PSY493H1 Lecture Notes - Lecture 7: Parahippocampal Gyrus, Brain Stimulation Reward, Olfactory Bulb
Darwin
Emotions have an evolutionary purpose
-
They are rational and inseparable from cognition and their influence on
behaviour
-
Nature vs Nurture
Culture determines when our 'hardwired' emotional expressions are displayed
(i.e. displayed rules)
Social constructionism
○
-
Emotions are not simply 'hardwired' by-products of evolution. They can only be
fully understood on a social level
-
What is an Emotion?
"emotion consists of neural circuits (that are at least partially dedicated),
response systems , and a feeling state/process that motivates and organizes
cognition and action"
-
Categorizing emotions
Valence (positive -negative)
Pleasure, displeasure
○
Approach, avoidance
○
-
Arousal (strength, intensity)
High or low intensity experience
○
Irrespective of valence
○
-
Distinctiveness
Qualitatively discrete emotions
Sadness, jealously, fear: all negative but different
§
○
-
What is emotion?
Subjective -> feeling
-
Bodily sensations -> physiological changes
Heart rate, sweat, adrenaline
○
-
Display of emotions
Facial expressions
○
Body language
○
-
Cognition
Rationalize emotion, regulate
○
-
Social aspects
Communication
○
Culture
○
-
Phylogenetic hierarchy
Forebrain
Thalamus (sensory integration)
○
Hippocampus (memory)
○
Hypothalamus (temp, hormones, sexual behaviour, aggression)
○
Limbic system (many subcortical areas)
○
-
Cerebral cortex: outer layer of forebrain
Cingulate gyrus (error monitoring, memory, emotion)
○
Parahippocampal gyrus (memory)
○
Association cortices (sensory integration)
○
-
Most cross-species evolutionary differences in cortex (e.g. PFC)
-
Neuroscience of Emotion
Limbic system
1937 J. Papez
Hypothalamus, hippocampus, anterior thalamus, cingulate cortex
§
Amygdala added later!
§
○
Cannon & Britton
Decorticated cats
§
No neo-cortical input
§
Shame rage
§
Cortex exhibits control on lower regions
§
○
Kluver & Bucy
Removal of anterior temporal lobes in rhesus monkeys
§
Became docile, hypersexual, hyperphagia, fearless
§
○
Olds & Milner
Implanted electrodes in septal regions of limbic system of rats
§
First evidence of rewards centers in the brain
§
First example of brain stimulation reward being used as operant
reinforcer
§
○
-
Amygdala
An 'emotion hub'
Integrates sensory input (across modalities)
Direct input from the olfactory bulb □
Visual and auditory cues via 'direct' thalamic routes □
§
Rapid, automatic evaluation
Arousal □
Valence □
§
○
A fear center
Involved in representations of negative states and detection of threat
across modalities
Negative facial expressions□
Threat-related words□
Aversive odors □
§
Acquisition of fear responses via conditioning paradigms
Ledoux 1998,2000 (read)□
Phelps (2001)□
§
○
Zeroing in on the amygdala
Can receive inputs from the visual and auditory cortices via the
thalamus - not always via routes that lead to recognition
§
Makes for rapid, non-processed recognition of fear
§
LeDoux used fear conditioning to study the amygdala in rats
Pair shock with tone or light □
§
Fear associations are formed quickly and long-lasting
These associations are persistent and hard to extinguish □
§
Cortex isn't necessary for learning fear associations
"high" road (conscious, slow) vs. 'low" road (unconscious, fast)□
Emotional learning can occur based on the simplest features of
a stimulus (e.g. shape, intensity)
□
§
LeDoux showed that you cannot form conditioned fear responses
without an intact thalamus and amygdala
§
○
-
Emotion (fear) pathways
○
-
What LeDoux's experiments revealed:
The amygdala is the core of a central emotional processing network that can
receive input unprocessed by cortex
-
The amygdala is where primary appraisals (good or bad) and automatic
evaluations of events occur
-
Amygdala is responsible for assigning emotional significance to events, with an
emphasis on negative salience
-
Three kinds of neuroimaging studies of humans supported LeDoux's claims
The amygdala is often activated during momentary emotional reactions to
evocative stimuli
1.
Individual differences in emotionality can be shown in amygdala activation 2.
Amygdala activity predicts whether people will recall emotionally significant
stimuli
3.
Amygdala known as centre for negative, fearful emotional processing, but this
prominent idea doesn't hold up:
40-50% of studies designed to elicit fear do not amygdala activation
-
Amygdala is activated for positive stimuli as well
-
Cunningham et al (2004) have shown that the amygdala responds to the
emotional intensity of a stimulus
Activation is irrespective for valence (positive/negative)
○
Depends on what you're motivated by, what is salient to you
○
-
Link to psychological theories
Dual process approach to brain function
Passion vs. Reason
○
Emotions vs. Cognition
○
-
System 1
Automatic
○
No voluntary control
○
Driven by affective impulses
○
-
System 2
Deliberative
○
Effortful and computational
○
Driven by rule-based thought
○
-
Challenges to the 'Limbic System'
Cingulate gyrus Monitoring
Regulation
salience
Parahippocampal gyrus Encoding/retrieval
Scene recognition
Visual perception
Hippocampus Episodic memory
Spatial navigation
Temporal processing
Thalamus Sensory/motor integration
Subcortical <-> cortical relay
Hypothalamus Autonomic Nervous System
Neuroendocrine functions
Amygdala Arousal
Relevance
Memory - reinforcement learning
Fear and reward
The hippocampus is critical for memory
-
Cortical regions are essential for emotional and social processing
-
Include PFC areas as part of "limbic system"?
-
-
No clean delineation b/w "affective" vs. "cognitive" brain structures
-
"cold" cognitive processes (e.g. memory, attention, perception) clearly contribute
to emotional experiences (e.g. psychological constructivism)
-
Affective processes contribute to decision-making (e.g. somatic marker
hypothesis (SMH))
-
Reciprocal relationship b/w emotion and cognition
-
Emotion and Cortical Processes
Frontal lobes
PFC centre of regulation and executive control
○
Primary affective sensations (i.e. pleasure/pain, arousal) are generated by
regions like the amygdala, ACC, NAc and PAG
○
These affective representations are integrated and held in STM to guide
behaviour in adaptive and socially appropriate ways
○
-
PFC elaborate emotion
Human subcortical systems receive greater cortical input
-
Lower levels responsible for primary affective sensations (pleasure and pain,
arousal)
-
Higher levels reproduce the lower levels as re-representations and add new
abstract features to them
-
Subcortical systems give up their autonomy relating to emotional functions. In
PFC, abstract representations become increasingly dominant
-
Complex emotional processes
Three PFC areas relevant to emotion
Orbitofrontal PFC
○
Dorsolateral PFC
○
Medial PFC
○
-
Important for emotion regulation
Ways in which we respond to and modify our emotional reactions and
experiences
○
-
Dorsolateral PFC (dIPFC) involved in:
Planning, abstract reasoning
○
Impulse control
Lying, selfishness
§
○
Social perspective taking
○
TMS disruption here results in more acceptance of unfair offers in
ultimatum game
○
Medial prefrontal cortex (MPFC) is involved in
Self- and socila representations (social brain)
○
Empathy
○
Experiences of reward
○
Orbitofrontal cortex (OFC)
Approach/ withdrawal tendencies
○
Represents goals, rewards and punishments
○
Important for extinction of learned rewards
○
Medial-lateral distinctions
Medial: monitoring, learning, memory
Overlaps with 'vmPFC'
®
□
Lateral: evaluation of rewarding vs. punishing properties,
leading to behavioural change
□
§
Posterior-Anterior distinctions
Posterior: multimodal sensory and motor integration
Integrate bodily (visceral info) - somatic marker
hypothesis
®
□
Anterior: increasingly abstract rewards
Rewards from more abstract stimuli (e.g. money)
®
Increasingly complexity in decisions b/w rewards
Choice A and B are both good!
