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Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University
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Page 1: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Affective Neuroscience

Leah Somerville, PhD

Sackler Institute for Developmental Psychobiology

Weill Medical College of Cornell University

Page 2: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

What is emotion?

• “one of the most significant things ever said about emotion may be that everyone knows what it is until they are asked to define it”– Joseph LeDoux (1996)

Page 3: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

What is emotion?• Emotion = reflects a kind of motion outward• An inferred complex sequence of reactions to a

stimulus including cognitive evaluations, subjective changes, autonomic and neural arousal, impulses to action, and behavior designed to have an effect (functional) upon the stimulus that initiated the complex sequence (Plutchik, 1982)

– Inferred– Reaction– Functional– ***Cognitive appraisal, feeling, and action***

Page 4: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Today’s agenda

1. What are emotions and do they have a purpose?

2. How does we study emotions in the laboratory?

3. What brain circuits support emotional processes?

4. How does emotion go awry in psychiatric conditions?

Page 5: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

What are emotions and do they have a purpose?

Page 6: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

A brief History of Affective Neuroscience

• The Expression of the Emotions in Man and Animal, Charles Darwin (1872)– Emotions are similar across species and cultures.

Page 7: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

James-Lange Theory of emotion (late 1800s)

Physiology Appraisal

“My heart is pounding, so I must be afraid.”

Page 8: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Cannon-Bard Theory of emotion(1920s)

Appraisal Physiology

“I feel afraid, so my heart pounds.”

Page 9: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Where these theories fall short

• J-L: Assumes there is a unique physiological signature to each emotion.

• C-B: Physiological responses are generated so quickly, it’s unlikely that we could have perceived the emotion first.

Page 10: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Schachter Two Factor Theory(Schachter and Singer, 1962)

Physiology + Context Feeling and action

Page 11: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Schachter & Singer’s classic study

• Shot of adrenaline to participants– Explained as having arousing

side effects or not mentioned• Placed in room with happy or angry

confederate• Participants with no explanation for

arousal experienced happiness or anger

There is still debate about what an emotion “is”, but nowadays it is agreed on that it involves interactions

between physiology, feeling, and context.

Page 12: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Adaptive purpose of emotions• Emotions induce motivation

Spring us into action

Lower sensory thresholds

Facilitates learning- enhance memory- modulates appropriate

approach/avoidance behavior- the arousal associated with

emotions facilitates performance (to a certain extent)

Yerkes-Dodson law

Page 13: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

How do we study emotions?

Page 14: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Affective Neuroscience Toolbox

• Animal models (especially fear)• Lesion studies• Psychophysiology

– Heart Rate– Skin conductance (ANS arousal)

• Neuroimaging:– fMRI (Hemodynamic response)

• Various other electrophysiologytechniques

– Electroencaphalography– Magnetoencephalography– Single unit recordings– Transcranial magnetic stimulation

Page 15: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

How to study emotion in the lab?• Tapping into emotional experiences and perception

– Make people emotional in the lab– Mood inductions– Paradigms that induce fear or anxiety (threat-of-shock) or other

emotions (displaying evocative imagery)– Measure responses to emotional cues (facial expressions)

• Tapping into emotional regulation and the outcome of experiencing emotion– Induce emotion measure subjects’ ability to dampen– Measure how emotions facilitate secondary behaviors (memory,

action)

• Directly test individuals who experience emotional dysregulation– Psychiatric illnesses involving fear, anxiety, depression

Page 16: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Understanding the neurobiology of emotions

Page 17: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Dalgleish, 2004

Functional Neuroanatomy of Emotion

Nucleus Accumbens

Prefrontal Cortex

Dorsomedial

Orbital

Hypothalamus

Ventral Pallidum

Amygdala

Anterior Cingulate

Page 18: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Appraisal

Experience

Action

Page 19: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

The Amygdala

The amygdalae are almond shapes bodies located in bilateral medial temporal lobe.

Amygdala

Hippocampus

© BrainConnection.com

Page 20: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Klüver-Bucy Syndrome (1939)• Bilateral removal of temporal cortex in monkeys.• Drastic Change in behavior:

– Loss of emotional reactivity,

– Hypersexuality,

– Orality,

– Disrupted social behavior,

– Falling in social standing.

• Weiskrantz (1956) bilateral lesions of amygdala produced similar behavioral changes.

• Improved methods (ibotenic acid lesions) showed that central site is amygdala (e.g. Murray et al., Behavioral Neuroscience, 1996)

Page 21: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Pavlovian ConditioningConditioned Stimulus (CS)

Unconditioned Stimulus (US)

Conditioned Response

Page 22: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Fear Conditioning

Ledoux, 1995

Defensive BehaviorANS arousalHypoalgesiaReflex potentiationStress hormones

Page 23: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Auditory fear

conditioning

Phelps and Ledoux, 2005

Information about the CS is integrated with information about the US within the amygdala.

