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Shackman Psyc210 Module16 SplittingConstituents Part1 042015
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Nuts and Bolts Plan for Today • Lecture (Grupe & Nitschke; Macleod) – If we run low on @me, we will finish during the next lecture
• Take-‐home cri@cal thinking ques@ons
PSYC 210:
Dissec@ng broad-‐band N/NE into its key cons@tuents
Part 1 of 2
AJ Shackman 20 April 2015
Today’s Conceptual Roadmap • In prior lectures, we’ve talked about N/NE and its facet, BI.
Exploded View of Porsche 917 Engine
Today’s Conceptual Roadmap • But what exactly does it mean to be neuro@c, to show high levels of NE or BI?
– What are the key ingredients of this anxious phenotype?
– How are these components physically organized in the brain?
– Can we break it down, psychologically and neurally?
– What do you guys think?
Exploded View of Porsche 917 Engine
Today’s Conceptual Roadmap • But what exactly does it mean to be neuro@c, to show high levels of NE or BI?
– What are the key ingredients of this anxious phenotype?
– How are these components physically organized in the brain?
– Can we break it down, psychologically and neurally?
– What is the value of dissecBng?
Exploded View of Porsche 917 Engine
Brief reminder of what we already know about intermediate phenotypes, using C/SC as an illustra@on
Students: How Might We Go About Determining the Substrates of a Trait (e.g., C/SC)?
Try to forge a link between… • T&P: Varia4on in C/SC and
• Candidate Cause: Some other process or measure (psychological or biological cause)
Students— How might we go about this…?
Quan@fy individual differences in C/SC
One-‐Shot Self-‐Report Mul@-‐Informant Behavioral Composite
In either case, you end up with a single number Students: Why is this potenBally problemaBc??
Quan@fy individual differences in C/SC
One-‐Shot Self-‐Report Mul@-‐Informant Behavioral Composite
In either case, you end up with a single number Students: Why is this potenBally problemaBc??
But ‘one number’ is not a sensible approach
Mayor Ford (Toronto) Mayor Barry (DC)
More than one process at work (psychological process, neural circuit, gene@c variants)
C/SC is Complex
C/SC is Complex
Complexity impedes the search for simple substrates Need to simplify! Focus on one key element at a @me.
Defined by constella@on of symptoms, not causes (‘pathophysiology’), including altera@ons in thought, language, behavior, and mood Complexity is compounded by the “Dim Sum Buffet” problem
• different ways to get there (‘polythe4c’ diagnos4c categories)
Outward manifesta@ons are oaen non-‐specific (aka transdiagnos@c)
C/SC is Complex
Complexity impedes the search for simple substrates Need to simplify! Focus on one key element at a @me.
Defined by constella@on of symptoms, not causes (‘pathophysiology’), including altera@ons in thought, language, behavior, and mood Complexity is compounded by the “Dim Sum Buffet” problem
• different ways to get there (‘polythe4c’ diagnos4c categories)
Outward manifesta@ons are oaen non-‐specific (aka transdiagnos@c)
C/SC is Complex
Complexity and heterogeneity impedes the search for simple substrates Need to dissect or decompose! Focus on one key element at a @me.
Defined by constella@on of symptoms, not causes (‘pathophysiology’), including altera@ons in thought, language, behavior, and mood Complexity is compounded by the “Dim Sum Buffet” problem
• different ways to get there (‘polythe4c’ diagnos4c categories)
Simpler Intermediate Phenotypes
Delay of GraBficaBon
Complexity impedes the search for simple substrates Need to simplify!
Let’s apply this strategy to N/NE
Hang on! -‐ Why Bother?
Students: What do we know about the impact of N/NE on important,
real-‐world outcomes such as mental health
Kessler et al 2012; Bystritsky 2006; Whiteford et al 2013
Disposi@onal anxiety is a key risk factor
increased risk
Anxiety, mood, and substance disorders
Barlow et al. 2013; Clauss & Blackford 2012; Kotov et al. 2010; Watson & Naragon-‐Gainey 2014
Students—
But exactly do we mean by N/NE?
What kinds of processes seem to be involved?
Barlow et al. 2013; Clauss & Blackford 2012; Kotov et al. 2010; Watson & Naragon-‐Gainey 2014
Neuro9cism, as measured by factor-‐analy9c [self-‐report] scales, is a conceptual hodgepodge of…cogni9ons, behavior, emo9ons, and symptoms — Seymour Epstein 1994
Epstein Psychol Inquiry 1994
Dan & Jack (UW-‐Madison)
John Cur4n (UW)
Chris4an Grillon (NIMH)
David Walker (Emory)
Mike Davis (Emory)
Me (UMD)
Dan & Jack (UW-‐Madison)
John Cur4n (UW)
Chris4an Grillon (NIMH)
David Walker (Emory)
Mike Davis (Emory)
Me (UMD)
Uncertainty is the Core Feature of Anxiety • Anxiety can be thought of as a future-‐oriented emo@onal state • Characterized by an@cipatory cogni@ve, behavioral, physio, and
emo@onal changes in response to uncertain threat
• Normal and adap@ve when appropriately @trated to the likelihood and severity of threat
• Maladap@ve when conducted excessively, e.g., when threat is distal, improbable, inconsequen@al
• “Mountain out of a molehill”
• Lost opportunity for alloca@ng resources to other ac@vi@es
that are rewarding & promote posi@ve affect, e.g., foraging, fornica@ng, playing, paren@ng, etc.
Uncertainty is the Core Feature of Anxiety • Anxiety can be thought of as a future-‐oriented emo@onal state • Characterized by an@cipatory cogni@ve, behavioral, physio, and
emo@onal changes in response to uncertain threat
• Normal and adap@ve when appropriately @trated to the likelihood and severity of threat
• Maladap@ve when conducted excessively, e.g., when threat is distal, improbable, inconsequen@al
• “Mountain out of a molehill”
• Lost opportunity for alloca@ng resources to other ac@vi@es
that are rewarding & promote posi@ve affect, e.g., foraging, fornica@ng, playing, paren@ng, etc.
Uncertainty is the Core Feature of Anxiety • Anxiety can be thought of as a future-‐oriented emo@onal state • Characterized by an@cipatory cogni@ve, behavioral, physio, and
emo@onal changes in response to uncertain threat
• Normal and adap@ve when appropriately @trated to the likelihood and severity of threat
• Maladap@ve when conducted excessively, e.g., when threat is distal, improbable, inconsequen@al
• “Mountain out of a molehill”
• Lost opportunity for alloca@ng resources to other ac@vi@es
that are rewarding & promote posi@ve affect, e.g., foraging, fornica@ng, playing, paren@ng, etc.
Uncertainty is the Core Feature of Anxiety • Anxiety can be thought of as a future-‐oriented emo@onal state • Characterized by an@cipatory cogni@ve, behavioral, physio, and
emo@onal changes in response to uncertain threat
• Normal and adap@ve when appropriately @trated to the likelihood and severity of threat (false alarms can be good)
• Maladap@ve when conducted excessively, e.g., when threat is remote, improbable, inconsequen@al
• “Mountain out of a molehill”
• Lost opportunity for alloca@ng resources to other ac@vi@es
that are rewarding & promote posi@ve affect, e.g., foraging, fornica@ng, playing, paren@ng, etc.
