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)

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***

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?

What are emotions and do they have a purpose?

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.

James-Lange Theory of emotion (late 1800s)

Physiology Appraisal

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

Cannon-Bard Theory of emotion(1920s)

Appraisal Physiology

“I feel afraid, so my heart pounds.”

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.

Schachter Two Factor Theory(Schachter and Singer, 1962)

Physiology + Context Feeling and action

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.

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

How do we study emotions?

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

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

Understanding the neurobiology of emotions

Dalgleish, 2004

Functional Neuroanatomy of Emotion

Nucleus Accumbens

Prefrontal Cortex

Dorsomedial

Orbital

Hypothalamus

Ventral Pallidum

Amygdala

Anterior Cingulate

Appraisal

Experience

Action

The Amygdala

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

Amygdala

Hippocampus

© BrainConnection.com

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)

Pavlovian ConditioningConditioned Stimulus (CS)

Unconditioned Stimulus (US)

Conditioned Response

Fear Conditioning

Ledoux, 1995

Defensive BehaviorANS arousalHypoalgesiaReflex potentiationStress hormones

Auditory fear

conditioning

Phelps and Ledoux, 2005

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

Fear conditioning in humans

LaBar et al., 1998

+

Insights on the role of the amygdala in appraising

emotions from Patient SM

S. M.

Insights on the role of the amygdala in appraising

emotions from Patient SM

Adolphs et al. 1994

Adolphs et al., 1995

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

Amygdala lesions disrupt physiological responding to conditioned cues in humans

Labar et al., 1998

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

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

et al., 1996).

•(Breiter et al., 1996)

Rapid processing in humans

Copyright ©1998 Society for Neuroscience

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

33 (17) msec

Whalen et al., 2004

Amygdala response habituates

Breiter et al., 1996

However, the role of the amygdala in emotion

processing is even more complicated than we thought

Resolving emotional ambiguity

Facilitating learning

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

AppraisalExperience

Action

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

able to put on the brakes.

On the Inside

On the outside

Emotion regulation

• The capacity to modify an emotional experience

– 2 examples• Fear extinction• Active reappraisal

Dalgleish, 2004

Functional Neuroanatomy of Emotion

Nucleus Accumbens

Prefrontal Cortex

Dorsomedial

Orbital

Hypothalamus

Ventral Pallidum

Amygdala

Anterior Cingulate

Fear extinction

Conditioned Response

Fear extinction

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

Animal findings

Milad & Quirk, 2002

Lesions to rodent infralimbic cortex prevent the retention of extinction memories

Human findings

VMPFC recruitment facilitates retention of extinction memory

VMPFC and regulation of reward approach

Bechara et al., 2005

Behavioral Results(Bechara et al., 1999)

$100 wins

$50 wins

Skin Conductance Results (Bechara et al., 1999)

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.

Kim et al., 2003

Kim et al., 2003

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

Ochsner et al., 2002

Amygdala activity modulated by regulation strategy

Ochsner et al., 2004

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

• 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

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!

Anxiety disorders and engagement of emotion circuitry

Meta-analysis Etkin & Wager, 2007

PTSD: failure to extinguish?

Summary by Milad et al., 2006

PTSD: Hyper-responsiveamygdala

Hypo-responsiveVMPFC

Depression: failure to reappraise?

Johnstone et al., 2008

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.