Shackman Psyc210 Module15 TPandMentalDisordersFocusExtendedAmygdala

PowerPoint Presentation

Nuts & Bolts Plan for TodayLecture (Davis, Fox, Feinstein papers)Focus on the neurobiology of BI, N/NE, and Emotional Disorders

PSYC 210:

How does N/NE contribute to emotional disorders?

Part 3 of 3

Focus on the Extended AmygdalaAJ Shackman16 April 2015Conceptual Roadmap for TodayWhat is the role of the amygdala in states of fear and anxiety?

How might it contribute to individual differences in N/NE/BI? What about social anxiety disorder?

Does the amygdala only contribute to arousal, or does it contribute to more complex features of T&P, such as attention, social affiliation, and relationship building?

Conceptual Roadmap for TodayWhat is the role of the amygdala in states of fear and anxiety?

How might it contribute to individual differences in N/NE/BI? What about social anxiety disorder?

Does the amygdala only contribute to arousal, or does it contribute to more complex features of T&P, such as attention, social affiliation, and relationship building?

Conceptual Roadmap for TodayWhat is the role of the amygdala in states of fear and anxiety?

How might it contribute to individual differences in N/NE/BI? What about social anxiety disorder?

Does the amygdala only contribute to arousal, or does it also contribute to more complex features of T&P, such as attention, social affiliation, and relationship building?

Jerry Kagan (Harvard)

Jerry Kagan (Harvard)The Hypothesized Root Cause

In the brain, these thoughts can often be traced to overreactivity in the amygdala, a small site in the middle of the brain thatresponds to novelty and threat.

In people born with a particular brain circuitry, the kind seen in Kagans high-reactive study Ss, the amygdala is hyperreactive, prickly as a haywire motion-detector light that turns on when nothings moving but the rain. Students?

Jerry Kagan (Harvard)The Hypothesized Root Cause

More Amygdala decreased thresholdincreased peakincreased recovery timeHow did Kagan come to this view?

Why the amygdala?

Why not the more ambiguous limbic system (a.k.a. Papez circuit) identified by Hans Eysenck?

Students, why was Kaganmore specific?

For a scathing critique of the limbic system concept, see JE LeDoux Concepts Neurosci. 1991How did Kagan come to this view?

Why the amygdala?

Why not the more ambiguous limbic system (a.k.a. Papez circuit) identified by Hans Eysenck?

Students, why was Kaganmore specific?

For a scathing critique of the limbic system concept, see JE LeDoux Concepts Neurosci. 1991Kagans view was profoundly influenced by Joe LeDoux and Mike DavisLedouxs band @ http://www.amygdaloids.com

Ledoux (NYU)Davis (Yale, Emory)Kagans view was profoundly influenced by Joe LeDoux and Mike Davis

Ledoux (NYU)Davis (Yale, Emory)Pavlovian Fear Conditioningin Rats

Kagans view was profoundly influenced by Joe LeDoux and Mike Davis

Pavlovian Fear Conditioningin RatsLedoux (NYU)Davis (Yale, Emory)Lesion studies demonstrate that the amygdala is requiredfor the normal acquisitionof new fear learningNot just rats

Students What have we already learned about amygdala damage and the conditioned emotional response?

Conditioned Emotional Response (SCR; Skin Conductance Response)

15Amygdala Lesions Block Conditioned FearAmygdala lesions attenuate conditionedFreezing (behavioral inhibition)

High-frequency vocalizations (help!)

Shock-probe avoidance

Potentiation of the startle reflex (a.k.a. fear-potentiated startle)Normal Full-Body Startle Reflex

0:13 ; watch using HD mode at 0.25x normal speedFear-Potentiated Startle in Humans

Schmitz & Grillon Nature Prot 2012Measure muscle activity (EMG) fromthe orbicularis oculi (muscle responsible for blinking the eye lid shut (and protecting the eye) in response to startling stimuliFear-Potentiated Startle in Humans

Schmitz & Grillon Nature Prot 2012Measure muscle activity (EMG) fromthe orbicularis oculi (muscle responsible for blinking the eye lid shut (and protecting the eye) in response to startling stimuliFear-Potentiated Startle in Humans

Schmitz & Grillon Nature Prot 2012Measure muscle activity (EMG) fromthe orbicularis oculi (muscle responsible for blinking the eye lid shut (and protecting the eye) in response to startling stimuliFear-Potentiated Startle in Humans

Schmitz & Grillon Nature Prot 2012

Safe/CS-Threat/CS+PotentiationMeasure muscle activity (EMG) fromthe orbicularis oculi (muscle responsible for blinking the eye lid shut (and protecting the eye) in response to startling stimuliFear-Potentiated Startle in Ratshttps://techtv.mit.edu/videos/16346-neurobiology-of-fear-anxiety-and-extinction-implications-for-psychotherapy (6:55 8:45)Fear-Potentiated Startle in Rats

https://techtv.mit.edu/videos/16346-neurobiology-of-fear-anxiety-and-extinction-implications-for-psychotherapy (6:55 8:45)accelerometerFear-Potentiated Startle in Rats

https://techtv.mit.edu/videos/16346-neurobiology-of-fear-anxiety-and-extinction-implications-for-psychotherapy (6:55 8:45)

accelerometerNot Just Learned Fear and AnxietyAmygdala Lesions Block Innate Fear in RodentsDavis & Whalen Mol Psych 2001 describing Blanchard & Blanchard 1972

Amygdala Lesions Block Innate Fear in Rodentsamygdala lesions dramatically increase the number of contacts a rat will make with a sedated cat. In fact, some of these lesioned animals crawl all over the cat and even nibble its ear, a behavior never shown by the non-lesioned animals.

Davis & Whalen Mol Psych 2001 describing Blanchard & Blanchard 1972

What about innate fear in primates?

Nothing (Empty Control)Assessing snake fear

Reach for TreatShackman, Fox et al., in prepDetails Are Not ImportantTo assess snake anxiety, the monkeys were trained to reach over a clear plastic box to obtain highly prefered treats, such as chocolate chips. Then we assessed performance in the presence of 29

Reach for TreatReal SnakeArtificial Rubber SnakeRoll of TapeNothing

Shackman, Fox et al., in prepAssessing snake fearDetails Are Not ImportantA live snake, a toy snake, a roll of tape, or nothing. This revealed30Kalin Shelton Davidson J Neuro 2004

Amygdala Lesions Reduce BI to Snake in Young MonkeysLesion GroupAsymmetric = lesion in only one hemisphereY 31How is this related to childhood BI?