Uncertainty is the Core Feature of Anxiety • Anxiety can be thought of as a future-‐oriented emo@onal state • Characterized by an@cipatory cogni@ve, behavioral, physio, and
emo@onal changes in response to uncertain threat
• Normal and adap@ve when appropriately @trated to the likelihood and severity of threat (false alarms can be good)
• Maladap@ve when conducted excessively, e.g., when threat is remote, improbable, inconsequen@al
• “Mountain out of a molehill”
• Lost opportunity for alloca@ng resources to other ac@vi@es
that are rewarding & promote posi@ve affect, e.g., foraging, fornica@ng, playing, paren@ng, etc.
Uncertainty is the Core Feature of Anxiety • Anxiety can be thought of as a future-‐oriented emo@onal state • Characterized by an@cipatory cogni@ve, behavioral, physio, and
emo@onal changes in response to uncertain threat
• Normal and adap@ve when appropriately @trated to the likelihood and severity of threat (false alarms can be good)
• Maladap@ve when conducted excessively, e.g., when threat is remote, improbable, inconsequen@al
• “Mountain out of a molehill”
• Lost opportunity for alloca@ng resources to other ac@vi@es
that are rewarding & promote posi@ve affect, e.g., foraging, fornica@ng, playing, paren@ng, etc.
Uncertainty is the Core Feature of Anxiety • Grupe’s central claim is that the common denominator across
disposi@onal anxiety (T&P) and the anxiety disorders is aberrant and excessive an@cipatory responding under condi@ons of uncertain or ambiguous threat
• And this reflects altera@ons in a core set of brain regions • Focus on the MCC
What if…??
Uncertainty is the Core Feature of Anxiety • Grupe’s central claim is that the common denominator across
disposi@onal anxiety (T&P) and the anxiety disorders is aberrant and excessive an@cipatory responding under condi@ons of uncertain or ambiguous threat
• And that this reflects altera@ons in 5 key neuropsychological processes • Including the MCC
What if…??
Dissec@ng Uncertainty: 5 Components 1. Elevated es@mates of threat likelihood and intensity
2. Elevated vigilance
3. Deficient safety learning
4. Elevated threat avoidance (behavioral / cogni@ve)
5. Elevated reac@vity (or deficient regula@on of reac@ons) to uncertain or ambiguous threat
………………. 5 transdiagnos@c intermediate phenotypes that support chronically elevated distress
Dissec@ng Uncertainty: 5 Components 1. Elevated es@mates of threat likelihood and intensity
2. Elevated vigilance
3. Deficient safety learning
4. Elevated threat avoidance (behavioral / cogni@ve)
5. Elevated reac@vity (or deficient regula@on of reac@ons) to uncertain or ambiguous threat
………………. 5 transdiagnos@c intermediate phenotypes that support chronically elevated distress
Dissec@ng Uncertainty: 5 Components 1. Elevated es@mates of threat likelihood and intensity
2. Elevated vigilance
3. Deficient safety learning
4. Elevated threat avoidance (behavioral / cogni@ve)
5. Elevated reac@vity (or deficient regula@on of reac@ons) to uncertain or ambiguous threat
………………. 5 transdiagnos@c intermediate phenotypes that support chronically elevated distress
Dissec@ng Uncertainty: 5 Components 1. Elevated es@mates of threat likelihood and intensity
2. Elevated vigilance
3. Deficient safety learning
4. Elevated threat avoidance
5. Elevated reac@vity (or deficient regula@on of reac@ons) to uncertain or ambiguous threat
………………. 5 transdiagnos@c intermediate phenotypes that support chronically elevated distress
Dissec@ng Uncertainty: 5 Components 1. Elevated es@mates of threat likelihood and intensity
2. Elevated vigilance
3. Deficient safety learning
4. Elevated threat avoidance
5. Elevated reac@vity (or deficient regula@on of reac@ons) to uncertain or ambiguous threat
………………. 5 transdiagnos@c intermediate phenotypes that support chronically elevated distress
Dissec@ng Uncertainty: 5 Components 1. Elevated es@mates of threat likelihood and intensity
2. Elevated vigilance
3. Deficient safety learning
4. Elevated threat avoidance
5. Elevated reac@vity (or deficient regula@on of reac@ons) to uncertain or ambiguous threat
………………. 5 ‘transdiagnos@c’ intermediate phenotypes
that support chronically elevated NE and pervasive anxiety
‘transdiagnos4c’ = more than one anxiety disorder (diagnosis)
Dissec@ng Uncertainty: 5 Components 1. Elevated es@mates of threat likelihood and intensity
2. Elevated vigilance
3. Deficient safety learning
4. Elevated threat avoidance (behavioral / cogni@ve)
5. Elevated reac@vity (or deficient regula@on of reac@ons) to uncertain or ambiguous threat
………………. 5 ‘transdiagnos@c’ intermediate phenotypes that support chronically elevated distress
‘transdiagnos4c’ = more than one anxiety disorder (diagnosis)
Under scru@ny, these processes tend to blur together.
For example, heightened vigilance and arousal
(startle) during periods of learned safety
So, “5” may be more heuris@c than “carving nature at her joints”
Let’s meet Pete and Paul
Adap@ve Anxiety: The Case of Pete Pete, home alone one night, hears rustling in the bushes and loud banging sounds outside his house. Pete feels uncertain about whether these noises are benign (curious raccoons) or threatening (burglars). An adap4ve response to this uncertainty begins with a ra4onal assessment of the probability of threat [EST]: few burglaries occur in this neighborhood, and similar noises have never turned out to be dangerous before. Pete turns down the television to give more aben4on to what may be outside, but this heightened vigilance [VIGIL] is balanced by aben4on to cues that indicate safety [SAFE LEARN]. Because Pete’s security system is silent and the windows and doors are locked, he has reliable signs that nobody has entered his house. Nevertheless, Pete explores the situa4on to reduce nagging ques4ons [AVOID]. Heading downstairs, he sees trash strewn about the garbage cans and surmises the likely culprit was a raccoon. Despite some unresolved uncertainty, Pete can calm his racing heart [REACT/REG] and fall asleep knowing that all signs point towards safety.
Adap@ve Anxiety: The Case of Pete Pete, home alone one night, hears rustling in the bushes and loud banging sounds outside his house. Pete feels uncertain about whether these noises are benign (curious raccoons) or threatening (burglars). An adap4ve response to this uncertainty begins with a ra4onal assessment of the probability of threat [EST]: few burglaries occur in this neighborhood, and similar noises have never turned out to be dangerous before. Pete turns down the television to give more aben4on to what may be outside, but this heightened vigilance [VIGIL] is balanced by aben4on to cues that indicate safety [SAFE LEARN]. Because Pete’s security system is silent and the windows and doors are locked, he has reliable signs that nobody has entered his house. Nevertheless, Pete explores the situa4on to reduce nagging ques4ons [AVOID]. Heading downstairs, he sees trash strewn about the garbage cans and surmises the likely culprit was a raccoon. Despite some unresolved uncertainty, Pete can calm his racing heart [REACT/REG] and fall asleep knowing that all signs point towards safety.
Adap@ve Anxiety: The Case of Pete Pete, home alone one night, hears rustling in the bushes and loud banging sounds outside his house. Pete feels uncertain about whether these noises are benign (curious raccoons) or threatening (burglars). An adap4ve response to this uncertainty begins with a ra4onal assessment of the probability of threat [EST]: few burglaries occur in this neighborhood, and similar noises have never turned out to be dangerous before. Pete turns down the television to give more aben4on to what may be outside, but this heightened vigilance [VIGIL] is balanced by aben4on to cues that indicate safety [SAFE LEARN]. Because Pete’s security system is silent and the windows and doors are locked, he has reliable signs that nobody has entered his house. Nevertheless, Pete explores the situa4on to reduce nagging ques4ons [AVOID]. Heading downstairs, he sees trash strewn about the garbage cans and surmises the likely culprit was a raccoon. Despite some unresolved uncertainty, Pete can calm his racing heart [REACT/REG] and fall asleep knowing that all signs point towards safety.
