fear, Gratitude, Grief, Guilt, Happiness, Honor, Jealousy, Liking, Love, Rage, Romantic love, Lust for revenge, Passion, Sadness, Self-control, Shame, Sympathy, Surprise; and the sham emotions and distrust induced by reciprocal altruism. 
.  They can mirror are part of the premotor cortex, responding to signals from the PFC and sending on signals to the motor cortex to drive muscles.  This subset of Pre-motor cortex neurons, also respond to observation of other higher animals performing the same act requested by the PFC.  The mirroring can be abstract: See and hear activate same mirror neurons, Activate only when the action has the same intentionality; and none has been shown to be causally related yet. 
their partner's expressions and movements and sense the emotions that are occurring with their gut feelings is ventromedial prefrontal cortex which is:
  • Focused on the impact of emotion on decision making
  • A participant in limbic system operations 
  • Many human behaviors involve interactions between the vmPFC, the limbic system & the dorsolateral prefrontal cortex.  Part of decision making is for the limbic system to internally simulate (often with the help of the sympathetic nervous system) what alternative outcomes of a decision will feel like with the results of these somatic marker analyses being reported to the vmPFC.  
  • Damage to the vmPFC results in bad decision making: Poor judgement in choosing friends & partners, Failure to respond to negative feedback; because they can't feel the issues; and are overly controlled by the logical contribution of the DLPFC. 
.  Males are typically not very effective at this.  Brizendine suggests women cry to signal when they are upset to their male partners.  That comes as a complete surprise to most males.  With these two different
The agents in complex adaptive systems (CAS) must model their environment to respond effectively to it.  Samuel modeling is described as an approach. 
models
of reality, females can conclude that males are emotionally insensitive, while males wonder 'why their partner doesn't realize he loves her.' 

Evolutionary psychologists asserts that human culture reflects adaptations that developed during human's long hunter-gatherer past living on the African savanna.  Its implications are described in The Adapted Mind.  Subsequent studies of the effects of selection on the human genome show significant changes due to our more recent history as well. 
speculate feeling another's pain and rapidly reading emotional nuance allowed hunter gatherer women advance warning of potential aggression or other dangers, to protect themselves and their children.  But this also results in women startling more easily and reacting more fearfully is an emotion which prepares the body for time sensitive action: Blood is sent to the muscles from the gut and skin, Adrenalin is released stimulating: Fuel to be released from the liver, Blood is encouraged to clot, and Face is wide-eyed and fearful.  The short-term high priority goal, experienced as a sense of urgency, is to flee, fight or deflect the danger.  There are both 'innate' - really high priority learning - which are mediated by the central amydala and learned fears which are mediated by the BLA which learns to fear a stimulus and then signals the central amygdala. 