◊
®
□
§
○
PFC reward representation
Overall, orbitofrontal cortex
Integrates multiple stimulus-reward associations across multiple modalities
○
Guides decision making and goal-directed behaviour
○
-
Connectivity allows convergence of
Current motivational state (represented in the PFC)
○
Affectively salient stimuli in the world (represented in the amygdala)
○
-
Anterior cingulate cortex
Dorsal (cognitive): connected to PFC, parietal, motor areas. Processes bottom-up
and top-down info and relaying control processes to other areas
-
Ventral (emotional): connected to amygdala, NAc, hypothalamus, insula.
Assesses emotional and motivational salience
-
Discrepancy detector: activated when you commit an error (pressed a key when
you shouldn't have)
-
Physical and social pain detector
Surgeons sometimes ablate the ACC of patients with intractable pain
○
Helps humans detect and respond to cues of rejection, separation and
exclusion
○
-
Emotional efficiency
Emotions as efficient heuristics for problem solving
Free up cognitive resources
○
Action tendencies allow for streamlined reactions with less deliberative
employment
○
-
Broadly allow for approach/avoidance strategies
-
We learn environmental risks and rewards from past experience
-
Emotion influences our judgements often without our knowledge
-
Emotion and cognition
Negative emotions: tied with specific action tendencies
Evolutionary utility
○
Narrowed thought- action repertoire promotes quick & decisive action -
immediate benefit
○
Associated with sympathetic activation
○
-
Positive emotions:
Broaden thought-action repertoires
○
Build enduring personal resources (physical, intellectual, social)
○
Allows for exploration, creativity, play, learning
○
Confers enduring benefits
○
-
Broaden and Build Theory
Emotions Bias Cognitive Processing
Positive emotions broaden awareness, build skills and resources 1.
When happy, we are more likely to:
See global patterns relative to specific details i.
See connection b/w groups and within relationshipsii.
2.
Positive emotions buffer negative life experiences
More resilient to bad experiences, physiology, returns to baseline
quicker
i.
3.
-
Emotion and Cognition Task
Mood manipulation: positive, negative, neutral images
-
Attend to faces, ignore houses
Report gender of faces (targets), ignore places (distractors)
○
-
Neurally: look at object-selective visual processing areas
Places: parahippocampal place area (PPA)
○
FACES: Fusiform face area (FFA)
○
-
Repetition reduction (RR) - neural adaptation or habituation
When an image is repeatedly presented and processed neurally, the neural
activation of that processing will be reduced with each subsequent
repetition of the stimulus
○
Specifically seen in visual processing areas (FFA, PPA)
○
Thought to reflect increased neural processing efficiency
○
This is used to neurally assess processing over time
If you are processing irrelevant task info (distractors), then you
should see RR for repeated place in PPA
§
○
Results:
Positive affect increased distractor processing (houses): Left PPA activation
for novel houses and greater repetition reduction (sign of attention) at
second exposure
○
Self-report of mood valence correlated with PPA activation 9more positive
states the greater PPA activation)
○
Emotional advantages
Can alter early perceptual processing
-
Emotion can confer benefits and deficits
-
Task dependent
Negative emotion better for visual search, more concrete and detailed
thinking
○
Positive emotions better for brainstorming, flexible, abstract thinking,
insight problem solving
○
-
Negative emotions are adaptive and important
-
Decision making and reward learning
This process has a lot of do with limbic structures, executive areas, emotion and
reward learning via dopamine activation
-
Stages of Decision Making
Learning -> (Representation -> valuation -> action selection) -> outcome
evaluation -> learning ……
Representation
Representation of the decision problem - context
"would you like fries or salad?"
®
□
Internal states:
"how hungry?"
®
□
External states:
"how much food?"
®
□
Different goals!
Lose weight vs. enjoy fries
®
□
§
Valuation
Options must be compared - value! □
Apples to oranges □
Salad to fries
How to compare them if not equal?
Common currency
◊
Subjective value (utility)
◊
®
□
§
Action selection
Implement decision -> eat SALAD!
How can we measure it?
Subjective value (utility)
◊
Common currency!
◊
®
□
Executive function □
Motor control □
§
Outcome evaluation
Reward vs. punishment
How good was the salad?
®
□
§
Learning
Update values - "salad better than expected"□
Influence future decision making - "order salad again"
How?
DOPAMINE!
◊
®
□
§
○
Dopamine in Basal Ganglia
3 main components
Striatum (largest component)
Caudate
§
Putamen
§
○
Globus pallidus
○
Substantia nigra ("black substance")
○
Subthalamic nucleus
○
-
-
How does dopamine work in reward/ learning?
Three subsystems:
Nigrostriatal (substantia nigra)
○
Mesolimbic (VTA)
○
Meocortical (VTA)
○
-
Mesolimbic Pathway
VTA(ventral tegmental area) -> NAc (Nucleus accumbens)
○
-
Stimulate to death
Olds 1958:
Rats will self-stimulate to death!
2000 presses/hour for 24 hrs
§
○
Reward -> pleasure
○
-
Dopamine
Pleasure neurotransmitter?
Blocking dopamine via lesioning or by genetically inactivation of tyrosine
hydroxylase does not stop happiness
Impair "wanting" but not "liking"
§
Dopamine transmission in NAc mediates the assignment of incentive
salience to rewards and reward-related cues
§
○
Dopamine plays a central role in reward-related learning
○
-
Dopamine and prediction errors
Positive prediction error:
Unexpected reward -> increase in phasic firing
○
-
No prediction error:
Expected reward -> no increase in firing
○
-
Negative prediction error:
Reward is withheld -> suppression of the tonic firing
○
-
DA firing is dependent on prediction error of reward
-
Reinforcement learning
Maximize future rewards
-
Memory/learning
-
Value prediction
-
Action selection
-
Rewards prediction error
-
Reward-related fMRI Responses
Reward (or reward anticipation) activities ventromedial prefrontal/orbitofrontal
cortex, striatum
-
Decision-making dysfunction: role in addiction?