Adap@ve Anxiety: The Case of Pete Pete, home alone one night, hears rustling in the bushes and loud banging sounds outside his house. Pete feels uncertain about whether these noises are benign (curious raccoons) or threatening (burglars). An adap4ve response to this uncertainty begins with a ra4onal assessment of the probability of threat [EST]: few burglaries occur in this neighborhood, and similar noises have never turned out to be dangerous before. Pete turns down the television to give more aben4on to what may be outside, but this heightened vigilance [VIGIL] is balanced by aben4on to cues that indicate safety [SAFE LEARN]. Because Pete’s security system is silent and the windows and doors are locked, he has reliable signs that nobody has entered his house. Nevertheless, Pete explores the situa4on to reduce nagging ques4ons [AVOID]. Heading downstairs, he sees trash strewn about the garbage cans and surmises the likely culprit was a raccoon. Despite some unresolved uncertainty, Pete can calm his racing heart [REACT/REG] and fall asleep knowing that all signs point towards safety.
Maladap@ve Anxiety: The Case of Paul Next door lives Paul, a chronic worrier with GAD, who hears the same noises and experiences similar feelings of uncertainty. Instead of objec4vely weighing the likelihood of alterna4ve outcomes, Paul immediately imagines burglars entering his home [EST]. Uncontrollable worries and cascading ‘what if…’ thoughts course through his head, and he generates increasingly elaborate scenarios of what evils may befall him. He becomes increasingly abuned to every movement in the branches or creak in the floorboards of his old house [VIGIL]. Owing to Paul’s exclusive aben4on towards poten4al threat, he does not no4ce that his security system is silent [SAFE LEARN]. Concerned for his safety, Paul locks his bedroom door instead of inves4ga4ng [AVOID]. Having avoided exploring the situa4on, Paul is leg with greater unresolved uncertainty than Pete about the source of the noises. He tries to sleep but his racing heart and sweaty palms keep him from relaxing [REACT/REG]. Not having learned that the situa4on was safe, Paul will be more likely to assume the worst the next 4me he hears a noise in the night.
Maladap@ve Anxiety: The Case of Paul Next door lives Paul, a chronic worrier with GAD, who hears the same noises and experiences similar feelings of uncertainty. Instead of objec4vely weighing the likelihood of alterna4ve outcomes, Paul immediately imagines burglars entering his home [EST]. Uncontrollable worries and cascading ‘what if…’ thoughts course through his head, and he generates increasingly elaborate scenarios of what evils may befall him. He becomes increasingly abuned to every movement in the branches or creak in the floorboards of his old house [VIGIL]. Owing to Paul’s exclusive aben4on towards poten4al threat, he does not no4ce that his security system is silent [SAFE LEARN]. Concerned for his safety, Paul locks his bedroom door instead of inves4ga4ng [AVOID]. Having avoided exploring the situa4on, Paul is leg with greater unresolved uncertainty than Pete about the source of the noises. He tries to sleep but his racing heart and sweaty palms keep him from relaxing [REACT/REG]. Not having learned that the situa4on was safe, Paul will be more likely to assume the worst the next 4me he hears a noise in the night.
Maladap@ve Anxiety: The Case of Paul Next door lives Paul, a chronic worrier with GAD, who hears the same noises and experiences similar feelings of uncertainty. Instead of objec4vely weighing the likelihood of alterna4ve outcomes, Paul immediately imagines burglars entering his home [EST]. Uncontrollable worries and cascading ‘what if…’ thoughts course through his head, and he generates increasingly elaborate scenarios of what evils may befall him. He becomes increasingly abuned to every movement in the branches or creak in the floorboards of his old house [VIGIL]. Owing to Paul’s exclusive aben4on towards poten4al threat, he does not no4ce that his security system is silent [SAFE LEARN]. Concerned for his safety, Paul locks his bedroom door instead of inves4ga4ng [AVOID]. Having avoided exploring the situa4on, Paul is leg with greater unresolved uncertainty than Pete about the source of the noises. He tries to sleep but his racing heart and sweaty palms keep him from relaxing [REACT/REG]. Not having learned that the situa4on was safe, Paul will be more likely to assume the worst the next 4me he hears a noise in the night.
Not just grown ups
See what it is, you might feel beber See what it is, you might feel beber Once you know what's there You might find you don't need to be scared I couldn't help but feel royally scared When I saw a strange lump on the floor But when I saw what was there My favorite stuffed bear I wasn't afraid anymore You know, I was grrr-‐ifficly scared When I saw a creepy shadow on the wall But it was just a light shining On silly Mr. Lizard That made him look so very very tall Once we saw what was there We knew he had nothing to fear
See what it is, you might feel beber See what it is, you might feel beber Once you know what's there You might find you don't need to be scared I heard a sound that gave me such a fright I couldn't see what it was, it was out of sight Let's see what it is It's a frog See what it is, you might feel beber See what it is, you might not be afraid We saw a large shape that gave us a scare It looked like a really really big bear Let's see what it is It's a rock See what it is, you might feel beber See what it is, you might not be afraid See what it is, you might feel beber Once you see what's there you might not feel so afraid
Start @ 19:15 hbps://www.youtube.com/watch?v=nisqIXwxHms
Drill into the 5 consBtuents
1. Inflated Es@mates of Threat Likelihood/Intensity
Instead of objec9vely weighing the likelihood of alterna9ve outcomes, Paul immediately imagines burglars entering his home
1. Inflated Es@mates of Threat Likelihood/Intensity
Evidence for inflated es@mates of threat? • Judgment Biases
• Anxious individuals overweight the probability of nega@ve events
1. Inflated Es@mates of Threat Likelihood/Intensity
Evidence for inflated es@mates of threat? Judgment Biases
• Anxious individuals overweight the probability of nega@ve events
2. Hypervigilance Paul becomes increasingly aHuned to every movement in the branches or creak in the floorboards of his old house
2. Hypervigilance Paul becomes increasingly aHuned to every movement in the branches or creak in the floorboards of his old house
Dot-‐Probe Vigilance Task
9me
Hypervigilance: Meta-‐AnalyBc Evidence
see also Van Boekstaele et al Psychol Bull in press
Hypervigilance: Meta-‐AnalyBc Evidence
see also Van Boekstaele et al Psychol Bull in press
Hypervigilance: Meta-‐AnalyBc Evidence
see also Van Boekstaele et al Psychol Bull in press
Can Hypervigilance be Re-‐Trained?
Ann Rev Clin Psychol 2012 see also Van Boekstaele et al Psychol Bull in press
Can Hypervigilance be Re-‐Trained?
Ann Rev Clin Psychol 2012 see also Van Boekstaele et al Psychol Bull in press
Students – What’s at stake? What’s the clinical or scienBfic value of studying retraining?