Scary RobotChoi & Kim PNAS 2010

Scary robot (kids)Choi & Kim PNAS 2010

Scary robot (kids)Scary robo-gator (rats)Choi & Kim PNAS 2010http://www.youtube.com/watch?v=rnxwQpDisRE

Each time the animal approached the vicinity of the pelletthe Robogator surged, snapped its jaws once, and returned to its original position. The rat immediately fled to the nesting area.

Scary robot (kids)Scary robo-gator (rats)Choi & Kim PNAS 2010http://www.youtube.com/watch?v=rnxwQpDisREExcitotoxic lesions of the amygdala abolish rats innate fear of the RoboGator

Choi & Kim PNAS 2010

Scary robot (kids)Scary robo-gator (rats)

Details Are Not Important

Details Are Not Important

Details Are Not Important

Details Are Not Important

Details Are Not ImportantMaybe its just rats

What about primates?Amygdala Lesions Reduce BI to Human Intruder in Young Monkeys

Kalin Shelton Davidson J Neuro 2004

Details Are Not ImportantAmygdala lesions attenuate freezing in response to potential threat, consistent with a role in BI

But what about individual differences in BI?

Does variation in amygdala activitypredict individual differences in BI?Amygdala lesions attenuate freezing in response to potential threat, consistent with a role in BI

But what about individual differences in BI?

Does variation in amygdala activitypredict individual differences in BI?

Amygdala Metabolism Predicts Trait-Like Differences inFreezing/Cooing (BI) and Cortisol in Young MonkeysShackman et al PNAS 2013Shackman et al PNAS 2013N = 238

Shackman et al PNAS 2013N = 238

Shackman et al PNAS 2013N = 238

Shackman et al PNAS 2013

N = 238. WE WERE able to localize the amygdala cluster to 50OK, so we have mechanistic (and imaging) evidence in rats and monkeys

What about people?Feinstein, Adolphs, Damasio & Tranel Curr Biol 2011http://abcnews.go.com/Health/MindMoodNews/woman-iowa-damaged-amygdala-shows-fear/story?id=12404875

http://blogs.discovermagazine.com/notrocketscience/2010/12/16/meet-the-woman-without-fear/#.UpH-MsSsjJ8

2 tests pet store, haunted houseFeinstein, Adolphs, Damasio & Tranel Curr Biol 2011

http://blogs.discovermagazine.com/notrocketscience/2010/12/16/meet-the-woman-without-fear/#.UpH-MsSsjJ8

Feinstein, Adolphs, Damasio & Tranel Curr Biol 2011While others show trepidation before walking down empty corridors, she leads the way and beckons her companions to follow. When monsters leap out, she never screams in fright; instead, she laughs, approaches and talks to them. She even scares one of themonstersby poking itin the head.

SM is a woman without fear. She doesnt feel it. She has been held at knifepoint without a tinge of panic. Shell happily handle live snakes and spiders, even though she claims not to like them. She can sit through reels of upsetting footage without a single start.

During her visit to Waverley Hills [Haunted House], SM rated her level of fear throughout the experience. She said that she was excited and enthusiastic in the same way that she feels when she rides a rollercoaster, but never scared her scores always stayed at zero.

In a similar trip to an exotic pet store, her levels of fear never climbed over a score of 2/10. Even though she claimed to hate snakes and spiders, she was drawn to the snake enclosure, was excited about holding a serpent (This is so cool!) and had to be told not to touch or poke the bigger, more dangerous snakes (and a nearby tarantula). Why? She was overcome with curiosity.http://blogs.discovermagazine.com/notrocketscience/2010/12/16/meet-the-woman-without-fear/#.UpH-MsSsjJ8 Feinstein, Adolphs, Damasio & Tranel Curr Biol 2011While others show trepidation before walking down empty corridors, she leads the way and beckons her companions to follow. When monsters leap out, she never screams in fright; instead, she laughs, approaches and talks to them. She even scares one of themonstersby poking itin the head.

SM is a woman without fear. She doesnt feel it. She has been held at knifepoint without a tinge of panic. Shell happily handle live snakes and spiders, even though she claims not to like them. She can sit through reels of upsetting footage without a single start.

During her visit to Waverley Hills [Haunted House], SM rated her level of fear throughout the experience. She said that she was excited and enthusiastic in the same way that she feels when she rides a rollercoaster, but never scared her scores always stayed at zero.

In a similar trip to an exotic pet store, her levels of fear never climbed over a score of 2/10. Even though she claimed to hate snakes and spiders, she was drawn to the snake enclosure, was excited about holding a serpent (This is so cool!) and had to be told not to touch or poke the bigger, more dangerous snakes (and a nearby tarantula). Why? She was overcome with curiosity.http://blogs.discovermagazine.com/notrocketscience/2010/12/16/meet-the-woman-without-fear/#.UpH-MsSsjJ8 Feinstein, Adolphs, Damasio & Tranel Curr Biol 2011While others show trepidation before walking down empty corridors, she leads the way and beckons her companions to follow. When monsters leap out, she never screams in fright; instead, she laughs, approaches and talks to them. She even scares one of themonstersby poking itin the head.

SM is a woman without fear. She doesnt feel it. She has been held at knifepoint without a tinge of panic. Shell happily handle live snakes and spiders, even though she claims not to like them. She can sit through reels of upsetting footage without a single start.

During her visit to Waverley Hills [Haunted House], SM rated her level of fear throughout the experience. She said that she was excited and enthusiastic in the same way that she feels when she rides a rollercoaster, but never scared her scores always stayed at zero.

In a similar trip to an exotic pet store, her levels of fear never climbed over a score of 2/10. Even though she claimed to hate snakes and spiders, she was drawn to the snake enclosure, was excited about holding a serpent (This is so cool!) and had to be told not to touch or poke the bigger, more dangerous snakes (and a nearby tarantula). Why? She was overcome with curiosity.http://blogs.discovermagazine.com/notrocketscience/2010/12/16/meet-the-woman-without-fear/#.UpH-MsSsjJ8 Feinstein, Adolphs, Damasio & Tranel Curr Biol 2011While others show trepidation before walking down empty corridors, she leads the way and beckons her companions to follow. When monsters leap out, she never screams in fright; instead, she laughs, approaches and talks to them. She even scares one of themonstersby poking itin the head.

SM is a woman without fear. She doesnt feel it. She has been held at knifepoint without a tinge of panic. Shell happily handle live snakes and spiders, even though she claims not to like them. She can sit through reels of upsetting footage without a single start.

During her visit to Waverley Hills [Haunted House], SM rated her level of fear throughout the experience. She said that she was excited and enthusiastic in the same way that she feels when she rides a rollercoaster, but never scared her scores always stayed at zero.