Brizendine explains that for males, emotions are processed rationally, rather than with gut feel.  Males respond to emotions by avoiding them: Simon Baron-Cohen suggests that Asperger is autism spectrum disorder.  All these disorders are characterized by difficulty connecting with others.  People who suffer from ASD show a reduced fusiform response to faces.  ASD is linked to gene variants affecting oxytocin and vasopressin, to nongenetic mechanisms that silence the oxytocin receptor gene and to lower levels of the receptor itself. 
's reflects this with sufferers avoiding the pain emerged as a mental experience, Damasio asserts, constructed by the mind using mapping structures and events provided by nervous systems.  But feeling pain is supported by older biological functions that support homeostasis.  These capabilities reflect the organism's underlying emotive processes that respond to wounds: antibacterial and analgesic chemical deployment, flinching and evading actions; that occur in organisms without nervous systems.  Later in evolution, after organisms with nervous systems were able to map non-neural events, the components of this complex response were 'imageable'.  Today, a wound induced by an internal disease is reported by old, unmyelinated C nerve fibers.  A wound created by an external cut is signalled by evolutionarily recent myelinated fibers that result in a sharp well-localized report, that initially flows to the dorsal root ganglia, then to the spinal cord, where the signals are mixed within the dorsal and ventral horns, and then are transmitted to the brain stem nuclei, thalamus and cerebral cortex.  The pain of a cut is located, but it is also felt through an emotive response that stops us in our tracks.  Pain amplifies the aggression response of people by interoceptive signalling of brain regions providing social emotions including the PAG projecting to the amygdala; making aggressive people more so and less aggressive people less so.  Fear of pain is a significant contributor to female anxiety.  Pain is the main reason people visit the ED in the US.  Pain is mediated by the thalamus and nucleus accumbens, unless undermined by sleep deprivation. 
of looking at emotion laden faces are neurons which respond when the features of a face are presented to the retina.  Faces are recognized by dedicated neural networks consisting of face cells grouped into 6 patches of 10,000 cells on each side of the brain in the cortex just behind the ear.  The face cells respond abstractly to the dimensions and features of faces.  Each face cell responds to a combination of facial dimensions, creating a holistic representation.  A single face cell represents a vector of about 6 dimensions.  Two hundred cells can together represent the 50 dimensions which are required to identify a face in a face space where an infinite number of faces can be represented.  Cal tech's Chang & Tsao argue there is an average face at the origin of the face space and each actual face is represented as differences from it in the face space (Jun 2017).  .  Men don't like being confronted with the helplessness they feel regarding responding usefully to their partner's crying, sadness is a feeling, which can induce empathy and compassion.  It can last for days, in contrast to the emotions, fear & anger.  Mild sadness induces a beneficial state in the brain: improved judgment, memory, motivation, and more socially sensitive and generous. 
and despair.  When in trouble, men work things out alone.  Women have to push hard to get males to process emotions, except for threats of abandonment or violence, and anger is an emotion which protects a person who has been cheated by a supposed friend.  When the exploitation of the altruism is discovered, Steven Pinker explains, the result is a drive for moralistic aggression to hurt the cheater.  .  Women are expecting the same level of social support they get all the time from their girlfriends.  Brizendine notes that women remember these emotional episodes in more detail and retain them for longer than men do.  This is because their amygdalae contains > 12 distinct areas: Central, Lateral.  It receives simple signals from the lower parts of the brain: pain from the PAG; and abstract complex information from the highest areas: Disgust from the insula cortex, allowing it to orchestrate emotion.  It sends signals to almost every other part of the brain, including to the decision making circuitry of the frontal lobes.  It has high levels of D(1) dopamine receptors.  During extreme fear the amygdala drives the hippocampus into fear learning.  It outputs directly to subcortical reflexive motor pathways when speed is required.  Its central nucleus projects to the BNST.  It signals the locus ceruleus.  It directly signals area 25.  The amygdala:
  • Promotes aggression.  Stimulating the amygdala promotes rage.  It converts anger into aggression and when impaired it impacts the ability to detect angry facial expressions.  
  • Participates in disgust
  • Perceives fear promoting stimuli.  In PTSD sufferers the Amygdala overreacts to mildly fearful stimuli and is slow to calm down and the amygdala expands in size over a period of months.  Fear is processed by the lateral nucleus which serves as the input from various senses, and the central nucleus which outputs to the brain stem (central grey - freezing, lateral hypothalamus - blood pressure, activates paraventricular hypothalamus => crf -> hormone adjustments). 
  • Has lots of receptors for and is highly sensitive to glucocorticoids.  Stress inhibits the GABA interneurons in the basolateral amygdala (BLA) allowing the excitatory glutamate releasing neurons to excite more. 
  • Is sensitive to unsettling/uncertain social situations where it promotes anxiety.  It is also interested in uncertain but potentially painful situations.  The amygdala contributes to social and emotional decision making where the BLA supports rejecting an unacceptable offer, as allowed in the Ultimatum Game, by injecting implicit mistrust and vigilance, generating an anger driven rejection that is used as punishment.  The amygdala is very rapidly excited by subliminal signals from the thalamus of outgroup skin color.  The amygdala subsequently tips social emotions against outgroups unless restrained by the frontal lobe or influenced by subliminal priming to prioritize inclusion.  The fast path from the thalamus rapidly but inaccurately signals its identified a weapon. 
  • Promotes male, but not female, sexual motivation when it is an uncertain potential pleasure. 
  • Responds to the longing for uncertain potential pleasures and fear that the reward will not be worth it if it happens.  The amygdala turns off during orgasm. 
  • Uses but is not directly involved in vision.  
are more sensitive to emotional nuance, more often activating the hippocampus is a part of the medial temporal lobe of the brain involved in the temporary storage or coding of long-term episodic memory.  It includes the dentate gyrus.  Memory formation in the cells of the hippocampus uses the MAP kinase signalling network which is impacted by sleep deprivation.  The hippocampus dependent memory system is directly affected by cholinergic changes throughout the wake-sleep cycle.  Increased acetylcholine during REM sleep promotes information attained during wakefulness to be stored in the hippocampus by suppressing previous excitatory connections while facilitating encoding without interference from previously stored information.  During slow-wave sleep low levels of acetylcholine cause the release of the suppression and allow for spontaneous recovery of hippocampal neurons resulting in memory consolidation.  It was initially associated with memory formation by McGill University's Dr. Brenda Milner, via studies of 'HM' Henry Molaison, whose medial temporal lobes had been surgically destroyed leaving him unable to create new explicit memories.  The size of neurons' dendritic trees expands and contracts over a female rat's ovulatory cycle, with the peak in size and cognitive skills at the estrogen high point.  Adult neurogenesis occurs in the hippocampus (3% of neurons are replaced each month) where the new neurons integrate into preexisting circuits.  It is enhanced by learning, exercise, estrogen, antidepressants, environmental enrichment, and brain injury and inhibited by various stressors explains Sapolsky.  Prolonged stress makes the hippocampus atrophy.  He notes the new neurons are essential for integrating new information into preexisting schemas -- learning that two things you thought were the same are actually different.  Specific cells within the hippocampus and its gateway, the entorhinal cortex, are compromised by Alzheimer's disease.  It directly signals area 25. 
to tag the event. 

