Nuts & Bolts Plan for Today Next week: Review session (bring clicker!) and exam

Lecture (Grupe & Nitschke; Shackman)

Take-home criHcal thinking quesHons We probably will not have Hme to review together

You are free to answer 2 of the quesHons detailed in this powerpoint -or- to address quesHons from the last lecture

Q #4 is to peer review a paper that I am wriHng

How many would be interested in hearing the 5-min ash talk that I will be giving in Boston on Saturday?

PSYC 210:

DissecHng broad-band N/NE into its key consHtuents

Part 2 of 2

AJ Shackman 22 April 2014

Dan & Jack (UW-Madison)

John Cur@n (UW)

Chris@an Grillon (NIMH)

David Walker (Emory)

Mike Davis (Emory)

Me (UMD)

DissecHng Uncertainty: 5 Components Students What were the 3 components or intermediate phenotypes that we discussed last Hme?

DissecHng Uncertainty: 5 Components 1. Elevated esHmates of threat likelihood and intensity

2. Hyper-vigilance

3. Decient safety learning (and over-generalizaHon)

4. Elevated threat avoidance

5. Elevated reacHvity (or decient regulaHon of reacHons) to uncertain or ambiguous threat

. 5 transdiagnosHc intermediate phenotypes

that support chronically elevated NE and pervasive anxiety

DissecHng Uncertainty: 5 Components 1. Elevated esHmates of threat likelihood and intensity

2. Hyper-vigilance

3. Decient safety learning (and over-generalizaHon)

4. Elevated threat avoidance

5. Elevated reacHvity (or decient regulaHon of reacHons) to uncertain or ambiguous threat

. 5 transdiagnosHc intermediate phenotypes

that support chronically elevated NE and pervasive anxiety

Concerned for his safety, Paul locks his bedroom door instead of inves8ga8ng. Having avoided exploring the situa8on, Paul is le> withunresolved uncertaintyabout the source of the noisesFurthermore, not having learned that the situa8on was safe, Paul will be more likely to assume the worst the next 8me he hears a noise in the night.

4. Avoidance: Deleterious Consequences

4. Avoidance: Deleterious Consequences

4. Avoidance: Deleterious Consequences Avoidant behavior and thoughts, including worrisome thoughts and safety behaviors, prevent anxious individuals from being exposed to evidence that might contradict negaHve predicHons about the future Avoidance can therefore heighten threat expectancies under condiHons of uncertainty Because events that are avoided or worried about typically fail to occur, maladapHve avoidance tendencies are reinforced and anxious individuals develop false beliefs that they prevented these negaHve outcomes In short, they do not take advantage of opportuniHes for exHncHon

4. Avoidance: Deleterious Consequences Avoidant behavior and thoughts, including worrisome thoughts and safety behaviors, prevent anxious individuals from being exposed to evidence that might contradict negaHve predicHons about the future Avoidance can therefore heighten threat expectancies under condiHons of uncertainty Because events that are avoided or worried about typically fail to occur, maladapHve avoidance tendencies are reinforced and anxious individuals develop false beliefs that they prevented these negaHve outcomes In short, they do not take advantage of opportuniHes for exHncHon

4. Avoidance: Deleterious Consequences Avoidant behavior and thoughts, including worrisome thoughts and safety behaviors, prevent anxious individuals from being exposed to evidence that might contradict negaHve predicHons about the future Avoidance can therefore heighten threat expectancies under condiHons of uncertainty Because events that are avoided or worried about typically fail to occur, maladapHve avoidance tendencies are reinforced and anxious individuals develop false beliefs that they prevented these negaHve outcomes In short, they do not take advantage of opportuniHes for exHncHon

4. Avoidance: Deleterious Consequences Avoidant behavior and thoughts, including worrisome thoughts and safety behaviors, prevent anxious individuals from being exposed to evidence that might contradict negaHve predicHons about the future Avoidance can therefore heighten threat expectancies under condiHons of uncertainty Because events that are avoided or worried about typically fail to occur, maladapHve avoidance tendencies are reinforced and anxious individuals develop false beliefs that they prevented these negaHve outcomes In short, they do not take advantage of opportuniHes for exHncHon

Students What might anxious avoidance look like in daily life?

Everyday manifestaHons of avoidance

Barlow et al. Clin Psychol Sci 2013; Grupe & Nitschke Nature Rev Neurosci 2013

I cross the street to avoid talking to someone I know. I avoid doing thingslike picking up the phone when it rings or going to parHesbecause of my anxiety.

Everyday manifestaHons of avoidance

Barlow et al. Clin Psychol Sci 2013; Grupe & Nitschke Nature Rev Neurosci 2013

I cross the street to avoid talking to someone I know. I avoid doing thingslike picking up the phone when it rings or going to parHesbecause of my anxiety.