In a similar trip to an exotic pet store, her levels of fear never climbed over a score of 2/10. Even though she claimed to hate snakes and spiders, she was drawn to the snake enclosure, was excited about holding a serpent (This is so cool!) and had to be told not to touch or poke the bigger, more dangerous snakes (and a nearby tarantula). Why? She was overcome with curiosity.http://blogs.discovermagazine.com/notrocketscience/2010/12/16/meet-the-woman-without-fear/#.UpH-MsSsjJ8 Feinstein, Adolphs, Damasio & Tranel Curr Biol 2011When Feinstein showed SM a set of film clips, she generally behaved on cue, laughing at the happy clips and shouting in revulsion at the disgusting ones. But in response to 10 scary film clips (includingThe Shining,Seven, andThe Ring) nothing. She showed no signs of terror, nor did she report any. She said thatmost peoplewould probably be scared by the films but she herself felt nothing.

SMs unusual reactions during these isolated scenarios are reflected in her day-to-day life. When Feinstein gave her an electronic handheld emotion diary, she reported feeling every basic emotion other than fear. In fact, out of a range of 50 possible emotional descriptions, the one she rated most highly over 3 months was fearless.

After more digging, Feinstein uncovered a history of behavior consistent with lack of fear. SMs eldest son cant remember a single instance when mom felt fear or looked like she was scared. His anecdotes even support the results of Feinsteins pet store trip. Me and my brothers see this snake on the road, he writes. I was like, Holy cow, thats a big snake! Well mom just ran over there and picked it up and brought it out of the street, put it in the grass and let it go on its way She would always tell me how she was scared of snakes and stuff like that, but then all of a sudden shes fearless of them. I thought that was kind of weird.http://blogs.discovermagazine.com/notrocketscience/2010/12/16/meet-the-woman-without-fear/#.UpH-MsSsjJ8 Feinstein, Adolphs, Damasio & Tranel Curr Biol 2011When Feinstein showed SM a set of film clips, she generally behaved on cue, laughing at the happy clips and shouting in revulsion at the disgusting ones. But in response to 10 scary film clips (includingThe Shining,Seven, andThe Ring) nothing. She showed no signs of terror, nor did she report any. She said thatmost peoplewould probably be scared by the films but she herself felt nothing.

SMs unusual reactions during these isolated scenarios are reflected in her day-to-day life. When Feinstein gave her an electronic handheld emotion diary, she reported feeling every basic emotion other than fear. In fact, out of a range of 50 possible emotional descriptions, the one she rated most highly over 3 months was fearless.

After more digging, Feinstein uncovered a history of behavior consistent with lack of fear. SMs eldest son cant remember a single instance when mom felt fear or looked like she was scared. His anecdotes even support the results of Feinsteins pet store trip. Me and my brothers see this snake on the road, he writes. I was like, Holy cow, thats a big snake! Well mom just ran over there and picked it up and brought it out of the street, put it in the grass and let it go on its way She would always tell me how she was scared of snakes and stuff like that, but then all of a sudden shes fearless of them. I thought that was kind of weird.http://blogs.discovermagazine.com/notrocketscience/2010/12/16/meet-the-woman-without-fear/#.UpH-MsSsjJ8 Feinstein, Adolphs, Damasio & Tranel Curr Biol 2011When Feinstein showed SM a set of film clips, she generally behaved on cue, laughing at the happy clips and shouting in revulsion at the disgusting ones. But in response to 10 scary film clips (includingThe Shining,Seven, andThe Ring) nothing. She showed no signs of terror, nor did she report any. She said thatmost peoplewould probably be scared by the films but she herself felt nothing.

SMs unusual reactions during these isolated scenarios are reflected in her day-to-day life. When Feinstein gave her an electronic handheld emotion diary, she reported feeling every basic emotion other than fear. In fact, out of a range of 50 possible emotional descriptions, the one she rated most highly over 3 months was fearless.

After more digging, Feinstein uncovered a history of behavior consistent with lack of fear. SMs eldest son cant remember a single instance when mom felt fear or looked like she was scared. His anecdotes even support the results of Feinsteins pet store trip. Me and my brothers see this snake on the road, he writes. I was like, Holy cow, thats a big snake! Well mom just ran over there and picked it up and brought it out of the street, put it in the grass and let it go on its way She would always tell me how she was scared of snakes and stuff like that, but then all of a sudden shes fearless of them. I thought that was kind of weird.http://blogs.discovermagazine.com/notrocketscience/2010/12/16/meet-the-woman-without-fear/#.UpH-MsSsjJ8 Feinstein, Adolphs, Damasio & Tranel Curr Biol 2011Other events in SMs life are less benign. Fourteen years ago, she was walking through a small park at 10pm, when a man beckoned her over to a bench. As she approached, he pulled her Down, stuck a knife to her throat, and said, Im going to cut you, bitch! SM didnt panic; she didnt feel afraid. Hearing a church choir sing in the distance, she confidently said, If youre going to kill me, youre gonna have to go through my Gods angels first. The man let her go and she walked (not ran) away. The next day, she returned to the same park.

These sorts of things happen to her a lot.

Its not that SM has had a cosseted life. She lives in a poor area replete with crime, drugs and danger. As Feinstein writes, she has been held up at knife point and at gun point, she was once physically accosted by a woman twice her size, she was nearly killed in an act of domestic violence, and on more than one occasion she has been explicitly threatened with death. But in most of these situations, she didnt act with urgency or desperation, something that police reports have corroborated.

Interestingly, a few years back, the team asked 2 clinical psychologists to interview SM without any knowledge of her lesions. They described her as a survivor, as resilient and even heroic in how she coped with adversity.

http://blogs.discovermagazine.com/notrocketscience/2010/12/16/meet-the-woman-without-fear/#.UpH-MsSsjJ8 Feinstein, Adolphs, Damasio & Tranel Curr Biol 2011Other events in SMs life are less benign. Fourteen years ago, she was walking through a small park at 10pm, when a man beckoned her over to a bench. As she approached, he pulled her Down, stuck a knife to her throat, and said, Im going to cut you, bitch! SM didnt panic; she didnt feel afraid. Hearing a church choir sing in the distance, she confidently said, If youre going to kill me, youre gonna have to go through my Gods angels first. The man let her go and she walked (not ran) away. The next day, she returned to the same park.

These sorts of things happen to her a lot.

Its not that SM has had a cosseted life. She lives in a poor area replete with crime, drugs and danger. As Feinstein writes, she has been held up at knife point and at gun point, she was once physically accosted by a woman twice her size, she was nearly killed in an act of domestic violence, and on more than one occasion she has been explicitly threatened with death. But in most of these situations, she didnt act with urgency or desperation, something that police reports have corroborated.