Men have a larger amygdala while women have a relatively larger PFC is prefrontal cortex which is:
  • The front part of the frontal lobe of the cerebral cortex.  It evolved most recently.  During adolescence when the PFC is still deploying, older brain agents provide equivalent strategies: ventral striatum.  The PFC has been implicated in planning, working memory: dorsolateral; decision making: Orbitofrontal cortex; and social behavior.  It regulates feelings.  Different PFC circuits track internal reward driven strategies and externally signalled advice.  The PFC chooses between conflicting options, letting go or restraint, especially between cognition and emotions.  It imposes an overarching strategy for managing working memory.  It is essential for thinking about multiple items with different labels.  It includes neurons that are interested in particular sub-categories: Dog, Cat.  Once it has made a decision it signals the rest of the frontal lobe just behind it.  Glucocorticoids decrease excitability of the PFC.  
, resulting in men expressing anger more readily.  Especially after puberty, male amygdala's have more testosterone is a hormone secreted by the testes, ovaries, and adrenal glands, in response to stimulation from the hypothalamic/pituitary/testicular cascade, that makes humans more willing to do what it takes to attain and maintain status, according to Sapolsky.  That means players of the Ultimatum Game, if previously given testosterone can become more generous.  High testosterone in a fetus masculinizes the brain.  Males generate 10 times the amount.  It is the trigger for sexual desire in males and females, stimulating the hypothalamus.  Testosterone's effect is highly socially contextual so it may encourage acts of kindness or aggression (when challenged).  The level of testosterone does not predict which individuals will be aggressive in: Birds, Fish, Mammals including primates.  Genes impact the potency of testosterone by altering the enzymes that: Construct it, Convert it to estrogen, code the androgen receptor.   This androgen receptor includes a variable polyglutamine repeat which alters the sensitivity to the testosterone signal.  The more potent form is associated with boys showing more dramatic 'masculinization' of the cortex.  But the detected genetic influences are small.  Testosterone decreases activity in the prefrontal cortex and its functional coupling to the amygdala while increasing the coupling between the amygdala & the thalamus.  Testosterone shortens the refactory period of amygdaloid & amygdaloid target neurons.  This results in impulsive risk taking and more focus on unfamiliar faces and distrust of them.  Testosterone increases activity in the ventral tegmentum projecting dopamine to enhance place preference.  Winners of fights become more willing to fight in part due to testosterone increasing confidence and optimism and reducing fear and anxiety.  And winning at: Chess, Athletics, Stock trades; induces the BNST to add testosterone receptors increasing its sensitivity to the hormone.  People become overconfident and overly optimistic. 
receptors, in biological cells these proteins are able to span the cell membrane and present an active site which is tailored to interact with a specific signal.  When the receptor pairs with its signal, its overall shape changes resulting in changes in the part internal to the cell which can be relayed by the cells signalling infrastructure.  In neuron synapses one type of receptor (fast) is associated with an ion channel.  The other (slow) is associated with a signalling enzyme chain and modulates the neuron's response. 
, stimulating and increasing its response to anger.  Women are more sensitive to rupturing relationships and the risk of aggression, so they avoid a rush to anger.  Once they commit to anger it will be supported verbally. 