What mechanisms support elevated avoidance?

Barlow et al. Clin Psychol Sci 2013; Grupe & Nitschke Nature Rev Neurosci 2013

Hyper-sensiHvity to punishment and errors

I cross the street to avoid talking to someone I know. I avoid doing thingslike picking up the phone when it rings or going to parHesbecause of my anxiety.

Barlow et al. Clin Psychol Sci 2013; Grupe & Nitschke Nature Rev Neurosci 2013

Hyper-sensiHvity to errors

Shackman et al. Nature Rev Neurosci 2011; Cavanagh & Shackman J Physiol Paris in press

Hyper-sensiHvity to errors

ploBed nega8ve up

Shackman et al. Nature Rev Neurosci 2011; Cavanagh & Shackman J Physiol Paris in press

The Error-Related NegaHvity (ERN) is generated in the midcingulate cortex

Shackman et al. Nature Rev Neurosci 2011; Cavanagh & Shackman J Physiol Paris in press

The Error-Related NegaHvity (ERN) is emoHonal

Shackman et al. Nature Rev Neurosci 2011; Cavanagh & Shackman J Physiol Paris in press

The Error-Related NegaHvity (ERN) is emoHonal

MCC

Error-Related NegaHvity (reduced by anxiolyHcs)

Shackman et al. Nature Rev Neurosci 2011; Cavanagh & Shackman J Physiol Paris in press

The Error-Related NegaHvity (ERN) is emoHonal

MCC

Error-Related NegaHvity (reduced by anxiolyHcs)

Error-PotenHated Startle

Shackman et al. Nature Rev Neurosci 2011; Cavanagh & Shackman J Physiol Paris in press

CogniHve potenHals are also generated in the midcingulate cortex

MCC

Shackman et al. Nature Rev Neurosci 2011; Cavanagh & Shackman J Physiol Paris in press

CogniHve potenHals are also generated in the midcingulate cortex

N2

MCC

Cogni@ve Control Models: e.g., Yeung, Botvinick & Cohen, Psych Bull, 2004 Shackman et al. Nature Rev Neurosci 2011; Cavanagh & Shackman J Physiol Paris in press

These cogniHve potenHals are also enhanced in anxious individuals

Shackman, Shackman et al. under review

Both emoHonal (ERN, FRN) and cogniHve (N2) potenHals are consistently enhanced

Cavanagh & Shackman J Physiol Paris in press

Ticks indicate the correla@on between anxiety and one of the ERP components for each of the 47 studies

FRN: feedback-related nega@vity

Shackman et al. Nature Reviews Neurosci 2011

Large-scale meta-analysis of the imaging literature

shackmanlab.org

FDR q

Shackman et al. Nature Reviews Neurosci 2011

Large-scale meta-analysis of the imaging literature

FDR q

Shackman et al. Nature Reviews Neurosci 2011

Regions of 3-way overlap

shackmanlab.org

FDR q

Shackman et al. Nature Reviews Neurosci 2011

Co-localization in the mid-cingulate cortex

shackmanlab.org

FDR q

Payano Sosa, Seminowicz & Shackman in prep. Maps are freely available for download @ NeuroVault.org and NeuroSynth.org

Replicated using dierent databases, studies, and more recently developed analytic tools

FDR q

FDR q

But theres a problem

Meta-analysis entails an enormous loss of information compared to any particular imaging study

Meta-analysis entails an enormous loss of information compared to any particular imaging study

Peakify Clusters

Meta-analysis entails an enormous loss of information compared to any particular imaging study

Bunch of Studies

Meta-analysis entails an enormous loss of information compared to any particular imaging study

Bunch of Studies

Bunch of Domains

Meta-analysis entails an enormous loss of information compared to any particular imaging study

Bunch of Studies

Bunch of Domains

Smooth Threshold

Furman, Keaser, Payano Sosa, Padmala, Smith, Pessoa, Seminowicz & Shackman in prep.

A unique dataset

shackmanlab.org

Furman, Keaser, Payano Sosa, Padmala, Smith, Pessoa, Seminowicz & Shackman in prep.

A unique dataset

shackmanlab.org

Furman, Keaser, Payano Sosa, Padmala, Smith, Pessoa, Seminowicz & Shackman in prep. shackmanlab.org

Advanced spatial normalization techniques

Furman, Keaser, Payano Sosa, Padmala, Smith, Pessoa, Seminowicz & Shackman in prep.

ConvenHonal (SPM)

Advanced (FSL-BBR + ANTS)

Mean of 23 fMRI (EPI) Datasets Advanced spatial normalization techniques

shackmanlab.org

Furman, Keaser, Payano Sosa, Padmala, Smith, Pessoa, Seminowicz & Shackman in prep.

