Effects of Low Intensity Focused Ultrasound Stimulation Combined With Functional Electrical Stimulation on Corticospinal Excitability and Upper Extremity Fine Motor Function
Naaz Desai, Talyta Grippe, Tarun Arora, Amitabh Bhattacharya, Carolyn Gunraj, Robert Chen
Brain and Behavior 2025, 15 · 10.1002/brb3.70318
Abstract
Introduction 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. Methods 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. Results 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. Conclusion 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.
Abstract via europepmc.
Exposures
Exposure 1: tbTUS of left M1 (real vs sham) immediately followed by FES
Target: primary motor cortex — “left primary motor cortex (M1), FDI hotspot”
Device: Sonic Concepts · Sonic Concepts, Bothell, WA · H246 ✓
| Waveform | theta burst | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 20 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 5 | ✓✓✓ |
| Duty cycle (%) | 10pulse duration × PRF gives 10% | ✓✓✓ |
| Sonication duration (s) | 80 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 11.73 | ✓✓✓ |
| Free-field Ispta (W/cm²) | 1.17 | ✓✓✓ |
| In-situ estimate | deratingsingle value | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | 2.93 | ✓✓✓ |
| In-situ Ispta (W/cm²) | 0.29 | ✓✓✓ |
Real tbTUS consisted of an 80-s train of 20 ms ultrasound bursts repeated every 200 ms (400 bursts total) targeted at the TMS-defined FDI motor hotspot, immediately followed by 30 min of functional electrical stimulation (FES, 40 Hz, 300 microsecond pulse width) of the FDI and opponens pollicis during a pinch-grip pick-up task. Sham tbTUS used an identical protocol with the transducer flipped so the active face pointed away from the scalp.
Flags from extraction
n_subjects— 15 participants enrolled and completed both visits with no adverse events, but MEP data were analysed for only 14 (one excluded for background EMG activity); enrolled n=15 recorded per instructions with this flag.exposures[0].unspecified_domain.isppa_w_cm2— Section 2.1 separately states 'The power of real tbTUS was set at 20 W/cm2', which conflicts with the free-water ISPPA of 11.73 W/cm2 reported for the same 30 mm depth/parameters a few sentences earlier; domain and metric for the 20 W/cm2 figure are not specified, so recorded in unspecified_domain with this discrepancy flagged.direction_of_effect— The significant MEP decrease at T45 for real tbTUS+FES did not survive Bonferroni correction for multiple comparisons (p>0.01), so classified as mixed_or_unclear rather than a confirmed inhibitory effect.