Midterm 2 Flashcards
Hormones and the Endocrine system
Endocrine system tries to solve a lot of the problem similar to the Nervous system -> releases chemical messages that travel to distant targets in the body
Endocrine system has role in development and behaviour
Nervous system tissue oftens governs the way the endocrine system is functioning
The “First” experiment on hormones: Berthold 1849
Loss of function experiment
3 conditions:
Control: let rooster grow up as usual (looks like a rooster -> has large comb and waddles, tries to initiate sex with hens, aggressive, and crows
Remove testes: resembles hen -> has small comb and waddle, does not mount on hens, not aggressive, and weak crows
Remove then reimplant either one of the testes or a donor testes from a different animal
No need to reconnect or rewire -> simply insert in abdominal cavity
The rooster develops normally -> has large comb and waddles, tries to initiate sex with hens, aggressive, and crows
Restoration of function with native or donor testes
Did not require innervation
The “First” experiment on hormones: Berthold 1849
conclusions
Organisational (development appearance) and activational (behavioural) effects
Behavioural effects are not as prominent in humans due to our cortex controlling much of our behaviour
Testes make a “secretory blood-borne chemical”
Some sort of chemical messenger being secreted by the testes and travels through blood to reach its targets
“Hormone” is quite a catch-all
Released primarily by glands (but also other tissues - e.g. stomach- releases ghrelin, heart, kidneys, bones)
Released primarily into the bloodstream to travel far distances (but also locally)
Released primarily by animals (but also plants)
Exocrine vs. endocrine glands
Endocrine glands release hormones into the bloodstream
Exocrine glands releases hormones outside the body
E.g. sweat glands, salivary glands, tear glands
Neurocrine
releases NT chemicals from AP
Endocrine
releases hormones into the bloodstream
Not as targeted - hormones spread out throughout the body
Autocrine
cell releases a signal to itself (autoreceptors at presynaptic cell - negative feedback)
Paracrine
localised chemically in the neighbouring cells; strongest effect on closer cells
The further away the paracrine cell, the effects are weaker as hormones are diffusing out further
Pheromone
secreting chemicals from us to another within species animal
Allomone
secreted by one organism and received by another type of organism
E.g. skunks spraying dogs
Principles of hormone function
- Slow-acting, gradual effects
- Behaviour changes in intensity/probability rather than polarity
- Behaviour and hormone release are reciprocal (behaviour can influence hormone release and hormone release can influence behaviour)
- Multiplicity of action - Hormones have a variety of different targets and effects on varying tissues and varying receptors
- Secretion is often pulsatile and rhythmic
- Hormones can interact - When 2 hormones are released at the same time, the interaction can cause unique effects
- Hormones need receptors! (cf. neurotransmitters)
Receptors are where hormones bind to
Hormones
Slow-acting, gradual effects
changes to behaviour, physiology, biology can be on the order of hours or weeks after hormone entered bloodstream
can be faster - e.g. stress hormones
The hormones must travel through bloodstream
Hormone
Behaviour changes in intensity/probability rather than polarity
Hormonal release can causes fundamental changes to behaviour
BUT more commonly, hormones changes the likelihood of the behaviour happening
OR, the hormones change the intensity of the behaviour
Hormone
Secretion is often pulsatile and rhythmic
Hormones are released in small burst sometimes at specific times (monthly, daily)
Sometimes we try to replace hormones with pills
If given pill exogenously - steady constant amount of hormone which does not mimic natural pulsing or rhythm of endogenous hormone release
Manner of which hormone is released is important
The hypothalamus and neuroendocrine cells
Hypothalamus (HTh): junction between NS and endocrine system
HTh nuclei contains neuroendocrine cells, aka neurosecretory cells
Neuroendocrine cells look like neurons with PSPs, APs, and release signal
They synapse onto the bloodstream rather than other neurons
Some hormones are also neurotransmitters
Some hormones are also neurotransmitters
E.g. epinephrine (adrenaline) and norepinephrine -> both NT and hormone
Some glands release their hormones into the brain where they affect how the neurons function
Some neurons release their chemical messages to affect how glands function
Some chemical messengers can be released by both glands and neurons (adrenaline, noradrenaline)
Norepinephrine is released by both the adrenal gland and the locus coeruleus in the brain stem -> shared evolutionary history
Hormone types
- Peptide (large) - NT
Mostly stuck outside cell - binding to receptors on the membrane
Strings of amino acids- mini protein - Amine (small)
Norepinephrine (noradrenaline)
Epinephrine (adrenaline)
Mostly stuck outside cell
Some can cross plasma membrane to inside of the cell - Steroid
Especially good at crossing the plasma membrane into the cell
Similar structurally to cholesterol
Hormone receptor types
- At the membrane (especially for amine and peptide hormones)
i.e. GPCRs - metabotropic receptors
faster type of the hormone receptors
Can cause effects in transcription and translation but usually a distant target and not common - Intracellular receptor for steroid hormones
usually near nucleus
I.e. usually transcription factor - causes changes to the expression of genes
Steroid (and some types of amines) receptors can bind to hormones and becomes an activated transcription factor
Increases certain proteins to be expressed and decreases certain proteins from being expressed
Slow acting- to build proteins from transcription factors
Note: some steroid hormones can have GPCRs on the PM -> faster effect
Methods in measuring hormones and receptors
- Radioimmunoassay
- Autoradiography
- Immunohistochemistry/immunocytochemistry
- In situ hybridization
Radioimmunoassay
Used to measure hormone levels in the blood
Take a blood sample and increasingly add antibodies to it
The antibodies bind to the hormone -> shows the amount of hormone in blood
Autoradiography
Looking for brain areas affected by the hormone
Take hormone and create a radioactive version of it (radioactively labelled hormone)
Inject radioactive hormone -> radioactive hormone circulates around -> bind to target (similar to PET)
When bound to target, it will stay there for a moment and give off radiation -> put photo paper on the brain slice (something electromagnetically sensitive next to it)
post-mortem
Immunohistochemistry/immunocytochemistry
Create an antibody for the receptor
Antibody binds to hormone receptor (target) -> shows where the receptors are in the tissue
Immunohistochemistry: take section of tissue
Immunocytochemistry: looking at cells grown in a petri dish or taken from an organism
In situ hybridization
Take a complementary strand of RNA (sometimes DNA) and add a fluorescent tag to it
Create a perfectly complementary strand of RNA for the hormone receptor RNA -> add a fluorescent tag that fluoresces when there is a fluorescent light shone on it
Shows where hormone receptor RNA is or where hormone receptor RNA is expressed
Shows activation of transcription or which cells have hormone receptor RNA being expressed
Whenever there are changes to the amount of RNA of interest (amount of hormone receptor RNA) in A CELL -> see changes in fluorescence image
Negative feedback mechanisms
E.g. presynaptic autoreceptors
when too much NT is released, it decreases the amount of NT being released, ensuring not too much NT is being released
Negative feedback mechanisms
Autocrine feedback in our endocrine cells
Hormone is released and sent to target cells
As hormones are released, some will bind to receptors on the endocrine cell that is releasing the hormones -> causes inhibitory effect and reduces the amount of hormone release
Negative feedback mechanisms
Endocrine cells
Endocrine cells release its hormones that reach the target cells -> the change in the target cell elicits a biological response -> in that response, the changes in behaviour causes a reduction in the amount of hormone released from the the endocrine cell
The biological response does not have the inhibit hormone release -> BUT can inhibit the hypothalamus (largely controlling many of the gland functions in your body by interacting with the anterior + posterior pituitary gland) and cause negative feedback by inhibiting hormone release from the endocrine cell
Negative feedback mechanisms
Regulation happens at every level
- presynaptic autoreceptors
- Endocrine cells
- Hippocampus regulating activity in hypothalamus
The pituitary gland
The other side of the NS (hypothalamus-containing neuroendocrine cells)/endocrine intersection (pituitary gland)
Targets of the neuroendocrine cells is often to elicit changes in the pituitary gland
NS and pituitary gland are connected via infundibulum, aka pit. stalk
Anterior and posterior divisions of pituitary gland
They come from different tissue types during development
Real meaningful differences
Play separate roles and separate wiring
Release different hormones
The posterior pituitary receieves from Hth how?