Furman, Keaser, Payano Sosa, Padmala, Smith, Pessoa, Seminowicz & Shackman in prep.

Payano Sosa & Shackman in prep.

Shackman et al. Nature Rev Neurosci 2011; Cavanagh & Shackman J Physiol Paris in press

Shackman et al. Nature Rev Neurosci 2011; Cavanagh & Shackman J Physiol Paris in press

Shackman et al. Nature Rev Neurosci 2011; Cavanagh & Shackman J Physiol Paris in press

Whadya mean control behavior?

Shackman et al. Nature Rev Neurosci 2011; Cavanagh & Shackman J Physiol Paris in press

Shackman et al. Nature Rev Neurosci 2011; Cavanagh & Shackman J Physiol Paris in press

Shackman et al. Nature Rev Neurosci 2011; Cavanagh & Shackman J Physiol Paris in press

Shackman et al. Nature Rev Neurosci 2011; Cavanagh & Shackman J Physiol Paris in press

Shackman et al. Nature Rev Neurosci 2011; Cavanagh & Shackman J Physiol Paris in press shackmanlab.org

Shackman et al. Nature Rev Neurosci 2011; Cavanagh & Shackman J Physiol Paris in press shackmanlab.org

Shackman et al. Nature Rev Neurosci 2011; Cavanagh & Shackman J Physiol Paris in press shackmanlab.org

Three generic ways to control behavior to avoid aversive outcomes

Shackman et al. Nature Rev Neurosci 2011; Cavanagh & Shackman J Physiol Paris in press

Three generic ways to control behavior to avoid aversive outcomes

1. If you get nega@ve feedback or commit an error, act in a more cau@ous, inhibited manner in the future.

Shackman et al. Nature Rev Neurosci 2011; Cavanagh & Shackman J Physiol Paris in press

Three generic ways to control behavior to avoid aversive outcomes

1. If you get nega@ve feedback or commit an error, act in a more cau@ous, inhibited manner in the future.

2. Avoid cues associated with nega@ve feedback (especially if its worse-than-expected). If there only 2 op@ons, pick the other one.

Shackman et al. Nature Rev Neurosci 2011; Cavanagh & Shackman J Physiol Paris in press

Three generic ways to control behavior to avoid aversive outcomes

1. If you get nega@ve feedback or commit an error, act in a more cau@ous, inhibited manner in the future.

2. Avoid cues associated with nega@ve feedback (especially if its worse-than-expected). If there only 2 op@ons, pick the other one.

3. Once you get nega@ve feedback, con@nue to avoid that cue.

Shackman et al. Nature Rev Neurosci 2011; Cavanagh & Shackman J Physiol Paris in press

Midcingulate signals predict inhibited, threat-avoidant behavior

Cavanagh & Shackman J Physiol Paris in press

Midcingulate signals predict inhibited, threat-avoidant behavior

Cavanagh & Shackman J Physiol Paris in press

Midcingulate signals predict inhibited, threat-avoidant behavior

Reten@on

Cavanagh & Shackman J Physiol Paris in press

Pharmacological manipulations reinforce the idea that emotion and cognition are functionally integrated in MCC

Structural equa@on model adapted from Bartholow et al J Abnormal Psychol 2012 Similar eects reported for benzodiazepines

Pharmacological manipulations reinforce the idea that emotion and cognition are functionally integrated in MCC

Structural equa@on model adapted from Bartholow et al J Abnormal Psychol 2012 Similar eects reported for benzodiazepines

Structural equa@on model adapted from Bartholow et al J Abnormal Psychol 2012

Pharmacological manipulations reinforce the idea that emotion and cognition are functionally integrated in MCC

Similar eects reported for benzodiazepines

Pharmacological manipulations reinforce the idea that emotion and cognition are functionally integrated in MCC

Structural equa@on model adapted from Bartholow et al J Abnormal Psychol 2012 Similar eects reported for benzodiazepines

Shackman et al. Nature Rev Neurosci 2011; Shackman , Shackman et al. under review; Cavanagh & Shackman J Physiol Paris in press

Shackman et al. Nature Rev Neurosci 2011; Shackman , Shackman et al. under review; Cavanagh & Shackman J Physiol Paris in press

Shackman et al. Nature Rev Neurosci 2011; Shackman , Shackman et al. under review; Cavanagh & Shackman J Physiol Paris in press

