Neurocognitive mechanisms of prefrontal stimulation

Abstract

The difficulty in treating mood and anxiety disorders has sparked clinical interest in novel treatments, such as transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC). However, underlying mechanisms of action are unclear. It is established that people with mood and anxiety disorders have negative cognitive biases, such as increased vigilance to threat. Psychiatric treatments have acute effects on these cognitive biases, which predict later therapeutic action. Such effects are proposed as cognitive biomarkers of response. A healthy volunteer investigation revealed an anxiolytic-like effect (reduced threat vigilance) of single-session tDCS on a behavioural test of proven clinical relevance (Ironside et al., 2016, Biological Psychiatry). Complementing this, we used functional imaging to reveal that, in a sample of trait anxious females, tDCS of the DLPFC increased activation in an attentional control network and reduced amygdala response to fearful face distractors (Ironside et al., under revision, JAMA Psychiatry). This provides causal evidence that modulating activity in the DLPFC inhibits amygdala response to threat, providing a potential neural mechanism for the previous reduction in vigilance to threat. Collectively, these results propose an emerging neurocognitive model of the mechanisms of action of tDCS. We also examined pairing tDCS with attentional bias modification training and found no effect of stimulation. However, DLPFC tDCS has been successfully paired with other paradigms such as cognitive control training. As highlighted in the next talks, we suggest that computationally specified learning tasks may be more sensitive. Together, findings point to an anxiolytic-like effect of DLPFC tDCS on cognitive and neural biomarkers relevant to mood and anxiety disorders, indicating potential neurocognitive mechanisms that may mediate the reported clinical efficacy of DLPFC tDCS. This has implications as the identification of treatment response markers that could aid patient selection for future trials and ultimately guide treatment selection for patients.