No dedicated endocrine cells in the posterior pituitary gland
Many axons coming from the hypothalamus
HTh has neuroendocrine cells in paraventricular nuclei and supraoptic nuclei
The 2 nuclei have neuroendocrine cells with axons
Axons travel down infundibulum to posterior pituitary
These HTh axons terminate and release hormones on capillaries
These axons release oxytocin and vasopressin/anti-diuretic hormone (ADH) into blood
Oxytocin
stimulate uterine contractions in pregnancy (induce labour- sometimes administered to women to induce labour)
milk letdown reflex (cf. pitocin) - ejects milk into breast ducts
Stimulation of nipple sends sensory signal to the brain and activates the hypothalamus -> causes oxytocin release into the posterior pituitary gland capillaries -> causes milk to be moved from mammary gland cells to breast ducts
anti-diuretic hormone (ADH) + alcohol
when dehydrate, it is released to conservation of water and reduce amount of urination
And causes blood vessel constriction when dehydrated or have too much salt in our system
Alcohol inhibits L-type calcium channels in HTh, which inhibits ADH release
Alcohol makes you urinate more frequently and makes you dehydrated because it blocks the ADH release
The anterior pituitary
Anterior pituitary has its own hormone-producing cells
HTh neuroendocrine cells terminate at median eminence (intersection between the HTh and the infundibulum)
Anterior pituitary gland is controlled by HTh -> HTh release releasing hormones that activated the tropic hormones
Releasing hormones carried (only a few mm) via hypophyseal portal veins (capillaries where they travel to the anterior pituitary)
Glands are controlled by anterior pituitary gland (tropic hormones) -> When releasing hormones arrive, anterior pituitary cells release tropic hormones
Tropic hormones travel to glands to other parts of the body and cause further hormone release -> affects tissue
The anterior pituitary
The common motif:
Releasing hormones (HTh endocrine cells) -> release tropic hormones (activated anterior pituitary gland) -> hormones (activate glands in body) -> cause changes in target tissue
Hormones of the anterior pituitary
Releasing hormones from the neuroendocrine cells of the anterior pituitary (all have RH at end) then to tropic hormones (6 types in anterior pituitary) -> gland in body -> hormone
- CRH (corticotropin-releasing hormone)
- TRH (thyrotropin-releasing hormone)
- GnRH (gonadotropin-releasing hormone) or GnIH (gonadotropin-inhibiting hormone)
- Prolactin-releasing peptide or Prolactin-inhibiting factor (dopamine)
- Somatocrinin (stimulates) or Somatostatin (inhibits)
CRH (corticotropin-releasing hormone)
ACTH (adrenocortico-tropic hormone) -> adrenal cortex -> corticosteroid (including cortisol)
Related to stress, and circadian rhythms (different levels of arousal
TRH (thyrotropin-releasing hormone)
TSH (thyroid-stimulating hormone) -> thyroid -> thyroid hormones
Changes in metabolism
GnRH (gonadotropin-releasing hormone) or GnIH (gonadotropin-inhibiting hormone)
LH (luteinizing hormone) OR, FSH (follicle-stimulating hormone) -> testes OR ovaries -> androgen (testosterone) OR estrogens, progestins
Causes changes in testes or ovaries
Prolactin-releasing peptide or Prolactin-inhibiting factor (dopamine)
Prolactin-releasing peptide or Prolactin-inhibiting factor (dopamine) -> Prolactin -> mammary glands (milk production)
Promotes lactation in female mammals
Promotes parental behaviour in males and females
Somatocrinin (stimulates) or Somatostatin (inhibits)
GH aka somatotropin or somatotropic hormone (growth hormone) -> bones (bone growth)
Affects metabolism and causes cells to grow
Only released while sleeping
Can be inhibited by starvation, intense stress, intense exercise
the adrenal gland
Adrenal cortex (80%) vs. adrenal medulla (20% - inner layer)
Different inputs to cortex (anterior pituitary) vs. medulla (ANS)
Adrenal cortex receives adrenal corticotropic hormone (tropic hormone coming from pituitary)
When ACTH reaches the adrenal cortex - causes the release of corticosteroid hormones
Cannot store these hormones and release it -> must manufacture on demand
Steroid hormones are Synthesized on demand via ACTH
Adrenal medulla (part of sympathetic NS) releases amine hormones
When ACTH reaches the adrenal cortex - causes the release of corticosteroid hormones
Adrenal cortex releases steroid hormones:
Glucocorticoids (e.g. cortisol) Related to stress and circadian function (rhythm) Mineralocorticoids (e.g. aldosterone) -> causes salt and water retention Sex steroids (e.g. androstenedione) -> influence body hair patterns
Adrenal medulla (part of sympathetic NS) releases amine hormones
Epinephrine
Norepinephrine
Two amines above are related to fight or flight response
the thyroid gland
Releases thyroid hormones: thyroxine, triiodothyronine
These are amines but act like steroids (meaning they can cross the membrane)
These thyroid hormones have intracellular receptors and membrane receptors
Regulate growth and metabolism levels
Also has a general activating effect on NS
Meaning, lack of release of thyroid hormones (Hypothyroidism) -> impairments on NS, cognition, alertness, reflexes, mood
Only substance in body that needs iodine (why we need iodine in our diet - e.g. iodized table salt)
Thyroid also releases calcitonin
the pineal gland
aka Your third eye! (Not really)
In reptiles and birds, the pineal gland has some photoreceptors -> measures how long the days are
Pineal gland is in skull but birds have very thin skull so light reaches pineal gland
Releases melatonin
Signal comes from outside of the brain via ganglia that are outside of the brain (sympathetic NS ganglia) -> travels back into the brain and provides inputs to the pineal gland
the pineal gland
Releases melatonin
Melatonin released at night Inputs: from sympathetic NS
Melatonin release goes up in darkness
Melatonin release goes down in light
In other animals, often relationship between melatonin release and gonads
Tracks day/seasons - animals will want to mate in certain seasons
As melatonin release goes up -> gonadotropin releasing hormone goes down -> shrinks gonads
the gonads
Two compartments in male and female gonads:
one for sex hormone production (androgens + estrogens)
one for gametes production
the gonads hormone release
GnRH and/or GnIH (HTh) -> FSH (follicle stimulating hormone) & LH (luteinizing hormone) (anterior pituitary) in bloodstream -> changes to gonads (testes or ovaries) and release sex hormones
And kisspeptin (peptide NT) stimulates GnRH
Peptin especially released during the onset of puberty -> playing a key role in driving the factors that create puberty
Testes:
Sertoli cells (sperm)
Area with Leydig cells (synthesis of androgens, e.g. testosterone)
Ovaries:
Ova (mature gametes)
Steroid hormones (progestins, e.g. progesterone, and estrogens, e.g. estradiol)
Hormones in behaviour
Hormones may have an important organisational role in body in all animals
Important for appearance, physiology, trajectory of development (e.g. puberty)
Yes, BUT bear in mind what we learned in hunger & eating
i.e. Cortex often supersedes/conflicts with many older controls for behaviour
We have systems on top of systems on top of systems that all sort of do the same thing
The highest level of the hierarchy is the cortex
The most vigorous responses are observed in animal models with hormone manipulation
the converse is true: behaviour influences hormones
The most vigorous responses are observed in animal models with hormone manipulation
E.g. iguana
More difficult to get clear relationships between hormonal changes (endocrine system changes) and behaviour
Little easier with stress
Psychosocial dwarfism
Parental neglect, social isolation, intense level of stress inhibits growth hormone released
When children are removed from psychosocial situation -> rapid onset of growth and rebound
behaviour influences hormones
Oxytocin and vasopressin/ADH
- Exogenous oxytocin in rats
- Oxytocin knock-outs in mice
Exogenous oxytocin in rats -> rats spend more times touching each other
Oxytocin knock-outs in mice -> social amnesia, do not recognize other rats they have met - not friendly
Can restore behaviour with oxytocin injection
Oxytocin & vasopressin receptors across brain:
ventral pallidum (VP) -> main target of NAcc - related to motivational circuits and DA There are circuits in this area that change how we socialise with other animals
2 vole species: Prairie voles vs. meadow voles
Behaviourally different
Prairie voles are monogamous
Females have high density of oxytocin receptors in VP
Males have high density of vasopressin receptors in VP
Meadow voles are not monogamous
Much lower levels of oxytocin receptors and vasopressin receptors in VP
the level of oxytocin receptors and vasopressin receptors in the voles brains is directly related to whether they are monogamous or not
blocking oxytocin receptors in mice
In mice, when they are super stressed out, they may be socially anxious
Can help with social anxiety by blocking oxytocin receptors
Blocking oxytocin makes them more social
In humans, there is a relationship between humans childhood history and cocaine addiction and ___ function
oxytocin
Trolley cart problem and oxytocin
decide whether to sacrifice one group or another in order to save more people or one important person
Oxytocin increases in-group bias -> less likely to sacrifice someone from ingroup and more likely to sacrifice someone outside of your group
Only builds love to people in in-group
A neurobiological association of revenge propensity during intergroup conflict
- study purpose
- and they suggest that
integrating functional MRI and measurements of endogenous oxytocin in participants who view an ingroup and an outgroup member’s suffering that is caused mutually (Revenge group) or by a computer (Control group)
we suggest that there may be a neurobiological mechanism that links perceived ingroup pain caused by an outgroup and the propensity to seek revenge upon an outgroup during intergroup conflict
The present work specifically examined the hormonal (i.e., oxytocin) and neural responses to ingroup suffering caused by an outgroup that predict revenge propensity against outgroups.
intergroup conflict encountered by the Revenge group is associated with an …..
increased level of oxytocin in saliva compared to that in the Control group.