Page 24: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.
Page 25: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Fear conditioning in humans

LaBar et al., 1998

+

Page 26: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Insights on the role of the amygdala in appraising

emotions from Patient SM

S. M.

Page 27: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Insights on the role of the amygdala in appraising

emotions from Patient SM

Adolphs et al. 1994

Page 28: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Adolphs et al., 1995

• Subject with bilateral amygdala lesions was asked to draw facial expressions of emotions.

Page 29: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Amygdala lesions disrupt physiological responding to conditioned cues in humans

Labar et al., 1998

Page 30: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Processing emotional cues in the environment

Something really bad is going on near us, and you’d do well to find out what I know

Page 31: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Amygdala and healthy adults• Amygdala responses to fearful faces in normal humans (Breiter

et al., 1996).

•(Breiter et al., 1996)

Page 32: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Rapid processing in humans

Copyright ©1998 Society for Neuroscience

Whalen, P. J. et al. J. Neurosci. 1998;18:411-418

33 (17) msec

Page 33: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Whalen et al., 2004

Page 34: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Amygdala response habituates

Breiter et al., 1996

Page 35: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

However, the role of the amygdala in emotion

processing is even more complicated than we thought

Resolving emotional ambiguity

Facilitating learning

Page 36: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

What conclusions can we draw about the role of the amygdala in

emotional processing?• An intact amygdala is necessary for the

acquisition and expression of fear (animal, lesion patients)

• In humans, the amygdala carries the more general role of detecting and learning about important information in the environment.– motivational salience account

Page 37: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

AppraisalExperience

Action

Page 38: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Emotions serve an important function, but we also need to be

able to put on the brakes.

On the Inside

On the outside

Page 39: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Emotion regulation

• The capacity to modify an emotional experience

– 2 examples• Fear extinction• Active reappraisal

Page 40: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Dalgleish, 2004

Functional Neuroanatomy of Emotion

Nucleus Accumbens

Prefrontal Cortex

Dorsomedial

Orbital

Hypothalamus

Ventral Pallidum

Amygdala

Anterior Cingulate

Page 41: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Fear extinction

Conditioned Response

Page 42: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Fear extinction

Page 43: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Extinction and the MPFC

• The ventromedial prefrontal cortex is critical to emotion regulation

• Enables new learning of a

positive interpretation of the

once-negative stimulus• Dampens amygdala response

via direct inhibitory gating• Behavior: no response to

previous fear cue

Page 44: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Animal findings

Milad & Quirk, 2002

Lesions to rodent infralimbic cortex prevent the retention of extinction memories

Page 45: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Human findings

VMPFC recruitment facilitates retention of extinction memory

Page 46: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

VMPFC and regulation of reward approach

Page 47: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Bechara et al., 2005

Page 48: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Behavioral Results(Bechara et al., 1999)

$100 wins

$50 wins

Page 49: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Skin Conductance Results (Bechara et al., 1999)

Page 50: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Results• Healthy control participants developed:

– “Hunches” about how to maximize wins.– Showed elevated SCR responses in anticipation of

outcomes after poor choices.

• Patients with ventromedial PFC damage:– Performed poorly on task (risky/low payoff

choices).• Did not maximize wins and losses.

– Did not show elevated SCR responses after poor choices.

Page 51: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.
Page 52: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Kim et al., 2003

Page 53: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Kim et al., 2003

Page 54: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Emotion regulation via Cognitive ReappraisalOchsner et al., 2002; 2004

Page 55: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Ochsner et al., 2002

Page 56: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Amygdala activity modulated by regulation strategy

Ochsner et al., 2004

Page 57: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

The story isn’t so simple – VMPFC may also be involved in reappraisal

• Other studies have used similar paradigms to show the VMPFC engaged while actively downregulating emotion

Page 58: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

• Extinction == learning a new interpretation of a previously aversive cue

• Reappraisal == using cognitive strategies to actively ‘spin’ a new interpretation of a previously aversive cue

VMPFC

VMPFC, VLPFC

Page 59: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Emotions & Psychopathology

• The symptoms of many psychiatric illnesses involve inappropriate emotional responses and/or ineffective emotion regulation

PTSD, phobias : Hyperresponsive emotional appraisal? Failure to extinguish?

Depression : Failure to reappraise?

This field is still a work-in-progress!

Page 60: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Anxiety disorders and engagement of emotion circuitry

Meta-analysis Etkin & Wager, 2007

Page 61: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

PTSD: failure to extinguish?

Summary by Milad et al., 2006

PTSD: Hyper-responsiveamygdala

Hypo-responsiveVMPFC

Page 62: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Depression: failure to reappraise?

Johnstone et al., 2008

Page 63: Affective Neuroscience Leah Somerville, PhD Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University.

Take-home points• Emotions are complex reactions involving feelings, physiological

reactions, and contextual interpretations.

• The generation and experience of emotion is primarily modulated through interactions between subcortical and cortical brain structures including the amygdala and subregions of the prefrontal cortex.

• The amygdala plays a critical role in emotional learning and generating appropriate responses to environmental cues.

• The VMPFC and VLPFC interact with subcortical structures like the amygdala to modulate emotional responses.

• Dysfunctional subcortical-cortical interactions play an important role in the pathophysiology of many psychiatric illnesses.


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