Neuroscience of fear extinction: Implications for assessment and treatment of fear-based and anxiety related disorders

Milad, Mohammed R.; Rosenbaum, Blake L.; Simon, Naomi M.

doi:10.1016/j.brat.2014.08.006

Cited by 134 publications

(108 citation statements)

References 99 publications

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“…In contrast to existing accounts of psychotherapy mechanisms (18, 32), we observed no limbic attenuation during emotional reactivity, no increased recruitment of posterior lateral prefrontal substrates implicated in top-down control (33), and no prefrontal change during emotional reactivity, emotional conflict, or emotional conflict regulation. Importantly, this contrasts with treatment moderation results in this sample, wherein emotional reactivity and emotional conflict regulation-related brain function predicted treatment outcome (34).…”

Section: Discussioncontrasting

confidence: 99%

Selective Effects of Psychotherapy on Frontopolar Cortical Function in PTSD

Fonzo

Goodkind

Oathes

et al. 2017

AJP

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Objective Exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD), but a comprehensive, emotion-focused perspective on how psychotherapy impacts brain function is lacking. Here, we assess changes in brain function following prolonged exposure therapy across three emotional reactivity and regulation paradigms. Methods Individuals with PTSD underwent functional magnetic resonance imaging (fMRI) at rest and while completing three tasks assessing emotional reactivity and regulation. Individuals were then randomized to prolonged exposure treatment (N=36) or waitlist (N=30) and underwent a second scan approximately four weeks following the last treatment session or a comparable waiting period, respectively. Results Treatment-specific changes were observed only during cognitive reappraisal of negative images. Psychotherapy increased lateral frontopolar cortex activity and its connectivity with the ventromedial prefrontal cortex/ventral striatum. Greater increases in frontopolar activation were associated with improvement in hyperarousal symptoms and psychological well-being. The frontopolar cortex also displayed a greater variety of temporal resting state signal pattern changes following treatment. Using concurrent transcranial magnetic stimulation and fMRI in healthy participants, we demonstrate the lateral frontopolar cortex exerts downstream influence on the ventromedial prefrontal cortex/ventral striatum. Conclusions Changes in frontopolar function during deliberate regulation of negative affect is one key mechanism of adaptive psychotherapeutic change in PTSD. Given that: a) frontopolar connectivity with ventromedial regions during emotion regulation is enhanced by psychotherapy; and b) frontopolar cortex exerts downstream influence on ventromedial regions in healthy individuals, these findings inform a novel conceptualization of how psychotherapy works and identify a promising target for stimulation-based therapeutics.

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Section: Discussioncontrasting

confidence: 99%

Selective Effects of Psychotherapy on Frontopolar Cortical Function in PTSD

Fonzo

Goodkind

Oathes

et al. 2017

AJP

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“…A number of so-called cognitive enhancers have been uncovered, including yohimbine, which increases central noradrenergic transmission or D-cycloserine, a partial agonist at the glycine site of Nmethyl-D-aspartate glutamate receptors (56,57). Even though the discovery of cognitive enhancers may be promising by accelerating treatment effectiveness, they do not prevent the return of fear because they leave the fear memory intact.…”

Section: Discussionmentioning

confidence: 96%

An Abrupt Transformation of Phobic Behavior After a Post-Retrieval Amnesic Agent

Soeter

Kindt

2015

Biological Psychiatry

184

234

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“…Several authors have reported reduced prefrontal cortex thickness in PTSD patients (78,198,325,352,419,420,422,521), while others who have looked for this have not (331). The prefrontal areas whose reduction in PTSD patients has been reported are not identical for all authors.…”

Section: Fear Extinction and Its Relation With Exposure Therapy Fomentioning

confidence: 96%

Fear Memory

Izquierdo

Furini

Myskiw

2016

Physiological Reviews

363

259

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Fear memory is the best-studied form of memory. It was thoroughly investigated in the past 60 years mostly using two classical conditioning procedures (contextual fear conditioning and fear conditioning to a tone) and one instrumental procedure (one-trial inhibitory avoidance). Fear memory is formed in the hippocampus (contextual conditioning and inhibitory avoidance), in the basolateral amygdala (inhibitory avoidance), and in the lateral amygdala (conditioning to a tone). The circuitry involves, in addition, the pre-and infralimbic ventromedial prefrontal cortex, the central amygdala subnuclei, and the dentate gyrus. Fear learning models, notably inhibitory avoidance, have also been very useful for the analysis of the biochemical mechanisms of memory consolidation as a whole. These studies have capitalized on in vitro observations on long-term potentiation and other kinds of plasticity. The effect of a very large number of drugs on fear learning has been intensively studied, often as a prelude to the investigation of effects on anxiety. The extinction of fear learning involves to an extent a reversal of the flow of information in the mentioned structures and is used in the therapy of posttraumatic stress disorder and fear memories in general.

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Neuroscience of fear extinction: Implications for assessment and treatment of fear-based and anxiety related disorders

Cited by 134 publications

References 99 publications

Selective Effects of Psychotherapy on Frontopolar Cortical Function in PTSD

Selective Effects of Psychotherapy on Frontopolar Cortical Function in PTSD

An Abrupt Transformation of Phobic Behavior After a Post-Retrieval Amnesic Agent

Fear Memory

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