1. Manipulate vigilance to test whether it causally contributes to anxiety
2. Test the therapeu@c efficacy of aqen@on retraining -‐ Conven@onal CBT
-‐ Introspec@ve ‘insight’ into thoughts that trigger anxiety and mentally ‘challenging’ those thoughts
-‐ Retraining -‐ Directly modify cogni@ve biases thru extended task
prac@ce -‐ Not dependent on introspec@on -‐ More akin to learning a new motor skill
Retraining Vigilance: Goals
Ann Rev Clin Psychol 2012 Van Boekstaele et al Psychol Bull in press [see also Tobon JCP 2011]; MacLeod & Clarke CPS 2015
1. Manipulate vigilance to test whether it causally contributes to anxiety
2. Test the therapeu@c efficacy of aqen@on retraining -‐ Conven@onal CBT
-‐ Introspec@ve ‘insight’ into thoughts that trigger anxiety and mentally ‘challenging’ those thoughts
-‐ Retraining -‐ Directly modify cogni@ve biases thru extended task
prac@ce -‐ Not dependent on introspec@on -‐ More akin to learning a new motor skill
Retraining Vigilance: Goals
Ann Rev Clin Psychol 2012 Van Boekstaele et al Psychol Bull in press [see also Tobon JCP 2011]; MacLeod & Clarke CPS 2015
1. Manipulate vigilance to test whether it causally contributes to anxiety
2. Test the therapeu@c efficacy of aqen@on retraining -‐ Conven@onal Cogni@ve-‐Behavioral Therapy (CBT)
-‐ Introspec@ve ‘insight’ into thoughts that trigger anxiety and mentally ‘challenging’ those thoughts
-‐ Retraining -‐ Directly modify cogni@ve biases thru extended task
prac@ce -‐ Not dependent on introspec@on -‐ More akin to learning a new motor skill
Retraining Vigilance: Goals
Ann Rev Clin Psychol 2012 Van Boekstaele et al Psychol Bull in press [see also Tobon JCP 2011]; MacLeod & Clarke CPS 2015
1. Manipulate vigilance to test whether it causally contributes to anxiety
2. Test the therapeu@c efficacy of aqen@on retraining -‐ Conven@onal Cogni@ve-‐Behavioral Therapy (CBT)
-‐ Introspec@ve ‘insight’ into thoughts that trigger anxiety and mentally ‘challenging’ those thoughts
-‐ Retraining -‐ Directly modify cogni@ve biases thru extended task
prac@ce -‐ Not dependent on introspec@on -‐ More akin to learning a new motor skill (or exposure Tx) -‐ Focused and can be ‘gameified’
Retraining Vigilance: Goals
Ann Rev Clin Psychol 2012 Van Boekstaele et al Psychol Bull in press [see also Tobon JCP 2011]; MacLeod & Clarke CPS 2015
Dennis Clin Psychol Sci 2014
Dennis Clin Psychol Sci 2014
In this game two animated characters will appear on the screen. Shortly aPer, they will burrow into a hole. One of them will cause a path of grass to rustle behind it. With your finger, trace the path of the rustling grass, beginning from the burrow. Try to complete this task as quickly and as accurately as possible.
Dennis Clin Psychol Sci 2014
In this game two animated characters will appear on the screen. Shortly aPer, they will burrow into a hole. One of them will cause a path of grass to rustle behind it. With your finger, trace the path of the rustling grass, beginning from the burrow. Try to complete this task as quickly and as accurately as possible. In the ABM condi4on, a trail of grass appeared in the loca4on of the non-‐threat sprite on every trial, whereas in the placebo training condi4on, trails were equally likely to appear in the loca4on of the angry/threat or neutral/non-‐threat sprites
Vigilance causally contributes to elevated anxiety In nonclinical samples exposed to one-‐shot lab sessions, retraining has been found to reduce • “stress” elicited by subsequent exposure to simple cogni@ve
stressors (anagram/puzzle challenges)
• anxiety ra@ngs and behaviors (assessed by raters) when delivering a public speech
• intrusive, apprehensive thoughts during a worry induc@on
Retraining Vigilance: Lessons Learned
Ann Rev Clin Psychol 2012 Van Boekstaele et al Psychol Bull in press [see also Tobon JCP 2011]; MacLeod & Clarke CPS 2015
Vigilance causally contributes to elevated anxiety In nonclinical samples exposed to one-‐shot lab sessions, retraining has been found to reduce • “stress” elicited by subsequent exposure to simple cogni@ve
stressors (anagram/puzzle challenges)
• anxiety ra@ngs and behaviors (assessed by raters) when delivering a public speech
• intrusive, apprehensive thoughts during a worry induc@on
Retraining Vigilance: Lessons Learned
Ann Rev Clin Psychol 2012 Van Boekstaele et al Psychol Bull in press [see also Tobon JCP 2011]; MacLeod & Clarke CPS 2015
Vigilance causally contributes to elevated anxiety In nonclinical samples exposed to one-‐shot lab sessions, retraining has been found to reduce • “stress” elicited by subsequent exposure to simple cogni@ve
stressors (anagram/puzzle challenges)
• anxiety ra@ngs and behaviors (assessed by raters) when delivering a public speech
• intrusive, apprehensive thoughts during a worry induc@on
Retraining Vigilance: Lessons Learned
Ann Rev Clin Psychol 2012 Van Boekstaele et al Psychol Bull in press [see also Tobon JCP 2011]; MacLeod & Clarke CPS 2015
Vigilance causally contributes to elevated anxiety In nonclinical samples exposed to one-‐shot lab sessions, retraining has been found to reduce • “stress” elicited by subsequent exposure to simple cogni@ve
stressors (anagram/puzzle challenges)
• anxiety ra@ngs and behaviors (assessed by raters) when delivering a public speech
• intrusive, apprehensive thoughts during a worry induc@on
Retraining Vigilance: Lessons Learned
Ann Rev Clin Psychol 2012 Van Boekstaele et al Psychol Bull in press [see also Tobon JCP 2011]; MacLeod & Clarke CPS 2015
Vigilance causally contributes to elevated anxiety In nonclinical samples exposed to one-‐shot lab sessions, retraining has been found to reduce • “stress” elicited by subsequent exposure to simple cogni@ve
stressors (anagram/puzzle challenges)
• anxiety ra@ngs and behaviors (assessed by raters) when delivering a public speech (e.g. Dennis mobile app study)
• intrusive, apprehensive thoughts during a worry induc@on
Retraining Vigilance: Lessons Learned
Ann Rev Clin Psychol 2012 Van Boekstaele et al Psychol Bull in press [see also Tobon JCP 2011]; MacLeod & Clarke CPS 2015
Vigilance causally contributes to elevated anxiety In nonclinical samples exposed to one-‐shot lab sessions, retraining has been found to reduce • “stress” elicited by subsequent exposure to simple cogni@ve