The possibility of pain, or a lack of safety, makes women fearful.  The brain learns from experience is the basolateral amygdala, a relatively recently evolved part of the amygdala which learns stimuli to fear and then signals the central amygdala.  It recieves inputs from all sensory networks.  Some are fast pathways that allow the BLA to detect and respond when the sensory cortex is unaware.  But it is far less accurate than the cortex.  The BLA's learning involves increased excitability of synapses coupling the BLA and central amygdala.  This is due to gene driven: Increased levels of growth factors promoting new connections, more receptors for excitatory neurotransmitters in dendritic spines.  The BLA also responds to signals from the frontal cortex that a stimulus no longer appears frightening.  This subset of BLA cells respond inhibiting the associating subset.  Stress and glucocorticoids increase levels of CRH and BDNF encouraging the building of new dendrites and synapses. 
, about what to fear.  Females find it hard to suppress the anticipation of danger or pain, activating the amygdala, resulting in anxiety is manifested in the amygdala mediating inhibition of dopamine rewards.  Anxiety disorders are now seen as a related cluster, including PTSD, panic attacks, and phobias.  Major anxiety, is typically episodic, correlated with increased activity in the amygdala, results in elevated glucocorticoids and reduces hippocampal dendrite & spine density.  Some estrogen receptor variants are associated with anxiety in women.  Michael Pollan concludes anxiety is fear of the future.  Sufferers of mild autism often develop anxiety disorders.  Treatments for anxiety differ.  50 to 70% of people with generalized anxiety respond to drugs increasing serotonin concentrations, where there is relief from symptoms: worry, guilt; linked to depression, which are treated with SSRIs (Prozac).  But many fear-related disorders respond better to psychotherapy: psychoanalysis, and intensive CBT. 
.  Women are four times more at risk, is an assessment of the likelihood of an independent problem occurring.  It can be assigned an accurate probability since it is independent of other variables in the system.  As such it is different from uncertainty. 
of this, across all cultures is how we do and think about things, transmitted by non-genetic means as defined by Frans de Waal.  CAS theory views cultures as operating via memetic schemata evolved by memetic operators to support a cultural superorganism.  Evolutionary psychology asserts that human culture reflects adaptations generated while hunting and gathering.  Dehaene views culture as essentially human, shaped by exaptations and reading, transmitted with support of the neuronal workspace and stabilized by neuronal recycling.  Damasio notes prokaryotes and social insects have developed cultural social behaviors.  Sapolsky argues that parents must show children how to transform their genetically derived capabilities into a culturally effective toolset.  He is interested in the broad differences across cultures of: Life expectancy, GDP, Death in childbirth, Violence, Chronic bullying, Gender equality, Happiness, Response to cheating, Individualist or collectivist, Enforcing honor, Approach to hierarchy; illustrating how different a person's life will be depending on the culture where they are raised.  Culture:
  • Is deployed during pregnancy & childhood, with parental mediation.  Nutrients, immune messages and hormones all affect the prenatal brain.  Hormones: Testosterone with anti-Mullerian hormone masculinizes the brain by entering target cells and after conversion to estrogen binding to intracellular estrogen receptors; have organizational effects producing lifelong changes.  Parenting style typically produces adults who adopt the same approach.  And mothering style can alter gene regulation in the fetus in ways that transfer epigenetically to future generations!  PMS symptoms vary by culture. 
  • Is also significantly transmitted to children by their peers during play.  So parents try to control their children's peer group.  
  • Is transmitted to children by their neighborhoods, tribes, nations etc. 
  • Influences the parenting style that is considered appropriate. 
  • Can transform dominance into honor.  There are ecological correlates of adopting honor cultures.  Parents in honor cultures are typically authoritarian. 
  • Is strongly adapted across a meta-ethnic frontier according to Turchin.  
  • Across Europe was shaped by the Carolingian empire. 
  • Can provide varying levels of support for innovation.  Damasio suggests culture is influenced by feelings: 
    • As motives for intellectual creation: prompting detection and diagnosis of homeostatic deficiencies, identifying desirable states worthy of creative effort.
    • As monitors of the success and failure of cultural instruments and practices
    • As participants in the negotiation of adjustments required by the cultural process over time 
  • Produces consciousness according to Dennet. 
, because it allows them to respond quickly to protect their children.  The intense sensitivity also increases the likelihood of depression is a debilitating episodic state of extreme sadness, typically beginning in late teens or early twenties. This is accompanied by a lack of energy and emotion, which is facilitated by genetic predisposition - for example genes coding for relatively low serotonin levels, estrogen sensitive CREB-1 gene which increases women's incidence of depression at puberty; and an accumulation of traumatic events.  There is a significant risk of suicide: depression is involved in 50% of the 43,000 suicides in the US, and 15% of people with depression commit suicide.  Depression is the primary cause of disability with about 20 million Americans impacted by depression at any time.  There is evidence of shifts in the sleep/wake cycle in affected individuals (Dec 2015).  The affected person will experience a pathological sense of loss of control, prolonged sadness with feelings of hopelessness, helplessness & worthlessness, irritability, sleep disturbances, loss of appetite, and inability to experience pleasure.  Michael Pollan concludes depression is fear of the past.  It affects 12% of men and 20% of women.  It appears to be associated with androgen deprivation therapy treatment for prostate cancer (Apr 2016).  Chronic stress depletes the nucleus accumbens of dopamine, biasing humans towards depression.  Depression easily leads to following unhealthy pathways: drinking, overeating; which increase the risk of heart disease.   It has been associated with an aging related B12 deficiency (Sep 2016).  During depression, stress mediates inhibition of dopamine signalling.  Both depression and stress activate the adrenal glands' release of cortisol, which will, over the long term, impact the PFC.  There is an association between depression and additional brain regions: Enlarged & more active amygdala, Hippocampal dendrite and spine number reductions & in longer bouts hippocampal volume reductions and memory problems, Dorsal raphe nucleus linked to loneliness, Defective functioning of the hypothalamus undermining appetite and sex drive, Abnormalities of the ACC.  Mayberg notes ACC area 25: serotonin transporters are particularly active in depressed people and lower the serotonin in area 25 impacting the emotion circuit it hubs, inducing bodily sensations that patients can't place or consciously do anything about; and right anterior insula: which normally generates emotions from internal feelings instead feel dead inside; are critical in depression.  