PSY493H1 Lecture Notes - Lecture 8: Opioid Antagonist, Ventromedial Prefrontal Cortex, Striatum

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School
Department
Course
Emotional construction
Emotions are socially constructed, depending on the cultures, country or groups
-
Psychological constructivism
Core affect
Neurophysiological state that comprises pleasure or displeasure and can
include arousal (high or low), believed to be the building blocks for
emotional experience
-
Conceptualization
Psychological elaboration and core affect result in the phenomenological
state of emotional feeling
-
Building blocks of emotion
Reward network
VTW, Amygdala, VMPFC, ventral striatum
-
-
Neural circuitry of reward
The brain's reward circuit
Orbitofrontal (OFC) and ventromedial prefrontal cortex (vmPFC)
Engaged by pleasing stimuli, maternal love
§
Ventral striatum and nucleus accumbens (NAc)
Drugs of addiction, food, sex, social reward
§
Ventral tegmental area (VTA)
Main brainstem nucleus where dopamine (DA) is synthesized
Innervates many cortical and subcortical areas
§
-
The nucleus accumbens: brain's pleasure centre
Rich in dopamine and opioid neurotransmitters receptors
-
Evidence that it's central to experiencing hedonia, positive affect and incentive
salience
Increase in activation and DA and opioid release when eating pleasurable
food
-
Depressed patients asked to maintain positive affect don’t show sustained
activity in NAc like controls do
Depressed patients have reduced activity in nucleus accumbens
-
Wanting vs. Liking
Activation of opioid receptors, but not dopamine receptors enhance the
gustatory value of sucrose in rats as indexed by behavioural reactions
-
In people, opioid antagonists reduce hedonic value of smells and food
consumption
Enjoy food and smell less, won't eat as much food
-
Opiate addicts perceive increase pleasantness to sweetness compared to
controls and this can be reversed with opioid antagonists
-
In drug addiction, the urge to take a drug (wanting) persists even though the
hedonic experience (liking) may be greatly diminished
Down regulation of u-opioid receptors in addiction and in obesity and
binge-eating disorder
-
-
Dopamine
The central to wanting
DA activation in the NAc motivates approach to rewards and potentiates
wanting, results in seeking behaviours for rewarding stimulus
Facilitates a variety of approach-oriented behaviours
Exploration, affiliation, aggression, sexual behaviour
§
Lesions to the NAc reduce the motivation to work for reward
In a gambling task, the anticipation of rewards activated the NAc and
medial prefrontal
-
Activation of Dopamine network potential rewards in our environment
-
Opioids
The central to liking
Liking is involved in the consummation and enjoyment of rewards
Opiates are released by lactation, nursing, sexual activity, maternal and
social interaction, touch, heroin, exercise
In contrast to DA, it produces a pleasant calmness like after a Thanksgiving
meal
-
What about social rewards?
Reward centres are also activated when people think about being in love
or give money to charity
-
Rewards and attachment - dopamine
DA and opioids are essential for affiliative bonding (oxytocin and vasopressin also
important)
-
Affiliative cues like smiles and gestures serve as incentive stimuli; they motivate
approach-related tendencies served by dopamine
-
These cues trigger dopamine which promotes actions that bring individuals
together
-
Rewards and attachment - opioids
We are very tuned to social interaction
-
Affiliative behaviours like touch and soothing vocalization elicit the release of
opiates and feelings of warmth and calm intimacy
-
When opiates are blocked in juvenile rats, they spend less time with their
mothers after separation
-
Human females given opioid antagonist spend more time alone, less time with
friends an enjoy social interactions less
-
Pain network
PAG, dACC (anterior cingulate cortex), Thalamus, Insula, somatosensory cortex
-
Nociception (pain processing)
Different domains
Sensory-discriminative domain involves detecting where noxious stimulus
is located and how intense it is (PAG and more posterior ACC)
Affective-motivational domain involves the affective component of pain
and is associated with valence (pleasant-unpleasant) distinctions (more
anterior ACC, particularly subgenual)
-
Anterior insula is also involved in its role in sensory coding, body state
assessment , and autonomic regulation
-
Periaqueductal gray: brain's pain center
Appears to be involved in 3 different processes related to emotion
Involved in the release of opioids
Inhibits ascending pain signals before they reach the cortex (e.g.
ACC): allows the escape from threat before attending to injuries
i.
1.
Activated by pain and negative valence images
Participants showed increase activation in the PAG in response to
thermal pain as well as viewing distressing slides
i.
2.
Involved in caregiving system in the mammalian brain
Studies in non-human mammals show that nurturant behaviours like
crouching over pups, licking and prolonged nursing engage the PAG
i.
In humans, OFC and PAG are highly engaged when viewing silent
video clips of their own children crying or smiling
ii.
3.
-
PAG id rich in vasopressin and oxytocin receptors -> PAG and OFC important for
maternal caregiving
-
PAG also responsible for species-typical defensive behaviours '
-
building blocks of emotions
Emotions can be seen to arise from these fundamental aspects of pleasure and
pain
-
Emotion responses and tendencies aid in our survival in numerous ways
-
They become more sophisticated and socially embedded in many context
-
Selfish genes
Emotions are genes' way of making sure thy are passes on
Fear ensures we flee from danger
Disgust ensures we don't eat hazardous foods
Love ensures we have interest in sex and child rearing
-
Many emotional reactions stem from ancestral action tendencies (e.g. motor
habits, startle response, defensive aggression)
-
If emotions serve an evolutionary purpose they should also be seen among other
animals
-
Genetic Influence
Our emotions derive from neural processes that generate instinctual emotional
behaviour in animals
-
Identified action tendencies seen in mammals
Seeking, fear, rage, lust, care, panic & play
Evolved to become quite elaborate in humans through evolution
-
Hypersociality
Like other mammals, we are dependent on others from birth
-
Unlike primates, we live in very large societies that generate culture
-
Human emotions are embedded in complex social contexts
-
Emotional evolution
Humans are only obligated bipedal primates
-
Evolutionary adaptations in bipedalism resulted in anatomical changes that
mostly likely shaped the evolution of human emotion
-
Cranial size and smaller birth canals -> shorter gestational lengths
-
Altriciality would require more social cohesiveness and pair bonding to ensure
survival of species
Rich emotions and social motivations developed
Altricial - like human
Precocial -horse, giraffe (once born, don’t really need care, can walk)
-
Affective Neuroscience
Jaak Panksepp
Primary-emotion systems of RAGE, FEAR, LUST, CARE, SEEKING,
PANIC/GRIEF, PLAY. Also the SELF
Associated with specific brain networks revealed by brain stimulation
studies of emotion
Suggest evolutionarily homologous experiences across different species
of mammals
Rats like to be tickled
§
Not all anxiety is the same (fear of predator attack vs. anxiety of maternal
separation)
Separation anxiety is only quelled with opiates whereas
benzodiazepines won't calm an animal separated from its mother
§
Not all aggression is the same (predatory vs. agitated)
Prefatory aggression: stalking, quiet biting attacks
Rats would repeatedly self-stimulate this area (related to
SEEKING)
§
Agitated aggression: tail wagging, irritated movements
Rats will press level to escape brain simulation of area
§
-
In rats, only have primary empathy: instincts (hypothalamus) but us humans have
highest mind functions for thinking and planning ( basal ganglia, amygdala, nucleus
accumbens, neocortex)
Rough-and -tumble play as an avenue for developing empathy
-
How does the use of psychostimulus to treat ADHD affect executive development?
