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

Social avoidance is a hallmark of social anxiety disorder. Difficulties in controlling avoidance behavior are the core maintaining factor of this impairing condition, hampering the efficacy of existing therapies. This preregistered study tested a physiologically-grounded non-invasive enhancement of control over social approach and avoidance behavior in socially anxious individuals. Their prefrontal and sensorimotor areas received dual-site phase-coupled electrical stimulation, to enhance endogenous inter-regional theta-gamma phase-amplitude coupling, a mechanism known to support emotion control in non-anxious individuals. We measured behavioral and fMRI-BOLD responses during in-phase, anti-phase, and sham stimulations, while participants performed a social approach-avoidance task, involving either automatic or controlled emotional actions. In-phase stimulation selectively enhanced control over approach-avoidance actions, and modulated neural responses in the same prefrontal region where stimulation-reactivity increased as a function of trait anxiety. These findings illustrate how human neurophysiological connectivity can be leveraged to improve control over social avoidance, opening the way for mechanistically grounded clinical interventions of persistent avoidance in anxiety disorders. SIGNIFICANCE STATEMENTControlling automatic approach-avoid behavior is essential for human social interactions. This ability is impaired in social anxiety, but we know how neurotypical brains use endogenous rhythmic coupling for social emotion control. In a preregistered study, we used noninvasive electrical brain stimulation to enhance endogenous rhythmic coupling between prefrontal theta- and sensorimotor gamma-band rhythms, while highly socially anxious individuals solved an emotional control challenge. In-phase stimulation selectively enhanced emotional action control and modulated neural activity in a prefrontal cortex region where brain stimulation reactivity increased as a function of trait anxiety. These findings provide evidence for the generalizability and clinical potential of this interventional approach to social anxiety.