Shackman et al. Nature Rev Neurosci 2011; Shackman , Shackman et al. under review; Cavanagh & Shackman J Physiol Paris in press

anxiety in the lab

fMRI eyetracking

Deep phenotyping in the wild

0

2

4

6

1 1 1 1 1 2 2 2 2 2 3 3 3 3 3 4 4 4 4 4 5 5 5 5 5 6 6 6 6 6 7 7 7 7 7

mood context / activities (GPS)

social behavior (text, voice)

day

anxiety in the lab

fMRI eyetracking

Deep phenotyping in the wild

Anxiety-related reacHons are enhanced when there is uncertainty about the nature, probability, or Hming of threat

e.g., Cues that precede either low- or high-intensity shocks vs. cues that invariably precede high-intensity shocks e.g., Cues preceding shock on either 20% or 60% of trials vs. 100% certainty e.g., Unpredictably @med, neutral tones elicit more amygdala ac@vity and anxious behaviour in mice and humans than than the iden@cal tones when they are predictable

Observa@ons indicate that uncertainty itself without aversive outcomes causes elevated anxiety

5. Increased ReacHvity to Uncertainty/Ambiguity

Anxiety-related reacHons are enhanced when there is uncertainty about the nature, probability, or Hming of threat

e.g., Cues that precede either low- or high-intensity shocks vs. cues that invariably precede high-intensity shocks e.g., Cues preceding shock on either 20% or 60% of trials vs. 100% certainty e.g., Unpredictably @med, neutral tones elicit more amygdala ac@vity and anxious behaviour in mice and humans than than the iden@cal tones when they are predictable

Observa@ons indicate that uncertainty itself without aversive outcomes causes elevated anxiety

5. Increased ReacHvity to Uncertainty/Ambiguity

Anxiety-related reacHons are enhanced when there is uncertainty about the nature, probability, or Hming of threat

e.g., Cues that precede either low- or high-intensity shocks >> cues that invariably precede high-intensity shocks e.g., Cues preceding shock on either 20% or 60% of trials >> 100% certainty e.g., Unpredictably @med, neutral tones elicit more amygdala ac@vity and anxious behavior in mice and humans than the iden@cal tones when they are predictable

Observa@ons indicate that uncertainty itself without aversive outcomes causes elevated anxiety

5. Increased ReacHvity to Uncertainty/Ambiguity

Anxiety-related reacHons are enhanced when there is uncertainty about the nature, probability, or Hming of threat

e.g., Cues that precede either low- or high-intensity shocks >> cues that invariably precede high-intensity shocks e.g., Cues preceding shock on either 20% or 60% of trials >> 100% certainty e.g., Unpredictably @med, neutral tones elicit more amygdala ac@vity and anxious behavior in mice and humans than the iden@cal tones when they are predictable

Observa@ons indicate that uncertainty itself without aversive outcomes causes elevated anxiety

5. Increased ReacHvity to Uncertainty/Ambiguity

Anxiety-related reacHons are enhanced when there is uncertainty about the nature, probability, or Hming of threat

e.g., Cues that precede either low- or high-intensity shocks >> cues that invariably precede high-intensity shocks e.g., Cues preceding shock on either 20% or 60% of trials >> 100% certainty e.g., Unpredictably @med, neutral tones elicit more amygdala ac@vity and anxious behavior in mice and humans than the iden@cal tones when they are predictable

Observa@ons indicate that uncertainty itself without aversive outcomes causes elevated anxiety

5. Increased ReacHvity to Uncertainty/Ambiguity

Unpredictably Hmed, neutral tones:

5. Increased ReacHvity to Uncertainty/Ambiguity

Herry et al J Neurosci 2007 Details Are Not Important

Unpredictably Hmed, neutral tones:

5. Increased ReacHvity to Uncertainty/Ambiguity

Herry et al J Neurosci 2007

Increase Amyg AcHvaHon

Details Are Not Important

Unpredictably Hmed, neutral tones:

5. Increased ReacHvity to Uncertainty/Ambiguity

Herry et al J Neurosci 2007

Increase Amyg AcHvaHon

Increase Anxiety

Details Are Not Important

Unpredictably Hmed, neutral tones:

5. Increased ReacHvity to Uncertainty/Ambiguity

Herry et al J Neurosci 2007

Increase Amyg AcHvaHon

Increase Anxiety

Increase Both

Details Are Not Important

Unpredictably Hmed, neutral tones:

5. Increased ReacHvity to Uncertainty/Ambiguity

Herry et al J Neurosci 2007

Increase Amyg AcHvaHon

Increase Anxiety

Increase Both

Details Are Not Important

Observa6ons indicate that uncertainty itself, in the absence of poten6al danger, can increase anxiety Suggests that uncertainty is another ac6ve ingredient that causally contributes to the anxious phenotype