stressors (anagram/puzzle challenges)
• anxiety ra@ngs and behaviors (assessed by raters) when delivering a public speech (e.g. Dennis mobile app study)
• intrusive, apprehensive thoughts during a worry induc@on
Retraining Vigilance: Lessons Learned
Ann Rev Clin Psychol 2012 Van Boekstaele et al Psychol Bull in press [see also Tobon JCP 2011]; MacLeod & Clarke CPS 2015
Vigilance causally contributes to elevated anxiety In nonclinical samples exposed to one-‐shot lab sessions, retraining has been found to reduce • “stress” elicited by subsequent exposure to simple cogni@ve
stressors (anagram/puzzle challenges)
• anxiety ra@ngs and behaviors (assessed by raters) when delivering a public speech
• intrusive, apprehensive thoughts during a worry induc@on
Retraining Vigilance: Lessons Learned
Ann Rev Clin Psychol 2012 Van Boekstaele et al Psychol Bull in press [see also Tobon JCP 2011]; MacLeod & Clarke CPS 2015
Retraining Vigilance: Lessons Learned
Biol Psychiatry 2010
Retraining appears to be effec@ve at reducing clinical anxiety
Van Boekstaele et al Psychol Bull in press [see also Tobon JCP 2011]; MacLeod & Clarke CPS 2015
Retraining Vigilance: Lessons Learned
Biol Psychiatry 2010
Retraining appears to be effec@ve at reducing clinical anxiety
Van Boekstaele et al Psychol Bull in press [see also Tobon JCP 2011]; MacLeod & Clarke CPS 2015
• Trained 57 individuals with social phobia
• Those trained to abend to nonthreatening cues demonstrated greater reduc4ons in self-‐reported, behavioral, and physiological (CSR) measures of anxiety in response to a public speaking challenge than those in the abend to threat and control condi4ons
Retraining Vigilance: Lessons Learned
Biol Psychiatry 2010
Retraining appears to be effec@ve at reducing clinical anxiety
Van Boekstaele et al Psychol Bull in press [see also Tobon JCP 2011]; MacLeod & Clarke CPS 2015
• Trained 57 individuals with social phobia
• Those trained to abend to nonthreatening cues demonstrated greater reduc4ons in self-‐reported, behavioral, and physiological (CSR) measures of anxiety in response to a public speaking challenge than those in the abend to threat and control condi4ons
Retraining Vigilance: Lessons Learned
Biol Psychiatry 2010
Retraining appears to be effec@ve at reducing clinical anxiety
Van Boekstaele et al Psychol Bull in press [see also Tobon JCP 2011]; MacLeod & Clarke CPS 2015
• Trained 57 individuals with social phobia
• Those trained to abend to nonthreatening cues demonstrated greater reduc4ons in self-‐reported, behavioral, and physiological (CSR) measures of anxiety in response to a public speaking challenge than those in the abend to threat and control condi4ons
• Similar effects reported for cor4sol and examina4on stress
Retraining appears to be effec@ve at reducing clinical anxiety
Retraining Vigilance: Lessons Learned
Biol Psychiatry 2010 Van Boekstaele et al Psychol Bull in press [see also Tobon JCP 2011]; MacLeod & Clarke CPS 2015
Retraining appears to be effec@ve at reducing clinical anxiety
Retraining Vigilance: Lessons Learned
Biol Psychiatry 2010 Van Boekstaele et al Psychol Bull in press [see also Tobon JCP 2011]; MacLeod & Clarke CPS 2015
Retraining appears to be effec@ve at reducing clinical anxiety
Retraining Vigilance: Lessons Learned
Biol Psychiatry 2010
Furthermore Van Boekstaele et al review evidence that conven@onal CBT reduces the aqen@onal bias to threat, consistent with the idea that hypervigilance is one of the “ac@ve ingredients” in clinically significant anxiety (see also Reinecke et al Biol Psychiatry 2013) Van Boekstaele et al Psychol Bull in press [see also Tobon JCP 2011]; MacLeod & Clarke CPS 2015
Where do hyper-‐vigilance and related kinds of risk assessment behaviors come from?
May reflect the direct influence of the amygdala on sensory cortex…
Vuillemier et al. Nat Neurosci 2004 FFA: Fusiform Face Area
Vuillemier et al. Nat Neurosci 2004 FFA: Fusiform Face Area
Hyper-‐vigilance could also reflect an indirect influence of the amygdala on corBcal sensory systems
Indirect Influence via the Basal Forebrain
Details Are Not Important
Details Are Not Important
Wake Up!
Details Are Not Important
Basal Forebrain (N.B. of M.)
Basal Forebrain (N.B. of M.)
Basal Forebrain (NB of M): CorBcal Arousal
Rabbits: Whalen et al J Neurosci; Kapp et al Beh Neurosci
Basal Forebrain (NB of M): CorBcal Arousal
Rabbits: Whalen et al J Neurosci; Kapp et al Beh Neurosci
Learned Threat (CS+) Increases Neuronal Spiking
in the NB of M
Learned Threat Increases Cor@cal Arousal (EEG Desynchroniza@on;
Less is More)
NB of M Spiking Predicts
Cor@cal Arousal
CeA S@mula@on Can Drive This Effect
(CeA à NB of M à Arousal
Details Are Not Important
Basal Forebrain (NB of M): CorBcal Arousal
Rabbits: Whalen et al J Neurosci; Kapp et al Beh Neurosci
Learned Threat (CS+) Increases Neuronal Spiking
in the NB of M
Learned Threat (CS+) Increases Cor@cal Arousal (EEG Desynchroniza@on;
Less is More)
NB of M Spiking Predicts
Cor@cal Arousal
CeA S@mula@on Can Drive This Effect
(CeA à NB of M à Arousal
Details Are Not Important
Basal Forebrain (NB of M): CorBcal Arousal
Rabbits: Whalen et al J Neurosci; Kapp et al Beh Neurosci
Learned Threat (CS+) Increases Neuronal Spiking
in the NB of M
Learned Threat (CS+) Increases Cor@cal Arousal (EEG Desynchroniza@on;
Less is More)
NB of M Spiking Predicts
Cor@cal Arousal
CeA S@mula@on Can Drive This Effect
(CeA à NB of M à Arousal
Details Are Not Important
Basal Forebrain (NB of M): CorBcal Arousal
Rabbits: Whalen et al J Neurosci; Kapp et al Beh Neurosci
Learned Threat (CS+) Increases Neuronal Spiking
in the NB of M
Learned Threat (CS+) Increases Cor@cal Arousal (EEG Desynchroniza@on;
Less is More)
NB of M Spiking Predicts
Cor@cal Arousal
CeA S@mula@on Can Drive This Effect
(CeA à NB of M à Arousal)
Indirect Influence via the Basal Forebrain
3. Deficient Safety Learning
3. Deficient Safety Learning
Owing to Paul’s exclusive aHen9on towards poten9al threat, he does not no9ce that his security system is silent [and so remains in a state of apprehensive distress]
Pete [aHends to] to cues that indicate safety. Because his security system is silent and the windows and doors are locked, he has reliable signs that nobody has entered his house.
