Entraining Movement-Related Brain Oscillations Using Peripheral Nerve Stimulation: Potential Clinical Application for Suppressing Tics and the Urge-to-Tic in Tourette Syndrome

Abstract

Tourette syndrome (TS) is a common neuropsychiatric disorder that is characterised by the occurrence of vocal and motor tics. Tics are involuntary, repetitive, stereotyped movements and vocalisations that occur in bouts, typically many times in a single day, and are often preceded by a strong urge-to-tic, referred to as a premonitory urge (PU). TS is associated with: dysfunction within cortical-striatal-thalamic-cortical (CSTC) brain circuits that are implicated in the selection of movements; impaired operation of GABA signalling within the striatum and cortical motor areas; and hyper-excitability of limbic and sensorimotor regions of the brain that may contribute to the occurrence of tics. Non-invasive brain stimulation techniques delivered to cortical motor areas have been shown to modulate cortical motor excitability, entrain brain oscillations, and to reduce tics in TS. However, these techniques are not optimal for treatment outside of the clinic or for use with young children. We investigated whether rhythmic pulses of median nerve stimulation (MNS) could be used to entrain brain oscillations linked to the suppression of movement, and as a result influence the initiation of tics in TS. We demonstrate that 10 pulses of rhythmic MNS, delivered at 12Hz can entrain Mu brain oscillations within the contralateral sensorimotor cortex while 10 pulses of arrhythmic MNS does not. Furthermore, we demonstrate that whereas rhythmic Mu stimulation has little or no effect on the initiation of volitional movements or performance of an attentionally demanding cognitive task, it nonetheless leads to a large reduction in tic frequency and tic intensity in individuals with TS. This approach has considerable potential in our view to be developed into a therapeutic device suitable for use outside of the research laboratory or the clinic to suppress tics and PU in TS.