All of the medications used to treat ADHD are trying to increase the activity
of these two neurotransmitters by triggering their increased release, by slowing
their reuptake or by mimicking their effect and by doing so increasing the
activity of the parts of the brain that are underactive.
-
Components of Empathy
Mentalizing, cognitive empathy, perspective taking, theory of mind
-
Prosocial concern, empathic motivation, sympathy, empathic concern
-
Experience sharing, affective empathy, shared self-other representations,
emotional contagion
-
Overlapping regions
Theory of Mind (ToM)
The ability to attribute mental states to yourself and others, and the
understanding that others' mental states are different from your own
-
Engages some similar and some different networks from empathy
Medial prefrontal cortex
Precuneus
Temporoparietal junction (TPJ)
-
Empathy in the brain
Different types of empathy: affective and cognitive
-
Affective empathy: anterior insula and medial cingulate cortex related to self-
reports of empathy
-
Cognitive empathy (affective ToM): related to understanding others' affective
states, mentalizing
Areas are the same of ToM but also involved more affective areas like
amygdala and vmPFC
-
Mirror Neurons
Simulation is the representation of another's motor actions, emotions,
cognitions etc. by activating those corresponding processes in oneself
However many studies do not show the key mirror neuron areas (i.e.
inferior frontal gyrus (IFG), inferior parietal lobule (IPL)) being active in
empathy
-
Simulation may be involved in empathy, but perhaps not a central process
-
What is empathy?
Our ability to simulate and read each others' mental states and feel what
others feel is, in many ways, what makes us human and is central to social life
-
Empathy in the Brain
Seeing someone else in pain doesn't make us feel the exact pain
-
Pain matrix
Activated during physical pain
PFC, anterior cingulate cortex (ACC)
Insula, amygdala, thalamus
Periacqueductal Grey (PAG)
Primary (S1) and secondary somatosensory cortex (S2)
Posterior parietal cortex (received input from S1 and S2 for planned
movement)
-
Empathy and pain (Singer 2014)
fMRI of 16 couples (female scanned)
-
Determine pain threshold for each couple before experiment
-
Electrodes placed on right hand of both people
-
Male partners seated next to scanner, mirror displayed view both hands
-
Cues for painful and non-painful conditions for self and other
-
After scan, measure individual differences in self-reported pain intensity rating
and general empathetic concern with 2 empathy questionnaires
-
Result
Findings show the importance of anterior cingulate cortex (ACC) and
anterior insular cortices for empathic experience related to pain
ACC can respond not only when a person receives a painful stimulus but
also when a person observes or anticipates a potentially painful stimulus
delivered
Anterior insular regions: anticipation of pain, more affective
(arousal, anxiety)
-
Posterior insular regions: experience of pain, more sensory related
-
These areas are not involved in the mirror neuron system
-
Results suggests a segregation of sensory-discriminative and autonomic-
affective attributes of the pain experience
ACC and AI appear to reflect the emotional experience that evokes our
reactions to pain and underlies neural basis for understanding our own
feelings and those of others
Social pain in the brain
How does social pain engage cortical processes?
Grief when a loved one passes away, betrayed by romantic partner,
separation from parents, getting into fights with friends
Research suggests that the dorsal region of the ACC is the mind's
'alarm system' that something bad happened
-
-
Social exclusion ball-toss game
Virtual confederates throw ball to participants, and then ppts can throw it
back to either 'confederate'
Manipulation
Inclusion condition: ball thrown to ppt 50% of time
Exclusion condition: ball thrown to ppt 8% of time
-
After scan, asked to complete a social distress questionnaire related
to how excluded they felt during the task
-
Then reported momentary social distress over the next 10 days
-
Also completed questions about end-of-day feelings of social
disconnectedness
Observed in dACC, amygdala and PAG
-
Cortical and subcortical involvement
MPFC: social considerations
-
Hippocampus: memory consolidation
-
Activation in areas involved in memory consolidation and self and social
cognition predicted feelings of social distress and disconnection over the
next 10 days
People with greater dACC, amygdala and PAG response to simulated social
rejection reported experiencing greater levels of momentary social distress
in their daily social interactions
The correspondence of momentary social distress and end-of-day
feelings of disconnectedness were associated with greater activation
in hippocampus and MPFC areas
-
Suggesting that people who are more sensitive to even simulated
social rejection also experience more social rejection in their daily
life
-
-
With human evolution, social connection became so important that social
rejection recruited the use of ancient pain regions for more social purposes
Much of our neural circuitry has been scaffolded upon the importance of
social inclusion and harmony
-
Emotional extensions
Self-referential emotions (pride, shame, guilt) are more culturally constructed,
directly embody cultural norms, and have less strongly hardwired circuitry than
survival-oriented negative emotions (fear, anger)
-
Intermediate emotions, such as disgust have not only hardwired origins but also
'moral" extensions
-
Moral transgressions "leave a bad taste in the mouth"
-
EMG recordings of facial expressions associated with:
Ingested beverages (sweet, bitter / salty, water)
Shown complex visual stimuli: (disgusting, sad, neutral)
Then played a game related to fairness
Levator labii is controlled by facial cranial nerve (CN 7)
-
-
Ultimatum Game
2 players split $10: the proposer makes offer on how money will be split,
responder can accept or reject. If accept, money split is proposed. If reject,
neither player receives anything
-
Ranged from 'fair' (5:5 split) to very 'unfair' (9:1 split)
Independent variables
Manipulation of moral disgust: ULTIMATUM GAME OFFERS
-
Dependent variables
EMG
-
Self-reported emotional state
-
-
Emotional extensions
Disgust was the most endorsed emotion during unfair offers
-
However, anger and sadness also increased as a function of unfairness but the
Levator labii did not.