Clinically eecHve anH-anxiety agents, such as benzodiazepines and mild alcohol intoxicaHon, selecHvely reduce anxiety elicited by uncertain threat (but are relaHvely ineecHve for acute fear in response to imminent, certain danger) This indicates that elevated reacHvity to uncertainty is another key acHve ingredient in the anxious phenotype

Pharmacological Evidence

Grupe & Nitschke NRN 2013; Bradford et al. Psychol Sci in press

Clinically eecHve anH-anxiety agents, such as benzodiazepines and mild alcohol intoxicaHon, selecHvely reduce anxiety elicited by uncertain threat (but are relaHvely ineecHve for acute fear in response to imminent, certain danger) Reinforces the idea that elevated reacHvity to uncertainty is another key acHve ingredient that causally contributes to N/NE and clinical anxiety

Pharmacological Evidence

Grupe & Nitschke NRN 2013; Bradford et al. Psychol Sci in press

Puong It All Back Together Again

Grupe & Nitschke NRN 2013

Puong It All Back Together Again

Grupe & Nitschke NRN 2013 Details Are Not Important

Puong It All Back Together Again

Grupe & Nitschke NRN 2013

The arrows represent educated guesses

but we know that these processes interact and recursively inuence one another (as with the unpredictable tones and vigilance)

Details Are Not Important

5 core consHtuents of the anxious phenotype 1. Inated esHmates of threat certainty or intensity/cost

2. Hypervigilance (apenHonal threat bias) AcHve ingredient/Causal Present in BI Amygdala, direct or indirect inuence on sensory cortex

3. Decient safety learning and overgeneralizaHon Anxious individuals learn certain, imminent threat just ne Predicts rst onset; present in BI dlPFC, vmPFC, BNST?

4. CogniHve and behavioral avoidance MCC Circuit centered on the MCC may help to orchestrate some of the other processes Key hub

5. Hyper-reacHvity to uncertainty and ambiguity AcHve 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 consHtuents of the anxious phenotype 1. Inated esHmates of threat certainty or intensity/cost (mountain out of a molehill)

2. Hypervigilance (bias to allocate excess apenHon to threat or scanning for threat-relevant informaHon) AcHve ingredient/Causal Present in BI Circuits centered on the amygdala, poised to directly/indirectly inuence sensory cortex

3. Decient safety learning and overgeneralizaHon of anxiety to other cues and contexts Anxious individuals learn about clear and imminent threats just ne Predicts rst onset; present in BI

4. Avoidance Circuit centered on the MCC may help to orchestrate behavioral avoidance

5. Hyper-reacHvity to uncertainty and ambiguity AcHve ingredient/Causal Extended amygdala (amygdala, BNST)

6. These processes likely interact in complex ways that reinforce pervasive, chronic distress and arousal a la Pete and Paul.

Key Take Homes

5 core consHtuents of the anxious phenotype 1. Inated esHmates of threat certainty or intensity/cost (mountain out of a molehill)

2. Hypervigilance (bias to allocate excess apenHon to threat or scanning for threat-relevant informaHon) AcHve ingredient/Causal Present in BI Circuits centered on the amygdala, poised to directly/indirectly inuence sensory cortex

3. Decient safety learning and overgeneralizaHon of anxiety to other cues and contexts Anxious individuals learn about clear and imminent threats just ne Predicts rst onset; present in BI

4. Avoidance Circuit centered on the MCC may help to orchestrate behavioral avoidance

5. Hyper-reacHvity to uncertainty and ambiguity AcHve ingredient/Causal Extended amygdala (amygdala, BNST)

6. These processes likely interact in complex ways that reinforce pervasive, chronic distress and arousal a la Pete and Paul.

Key Take Homes

5 core consHtuents of the anxious phenotype 1. Inated esHmates of threat certainty or intensity/cost (mountain out of a molehill)

2. Hypervigilance (bias to allocate excess apenHon to threat or scanning for threat-relevant informaHon) AcHve ingredient/Causal Present in BI Circuits centered on the amygdala, poised to directly/indirectly inuence sensory cortex

3. Decient safety learning and overgeneralizaHon of anxiety to other cues and contexts Anxious individuals learn about clear and imminent threats just ne Predicts rst onset; present in BI Reects extended amygdala (BNST)

4. Avoidance Circuit centered on the MCC may help to orchestrate behavioral avoidance

5. Hyper-reacHvity to uncertainty and ambiguity AcHve ingredient/Causal Extended amygdala (amygdala, BNST)

6. These processes likely interact in complex ways that reinforce pervasive, chronic distress and arousal a la Pete and Paul.