A neurobiological illness whereby repetitive drug use corrupts and disorganizes
the normal circuitry of rewarding and adaptive behaviours
Compulsive drug-seeking behaviour
○
Inability to regulate such behaviours
○
Continued use of substances despite negative consequences
○
Reduced drive to acquire biological relevant natural rewards
○
Continued vulnerability to relapse
○
-
-
Tolerance
Increased dosage needed to maintain a "pleasurable" effect
-
Dependence
Need regular drug administration to "feel" normal
Dependence is not necessary or sufficient
○
-
Sensitization
Response increase with repeated dosing
These is a lack of compelling evidence for sensitization in humans
○
-
Homeostatic adaptation is believed to underlie tolerance and dependence
Natural rewards
Organisms learn factors critical for survival and continuation of a species such as
obtaining food, sex, social affiliation
Such goals function as rewards!
○
-
Additive drugs have many commonalities:
Hedonic responses (pleasure)
○
Desire (wanting)
○
Reinforcing
○
Social aspects
○
-
Olds 1958:
Rats self-stimulate to death
reward -> Pleasure
○
Dopamine -> pleasure? NO!
Motivation/salience? YES!
○
-
Neurobiology of Rewards
Rewards increase synaptic dopamine in Nac
-
Dopamine projections to the forebrain.
From ventral tegmental area to the nucleus accumbens and
prefrontal cerebral cortex and projections from the substantia nigra
to the dorsal striatum (caudate and putamen and related
structures)
§
○
-
Initiation of Addiction
Increase extracellular dopamine (DA) levels in the Nac
-
Other neuromodulators
GABA, opioid peptides (opiates, Alcohol, nicotine)
○
Serotonin
○
Acetylcholine
○
Endocannabinoids
○
Glutamate (nicotine)
○
-
-Positive prediction error:
Unexpected reward -> increase in phasic firing
○
-No prediction error:
Expected reward -> increase in firing
○
-Negative prediction error:
Reward is withheld -> suppression of the tonic firing
○
In addiction, drugs are always better than expected
From Reward learning to addiction
-Drugs are always better than expected!
-Release of dopamine will produce what the brain interprets as a positive
prediction-error signal
-Drugs more valuable than all other rewards
-Repetitive pathological over learning of drug-related cues and drug experiences
-Even if subjective effects fall short of the expectation created by drug cues, the
massive surge of DA from the drugs in interpreted as a positive prediction error
signal
PFC
-Representation of goals (vmPFC) - valuation
-Assignment of value
-Action selection
-Executive control (OFC)
-Phasic dopamine gates the updating info in the PFC
-Overvaluation of drug related cues and impairment of top-down control
contribute significantly to addiction
Mechanisms in Striatum
-NAc and dorsal striatum are in ideal position for integration info about
motivation (VTA), and sensory-rich info (PFC)
From reward to addiction
-NAc -> Dorsal striatum
-Seeking of goals -> stimulate response habits
-Dopamine in NAc critical for establishment of drug-seeking behavior,
then activation shifts
-As addiction progresses, NAc activation shifts to dorsal striatum
activation involved in stimulus-response habits
Glutamate: a final common pathway
-Dopamine -> glutamate
-Hyperglutamatergic for drug-related stimuli
-Hypoglutamatergic for natural rewards
-The role of glutamate in addiction remains understudied
Relapse
-Drug-related cues
-DA release into the PFC and basolateral amygdala
-Stress
-CRF and noradrenaline
-Drug priming
-DA release into the PFC and NA shell
Treatment
-Key: stage of illness
-Initiation -> drug abuse -> dependence -> relapse
-Prevention approach:
-Identify and treat individuals at high risk (Vaccinations) - NOT AVAILABLE
-Disruption of acute reinforcement and conditioning
-Replacement therapy
○Methadone
-Relapse prevention
-Based on reinstatement paradigms
○Drug-related cues: blocking glutamate (Acamprosate + psychosocial)
-Stress
○Interruption of stress response - not available yet
○CRF1 and glucocorticoids antagonist
Conclusions
-Dopamine action can help us understand the progression from pleasurable
experimentation with drugs to a long-lived compulsion
-It's clear that neurotransmitters other than dopamine must play important roles
-Glutamate action may be a final common path
-Translational work remains a high priority
Striatum = caudate + putamen
NAc= most anterior part of ventral
striatum
More cravings -
hypermetabolism in
right OFC and
putamen during drug
use
Lecture 7
Sunday, June 10, 2018
8:39 PM
Darwin
Emotions have an evolutionary purpose
-
They are rational and inseparable from cognition and their influence on
behaviour
-
Nature vs Nurture
Culture determines when our 'hardwired' emotional expressions are displayed
(i.e. displayed rules)
Social constructionism
○
-
Emotions are not simply 'hardwired' by-products of evolution. They can only be
fully understood on a social level
-
What is an Emotion?
"emotion consists of neural circuits (that are at least partially dedicated),
response systems , and a feeling state/process that motivates and organizes
cognition and action"
-
Categorizing emotions
Valence (positive -negative)
Pleasure, displeasure
○
Approach, avoidance
○
-
Arousal (strength, intensity)
High or low intensity experience
○
Irrespective of valence
○
-
Distinctiveness
Qualitatively discrete emotions
Sadness, jealously, fear: all negative but different
§
○
-
What is emotion?
Subjective -> feeling
-
Bodily sensations -> physiological changes
Heart rate, sweat, adrenaline
○
-
Display of emotions
Facial expressions
○
Body language
○
-
Cognition
Rationalize emotion, regulate
○
-
Social aspects
Communication
○
Culture
○
-
Phylogenetic hierarchy
Forebrain
Thalamus (sensory integration)
○
Hippocampus (memory)
○
Hypothalamus (temp, hormones, sexual behaviour, aggression)
○
Limbic system (many subcortical areas)
○
-
Cerebral cortex: outer layer of forebrain
Cingulate gyrus (error monitoring, memory, emotion)
○
Parahippocampal gyrus (memory)
○
Association cortices (sensory integration)
○
-
Most cross-species evolutionary differences in cortex (e.g. PFC)
-
Neuroscience of Emotion
Limbic system
1937 J. Papez
Hypothalamus, hippocampus, anterior thalamus, cingulate cortex
§
Amygdala added later!
