Low-intensity transcranial ultrasound (TUS) can non-invasively modulate human neural activity. We investigated how different fundamental sonication parameters influence the effects of TUS on the motor cortex (M1) of 16 healthy subjects by probing cortico-cortical excitability and behaviour. A low-intensity 500 kHz TUS transducer was coupled to a transcranial magnetic stimulation (TMS) coil. TMS was delivered 10 ms before the end of TUS to the left M1 hotspot of the first dorsal interosseous muscle. Varying acoustic parameters (pulse repetition frequency, duty cycle and sonication duration) on motor-evoked potential amplitude were examined. Paired-pulse measures of cortical inhibition and facilitation, and performance on a visuomotor task was also assessed. TUS safely suppressed TMS-elicited motor cortical activity, with longer sonication durations and shorter duty cycles when delivered in a blocked paradigm. TUS increased GABAA-mediated short-interval intracortical inhibition and decreased reaction time on visuomotor task but not when controlled with TUS at near-somatosensory threshold intensity.

In this review, we discuss the clinical and electrophysiological effects and the future directions of invasive and noninvasive brain stimulations in Parkinson's disease (PD). Deep brain stimulation (DBS) can improve motor symptoms in moderate to advanced PD. However, the optimal stimulation paradigm for nonmotor symptoms (NMS), freezing of gait, and the optimal timing of DBS are still under investigation. The findings of pathological oscillations and abnormal frequency to amplitude coupling provide models to develop adaptive DBS. Transcranial magnetic stimulation (TMS) revealed abnormal cortical excitability and plasticity in PD. Consecutive sessions of high‐frequency, repetitive TMS on the motor cortex showed promising results. Paired TMS and DBS at specific times provided a novel way to investigate PD pathophysiology and have potential as a future treatment. Transcranial direct current stimulation or transcranial alternating current stimulation with multifocal electrodes or at specific phases of oscillation are also potential future strategies.

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