Transient Modulation of the Nucleus Accumbens by Transcranial Temporal Interference Stimulation: An fMRI Study in Healthy Adults.

The nucleus accumbens (NAcc) plays a central role in motivation and reward processing, and its dysfunction is implicated in various psychiatric disorders. While invasive neuromodulation of the NAcc has shown therapeutic benefits, current noninvasive techniques cannot effectively reach this deep target. Recently, transcranial temporal interference stimulation (tTIS) has emerged as a promising approach to noninvasively modulate deep brain regions. Here, we explored whether tTIS could noninvasively modulate NAcc activity and its associated networks in humans. Fifteen healthy adults received a single 30-minute tTIS session targeting the right NAcc; resting-state fMRI was acquired immediately before stimulation (T0), immediately after (T1), and again 30 minutes later (T2). Analyses focused on local spontaneous activity, functional connectivity (FC), and effective connectivity (EC) using ROI-based linear mixed models and voxel-wise whole-brain contrasts. Electric-field simulations confirmed focal targeting of the NAcc with minimal current spread. Although no significant change in the amplitude of spontaneous activity was observed, local activity coherence within the NAcc significantly increased immediately after stimulation. FC between the NAcc and the limbic network and caudate, as well as EC from the NAcc to the default mode network and limbic network, were significantly enhanced at T1. These effects largely returned to baseline by T2, indicating transient short-term modulation. Collectively, these findings show that a single tTIS session can modulate both local NAcc dynamics and large-scale network interactions, supporting the feasibility of noninvasive deep-brain modulation of the NAcc and highlighting its potential as a neuromodulatory approach for disorders involving dysregulated reward and affective processing.