Key Take Homes

5 core consHtuents of the anxious phenotype 1. Inated esHmates of threat certainty or intensity/cost (mountain out of a molehill)

2. Hypervigilance (bias to allocate excess apenHon to threat or scanning for threat-relevant informaHon) AcHve ingredient/Causal Present in BI Circuits centered on the amygdala, poised to directly/indirectly inuence sensory cortex

3. Decient safety learning and overgeneralizaHon of anxiety to other cues and contexts Anxious individuals learn about clear and imminent threats just ne Predicts rst onset; present in BI Reects extended amygdala (BNST)

4. Avoidance Circuit centered on the MCC may help to orchestrate behavioral avoidance

5. Hyper-reacHvity to uncertainty and ambiguity AcHve ingredient/Causal Extended amygdala (amygdala, BNST)

6. These processes likely interact in complex ways that reinforce pervasive, chronic distress and arousal a la Pete and Paul.

Key Take Homes

5 core consHtuents of the anxious phenotype 1. Inated esHmates of threat certainty or intensity/cost (mountain out of a molehill)

2. Hypervigilance (bias to allocate excess apenHon to threat or scanning for threat-relevant informaHon) AcHve ingredient/Causal Present in BI Circuits centered on the amygdala, poised to directly/indirectly inuence sensory cortex

3. Decient safety learning and overgeneralizaHon of anxiety to other cues and contexts Anxious individuals learn about clear and imminent threats just ne Predicts rst onset; present in BI Reects extended amygdala (BNST)

4. Avoidance Circuit centered on the MCC may help to orchestrate behavioral avoidance

5. Hyper-reacHvity to uncertainty and ambiguity AcHve ingredient/Causal Extended amygdala

6. These processes likely interact in complex ways that reinforce pervasive, chronic distress and arousal a la Pete and Paul.

Key Take Homes

5 core consHtuents of the anxious phenotype 1. Inated esHmates of threat certainty or intensity/cost (mountain out of a molehill)

2. Hypervigilance (bias to allocate excess apenHon to threat or scanning for threat-relevant informaHon) AcHve ingredient/Causal Present in BI Circuits centered on the amygdala, poised to directly/indirectly inuence sensory cortex

3. Decient safety learning and overgeneralizaHon of anxiety to other cues and contexts Anxious individuals learn about clear and imminent threats just ne Predicts rst onset; present in BI Reects extended amygdala (BNST)

4. Avoidance

Circuit centered on the MCC may help to orchestrate behavioral avoidance

5. Hyper-reacHvity to uncertainty and ambiguity AcHve ingredient/Causal Extended amygdala

6. These processes likely interact in complex ways that reinforce pervasive, chronic distress and arousal a la Pete and Paul.

Key Take Homes

Take Home CriHcal Thinking QuesHons

Take Home CriHcal Thinking QuesHons Please select any 2 You are also free to respond to any of the ques6ons from the last lecture that you have not already answered.

Take Home CriHcal Thinking QuesHons 1. Tradi@onally, psychology and philosophy have divided

the mind into 3 facul@es: emo@on, cogni@on, and will. Does this trichotomy make sense? E.g., throughout the semester, we have discussed the key features of E and N. Ojen@mes, these traits and their associated states (PE and NE) are conceptualized as emo@onal. Hence, their neural correlates have been considered the emo@onal brain, consistent with the tradi@onal trichotomy. But are they really just emo@onal (hot) or do they fundamentally involve processes that we usually consider cogni@ve (cold)? What are the implica@ons for the emo@onal vs. cogni@ve brain? For the trichotomy?

Take Home CriHcal Thinking QuesHons 2. Briey describe an example from your own life, that of a friend, or a hypothe@cal example that exemplies 1 of the 5 intermediate phenotypes described by Grupe & Nitschke.

Take Home CriHcal Thinking QuesHons 3. Briey describe some specic ways (psychological or neural) in which decient safety learning might be related to heightened reac@vity to uncertain/ambiguous threat.

Take Home CriHcal Thinking QuesHons 4. I am in the midst of wri@ng a review that closely parallels the structure of our class. Download the paper from Canvas: shackman_stock_lemay_fox_Q2_041515.docx What do you think? What are your sugges@ons for strengthening the not-quite-done manuscript? What are the most important future research challenges for me to highlight in the Discussion?

Time-Permiong Review QuesHons

Individuals with high levels of N/NE are characterized by

A. Inated es@mates of threat likelihood

B. Abnormally low es@mates of threat intensity

Inflated estim

ates of th

rea...

Abnormally lo

w estimate

s...

0%0%

Anxious individuals aqen@onal bias to threat can be re-trained using

computerized tasks. Which is the best answer?

A. This is clinically eec@ve, albeit weakly

B. Retraining the bias produces a las@ng diminu@on in anxiety (e.g. in a public speaking task)

C. Furthermore, CBT targe@ng excess anxiety reduces the aqen@onal bias (reverse eect)

D. Collec@vely, these mechanis@c ndings indicate a causal role This

is clinically effective, ...