-
Disgust is unique
Only disgust was significantly correlated with levator labii activation
-
Only self-reported disgust following unfairness correlated with elevation of
levator labii
-
Feelings of disgust were best predictor of decision making. Feelings of disgust
result in irrational economic choices
-
Epigenetics
A mechanisms of gene regulation that is independent of DNA sequence that
determines which genes are expresses (switch on or off)
These epigenetic expressions can manifest in:
Certain cell types
-
Particular diseases (e.g. cancer, addiction)
-
Or in behavioural response patterns
-
These epigenetic effects can be passed on and or mediated by
environmental factors
-
Epigenetic mechanisms are affected by
Development in utero
Environmental chemicals
Drugs
Aging
Diet
-
Two modifications
Active chromatin (euchromatin) Closed chromatin (heterochromatin)
Acetylated histone tail
-
Unmethylated cytosine
Designates transcription
-
Methylated histone tail
-
Methylated cytosine
-
Chromatin and Histones
Gene "switched on"
Active (open) chromatin
Unmethylated cytosines (white circles)
Acetylated histones
-
Gene "switched off"
Silent (condensed) chromatin
Methylated cytosines (red circle)
Deacetylated histones
-
Epigenetic & Behaviour
Environmental factors such as early developmental adversity and the type of
parental caregiving can permanently alter the genome via epigenetic
mechanisms (i.e. histone acetylation and DNA methylation)
-
These mechanisms change gene transcription, thus altering biochemical and
behavioural patterns (e.g. learning and memory, addiction, mental illnesses),
which persists through the lifespan and can be passes on to offspring
-
Developmental sensitivity
Sensitive time windows in development relate to neural plasticity circuit growth
and neuronal migration. Disruptions in neural development in these windows
can cause permanent deficits in the lifespan of the animal
-
Monocular deprivation
Kittens has one of their eyes sewn shut
Drastic deficits in V1 ocular columns that never recovered function for
visual processing
-
Epigenetics in development
Post-natal development in rats
Maternal behaviour in sensitive time windows changes chromatin
structure
High LG-ABN mothers: lots of nurturing behaviour (licking, grooming and
arched-back nursing)
Low LG-ABN mothers: much less nurturing, caregiving behaviours
Adult rats raised by high LG-ABN mothers grew up to have decreased
stress responses and less fear in novel situations compared to rats raised
by low LG-ABN mothers
-
Hypothalamic-pituitary-adrenal axis (HPA axis)
Hypothalamus -> anterior pituitary -> adrenal cortex
-
-
Stress
Stress is beneficial in short term
Boosts learning & memory, and immune system, arousal and energy levels
-
Chronic stress is disastrous
Immune suppression, disruptions in glucose signaling, appetite, sleep,
learning & memory
Inhibits neurogenesis , causes dendritic retraction, granule cell death from
neurotoxicity (mainly in hippocampus)
-
HPA-axis modification in caregiving
These behavioral change in rats pups related to better maternal caregiving were
found to also include alterations of the HPA-axis
↑hippocampal glucocorticoid receptor (GR) expression (moderates stress
response by inhibiting HPA activation)
↓ corticotropin releasing hormone (CRH) expression
↑ glucocorticoid feedback sensitivity (less activation due to negative
feedback)
-
Epigenetics of caregiving
These HPA-axis modifications were related to epigenetic changes
DNA methylation of glucocorticoid receptors (GR) in hippocampus
Adult rats raised by LG-ABN moms had fewer hippocampal GR DNA
methylation and more histone acetylation than the low LG-ABN raised
rates (more hippocampal feedback to inhibit hypothalamus)
But could this be related to being raised in more nurturant ways
throughout development and not related to early sensitive times periods?
Cross-fostering experiments showed that it was the mothers
caregiving during the critical post-natal period were related to these
changes
-
-
Beyond the HPA-axis
Childhood abuse is related to numerous deleterious outcomes (e.g. cognitive
dysfunction, psychopathologies, autonomic dysregulation, and volumetric
changes in brain areas (e.g. PFC, amygdala, hippocampus)
-
Evidence suggests that abuse early in life causes alterations in neural functioning
related to plasticity and wiring
-
Brain-derived neurotropic factor (BDNF)
Involved in many neuronal processes including synaptogenesis,
neurogenesis, synapse stability, glutamatergic, NMDA receptor and
GABAergic signaling
-
Epigenetics of abuse
Expose infant rats to 1 of 3 conditions
Abusive caregiver
Nurturing care-giver
Home cage with normal littermates
-
For 1st week of life, they were put in 1 of these conditions for 30 mins daily then
returned to normal home cage
-
Infant maltreatment was related to BDNF methylation (gene silencing) in PFC
that lasted into adulthood
-
Causal link
They then looked at if this gene silencing in PFC could be altered via
neurochemical infusions that disrupt methylation
-
Adult rats maltreated as infants were given intracranial infusions of a DNA
methylation inhibitor, which reversed the DNA methylation and associated gene
transcription effects
-
These epigenetic changes, though stable, are potentially malleable with target
interventions
-
What kind of caregivers are female rats who were abused as infants>
Rat moms who were abused as pups showed these behaviours to their own pups
-
Rat moms who were not abused as pups showed these behaviours to their own
Maybe these changes are due to the postnatal environment and not the
kind of mom they came from.
Try cross-fostering
-
-
-
Epigenetic transmission
What kind of caregivers are female rats who were abused as infants?
Showed similar rated of abusive behaviours towards their offspring that
they endured as infants
-
Are these epigenetic effects passed on down the germ line?
Yes, offspring of maltreated female adult rats showes
↑ methylation of BDNF DNA in PFC and hippocampus compared to
offspring born of non-maltreated females
-
-
Lecture 8
Monday, June 11, 2018
3:59 PM
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Emotional construction
Emotions are socially constructed, depending on the cultures, country or groups
-
Psychological constructivism
Core affect
Neurophysiological state that comprises pleasure or displeasure and can
include arousal (high or low), believed to be the building blocks for
emotional experience
-
Conceptualization
Psychological elaboration and core affect result in the phenomenological
state of emotional feeling
-
Building blocks of emotion
Reward network
VTW, Amygdala, VMPFC, ventral striatum
-
-
Neural circuitry of reward
The brain's reward circuit
Orbitofrontal (OFC) and ventromedial prefrontal cortex (vmPFC)
Engaged by pleasing stimuli, maternal love
Ventral striatum and nucleus accumbens (NAc)
Drugs of addiction, food, sex, social reward
Ventral tegmental area (VTA)
Main brainstem nucleus where dopamine (DA) is synthesized
Innervates many cortical and subcortical areas
-
The nucleus accumbens: brain's pleasure centre
Rich in dopamine and opioid neurotransmitters receptors
-
Evidence that it's central to experiencing hedonia, positive affect and incentive
salience
Increase in activation and DA and opioid release when eating pleasurable
food
-
Depressed patients asked to maintain positive affect don’t show sustained
activity in NAc like controls do
Depressed patients have reduced activity in nucleus accumbens
-
Wanting vs. Liking
Activation of opioid receptors, but not dopamine receptors enhance the
gustatory value of sucrose in rats as indexed by behavioural reactions
-
In people, opioid antagonists reduce hedonic value of smells and food
consumption
Enjoy food and smell less, won't eat as much food
-
Opiate addicts perceive increase pleasantness to sweetness compared to
controls and this can be reversed with opioid antagonists
-
In drug addiction, the urge to take a drug (wanting) persists even though the
hedonic experience (liking) may be greatly diminished
Down regulation of u-opioid receptors in addiction and in obesity and
binge-eating disorder
-
-
Dopamine
The central to wanting
DA activation in the NAc motivates approach to rewards and potentiates
wanting, results in seeking behaviours for rewarding stimulus
Facilitates a variety of approach-oriented behaviours
Exploration, affiliation, aggression, sexual behaviour
§
Lesions to the NAc reduce the motivation to work for reward
In a gambling task, the anticipation of rewards activated the NAc and
medial prefrontal
-
Activation of Dopamine network potential rewards in our environment
-
Opioids
The central to liking
Liking is involved in the consummation and enjoyment of rewards
Opiates are released by lactation, nursing, sexual activity, maternal and
social interaction, touch, heroin, exercise
In contrast to DA, it produces a pleasant calmness like after a Thanksgiving
meal
-
What about social rewards?