§
○
Cannon & Britton
Decorticated cats
§
No neo-cortical input
§
Shame rage
§
Cortex exhibits control on lower regions
§
○
Kluver & Bucy
Removal of anterior temporal lobes in rhesus monkeys
§
Became docile, hypersexual, hyperphagia, fearless
§
○
Olds & Milner
Implanted electrodes in septal regions of limbic system of rats
§
First evidence of rewards centers in the brain
§
First example of brain stimulation reward being used as operant
reinforcer
§
○
-
Amygdala
An 'emotion hub'
Integrates sensory input (across modalities)
Direct input from the olfactory bulb
□
Visual and auditory cues via 'direct' thalamic routes
□
§
Rapid, automatic evaluation
Arousal □
Valence □
§
○
A fear center
Involved in representations of negative states and detection of threat
across modalities
Negative facial expressions□
Threat-related words□
Aversive odors □
§
Acquisition of fear responses via conditioning paradigms
Ledoux 1998,2000 (read)□
Phelps (2001)□
§
○
Zeroing in on the amygdala
Can receive inputs from the visual and auditory cortices via the
thalamus - not always via routes that lead to recognition
§
Makes for rapid, non-processed recognition of fear
§
LeDoux used fear conditioning to study the amygdala in rats
Pair shock with tone or light □
§
Fear associations are formed quickly and long-lasting
These associations are persistent and hard to extinguish □
§
Cortex isn't necessary for learning fear associations
"high" road (conscious, slow) vs. 'low" road (unconscious, fast)□
Emotional learning can occur based on the simplest features of
a stimulus (e.g. shape, intensity)
□
§
LeDoux showed that you cannot form conditioned fear responses
without an intact thalamus and amygdala
§
○
-
Emotion (fear) pathways
○
-
What LeDoux's experiments revealed:
The amygdala is the core of a central emotional processing network that can
receive input unprocessed by cortex
-
The amygdala is where primary appraisals (good or bad) and automatic
evaluations of events occur
-
Amygdala is responsible for assigning emotional significance to events, with an
emphasis on negative salience
-
Three kinds of neuroimaging studies of humans supported LeDoux's claims
The amygdala is often activated during momentary emotional reactions to
evocative stimuli
1.
Individual differences in emotionality can be shown in amygdala activation 2.
Amygdala activity predicts whether people will recall emotionally significant
stimuli
3.
Amygdala known as centre for negative, fearful emotional processing, but this
prominent idea doesn't hold up:
40-50% of studies designed to elicit fear do not amygdala activation
-
Amygdala is activated for positive stimuli as well
-
Cunningham et al (2004) have shown that the amygdala responds to the
emotional intensity of a stimulus
Activation is irrespective for valence (positive/negative)
○
Depends on what you're motivated by, what is salient to you
○
-
Link to psychological theories
Dual process approach to brain function
Passion vs. Reason
○
Emotions vs. Cognition
○
-
System 1
Automatic
○
No voluntary control
○
Driven by affective impulses
○
-
System 2
Deliberative
○
Effortful and computational
○
Driven by rule-based thought
○
-
Challenges to the 'Limbic System'
Cingulate gyrus Monitoring
Regulation
salience
Parahippocampal gyrus Encoding/retrieval
Scene recognition
Visual perception
Hippocampus Episodic memory
Spatial navigation
Temporal processing
Thalamus Sensory/motor integration
Subcortical <-> cortical relay
Hypothalamus Autonomic Nervous System
Neuroendocrine functions
Amygdala Arousal
Relevance
Memory - reinforcement learning
Fear and reward
The hippocampus is critical for memory
-
Cortical regions are essential for emotional and social processing
-
Include PFC areas as part of "limbic system"?
-
-
No clean delineation b/w "affective" vs. "cognitive" brain structures
-
"cold" cognitive processes (e.g. memory, attention, perception) clearly contribute
to emotional experiences (e.g. psychological constructivism)
-
Affective processes contribute to decision-making (e.g. somatic marker
hypothesis (SMH))
-
Reciprocal relationship b/w emotion and cognition
-
Emotion and Cortical Processes
Frontal lobes
PFC centre of regulation and executive control
○
Primary affective sensations (i.e. pleasure/pain, arousal) are generated by
regions like the amygdala, ACC, NAc and PAG
○
These affective representations are integrated and held in STM to guide
behaviour in adaptive and socially appropriate ways
○
-
PFC elaborate emotion
Human subcortical systems receive greater cortical input
-
Lower levels responsible for primary affective sensations (pleasure and pain,
arousal)
-
Higher levels reproduce the lower levels as re-representations and add new
abstract features to them
-
Subcortical systems give up their autonomy relating to emotional functions. In
PFC, abstract representations become increasingly dominant
-
Complex emotional processes
Three PFC areas relevant to emotion
Orbitofrontal PFC
○
Dorsolateral PFC
○
Medial PFC
○
-
Important for emotion regulation
Ways in which we respond to and modify our emotional reactions and
experiences
○
-
Dorsolateral PFC (dIPFC) involved in:
Planning, abstract reasoning
○
Impulse control
Lying, selfishness
§
○
Social perspective taking
○
TMS disruption here results in more acceptance of unfair offers in
ultimatum game
○
Medial prefrontal cortex (MPFC) is involved in
Self- and socila representations (social brain)
○
Empathy
○
Experiences of reward
○
Orbitofrontal cortex (OFC)
Approach/ withdrawal tendencies
○
Represents goals, rewards and punishments
○
Important for extinction of learned rewards
○
Medial-lateral distinctions
Medial: monitoring, learning, memory
Overlaps with 'vmPFC'
®
□
Lateral: evaluation of rewarding vs. punishing properties,
leading to behavioural change
□
§
Posterior-Anterior distinctions
Posterior: multimodal sensory and motor integration
Integrate bodily (visceral info) - somatic marker
hypothesis
®
□
Anterior: increasingly abstract rewards
Rewards from more abstract stimuli (e.g. money)
®
Increasingly complexity in decisions b/w rewards
Choice A and B are both good!
◊
®
□
§
○
PFC reward representation
Overall, orbitofrontal cortex
Integrates multiple stimulus-reward associations across multiple modalities
○
Guides decision making and goal-directed behaviour
○
-
Connectivity allows convergence of
Current motivational state (represented in the PFC)
○
Affectively salient stimuli in the world (represented in the amygdala)
○
-
Anterior cingulate cortex
Dorsal (cognitive): connected to PFC, parietal, motor areas. Processes bottom-up
and top-down info and relaying control processes to other areas
-
Ventral (emotional): connected to amygdala, NAc, hypothalamus, insula.
Assesses emotional and motivational salience
-
Discrepancy detector: activated when you commit an error (pressed a key when
you shouldn't have)
-
Physical and social pain detector
Surgeons sometimes ablate the ACC of patients with intractable pain
○
Helps humans detect and respond to cues of rejection, separation and
exclusion
○
-
Emotional efficiency
Emotions as efficient heuristics for problem solving
Free up cognitive resources
○
Action tendencies allow for streamlined reactions with less deliberative
employment
○
-
Broadly allow for approach/avoidance strategies
-
We learn environmental risks and rewards from past experience
-
Emotion influences our judgements often without our knowledge
-
Emotion and cognition
Negative emotions: tied with specific action tendencies
Evolutionary utility
○
Narrowed thought- action repertoire promotes quick & decisive action -
immediate benefit
○
Associated with sympathetic activation
○
-
Positive emotions:
Broaden thought-action repertoires
○
Build enduring personal resources (physical, intellectual, social)
○
Allows for exploration, creativity, play, learning
○
Confers enduring benefits
○
-
Broaden and Build Theory
Emotions Bias Cognitive Processing
Positive emotions broaden awareness, build skills and resources 1.