Retraining the bias produ...

Furtherm

ore, CBT targeti..

Collectively, these

mech

a...

0% 0%0%0%

Anxious individuals tend to

A. Allocate excess aqen@on to threat

B. Are faster to respond to the dot-probe when it occurs at the same loca@on as a nega@ve word

C. Both Allocate

exces

s attention ..

Are faster to respond to ... Bo

th

0% 0%0%

Hypervigilance may reect A. The direct inuence of the

amygdala on sensory cortex

B. Robust projec@ons from the amygdala to the visual cortex

C. An indirect inuence of the amygdala, mediated by acetylcholine neurons sirng in the basal forebrain (nucleus basalis of Meynert); wake up!

D. All of the above The direct influence of th

...

Robust pro

jections fro

m ...

An indirect influence of t..

All of the above

0% 0%0%0%

Anxious individuals tend to show

A. Heightened anxiety (startle) in response to clear and imminent threat (CS+)

B. Excess anxiety to uncertain and ambiguous danger (CS- , ITI)

Heighten

ed an

xiety (startl..

Exces

s anxiety to u

ncerta..

0%0%

Anxious individuals tend to

A. Overgeneralize anxiety to cues that resemble genuine dangers (e.g., Lisseks parametric rings)

B. Show anxiety that is strictly limited to threat

Overg

enera

lize anxiety to...

Show

anxiety tha

t is strictl...

0%0%

Individuals with anxiety disorders A. Have dicul@es tuning

their anxiety and learning what is safe (safety learning decit)

B. This promotes to chronic, pervasive anxiety, arousal, and stress; they dont know when its safe to relax

C. And predicts who will develop an anxiety disorder

D. All of the above Have difficulties tu

ning t...

This p

romote

s to chro

nic,...

And pred

icts w

ho will de...

All of the above

0% 0%0%0%

Individuals with a childhood history of extreme BI, a facet of N/NE, show

A. Hypervigilance on the dot-probe task

B. Elevated startle during periods of objec@ve safety

C. Both

Hypervigilance on the do...

Elevated

startle during p... Bo

th

0% 0%0%

The End

Extra Slides

Cavanagh & Shackman J Physiol Paris in press

Cavanagh & Shackman J Physiol Paris in press

Cavanagh & Shackman J Physiol Paris in press

Cavanagh & Shackman J Physiol Paris in press

Cavanagh & Shackman J Physiol Paris in press; Cavanagh & Frank TiCS 2014

Cavanagh & Shackman J Physiol Paris in press; Cavanagh & Frank TiCS 2014

N2

Cavanagh & Shackman J Physiol Paris in press; Cavanagh & Frank TiCS 2014

Cavanagh & Shackman J Physiol Paris in press; Cavanagh & Frank TiCS 2014

ERN

Cavanagh & Shackman J Physiol Paris in press; Cavanagh & Frank TiCS 2014

Shackman et al. Nature Rev Neurosci 2011; Cavanagh & Shackman J Physiol Paris in press

Shackman et al. Nature Rev Neurosci 2011; Cavanagh & Shackman J Physiol Paris in press

Shackman et al. Nature Rev Neurosci 2011; Cavanagh & Shackman J Physiol Paris in press

Shackman et al. Nature Rev Neurosci 2011; Cavanagh & Shackman J Physiol Paris in press

Shackman et al. Nature Rev Neurosci 2011; Cavanagh & Shackman J Physiol Paris in press

Shackman et al. Nature Rev Neurosci 2011; Cavanagh & Shackman J Physiol Paris in press

Shackman et al. Nature Rev Neurosci 2011; Cavanagh & Shackman J Physiol Paris in press

Shackman et al. Nature Rev Neurosci 2011; Cavanagh & Shackman J Physiol Paris in press

Shackman et al. Nature Rev Neurosci 2011; Cavanagh & Shackman J Physiol Paris in press

Payano Sosa & Shackman in prep.

Payano Sosa & Shackman in prep.

Neurosynth.org search terms: anxiety, pain, cogni@ve control (forward inference) Payano Sosa & Shackman in prep.

Neurosynth.org search terms: anxiety, pain, cogni@ve control (forward inference) Payano Sosa & Shackman in prep.

Neurosynth.org search terms: anxiety, pain, cogni@ve control (forward inference) Payano Sosa & Shackman in prep.

Neurosynth.org search terms: anxiety, pain, cogni@ve control (forward inference) Payano Sosa & Shackman in prep.

Furman, Keaser, Payano Sosa, Padmala, Smith, Pessoa, Seminowicz & Shackman in prep.

