Effects of Low Intensity Focused Ultrasound Stimulation Combined With Functional Electrical Stimulation on Corticospinal Excitability and Upper Extremity Fine Motor Function.

Functional electrical stimulation (FES) is used to retrain motor function in neurological disorders but typically requires multiple sessions and shows limited benefits in chronic cases. Low-intensity transcranial focused ultrasound stimulation (TUS) is a noninvasive brain stimulation (NIBS) method offering greater focality and deeper penetration than current NIBS techniques. TUS delivered in a theta burst pattern (tbTUS) for 80 s produces neuroplastic changes with long-term potentiation-like effects lasting up to 60 min in healthy adults. Since tbTUS increases cortical excitability, combining it with FES may enhance neuroplasticity. We hypothesized that combining tbTUS with FES would result in increased corticospinal excitability compared to FES alone and lead to greater improvement in fine motor skills as assessed by Nine-Hole Peg Test (NHPT) scores. Fifteen healthy participants underwent two study visits consisting of real or sham tbTUS of the left motor cortex immediately followed by 30 min of FES of the first dorsal interosseous (FDI) and the opponens pollicis (OP) muscles for fine motor function training of the right hand. Motor-evoked potentials (MEPs) were recorded from the right FDI, OP, and abductor digiti minimi (ADM) muscles at baseline (BL), immediately after real or sham tbTUS (T0), immediately after 30 min of FES training (T45), and at 15 (T65) and 30 min (T80) post-FES. NHPT was delivered at BL and at T80. Data from 14 participants were analyzed. It showed a significant decrease in MEP amplitudes of FDI and OP at T45 following only real tbTUS+FES with a return to BL at T80. No significant changes were seen in the NHPT scores in either condition. Real tbTUS+FES combined with voluntary movement results in immediate corticospinal inhibition with a return to BL at ∼20 min post-stimulation suggestive of homeostatic metaplasticity. These findings highlight the potential of tbTUS+FES as a neuromodulatory intervention, warranting further exploration in neurological conditions for therapeutic applications.