Inhibition of midfrontal theta with transcranial ultrasound predicts greater approach versus withdrawal behavior in humans

Low-intensity transcranial focused ultrasound (LITFUS) is an emerging non-invasive neuromodulation technique that holds potential for precision targeting of deep brain regions while avoiding side effects such as headaches or skin irritations. Our double-blind within-subjects study (N = 152) utilized LITFUS targeting the right prefrontal cortex, which was found to positively enhance self-reported global mood in earlier work. Building on prior studies, we utilized a virtual T-maze task that enabled us to operationalize conflicts in approach versus withdrawal behavior while recording electroencephalographic midfrontal theta (MFT). As MFT has repeatedly been shown to be a marker of cognitive load and cognitive conflict, MFT power was predicted to be related to reduced approach and heightened withdrawal in behavioral conflict situations. We hypothesized LITFUS would positively enhance self-reported mood and decrease MFT, with the LITFUS-induced downregulation of MFT resulting in an amplification of approach behavior and a reduction of withdrawal behavior. Results indicated that LITFUS led to significant MFT decreases, which significantly predicted increases in approach behavior and decreases in withdrawal behavior. This study expands LITFUS evidence on a physiological and behavioral level with a large sample size of human subjects, suggesting the promise of further research based on this distinct LITFUS-MFT-behavior link to influence conflict monitoring and its behavioral consequences. Eventually, this can serve as a foundation for future clinical work to establish LITFUS interventions for emotional and motivational mental health.