Effect of Prefrontal Cortex Stimulation on Regulation of Amygdala Response to Threat in Individuals With Trait Anxiety

Abstract

IMPORTANCE Transcranial 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). OBJECTIVE To determine whether stimulation of the prefrontal cortex reduces amygdala threat reactivity in individuals with trait anxiety. DESIGN, SETTING, AND PARTICIPANTS This 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 MEASURES Amygdala threat response, measured with functional magnetic resonance imaging. RESULTS Data 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]; t 15 = 1.94, P = .04) after active DLPFC stimulation. CONCLUSIONS AND RELEVANCE These 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.

Transcranial direct current stimulation: a roadmap for research, from mechanism of action to clinical implementation

“…There is also evidence of anatomical selectivity: montages focusing on inferior rather than dorsolateral regions of the prefrontal cortex, particularly on the right hemisphere, can influence inhibitory function 60,61 . Moreover, other domains such as emotion regulation 62,63 and risk taking 64 , which may also depend on inhibitory processes, can also be modulated by right prefrontal cortical tDCS.…”

Case Series of Transcranial Direct Current Stimulation as an Augmentation Strategy for Attention Bias Modification Treatment in Adolescents with Anxiety Disorders

“…Adolescents and parents independently rated the quality of and satisfaction with treatment on a 4-point likert scale (1 -"poor/quite dissatisfied", 2 -"fair/indifferent or mildly dissatisfied", 3 -"good/mostly satisfied", 4 -"excellent/very satisfied"). Overall satisfaction ratings were categorized as ''poor'' (8-13), ''fair'' (14-19), ''good'' (20-25), and ''excellent'' (26)(27)(28)(29)(30)(31)(32).…”

Precision non-implantable neuromodulation therapies: a perspective for the depressed brain

“…115 For instance, a recent study of volunteers with high trait anxiety showed, through fMRI observation, that a single session of the typical tDCS protocol used in depression suppressed hyperactive fear signaling in the amygdala and increased activity in frontoparietal attentional top-down control regions. 121 By these approaches, different combinations of NIBS modalities can be synchronized with neural oscillatory network activities, through real-time EEG or fMRI readouts which are further analyzed, thus closing the loop between stimulation and neurobiological response. 116 The ''where'': positioning and dose quantification Optimal coil/electrode positioning is important to decrease within-and between-subject heterogeneity in the induced electric field and enhance clinical efficacy.…”