Effects of striatal transcranial temporal interference stimulation on motor learning after a traumatic brain injury

Traumatic Brain Injury (TBI) is a prevalent neurological condition that follows an externally induced cerebral lesion and is often characterized by impaired cognitive functions. As a result, one domain frequently affected is learning, or the ability to acquire new knowledge or skills. Specifically, during motor skill learning, the striatum plays a crucial role in supporting the acquisition and consolidation of the motor program, making this region an ideal target for restoring motor learning in affected individuals. As the striatum is located deep in the brain, the non-invasive yet focal modulation of its activity was not possible thus far. However recently, the novel technique of transcranial temporal interference stimulation (tTIS) demonstrated promising results in the field of non-invasive deep brain stimulation, especially of the striatum (Wessel & Beanato et al., 2023; Vassiliadis et al., 2024). Here, a cohort of TBI patients performed a motor learning task while receiving plasticity-supporting striatal tTIS in an intermittent-theta-burst (iTBS) pattern and sham stimulation in a randomized, cross-over, double-blinded design. Our results show that tTIS led to an improvement in motor learning retention that persisted for at least 24h after the stimulation (stimulation effect during follow-ups p < 0.001). Moreover, age played a significant role, with tTIS inducing larger improvements in older patients than their younger counterparts. These results support the hypothesis that individuals with lower performances in the targeted function can benefit more from the stimulation. As a quality control, individualized modeling based on brain anatomy and electrode positions confirmed good targeting of the striatum. Overall, this study highlights the promising potential of tTIS to support the recovery of impaired learning and motor functions. These proof-of-concept findings might pave the way toward developing striatal tTIS as an interventional clinical strategy to enhance learning and memory in brain-lesioned patients.