the _____ ______ activity in response to ingroup pain in the Revenge group but not in the Control group mediates the association between endogenous oxytocin and the propensity to give painful electric shocks to
medial prefrontal
outgroup members, regardless of whether they were directly involved in the conflict ______ ___ plays a key role in driving economic punishment towards the outgroup
ingroup love
fMRI brain activity in response to ingroup pain
(fMRI) studies have identified increased activity in both the empathy network (e.g., the anterior midcingulate [aMCC] and anterior insula [AI]) and the theory-of-mind network (e.g., the medial prefrontal cortex [mPFC] and the temporoparietal junction [TPJ]) in response to ingroup pain
the mPFC activity in response to perceived pain is associated with decisions to help ingroup members
the activity in the nucleus accumbens predicts decisions not to help outgroup members
if the goal of revenge is to help ingroup members who suffer from physical harm caused by an outgroup
the mPFC, which responds to ingroup pain and is associated with ingroup help may be associated with tendencies to punish the outgroup
Punishment decisions to prevent social norm violations have been associated with increased activities in both the empathy and theory-of-mind networks, including the aMCC, AI, and mPFC
fMRI brain activity in response to outgroup pain
Outgroup pain, on the other hand, is related to enhanced activity in the reward system (e.g., the ventral striatum and nucleus accumbens)
brain regions in both the __________ express OT receptors and as activities in both networks are modulated by administered OT, activities in both networks in response to ingroup members’ pain may be associated with endogenous OT in the context of intergroup conflict that involves physical harm
empathy network and the theory-of-mind network
Our whole-brain analyses revealed that salivary levels of OT were associated with ____ activity in the Revenge group; …
mPFC; an association between endogenous OT and mPFC activity in response to ingroup pain as a neurobiological correlate of revenge propensity during intergroup conflict
Punishment tendencies in Revenge and Control groups
participants in both conditions reported greater tendencies to punish outgroup targets
ingroup favoritism in attitudes, emotions, and punishment tendencies did not differ significantly between the Revenge and Control groups and between the involved and uninvolved targets
Previous research has shown that people tend to view their ingroup members as victims and outgroup members as perpetrators during intergroup conflicts
Participants reported a greater number of painful shocks received by ingroup than by outgroup members, even though Involved_Ingroup and Involved_Outgroup targets actually received the same numbers of painful shocks
endogenous OT in Revenge groups when compared to Control groups
the Revenge (vs. Control) group showed higher endogenous OT levels immediately after the initial conflict was observed, and OT levels continued to rise in response to later intergroup conflict in the revenge condition the level of endogenous OT seemed to begin to rise immediately after participants initially witnessed intergroup conflict the OT level increased further after fMRI scanning during which the participants had more experiences of intergroup conflict empirical evidence that intergroup conflict in primates including humans is associated with increased levels of endogenous OT
Brain responses to perceived pain in the Revenge and Control groups
whole-brain analyses of the contrast of painful vs. neutral expressions revealed activations in both the empathy network, including the anterior cingulate and bilateral AI/inferior frontal gyrus (IFG), and the theory-of-mind network, including the mPFC, left TPJ, and right temporal pole (TP)
Separate whole-brain analyses that collapsed all participants in the Revenge and Control groups identified activations in the mPFC, aMCC, bilateral AI/IFG, and left TPJ in response to ingroup targets’ pain but only in the mPFC in response to outgroup targets’ pain
The results confirmed greater neural responses to ingroup than outgroup targets’ pain in the empathy network, including the left IFG/AI and right IFG/AI but not in the theory-of-mind network (mPFC)
the results provide no evidence for difference in ingroup favoritism in empathic neural responses between the Revenge and Control groups
Endogenous OT predicts mPFC activity in response to ingroup pain
for the Revenge (but not the Control) group, OT level at Time-1 reliably predicted the mPFC activity in response to Involved_Ingroup target’s pain
The results suggest that the association between endogenous OT and mPFC activity was specific to Revenge group
The results suggest a stronger coupling between endogenous OT and mPFC activity in response to Involved_Ingroup (compared to Uninvolved_Ingroup) targets’ pain during intergroup conflict
Association between mPFC activity and revenge propensity
The results of correlation analyses showed that, for the Revenge (but not the Control) group, the mPFC activity in response to Involved_Ingroup targets’ pain positively predicted punishment tendencies toward both Involved_Outgroup and Uninvolved_Outgroup targets
individuals with stronger mPFC activity in response to ingroup pain tended to apply more painful shocks to outgroup members, regardless of whether they were directly involved in the conflict
These results indicate that the mPFC activity in response to ingroup pain caused by an outgroup mediates the association between endogenous OT measured after initially witnessing intergroup conflict and tendencies to retaliate upon outgroup members, regardless of whether they directly brought physical harm to ingroup members
The results of these mediation analyses provide additional evidence for the endogenous-OT/mPFC association as a neurobiological correlate of revenge propensity during intergroup conflict
Discussion: findings suggest that endogenous OT is an influential physiological mechanism in humans that is activated in response to intergroup conflicts that involve physical harm between ingroup and outgroup members.
our results suggest that endogenous OT increases after initially witnessing intergroup conflict
the mPFC activity in response to ingroup pain predicted the propensity for subsequent revenge behavior during intergroup conflict.
The mPFC is well-known for its functional role in representing mental states, social emotion, and group identity
our results suggest that the context of intergroup conflict may shift the key function of the oxytocinergic system from mediating ingroup love (a desire to help the ingroup) to facilitating outgroup hate (an aggressive motivation to hurt the outgroup).
Such variation in the social function of OT may assist individuals to adapt to changing social contexts
Increasing evidence suggests that the oxytocinergic system is involved in modulating multiple social emotions that are either positively or negatively related to social behaviors
We showed that the mPFC activity in response to ingroup pain similarly predicted punishment tendencies toward Involved-Outgroup targets and Uninvolved-Outgroup targets
The mPFC activity also mediated the relationship between endogenous OT and tendency to punish Involved_Outgroup targets as well as Uninvolved_Outgroup targets
the mPFC activity mediates the association between endogenous OT and propensity to seek revenge by giving painful electric shocks to outgroup members.
in a scenario in which an observer punishes transgressors due to social norm violation (i.e., third-party punishment), the willingness to punish severely was associated with increased _____ activity; did not find evidence of an association between _______ activity and punishment tendencies during intergroup conflict
amygdala; amygdala
pheromones: Do they mediate behaviour?
non-human animals
Non-human animals: yes, definitely, via the vomeronasal organ (VNO)
VNO has unique receptors- own proteins different than the receptor proteins in the main olfactory organ
pheromones: Do they mediate behaviour?
in humans
Humans: Not so much
Our VNO and its related genes are basically non-existent (super tiny)
Genes of our pheromone receptors have all become nonfunctional
Over time, when proteins are not used for a long time, mutations can render them nonfunctional
Very vey low likelihood that we are picking up any pheromone activity through our VMO
No similar VMO activity from humans compared to animals
Putative human pheromone effects (McClintock effect, men’s sweat)
often don’t replicate
Synchronising women’s menstrual cycle
Women were asked to smell mens armpit sweat in bag
Women rated individuals with a complementary immune system to the women as highest in smell
Women were more attracted to the smell because if they were to have children, the children would be protected from larger amount of bacteria/viruses
stress hormones: Do they mediate behaviour?
All animals (including humans): yes, definitely BUT part of stress response is central NS (i.e. in the brain) and HPA axis Dual pathways for stress -> causes immediate changes to immediate physiology and changes to brain
Dual pathways for stress
causes immediate changes to immediate physiology and changes to brain
- HPA axis - hypothalamus-pituitary-adrenal cortex: releasing hormones from HTh -> anterior pituitary sends tropic hormones to the adrenal cortex -> release of stress hormones
- Sympathetic NS activates adrenal medulla -> causes releases of adrenaline + noradrenaline
Hippocampus and the HPA axis
Hippocampus provides applies important negative feedback onto the HTh
Normally when stressed, Hippocampus will inhibit the HTh and inhibit HPA axis
Under chronic stress conditions -> hippocampus is one of the places that sufferers worst
Hippocampus dendrites/branches diminish and become smaller (but cells do not die)
Hippocampus sends less negative feedback to hypothalamus
Very small things can feel like very big things
Must interpret stress response and figure out what it means
Schacter & Singer 1962: stress response is interpreted
Experiment to test “new vitamin” (epinephrine)
Had a confederate
Happy confederate -> participant would feel like they are in a stressed good mood
Grumpy confederate -> participant would interpret stress and being annoyed with the confederate
The arousal stimuli must be evaluated and the individual will put the stress into context
Biological sex
can be genetic, anatomical features, and physiological features
Gender identity
typically aligns with sex, but not always
Person’s private subjectively experience of themselves/ sense of gender
Sexual behaviour
sexual acts
seperate from sexual orientation
Sexual orientation
typically heterosexual and more Includes asexuality (>1%; people who report having no strong sexual feelings towards anyone)
Intersex
births are also common (0.1 -2% depending on classification and criteria)
No firm criteris but typically individuals born with several sex characteristics (e.g. someone may have female chromosomes but physiologically or anatomically they resemble male characteristics)
Individuals born with ambiguous genitalia
Corrective surgery - happens in ~1/1000 births
Chromosomes, genes, and sexual organization
Your chromosomes are not your sex although chromosomes are strong predictors of sex
Female body pattern is the default XX
Y chromosome: sex-determining region Y (SRY; aka testes determining factor TDF) gene which expresses SRY protein
SRY protein: transcription factor- binds to a bunch of select genes in genome which leads to pattern of development -> causes testes formation
Testes
release testosterone (T) and anti-Müllerian hormone (AMH) Combination of presence of hormones T + AMH -> cause male phenotype
changes with ___________ (3) can influence development of phenotype
SRY/T/AMH/way testosterone is received
Two different individuals with similar mutations may or may not end up presenting the same in terms of biological sex or gender or sexuality?