When happy, we are more likely to:
See global patterns relative to specific details i.
See connection b/w groups and within relationshipsii.
2.
Positive emotions buffer negative life experiences
More resilient to bad experiences, physiology, returns to baseline
quicker
i.
3.
-
Emotion and Cognition Task
Mood manipulation: positive, negative, neutral images
-
Attend to faces, ignore houses
Report gender of faces (targets), ignore places (distractors)
○
-
Neurally: look at object-selective visual processing areas
Places: parahippocampal place area (PPA)
○
FACES: Fusiform face area (FFA)
○
-
Repetition reduction (RR) - neural adaptation or habituation
When an image is repeatedly presented and processed neurally, the neural
activation of that processing will be reduced with each subsequent
repetition of the stimulus
○
Specifically seen in visual processing areas (FFA, PPA)
○
Thought to reflect increased neural processing efficiency
○
This is used to neurally assess processing over time
If you are processing irrelevant task info (distractors), then you
should see RR for repeated place in PPA
§
○
Results:
Positive affect increased distractor processing (houses): Left PPA activation
for novel houses and greater repetition reduction (sign of attention) at
second exposure
○
Self-report of mood valence correlated with PPA activation 9more positive
states the greater PPA activation)
○
Emotional advantages
Can alter early perceptual processing
-
Emotion can confer benefits and deficits
-
Task dependent
Negative emotion better for visual search, more concrete and detailed
thinking
○
Positive emotions better for brainstorming, flexible, abstract thinking,
insight problem solving
○
-
Negative emotions are adaptive and important
-
Decision making and reward learning
This process has a lot of do with limbic structures, executive areas, emotion and
reward learning via dopamine activation
-
Stages of Decision Making
Learning -> (Representation -> valuation -> action selection) -> outcome
evaluation -> learning ……
Representation
Representation of the decision problem - context
"would you like fries or salad?"
®
□
Internal states:
"how hungry?"
®
□
External states:
"how much food?"
®
□
Different goals!
Lose weight vs. enjoy fries
®
□
§
Valuation
Options must be compared - value! □
Apples to oranges □
Salad to fries
How to compare them if not equal?
Common currency
◊
Subjective value (utility)
◊
®
□
§
Action selection
Implement decision -> eat SALAD!
How can we measure it?
Subjective value (utility)
◊
Common currency!
◊
®
□
Executive function □
Motor control □
§
Outcome evaluation
Reward vs. punishment
How good was the salad?
®
□
§
Learning
Update values - "salad better than expected"□
Influence future decision making - "order salad again"
How?
DOPAMINE!
◊
®
□
§
○
Dopamine in Basal Ganglia
3 main components
Striatum (largest component)
Caudate
§
Putamen
§
○
Globus pallidus
○
Substantia nigra ("black substance")
○
Subthalamic nucleus
○
-
-
How does dopamine work in reward/ learning?
Three subsystems:
Nigrostriatal (substantia nigra)
○
Mesolimbic (VTA)
○
Meocortical (VTA)
○
-
Mesolimbic Pathway
VTA(ventral tegmental area) -> NAc (Nucleus accumbens)
○
-
Stimulate to death
Olds 1958:
Rats will self-stimulate to death!
2000 presses/hour for 24 hrs
§
○
Reward -> pleasure
○
-
Dopamine
Pleasure neurotransmitter?
Blocking dopamine via lesioning or by genetically inactivation of tyrosine
hydroxylase does not stop happiness
Impair "wanting" but not "liking"
§
Dopamine transmission in NAc mediates the assignment of incentive
salience to rewards and reward-related cues
§
○
Dopamine plays a central role in reward-related learning
○
-
Dopamine and prediction errors
Positive prediction error:
Unexpected reward -> increase in phasic firing
○
-
No prediction error:
Expected reward -> no increase in firing
○
-
Negative prediction error:
Reward is withheld -> suppression of the tonic firing
○
-
DA firing is dependent on prediction error of reward
-
Reinforcement learning
Maximize future rewards
-
Memory/learning
-
Value prediction
-
Action selection
-
Rewards prediction error
-
Reward-related fMRI Responses
Reward (or reward anticipation) activities ventromedial prefrontal/orbitofrontal
cortex, striatum
-
Decision-making dysfunction: role in addiction?
A neurobiological illness whereby repetitive drug use corrupts and disorganizes
the normal circuitry of rewarding and adaptive behaviours
Compulsive drug-seeking behaviour
○
Inability to regulate such behaviours
○
Continued use of substances despite negative consequences
○
Reduced drive to acquire biological relevant natural rewards
○
Continued vulnerability to relapse
○
-
-
Tolerance
Increased dosage needed to maintain a "pleasurable" effect
-
Dependence
Need regular drug administration to "feel" normal
Dependence is not necessary or sufficient
○
-
Sensitization
Response increase with repeated dosing
These is a lack of compelling evidence for sensitization in humans
○
-
Homeostatic adaptation is believed to underlie tolerance and dependence
Natural rewards
Organisms learn factors critical for survival and continuation of a species such as
obtaining food, sex, social affiliation
Such goals function as rewards!
○
-
Additive drugs have many commonalities:
Hedonic responses (pleasure)
○
Desire (wanting)
○
Reinforcing
○
Social aspects
○
-
Olds 1958:
Rats self-stimulate to death
reward -> Pleasure
○
Dopamine -> pleasure? NO!
Motivation/salience? YES!
○
-
Neurobiology of Rewards
Rewards increase synaptic dopamine in Nac
-
Dopamine projections to the forebrain.
From ventral tegmental area to the nucleus accumbens and
prefrontal cerebral cortex and projections from the substantia nigra
to the dorsal striatum (caudate and putamen and related
structures)
§
○
-
Initiation of Addiction
Increase extracellular dopamine (DA) levels in the Nac
-
Other neuromodulators
GABA, opioid peptides (opiates, Alcohol, nicotine)
○
Serotonin
○
Acetylcholine
○
Endocannabinoids
○
Glutamate (nicotine)
○
-
-Positive prediction error:
Unexpected reward -> increase in phasic firing
○
-No prediction error:
Expected reward -> increase in firing
○
-Negative prediction error:
Reward is withheld -> suppression of the tonic firing
○
In addiction, drugs are always better than expected
From Reward learning to addiction
-Drugs are always better than expected!