Reward centres are also activated when people think about being in love
or give money to charity
-
Rewards and attachment - dopamine
DA and opioids are essential for affiliative bonding (oxytocin and vasopressin also
important)
-
Affiliative cues like smiles and gestures serve as incentive stimuli; they motivate
approach-related tendencies served by dopamine
-
These cues trigger dopamine which promotes actions that bring individuals
together
-
Rewards and attachment - opioids
We are very tuned to social interaction
-
Affiliative behaviours like touch and soothing vocalization elicit the release of
opiates and feelings of warmth and calm intimacy
-
When opiates are blocked in juvenile rats, they spend less time with their
mothers after separation
-
Human females given opioid antagonist spend more time alone, less time with
friends an enjoy social interactions less
-
Pain network
PAG, dACC (anterior cingulate cortex), Thalamus, Insula, somatosensory cortex
-
Nociception (pain processing)
Different domains
Sensory-discriminative domain involves detecting where noxious stimulus
is located and how intense it is (PAG and more posterior ACC)
Affective-motivational domain involves the affective component of pain
and is associated with valence (pleasant-unpleasant) distinctions (more
anterior ACC, particularly subgenual)
-
Anterior insula is also involved in its role in sensory coding, body state
assessment , and autonomic regulation
-
Periaqueductal gray: brain's pain center
Appears to be involved in 3 different processes related to emotion
Involved in the release of opioids
Inhibits ascending pain signals before they reach the cortex (e.g.
ACC): allows the escape from threat before attending to injuries
i.
1.
Activated by pain and negative valence images
Participants showed increase activation in the PAG in response to
thermal pain as well as viewing distressing slides
i.
2.
Involved in caregiving system in the mammalian brain
Studies in non-human mammals show that nurturant behaviours like
crouching over pups, licking and prolonged nursing engage the PAG
i.
In humans, OFC and PAG are highly engaged when viewing silent
video clips of their own children crying or smiling
ii.
3.
-
PAG id rich in vasopressin and oxytocin receptors -> PAG and OFC important for
maternal caregiving
-
PAG also responsible for species-typical defensive behaviours '
-
building blocks of emotions
Emotions can be seen to arise from these fundamental aspects of pleasure and
pain
-
Emotion responses and tendencies aid in our survival in numerous ways
-
They become more sophisticated and socially embedded in many context
-
Selfish genes
Emotions are genes' way of making sure thy are passes on
Fear ensures we flee from danger
Disgust ensures we don't eat hazardous foods
Love ensures we have interest in sex and child rearing
-
Many emotional reactions stem from ancestral action tendencies (e.g. motor
habits, startle response, defensive aggression)
-
If emotions serve an evolutionary purpose they should also be seen among other
animals
-
Genetic Influence
Our emotions derive from neural processes that generate instinctual emotional
behaviour in animals
-
Identified action tendencies seen in mammals
Seeking, fear, rage, lust, care, panic & play
Evolved to become quite elaborate in humans through evolution
-
Hypersociality
Like other mammals, we are dependent on others from birth
-
Unlike primates, we live in very large societies that generate culture
-
Human emotions are embedded in complex social contexts
-
Emotional evolution
Humans are only obligated bipedal primates
-
Evolutionary adaptations in bipedalism resulted in anatomical changes that
mostly likely shaped the evolution of human emotion
-
Cranial size and smaller birth canals -> shorter gestational lengths
-
Altriciality would require more social cohesiveness and pair bonding to ensure
survival of species
Rich emotions and social motivations developed
Altricial - like human
Precocial -horse, giraffe (once born, don’t really need care, can walk)
-
Affective Neuroscience
Jaak Panksepp
Primary-emotion systems of RAGE, FEAR, LUST, CARE, SEEKING,
PANIC/GRIEF, PLAY. Also the SELF
Associated with specific brain networks revealed by brain stimulation
studies of emotion
Suggest evolutionarily homologous experiences across different species
of mammals
Rats like to be tickled
§
Not all anxiety is the same (fear of predator attack vs. anxiety of maternal
separation)
Separation anxiety is only quelled with opiates whereas
benzodiazepines won't calm an animal separated from its mother
§
Not all aggression is the same (predatory vs. agitated)
Prefatory aggression: stalking, quiet biting attacks
Rats would repeatedly self-stimulate this area (related to
SEEKING)
§
Agitated aggression: tail wagging, irritated movements
Rats will press level to escape brain simulation of area
§
-
In rats, only have primary empathy: instincts (hypothalamus) but us humans have
highest mind functions for thinking and planning ( basal ganglia, amygdala, nucleus
accumbens, neocortex)
Rough-and -tumble play as an avenue for developing empathy
-
How does the use of psychostimulus to treat ADHD affect executive development?
All of the medications used to treat ADHD are trying to increase the activity
of these two neurotransmitters by triggering their increased release, by slowing
their reuptake or by mimicking their effect and by doing so increasing the
activity of the parts of the brain that are underactive.
-
Components of Empathy
Mentalizing, cognitive empathy, perspective taking, theory of mind
-
Prosocial concern, empathic motivation, sympathy, empathic concern
-
Experience sharing, affective empathy, shared self-other representations,
emotional contagion
-
Overlapping regions
Theory of Mind (ToM)
The ability to attribute mental states to yourself and others, and the
understanding that others' mental states are different from your own
-
Engages some similar and some different networks from empathy
Medial prefrontal cortex
Precuneus
Temporoparietal junction (TPJ)
-
Empathy in the brain
Different types of empathy: affective and cognitive
-
Affective empathy: anterior insula and medial cingulate cortex related to self-
reports of empathy
-
Cognitive empathy (affective ToM): related to understanding others' affective
states, mentalizing
Areas are the same of ToM but also involved more affective areas like
amygdala and vmPFC
-
Mirror Neurons
Simulation is the representation of another's motor actions, emotions,
cognitions etc. by activating those corresponding processes in oneself
However many studies do not show the key mirror neuron areas (i.e.
inferior frontal gyrus (IFG), inferior parietal lobule (IPL)) being active in
empathy
-
Simulation may be involved in empathy, but perhaps not a central process
-
What is empathy?
Our ability to simulate and read each others' mental states and feel what
others feel is, in many ways, what makes us human and is central to social life
-
Empathy in the Brain
Seeing someone else in pain doesn't make us feel the exact pain
-
Pain matrix
Activated during physical pain
PFC, anterior cingulate cortex (ACC)
Insula, amygdala, thalamus
Periacqueductal Grey (PAG)
Primary (S1) and secondary somatosensory cortex (S2)
Posterior parietal cortex (received input from S1 and S2 for planned
movement)
-
Empathy and pain (Singer 2014)
fMRI of 16 couples (female scanned)
-
Determine pain threshold for each couple before experiment
-
Electrodes placed on right hand of both people
-
Male partners seated next to scanner, mirror displayed view both hands
-
Cues for painful and non-painful conditions for self and other
-
After scan, measure individual differences in self-reported pain intensity rating
and general empathetic concern with 2 empathy questionnaires
-
Result
Findings show the importance of anterior cingulate cortex (ACC) and
anterior insular cortices for empathic experience related to pain
ACC can respond not only when a person receives a painful stimulus but
also when a person observes or anticipates a potentially painful stimulus
delivered
Anterior insular regions: anticipation of pain, more affective
(arousal, anxiety)
-
Posterior insular regions: experience of pain, more sensory related
-
These areas are not involved in the mirror neuron system
-
Results suggests a segregation of sensory-discriminative and autonomic-
affective attributes of the pain experience
ACC and AI appear to reflect the emotional experience that evokes our
reactions to pain and underlies neural basis for understanding our own
feelings and those of others
Social pain in the brain
How does social pain engage cortical processes?
