Dataset Information

Threat-induced anxiety during goal pursuit disrupts amygdala-prefrontal cortex connectivity in posttraumatic stress disorder.

ABSTRACT: To investigate how unpredictable threat during goal pursuit impacts fronto-limbic activity and functional connectivity in posttraumatic stress disorder (PTSD), we compared military veterans with PTSD (n?=?25) vs. trauma-exposed control (n?=?25). Participants underwent functional magnetic resonance imaging (fMRI) while engaged in a computerized chase-and-capture game task that involved optimizing monetary rewards obtained from capturing virtual prey while simultaneously avoiding capture by virtual predators. The game was played under two alternating contexts-one involving exposure to unpredictable task-irrelevant threat from randomly occurring electrical shocks, and a nonthreat control condition. Activation in and functional connectivity between the amygdala and ventromedial prefrontal cortex (vmPFC) was tested across threat and nonthreat task contexts with generalized psychophysiological interaction (gPPI) analyses. PTSD patients reported higher anxiety than controls across contexts. Better task performance represented by successfully avoiding capture by predators under threat compared with nonthreat contexts was associated with stronger left amygdala-vmPFC functional connectivity in controls and greater vmPFC activation in PTSD patients. PTSD symptom severity was negatively correlated with vmPFC activation in trauma-exposed controls and with right amygdala-vmPFC functional connectivity across all participants in the threat relative to nonthreat contexts. The findings showed that veterans with PTSD have disrupted amygdala-vmPFC functional connectivity and greater localized vmPFC processing under threat modulation of goal-directed behavior, specifically related to successfully avoiding loss of monetary rewards. In contrast, trauma survivors without PTSD relied on stronger threat-modulated left amygdala-vmPFC functional connectivity during goal-directed behavior, which may represent a resilience-related functional adaptation.

SUBMITTER: Sun D

PROVIDER: S-EPMC7026403 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Threat-induced anxiety during goal pursuit disrupts amygdala-prefrontal cortex connectivity in posttraumatic stress disorder.

Sun Delin D Gold Andrea L AL Swanson Chelsea A CA Haswell Courtney C CC Brown Vanessa M VM Stjepanovic Daniel D LaBar Kevin S KS Morey Rajendra A RA

Translational psychiatry 20200210 1

To investigate how unpredictable threat during goal pursuit impacts fronto-limbic activity and functional connectivity in posttraumatic stress disorder (PTSD), we compared military veterans with PTSD (n = 25) vs. trauma-exposed control (n = 25). Participants underwent functional magnetic resonance imaging (fMRI) while engaged in a computerized chase-and-capture game task that involved optimizing monetary rewards obtained from capturing virtual prey while simultaneously avoiding capture by virtua ...[more]

PMID: 32066690

Similar Datasets

Project description:Conditioned changes in the emotional response to threat (e.g. aversive unconditioned stimulus; UCS) are mediated in part by the prefrontal cortex (PFC). Unpredictable threats elicit large emotional responses, while the response is diminished when the threat is predictable. A better understanding of how PFC connectivity to other brain regions varies with threat predictability would provide important insights into the neural processes that mediate conditioned diminution of the emotional response to threat. The present study examined brain connectivity during predictable and unpredictable threat exposure using a fear conditioning paradigm (previously published in Wood et al., 2012) in which unconditioned functional magnetic resonance imaging data were reanalyzed to assess effective connectivity. Granger causality analysis was performed using the time series data from 15 activated regions of interest after hemodynamic deconvolution, to determine regional effective connectivity. In addition, connectivity path weights were correlated with trait anxiety measures to assess the relationship between negative affect and brain connectivity. Results indicate the dorsomedial PFC (dmPFC) serves as a neural hub that influences activity in other brain regions when threats are unpredictable. In contrast, the dorsolateral PFC (dlPFC) serves as a neural hub that influences the activity of other brain regions when threats are predictable. These findings are consistent with the view that the dmPFC coordinates brain activity to take action, perhaps in a reactive manner, when an unpredicted threat is encountered, while the dlPFC coordinates brain regions to take action, in what may be a more proactive manner, to respond to predictable threats. Further, dlPFC connectivity to other brain regions (e.g. ventromedial PFC, amygdala, and insula) varied with negative affect (i.e. trait anxiety) when the UCS was predictable, suggesting that stronger connectivity may be required for emotion regulation in individuals with higher levels of negative affect.

Project description:ImportanceTranscranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC) is under clinical investigation as a treatment for major depressive disorder. However, the mechanisms of action are unclear, and there is a lack of neuroimaging evidence, particularly among individuals with affective dysfunction. Furthermore, there is no direct causal evidence among humans that the prefrontal-amygdala circuit functions as described in animal models (ie, that increasing activity in prefrontal cortical control regions inhibits amygdala response to threat).ObjectiveTo determine whether stimulation of the prefrontal cortex reduces amygdala threat reactivity in individuals with trait anxiety.Design, setting, and participantsThis community-based randomized clinical trial used a double-blind, within-participants design (2 imaging sessions per participant). Eighteen women with high trait anxiety (age range, 18-42 years) who scored greater than 45 on the trait measure of State-Trait Anxiety Inventory were randomized to receive active or sham tDCS of the DLPFC during the first session and the other intervention during the next session. Each intervention was followed immediately by a functional imaging scan during which participants performed an attentional task requiring them to ignore threatening face distractors. Data were collected from May 7 to October 6, 2015.Main outcomes and measuresAmygdala threat response, measured with functional magnetic resonance imaging.ResultsData from 16 female participants (mean age, 23 years; range, 18-42 years), with 8 in each group, were analyzed. Compared with sham stimulation, active DLPFC stimulation significantly reduced bilateral amygdala threat reactivity (z = 3.30, P = .04) and simultaneously increased activity in cortical regions associated with attentional control (z = 3.28, P < .001). In confirmatory behavioral analyses, there was a mean improvement in task accuracy of 12.2% (95% CI, 0.30%-24.0%; mean [SD] difference in number of correct answers, 2.2 [4.5]; t15 = 1.94, P = .04) after active DLPFC stimulation.Conclusions and relevanceThese results reveal a causal role for prefrontal regulation of amygdala function in attentional capture by threat in individuals with high trait anxiety. The finding that prefrontal stimulation acutely increases attentional control signals and reduces amygdala threat reactivity may indicate a neurocognitive mechanism that could contribute to tDCS treatment effects in affective disorders.Trial registrationisrctn.org Identifier: ISRCTN78638425.

Dataset Information

Threat-induced anxiety during goal pursuit disrupts amygdala-prefrontal cortex connectivity in posttraumatic stress disorder.

Publications

Threat-induced anxiety during goal pursuit disrupts amygdala-prefrontal cortex connectivity in posttraumatic stress disorder.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets