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

2. 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)

3. 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***

4. 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?

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

6. 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.

7. James-Lange Theory of emotion (late 1800s) Physiology  Appraisal “My heart is pounding, so I must be afraid.”

8. Cannon-Bard Theory of emotion (1920s) Appraisal  Physiology “I feel afraid, so my heart pounds.”

9. 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.

10. Schachter Two Factor Theory (Schachter and Singer, 1962) Physiology + Context  Feeling and action

11. 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.

12. 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

13. How do we study emotions?

14. 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

15. 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

16. Understanding the neurobiology of emotions

17. Dalgleish, 2004 Functional Neuroanatomy of Emotion Nucleus Accumbens Prefrontal Cortex Dorsomedial Orbital Hypothalamus Ventral Pallidum Amygdala Anterior Cingulate

18. Appraisal Experience Action

19. The Amygdala The amygdalae are almond shapes bodies located in bilateral medial temporal lobe. Amygdala Hippocampus © BrainConnection.com

20. 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)

21. Pavlovian Conditioning Conditioned Stimulus (CS) Unconditioned Stimulus (US) Conditioned Response

22. Fear Conditioning Ledoux, 1995 Defensive Behavior ANS arousal Hypoalgesia Reflex potentiation Stress hormones

23. Auditory fear conditioning Phelps and Ledoux, 2005 Information about the CS is integrated with information about the US within the amygdala.

25. Fear conditioning in humans LaBar et al., 1998 +

26. Insights on the role of the amygdala in appraising emotions from Patient SM S. M.

27. Insights on the role of the amygdala in appraising emotions from Patient SM Adolphs et al. 1994

28. Adolphs et al., 1995 Subject with bilateral amygdala lesions was asked to draw facial expressions of emotions.

29. Amygdala lesions disrupt physiological responding to conditioned cues in humans Labar et al., 1998

30. 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

31. Amygdala and healthy adults Amygdala responses to fearful faces in normal humans (Breiter et al., 1996). (Breiter et al., 1996)

32. Rapid processing in humans Copyright ©1998 Society for Neuroscience Whalen, P. J. et al. J. Neurosci. 1998;18:411-418 33 (17) msec

33. Whalen et al., 2004

34. Amygdala response habituates Breiter et al., 1996

35. However, the role of the amygdala in emotion processing is even more complicated than we thought Resolving emotional ambiguity Facilitating learning

36. 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

37. Appraisal Experience Action

38. Emotions serve an important function, but we also need to be able to put on the brakes. On the Inside On the outside

39. Emotion regulation The capacity to modify an emotional experience –2 examples Fear extinction Active reappraisal

40. Dalgleish, 2004 Functional Neuroanatomy of Emotion Nucleus Accumbens Prefrontal Cortex Dorsomedial Orbital Hypothalamus Ventral Pallidum Amygdala Anterior Cingulate

41. Fear extinction Conditioned Response

42. Fear extinction

43. 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

44. Animal findings Milad & Quirk, 2002 Lesions to rodent infralimbic cortex prevent the retention of extinction memories

45. Human findings VMPFC recruitment facilitates retention of extinction memory

46. VMPFC and regulation of reward approach

47. Bechara et al., 2005

48. Behavioral Results (Bechara et al., 1999) $100 wins $50 wins

49. Skin Conductance Results (Bechara et al., 1999)

50. 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.

52. Kim et al., 2003

54. Emotion regulation via Cognitive Reappraisal Ochsner et al., 2002; 2004

55. Ochsner et al., 2002

56. Amygdala activity modulated by regulation strategy Ochsner et al., 2004

57. 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

58. 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

59. 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!

60. Anxiety disorders and engagement of emotion circuitry Meta-analysis Etkin & Wager, 2007

61. PTSD: failure to extinguish? Summary by Milad et al., 2006 PTSD: Hyper-responsive amygdala Hypo-responsive VMPFC

62. Depression: failure to reappraise? Johnstone et al., 2008

63. 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.