Dataset Information

Skin Conductance Responses and Neural Activations During Fear Conditioning and Extinction Recall Across Anxiety Disorders.

ABSTRACT:

Importance

The fear conditioning and extinction neurocircuitry has been extensively studied in healthy and clinical populations, with a particular focus on posttraumatic stress disorder. Despite significant overlap of symptoms between posttraumatic stress disorder and anxiety disorders, the latter has received less attention. Given that dysregulated fear levels characterize anxiety disorders, examining the neural correlates of fear and extinction learning may shed light on the pathogenesis of underlying anxiety disorders.

Objectives

To investigate the psychophysiological and neural correlates of fear conditioning and extinction recall in anxiety disorders and to document how these features differ as a function of multiple diagnoses or anxiety severity.

Design, setting, and participants

This investigation was a cross-sectional, case-control, functional magnetic resonance imaging study at an academic medical center. Participants were healthy controls and individuals with at least 1 of the following anxiety disorders: generalized anxiety disorder, social anxiety disorder, specific phobia, and panic disorder. The study dates were between March 2013 and May 2015.

Exposures

Two-day fear conditioning and extinction paradigm.

Main outcomes and measures

Skin conductance responses, blood oxygenation level-dependent responses, trait anxiety scores from the State Trait Anxiety Inventory-Trait Form, and functional connectivity.

Results

This study included 21 healthy controls (10 women) and 61 individuals with anxiety disorders (36 women). P values reported for the neuroimaging results are all familywise error corrected. Skin conductance responses during extinction recall did not differ between individuals with anxiety disorders and healthy controls (ηp2 = 0.001, P = .79), where ηp2 is partial eta squared. The anxiety group had lower activation of the ventromedial prefrontal cortex (vmPFC) during extinction recall (ηp2 = 0.178, P = .02). A similar hypoactive pattern was found during early conditioning (ηp2 = 0.106, P = .009). The vmPFC hypoactivation was associated with anxiety symptom severity (r = -0.420, P = .01 for conditioning and r = -0.464, P = .004 for extinction recall) and the number of co-occuring anxiety disorders diagnosed (ηp2 = 0.137, P = .009 for conditioning and ηp2 = 0.227, P = .004 for extinction recall). Psychophysiological interaction analyses revealed that the fear network connectivity differed between healthy controls and the anxiety group during fear learning (ηp2 range between 0.088 and 0.176 and P range between 0.02 and 0.003) and extinction recall (ηp2 range between 0.111 and 0.235 and P range between 0.02 and 0.002).

Conclusions and relevance

Despite no skin conductance response group differences during extinction recall, brain activation patterns between anxious and healthy individuals differed. These findings encourage future studies to examine the conditions longitudinally and in the context of treatment trials to improve and guide therapeutics via advanced neurobiological understanding of each disorder.

SUBMITTER: Marin MF

PROVIDER: S-EPMC5539837 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Skin Conductance Responses and Neural Activations During Fear Conditioning and Extinction Recall Across Anxiety Disorders.

Marin Marie-France MF Zsido Rachel G RG Song Huijin H Lasko Natasha B NB Killgore William D S WDS Rauch Scott L SL Simon Naomi M NM Milad Mohammed R MR

JAMA psychiatry 20170601 6

<h4>Importance</h4>The fear conditioning and extinction neurocircuitry has been extensively studied in healthy and clinical populations, with a particular focus on posttraumatic stress disorder. Despite significant overlap of symptoms between posttraumatic stress disorder and anxiety disorders, the latter has received less attention. Given that dysregulated fear levels characterize anxiety disorders, examining the neural correlates of fear and extinction learning may shed light on the pathogenes ...[more]

PMID: 28403387

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Project description:Dentate gyrus (DG) is widely thought to provide a teaching signal that enables hippocampal encoding of memories, but its role during retrieval is poorly understood. Some data and models suggest that DG plays no role in retrieval; others encourage the opposite conclusion. To resolve this controversy, we evaluated the effects of optogenetic inhibition of dorsal DG during context fear conditioning, recall, generalization, and extinction in male mice. We found that (1) inhibition during training impaired context fear acquisition; (2) inhibition during recall did not impair fear expression in the training context, unless mice had to distinguish between similar feared and neutral contexts; (3) inhibition increased generalization of fear to an unfamiliar context that was similar to a feared one and impaired fear expression in the conditioned context when it was similar to a neutral one; and (4) inhibition impaired fear extinction. These effects, as well as several seemingly contradictory published findings, could be reproduced by BACON (Bayesian Context Fear Algorithm), a physiologically realistic hippocampal model positing that acquisition and retrieval both involve coordinated activity in DG and CA3. Our findings thus suggest that DG contributes to retrieval and extinction, as well as to the initial establishment of context fear.SIGNIFICANCE STATEMENT Despite abundant evidence that the hippocampal dentate gyrus (DG) plays a critical role in memory, it remains unclear whether the role of DG relates to memory acquisition or retrieval. Using contextual fear conditioning and optogenetic inhibition, we show that DG contributes to both of these processes. Using computational simulations, we identify specific mechanisms through which the suppression of DG affects memory performance. Finally, we show that DG contributes to fear extinction learning, a process in which learned fear is attenuated through exposures to a fearful context in the absence of threat. Our data resolve a long-standing question about the role of DG in memory and provide insight into how disorders affecting DG, including aging, stress, and depression, influence cognitive processes.

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Dataset Information

Skin Conductance Responses and Neural Activations During Fear Conditioning and Extinction Recall Across Anxiety Disorders.

Importance

Objectives

Design, setting, and participants

Exposures

Main outcomes and measures

Results

Conclusions and relevance

Publications

Skin Conductance Responses and Neural Activations During Fear Conditioning and Extinction Recall Across Anxiety Disorders.

Similar Datasets

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