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 electrophysiology techniques – – – – 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 Functional Neuroanatomy of Emotion Anterior Cingulate Dorsomedial Prefrontal Cortex Orbital Nucleus Accumbens Amygdala Ventral Pallidum Dalgleish, 2004 Hypothalamus Appraisal Experience Action The Amygdala Hippocampus Amygdala © BrainConnection.com The amygdalae are almond shapes bodies located in bilateral medial temporal lobe. 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 Conditioning Conditioned Stimulus (CS) Unconditioned Stimulus (US) Conditioned Response Fear Conditioning Defensive Behavior ANS arousal Hypoalgesia Reflex potentiation Stress hormones Ledoux, 1995 Auditory fear conditioning Information about the CS is integrated with information about the US within the amygdala. Phelps and Ledoux, 2005 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 33 (17) msec Whalen, P. J. et al. J. Neurosci. 1998;18:411-418 Copyright ©1998 Society for Neuroscience 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 Appraisal Experience Action Emotions serve an important function, but we also need to be able to put on the brakes. On the outside On the Inside Emotion regulation • The capacity to modify an emotional experience – 2 examples • Fear extinction • Active reappraisal Functional Neuroanatomy of Emotion Anterior Cingulate Dorsomedial Prefrontal Cortex Orbital Nucleus Accumbens Amygdala Ventral Pallidum Dalgleish, 2004 Hypothalamus 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 Reappraisal Ochsner 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 VMPFC • Reappraisal == using cognitive strategies to actively ‘spin’ a new interpretation of a previously aversive VMPFC, VLPFC cue 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? PTSD: Hyper-responsive amygdala Hypo-responsive VMPFC Summary by Milad et al., 2006 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.