Two different individuals with similar mutations may not end up presenting the same in terms of biological sex or gender or sexuality
Ambien (Zolpidem) doses for men vs. women (2013)
Dose in mg/kg -> larger the individual, higher the dose
Metabolism, in general, seems to be a major difference for many drugs
Ambien is metabolised twice as quickly in men compared to women
Ambien -> GABA agonist - increase inhibition in brain, drowsy, sleepy, relaxer
Sex differences in pain and response to pain medication
Increased pain sensitivity is more common in women
Estrogen/progesterone and opioid system interactions
Women would self-administer less pain medication than men
Suggesting that opioids have a stronger effect on women
As menstrual cycle goes through different stage, there are different sensitivities to opioid drugs
Differences in sex are related to meaningful differences in biology, physiology, pathology
- Ambien (Zolpidem) doses for men vs. women (2013)
- Sex differences in pain and response to pain medication
- Sex differences in acute and chronic stress (Liisa Galea’s)
- Women are more likely to develop depression, Alzheimer’s disease, lung cancers
- Men are more likely to have addiction, commit suicide, or develop Parkinson’s disease
Do androgens and estrogens mediate behaviour?
- Non-human animals (e.g. reptiles):
- Humans:
Non-human animals (e.g. reptiles): sexual hormones do mediate behaviour
e.g. iguanas will set up their territoriality by doing push up contests
Territoriality is strongest in october
Sexual behaviour is most present in october
October is when testosterone is most present
Testosterone levels correlates with aggression and territoriality in animals
Humans: at least somewhat
Rats and humans: Are Individual differences in male sexual activity determined by differences in androgen levels?
Rats and humans: Individual differences in male sexual activity are not determined by differences in androgen levels
Loss of function: remove testes -> strongly reduce sexual behaviours in male rats
Do not need to fully replace testes to restore sexual behaviour -> Only needs a small amount of testosterone for male sexual behaviour to be restored
Having more testosterone doesn’t necessarily correlate with more sexual behaviour
Some testosterone needed for men’s sexual interest
e.g. loss of function case studies
men had prostate cancer and had their prostate removed
These men may get testosterone supplemental therapy -> does not need much testosterone for sexual behaviours to reemerge
Amount of testosterone does not correspond with their lobido (sex drive)
Testosterone and estrogens in women sexual interest
modest effects
Post-menopausal women -> estrogen therapy or mild testosterone therapy will lead to a modest small increase in sexual activity in women but not alot
Need a baseline amount of sex hormones for sexual behaviours to emerge
Not a linear correlation for the amount of sex hormones and the sexual actvity
Weak evidence of vicarious victory in human males
E.g. vicarious victory studies
Higher levels of Testosterone in saliva after your team wins
Lower levels of testosterone after your team losing
E.g. on the night that obama won
- Decrease in testosterone levels in people who were voting republican
Gendered behaviours
Gendered behaviours are certainly present almost immediately in childhood, BUT differentiating social from biological (developmental pattern) influences on behaviour is challenging
There are changes in behaviour between male and female babies
Boys and girls will have slight differences in cognitive capabilities, interest in different objects in the environment
Studies done on how we interact with kids
Boys tend to be more physically held or wrestled with as babies
Girls tend to be talked to/at more and more gentle
Boys and girls are treated different as babies/children and are socialised to wear certain thing, play with certain toys, etc
Observable sex differences in cognitive abilities
(small differences but reliably found across studies)
Men tend to have a slight advantage in tasks related to spatial rotation or mental rotation
Men tend to be slightly better at paper folding tasks, embedded images (looking for images in images), and target throwing tasks
Women tend to be better at perceptual tasks (identifying what’s different or the same)
Women tend to be better at fine motor control, verbal fluency, and visual memory
Homosexuality (relatively normal in animal kingdom) is reported in ~__ of species
450
Men: some evidence for hypothalamic differences in homosexuality
Homosexuality (relatively normal in animal kingdom) is reported in ~450 of species
Men: some evidence for hypothalamic differences in homosexuality
Rats: the preoptic area
Humans: INAH-3 (SDN- sexually diamorphic nucleus) of the preoptic area -> set of nuclei in the hypothalamus
Tend to be slight differences in heterosexual and homosexual men -> homosexual males have smaller SDN (but heavily overlap and not a huge difference)
Studies done post mortem at end of AIDS epidemic
Homosexuality in men also related to fraternal birth order effect
For every additional older brother a male has, 1/3 increase in likelihood of homosexuality
Number of female siblings does not matter
Potentially related to womens androgen insensitivity from having multiple male babies who expose her to androgens repeatedly -> lead child to have slightly different patterns of development
But Androgens do not easily line up with sexual behaviur/orientation so phenomenon is not well understood
Women: some indirect evidence for higher fetal androgen exposure for homosexual women
may have lead to sexual orientation changes
Often reported: 2D:4D finger digit ratio will be different in homosexual women and heterosexual women -> suggest higher levels of androgen exposure but not concrete evidence
Sex hormones are steroid
crosses the membranes easily; intracellular receptors for testosterone
Someone who has applied testosterone cream around another person can expose that person to more testosterone
Emotions are ambiguous without ____;
context; Emotions are often portrayed as categorical but emotions can be very ambiguous
emotions cloud judgement
T or F?
Loss of function experiment by lesion of emotion producing regions cause judgement impairment outcomes
Emotions vs. logic, emotions vs. reason, emotions rational?
(decision that benefits organism)
Emotions are be valuable in guiding our rationality
But emotions play a big role in our decision making machinery
Darwins, James: emotions selected for not against
Emotions are seen all throughout mammalian lineage -> evolutionary fitness benefit from emotions
Perhaps that evolutionary benefit was applicable before but not now in term so of evolution
Are Emotions separate from cognition?
Most of 20th c: understudied due to emphasis and focus in cognition
Many studies that did start to look at emotions were from classical and operant conditioning perspectives for emotions
Mr. Spock
Mr. spock from star trek is supposed to be an individual who is very smart because he can turn off his emotions and think and make decisions logically -> but we see that without emotion, decision-making is greatly impaired
Defining emotions
Some hypotheses/assumption/principles
- Emotions are all processes that involve the assessment of value
- Emotions help us seek pleasure and avoid discomfort -> Pleasure is not entirely biological relevant
- Emotions influence our behaviour
- Emotions are adaptive
- Emotions can be considered an intervening variable between stimulus response
- Emotions can be conscious but aren’t always easily consciously identified
- Emotions are comprised of subjective, physiological (sympathetic NS), expressive (face expression and body language), and behavioural changes
Emotions are all processes that involve the assessment of value
Emotions are often directed towards something (thing, organism)
If something is value neutral (has no value to us), it is unlikely to have a strong emotional experience to it
Emotions influence our behaviour
Emotions manifests in many different ways -> behavioural effect is flexible
Choosing particular behaviour based on context
We have emotions not just to feel something but because it shapes our subsequent behaviour
Emotions are adaptive
Some sort of evolutionary benefit
Emotions played a valuable role in being an animal in the world
E.g. rats laugh/squeal when they are tickled -> adaptive value to emotions
Emotions can be considered an intervening variable between stimulus response
Lots of Sensory info and other info coming in
Lots of motor output
Emotions modifies, integrates output
Emotions can be conscious but aren’t always easily consciously identified
Overlapping similarities between certain emotions although they are categorically different
Our emotional experience and conscious identification of what we are feeling is one of the things we learn across the lifespan
Just because there are lots of words for all these emotions does not mean we can experience them, just means that we have a more sophisticated interpretation of the world
Many people believe that emotions are constructed, understanding of emotions is based on life experience and context
Or we can be feeling something which influences how we act in our context but we may not know exactly what that feeling is
Emotions are comprised of subjective, physiological (sympathetic NS), expressive (face expression and body language), and behavioural changes
Must have biological and behavioural evidence to capture all the different sophisticated aspects of emotions
Many consider the subjective factor of emotion to be the essential factor of emotion but in terms of behavioural neuroscience other factors are important when studying emotion
Operationalizing emotions
Physiological
SCR (skin conductance response- sweat/skin pore behaviour); ECG; other autonomic measures (pupil dilation, heart rate)
These physiological measures are useful but not enough to indicate a certain emotion
Physiological response influence the way we interpret emotions
Operationalizing emotions
Expressive
EMG (electromyogram -> measuring muscle contractions in face)
coding of facial expressions and body language
sorting images - coded facial expressions can be sorted into files/categories of emotions
Expressions of emotions are much stronger in social settings
Operationalizing emotions
Subjective
self-report; brain activity (EEG, fMRI); measure behaviour
Socially inappropriate contexts tend to be inaccurate measurements of subjective self-report
There is a level of social permissibility for some emotions vs. others
Happiness self-reports tend to be quite accurate
Anger (especially in women) are less socially permissible -> less accurate self-report measures
Operationalizing emotions
Behavioural
startle response; decision making (based on different emotions); social interactions; vocal content/tone (words, pitch and volume of voice with certain emotions)
Operationalizing emotions
Cognitive
tests of memory under different emotions, perception, attention, decision making
Classic cognitive psychology tests with some sort of experimental condition either inducing or neutral emotions
Operationalizing emotions
Neural
functional neuroimaging, loss/gain of function studies