Childhood adversity can increase depression risk by linking recollections of uncontrollable situations to overgeneralizations that life will always be terrible and uncontrollable.  Sufferers of mild autism often develop depression.  Treatments include: CBT which works well for cases with below average activity of the right anterior insula (mild and moderate depression), UMHS depression management, deep-brain stimulation of the anterior insula to slow firing of area 25.  Drug treatments are required for cases with above average activity of the right anterior insula.  As of 2010 drug treatments: SSRIs (Prozac), MAO, monoamine reuptake inhibitors; take weeks to facilitate a response & many patients do not respond to the first drug applied, often prolonging the agony.  By 2018, Kandel notes, Ketamine is being tested as a short term treatment, as it acts much faster, reversing the effect of cortisol in stimulating glutamate signalling, and because it reverses the atrophy induced by chronic stress.   Genomic predictions of which treatment will be effective have not been possible because: Not all clinical depressions are the same, a standard definition of drug response is difficult; in girls and women in their reproductive years.  Severe stress is a multi-faceted condition reflecting high cortisol levels.  Dr. Robert Sapolsky's studies of baboons indicate that stress helps build readiness for fight or flight.  As these actions occur the levels of cortisol return to the baseline rate.  A stressor is anything that disrupts the regular homeostatic balance.  The stress response is the array of neural and endocrine changes that occur to respond effectively to the crisis and reestablish homeostasis. 
  • The short term response to the stressor
    • activates the amygdala which: Stimulates the brain stem resulting in inhibition of the parasympathetic nervous system and activation of the sympathetic nervous system with the hormones epinephrine and norepinephrine deployed around the body, Activates the PVN which generates a cascade resulting in glucocorticoid secretion to: get energy to the muscles with increased blood pressure for a powerful response.  The brain's acuity and cognition are stimulated.  The immune system is stimulated with beta-endorphin and repair activities curtail.  But when the stressor is
  • long term: loneliness, debt; and no action is necessary, or possible, long term damage ensues.  Damage from such stress may only occur in specific situations: Nuclear families coping with parents moving in.  Sustained stress provides an evolved amplifier of a position of dominance and status.  It is a strategy in female aggression used to limit reproductive competition.  Sustained stress:
    • Stops the frontal cortex from ensuring we do the harder thing, instead substituting amplification of the individual's propensity for risk-taking and impairing risk assessment! 
    • Activates the integration between the thalamus and amygdala. 
      • Acts differently on the amygdala in comparison to the frontal cortex and hippocampus: Stress strengthens the integration between the Amygdala and the hippocampus, making the hippocampus fearful. 
      • BLA & BNST respond with increased BDNF levels and expanded dendrites persistently increasing anxiety and fear conditioning. 
    • Makes it easier to learn a fear association and to consolidate it into long-term memory.  Sustained stress makes it harder to unlearn fear by making the prefrontal cortex inhibit the BLA from learning to break the fear association and weakening the prefrontal cortex's hold over the amygdala.  And glucocorticoids decrease activation of the medial prefrontal cortex during processing of emotional faces.  Accuracy of assessing emotions from faces suffers.  A terrified rat generating lots of glucocorticoids will cause dendrites in the hippocampus to atrophy but when it generates the same amount from excitement of running on a wheel the dendrites expand.  The activation of the amygdala seems to determine how the hippocampus responds. 
    • Depletes the nucleus accumbens of dopamine biasing rats toward social subordination and biasing humans toward depression. 
    • Disrupts working memory by amplifying norepinephrine signalling in the prefrontal cortex and amygdala to prefrontal cortex signalling until they become destructive.  It also desynchronizes activation in different frontal lobe regions impacting shifting of attention.  
    • Increases the risk of autoimmune disease (Jan 2017) 
  • During depression, stress inhibits dopamine signalling.  
  • Strategies for stress reduction include: Mindfulness. 
often induces depression in women whose families display a genetic disposition.  Estrogen is a generic term for a number of related steroid hormones each of which works differently.  Estrogen:
  • Is generated in the ovaries.  It supports the generation of oxytocin, and so is associated with attachment, nurturing and other affiliative behaviors. 
  • Supports verbal memory.  Removal of ovaries without immediate estrogen replacement therapy degrades verbal memory performance.  The HT reduces age-related shrinkage of the PFC, parietal cortex, and temporal lobe in women, and made them less depressed and angry. 
  • Supports mitochondrial operation in the blood vessels of the brain. 
  • Contributes to maternal aggression but it can reduce aggression and enhance empathy, depending on brain state.  There are two different estrogen receptor types which mediate these conflicting effects.  The level of each type of receptor is independently regulated.  Different receptor variants are associated with:
    • Higher rates of anxiety among women
    • Higher rates of antisocial behavior and conduct disorder in men
  • Is essential for vaginal lubrication
's contribution, altering: circadian rhythms is a CAS process that has a 24 hour oscillation driven by a circadian clock.  In humans there are many such processes: sleep cycle (Dec 2015), liver, metabolism, immune system, oxidative stress;
, sleep facilitates salient memory formation and removal of non-salient memories.  The five different stages of the nightly sleep cycles support different aspects of memory formation.  The sleep stages follow Pre-sleep and include: Stage one characterized by light sleep and lasting 10 minutes, Stage two where theta waves and sleep spindles occur, Stage three and Stage four together represent deep slow-wave sleep (SWS) with delta waves, Stage five is REM sleep; sleep cycles last between 90-110 minutes each and as the night progresses SWS times reduce and REM times increase.   Sleep includes the operation of synapse synthesis and maintenance through DNA based activity including membrane trafficking, synaptic vesicle recycling, myelin structural protein formation and cholesterol and protein synthesis.  Sleep also controls inflammation (Jan 2019)  Sleep deprivation undermines the thalamus & nucleus accumbens management of pain. 
cycles; indicates to Brizendine why seasonal affective disorder impacts three times more women than men.  Other hormonal events: pregnancy, postpartum depression, premenstrual syndrome is Louann Brizendine's label for of patient's with an extreme form of PMS, who felt undermined by their hormones on some days so that they couldn't work or speak to anyone for fear of bursting into tears or responding angrily.  Their future looked bleak, they hated themselves, and their lives, and the thoughts felt legitimate.  At other times they were engaged, intelligent, productive and optimistic. 
, perimenopause; disrupt the female brain's emotional balance requiring chemical or hormonal rebalancing. 