Interestingly, a few years back, the team asked 2 clinical psychologists to interview SM without any knowledge of her lesions. They described her as a survivor, as resilient and even heroic in how she coped with adversity.

http://blogs.discovermagazine.com/notrocketscience/2010/12/16/meet-the-woman-without-fear/#.UpH-MsSsjJ8So amygdala damage reduces normative, adaptive fear in humans

What about self-reported trait anxiety?

Adolphs in pressSo amygdala damage reduces negative emotion (states/traits) in humans

What about Kagan-ian BI?

See Blackford & Pine for a review of other relevant data

See Blackford & Pine for a review of other relevant dataNot just Schwartz

Fox & Kalin Amer J Psychiatry 2014BI is a facet of N/NE

Does the amygdalapredict individualdifferences in N/NE?

BI is a facet of N/NE

Do individualdifferences in N/NE also predict amygdala activation?

High-N/NE Individuals Show Increased Amygdala Activation to Threat

Meta-Analysis of Imaging Studies: Calder et al PTRSB 2011N/NE and BI are associated with heightenedamygdala activation

Kids with stable, high levels of BI are more likely to develop anxiety disorders (e.g., SAD)

Do we see increased amygdala activation in patients?N/NE and BI are associated with heightenedamygdala activation

Kids with stable, high levels of BI are more likely to develop anxiety disorders (e.g., SAD)

Do we see increased amygdala activation in patients?N/NE and BI are associated with heightenedamygdala activation

Kids with stable, high levels of BI are more likely to develop anxiety disorders (e.g., SAD)

Do we see increased amygdala activation in anxiety patients?

Meta-Analysis of Imaging Studies; Etkin & Wager Amer J Psychiatry 2007Yes. Amygdala is More ReactiveThe imaging data are cross-sectionaland could represent a symptomrather than a cause

Does amygdala reactivity prospectively predict disorder onset?The imaging data are cross-sectionaland could represent a symptomrather than a cause

Does amygdala reactivity prospectively predict disorder onset?McLaughlin et al Dep and Anx 2014; see also Admon et al. (Talma Hendlers group at Tel Aviv) Cer Cortex and PNAS

Serendipitousstudy of the BostonMarathon bombing Details Are Not ImportantMcLaughlin et al Dep and Anx 2014; see also Admon et al. (Talma Hendlers group at Tel Aviv) Cer Cortex and PNAS

Terrorist attack at the 2013 Boston MarathonKilled three spectators and injured hundredsFour days after the attack, a manhunt for the perpetrators resulted in an unprecedented shelter in place order that required residents of Boston and surrounding communities to remain indoorsPublic transportation, educational institutions, government offices, and most businesses were closedAlthough direct exposure to the attack was limited to spectators at the finish line of the marathon, hundreds of thousands of Boston residents watched the manhunt unfold live on television, while the shelter in place order was in effect (~12 hr)This kind of indirect media exposure to terrorist attacks can precipitate PTSD symptoms in individuals living in proximity to the attackDoes amygdala function assessed 1 year prior to the bombing predict PTSD onset?Serendipitousstudy of the BostonMarathon bombing McLaughlin et al Dep and Anx 2014; see also Admon et al. (Talma Hendlers group at Tel Aviv) Cer Cortex and PNAS

Terrorist attack at the 2013 Boston MarathonKilled three spectators and injured hundredsFour days after the attack, a manhunt for the perpetrators resulted in an unprecedented shelter in place order that required residents of Boston and surrounding communities to remain indoorsPublic transportation, educational institutions, government offices, and most businesses were closedAlthough direct exposure to the attack was limited to spectators at the finish line of the marathon, hundreds of thousands of Boston residents watched the manhunt unfold live on television, while the shelter in place order was in effect (~12 hr)This kind of indirect media exposure to terrorist attacks can precipitate PTSD symptoms in individuals living in proximity to the attackDoes amygdala function assessed 1 year prior to the bombing predict PTSD onset?Serendipitousstudy of the BostonMarathon bombing McLaughlin et al Dep and Anx 2014; see also Admon et al. (Talma Hendlers group at Tel Aviv) Cer Cortex and PNAS

Terrorist attack at the 2013 Boston MarathonKilled three spectators and injured hundredsFour days after the attack, a manhunt for the perpetrators resulted in an unprecedented shelter in place order that required residents of Boston and surrounding communities to remain indoorsPublic transportation, educational institutions, government offices, and most businesses were closedAlthough direct exposure to the attack was limited to spectators at the finish line of the marathon, hundreds of thousands of Boston residents watched the manhunt unfold live on television, while the shelter in place order was in effect (~12 hr)This kind of indirect media exposure to terrorist attacks can precipitate PTSD symptoms in individuals living in proximity to the attackDoes amygdala function assessed 1 year prior to the bombing predict PTSD onset?Serendipitousstudy of the BostonMarathon bombing McLaughlin et al Dep and Anx 2014; see also Admon et al. (Talma Hendlers group at Tel Aviv) Cer Cortex and PNAS

Terrorist attack at the 2013 Boston MarathonKilled three spectators and injured hundredsFour days after the attack, a manhunt for the perpetrators resulted in an unprecedented shelter in place order that required residents of Boston and surrounding communities to remain indoorsPublic transportation, educational institutions, government offices, and most businesses were closedAlthough direct exposure to the attack was limited to spectators at the finish line of the marathon, hundreds of thousands of Boston residents watched the manhunt unfold live on television, while the shelter in place order was in effect (~12 hr)This kind of indirect media exposure to terrorist attacks can precipitate PTSD symptoms in individuals living in proximity to the attackDoes amygdala function assessed 1 year prior to the bombing predict PTSD onset?Serendipitousstudy of the BostonMarathon bombing McLaughlin et al Dep and Anx 2014; see also Admon et al. (Talma Hendlers group at Tel Aviv) Cer Cortex and PNASYes.

Not just in Boston

Not just in Boston

2015

Suggesting that heightened amygdala reactivity represents a diathesis for the development of mood and anxiety disorders in the presence of stressors, trauma, and negative life eventsThe imaging data are correlational

Do anxiety-reducing drugs reduce amygdala reactivity?The imaging data are correlational

Do anxiety-reducing drugs reduce amygdala reactivity?