Lesion certain areas in the brain which are important for expression or subjective experience and see how it changes the animals’ outcome behaviour
Operationalizing emotions (6)
- Physiological
- Expressive
- Subjective
- Behavioural
- cognitive
- neural
Studies on fairness in non-human animals
The monkey got angry because the 2 monkeys were paid unequally (one given cucumber and one given grapes for the same task)
Monkey is willing to throw away its cucumber to show its anger to encourage a change in researchers behaviour to receive a grape instead
Anger is not about aggression but about encouraging fairness
The ultimatum game
2 players: Proposer (1) and Responder (2)
The proposer is asked to split up money however they see fit for how much goes to themselves and how much goes to the other player
The responder can simply accept the offer or reject the offer
If they reject the offer, neither of the players get any money
Economical perspective
The rational thing for the proposer to do is take the maximal amount of money they can and give the other person as little as possible
The responder to accept every single offer because any amount of money is better than nothing at all
Results of The ultimatum game
When it’s a fair split, everyone accepts the split
But as the split becomes less fair, responders are less likely to accept the split
When receiving $1 as opposed to $9 for the proposer, the responder is rejecting the offer more than 60% of the time
Willing to sacrifice money to punish the other player
Responder rejects the offer because over the long term, we want to tell people that unjust behaviour will not be tolerated -> encourage fairness over the long term
In the long term, encouraging fairness at a cost of receiving nothing will benefit them in the future as well as other interacting with the person
Anger, where you pay a cost to make someone’s behaviour) better guides behaviour toward altruism because you are paying a cost to ensure others benefit from it over the long term
Anger directed at an entity (mostly)
Angry behaviour corresponded with SCR (skin conductance response - measures sweating, how open pores are), self report, brain activity
Anger directed at an entity (mostly)
Participants behaviour changes when told they are playing with a computer
As the split becomes more and more unfair the acceptance rate goes slightly down
Participants accept at a much higher rate for the computer than another person because they do not think the computer is badly behaving rather merely an algorithm
Frustration
most likely to occur when you are very close to winning but fail at the last minute
Usually, emotions guide us toward beneficial behaviours (i.e. increase our fitness)
E.g. frustration -> supposed to be motivationally invigorating to work harder to achieve near success - signal that we are getting close to success usually
Frustration and gambling
This sense of frustration is manipulated or sometimes used to exploit us
e.g. gambling -> get the same sense of frustration without actually getting any closer
Slot machine: it may feel subjectively that you are getting closer to success when in reality you are not close to winning
we occasionally misapply our emotions (behaviourally speaking)
Near misses feel bad but spur further play
Much stronger for after vs. before the payline of slot machine
Decorticate animals and “sham rage”
Hypothalamus still connected to midbrain, hindbrain, spinal cord
Exaggerated response or version of anger that is prolonged time (upwards of an hour or more)
Sham rage elicited by stimuli in the environment
Normally these behaviours are inhibited - modulatory effect from the cortex on to the responses of the hypothalamus
When cortex is no longer connected to diencephalon, midbrain, hindbrain (decorticate animals) then the hypothalamus is free to have these exaggerated responses
Suggested that the hypothalamus plays a critical in some time of emotional responses
Hypothalamus is important for a variety of…
interpersonal or social behaviours (e.g. aggression, bonding, mating)
There are a variety of types of aggression driven by different parts of your hypothalamus
Some aggression can be emotional
Some aggression can be instrumental
Klüver-Bucy Syndrome
emerges when an animal specifically when an animal’s anterior temporal lobe has been removed commonly done in nonhuman primates
Typically primates are afraid of a lot of things: snakes, humans, etc
When the anterior temporal lobe is removed, they are happy to interact with snakes and inspect humans
Amygdala - in anterior temporal lobe that is related to the expression of fear or fear related behaviours
Not the only part involved in fear and amygdala is involved in a variety of other behaviours, cognitions, learning, etc
These animals also tended to be hyperoral (investigate many things with their mouths) which may be because some of their visual regions have been damaged
These animals also had an intense indiscriminate hypersexuality towards animals and inanimate objects
The Papez Circuit
aka the Limbic “System” (not system)
amygdala, HTh, mammillary body, hippocampus, fornix, cingulate cortex, septum, olfactory bulb
All of these regions are on the border of the thalamus (“limbic”)
Some of these areas do communicate with one another but many have strong connections that are independent of limbic system
strong connections to nucleus accumbens and frontal cortex
Papez studied animals who had rabies with a variety of symptoms -> difficult time drinking (hydrophobia), fever, intense aggression, emotional dysregulation
Rabid animals had damage to a lot of the limbic system structures
HTh may play a disproportionately large role in this
Papez thought thought the limbic system were involved in emotional and emotional motivation
Neural: distinct yet overlapping areas for emotions
In most studies, emotion does not involve one anatomical region
Subjective experience with often be more cortical in nature
Subcortical regions are more involved in emotional learning, emotional behaviour, emotional expression
Although there are many overlapping areas for different emotions, emotions are referred to mostly categorically
Some areas have disproportionately large activity in relation to one emotion vs. another
Lots of overlap with non-emotional functions (especially as regards decision making, learning)
Amygdala
the “fear centre” - learning and expressing fears
But the subjective experience of fear is more cortical in nature
Insula
disgust and anger centre
interoception (knowledge of internal states/viscera), gustation (taste/sensation of eating)
Anterior cingulate cortex (ACC)
pain, anguish, frustration decision making (esp. Higher activity with decision conflict, cost-benefit decision-making, two similar/hard decisions), error monitoring (paying attention to own performance and seeing how you did is governed by ACC)
Orbitofrontal cortex, aka vmPFC
many emotions are related to activity in these areas
No, not exactly, but some patterns
Orbitofrontal cortex is not the same as vmPFC but they overlap
No 1:1 region:function
Emotions expressed differently in different contexts generating a different circuit
E.g. anger towards one stimuli is different from another
Different brain areas for different aspects of the same emotions
One emotion will have different brain areas (for behaviours, or subjective emotion, etc.)
Neural: emotional priming suggests circuitry
Implies a “two-track” mind
Using an emotional stimulus to change someone’s appraisal or someone’s interaction with the world
After priming, the researchers asked them questions -> simply showed a series of faces and were asked to rate the faces
When primed with pleasant image, we will rate those faces higher
When primed with unpleasant/aversive image, we will rate those faces lower
These results suggest that there is emotional processes involved -> influences our conscious appraisal of things
Priming is influences our conscious appraisals -> there is a strong faster route that is below the level of consciousness
Priming
present a cue for a short amount of time (< 20 msec for visual things), the cue will not be consciously perceived at all
Emotional priming duration
Emotional priming effects are very short lived -> priming cannot be used to elicit any long term changes
LeDoux’s fear conditioning experiment
Skinner box -> first day expose to box (habituation)
Unconditioned stimulus: electric shock
Conditioned stimulus (CS+): everytime a tone is played, the grid will provide an electric shock -> tone is predicting that a shock is coming
Animal learns that whenever a tone is present, the shock is coming
Control stimulus (CS-): must have other types of tones that play that do not predict an electric shock
Trial: present tone without shock -> animal freezes when tone goes off as they predict a shock is coming
Acquisition: interfere with the process of learning
Expression: Inferfere with the expression of the learning
Amygdala is a complicated region with a lot of subregions but primarily talking about
lateral amygdala (LA) and the central amygdala (CE)
Lesion Lateral Amygdala
impairs learning of fear conditioning (aquisition)
Animals will have difficulty learning the association between a tone and a stimulus
Coincidence detector centre
Amygdala is working as coincidence detector centre (that two stimuli are presented at the same time- fear conditioning)
Animal is learning information about a tone (auditory information) -> sound comes in through ears travelling along vestibular cochlear nerve into brain and auditory thalamus to the auditory cortex and into the LA
Shock information is somatosensory info -> from skin travels in from afferent nerves from body, travels to somatosensory thalamus to the somatosensory cortex (postcentral gyrus)
Shock info does not have the be learned -> will already cause a series of responses/outputs from the amygdala -> changes in the hypothalamus, periaquaductal grey
Ledoux said that when somatosensory and auditory information comes in at the same time or immediately subsequently -> amygdala learns to be afraid of the tone and the shock
High road to fear
going from sensory information through the thalamus, through the cortex and finally to the amygdala -> amygdala outputs causes changes to our behaviour, physiology (e.g. hormonal release), sympathetic NS
We often do not have conscious experience of the things that are shaping your emotional experience -> suggests there must be some pathway going outside of the cortex
Low road to fear
auditory thalamus also sends info (axon collateral) that goes directly to the amygdala
Somatosensory thalamus also sends info directly to the amygdala
Information coming from the world does not have to travel through the cortex -> can go from thalamus directly to the amygdala
Lower road is much faster and not require any conscious processing
Happens for very briefly presented events (priming)
Very little perceptual processing has occurred, stimuli discriminations is very poor and not as sophisticated
damage to the auditory or somatosensory cortex
If you damage the auditory or somatosensory cortex, you can still learn basic fear conditioning BUT if the CS+ and the CS- stimuli are very similar, the thalamus cannot discriminate between those stimuli and will send fear response for both stimuli which requires high road processing to discriminate