• Safety signals indicate the absence of threat; relieve individuals from a state of an@cipatory anxiety
• Under condi@ons of uncertainty, weak or non-‐existent con@ngencies between cues and aversive outcomes make it difficult to discriminate safety from threat (CS-‐ vs. CS+)
• Heightened reac@vity (startle) to objec@vely safe condi@ons (CS-‐, ITI) has been observed across anxiety disorders
3. Deficient Safety Learning
Lissek et al Biol Psychiatry in press
• Safety signals indicate the absence of threat; relieve individuals from a state of an@cipatory anxiety
• Heightened reac@vity (startle) to objec@vely safe condi@ons (CS-‐, ITI) has been consistently observed across anxiety disorders
3. Deficient Safety Learning
Lissek et al Biol Psychiatry in press
• Safety signals indicate the absence of threat; relieve individuals from a state of an@cipatory anxiety
• Heightened reac@vity (startle) to objec@vely safe condi@ons (CS-‐, ITI) has been consistently observed across anxiety disorders
3. Deficient Safety Learning
Lissek et al Biol Psychiatry in press
• Safety signals indicate the absence of threat; relieve individuals from a state of an@cipatory anxiety
• Heightened reac@vity (startle) to objec@vely safe condi@ons (CS-‐, ITI) has been consistently observed across anxiety disorders
3. Deficient Safety Learning
Lissek et al Biol Psychiatry in press
• Safety signals indicate the absence of threat; relieve individuals from a state of an@cipatory anxiety
• Heightened reac@vity (startle) to objec@vely safe condi@ons (CS-‐, ITI) has been consistently observed across anxiety disorders • Not just startle…
3. Deficient Safety Learning
Lissek et al Biol Psychiatry in press
• Safety signals indicate the absence of threat; relieve individuals from a state of an@cipatory anxiety
• Heightened reac@vity (startle) to objec@vely safe condi@ons (CS-‐, ITI) has been consistently observed
3. Deficient Safety Learning
• Safety signals indicate the absence of threat; relieve individuals from a state of an@cipatory anxiety
• Heightened reac@vity (startle) to objec@vely safe condi@ons (CS-‐, ITI) has been consistently observed • 44 studies (>2,000 Ss), including a broad spectrum of self-‐report and physiological measures of condi@oned fear/anxiety
3. Deficient Safety Learning
• Safety signals indicate the absence of threat; relieve individuals from a state of an@cipatory anxiety
• Heightened reac@vity (startle) to objec@vely safe condi@ons (CS-‐, ITI) has been consistently observed • 44 studies (>2,000 Ss), including a broad spectrum of self-‐report and physiological measures of condi@oned fear/anxiety • Pa@ents with anxiety disorders do not differ in their response to condi@oned threat cues (CS+), but do show elevated responses to safety cues (CS-‐)
3. Deficient Safety Learning
3. Deficient Safety Learning This is a Really Big Deal • For a long 4me, it was thought that
neuro4c, anxious individuals are characterized by heightened fear learning and excessive responsiveness to the CS+ (the black bars in the figure)…and that we could understand anxiety by elucida4ng the substrates of fear learning
• But it has grown increasingly clear that this is generally not the case
• Rather, neuro4c/anxious individuals show difficul4es discrimina4ng threat from safety, manifes4ng as heightened reac4ons to ostensibly safe cues and contexts (white and grey bars in the figure)
3. Deficient Safety Learning This is a Really Big Deal • For a long 4me, it was thought that
neuro4c, anxious individuals are characterized by heightened fear learning and excessive responsiveness to the CS+ and that we could understand anxiety by elucida4ng the substrates of fear learning
• But it has grown increasingly clear that this is generally not the case
• Rather, neuro4c/anxious individuals show difficul4es discrimina4ng threat from safety, manifes4ng as heightened reac4ons to ostensibly safe cues and contexts (white and grey bars in the figure)
3. Deficient Safety Learning This is a Really Big Deal • For a long 4me, it was thought that
neuro4c, anxious individuals are characterized by heightened fear learning and excessive responsiveness to the CS+ and that we could understand anxiety by elucida4ng the substrates of fear learning
• But it has grown increasingly clear that this is generally not the case
• Rather, neuro4c/anxious individuals show difficul4es discrimina4ng threat from safety, manifes4ng as heightened reac4ons to ostensibly safe cues and contexts (white and grey bars in the figure)
3. Deficient Safety Learning This is a Really Big Deal • For a long 4me, it was thought that
neuro4c, anxious individuals are characterized by heightened fear learning and excessive responsiveness to the CS+ and that we could understand anxiety by elucida4ng the substrates of fear learning
• But it has grown increasingly clear that this is generally not the case
• Rather, neuro4c/anxious individuals show difficul4es discrimina4ng threat from safety, manifes4ng as heightened reac4ons to ostensibly safe cues and contexts (CS-‐, ITI)
3. Deficient Safety Learning This is a Really Big Deal • This is specific to studies involving the use
of noxious electric shock (or darkness)
• Anxious individuals show exaggerated FPS when you turn out the lights—another kind of diffuse threat—and this is reduced by benzodiazepines
• Increased ITI/Baseline startle is not
observed in other kinds of ‘non-‐emo4onal’ startle studies
• Suggests that it does not simply reflect hyper-‐reac4vity to the novelty of the lab, personnel, or procedures, but instead reflects a response to diffuse or remote threat: ‘being in a shock study’ / having electrodes in-‐place / darkness
cf. Grillon et al PlosOne 2013
3. Deficient Safety Learning This is a Really Big Deal • This is specific to studies involving the use
of noxious electric shock (or darkness)
• Anxious individuals show exaggerated FPS when you turn out the lights—another kind of diffuse threat—and this is reduced by benzodiazepines
• Increased ITI/Baseline startle is not
observed in other kinds of ‘non-‐emo4onal’ startle studies
• Suggests that it does not simply reflect hyper-‐reac4vity to the novelty of the lab, personnel, or procedures, but instead reflects a response to diffuse or remote threat: ‘being in a shock study’ / having electrodes in-‐place / darkness
cf. Grillon et al PlosOne 2013
3. Deficient Safety Learning This is a Really Big Deal • This is specific to studies involving the use
of noxious electric shock (or darkness)
• Anxious individuals show exaggerated FPS when you turn out the lights—another kind of diffuse threat—and this is reduced by benzodiazepines
• Increased ITI/Baseline startle is not
observed in other kinds of ‘non-‐emo4onal’ startle studies
• Suggests that it does not simply reflect hyper-‐reac4vity to the novelty of the lab, personnel, or procedures, but instead reflects a response to diffuse or remote threat: ‘being in a shock study’ / having electrodes in-‐place / darkness
cf. Grillon et al PlosOne 2013
3. Deficient Safety Learning This is a Really Big Deal • This is specific to studies involving the use
of noxious electric shock (or darkness)
• Anxious individuals show exaggerated FPS when you turn out the lights—another kind of diffuse threat—and this is reduced by benzodiazepines
• Increased ITI/Baseline startle is not
observed in other kinds of ‘non-‐emo4onal’ startle studies
• Suggests that it does not simply reflect hyper-‐reac4vity to the novelty of the lab, personnel, or procedures, but instead reflects a response to diffuse or remote threat: ‘being in a shock study’ / having electrodes in-‐place / darkness
cf. Grillon et al PlosOne 2013
Lissek (NIMH, Minnesota)
Hypothesized that heightened reac@ons to safety cues might reflect a kind of “over-‐generaliza@on”
• Because the CS+ and CS, in a given study, are similar (e.g., both colored lights, both faces), pa@ents appear to emo@onally mistake the CS-‐ for the CS+
Lissek (NIMH, Minnesota)
Hypothesized that heightened reac@ons to safety cues might reflect a kind of “over-‐generaliza@on”
• Noted that the CS+ and CS in a given study tend to be physically similar (e.g., both colored lights, both faces)
• Anxious individuals appear to over-‐generalize from the CS+ to the CS-‐, in terms of their emo@onal response (but not in terms of con@ngency reports)
Lissek (NIMH, Minnesota)
Hypothesized that heightened reac@ons to safety cues might reflect a kind of “over-‐generaliza@on”
• Noted that the CS+ and CS in a given study tend to be physically similar (e.g., both colored lights, both faces)
• Hypothesized that anxious individuals over-‐generalize from the CS+ to the physically similar CS-‐, in terms of their emo@onal response (but not in terms of con@ngency reports)
Students: How might you test this ‘overgeneralizaBon’ hypothesis
in the lab?
Overgeneralize?
Lissek Dep and Anx 2012
Overgeneralize?
Lissek Dep and Anx 2012
Overgeneralize?
Lissek Dep and Anx 2012
Elevated startle (FPS) rela@ve to CS-‐
Overgeneralize?