Yes! Amygdala activation is attenuated by anxiolytic administrationPaulus et al Arch Gen Psychiatry 2005

Dose-dependent decreaseYes! Amygdala activation in response to public speaking is attenuated in social phobia by anxiolytics and CBTArch Gen Psychiatry 2002

The amygdala orchestrates fear

This is consistent with the amygdalas connectivity, its inputs and outputsThe amygdala orchestrates fear

This is consistent with the amygdalas connectivity, its inputs and outputsAmygdala is a Neural Hub:Receives Rich Sensory Information About the World (Inputs)

Amygdala is a Neural Hub:Receives Rich Sensory Information About the World (Inputs)Details Are Not ImportantAmygdala projects to the regions that mediate components of fear

Amygdala projects to the regions that mediate components of fear

Details Are Not ImportantStudents Are these data sufficient to explain the BI Phenotype (or SAD)?

Is high BI more than just a pounding heart and distress?

What are some other hallmarks?

If low on time, skip this next chunkThe amygdala does much more than just orchestrate arousal:

Vigilance

Vigilance / Risk AssessmentBI. Toddlers who avoid unfamiliar events and people. When faced with such challenges, these children ceased their play and withdrew to the proximity of their caregivers. They remainedvigilant and rarely approached novel objects or unfamiliar people.

105Amaral Biol Psych 2002

106Vuillemier et al. Nat Neurosci 2004

FFA: Fusiform Face AreaAND Amyg lesions eliminate the enhanced activity typically elicited by fear faces in the visual cortex. Furthermore, as one would expect, this circuit appears to be sensitive to stress. In particular, 107The amygdala does much more than just orchestrate arousal:

Trust & Social Reticence

Trust and Social ReticenceBI. Toddlers who avoid unfamiliar events and people. When faced with such challenges, these children ceased their play and withdrew to the proximity of their caregivers. They remainedvigilant and rarely approached novel objects or unfamiliar people.Perhaps high BI individualsperceive others as less trustworthy or more threatening?Faces differ in how trustworthy they appear

Faces differ in how trustworthy they appear

Does the amygdala contribute to these kinds of trustworthiness perceptions?Does amygdala damage change how much trust others?

Yes. Amygdala damage increases trust / approachability ratings

Yes. Amygdala damage increases trust / approachability ratingsYes, but thats just self-report ratings

What about actual behavior?

Does amygdala damage alter actual social approach?

Amygdala Damage Reduces Social DistanceOr, Amygdala Damage Makes You a Close-TalkerWe all have a personal bubble, an invisible zone of privacy around our bodies. When strangers cross this boundary, it makes us feel uncomfortable.

Kennedy asked Patient SM to say when she felt most comfortable as a female experimenter walked towards her. On average, she preferred a distance of around a foot, about half the usual two-foot gap that 20 other normal people demanded.

The fact that SM had a boundary at all was probably because at close distances, its hard to see people. She said time and time again that she was actually comfortable at any distance, and during one trial, she actually walked all the way to her partner until they were actually touching. Even when they were making direct eye contact and touching nose-to-nose, she only rated the experience as 1 on a comfort scale of 1 to 10, where 1 is perfectly comfortable and 10 is a level of discomfort that only the British can survive. When a male stranger talked to her up close, she again rated the chat as a 1 (even though he gave it a 7).

http://blogs.discovermagazine.com/notrocketscience/2009/08/30/brain-damage-pops-womans-personal-bubble/#.UpIB98SsjJ8Kennedy, Glaescher, Tyszka JM & Adolphs Nat Neurosci 2009Amygdala Damage Reduces Social DistanceOr, Amygdala Damage Makes You a Close-TalkerWe all have a personal bubble, an invisible zone of privacy around our bodies. When strangers cross this boundary, it makes us feel uncomfortable.

Kennedy asked Patient SM to say when she felt most comfortable as a female experimenter walked towards her. On average, she preferred a distance of around a foot, about half the usual two-foot gap that 20 other normal people demanded.

The fact that SM had a boundary at all was probably because at close distances, its hard to see people. She said time and time again that she was actually comfortable at any distance, and during one trial, she actually walked all the way to her partner until they were actually touching. Even when they were making direct eye contact and touching nose-to-nose, she only rated the experience as 1 on a comfort scale of 1 to 10, where 1 is perfectly comfortable and 10 is a level of discomfort that only the British can survive. When a male stranger talked to her up close, she again rated the chat as a 1 (even though he gave it a 7).

http://blogs.discovermagazine.com/notrocketscience/2009/08/30/brain-damage-pops-womans-personal-bubble/#.UpIB98SsjJ8Kennedy, Glaescher, Tyszka JM & Adolphs Nat Neurosci 2009Amygdala Damage Reduces Social DistanceOr, Amygdala Damage Makes You a Close-TalkerWe all have a personal bubble, an invisible zone of privacy around our bodies. When strangers cross this boundary, it makes us feel uncomfortable.

Kennedy asked Patient SM to say when she felt most comfortable as a female experimenter walked towards her. On average, she preferred a distance of around a foot, about half the usual two-foot gap that 20 other normal people demanded.

The fact that SM had a boundary at all was probably because at close distances, its hard to see people. She said time and time again that she was actually comfortable at any distance, and during one trial, she actually walked all the way to her partner until they were actually touching. Even when they were making direct eye contact and touching nose-to-nose, she only rated the experience as 1 on a comfort scale of 1 to 10, where 1 is perfectly comfortable and 10 is a level of discomfort that only the British can survive. When a male stranger talked to her up close, she again rated the chat as a 1 (even though he gave it a 7).

http://blogs.discovermagazine.com/notrocketscience/2009/08/30/brain-damage-pops-womans-personal-bubble/#.UpIB98SsjJ8Kennedy, Glaescher, Tyszka JM & Adolphs Nat Neurosci 2009What about more complexchoices and decisions?

Or situations where there is apotential downside to trusting?

(Remember the MTV patients)

PNAS 20131. Subject is endowed with 12 points

PNAS 20132. Subject chooses how much to keep vs. invest

PNAS 20133. Invested points are multiplied by 3 and given to trustee

PNAS 20134. Trustee can back-transfer none, some, or all of it.If the trustee is fair, both benefit. If the trustee is selfish, you lose.

PNAS 2013What happens when patients with amygdaladamage play the trust game?

humans with selective [amydala] damage invest nearly 100% more money in unfamiliar others in [an economic game that requires trusting the other player] than do healthy controls.

