The role of ventromedial and dorsolateral prefrontal cortex in attention and interpretation biases in individuals with general anxiety disorder (GAD): A tDCS study

and purpose of the study: Individuals with general anxiety disorder (GAD) have deficits in emotional and cognitive processing, including cognitive bias, which plays a causal role in anxiety. Hyperactivity of the ventromedial prefrontal cortex (vmPFC) and dorsolateral prefrontal cortex (dlPFC) is assumed to be involved in cognitive bias. We aimed to explore the causal contribution of the dorsolateral and ventromedial prefrontal cortices (dlPFC, vmPFC) on cognitive bias via non-invasive brain stimulation, and expected a bias-reducing effect of cortical activity enhancement over these areas in GAD, with a larger contribution of the vmPFC to perceptual, and of the dlPFC to interpretation bias.The study was conducted in a randomized, single-blinded, and complete crossover design. Thirty-four adults with GAD, received transcranial direct current stimulation (tDCS) in 5 separate sessions (1.5 mA, 20 min) with the following electrode montages: anodal dlPFC/cathodal vmPFC, anodal vmPFC/cathodal dlPFC, anodal dlPFC/cathodal right shoulder, anodal vmPFC/cathodal left shoulder, and sham stimulation. During stimulation, in each session, participants performed the Dot-Probe and Reading Mind from Eyes tests to measure attention and interpretation biases.A significant effect of stimulation condition on attention and interpretation biases was observed. Anodal vmPFC and dlPFC stimulation coupled with an extracranial cathodal electrode reduced attention bias to threat-related stimuli in the dot-probe test. Furthermore, anodal dlPFC/cathodal vmPFC stimulation reduced negative interpretation bias in reading from eyes test.As suggested by the results of this study, both dlPFC and vmPFC are involved in cognitive bias in GAD, but with partially different roles. Anodal stimulation over the right vmPFC and the left dlPFC reduced attention bias, supporting the relevance of these areas for attention bias. For interpretation bias, the significant effect of anodal dlPFC/cathodal vmPFC stimulation, but only trendwise effect of anodal tDCS over the dlPFC combined with an extracephalic return electrode is in accordance with a predominant effect of the dlPFC on interpretation bias, but does not rule out an additional minor involvement of the vmPFC. Based on these results, a new model is suggested for the neural underpinnings of anxiety symptoms.