-Release of dopamine will produce what the brain interprets as a positive
prediction-error signal
-Drugs more valuable than all other rewards
-Repetitive pathological over learning of drug-related cues and drug experiences
-Even if subjective effects fall short of the expectation created by drug cues, the
massive surge of DA from the drugs in interpreted as a positive prediction error
signal
PFC
-Representation of goals (vmPFC) - valuation
-Assignment of value
-Action selection
-Executive control (OFC)
-Phasic dopamine gates the updating info in the PFC
-Overvaluation of drug related cues and impairment of top-down control
contribute significantly to addiction
Mechanisms in Striatum
-NAc and dorsal striatum are in ideal position for integration info about
motivation (VTA), and sensory-rich info (PFC)
From reward to addiction
-NAc -> Dorsal striatum
-Seeking of goals -> stimulate response habits
-Dopamine in NAc critical for establishment of drug-seeking behavior,
then activation shifts
-As addiction progresses, NAc activation shifts to dorsal striatum
activation involved in stimulus-response habits
Glutamate: a final common pathway
-Dopamine -> glutamate
-Hyperglutamatergic for drug-related stimuli
-Hypoglutamatergic for natural rewards
-The role of glutamate in addiction remains understudied
Relapse
-Drug-related cues
-DA release into the PFC and basolateral amygdala
-Stress
-CRF and noradrenaline
-Drug priming
-DA release into the PFC and NA shell
Treatment
-Key: stage of illness
-Initiation -> drug abuse -> dependence -> relapse
-Prevention approach:
-Identify and treat individuals at high risk (Vaccinations) - NOT AVAILABLE
-Disruption of acute reinforcement and conditioning
-Replacement therapy
○Methadone
-Relapse prevention
-Based on reinstatement paradigms
○Drug-related cues: blocking glutamate (Acamprosate + psychosocial)
-Stress
○Interruption of stress response - not available yet
○CRF1 and glucocorticoids antagonist
Conclusions
-Dopamine action can help us understand the progression from pleasurable
experimentation with drugs to a long-lived compulsion
-It's clear that neurotransmitters other than dopamine must play important roles
-Glutamate action may be a final common path
-Translational work remains a high priority
Striatum = caudate + putamen
NAc= most anterior part of ventral
striatum
More cravings -
hypermetabolism in
right OFC and
putamen during drug
use
Lecture 7
Sunday, June 10, 2018 8:39 PM
Darwin
Emotions have an evolutionary purpose
-
They are rational and inseparable from cognition and their influence on
behaviour
-
Nature vs Nurture
Culture determines when our 'hardwired' emotional expressions are displayed
(i.e. displayed rules)
Social constructionism
○
-
Emotions are not simply 'hardwired' by-products of evolution. They can only be
fully understood on a social level
-
What is an Emotion?
"emotion consists of neural circuits (that are at least partially dedicated),
response systems , and a feeling state/process that motivates and organizes
cognition and action"
-
Categorizing emotions
Valence (positive -negative)
Pleasure, displeasure
○
Approach, avoidance
○
-
Arousal (strength, intensity)
High or low intensity experience
○
Irrespective of valence
○
-
Distinctiveness
Qualitatively discrete emotions
Sadness, jealously, fear: all negative but different
§
○
-
What is emotion?
Subjective -> feeling
-
Bodily sensations -> physiological changes
Heart rate, sweat, adrenaline
○
-
Display of emotions
Facial expressions
○
Body language
○
-
Cognition
Rationalize emotion, regulate
○
-
Social aspects
Communication
○
Culture
○
-
Phylogenetic hierarchy
Forebrain
Thalamus (sensory integration)
○
Hippocampus (memory)
○
Hypothalamus (temp, hormones, sexual behaviour, aggression)
○
Limbic system (many subcortical areas)
○
-
Cerebral cortex: outer layer of forebrain
Cingulate gyrus (error monitoring, memory, emotion)
○
Parahippocampal gyrus (memory)
○
Association cortices (sensory integration)
○
-
Most cross-species evolutionary differences in cortex (e.g. PFC)
-
Neuroscience of Emotion
Limbic system
1937 J. Papez
Hypothalamus, hippocampus, anterior thalamus, cingulate cortex
§
Amygdala added later!
§
○
Cannon & Britton
Decorticated cats
§
No neo-cortical input
§
Shame rage
§
Cortex exhibits control on lower regions
§
○
Kluver & Bucy
Removal of anterior temporal lobes in rhesus monkeys
§
Became docile, hypersexual, hyperphagia, fearless
§
○
Olds & Milner
Implanted electrodes in septal regions of limbic system of rats
§
First evidence of rewards centers in the brain
§
First example of brain stimulation reward being used as operant
reinforcer
§
○
-
Amygdala
An 'emotion hub'
Integrates sensory input (across modalities)
Direct input from the olfactory bulb □
Visual and auditory cues via 'direct' thalamic routes □
§
Rapid, automatic evaluation
Arousal
□
Valence
□
§
○
A fear center
Involved in representations of negative states and detection of threat
across modalities
Negative facial expressions
□
Threat-related words
□
Aversive odors
□
§
Acquisition of fear responses via conditioning paradigms
Ledoux 1998,2000 (read)
□
Phelps (2001)
□
§
○
Zeroing in on the amygdala
Can receive inputs from the visual and auditory cortices via the
thalamus - not always via routes that lead to recognition
§
Makes for rapid, non-processed recognition of fear
§
LeDoux used fear conditioning to study the amygdala in rats
Pair shock with tone or light
□
§
Fear associations are formed quickly and long-lasting
These associations are persistent and hard to extinguish
□
§
Cortex isn't necessary for learning fear associations
"high" road (conscious, slow) vs. 'low" road (unconscious, fast)
□
Emotional learning can occur based on the simplest features of
a stimulus (e.g. shape, intensity)
□
§
LeDoux showed that you cannot form conditioned fear responses
without an intact thalamus and amygdala
§
○
-
Emotion (fear) pathways
○
-
What LeDoux's experiments revealed:
The amygdala is the core of a central emotional processing network that can
receive input unprocessed by cortex
-
The amygdala is where primary appraisals (good or bad) and automatic
evaluations of events occur
-
Amygdala is responsible for assigning emotional significance to events, with an
emphasis on negative salience
-
Three kinds of neuroimaging studies of humans supported LeDoux's claims
The amygdala is often activated during momentary emotional reactions to
evocative stimuli
1.
Individual differences in emotionality can be shown in amygdala activation 2.
Amygdala activity predicts whether people will recall emotionally significant
stimuli
3.