PNAS 2013In short, a circuit centered on the amygdala likely contributes to diverse features of N/NE, BI, and social phobia

From a basic neuroscience perspective, the amygdala does so much more than just orchestrate fear and anxiety

In short, a circuit centered on the amygdala likely contributes to diverse features of N/NE, BI, and social phobia

From a basic neuroscience perspective, the amygdala does so much more than just orchestrate fear and anxietyFor instance

Adolphs ANYAS 2010Details Are Not ImportantThe point here is that the amygdala is not a fear center in the brain

It contributes to a broadspectrum of functions, including

Emotional learning

Emotional memory

Processing of social cues, likefaces and voices

Normative social interactions

Take Home Points

The root cause of BI is thought to be elevated amygdala reactivity (exact parameter unclear). AmygdalaRequired for new fear conditioning and innate fear e.g. snakesOrchestrates broad spectrum of responsesAmyg damage in humans reduces fearCeA damage in rats/monkeys Reduces BICeA metabolism predicts individual differences in BI in monkeysAmygdala more reactive in BI kids all grown up and patients with a variety of anx disAmygdala activation prospectively predicts the first onset of anx. DxAnti-anxiety drugs reduce amygdala activationAmygdala not just fear/anxietyVigilanceSocial distanceTrustTake Home Points

The root cause of BI is thought to be elevated amygdala reactivity (exact parameter unclear). AmygdalaRequired for new fear conditioning and innate fear e.g. snakesOrchestrates broad spectrum of responsesAmyg damage in humans reduces fearCeA damage in rats/monkeys Reduces BICeA metabolism predicts individual differences in BI in monkeysAmygdala more reactive in BI kids all grown up and patients with a variety of anx disAmygdala activation prospectively predicts the first onset of anx. DxAnti-anxiety drugs reduce amygdala activationAmygdala not just fear/anxietyVigilanceSocial distanceTrustTake Home Points

The root cause of BI is thought to be elevated amygdala reactivity (exact parameter unclear). AmygdalaOrchestrates broad spectrum of responsesOrchestrates broad spectrum of responsesAmyg damage in humans reduces fearCeA damage in rats/monkeys Reduces BICeA metabolism predicts individual differences in BI in monkeysAmygdala more reactive in BI kids all grown up and patients with a variety of anx disAmygdala activation prospectively predicts the first onset of anx. DxAnti-anxiety drugs reduce amygdala activationAmygdala not just fear/anxietyVigilanceSocial distanceTrustTake Home Points

The root cause of BI is thought to be elevated amygdala reactivity (exact parameter unclear). AmygdalaOrchestrates broad spectrum of responsesRequired for new fear conditioning and innate fear e.g. snakesAmyg damage in humans reduces fearCeA damage in rats/monkeys Reduces BICeA metabolism predicts individual differences in BI in monkeysAmygdala more reactive in BI kids all grown up and patients with a variety of anx disAmygdala activation prospectively predicts the first onset of anx. DxAnti-anxiety drugs reduce amygdala activationAmygdala not just fear/anxietyVigilanceSocial distanceTrustTake Home Points

The root cause of BI is thought to be elevated amygdala reactivity (exact parameter unclear). AmygdalaOrchestrates broad spectrum of responsesRequired for new fear conditioning and innate fear e.g. snakesAmyg damage in humans reduces fear and dispositional anxietyCeA damage in rats/monkeys Reduces BICeA metabolism predicts individual differences in BI in monkeysAmygdala more reactive in BI kids all grown up and patients with a variety of anx disAmygdala activation prospectively predicts the first onset of anx. DxAnti-anxiety drugs reduce amygdala activationAmygdala not just fear/anxietyVigilanceSocial distanceTrustTake Home Points

The root cause of BI is thought to be elevated amygdala reactivity (exact parameter unclear). AmygdalaOrchestrates broad spectrum of responsesRequired for new fear conditioning and innate fear e.g. snakesAmyg damage in humans reduces fear and dispositional anxietyCeA damage in rats/monkeys Reduces freezingCeA metabolism predicts individual differences in BI in monkeysAmygdala more reactive in BI kids all grown up and patients with a variety of anx disAmygdala activation prospectively predicts the first onset of anx. DxAnti-anxiety drugs reduce amygdala activationAmygdala not just fear/anxietyVigilanceSocial distanceTrustTake Home Points

The root cause of BI is thought to be elevated amygdala reactivity (exact parameter unclear). AmygdalaOrchestrates broad spectrum of responsesRequired for new fear conditioning and innate fear e.g. snakesAmyg damage in humans reduces fear and dispositional anxietyCeA damage in rats/monkeys Reduces freezingCeA metabolism predicts individual differences in BI in monkeysAmygdala more reactive in BI kids all grown up and patients with a variety of anx disAmygdala activation prospectively predicts the first onset of anx. DxAnti-anxiety drugs reduce amygdala activationAmygdala not just fear/anxietyVigilanceSocial distanceTrustTake Home Points

The root cause of BI is thought to be elevated amygdala reactivity (exact parameter unclear). AmygdalaOrchestrates broad spectrum of responsesRequired for new fear conditioning and innate fear e.g. snakesAmyg damage in humans reduces fear and dispositional anxietyCeA damage in rats/monkeys Reduces freezingCeA metabolism predicts individual differences in BI in monkeysAmygdala more reactive in BI kids all grown up and patients with a variety of anxiety disordersAmygdala activation prospectively predicts the first onset of anx. DxAnti-anxiety drugs reduce amygdala activationAmygdala not just fear/anxietyVigilanceSocial distanceTrustTake Home Points

The root cause of BI is thought to be elevated amygdala reactivity (exact parameter unclear). AmygdalaOrchestrates broad spectrum of responsesRequired for new fear conditioning and innate fear e.g. snakesAmyg damage in humans reduces fear and dispositional anxietyCeA damage in rats/monkeys Reduces freezingCeA metabolism predicts individual differences in BI in monkeysAmygdala more reactive in BI kids all grown up and patients with a variety of anxiety disordersAmygdala activation prospectively predicts the first onset of anx. DxAnti-anxiety drugs reduce amygdala activationAmygdala not just fear/anxietyVigilanceSocial distanceTrustTake Home Points

The root cause of BI is thought to be elevated amygdala reactivity (exact parameter unclear). AmygdalaOrchestrates broad spectrum of responsesRequired for new fear conditioning and innate fear e.g. snakesAmyg damage in humans reduces fear and dispositional anxietyCeA damage in rats/monkeys Reduces freezingCeA metabolism predicts individual differences in BI in monkeysAmygdala more reactive in BI kids all grown up and patients with a variety of anxiety disordersAmygdala activation prospectively predicts the first onset of anx. DxAnti-anxiety drugs reduce amygdala activationAmygdala not just fear/anxietyVigilanceSocial distanceTrustTake Home Points

