Personalized High-Intensity Temporal Interference Stimulation Decouples Cerebellar Networks to Enhance Implicit Learning

Objective Despite the central role of deep brain structures such as the striatum in motor learning, existing noninvasive stimulation methods are hindered by limited depth and precision. Temporal interference (TI) stimulation presents the potential for precise, individualized modulation of deep regions. However, how TI stimulation influences deep brain activity and large-scale network reorganization to facilitate motor learning is still unclear. Therefore, this study aimed to clarify these mechanisms by investigating how personalized, high-intensity TI targeting the striatum modulates neural activity and enhances motor learning. Methods Twenty-six healthy right-handed male participants were enrolled in a randomized, double-blind, sham-controlled crossover study. Each participant received both TI and sham stimulation targeting the right striatum (10 mA, Δf = 20 Hz) through individualized electrode montage. Resting-state functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), and serial reaction time (SRT) task performance were assessed before and after each intervention. Neural analyses included static and dynamic fractional amplitude of low-frequency fluctuation (fALFF) in the target region, structure–function coupling (SC-FC) and topological metrics across six major brain networks, as well as brain-behavior correlations related to learning performance. Results (1) Target region activity: TI stimulation significantly increased both static and dynamic fALFF in the right striatum (p = 0.030 and p = 0.036). (2) Brain network reorganization: Compared with sham, the TI group exhibited significantly reduced SC-FC coupling in the cerebellar network (CN) (t=-2.279, p = 0.027), along with enhanced intra-network functional connectivity and increased nodal efficiency and degree in the CN and cingulo-opercular network (CON) (all FDR-corrected, p < 0.05). (3) Behavioral performance: The TI group demonstrated significant improvement in second-stage implicit learning (SIL) after stimulation (p < 0.01). (4) Brain-behavior correlation: Decreased SC-FC coupling in the CN was significantly negatively correlated with improvement in SIL (r=-0.372, p = 0.040). Conclusion Personalized high-intensity TI of the striatum enhances deep target activity and promotes selective network reorganization, particularly by reducing SC-FC coupling and strengthening intra-network connectivity in the CN. These network-level modulations underlie improved implicit learning performance, highlighting the potential of TI neuromodulation as a precise and effective approach for promoting motor learning by targeting deep nuclei and large-scale brain networks. Trial registration: ChiCTR2500098699