fearful faces shown very briefly, even if they’re masked by noise
Pictures of eyes that are scared look and happy eyes
Fearful eyes or fearful images were associate with increased activity in the left amygdala
Artificial stimulation (electrodes) of amygdala in humans
Increased vigilance, attention, anxiety/fear
Can induce heightened sense of awareness which can manifest as anxiety/fear
amygdala is important for fear learning but not for the ___
conscious experience of fear
PTSD and amygdala
Enhanced amygdala activation to fearful vs. happy faces in PTSD patients
Heightened fear responses or startle reflexes often generalized to experiences that wouldnt cause fearful experience
Patient SM
the woman with contained damage to amygdala (urbacvic disease - causes specific lesion by calcification) experienced no fear
She is incapable of experiencing fear subjectively, physiologically, behaviourally
Remarkably poor job of identifying scared faces and some other faces
They showed her a series of scary movies and noticed she basically had no fear for any of them compared to controls
Researchers have exposed her to normally scary situations -> she will respond with interest, curiosity, or excitement but no sense of fear
SM has been exposed to a variety of unfortunate situations in her life -> she’s been robbed at gunpoint and knifepoint multiple times, a number of domestic situations
She is incapable of judging the trustworthiness of a face
Lack of fear has led her into unnecessarily dangerous situations
She has no sense of personal space but understands that others need it
When did paitent SM feel fear
the amygdala circuit is not strictly necessary to experience fear
Patient SM: CO2 exposure -> feeling of suffication -> patient SM felt an intense sense of panic for the first time and removed the helmet
Subjective experiences of fear will be manifested in the cortex
Some rat and non-human primate studies -> amygdala and fear
Amygdala (specifically LA) necessary for acquisition but not expression of fear
Do not need amygdala to experience fear but maybe the amygdala normally triggered a pattern of activity in the cortex to subjectively experience fear
Central amygdala seems to be important for expression (necessary)
Temporarily deactivating the amygdala changes how animals make their choices
Risk based decision making
choosing between small & sure reward, and large yet riskier award
As the high reward option gets riskier and risker, the animal will steer more towards the small & sure option
When you inactivate the amygdala - they become risk averse
Temporarily deactivating the amygdala changes how animals make their choices
Effort-based decision-making
small easy to obtain reward and a reward that requires more physical effort (more lever presses)
With inactivation of the amygdala, the animal no longer willing to spend the same amount of effort in order to get the larger reward
which brain area is important for stimulus-value associations
amygdala appears to be critical for many stimulus-value associations (cost-benefit decision-making) -> associating inherent value to a given stimuli
Primate and rodent electrophysiology experiments -> putting electrodes in animals’ brain and seeing how it fires
amygdala
Amygdala is not negatively valenced for something that is primarily interested in fear
Some of the amygdala neurons are firing specifically for fearful or aversive stimuli but nearly the same amount of neurons are firing to positively valenced stimuli
Some of the amygdala neurons are firing for both positively and negatively valenced stimuli
damage to the amygdala and value assignment
Critical for learning and updating value, continuing to learn as the value changes
E.g. damage to the amygdala causes blunting of sensory specific satiety -> animals continue to eat the same food for much longer than controls
Updating of the value of sensory specific satiety seems to be driven by the amygdala
Patient NK - lesioning due to stroke in their insula and the basal ganglia
Great difficulty in recognizing faces and disgust
Insula and basal ganglia may be associated with the processing of disgust
Huntington’s disease - related to basal ganglia
damage to striatal neurons in the indirect pathway
HD patients often have difficulty detecting disgust in facial expressions
The ultimatum game - insula
The ultimatum game (think you are playing against human when in reality you are playing against a computer - task is to accept or reject the money split offers as offers become increasingly unfair)
Activity in the insula correlate with rejecting offers in the ultimatum game
As the likelihood of rejecting offers get higher, there is higher insula activity
slot machine game - insula
slot machine game (induces artificial feeling of frustration) - near miss effect
Anterior insula’s bold levels are correlated with frustration (feeling of almost succeeding)
Disgust is often implicated in the amygdala as well, specifically related to disgusting images
the anterior cingulate cortex
- Ultimatum Game
- Slot Machine Task
Whereas physical pain is experienced due to somatosensory information, ACC is more interested in physical pain and pain as an abstract concept (social pain - social exclusion, existential pain - imagine what you are gonna do for the rest of your life)
The Ultimatum Game ->Activity in ACC somewhat correlated with rejecting the unfair offers
Slot Machine Task -> near misses vs. full misses would cause increased ACC activity
insula, basal ganglia, and ACC have numerous other non-emotional functions
perception, decision-making, aspects of cognition in relation to decisions -> emotions are linked to cognition/decision-making/motivation
Neural: the story of aggression and the brain
(Aggression is related to emotion but not an emotion)
Aggression often linked to anger in studies
Stimulate different parts of the hypothalamus and see different types of aggression emerge -> different nuclei in different parts of the HTh that are responsible for different types of aggression
Types of aggression
- Predatory aggression
- Affective aggression
Affective aggression
aggression driven by emotion -> often for show, often a lot of communication
Ventromedial / Medial HTh, PAG
Stimulation of Ventromedial / Medial HTh -> affective aggression emerges
PAG (periaqueductal grey) is one of the main targets of the amygdala
High ANS response - high levels of sympathetic NS activity
showy - yelling, hissing, growling, threatening postures and vocalisations
Predatory aggression
Not emotional in nature -> it is instrumental => animal seeking out prey and attacking/killing it
If an animal is being predatorily aggressive -> they are aiming to kill (needs food)
Lateral HTh, MFB (medial forebrain bundle), VTA
Lateral HTh stimulation -> see predatory aggression
MFB: bundle of axons travelling from the VTA to the NAcc (dopamine - motivated behaviours)
Androgens related to aggression
unclear role in humans
Emergence of aggression in certain seasons in nonhuman animals
Aggression and testosterone does not have a strong linear correlation in humans
Bilateral amygdalectomy
- in animals
- in humans
Bilateral amygdalectomy reduces aggression and fear in virtually all kinds of animals -> people have suggested to remove amygdala in aggressive animals but moral questions involved
How about human amygdalectomy for humans with disorders of aggression -> we currently do not remove brain regions for people who are not struggling with epilepsy or seizures
Small but significant benefits in that way but draw backs (mortality rate: 4%, complication rate: >40%)
evidence for the relationship between aggression and low serotonin levels
When serotonin levels dip below a certain threshold, observe increased aggression
5,7-DHT lesions in rodents -> specifically damages serotonergic neurons
These rats become extremely aggressive and scary
Drugs that block serotonin synthesis - block enzymatic step to convert serotonin precursor (tryptophan) into serotonin in the brain -> lowers serotonin and increases aggression
Aggression levels in monkey colonies
Most aggressive monkeys in the monkey colonies have the lowest level of serotonin
Serotonin receptor knock-out mice - knocking out serotonin signalling -> increase aggrssion
Serotonin depletion studies in humans -> by tryptophan depletion -> increases aggression in computer games
Actual r of serotonin and aggression is weak, though (r ~ -0.12; Duke et al. 2013)
Serotonergic projections to PFC, HTh, other limbic structures - wide variety of areas
Stress
Can be significant life events (e.g. death of a loved one, marriage)
But also “the daily grind”, lives of “quiet desperation”
Can be active or passive, short-term or long-term
Stress immunization — i.e. exposure to controllable stress
cf. exposure to uncontrollable stress
Sympathetic response HPA axis
Degree of stress relates to degree of ______ __________
stress response
Acute stress
- drawbacks
- benefits
Stress is an adaptive response to threat!
Benefits: implicit memory, simple tasks, habitual and well-rehearsed tasks
Costs: cognitive flexibility, working memory, executive functions
the PFC & “executive functions”
Planning Organization Flexible thinking Monitoring performance Multi-tasking Solving unusual problems Self-awareness Learning rules Social behaviour Decision making Motivation Initiating appropriate behaviour Inhibiting inappropriate behaviour Regulating emotions Concentrating
Chronic stress
Chronic stress is real bad
Compromises immune functioning
Compromises mental health
Reduces hippocampal volume (dendritic branching)
Increases PFC catecholamines (NE, DA), decreases PFC function, decreases PFC dendritic spines
Reduces performance on hippocampal- or PFC-dependent tasks
Impairs decision making
Stress, catecholamines, and the PFC
Behavioural observations: stress impairs working memory, attention (sort of), planning, etc.
BUT stress improves habitual behaviour
We also see PFC inhibition and amygdala/basal ganglia/HTh activation
bilateral vmPFC damage
Commonly studied: vmPFC (OFC) damage
But executive dysfunction can happen from a variety of PFC damage
Commonly studied: bilateral damage, as it’s more commonly observed in patients
Most intellectual ability preserved
Problems with prioritization (e.g. lost in the filing cabinet)
Emotional dysregulation
Repeat mistakes despite often “knowing” it’s suboptimal
Loss of “get up and go”
Problems thinking ahead, sequencing steps for a task
Rigidity in thoughts and actions
Problems with attention and concentration
The chronic stress of poverty
An implication of modern society: people are poor because they are bad decision makers
BUT Poverty, in and of itself, reduces IQ by ~13 points
Exposure to irregular reward intervals guides even individuals with high baseline self-control to act impulsively
Poverty affects executive functions and cost/benefit decision making
Poverty disproportionately affects children and their brains
poverty is chronic exposure to uncontrollable stress -> effect on brain?
“The evidence indicates that poverty causes stress and negative affective states which in turn may lead to short-sighted and risk-averse decision-making, possibly by limiting attention and favouring habitual behaviors at the expense of goal-directed ones.”