The root cause of BI is thought to be elevated amygdala reactivity (exact parameter unclear). AmygdalaOrchestrates broad spectrum of responsesRequired for new fear conditioning and innate fear e.g. snakesAmyg damage in humans reduces fear and dispositional anxietyCeA damage in rats/monkeys Reduces freezingCeA metabolism predicts individual differences in BI in monkeysAmygdala more reactive in BI kids all grown up and patients with a variety of anxiety disordersAmygdala activation prospectively predicts the first onset of anx. DxAnti-anxiety drugs reduce amygdala activationAmygdala not just fear/anxietyVigilanceSocial distanceTrust ..and, as we shall see later in the term, substance abuseCritical Thinking Questions

Please respond to any 2Critical Thinking Question #1Watch Ralph Adolphs TEDx Lecturehttps://www.youtube.com/watch?v=nPj01uzRHY0

-or-

Watch Joe LeDouxs Copernicus Lecture https://www.youtube.com/watch?v=tjhCPhhzBqQ

-or-

Watch Paul Whalens Copernicus Lecturehttps://www.youtube.com/watch?v=nLTJaqew7I8

What do you think??

Briefly describe the most important or interesting things that you learned and a key challenge for future research.

Critical Thinking Question #2Animal research is controversial. This plays out in my own Facebook news feed. One dear friend, from undergraduate days at Wisconsin, is vehemently opposed to the kinds of work that I did in nonhuman primates and posted a petition denouncing the research on the grounds that it is inhumane. Another friend, from my post-doc years, recently wrote a long post defending the research (see following slides for excerpts).

What do you think?Briefly describe the potential pros and cons (scientific and/or ethical) of using nonhuman animal models to understand the mechanisms underlying psychiatric disease.

(Optional Video: Bioethics roundtable on the work:

You should feel comfortable opposing or attacking animal research. You have complete freedom of expression and it will not affect your grade in any way.FB Post #1

Critical Thinking Question #2Animal research is controversial. This plays out in my own Facebook news feed. One dear friend, from undergraduate days at Wisconsin, is vehemently opposed to the kinds of work that I did in nonhuman primates and posted a petition denouncing the research on the grounds that it is inhumane. Another friend, from my post-doc years, recently wrote a long post defending the research (see following slides for excerpts). In part, she pointed out that

What do you think?Briefly describe the potential pros and cons (scientific and/or ethical) of using nonhuman animal models to understand the mechanisms underlying psychiatric disease.

(Optional Video: Bioethics roundtable on the work:

You should feel comfortable opposing or attacking animal research. You have complete freedom of expression and it will not affect your grade in any way.The goal of the work is to discover, understand, and ultimately treat the root causes of severe childhood anxiety

https://www.youtube.com/watch?v=4VbxjsO9IYI

Critical Thinking Question #2Animal research is controversial. This plays out in my own Facebook news feed. One dear friend, from undergraduate days at Wisconsin, is vehemently opposed to the kinds of work that I did in nonhuman primates and posted a petition denouncing the research on the grounds that it is inhumane. Another friend, from my post-doc years, recently wrote a long post defending the research (see following slides for excerpts).

What do you think?Briefly describe the potential pros and cons (scientific and/or ethical) of using nonhuman animal models to understand the mechanisms underlying psychiatric disease.

(Optional Video: Bioethics roundtable on this work:https://www.youtube.com/watch?v=-dKlKaMwoVE)

You should feel comfortable opposing or attacking animal research. You have complete freedom of expression and it will not affect your grade in any way. I only ask that you take the time to reflect before writing.

Excerpts from FB Post #2The University of Wisconsin responds to the Animal Rights controversy regarding Dr. Kalin's research and it is spot on! Go UW, go Dr. Kalin!!!Responding to Ruth Deckers change.org petition

Since September, many people have taken interest in a University of WisconsinMadison study on the impact of early life stress on young rhesus monkeys. Thousands have added their names to a petition on the website change.org, calling for an end to the work, and we appreciate and share their concern for animals.

But we dont appreciate the way petitions author, Dr. Ruth Decker, misrepresents the research. By piling up mistakes, myths and exaggerations, and omitting important information, she asks well-meaning people to speak out with little understanding of the real science and the long, deliberative process through which it was approved.

This isnt fair to the people who signed the petition, or to UWMadison psychiatry professor Ned Kalin and the scientists involved in the work, or to the millions of people who suffer from mental illness for whom available treatment methods offer little relief.

The truth is of little concern to activists who wish to end animal research, no matter the benefit to humans and animals. We dont share that sentiment. We prefer people make their judgments on animal research with a fuller understanding of the research of both its costs and potential benefits.

So, if you have read the change.org petition, please also consider these corrections and additional information: This is not a repeat of experiments UWMadison psychology professor Harry Harlow conducted as many as five decades ago, some of which subjected animals to extreme stress and isolation. The methods for the modern work were selected specifically because they can reliably create mild to moderate symptoms of anxiety in the monkeys. They were chosen to minimize discomfort for the animals, and to minimize the number of animals required to provide researchers with answers to their questions.

There is no solitary confinement. The animals live in cages with other monkeys of their own age, a method of care called peer rearing. This method is often used when mothers reject their infant monkeys, which happens regularly in situations from nature to zoos to clinical nurseries with first-time mothers or following caesarean-section births. In a group setting, even veterinarians would have difficulty distinguishing the peer-reared animals from those that that were maternally reared.

The purpose of peer rearing is not to demonstrate that removing a monkey from its mother causes anxiety, a common misconception we have heard from people who have signed the petition.

Again: peer rearing was chosen because it is known to produce mild to moderate anxiety symptoms. With a group of animals predisposed to anxiety raised in a controlled setting, researchers can use state-of-the-art techniques to observe and measure even very subtle differences in brain chemistry and structure. Those chemical and anatomical differences may suggest new treatments via nutrition, exercise, meditation, drugs or another approach for people suffering from mental illness.

The animals in the study are not terrorized, and do not experience relentless torture. Most of their time is spent as a house pet would spend its days grooming, sleeping, eating and playing with toys, puzzles and other animals.

On occasion, to assess the monkeys level of anxious temperament, they are observed under two anxiety-provoking conditions. The first involves the presence of an unknown person who briefly enters the room, but does not make eye contact with the monkey. The second involves the monkey being able to see a snake, which is enclosed in a covered Plexiglas container in the same room, but outside the monkeys cage.

After each event, the animals brain activity is monitored by a non-invasive functional magnetic resonance scan, and blood samples are taken. The stress the monkeys experience is comparable to what an anxious human might feel when encountering a stranger or a snake or a nurse with a needle.