Furman, Keaser, Payano Sosa, Padmala, Smith, Pessoa, Seminowicz & Shackman in prep.

Furman, Keaser, Payano Sosa, Padmala, Smith, Pessoa, Seminowicz & Shackman in prep.

Furman, Keaser, Payano Sosa, Padmala, Smith, Pessoa, Seminowicz & Shackman in prep.

Furman, Keaser, Payano Sosa, Padmala, Smith, Pessoa, Seminowicz & Shackman in prep.

Furman, Keaser, Payano Sosa, Padmala, Smith, Pessoa, Seminowicz & Shackman in prep.

Furman, Keaser, Payano Sosa, Padmala, Smith, Pessoa, Seminowicz & Shackman in prep.

Conclusions

Shackman, Fox & Seminowicz in press; Okon-Singer, Hendler, Pessoa & Shackman under review

Conclusions

Shackman, Fox & Seminowicz in press; Okon-Singer, Hendler, Pessoa & Shackman under review

Conclusions

Shackman, Fox & Seminowicz in press; Okon-Singer, Hendler, Pessoa & Shackman under review

Conclusions

Shackman, Fox & Seminowicz in press; Okon-Singer, Hendler, Pessoa & Shackman under review

Lyn = Lyn Abramson

Aberrant InterpretaHon of Ambiguity Not just uncertainty, also ambiguity InterpretaHon Biases:

Anxious individuals view ambiguous sHmuli as threatening GAD (everything is poten@ally dangerous)

SAD (every face or social scenario is poten@ally dangerous)

PTSD (ambiguous cues are interpreted as combat-related)

Grupe & Nitschke NRN 2013

Aberrant InterpretaHon of Ambiguity Not just uncertainty, also ambiguity InterpretaHon Biases:

Anxious individuals view ambiguous sHmuli as threatening GAD (everything is poten@ally dangerous)

SAD (every face or social scenario is poten@ally dangerous)

PTSD (ambiguous cues are interpreted as combat-related)

Grupe & Nitschke NRN 2013

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Retraining the InterpretaHon of Ambiguity

Ann Rev Clin Psychol 2012 see also Van Boekstaele et al Psychol Bull in press

How might we re-train?

Retraining the InterpretaHon of Ambiguity

Ann Rev Clin Psychol 2012

Present an ambiguous homograph (same lepers, dierent meaning) e.g. growth

Followed by a target word fragment

NegaHve Training: fragment = C-NC-R (cancer) PosiHve Training: fragment GR-AT-R (greater)

In eect, you train subjects to expect good or bad things following ambiguous cues Assessment

Latency to respond to posiHve and negaHve target words

Retraining the InterpretaHon of Ambiguity

Ann Rev Clin Psychol 2012

Present an ambiguous homograph (same lepers, dierent meaning) e.g. growth

Followed by a target word fragment

NegaHve Training: fragment = C-NC-R (cancer) PosiHve Training: fragment GR-AT-R (greater)

In eect, you train subjects to expect good or bad things following ambiguous cues Assessment

Latency to respond to posiHve and negaHve target words

Retraining the InterpretaHon of Ambiguity

Ann Rev Clin Psychol 2012

Present an ambiguous homograph (same lepers, dierent meaning) e.g. growth

Followed by a target word fragment

NegaHve Training: fragment = C-NC-R (cancer) PosiHve Training: fragment GR-AT-R (greater)

In eect, you train subjects to expect good or bad things following ambiguous cues Assessment

Latency to respond to posiHve and negaHve target words

Retraining the InterpretaHon of Ambiguity

Ann Rev Clin Psychol 2012

Limited evidence that the posiHve training procedure produces lasHng changes in the interpretaHon of ambiguity

E.g., reduces trait anxiety (replicated in several studies)

E.g., Worriers report fewer worries during worry inducHon post training Evidence that negaHve interpretaHons of ambiguity are another acHve ingredient

Retraining the InterpretaHon of Ambiguity

Ann Rev Clin Psychol 2012

Limited evidence that the posiHve training procedure produces lasHng changes in the interpretaHon of ambiguity

E.g., reduces trait anxiety (replicated in several studies)

E.g., Worriers report fewer worries during worry inducHon post training Evidence that negaHve interpretaHons of ambiguity are another acHve ingredient

Retraining the InterpretaHon of Ambiguity

Ann Rev Clin Psychol 2012

Limited evidence that the posiHve training procedure produces lasHng changes in the interpretaHon of ambiguity

E.g., reduces trait anxiety (replicated in several studies)

E.g., Worriers report fewer worries during worry inducHon post training Evidence that negaHve interpretaHons of ambiguity are another acHve ingredient

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