Shifting from executive function driven by long term goals to dealing with the short term and the immediate when the PFC is quieter and the basal ganglia, HTh, and amygdala can take over more functions
Concluding thoughts on emotions
Emotions are complex in their manifestation and their underlying neurobiological structures
Emotions are clearly linked to value and motivation, and guide our actions
Impairments in emotion impair our ability to navigate the world -> from Dysregulation of the amygdala, HTh, or PFC
Why emotions have different qualities than other cognitions is unclear
Cognitions are uniform and do not have “colour”
Emotions are linked to cognition but they have a quality/”colour” to them
While some emotion categories seem relatively universal, others seem less so
Impairments to emotion impair our ability to successfully navigate our world
Concluding thoughts on stress
Stress is a beneficial adaptation that is maladaptively triggered in contemporary society
While acute stress is beneficial, chronic stress is severely detrimental, especially in its effects on the PFC and hippocampu
Organisms are blended with these rhythms
Rhythms can be behavioral, physiological, and biochemical
Sleep rhythms, season -> organized
Rhythms extend to culture -> weeks, calender
Zeitgeber
a cue that an organism uses to synchronize with its environment (German for “time-giver” - e.g. light)
shifting of circadian rhythm
Process of shifting rhythm (e.g., synchronizing with a zeitgeber)
Primary zeitgeber for a circadian rhythm: sun, life cycle
This results in organisms who are:
Diurnal—active during the light
Nocturnal—active during the dark
Period
Time between two similar points of successive cycles (e.g., every 24-hours for a sleep-wake cycle)
Phase shift
Shift in periodic activity due to a synchronizing stimulus, such as light or food
E.g. jet-lag
Free-running
Organism maintaining its own cycle without external - endogenous clocks drive circadian rhythm
Ultradian Rhythms
Occur more than once a day e.g. food
Circadian Rhythms
Occur about once per day e.g. sleep
Slightly more than 24-hours, causing a rightward shift in data
Human free-run is ~25 hours
25 hours, but this was based off older research
Modern findings suggest 24.2 ± 16 minutes
No good explanation for deviation but given the small discrepancy from 24 and limited sample size it could just be sampling error.
Infradian Rhythms
Occur less than once a day
Experimental measurement of circadian rhythms with hamsters
Compare activity from successive 24-hour periods to evaluate characteristics of circadian rhythm
Measure rodent activity as wheel rotation
Manipulate presence of light to see how it affects activity
Consistent nocturnal bouts of activity (most rodents are nocturnal)
Rodent is entrained to the light zeitgeber
Pre-dark activity suggests endogenous prediction of cycle
Rodents are more active in the dark (black line)
When darkness period shifts, rodent behavior adapts
This is a phase shift, where entrainment is shifted
Constant light removes the zeitgeber functionality of light
Can no longer organize behavior, physiology, and biochemistry around light cycles
Periodic activity continues, but now as free-running periods without external cues
Evidence of endogenous rhythm, or biological clock
Biological Circadian Clock
In mammals, circadian rhythms are maintained by the suprachiasmatic nucleus (SCN)
Located in the hypothalamus, above the optic chiasm
SCN neurons can maintain electrical activity synchronized to the previous light cycle
SCN electrical activity is an embodiment of entrainment to a zeitgeber
Suprachiasmatic Nucleus (SCN)
Part of the retinohypothalamic pathway
Specialized, intrinsically photosensitive retinal ganglion cells (ipRGCs) project to the SCN
Retinal ganglion cells (RGC): cells in the retina above the photoreceptor and receive light info from rods and cones and create a composite signal and transfer to the brain
Make up ~1% of total RGCs
Express melanopsin, which is slowly excited by light (response latencies up to ~1 minute after they receive light energy)
Consider what this would mean for if these were used in vision
Invariant to rod and cone activity - melanopsin does all the light sensing by itself as ipRGCs are intrinsically photosensitive
Melanopsin is especially sensitive to blue light
Electronic screens produce large amount of blue light -> can entrain yourself to sleep later
Amphibian pineal gland
Amphibian pineal gland is sensitive to light via parietal eye instead of having SCN
Their pineal gland retains great structural homology with retina
They have a third eye on top of their heads that directly connects to the pineal gland
SCN lesions
SCN lesions disrupt circadian rhythm
With intact SCN, entrained circadian rhythms appear normal
Following SCN lesion, activity becomes significantly more disorganised
They are active and inactive all over the place
Entrainment still in play (still more activity in the dark), but significantly impaired
With light zeitgeber removed and free-running online, disruption of endogenous circadian rhythm becomes apparent
It is apartment and the SCN is integral for the endogenous circadian rhythm
SCN transplants transfer circadian rhythm
Circadian rhythm begins normal
Following SCN lesion, the activity becomes significantly more disorganized
Receive SCN transplant from rodent with a shorter circadian period (called a tau mutation)
Tau dysregulates structural plasticity of the small ventral lateral circadian pacemaker neurons by disrupting the temporal cytoskeletal remodeling of its dorsal axonal projections and by inducing a slight increase in the cytoplasmic accumulation of core clock proteins
Tau knockout = less sleep, or shorter cycles
tau appears to regulate circadian rhythms by modulating the correct operation and connectivity of core circadian networks and related behavior
Following delay period, transplanted circadian rhythm is expressed during Free-running
Great evidence that SCN is the endogenous driver of circadian rhythm
how does the SNC encode circadian rhythms?
The molecular clock of SCN
SCN cells in mammals produce two unique proteins:
Clock
Cycle
Clock and cycle proteins bind together to form a dimer (molecule of multiple components)
Clock/cycle dimer promotes transcription of two genes:
Period (per)
Cryptochrome (cry)
Per and cry proteins then dimerize to create a compositie protein
Per/cry protein complex enters nucleus and inhibits transcription of more per/cry genes
Negative transcriptional feedback loop -> more of the per/cry protein in creates less of the transcription of it
No new per/cry proteins are made until the blocking per/cry proteins degrade
Degradation Cycle takes about 24 hours in humans
Light-induced ipRGC activation releases glutamate onto the SCN
Glutamate promotes increased transcription of per gene
This shifts the phase of the molecular clock -> entrains SCN
Human 24-hour cycle
In morning, transcription of per and cry genes begins
During the day, per/cry mRNA is translated into per and cry proteins, which then dimerize
At night, per/cry dimers begin to enter the nucleus and inhibit the transcription of per/cry genes
Overnight, the per/cry proteins degrade
Sleep
the inactive portion of circadian rhythms -> but still very active
Electroencephalography (EEG)
records electrical activity in the brain
Measures neuronal electrical fields
Excitatory post-synaptic potentials/inhibitory post-synaptic potentials
Measuring neurons specifically in vertical orientation
EEG is not picking up horizontal neurons because the positive and negative ions will cancel each other out
EEG is sensitive to specific orientation of neurons
NOT action potentials
Too short, go in too many directions relative to cortical surface, and are less synchronized
More specifically, measures synchronized electrical fields of neural populations
If there was only one neuron, EEG would not pick it up
EEG is picking up large populations of neurons in the same pattern of EPSP or IPSP
This manifests as electrical oscillations, or ‘brain waves’
Electro-oculography (EOG)
records eye movements by electricity they produce
Electromyography (EMG)
records muscle activity
Multiple frequency bands with different rates of ociliation
Gamma: 32-100Hz Alpha: 8-13 Hz Beta: 13-32 Hz Delta: 05-4Hz Theta: 4-8 Hz
Example whole-brain EEG data
notice this activity is composed of different frequencies -> we can perform frequency decomposition
Decompose whole-brain EEG data into frequency bands
These frequency bands often correlate with particular cognitive states and processes
Neural rhythms coordinate activity of brain systems
Synchronizing oscillations may allow for information to be bound into more unified wholes (e.g., percepts- synchronication of acitivty of neurons allows for holistic perception of anything)
Sleep can be dissociated into classes
Non-REM sleep (NREM)
Rapid-eye-movement sleep (REM)
Sleep can be dissociated into stages
NREM 1
NREM 2
NREM 3-4
REM
LREM Can dissociate in terms of: - Phenomenology - Electrophysiology - Neurochemistry- NT and neuromodulatory states
Non-REM sleep (NREM)
can be divided into three stages and is characterized by lack of rapid eye movements
Rapid-eye-movement sleep (REM)
characterized by small-amplitude, fast-EEG waves, no postural tension, and rapid eye movements
NREM 1 (sleep onset)
Transition out of wakefulness
Heart rate slows, muscle tension decreases, eyes roll about
Diminishing control over thought processes
Falling sensations occur here
Decreasing alpha power (8-13 Hz)
Appearance of theta ripples (4-8 Hz)
Medial temporal lobe; hippocampal
Vertex spikes -> Function unclear
Sharp wave
Incomplete spindles
Synchronized activation of neurons of the Thalamocortical loops
NREM 1 is characterized by a turning on of neural systems of sleep
NREM 2
Diminished probability of dreaming Theta wave dominant (4-8 Hz) Complete spindles Thalamocortical circuits fully synchronous with each other - exchanging info Waves of 12-14 Hz that appear in bundles K-complexes appear Sharp negative EEG potentials Function unclear; perhaps related to stabilizing NREM 2, or creating brief cortical ‘OFF’ states (decrease waiting of synaptic connections in the brain for new synapses to form)
NREM 3-4
(Slow-wave sleep; SWS)
Lowest probability of dreaming or other experiential cognitive activity (half thoughts, motor jumps, but not full blown sequences)
Consistent with the deactivation of major brain networks implicated in thought, and various subcortical structures
Most difficult to awake from ->‘Anesthetic-esque’
Large-amplitude, slow waves called delta waves (0.5-4 Hz)
And slower non-delta waves (~ 0.1 Hz)
Hippocampal sharp-wave ripples (80-140 Hz)