Grief when a loved one passes away, betrayed by romantic partner,
separation from parents, getting into fights with friends
Research suggests that the dorsal region of the ACC is the mind's
'alarm system' that something bad happened
-
-
Social exclusion ball-toss game
Virtual confederates throw ball to participants, and then ppts can throw it
back to either 'confederate'
Manipulation
Inclusion condition: ball thrown to ppt 50% of time
Exclusion condition: ball thrown to ppt 8% of time
-
After scan, asked to complete a social distress questionnaire related
to how excluded they felt during the task
-
Then reported momentary social distress over the next 10 days
-
Also completed questions about end-of-day feelings of social
disconnectedness
Observed in dACC, amygdala and PAG
-
Cortical and subcortical involvement
MPFC: social considerations
-
Hippocampus: memory consolidation
-
Activation in areas involved in memory consolidation and self and social
cognition predicted feelings of social distress and disconnection over the
next 10 days
People with greater dACC, amygdala and PAG response to simulated social
rejection reported experiencing greater levels of momentary social distress
in their daily social interactions
The correspondence of momentary social distress and end-of-day
feelings of disconnectedness were associated with greater activation
in hippocampus and MPFC areas
-
Suggesting that people who are more sensitive to even simulated
social rejection also experience more social rejection in their daily
life
-
-
With human evolution, social connection became so important that social
rejection recruited the use of ancient pain regions for more social purposes
Much of our neural circuitry has been scaffolded upon the importance of
social inclusion and harmony
-
Emotional extensions
Self-referential emotions (pride, shame, guilt) are more culturally constructed,
directly embody cultural norms, and have less strongly hardwired circuitry than
survival-oriented negative emotions (fear, anger)
-
Intermediate emotions, such as disgust have not only hardwired origins but also
'moral" extensions
-
Moral transgressions "leave a bad taste in the mouth"
-
EMG recordings of facial expressions associated with:
Ingested beverages (sweet, bitter / salty, water)
Shown complex visual stimuli: (disgusting, sad, neutral)
Then played a game related to fairness
Levator labii is controlled by facial cranial nerve (CN 7)
-
-
Ultimatum Game
2 players split $10: the proposer makes offer on how money will be split,
responder can accept or reject. If accept, money split is proposed. If reject,
neither player receives anything
-
Ranged from 'fair' (5:5 split) to very 'unfair' (9:1 split)
Independent variables
Manipulation of moral disgust: ULTIMATUM GAME OFFERS
-
Dependent variables
EMG
-
Self-reported emotional state
-
-
Emotional extensions
Disgust was the most endorsed emotion during unfair offers
-
However, anger and sadness also increased as a function of unfairness but the
Levator labii did not.
-
Disgust is unique
Only disgust was significantly correlated with levator labii activation
-
Only self-reported disgust following unfairness correlated with elevation of
levator labii
-
Feelings of disgust were best predictor of decision making. Feelings of disgust
result in irrational economic choices
-
Epigenetics
A mechanisms of gene regulation that is independent of DNA sequence that
determines which genes are expresses (switch on or off)
These epigenetic expressions can manifest in:
Certain cell types
-
Particular diseases (e.g. cancer, addiction)
-
Or in behavioural response patterns
-
These epigenetic effects can be passed on and or mediated by
environmental factors
-
Epigenetic mechanisms are affected by
Development in utero
Environmental chemicals
Drugs
Aging
Diet
-
Two modifications
Active chromatin (euchromatin) Closed chromatin (heterochromatin)
Acetylated histone tail
-
Unmethylated cytosine
Designates transcription
-
Methylated histone tail
-
Methylated cytosine
-
Chromatin and Histones
Gene "switched on"
Active (open) chromatin
Unmethylated cytosines (white circles)
Acetylated histones
-
Gene "switched off"
Silent (condensed) chromatin
Methylated cytosines (red circle)
Deacetylated histones
-
Epigenetic & Behaviour
Environmental factors such as early developmental adversity and the type of
parental caregiving can permanently alter the genome via epigenetic
mechanisms (i.e. histone acetylation and DNA methylation)
-
These mechanisms change gene transcription, thus altering biochemical and
behavioural patterns (e.g. learning and memory, addiction, mental illnesses),
which persists through the lifespan and can be passes on to offspring
-
Developmental sensitivity
Sensitive time windows in development relate to neural plasticity circuit growth
and neuronal migration. Disruptions in neural development in these windows
can cause permanent deficits in the lifespan of the animal
-
Monocular deprivation
Kittens has one of their eyes sewn shut
Drastic deficits in V1 ocular columns that never recovered function for
visual processing
-
Epigenetics in development
Post-natal development in rats
Maternal behaviour in sensitive time windows changes chromatin
structure
High LG-ABN mothers: lots of nurturing behaviour (licking, grooming and
arched-back nursing)
Low LG-ABN mothers: much less nurturing, caregiving behaviours
Adult rats raised by high LG-ABN mothers grew up to have decreased
stress responses and less fear in novel situations compared to rats raised
by low LG-ABN mothers
-
Hypothalamic-pituitary-adrenal axis (HPA axis)
Hypothalamus -> anterior pituitary -> adrenal cortex
-
-
Stress
Stress is beneficial in short term
Boosts learning & memory, and immune system, arousal and energy levels
-
Chronic stress is disastrous
Immune suppression, disruptions in glucose signaling, appetite, sleep,
learning & memory
Inhibits neurogenesis , causes dendritic retraction, granule cell death from
neurotoxicity (mainly in hippocampus)
-
HPA-axis modification in caregiving
These behavioral change in rats pups related to better maternal caregiving were
found to also include alterations of the HPA-axis
↑hippocampal glucocorticoid receptor (GR) expression (moderates stress
response by inhibiting HPA activation)
↓ corticotropin releasing hormone (CRH) expression
↑ glucocorticoid feedback sensitivity (less activation due to negative
feedback)
-
Epigenetics of caregiving
These HPA-axis modifications were related to epigenetic changes
DNA methylation of glucocorticoid receptors (GR) in hippocampus
Adult rats raised by LG-ABN moms had fewer hippocampal GR DNA
methylation and more histone acetylation than the low LG-ABN raised
rates (more hippocampal feedback to inhibit hypothalamus)
But could this be related to being raised in more nurturant ways
throughout development and not related to early sensitive times periods?