Brizendine concludes women have different emotional:
This page discusses the interdependence of perception and representation in a complex adaptive system (CAS).  Hofstadter and Mitchell's research with Copycat is reviewed.  The bridging of a node from a network of 'well known' percepts to a new representational instance is discussed as it occurs in biochemistry, in consciousness and abstractly. 
perceptions
, memories; to men, resulting in many misunderstandings.  And she notes each hormonal transition introduces additional possibilities. 

The Mature Female Brain
Brizendine explains that menopausal women, feel that their attitude to the world has changed.  She details one patient who, having spent her prior life supporting needy, self-absorbed people, decided to change everything, including divorcing her husband.  65% of divorces after age 50 are initiated by women.  This was because:
Perimenopause, when for 24 months the ovaries sporadically make estrogen before stopping completely, starting around age 45, can be very traumatic for about 30% of women.  The female brain becomes less receptive to estrogen, initiating a cascade of symptoms: hot flashes indicating estrogen withdrawal has altered the hypothalamus is essential to many instinctive operations of the body.  It can be viewed as the executor of emotion: happiness, sadness, aggression, eroticism and mating, relaying the amygdala's responses to low level sensory signals.  It has many small sub-regions whose main functions are to regulate hunger, thirst, temperature, sexual behavior, parenting, heart rate, blood pressure, sleep cycles, and similar body operations.  Kandel notes it includes a nucleus containing two distinct populations of neurons: one that regulates aggression and one that regulates sex and mating.  At the intersection neurons are active in both.  Depending on the intensity of the stimulus applied to these neurons mating (weak) or aggression (danger) is activated.  This probably contributes to sexual rage and is why some couples derive extra pleasure from sexual experiences following an argument.  The hypothalamus's (paraventricular nucleus) is closely connected to the pituitary which secrets hormones into the bloodstream ( => acth -> adrenal cortex => cortisol (+)->  amygdala & (-)-> hippocampus).  It directly signals area 25. 
's heat-regulating cells, joint pain, altered sex drive from reduced testosterone is a hormone secreted by the testes, ovaries, and adrenal glands, in response to stimulation from the hypothalamic/pituitary/testicular cascade, that makes humans more willing to do what it takes to attain and maintain status, according to Sapolsky.  That means players of the Ultimatum Game, if previously given testosterone can become more generous.  High testosterone in a fetus masculinizes the brain.  Males generate 10 times the amount.  It is the trigger for sexual desire in males and females, stimulating the hypothalamus.  Testosterone's effect is highly socially contextual so it may encourage acts of kindness or aggression (when challenged).  The level of testosterone does not predict which individuals will be aggressive in: Birds, Fish, Mammals including primates.  Genes impact the potency of testosterone by altering the enzymes that: Construct it, Convert it to estrogen, code the androgen receptor.   This androgen receptor includes a variable polyglutamine repeat which alters the sensitivity to the testosterone signal.  The more potent form is associated with boys showing more dramatic 'masculinization' of the cortex.  But the detected genetic influences are small.  Testosterone decreases activity in the prefrontal cortex and its functional coupling to the amygdala while increasing the coupling between the amygdala & the thalamus.  Testosterone shortens the refactory period of amygdaloid & amygdaloid target neurons.  This results in impulsive risk taking and more focus on unfamiliar faces and distrust of them.  Testosterone increases activity in the ventral tegmentum projecting dopamine to enhance place preference.  Winners of fights become more willing to fight in part due to testosterone increasing confidence and optimism and reducing fear and anxiety.  And winning at: Chess, Athletics, Stock trades; induces the BNST to add testosterone receptors increasing its sensitivity to the hormone.  People become overconfident and overly optimistic. 
, anxiety is manifested in the amygdala mediating inhibition of dopamine rewards.  Anxiety disorders are now seen as a related cluster, including PTSD, panic attacks, and phobias.  Major anxiety, is typically episodic, correlated with increased activity in the amygdala, results in elevated glucocorticoids and reduces hippocampal dendrite & spine density.  Some estrogen receptor variants are associated with anxiety in women.  Michael Pollan concludes anxiety is fear of the future.  Sufferers of mild autism often develop anxiety disorders.  Treatments for anxiety differ.  50 to 70% of people with generalized anxiety respond to drugs increasing serotonin concentrations, where there is relief from symptoms: worry, guilt; linked to depression, which are treated with SSRIs (Prozac).  But many fear-related disorders respond better to psychotherapy: psychoanalysis, and intensive CBT. 
