Evidence for temporal interference (TI) stimulation effects on motor striatum

Abstract Motor learning, the process of acquiring novel motor skills with practice, plays a fundamental role in everyday life and may also be relevant for motor rehabilitation after brain injury. This process is the result of complex interactions between both cortical and subcortical brain regions, with the striatum as one of the main hubs. Temporal interference electrical stimulation (TI) has been proposed as an innovative non-invasive brain stimulation technique, which is able to neuromodulate deep brain structures while minimizing effects on overlying cortical areas (Grossman et al. 2017). Combined (online) with MR imaging, this technique might advance the understanding of brain-behaviour relationships and the underlying neural mechanisms, uncovering important information about the physiological role of such subcortical structures. In the current study, TI stimulation was applied with an intermittent theta-burst pattern (iTBS-TI) targeting the striatum in healthy young participants (n=15), during resting state and task-based fMRI blocks, in which subjects performed a well-established sequential finger tapping task (Wessel et al. 2020). The stimulation protocol was optimized using EM simulations involving detailed anatomical head models. The experiment was conducted in a double-blind, cross-over design. Unpatterned, high frequency stimulation served as control intervention. Behavioural results point to an effect of active versus control stimulation, with decreased motor learning when iTBS-TI is applied. Imaging analyses reveal increased brain activity within the motor network (including the striatum) associated with iTBS-TI with respect to the control stimulation during task-based fMRI. This is one of the first studies applying TI stimulation to the striatum in humans. The results support the promising possibility of directly and non-invasively modulating the activity of deep brain structures and influence behaviour by means of TI stimulation, overcoming one of the main limitations of current non-invasive stimulation techniques. These results encourage cautious optimism for the therapeutic non-invasive neuromodulation of deep brain structures. Keywords: Temporal Interference (TI), Functional imaging, Motor learning