Cross-fostering experiments showed that it was the mothers
caregiving during the critical post-natal period were related to these
changes
-
-
Beyond the HPA-axis
Childhood abuse is related to numerous deleterious outcomes (e.g. cognitive
dysfunction, psychopathologies, autonomic dysregulation, and volumetric
changes in brain areas (e.g. PFC, amygdala, hippocampus)
-
Evidence suggests that abuse early in life causes alterations in neural functioning
related to plasticity and wiring
-
Brain-derived neurotropic factor (BDNF)
Involved in many neuronal processes including synaptogenesis,
neurogenesis, synapse stability, glutamatergic, NMDA receptor and
GABAergic signaling
-
Epigenetics of abuse
Expose infant rats to 1 of 3 conditions
Abusive caregiver
Nurturing care-giver
Home cage with normal littermates
-
For 1st week of life, they were put in 1 of these conditions for 30 mins daily then
returned to normal home cage
-
Infant maltreatment was related to BDNF methylation (gene silencing) in PFC
that lasted into adulthood
-
Causal link
They then looked at if this gene silencing in PFC could be altered via
neurochemical infusions that disrupt methylation
-
Adult rats maltreated as infants were given intracranial infusions of a DNA
methylation inhibitor, which reversed the DNA methylation and associated gene
transcription effects
-
These epigenetic changes, though stable, are potentially malleable with target
interventions
-
What kind of caregivers are female rats who were abused as infants>
Rat moms who were abused as pups showed these behaviours to their own pups
-
Rat moms who were not abused as pups showed these behaviours to their own
Maybe these changes are due to the postnatal environment and not the
kind of mom they came from.
Try cross-fostering
-
-
-
Epigenetic transmission
What kind of caregivers are female rats who were abused as infants?
Showed similar rated of abusive behaviours towards their offspring that
they endured as infants
-
Are these epigenetic effects passed on down the germ line?
Yes, offspring of maltreated female adult rats showes
↑ methylation of BDNF DNA in PFC and hippocampus compared to
offspring born of non-maltreated females
-
-
Lecture 8
Monday, June 11, 2018 3:59 PM
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Emotional construction
Emotions are socially constructed, depending on the cultures, country or groups
-
Psychological constructivism
Core affect
Neurophysiological state that comprises pleasure or displeasure and can
include arousal (high or low), believed to be the building blocks for
emotional experience
-
Conceptualization
Psychological elaboration and core affect result in the phenomenological
state of emotional feeling
-
Building blocks of emotion
Reward network
VTW, Amygdala, VMPFC, ventral striatum
-
-
Neural circuitry of reward
The brain's reward circuit
Orbitofrontal (OFC) and ventromedial prefrontal cortex (vmPFC)
Engaged by pleasing stimuli, maternal love
§
Ventral striatum and nucleus accumbens (NAc)
Drugs of addiction, food, sex, social reward
§
Ventral tegmental area (VTA)
Main brainstem nucleus where dopamine (DA) is synthesized
Innervates many cortical and subcortical areas
§
-
The nucleus accumbens: brain's pleasure centre
Rich in dopamine and opioid neurotransmitters receptors
-
Evidence that it's central to experiencing hedonia, positive affect and incentive
salience
Increase in activation and DA and opioid release when eating pleasurable
food
-
Depressed patients asked to maintain positive affect don’t show sustained
activity in NAc like controls do
Depressed patients have reduced activity in nucleus accumbens
-
Wanting vs. Liking
Activation of opioid receptors, but not dopamine receptors enhance the
gustatory value of sucrose in rats as indexed by behavioural reactions
-
In people, opioid antagonists reduce hedonic value of smells and food
consumption
Enjoy food and smell less, won't eat as much food
-
Opiate addicts perceive increase pleasantness to sweetness compared to
controls and this can be reversed with opioid antagonists
-
In drug addiction, the urge to take a drug (wanting) persists even though the
hedonic experience (liking) may be greatly diminished
Down regulation of u-opioid receptors in addiction and in obesity and
binge-eating disorder
-
-
Dopamine
The central to wanting
DA activation in the NAc motivates approach to rewards and potentiates
wanting, results in seeking behaviours for rewarding stimulus
Facilitates a variety of approach-oriented behaviours
Exploration, affiliation, aggression, sexual behaviour
Lesions to the NAc reduce the motivation to work for reward
In a gambling task, the anticipation of rewards activated the NAc and
medial prefrontal
-
Activation of Dopamine network potential rewards in our environment
-
Opioids
The central to liking
Liking is involved in the consummation and enjoyment of rewards
Opiates are released by lactation, nursing, sexual activity, maternal and
social interaction, touch, heroin, exercise
In contrast to DA, it produces a pleasant calmness like after a Thanksgiving
meal
-
What about social rewards?
Reward centres are also activated when people think about being in love
or give money to charity
-
Rewards and attachment - dopamine
DA and opioids are essential for affiliative bonding (oxytocin and vasopressin also
important)
-
Affiliative cues like smiles and gestures serve as incentive stimuli; they motivate
approach-related tendencies served by dopamine
-
These cues trigger dopamine which promotes actions that bring individuals
together
-
Rewards and attachment - opioids
We are very tuned to social interaction
-
Affiliative behaviours like touch and soothing vocalization elicit the release of
opiates and feelings of warmth and calm intimacy
-
When opiates are blocked in juvenile rats, they spend less time with their
mothers after separation
-
Human females given opioid antagonist spend more time alone, less time with
friends an enjoy social interactions less
-
Pain network
PAG, dACC (anterior cingulate cortex), Thalamus, Insula, somatosensory cortex
-
Nociception (pain processing)
Different domains
Sensory-discriminative domain involves detecting where noxious stimulus
is located and how intense it is (PAG and more posterior ACC)
Affective-motivational domain involves the affective component of pain
and is associated with valence (pleasant-unpleasant) distinctions (more
anterior ACC, particularly subgenual)
-
Anterior insula is also involved in its role in sensory coding, body state
assessment , and autonomic regulation
-
Periaqueductal gray: brain's pain center
Appears to be involved in 3 different processes related to emotion
Involved in the release of opioids
Inhibits ascending pain signals before they reach the cortex (e.g.
ACC): allows the escape from threat before attending to injuries
i.
1.
Activated by pain and negative valence images
Participants showed increase activation in the PAG in response to
thermal pain as well as viewing distressing slides
i.
2.
Involved in caregiving system in the mammalian brain
Studies in non-human mammals show that nurturant behaviours like
crouching over pups, licking and prolonged nursing engage the PAG
i.
In humans, OFC and PAG are highly engaged when viewing silent
video clips of their own children crying or smiling
ii.
3.