, and depression is a debilitating episodic state of extreme sadness, typically beginning in late teens or early twenties. This is accompanied by a lack of energy and emotion, which is facilitated by genetic predisposition - for example genes coding for relatively low serotonin levels, estrogen sensitive CREB-1 gene which increases women's incidence of depression at puberty; and an accumulation of traumatic events.  There is a significant risk of suicide: depression is involved in 50% of the 43,000 suicides in the US, and 15% of people with depression commit suicide.  Depression is the primary cause of disability with about 20 million Americans impacted by depression at any time.  There is evidence of shifts in the sleep/wake cycle in affected individuals (Dec 2015).  The affected person will experience a pathological sense of loss of control, prolonged sadness with feelings of hopelessness, helplessness & worthlessness, irritability, sleep disturbances, loss of appetite, and inability to experience pleasure.  Michael Pollan concludes depression is fear of the past.  It affects 12% of men and 20% of women.  It appears to be associated with androgen deprivation therapy treatment for prostate cancer (Apr 2016).  Chronic stress depletes the nucleus accumbens of dopamine, biasing humans towards depression.  Depression easily leads to following unhealthy pathways: drinking, overeating; which increase the risk of heart disease.   It has been associated with an aging related B12 deficiency (Sep 2016).  During depression, stress mediates inhibition of dopamine signalling.  Both depression and stress activate the adrenal glands' release of cortisol, which will, over the long term, impact the PFC.  There is an association between depression and additional brain regions: Enlarged & more active amygdala, Hippocampal dendrite and spine number reductions & in longer bouts hippocampal volume reductions and memory problems, Dorsal raphe nucleus linked to loneliness, Defective functioning of the hypothalamus undermining appetite and sex drive, Abnormalities of the ACC.  Mayberg notes ACC area 25: serotonin transporters are particularly active in depressed people and lower the serotonin in area 25 impacting the emotion circuit it hubs, inducing bodily sensations that patients can't place or consciously do anything about; and right anterior insula: which normally generates emotions from internal feelings instead feel dead inside; are critical in depression.  Childhood adversity can increase depression risk by linking recollections of uncontrollable situations to overgeneralizations that life will always be terrible and uncontrollable.  Sufferers of mild autism often develop depression.  Treatments include: CBT which works well for cases with below average activity of the right anterior insula (mild and moderate depression), UMHS depression management, deep-brain stimulation of the anterior insula to slow firing of area 25.  Drug treatments are required for cases with above average activity of the right anterior insula.  As of 2010 drug treatments: SSRIs (Prozac), MAO, monoamine reuptake inhibitors; take weeks to facilitate a response & many patients do not respond to the first drug applied, often prolonging the agony.  By 2018, Kandel notes, Ketamine is being tested as a short term treatment, as it acts much faster, reversing the effect of cortisol in stimulating glutamate signalling, and because it reverses the atrophy induced by chronic stress.   Genomic predictions of which treatment will be effective have not been possible because: Not all clinical depressions are the same, a standard definition of drug response is difficult;.  And the brain's response to glucose alters, causing energy surges, as well as cravings for carbs.  The day of maximum fertility drifts unpredictably.  It can be treated with estrogen and an antidepressant or SSRI is a selective serotonin reuptake inhibitor:
  • Is a class of drugs used to treat anxiety and major depression. 
  • These limit reuptake of the modulatory neurotransmitter serotonin into the presynaptic vesicles in effect
  • Increases the level of active serotonin.  But boosting serotonin does not help all patients get better.  And SSRIs increase serotonin levels very rapidly, but people's mood and synaptic connection levels do not alter for weeks. 
  • Use increases the risk of: Suicide in children & adolescents, Osteoporosis, Bleeding by interacting with warfarin & aspirin, problems for patients with severe pre-existing cardiovascular disease. 