No one was left out of the review by UWMadison oversight committees. Several university committees spent a great deal of time assessing Dr. Kalins anxiety research, and each committee found it to be acceptable and ethical. These were groups of researchers, veterinarians and public representatives tasked with considering animal research on ethical grounds, and with ensuring potentially beneficial research will subject the fewest animals to the least invasive measures.

As the petition notes, an animal rights group took allegations about the committee process to the U.S. Department of Agriculture. What the petition does not mention is that USDA conducted an investigation in August in response to that complaint. Inspectors found the complaint lacking merit, and the process to be entirely within compliance with federal regulations.

And, as with all animal research on campus, specially trained veterinarians will care for the monkeys involved and ensure that all the work is done in accordance with federal regulations enforced by the National Institutes of Health and the USDA.

Most importantly, the petition repeatedly maligns the research as needless and unnecessary. We and many others think otherwise. Dr. Kalin, who treats human patients with anxiety and depression disorders, has worked for more than 30 years to understand both inherited and environmental causes of mental illness. His research was also reviewed and supported by panels of scientists at the National Institutes of Mental Health.

The decision to study animal models to understand human psychiatric disorders is not made lightly. Roughly a quarter of the people in the United States, including children, suffer from mental illness. Their conditions subject them to immeasurable disability and dysfunction. And the worst outcome, suicide, is increasing and already among the leading causes of death in adolescents. To develop effective treatments that may alleviate the suffering of millions, it is necessary to understand the root cause of psychiatric illnesses.

In this case, the human suffering is so great that Kalin, the National Institutes of Health and UWMadisons review committees believe the potential benefit of the knowledge gained from this research justifies the use of an animal model.

More information on the anxiety and depression research is available at animalresearch.wisc.edu.Critical Thinking Question #3Listen to this brief NPR podcast on Patient SM (includes the 1st ever public interview)

http://www.npr.org/programs/invisibilia/377515477/fearless?showDate=2015-01-16

Briefly comment on what you found most interesting about the podcast, as well as any concerns or criticisms you have about the way in which emotion, fear, or the amygdala was framed in the story.Critical Thinking Question #4Scanning the amygdala is hard! Read this brief excerpt from Rutishauser and colleagues (Trends in the Neurosciences, 2015)

What do you think?

Briefly comment on the implications of these concerns for what we have learned in class about the role of the extended amygdala in T&P and psychopathology

Critical Thinking Question #4Scanning the amygdala is hard! Read this brief excerpt from Rutishauser and colleagues (Trends in the Neurosciences, 2015)

What do you think?

Briefly comment on the implications of these concerns for what we have learned in class about the role of the extended amygdala in T&P and psychopathology

Critical Thinking Question #4Scanning the amygdala is hard! Read this brief excerpt from Rutishauser and colleagues (Trends in the Neurosciences, 2015)

What do you think?

Briefly comment on the implications of these concerns for what we have learned in class about the role of the extended amygdala in T&P and psychopathology

The EndTurn this into a critical thinking question

Things to Consider TweakingSpring 2015

Nims 2011 paper would be good for a Take Home Q so would Gamers J Neuro

Alex fox thesisAlex - mohantyExtra Slides

N/BI Take Home Points

BI is an early-emerging facet of N/NE

BI is a risk factor for the development of psychopathology, esp SAD

BI is moderately heritable and stable over time; its a candidate (transdiagnostic) endophenotype

Given that most kids with extreme BI very early in life grow out of it, BI is not isomorphic with psychopathology more likely a diathesis that precedes onset of Dx and requires adversity, sub-optimal parenting, or stress to presentAmygdala Damage Reduces Fear & AnxietyFeinstein, Adolphs, Damasio & Tranel Curr Biol 2011If you ask the woman herself, shell say that she feels upset or angry in the face of danger, but never fearful. Feinstein even thinks that because of her brain damage, she could be immune to posttraumatic stress disorder, a trait that sheshares with some combat veterans.

It wasnt always like this. She remembers being afraid of the dark as a young child, running away screaming when her older brother jumped out from behind a tree, and being pinned to a corner by a large Doberman (Thats the only time I really felt scared. Like gut-wrenching scared). But all of these events happened before her disease wrecked her amygdalae. During her adult life, Feinstein couldnt find a single episode where she clearly experienced fear.

http://abcnews.go.com/Health/MindMoodNews/woman-iowa-damaged-amygdala-shows-fear/story?id=12404875Alex add susskind/anderson paper

Jackie Clauss (Grad Student) & Jenni Blackford (Asst Prof), Vanderbilt PsychiatryFriends and colleagues who collaborate with Ned Kalins lab at Wisconsin, where I did postdoctoral work

http://www.youtube.com/watch?v=rnxwQpDisRE

Aside: Fear-Potentiated Startle in Ratshttps://techtv.mit.edu/videos/16346-neurobiology-of-fear-anxiety-and-extinction-implications-for-psychotherapy (6:55 8:45)

Amygdala is a Neural Hub:Orchestrates Fear (Outputs I)

If low on time, skip the next studyDoes the amygdala play a role in switching the focus of attention?

the active scanning for potential threat?

Amygdala Activity Predicts the Active Interrogation of the Environment (Risk Assessment)

Gamer & Buchel J Neurosci 2009; Gamer et al Curr Biol 2013

Amygdala Activity Predicts the Active Interrogation of the Environment (Risk Assessment)

Gamer & Buchel J Neurosci 2009; Gamer et al Curr Biol 2013

Amygdala Activity Predicts the Active Interrogation of the Environment (Risk Assessment)

Gamer & Buchel J Neurosci 2009; Gamer et al Curr Biol 2013Amygdala damage attenuates this active risk assessment behaviorMonkeys with precise amygdala lesions are less socially reticient / inhibitedAmygdala-lesioned animals are socially disinhibitedAcross social partners, amygdala-lesioned animals initiated more affiliative social behaviors

Amygdala-lesioned animals showed heightened affiliative social behaviors (e.g., approaches, withdrawals, solicitations for grooming, physical contact, grooming)

These overtures were reciprocated by control animals; amygdala-lesioned animals also received more groom solicitations, walk-bys (transient proximity) and extended time in close proximity from control animals than did other control animals

Suggests that heightened affiliative social interactions following amygdala lesions stems from a more general inability to properly perceive danger or threat in the environment and use such information to modulate social behavior adaptively.

In line with this view, deficits in threat detection or fear reactivity have been specifically demonstrated for monkeys with bilateral neurotoxic amygdala lesions in both social and nonsocial settingsDavid Amarals Group: Machado et al Behav Neurosci 2008; Mason et al., Emotion 2006