-
PAG id rich in vasopressin and oxytocin receptors -> PAG and OFC important for
maternal caregiving
-
PAG also responsible for species-typical defensive behaviours '
-
building blocks of emotions
Emotions can be seen to arise from these fundamental aspects of pleasure and
pain
-
Emotion responses and tendencies aid in our survival in numerous ways
-
They become more sophisticated and socially embedded in many context
-
Selfish genes
Emotions are genes' way of making sure thy are passes on
Fear ensures we flee from danger
Disgust ensures we don't eat hazardous foods
Love ensures we have interest in sex and child rearing
-
Many emotional reactions stem from ancestral action tendencies (e.g. motor
habits, startle response, defensive aggression)
-
If emotions serve an evolutionary purpose they should also be seen among other
animals
-
Genetic Influence
Our emotions derive from neural processes that generate instinctual emotional
behaviour in animals
-
Identified action tendencies seen in mammals
Seeking, fear, rage, lust, care, panic & play
Evolved to become quite elaborate in humans through evolution
-
Hypersociality
Like other mammals, we are dependent on others from birth
-
Unlike primates, we live in very large societies that generate culture
-
Human emotions are embedded in complex social contexts
-
Emotional evolution
Humans are only obligated bipedal primates
-
Evolutionary adaptations in bipedalism resulted in anatomical changes that
mostly likely shaped the evolution of human emotion
-
Cranial size and smaller birth canals -> shorter gestational lengths
-
Altriciality would require more social cohesiveness and pair bonding to ensure
survival of species
Rich emotions and social motivations developed
Altricial - like human
Precocial -horse, giraffe (once born, don’t really need care, can walk)
-
Affective Neuroscience
Jaak Panksepp
Primary-emotion systems of RAGE, FEAR, LUST, CARE, SEEKING,
PANIC/GRIEF, PLAY. Also the SELF
Associated with specific brain networks revealed by brain stimulation
studies of emotion
Suggest evolutionarily homologous experiences across different species
of mammals
Rats like to be tickled
§
Not all anxiety is the same (fear of predator attack vs. anxiety of maternal
separation)
Separation anxiety is only quelled with opiates whereas
benzodiazepines won't calm an animal separated from its mother
§
Not all aggression is the same (predatory vs. agitated)
Prefatory aggression: stalking, quiet biting attacks
Rats would repeatedly self-stimulate this area (related to
SEEKING)
§
Agitated aggression: tail wagging, irritated movements
Rats will press level to escape brain simulation of area
§
-
In rats, only have primary empathy: instincts (hypothalamus) but us humans have
highest mind functions for thinking and planning ( basal ganglia, amygdala, nucleus
accumbens, neocortex)
Rough-and -tumble play as an avenue for developing empathy
-
How does the use of psychostimulus to treat ADHD affect executive development?
All of the medications used to treat ADHD are trying to increase the activity
of these two neurotransmitters by triggering their increased release, by slowing
their reuptake or by mimicking their effect and by doing so increasing the
activity of the parts of the brain that are underactive.
-
Components of Empathy
Mentalizing, cognitive empathy, perspective taking, theory of mind
-
Prosocial concern, empathic motivation, sympathy, empathic concern
-
Experience sharing, affective empathy, shared self-other representations,
emotional contagion
-
Overlapping regions
Theory of Mind (ToM)
The ability to attribute mental states to yourself and others, and the
understanding that others' mental states are different from your own
-
Engages some similar and some different networks from empathy
Medial prefrontal cortex
Precuneus
Temporoparietal junction (TPJ)
-
Empathy in the brain
Different types of empathy: affective and cognitive
-
Affective empathy: anterior insula and medial cingulate cortex related to self-
reports of empathy
-
Cognitive empathy (affective ToM): related to understanding others' affective
states, mentalizing
Areas are the same of ToM but also involved more affective areas like
amygdala and vmPFC
-
Mirror Neurons
Simulation is the representation of another's motor actions, emotions,
cognitions etc. by activating those corresponding processes in oneself
However many studies do not show the key mirror neuron areas (i.e.
inferior frontal gyrus (IFG), inferior parietal lobule (IPL)) being active in
empathy
-
Simulation may be involved in empathy, but perhaps not a central process
-
What is empathy?
Our ability to simulate and read each others' mental states and feel what
others feel is, in many ways, what makes us human and is central to social life
-
Empathy in the Brain
Seeing someone else in pain doesn't make us feel the exact pain
-
Pain matrix
Activated during physical pain
PFC, anterior cingulate cortex (ACC)
Insula, amygdala, thalamus
Periacqueductal Grey (PAG)
Primary (S1) and secondary somatosensory cortex (S2)
Posterior parietal cortex (received input from S1 and S2 for planned
movement)
-
Empathy and pain (Singer 2014)
fMRI of 16 couples (female scanned)
-
Determine pain threshold for each couple before experiment
-
Electrodes placed on right hand of both people
-
Male partners seated next to scanner, mirror displayed view both hands
-
Cues for painful and non-painful conditions for self and other
-
After scan, measure individual differences in self-reported pain intensity rating
and general empathetic concern with 2 empathy questionnaires
-
Result
Findings show the importance of anterior cingulate cortex (ACC) and
anterior insular cortices for empathic experience related to pain
ACC can respond not only when a person receives a painful stimulus but
also when a person observes or anticipates a potentially painful stimulus
delivered
Anterior insular regions: anticipation of pain, more affective
(arousal, anxiety)
-
Posterior insular regions: experience of pain, more sensory related
-
These areas are not involved in the mirror neuron system
-
Results suggests a segregation of sensory-discriminative and autonomic-
affective attributes of the pain experience
ACC and AI appear to reflect the emotional experience that evokes our
reactions to pain and underlies neural basis for understanding our own
feelings and those of others
Social pain in the brain
How does social pain engage cortical processes?
Grief when a loved one passes away, betrayed by romantic partner,
separation from parents, getting into fights with friends
Research suggests that the dorsal region of the ACC is the mind's
'alarm system' that something bad happened
-
-
Social exclusion ball-toss game
Virtual confederates throw ball to participants, and then ppts can throw it
back to either 'confederate'
Manipulation
Inclusion condition: ball thrown to ppt 50% of time
Exclusion condition: ball thrown to ppt 8% of time
-
After scan, asked to complete a social distress questionnaire related
to how excluded they felt during the task
-
Then reported momentary social distress over the next 10 days
-
Also completed questions about end-of-day feelings of social
disconnectedness
Observed in dACC, amygdala and PAG
-
Cortical and subcortical involvement
MPFC: social considerations
-
Hippocampus: memory consolidation
-
Activation in areas involved in memory consolidation and self and social
cognition predicted feelings of social distress and disconnection over the
next 10 days
People with greater dACC, amygdala and PAG response to simulated social
rejection reported experiencing greater levels of momentary social distress
in their daily social interactions
The correspondence of momentary social distress and end-of-day
feelings of disconnectedness were associated with greater activation
in hippocampus and MPFC areas
-
Suggesting that people who are more sensitive to even simulated
social rejection also experience more social rejection in their daily
life
-
-
With human evolution, social connection became so important that social
rejection recruited the use of ancient pain regions for more social purposes
Much of our neural circuitry has been scaffolded upon the importance of
social inclusion and harmony
-
Emotional extensions
Self-referential emotions (pride, shame, guilt) are more culturally constructed,
directly embody cultural norms, and have less strongly hardwired circuitry than
survival-oriented negative emotions (fear, anger)
-
Intermediate emotions, such as disgust have not only hardwired origins but also
'moral" extensions
-
Moral transgressions "leave a bad taste in the mouth"
-
EMG recordings of facial expressions associated with:
Ingested beverages (sweet, bitter / salty, water)
Shown complex visual stimuli: (disgusting, sad, neutral)
Then played a game related to fairness
Levator labii is controlled by facial cranial nerve (CN 7)
-
-
Ultimatum Game
2 players split $10: the proposer makes offer on how money will be split,
responder can accept or reject. If accept, money split is proposed. If reject,
neither player receives anything
-
Ranged from 'fair' (5:5 split) to very 'unfair' (9:1 split)
Independent variables
Manipulation of moral disgust: ULTIMATUM GAME OFFERS
-
Dependent variables
EMG
-
Self-reported emotional state
-
-
Emotional extensions
Disgust was the most endorsed emotion during unfair offers
-
However, anger and sadness also increased as a function of unfairness but the
Levator labii did not.