Lissek Dep and Anx 2012
Elevated startle (FPS) rela@ve to CS-‐
Lissek Dep and Anx 2012
Elevated startle (FPS) rela@ve to CS-‐
Overgeneralized Fear Learning
J Abnormal Psychol 2012
Prospec@vely Predicts Disorder Onset
J Abnormal Psychol 2012
Prospec@vely Predicts Disorder Onset
Reeb-‐Sutherland JAACAP 2009
Present in Teens with High Childhood BI
Reeb-‐Sutherland JAACAP 2009
Present in Teens with High Childhood BI
What brain circuits support sustained anxiety in response to diffuse, uncertain, or remote threat?
To understand the relevance of this circuit in primates, we focused on a group of young monkeys with stable and extreme behavioral inhibiBon (BI)
Extreme behavioral inhibi@on (BI) confers risk
Stable and extreme behavioral inhibi@on (BI)
Total N = 109 Details Are Not Important
Nothing (Empty Control)
18-‐FDG Injec@on
18-‐FDG Injec@on
No Intruder
Intruder Threat
Control
Ac@v
e
No Intruder (FDG uptake)
No Intruder (FDG uptake)
Shackman*, Fox* et al in prep
Assessing sustained anxiety following threat
Details Are Not Important
Nothing (Empty Control)
18-‐FDG Injec@on
18-‐FDG Injec@on
No Intruder
Intruder Threat
Control
Ac@v
e
No Intruder (FDG uptake)
No Intruder (FDG uptake)
Shackman*, Fox* et al in prep
Assessing sustained anxiety following threat
Details Are Not Important
Nothing (Empty Control)
18-‐FDG Injec@on
18-‐FDG Injec@on
No Intruder
Intruder Threat
Control
Ac@v
e
No Intruder (FDG uptake)
No Intruder (FDG uptake)
Shackman*, Fox* et al in prep
Assessing sustained anxiety following threat
Details Are Not Important
Nothing (Empty Control)
18-‐FDG Injec@on
18-‐FDG Injec@on
No Intruder
Intruder Threat
Control
Ac@v
e
No Intruder (FDG uptake)
No Intruder (FDG uptake)
Shackman*, Fox* et al in prep
Assessing sustained anxiety following threat
Details Are Not Important
Shackman*, Fox* et al in prep
Shackman*, Fox* et al in prep Paxinos et al 2009
Shackman et al. PNAS 2013; Birn*, Shackman* et al. under review; Shackman, Fox et al., in prep
5 core cons@tuents of the anxious phenotype (3 down, 2 to go!) 1. Inflated es@mates of threat certainty or intensity/cost
2. Hypervigilance (“aqen@onal threat bias”) • Ac@ve ingredient/Causal • Present in BI • Amygdala, direct or indirect influence on sensory cortex
3. Deficient safety learning and overgeneraliza@on • Anxious individuals learn certain, imminent threat just fine • Predicts first onset; present in BI • dlPFC, vmPFC, BNST?
4. Cogni@ve and behavioral avoidance • MCC • Circuit centered on the MCC may help to orchestrate some of the other processes • Key hub
5. Hyper-‐reac@vity to uncertainty and ambiguity • Ac@ve ingredient/Causal • Extended amygdala (amygdala, BNST)
6. These processes interact in ways that reinforce pervasive, chronic distress and arousal a la Pete and Paul.
Key Take Homes
5 core cons@tuents of the anxious phenotype (3 down, 2 to go!) 1. Inflated es@mates of threat certainty or intensity/cost
2. Hypervigilance (“aqen@onal threat bias”) • Ac@ve ingredient/Causal • Present in BI • Amygdala, direct or indirect influence on sensory cortex
3. Deficient safety learning and overgeneraliza@on • Anxious individuals learn certain, imminent threat just fine • Predicts first onset; present in BI • dlPFC, vmPFC, BNST?
4. Cogni@ve and behavioral avoidance • MCC • Circuit centered on the MCC may help to orchestrate some of the other processes • Key hub
5. Hyper-‐reac@vity to uncertainty and ambiguity • Ac@ve ingredient/Causal • Extended amygdala (amygdala, BNST)
6. These processes interact in ways that reinforce pervasive, chronic distress and arousal a la Pete and Paul.
Key Take Homes
5 core cons@tuents of the anxious phenotype (3 down, 2 to go!) 1. Inflated es@mates of threat certainty or intensity/cost (mountain out of a molehill)
2. Hypervigilance (“aqen@onal threat bias”) • Ac@ve ingredient/Causal • Present in BI • Amygdala, direct or indirect influence on sensory cortex
3. Deficient safety learning and overgeneraliza@on • Anxious individuals learn certain, imminent threat just fine • Predicts first onset; present in BI • dlPFC, vmPFC, BNST?
4. Cogni@ve and behavioral avoidance • MCC • Circuit centered on the MCC may help to orchestrate some of the other processes • Key hub
5. Hyper-‐reac@vity to uncertainty and ambiguity • Ac@ve ingredient/Causal • Extended amygdala (amygdala, BNST)
6. These processes interact in ways that reinforce pervasive, chronic distress and arousal a la Pete and Paul.
Key Take Homes
5 core cons@tuents of the anxious phenotype (3 down, 2 to go!) 1. Inflated es@mates of threat certainty or intensity/cost (mountain out of a molehill)
2. Hyper-‐vigilance (bias to allocate excess aqen@on to threat or scanning for threat-‐relevant informa@on)
• Ac@ve ingredient/Causal • Present in BI • Circuits centered on the amygdala, poised to directly/indirectly influence sensory cortex
3. Deficient safety learning and overgeneraliza@on • Anxious individuals learn certain, imminent threat just fine • Predicts first onset; present in BI • dlPFC, vmPFC, BNST?
4. Cogni@ve and behavioral avoidance • MCC • Circuit centered on the MCC may help to orchestrate some of the other processes • Key hub
5. Hyper-‐reac@vity to uncertainty and ambiguity • Ac@ve ingredient/Causal • Extended amygdala (amygdala, BNST)
6. These processes interact in ways that reinforce pervasive, chronic distress and arousal a la Pete and Paul.
Key Take Homes
5 core cons@tuents of the anxious phenotype (3 down, 2 to go!) 1. Inflated es@mates of threat certainty or intensity/cost (mountain out of a molehill)
2. Hyper-‐vigilance (bias to allocate excess aqen@on to threat or scanning for threat-‐relevant informa@on)
• Ac@ve ingredient/Causal • Circuits centered on the amygdala, poised to directly/indirectly influence sensory cortex
3. Deficient safety learning and overgeneraliza@on • Anxious individuals learn certain, imminent threat just fine • Predicts first onset; present in BI • dlPFC, vmPFC, BNST?
4. Cogni@ve and behavioral avoidance • MCC • Circuit centered on the MCC may help to orchestrate some of the other processes • Key hub
5. Hyper-‐reac@vity to uncertainty and ambiguity • Ac@ve ingredient/Causal • Extended amygdala (amygdala, BNST)
6. These processes interact in ways that reinforce pervasive, chronic distress and arousal a la Pete and Paul.
Key Take Homes
5 core cons@tuents of the anxious phenotype (3 down, 2 to go!) 1. Inflated es@mates of threat certainty or intensity/cost (mountain out of a molehill)
2. Hyper-‐vigilance (bias to allocate excess aqen@on to threat or scanning for threat-‐relevant informa@on)
• Ac@ve ingredient/Causal • Circuits centered on the amygdala, poised to directly/indirectly influence sensory cortex
3. Deficient safety learning and overgeneraliza@on of anxiety to other cues and contexts • Anxious individuals learn about clear and imminent threats just fine • Predicts first onset; present in BI
Key Take Homes
5 core cons@tuents of the anxious phenotype (3 down, 2 to go!) 1. Inflated es@mates of threat certainty or intensity/cost (mountain out of a molehill)
2. Hyper-‐vigilance (bias to allocate excess aqen@on to threat or scanning for threat-‐relevant informa@on)
• Ac@ve ingredient/Causal • Circuits centered on the amygdala, poised to directly/indirectly influence sensory cortex
3. Deficient safety learning and overgeneraliza@on of anxiety to other cues and contexts • Anxious individuals learn about clear and imminent threats just fine • Predicts first onset; present in BI • Reflects extended amygdala (BNST)
Key Take Homes
Take Home Cri@cal Thinking Ques@ons 1. Dan Grupe highlighted the importance of 5
intermediate phenotypes. Did he miss anything important?