For those perimenopausal women whose testosterone drops to near zero, their interest in sex shifts to irritation.  That can precipitate relationship problems, but is treatable with a patch, pill or gel. 

Many women fear their husband's retirement will remove much of their freedom and space.  This fear often leads to stress is a multi-faceted condition reflecting high cortisol levels.  Dr. Robert Sapolsky's studies of baboons indicate that stress helps build readiness for fight or flight.  As these actions occur the levels of cortisol return to the baseline rate.  A stressor is anything that disrupts the regular homeostatic balance.  The stress response is the array of neural and endocrine changes that occur to respond effectively to the crisis and reestablish homeostasis. 
  • The short term response to the stressor
    • activates the amygdala which: Stimulates the brain stem resulting in inhibition of the parasympathetic nervous system and activation of the sympathetic nervous system with the hormones epinephrine and norepinephrine deployed around the body, Activates the PVN which generates a cascade resulting in glucocorticoid secretion to: get energy to the muscles with increased blood pressure for a powerful response.  The brain's acuity and cognition are stimulated.  The immune system is stimulated with beta-endorphin and repair activities curtail.  But when the stressor is
  • long term: loneliness, debt; and no action is necessary, or possible, long term damage ensues.  Damage from such stress may only occur in specific situations: Nuclear families coping with parents moving in.  Sustained stress provides an evolved amplifier of a position of dominance and status.  It is a strategy in female aggression used to limit reproductive competition.  Sustained stress:
    • Stops the frontal cortex from ensuring we do the harder thing, instead substituting amplification of the individual's propensity for risk-taking and impairing risk assessment! 
    • Activates the integration between the thalamus and amygdala. 
      • Acts differently on the amygdala in comparison to the frontal cortex and hippocampus: Stress strengthens the integration between the Amygdala and the hippocampus, making the hippocampus fearful. 
      • BLA & BNST respond with increased BDNF levels and expanded dendrites persistently increasing anxiety and fear conditioning. 
    • Makes it easier to learn a fear association and to consolidate it into long-term memory.  Sustained stress makes it harder to unlearn fear by making the prefrontal cortex inhibit the BLA from learning to break the fear association and weakening the prefrontal cortex's hold over the amygdala.  And glucocorticoids decrease activation of the medial prefrontal cortex during processing of emotional faces.  Accuracy of assessing emotions from faces suffers.  A terrified rat generating lots of glucocorticoids will cause dendrites in the hippocampus to atrophy but when it generates the same amount from excitement of running on a wheel the dendrites expand.  The activation of the amygdala seems to determine how the hippocampus responds. 
    • Depletes the nucleus accumbens of dopamine biasing rats toward social subordination and biasing humans toward depression. 
    • Disrupts working memory by amplifying norepinephrine signalling in the prefrontal cortex and amygdala to prefrontal cortex signalling until they become destructive.  It also desynchronizes activation in different frontal lobe regions impacting shifting of attention.  
    • Increases the risk of autoimmune disease (Jan 2017) 
  • During depression, stress inhibits dopamine signalling.  
  • Strategies for stress reduction include: Mindfulness. 
, worry and failure to sleep facilitates salient memory formation and removal of non-salient memories.  The five different stages of the nightly sleep cycles support different aspects of memory formation.  The sleep stages follow Pre-sleep and include: Stage one characterized by light sleep and lasting 10 minutes, Stage two where theta waves and sleep spindles occur, Stage three and Stage four together represent deep slow-wave sleep (SWS) with delta waves, Stage five is REM sleep; sleep cycles last between 90-110 minutes each and as the night progresses SWS times reduce and REM times increase.   Sleep includes the operation of synapse synthesis and maintenance through DNA based activity including membrane trafficking, synaptic vesicle recycling, myelin structural protein formation and cholesterol and protein synthesis.  Sleep also controls inflammation (Jan 2019)  Sleep deprivation undermines the thalamus & nucleus accumbens management of pain. 
, since they do not see they can renegotiate that agreement.  Brizendine asserts they can and they must do so. 

Post menopausal women can benefit from the positive feedback of a rewarding job.  And they typically enjoy supporting their grandchildren, which can also reduce the stress on the new mother

The shift in hormones alters the brain regions that respond to these signals.  The neurons that depended on estrogen soon shrivel up.  Women who had estrogen replacement therapy soon after removal of their ovaries maintained their memory in the brain includes functionally different types: Declarative, or explicit, (episodic and semantic), Implicit, Procedural, Spatial, Temporal, Verbal; Hebb suggested that glutamate receptive neurons learn by (NMDA channel based) synaptic strengthening: short term memory.  This was shown to happen for explicit memory formation in the hippocampus.  This strengthening is sustained by subsequent LTP.  The non-real-time learning and planning processes operate through consciousness using the working memory structures, and then via sleep, the salient ones are consolidated while the rest are destroyed and garbage collected.   function.  But women who did not have the treatment had declining verbal memory occurs in the sleep supported brain in the prefrontal cortex, premotor cortex, and temporal lobes.  The brain can compensate for sleep deprivation by leveraging the parietal lobes, left middle frontal gyrus and right interrior frontal gyrus. 


The Future of the Female Brain
Brizendine concludes that the 21st century provides an opportunity for women to leverage their new economic power, understanding of their unique biology and control over their bodies to create a new paradigm where a new social contract will take them and their needs into account, for the sake of our children and each woman's future. 



CAS support for the female brain:

The Female Brain is a focused book highlighting key details of women's psychology and framing them with underlying evolution, neuroscience and endocrinology. 






































































.
Market Centric Workshops
The Physics - Politics, Economics & Evolutionary Psychology
Politics, Economics & Evolutionary Psychology

Business Physics
Nature and nurture drive the business eco-system
Human nature
Emerging structure and dynamic forces of adaptation


integrating quality appropriate for each market
 
This page looks at schematic structures and their uses.  It discusses a number of examples:
  • Schematic ideas are recombined in creativity. 
  • Similarly designers take ideas and rules about materials and components and combine them. 
  • Schematic Recipes help to standardize operations. 
  • Modular components are combined into strategies for use in business plans and business models. 

As a working example it presents part of the contents and schematic details from the Adaptive Web Framework (AWF)'s operational plan. 

Finally it includes a section presenting our formal representation of schematic goals. 
Each goal has a series of associated complex adaptive system (CAS) strategy strings. 
These goals plus strings are detailed for various chess and business examples. 
Strategy
| Design |
This page uses an example to illustrate how:
  • A business can gain focus from targeting key customers,
  • Business planning activities performed by the whole organization can build awareness, empowerment and coherence. 
  • A program approach can ensure strategic alignment. 
Program Management
| Home

Profiles | Papers | Glossary | E-mail us