-
Disgust is unique
Only disgust was significantly correlated with levator labii activation
-
Only self-reported disgust following unfairness correlated with elevation of
levator labii
-
Feelings of disgust were best predictor of decision making. Feelings of disgust
result in irrational economic choices
-
Epigenetics
A mechanisms of gene regulation that is independent of DNA sequence that
determines which genes are expresses (switch on or off)
These epigenetic expressions can manifest in:
Certain cell types
-
Particular diseases (e.g. cancer, addiction)
-
Or in behavioural response patterns
-
These epigenetic effects can be passed on and or mediated by
environmental factors
-
Epigenetic mechanisms are affected by
Development in utero
Environmental chemicals
Drugs
Aging
Diet
-
Two modifications
Active chromatin (euchromatin) Closed chromatin (heterochromatin)
Acetylated histone tail
-
Unmethylated cytosine
Designates transcription
-
Methylated histone tail
-
Methylated cytosine
-
Chromatin and Histones
Gene "switched on"
Active (open) chromatin
Unmethylated cytosines (white circles)
Acetylated histones
-
Gene "switched off"
Silent (condensed) chromatin
Methylated cytosines (red circle)
Deacetylated histones
-
Epigenetic & Behaviour
Environmental factors such as early developmental adversity and the type of
parental caregiving can permanently alter the genome via epigenetic
mechanisms (i.e. histone acetylation and DNA methylation)
-
These mechanisms change gene transcription, thus altering biochemical and
behavioural patterns (e.g. learning and memory, addiction, mental illnesses),
which persists through the lifespan and can be passes on to offspring
-
Developmental sensitivity
Sensitive time windows in development relate to neural plasticity circuit growth
and neuronal migration. Disruptions in neural development in these windows
can cause permanent deficits in the lifespan of the animal
-
Monocular deprivation
Kittens has one of their eyes sewn shut
Drastic deficits in V1 ocular columns that never recovered function for
visual processing
-
Epigenetics in development
Post-natal development in rats
Maternal behaviour in sensitive time windows changes chromatin
structure
High LG-ABN mothers: lots of nurturing behaviour (licking, grooming and
arched-back nursing)
Low LG-ABN mothers: much less nurturing, caregiving behaviours
Adult rats raised by high LG-ABN mothers grew up to have decreased
stress responses and less fear in novel situations compared to rats raised
by low LG-ABN mothers
-
Hypothalamic-pituitary-adrenal axis (HPA axis)
Hypothalamus -> anterior pituitary -> adrenal cortex
-
-
Stress
Stress is beneficial in short term
Boosts learning & memory, and immune system, arousal and energy levels
-
Chronic stress is disastrous
Immune suppression, disruptions in glucose signaling, appetite, sleep,
learning & memory
Inhibits neurogenesis , causes dendritic retraction, granule cell death from
neurotoxicity (mainly in hippocampus)
-
HPA-axis modification in caregiving
These behavioral change in rats pups related to better maternal caregiving were
found to also include alterations of the HPA-axis
↑hippocampal glucocorticoid receptor (GR) expression (moderates stress
response by inhibiting HPA activation)
↓ corticotropin releasing hormone (CRH) expression
↑ glucocorticoid feedback sensitivity (less activation due to negative
feedback)
-
Epigenetics of caregiving
These HPA-axis modifications were related to epigenetic changes
DNA methylation of glucocorticoid receptors (GR) in hippocampus
Adult rats raised by LG-ABN moms had fewer hippocampal GR DNA
methylation and more histone acetylation than the low LG-ABN raised
rates (more hippocampal feedback to inhibit hypothalamus)
But could this be related to being raised in more nurturant ways
throughout development and not related to early sensitive times periods?
Cross-fostering experiments showed that it was the mothers
caregiving during the critical post-natal period were related to these
changes
-
-
Beyond the HPA-axis
Childhood abuse is related to numerous deleterious outcomes (e.g. cognitive
dysfunction, psychopathologies, autonomic dysregulation, and volumetric
changes in brain areas (e.g. PFC, amygdala, hippocampus)
-
Evidence suggests that abuse early in life causes alterations in neural functioning
related to plasticity and wiring
-
Brain-derived neurotropic factor (BDNF)
Involved in many neuronal processes including synaptogenesis,
neurogenesis, synapse stability, glutamatergic, NMDA receptor and
GABAergic signaling
-
Epigenetics of abuse
Expose infant rats to 1 of 3 conditions
Abusive caregiver
Nurturing care-giver
Home cage with normal littermates
-
For 1st week of life, they were put in 1 of these conditions for 30 mins daily then
returned to normal home cage
-
Infant maltreatment was related to BDNF methylation (gene silencing) in PFC
that lasted into adulthood
-
Causal link
They then looked at if this gene silencing in PFC could be altered via
neurochemical infusions that disrupt methylation
-
Adult rats maltreated as infants were given intracranial infusions of a DNA
methylation inhibitor, which reversed the DNA methylation and associated gene
transcription effects
-
These epigenetic changes, though stable, are potentially malleable with target
interventions
-
What kind of caregivers are female rats who were abused as infants>
Rat moms who were abused as pups showed these behaviours to their own pups
-
Rat moms who were not abused as pups showed these behaviours to their own
Maybe these changes are due to the postnatal environment and not the
kind of mom they came from.
Try cross-fostering
-
-
-
Epigenetic transmission
What kind of caregivers are female rats who were abused as infants?
Showed similar rated of abusive behaviours towards their offspring that
they endured as infants
-
Are these epigenetic effects passed on down the germ line?
Yes, offspring of maltreated female adult rats showes
↑ methylation of BDNF DNA in PFC and hippocampus compared to
offspring born of non-maltreated females
-
-
Lecture 8
Monday, June 11, 2018 3:59 PM
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Document Summary

Emotions are socially constructed, depending on the cultures, country or groups. Neurophysiological state that comprises pleasure or displeasure and can include arousal (high or low), believed to be the building blocks for emotional experience. Psychological elaboration and core affect result in the phenomenological state of emotional feeling. Main brainstem nucleus where dopamine (da) is synthesized. Evidence that it"s central to experiencing hedonia, positive affect and incentive salience. Increase in activation and da and opioid release when eating pleasurable food. Depressed patients asked to maintain positive affect don"t show sustained activity in nac like controls do. Depressed patients have reduced activity in nucleus accumbens. Activation of opioid receptors, but not dopamine receptors enhance the gustatory value of sucrose in rats as indexed by behavioural reactions. In people, opioid antagonists reduce hedonic value of smells and food. In people, opioid antagonists reduce hedonic value of smells and food consumption. Enjoy food and smell less, won"t eat as much food.

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