Dataset Information

Neural functional architecture and modulation during decision making under uncertainty in individuals with generalized anxiety disorder.

ABSTRACT: BACKGROUND:Recent evidence suggests that repetitive transcranial magnetic stimulation (rTMS) might be effective in treating generalized anxiety disorder (GAD). Cognitive models of GAD highlight the role of intolerance of uncertainty (IU) in precipitating and maintaining worry, and it has been hypothesized that patients with GAD exhibit decision-making deficits under uncertain conditions. Improving understanding of the neural mechanisms underlying cognitive deficits associated with IU may lead to the identification of novel rTMS treatment targets and optimization of treatment parameters. The current report describes two interrelated studies designed to identify and verify a potential neural target for rTMS treatment of GAD. METHODS:Study I explored the integrity of prefrontal cortex (PFC) and amygdala neural networks, which underlie decision making under conditions of uncertainty, in GAD. Individuals diagnosed with GAD (n = 31) and healthy controls (n = 20) completed a functional magnetic resonance imaging (fMRI) gambling task that manipulated uncertainty using high versus low error rates. In a subsequent randomized-controlled trial (Study II), a subset of the GAD sample (n = 16) completed the fMRI gambling task again after 30 sessions of active versus sham rTMS (1 Hz, right dorsolateral prefrontal cortex) to investigate the modulation of functional networks and symptoms. RESULTS:In Study I, participants with GAD demonstrated impairments in PFC-PFC and PFC-amygdala functional connectivity (FC) mostly during the high uncertainty condition. In Study II, one region of interest pair, dorsal anterior cingulate (ACC) - subgenual ACC, showed "normalization" of FC following active, but not sham, rTMS, and neural changes were associated with improvement in worry symptoms. CONCLUSIONS:These results outline a possible treatment mechanism of rTMS in GAD, and pave the way for future studies of treatment optimization.

SUBMITTER: Assaf M

PROVIDER: S-EPMC6085921 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Neural functional architecture and modulation during decision making under uncertainty in individuals with generalized anxiety disorder.

Assaf Michal M Rabany Liron L Zertuche Luis L Bragdon Laura L Tolin David D Goethe John J Diefenbach Gretchen G

Brain and behavior 20180621 8

<h4>Background</h4>Recent evidence suggests that repetitive transcranial magnetic stimulation (rTMS) might be effective in treating generalized anxiety disorder (GAD). Cognitive models of GAD highlight the role of intolerance of uncertainty (IU) in precipitating and maintaining worry, and it has been hypothesized that patients with GAD exhibit decision-making deficits under uncertain conditions. Improving understanding of the neural mechanisms underlying cognitive deficits associated with IU may ...[more]

PMID: 29931835

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Project description:OBJECTIVE:Deficits in reinforcement-based decision making have been reported in generalized anxiety disorder. However, the pathophysiology of these deficits is largely unknown; published studies have mainly examined adolescents, and the integrity of core functional processes underpinning decision making remains undetermined. In particular, it is unclear whether the representation of reinforcement prediction error (PE) (the difference between received and expected reinforcement) is disrupted in generalized anxiety disorder. This study addresses these issues in adults with the disorder. METHOD:Forty-six unmedicated individuals with generalized anxiety disorder and 32 healthy comparison subjects group-matched on IQ, gender, and age performed a passive avoidance task while undergoing functional MRI. Data analyses were performed using a computational modeling approach. RESULTS:Behaviorally, individuals with generalized anxiety disorder showed impaired reinforcement-based decision making. Imaging results revealed that during feedback, individuals with generalized anxiety disorder relative to healthy subjects showed a reduced correlation between PE and activity within the ventromedial prefrontal cortex, ventral striatum, and other structures implicated in decision making. In addition, individuals with generalized anxiety disorder relative to healthy participants showed a reduced correlation between punishment PEs, but not reward PEs, and activity within the left and right lentiform nucleus/putamen. CONCLUSIONS:This is the first study to identify computational impairments during decision making in generalized anxiety disorder. PE signaling is significantly disrupted in individuals with the disorder and may lead to their decision-making deficits and excessive worry about everyday problems by disrupting the online updating ("reality check") of the current relationship between the expected values of current response options and the actual received rewards and punishments.

Dataset Information

Neural functional architecture and modulation during decision making under uncertainty in individuals with generalized anxiety disorder.

Publications

Neural functional architecture and modulation during decision making under uncertainty in individuals with generalized anxiety disorder.

Similar Datasets

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