October 17, 2018
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Prefrontal cortex stimulation reduces amygdala fear signaling in trait anxiety

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Findings from a randomized clinical trial showed that transcranial direct current stimulation of the prefrontal cortex reduced amygdala fear signaling and increased frontoparietal attentional control in a small sample of individuals with trait anxiety.

“It has been shown through a behavioral study that bilateral [transcranial direct current stimulation of the dorsolateral prefrontal cortex] is associated with a reduction in vigilance to threat in an attentional task validated to predict the clinical response to anxiolytic drug treatment,” Maria Ironside, DPhil, from the department of psychiatry at the University of Oxford, and colleagues wrote. “This reduction in attentional bias to threat has been replicated among healthy volunteers and among individuals with social anxiety disorder.”

The investigators conducted a community-based randomized clinical trial using a double-blind, within-participants design to examine whether stimulation of the prefrontal cortex reduces amygdala threat reactivity in women with high trait anxiety.

Participants received either active or sham transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC) during the first imaging session and the other intervention during the next session, followed immediately by a functional imaging scan. During the scan, participants performed an attentional task that asked them to ignore threatening face distractors. Researchers measured amygdala threat response during this task via functional MRI.

The analysis included data from eight women who received active tDCS and eight who received sham tDCS.

Active DLPFC stimulation significantly reduced bilateral amygdala threat reactivity (P = .04) compared with sham stimulation while simultaneously increasing activity in cortical regions linked to attentional control (P < .001) in response to fearful face distractors, according to the results. Specifically, whole-brain analysis showed that stimulation significantly boosted activation in frontal, temporal and parietal clusters.

After performing confirmatory behavioral analyses, Ironside and colleagues also found task accuracy improved 12.2% on average (95% CI, 0.3-24) after active stimulation of the DLPFC.

“Our results from a single session among a sample of participants with trait anxiety revealed an effect of DLPFC tDCS on a neural biomarker relevant to comorbid clinical depression and anxiety,” the researchers concluded.

“Taken together with earlier behavioral findings obtained with the same stimulation protocol, these findings indicate a potential neurocognitive mechanism that may partially mediate the reported clinical efficacy of DLPFC tDCS,” they continued. “This biomarker may have potential for testing and benchmarking novel stimulation protocols in the development phase to accelerate treatment development for major depressive disorder and anxiety disorders.” – by Savannah Demko

Disclosure: Ironside reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.