Amygdala known as centre for negative, fearful emotional processing, but this
prominent idea doesn't hold up:
40-50% of studies designed to elicit fear do not amygdala activation
-
Amygdala is activated for positive stimuli as well
-
Cunningham et al (2004) have shown that the amygdala responds to the
emotional intensity of a stimulus
Activation is irrespective for valence (positive/negative)
○
Depends on what you're motivated by, what is salient to you
○
-
Link to psychological theories
Dual process approach to brain function
Passion vs. Reason
○
Emotions vs. Cognition
○
-
System 1
Automatic
○
No voluntary control
○
Driven by affective impulses
○
-
System 2
Deliberative
○
Effortful and computational
○
Driven by rule-based thought
○
-
Challenges to the 'Limbic System'
Cingulate gyrus Monitoring
Regulation
salience
Parahippocampal gyrus Encoding/retrieval
Scene recognition
Visual perception
Hippocampus Episodic memory
Spatial navigation
Temporal processing
Thalamus Sensory/motor integration
Subcortical <-> cortical relay
Hypothalamus Autonomic Nervous System
Neuroendocrine functions
Amygdala Arousal
Relevance
Memory - reinforcement learning
Fear and reward
The hippocampus is critical for memory
-
Cortical regions are essential for emotional and social processing
-
Include PFC areas as part of "limbic system"?
-
-
No clean delineation b/w "affective" vs. "cognitive" brain structures
-
"cold" cognitive processes (e.g. memory, attention, perception) clearly contribute
to emotional experiences (e.g. psychological constructivism)
-
Affective processes contribute to decision-making (e.g. somatic marker
hypothesis (SMH))
-
Reciprocal relationship b/w emotion and cognition
-
Emotion and Cortical Processes
Frontal lobes
PFC centre of regulation and executive control
○
Primary affective sensations (i.e. pleasure/pain, arousal) are generated by
regions like the amygdala, ACC, NAc and PAG
○
These affective representations are integrated and held in STM to guide
behaviour in adaptive and socially appropriate ways
○
-
PFC elaborate emotion
Human subcortical systems receive greater cortical input
-
Lower levels responsible for primary affective sensations (pleasure and pain,
arousal)
-
Higher levels reproduce the lower levels as re-representations and add new
abstract features to them
-
Subcortical systems give up their autonomy relating to emotional functions. In
PFC, abstract representations become increasingly dominant
-
Complex emotional processes
Three PFC areas relevant to emotion
Orbitofrontal PFC
○
Dorsolateral PFC
○
Medial PFC
○
-
Important for emotion regulation
Ways in which we respond to and modify our emotional reactions and
experiences
○
-
Dorsolateral PFC (dIPFC) involved in:
Planning, abstract reasoning
○
Impulse control
Lying, selfishness
§
○
Social perspective taking
○
TMS disruption here results in more acceptance of unfair offers in
ultimatum game
○
Medial prefrontal cortex (MPFC) is involved in
Self- and socila representations (social brain)
○
Empathy
○
Experiences of reward
○
Orbitofrontal cortex (OFC)
Approach/ withdrawal tendencies
○
Represents goals, rewards and punishments
○
Important for extinction of learned rewards
○
Medial-lateral distinctions
Medial: monitoring, learning, memory
Overlaps with 'vmPFC'
®
□
Lateral: evaluation of rewarding vs. punishing properties,
leading to behavioural change
□
§
Posterior-Anterior distinctions
Posterior: multimodal sensory and motor integration
Integrate bodily (visceral info) - somatic marker
hypothesis
®
□
Anterior: increasingly abstract rewards
Rewards from more abstract stimuli (e.g. money)
®
Increasingly complexity in decisions b/w rewards
Choice A and B are both good!
◊
®
□
§
○
PFC reward representation
Overall, orbitofrontal cortex
Integrates multiple stimulus-reward associations across multiple modalities
○
Guides decision making and goal-directed behaviour
○
-
Connectivity allows convergence of
Current motivational state (represented in the PFC)
○
Affectively salient stimuli in the world (represented in the amygdala)
○
-
Anterior cingulate cortex
Dorsal (cognitive): connected to PFC, parietal, motor areas. Processes bottom-up
and top-down info and relaying control processes to other areas
-
Ventral (emotional): connected to amygdala, NAc, hypothalamus, insula.
Assesses emotional and motivational salience
-
Discrepancy detector: activated when you commit an error (pressed a key when
you shouldn't have)
-
Physical and social pain detector
Surgeons sometimes ablate the ACC of patients with intractable pain
○
Helps humans detect and respond to cues of rejection, separation and
exclusion
○
-
Emotional efficiency
Emotions as efficient heuristics for problem solving
Free up cognitive resources
○
Action tendencies allow for streamlined reactions with less deliberative
employment
○
-
Broadly allow for approach/avoidance strategies
-
We learn environmental risks and rewards from past experience
-
Emotion influences our judgements often without our knowledge
-
Emotion and cognition
Negative emotions: tied with specific action tendencies
Evolutionary utility
○
Narrowed thought- action repertoire promotes quick & decisive action -
immediate benefit
○
Associated with sympathetic activation
○
-
Positive emotions:
Broaden thought-action repertoires
○
Build enduring personal resources (physical, intellectual, social)
○
Allows for exploration, creativity, play, learning
○
Confers enduring benefits
○
-
Broaden and Build Theory
Emotions Bias Cognitive Processing
Positive emotions broaden awareness, build skills and resources 1.
When happy, we are more likely to:
See global patterns relative to specific details i.
See connection b/w groups and within relationshipsii.
2.
Positive emotions buffer negative life experiences
More resilient to bad experiences, physiology, returns to baseline
quicker
i.
3.
-
Emotion and Cognition Task
Mood manipulation: positive, negative, neutral images
-
Attend to faces, ignore houses
Report gender of faces (targets), ignore places (distractors)
○
-
Neurally: look at object-selective visual processing areas
Places: parahippocampal place area (PPA)
○
FACES: Fusiform face area (FFA)
○
-
Repetition reduction (RR) - neural adaptation or habituation
When an image is repeatedly presented and processed neurally, the neural
activation of that processing will be reduced with each subsequent
repetition of the stimulus
○
Specifically seen in visual processing areas (FFA, PPA)
○
Thought to reflect increased neural processing efficiency
○
This is used to neurally assess processing over time
If you are processing irrelevant task info (distractors), then you
should see RR for repeated place in PPA
§
○
Results:
Positive affect increased distractor processing (houses): Left PPA activation
for novel houses and greater repetition reduction (sign of attention) at
second exposure
○
Self-report of mood valence correlated with PPA activation 9more positive
states the greater PPA activation)
○
Emotional advantages
Can alter early perceptual processing
-
Emotion can confer benefits and deficits
-
Task dependent
Negative emotion better for visual search, more concrete and detailed
thinking
○
Positive emotions better for brainstorming, flexible, abstract thinking,
insight problem solving
○
-
Negative emotions are adaptive and important
-
Decision making and reward learning
This process has a lot of do with limbic structures, executive areas, emotion and
reward learning via dopamine activation
-
Stages of Decision Making
Learning -> (Representation -> valuation -> action selection) -> outcome
evaluation -> learning ……
Representation
Representation of the decision problem - context
"would you like fries or salad?"
