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The structural integrity of an amygdala-prefrontal pathway predicts trait anxiety.

ABSTRACT: Here, we used diffusion tensor imaging (DTI) and showed that the strength of an axonal pathway identified between the amygdala and prefrontal cortex predicted individual differences in trait anxiety. A functional magnetic resonance imaging (fMRI) functional localizer that has been shown to produce reliable amygdala activation was collected in 20 psychiatrically healthy subjects. Voxelwise regression analyses using this fMRI amygdala reactivity as a regressor were performed on fractional anisotropy images derived from DTI. This analysis identified a white matter pathway between the amygdala and ventromedial prefrontal cortex. Individual differences in the structural integrity of this putative amygdala-prefrontal pathway were inversely correlated with trait anxiety levels (i.e., higher pathway strength predicted lower anxiety). More generally, this study illustrates a strategy for combining fMRI and DTI to identify individual differences in structural pathways that predict behavioral outcomes.

SUBMITTER: Kim MJ

PROVIDER: S-EPMC2791525 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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The structural integrity of an amygdala-prefrontal pathway predicts trait anxiety.

Kim M Justin MJ Whalen Paul J PJ

The Journal of neuroscience : the official journal of the Society for Neuroscience 20090901 37

Here, we used diffusion tensor imaging (DTI) and showed that the strength of an axonal pathway identified between the amygdala and prefrontal cortex predicted individual differences in trait anxiety. A functional magnetic resonance imaging (fMRI) functional localizer that has been shown to produce reliable amygdala activation was collected in 20 psychiatrically healthy subjects. Voxelwise regression analyses using this fMRI amygdala reactivity as a regressor were performed on fractional anisotro ...[more]

PMID: 19759308

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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

The structural integrity of an amygdala-prefrontal pathway predicts trait anxiety.

Publications

The structural integrity of an amygdala-prefrontal pathway predicts trait anxiety.

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