Improving approach-avoidance control in social anxiety by targeting phase-amplitude coupling between prefrontal and sensorimotor cortex

Abstract Avoidance behavior is a major causal and maintaining factor in anxiety. As anxious individuals avoid social situations, their fear cannot be extinguished and context-appropriate behavior cannot be learned. It has been shown that successful emotion control over social approach-avoidance actions relies on theta-gamma phase-amplitude coupling between the lateral prefrontal cortex (lPFC) and the sensorimotor cortices (SMC). Emotional action control can also be facilitated by targeting theta-gamma phase-amplitude coupling between lPFC and SMC using dual-site transcranial alternating current stimulation (dual-tACS), in non-anxious individuals (Bramson et al., 2020). However, it remains unclear whether this intervention is effective where it is needed: For instance, socially anxious individuals fail to recruit lPFC and rely on the dorsolateral prefrontal cortex (dlPFC) for emotional action control (Bramson et al., 2023). Here, we show that dual-tACS improves emotional action control in social anxiety, acting on dlPFC-SMC coupling instead of lPFC-SMC coupling. Forty-nine highly socially anxious individuals performed a social approach-avoidance task while receiving dual-site in-phase, anti-phase, and sham tACS. Concurrent BOLD fMRI measurements revealed that the neural response to tACS in dlPFC mediates improvement in emotional action control induced by the in-phase stimulation. Notably, the extent of dlPFC engagement scaled to individuals’ trait anxiety levels. These findings illustrate how human neurophysiological connectivity can be leveraged to improve emotion control over social avoidance, opening the way for mechanistically-grounded clinical interventions of persistent avoidance in anxiety disorders.