‘transfer info from hipp. to neocortex’
Spindles continue -> Thalamocortical loops
REM
Muscles are relaxed—flaccid and unresponsive
Active EEG with small-amplitude, high-frequency waves, like an awake person
Increased theta and beta band activity
Not really alpha because there is no sensory information coming up to normal hierarchies of processing
Paradoxical sleep—waking-like brain activity, no muscle activity
Highest probability of dreaming
Pronounced sensorial vividness and narrative organization
No more bizarre than waking - we artificially inflate the value or perceived spontaneity of our dreaming thoughts
Typical night of sleep for young adult
Awake -> 1 -> 3 -> 2 -> REM -> 2 -> 3 -> 2 -> REM -> brief awakening -> 1 -> 2 -> 3 -> 2 -> REM -> 1 -> 2 -> brief awakening -> 1 -> 2 -> REM -> 2 -> REM -> awake
7-8 hour duration
45-50% is NREM 2
Cycles last 90-110 minutes
Earlier cycles feature more NREM 3/4 SWS
Later cycles feature more REM - remember dreams in the morning
Wont take much to push into waking from REM as it is close to waking brain activity
Stress makes it harder to fall asleep
Differences in sleep across species
Across-species differences provide clues about the evolution and functions of sleep
Nearly all mammals display both NREM and REM sleep
Birds do too
‘Sleep-like’ states in insects, fish, amphibians, plants
Marine mammals do not exhibit REM sleep
Relaxed muscles incompatible with need for air
In dolphins and birds, only one hemisphere enters SWS at a time, while the other remains awake
Enables continued movement
The predominance of counter-clockwise swimming during rest in Northern Hemisphere dolphins
VS. Predominance of clockwise swimming during rest in southern Hemisphere dolphins
explanations:
- Magnetic field
No conclusive evidence of magnetic sense in dolphins - Coriolis force (earth rotation affecting fluid)
Counter-intuitive: dolphins swimming against rotational currents of their respective hemisphere
Sleep conserves energy
Period of reduced muscular tension, heart rate, blood pressure, temperature, and rate of respiration
Among plant-eaters, small animals sleep more than large ones, in correlation with their normal, high metabolic rate
Reduced energy usage
As the animal gets heavier, they sleep less
When you weight less, they sleep much more
If you need food constantly, cannot store much food -> sleep more
High metabolic rate is taxing on body so you want to avoid using being highly metabolizing all the time
No such correlation in predatory species
Sleep enforces niche adaptation
Avoid predators by sleeping during time of day when most vulnerable
E.g., rodents being nocturnal
Being nocturnal or diurnal is part of an organism’s ecological niche
The benefits and challenges with the sleep patterns of different animals
Sleep restores the body and brain
Replenish metabolic requirements, such as proteins
Most growth hormone is released during SWS
Growth hormone involved in growth and repair (e.g. after exercise)
Pause high waste generation of wakefulness
Greater waste clearance than wakefulness
Waste clearance – Glymphatic system
Fluid-transport system that accesses all regions of the brain
Clears waste from the metabolically active brain
Occurs in extracellular (spaces between cell bodies) and perivascular spaces (space around capillaries and blood vessels which is encapulated by glial cells)
Through an exchange of cerebrospinal fluid (CSF; made in ventricles) and interstitial fluid (ISF; fluid in extracellular space)
Glymphatic waste clearance during sleep
Glymphatic system is most active during sleep
Extracellular space expanded by about ~ 60%
Neural activity elicits local changes in blood volume through lagged neurovascular coupling
When neurons fire, they must be replenished
a lot of nutrients is carried to the blood stream
Lag: blood flow slower than the neural activity
Increased blood volume displaces CSF by increases pressure which pushes CSF out, thereby ‘flushing’ the brain of waste-filled ISF due to increase in extracellular space (i.e., CSF and blood flow are anticorrelated)
Flushed down into the body where the lymph nodes
Done due to vascular response to neural activity
This flushing is tied to when the multiple frequency bands all line up during sleep
Basis for fMRI research
Glymphatic waste clearance during sleep
blood oxygenation level dependent (BOLD) signal - lag hemodynamic response to neural activity through measuring how H+ ions change
Sleep promotes memory consolidation
Hippocampal indexing theory
Sleep facilitates reactivation of cortical-hippocampal neural ensembles
NREM SWS appears more important than REM for memory consolidation -> when the memory odor is present during NREM SWS, there is better consolidation
* = hippocampal reactivations during NREM SWS are more likely to undergo reactivation during REM, where they may be elaborated into a dream/longer sensorial sequence
Hippocampal indexing theory
indexes associated corical activity with an experiences saves the memory
Binds synchronized activation of cortical neurons to bind the different features of memory
Over time memory becomes long term and the info is transferred to other regions of the brain
Sleep (esp. REM) promotes neurocognitive development
REM provides nervous system with unique stimulation
Alpha band decreases in power during sleep; alpha bands characterize the normal sensory hierarchy processing
During sleep, entering novel hierarchical arrangement of functional relationships
When young, sleep is super important for developing new avenues of activity that do not hace opportunities to occur when awake
REM provides unique stimulations for the strengthenig of those relationships
Habitual napping duration is positively associated with hippocampal volume in young children (4-6 yr olds)
napping and hippocampus in children
Habitual napping duration is positively associated with hippocampal volume in young children (4-6 yr olds)
The more you nap at 4-6 years old, the bigger the hippocampal volume
Amount of REM during naps correlates with performance on object-label association tasks that were encoded before sleep
In children REM is more important with memory function
Are dreams an ‘intensified form of mind-wandering’?
Mind-wandering
Dreaming is supported by brain networks that also support waking thought/imagination
In this sense, dreaming may appear to be a certain style of thinking
Dreaming is plotted where there is low deliberate constraints, but low to high automatic constraints
Intensified: immersive and largely uncontrollable -> Feel distinctly unlike waking thoughts
Mind-wandering
a special case of spontaneous thought that tends to be more-deliberately constrained than dreaming, but less-deliberately constrained than creative thinking and goal-directed thought
Is dreaming a spontaneous thought process? ≠ Do spontaneous thoughts occur in dreams?
If dreaming is thinking, then that means I am incapable for thoughts to arrive during dreams (dreaming of thinking) because that would require the same neural systems to be mediating it
May be worthwhile to distinguish between thoughts and dreams while appreciating their somewhat overlapping mechanisms
Thinking in a dream is usually closest to waking because that would push you into wakefulness
Dreaming is mostly a constant experience and not often experiencing perceptions of thoughts arising
Lucid REM (LREM)
Dreams where self-reflection, voluntary control, and other characteristics of waking become associated with subjective experience -> Dreamer is aware of being asleep
‘False’ LREM: Experience of incorrectly concluding oneself is awake in a dream
LREM is a very rare and very precarious neurocognitive state
Precarious: has a complex configuration of enabling conditions, such that if the dependencies are altered the process stops -> easy to awake
Hybrid state: lucidity occurs with features of both REM and waking
Hybrid state of LREM
This hybridity appears especially related to the function of control networks involved in deliberate/voluntary cognition
Cannot fully constrain thoughts around goals of dream
LREM is very similar to awaking cognition and its neurophysiological signature
During dreamless sleep, the cortex is somewhat isolated into distinct modular units - there is not all frequency bands that connecting everything together
During REM, you move toward more interconnected cortex
To reach REM sleep, there must be a shift in brain activity in direction of waking
Induction of self-awareness in dreams through frontal low current stimulation of gamma activity
Can induce LREM by inducing certain frequency bands when in REM sleep
Measure when someone is going into REM sleep by tracking them
Electrode current stimulation at 40 HZ over their frontal cortex -> increases power of 40 Hz oscillations in the brain
That increase is associated with people’s reports of LREM when waking them after
Induce gamma band when in REM to induce lucid dreaming
So does beta band, but with reduced effect size
REM Sleep Eye Movements
73–86% of REM sleep is devoid of/does not actually have REMs
Eye movements during stimulus encoding and retrieval are associated with improved performance on various memory tasks
Eye movements and memory processes have a deep connection
Consider how your eyes move when thinking
‘Movement in representational space’
REM-locked BOLD activation in left SMA
SMA – “planning, internally guided”
Scanning dream scene, but also generating dream conten
Generating – why should content dream exist if not attended to?
*Same can be said for external perception – why should high-quality perceptual contents exist if unattended to?
Why do dream narratives and contents sometimes align with waking?
e.g. needing to pee during REM
Consider this decision process in the REM sleep context
Salience of urinary pressure promotes wakeful brain state
Salience network; network switchboard theory
Default networks -> control networks
Fits with notion of control network-related REM hybridity and instability
Are the altered dream narrative and contents (i.e,. alarm sound) the decision process manifesting in REM sleep?
Physiological signal for the need to urinate gets sent to the same systems during wakefulness to influence decision making when brain is in a stable state of dreaming, having its own neurocognitive dynamics
That physiological signal is incorporated into the ongoing neurodynamic which manifests into the dream content which serves as the decision process of whether to attend to the stimulus
OR, The process of waking up influences the dream activity
new research trying to answer: Does narrative change play a causal role in initiating waking, or is it driven by other waking processes? Both? Or epiphenomenal?