®
□
Internal states:
"how hungry?"
®
□
External states:
"how much food?"
®
□
Different goals!
Lose weight vs. enjoy fries
®
□
§
Valuation
Options must be compared - value! □
Apples to oranges □
Salad to fries
How to compare them if not equal?
Common currency
◊
Subjective value (utility)
◊
®
□
§
Action selection
Implement decision -> eat SALAD!
How can we measure it?
Subjective value (utility)
◊
Common currency!
◊
®
□
Executive function □
Motor control □
§
Outcome evaluation
Reward vs. punishment
How good was the salad?
®
□
§
Learning
Update values - "salad better than expected"□
Influence future decision making - "order salad again"
How?
DOPAMINE!
◊
®
□
§
○
Dopamine in Basal Ganglia
3 main components
Striatum (largest component)
Caudate
§
Putamen
§
○
Globus pallidus
○
Substantia nigra ("black substance")
○
Subthalamic nucleus
○
-
-
How does dopamine work in reward/ learning?
Three subsystems:
Nigrostriatal (substantia nigra)
○
Mesolimbic (VTA)
○
Meocortical (VTA)
○
-
Mesolimbic Pathway
VTA(ventral tegmental area) -> NAc (Nucleus accumbens)
○
-
Stimulate to death
Olds 1958:
Rats will self-stimulate to death!
2000 presses/hour for 24 hrs
§
○
Reward -> pleasure
○
-
Dopamine
Pleasure neurotransmitter?
Blocking dopamine via lesioning or by genetically inactivation of tyrosine
hydroxylase does not stop happiness
Impair "wanting" but not "liking"
§
Dopamine transmission in NAc mediates the assignment of incentive
salience to rewards and reward-related cues
§
○
Dopamine plays a central role in reward-related learning
○
-
Dopamine and prediction errors
Positive prediction error:
Unexpected reward -> increase in phasic firing
○
-
No prediction error:
Expected reward -> no increase in firing
○
-
Negative prediction error:
Reward is withheld -> suppression of the tonic firing
○
-
DA firing is dependent on prediction error of reward
-
Reinforcement learning
Maximize future rewards
-
Memory/learning
-
Value prediction
-
Action selection
-
Rewards prediction error
-
Reward-related fMRI Responses
Reward (or reward anticipation) activities ventromedial prefrontal/orbitofrontal
cortex, striatum
-
Decision-making dysfunction: role in addiction?
A neurobiological illness whereby repetitive drug use corrupts and disorganizes
the normal circuitry of rewarding and adaptive behaviours
Compulsive drug-seeking behaviour
○
Inability to regulate such behaviours
○
Continued use of substances despite negative consequences
○
Reduced drive to acquire biological relevant natural rewards
○
Continued vulnerability to relapse
○
-
-
Tolerance
Increased dosage needed to maintain a "pleasurable" effect
-
Dependence
Need regular drug administration to "feel" normal
Dependence is not necessary or sufficient
○
-
Sensitization
Response increase with repeated dosing
These is a lack of compelling evidence for sensitization in humans
○
-
Homeostatic adaptation is believed to underlie tolerance and dependence
Natural rewards
Organisms learn factors critical for survival and continuation of a species such as
obtaining food, sex, social affiliation
Such goals function as rewards!
○
-
Additive drugs have many commonalities:
Hedonic responses (pleasure)
○
Desire (wanting)
○
Reinforcing
○
Social aspects
○
-
Olds 1958:
Rats self-stimulate to death
reward -> Pleasure
○
Dopamine -> pleasure? NO!
Motivation/salience? YES!
○
-
Neurobiology of Rewards
Rewards increase synaptic dopamine in Nac
-
Dopamine projections to the forebrain.
From ventral tegmental area to the nucleus accumbens and
prefrontal cerebral cortex and projections from the substantia nigra
to the dorsal striatum (caudate and putamen and related
structures)
§
○
-
Initiation of Addiction
Increase extracellular dopamine (DA) levels in the Nac
-
Other neuromodulators
GABA, opioid peptides (opiates, Alcohol, nicotine)
○
Serotonin
○
Acetylcholine
○
Endocannabinoids
○
Glutamate (nicotine)
○
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-Positive prediction error:
Unexpected reward -> increase in phasic firing
○
-No prediction error:
Expected reward -> increase in firing
○
-Negative prediction error:
Reward is withheld -> suppression of the tonic firing
○
In addiction, drugs are always better than expected
From Reward learning to addiction
-Drugs are always better than expected!
-Release of dopamine will produce what the brain interprets as a positive
prediction-error signal
-Drugs more valuable than all other rewards
-Repetitive pathological over learning of drug-related cues and drug experiences
-Even if subjective effects fall short of the expectation created by drug cues, the
massive surge of DA from the drugs in interpreted as a positive prediction error
signal
PFC
-Representation of goals (vmPFC) - valuation
-Assignment of value
-Action selection
-Executive control (OFC)
-Phasic dopamine gates the updating info in the PFC
-Overvaluation of drug related cues and impairment of top-down control
contribute significantly to addiction
Mechanisms in Striatum
-NAc and dorsal striatum are in ideal position for integration info about
motivation (VTA), and sensory-rich info (PFC)
From reward to addiction
-NAc -> Dorsal striatum
-Seeking of goals -> stimulate response habits
-Dopamine in NAc critical for establishment of drug-seeking behavior,
then activation shifts
-As addiction progresses, NAc activation shifts to dorsal striatum
activation involved in stimulus-response habits
Glutamate: a final common pathway
-Dopamine -> glutamate
-Hyperglutamatergic for drug-related stimuli
-Hypoglutamatergic for natural rewards
-The role of glutamate in addiction remains understudied
Relapse
-Drug-related cues
-DA release into the PFC and basolateral amygdala
-Stress
-CRF and noradrenaline
-Drug priming
-DA release into the PFC and NA shell
Treatment
-Key: stage of illness
-Initiation -> drug abuse -> dependence -> relapse
-Prevention approach:
-Identify and treat individuals at high risk (Vaccinations) - NOT AVAILABLE
-Disruption of acute reinforcement and conditioning
-Replacement therapy
○Methadone
-Relapse prevention
-Based on reinstatement paradigms
○Drug-related cues: blocking glutamate (Acamprosate + psychosocial)
-Stress
○Interruption of stress response - not available yet
○CRF1 and glucocorticoids antagonist
Conclusions
-Dopamine action can help us understand the progression from pleasurable
experimentation with drugs to a long-lived compulsion
-It's clear that neurotransmitters other than dopamine must play important roles
-Glutamate action may be a final common path
-Translational work remains a high priority
Striatum = caudate + putamen
NAc= most anterior part of ventral
striatum
More cravings -
hypermetabolism in
right OFC and
putamen during drug
use
Lecture 7
Sunday, June 10, 2018 8:39 PM