Take Home Cri@cal Thinking Ques@ons 2. Watch Paul Whalen’s brief TEDx talk (hbps://www.youtube.com/watch?v=DeAMRUnrgbA) [<20 min]. Briefly comment on what you found most interes4ng, thought-‐provoking, mind-‐blowing, entertaining, objec4onable, or misleading about Paul’s claims. 3. Paul started his professional career performing mechanis4c studies in a rabbit model (in Bruce Kapp’s lab at U VT), before doing a post-‐doc at MGH with Scob Rauch and learning fMRI. As a professor at Dartmouth, Paul and his students con4nue to use fMRI to understand the role of the amygdala in humans. Briefly comment on the trade-‐offs of Paul’s professional decision in rela4on to understanding the neurobiology of anxiety. What did he gain, what did he lose? (Please pick 2 of the 3 ques9ons)
Take Home Cri@cal Thinking Ques@ons 2. Watch Paul Whalen’s brief TEDx talk (hbps://www.youtube.com/watch?v=DeAMRUnrgbA) [<20 min]. Briefly comment on what you found most interes4ng, thought-‐provoking, mind-‐blowing, entertaining, objec4onable, or misleading about Paul’s claims. 3. Paul started his professional career performing mechanis4c studies in a rabbit model (in Bruce Kapp’s lab at U VT), before doing a post-‐doc at MGH with Scob Rauch and learning fMRI. As a professor at Dartmouth, Paul and his students con4nue to use fMRI to understand the role of the amygdala in humans. Briefly comment on the trade-‐offs of Paul’s professional decision in rela4on to understanding the neurobiology of anxiety. What did he gain, what did he lose by switching from a rabbit model to fMRI studies of humans? ….Con9nued
Take Home Cri@cal Thinking Ques@ons 4. “Researchers at Princeton set out to build a tool that could show people what their brains are doing in real 4me, and signal the moments when their minds begin to wander. And they've largely succeeded, a paper published today in the journal Nature Neuroscience reports. The scien4sts who invented this aben4on machine, led by professor Nick Turk-‐Browne, are calling it a “mind booster.” It could, they say, change the way we think about paying aben4on—and even introduce new ways of trea4ng illnesses like anxiety” What do you think? Read the brief popular press story in The Atlan4c and then, based on what we discussed in class today, comment on how this emergent technology might be applied to anxiety disorders (treatment) or N/NE (preven4on).
hbp://www.theatlan4c.com/technology/archive/2015/02/the-‐aben4on-‐machine/385284/ and hbp://www.nature.com/neuro/journal/v18/n3/abs/nn.3940.html
Take Home Cri@cal Thinking Ques@ons 4. “Researchers at Princeton set out to build a tool that could show people what their brains are doing in real 4me, and signal the moments when their minds begin to wander. And they've largely succeeded, a paper published today in the journal Nature Neuroscience reports. The scien4sts who invented this aben4on machine, led by professor Nick Turk-‐Browne, are calling it a “mind booster.” It could, they say, change the way we think about paying aben4on—and even introduce new ways of trea4ng illnesses like anxiety” What do you think? Read the brief popular press story in The Atlan9c and then, based on what we discussed in class today, comment on how this emergent technology might be applied to anxiety disorders (treatment) or N/NE (preven4on). What are the advantages of using signals from the brain to boost or enhance learning (aka “cogni4ve-‐behavioral therapy”)
hbp://www.theatlan4c.com/technology/archive/2015/02/the-‐aben4on-‐machine/385284/
The End (No Review Ques@ons)
Things to Consider Tweaking for Spring 2015
• Introduce duvarci/pare bnst? • Roy/Wager 2014 avoidance learning • Bradford baseline stl • Connec4on from mcc to gray’s model • Upon reflec4on, do not merge the uncertainty and safety learning into one sec4on (broken out by learned/unlearned or cues/contexts)
due to a diminished reduc4on of startle responding to the safety s4mulus (CS2–) in individuals who show more SR.
• Summary fear condi9oning (Day 1). Together, our • main fear-‐condi4oning results indicated that enhanced SR • resulted in a weaker differen4a4on between the threat • (CS1+) and the safety (CS2–) s4mulus over the course of • fear condi4oning. This weakened differen4al condi4oning • was due to a diminished reduc4on of startle responding • to the safety s4mulus (CS2–) in individuals who show • more SR. • During fear condi4oning, individuals with high levels of • SR showed weaker discrimina4on between threat and • safety due to elevated fear responding to the safety s4mulus • (CS2–).
• The transi4on from normal • fear to pathological anxiety (Rosen & Schulkin, 1998) • is characterized by maladap4ve generaliza9on of specific • fear learning to other classes of s4muli or contexts • that are intrinsically safe but somehow related to the • original fear learning and persistence of fear responses • while the threat is no longer present.
Extra Slides
Hypervigilance in BI
Perez-‐Edgar et al JACP 2011
Hypervigilance in BI
Perez-‐Edgar et al JACP 2011
May reflect aberrant interac@ons between the dorsolateral PFC and the amygdala
Discrimina@ng Threat from Safe
Lau et al PNAS 2011; Lissek et al SCAN in press
Amyg
dlPFC
May reflect aberrant interac@ons between the dorsolateral PFC and the amygdala
Discrimina@ng Threat from Safe
Lau et al PNAS 2011; Lissek et al SCAN in press
Amyg
dlPFC
May reflect aberrant interac@ons between the dorsolateral PFC and the amygdala
Discrimina@ng Threat from Safe
Lau et al PNAS 2011; Lissek et al SCAN in press
Amyg
dlPFC
Amygdala Ac@vity Predicts the Ac@ve
Interroga@on of the Environment (Risk Assessment)
Gamer & Buchel J Neurosci 2009; Gamer et al Curr Biol 2013
Amygdala Ac@vity Predicts the Ac@ve
Interroga@on of the Environment (Risk Assessment)
Gamer & Buchel J Neurosci 2009; Gamer et al Curr Biol 2013
Amygdala Ac@vity Predicts the Ac@ve
Interroga@on of the Environment (Risk Assessment)
Gamer & Buchel J Neurosci 2009; Gamer et al Curr Biol 2013
Amygdala damage aqenuates this ac@ve risk assessment behavior
This hypothesis seems to map onto the presentaBon of some
anxiety disorders, such as PTSD
Kheirbek et al Nature Rev Neurosci 2012
Context = Fire/Smoke Learn to associate context with anxiety and arousal
Kheirbek et al Nature Rev Neurosci 2012
Context = Fire/Smoke Learn to associate context with anxiety and arousal
Kheirbek et al Nature Rev Neurosci 2012
Context = Fire/Smoke Learn to associate context with anxiety and arousal
Kheirbek et al Nature Rev Neurosci 2012
Context = Fire/Smoke Learn to associate context with anxiety and arousal
Kheirbek et al Nature Rev Neurosci 2012
