A secondary head-to-head comparison of low-intensity focused ultrasound and repetitive transcranial magnetic stimulation for motor recovery after stroke

Clinical Snapshot

Key Findings

• P Value: Between-group change-from-baseline: p = 0.001 (upper limb), p < 0.001 (lower limb)

• Effect Size: Change-from-baseline FMA upper limb: LIFU median 7 (IQR 3-10.5) vs rTMS median 2 (IQR 1-3)

• Primary Outcome: No significant between-group differences in post-intervention FMA, MBI, or Brunnstrom stages (all p > 0.05)

• Nnt Or Sensitivity: Not calculable due to lack of dichotomous outcomes and confidence intervals

• Confidence Interval: Not reported

Clinical Application

Both interventions require specialised equipment and trained operators. LIFU technology less widely available than rTMS in Australian centres rTMS more established in Australian stroke rehabilitation services. LIFU emerging technology requiring TGA approval pathways. Both align with ACSQHC stroke rehabilitation guidelines emphasising evidence-based neuromodulation Adults with subacute stroke (timing not specified) requiring motor rehabilitation in inpatient or outpatient settings

Abstract

BACKGROUND: Low-intensity focused ultrasound (LIFU) is a non-invasive neuromodulation technique with high spatial precision and the ability to reach deeper brain regions, offering potential advantages for post-stroke rehabilitation. Repetitive transcranial magnetic stimulation (rTMS) is a widely adopted non-invasive brain stimulation technique that modulates cortical excitability to promote neuroplasticity. However, direct head-to-head comparisons between these two modalities for post-stroke motor recovery remain limited. OBJECTIVE: To perform a secondary head-to-head comparison of LIFU and repetitive transcranial magnetic stimulation (rTMS) for motor recovery after stroke, based on a prospectively registered randomized controlled trial. METHODS: This secondary analysis included patients with subacute stroke who received two weeks of standard rehabilitation combined with either LIFU (n = 25) or rTMS (n = 25) targeting the ipsilesional primary motor cortex. LIFU parameters: 0.5 MHz, spatial-peak pulse-average intensity (ISPPA) 10.2 W/cm² (free-field), pulse duration 0.2 ms, duty cycle 20%, 20 minutes per session, five days per week for two weeks (10 sessions total). rTMS parameters: 10 Hz, 80% resting motor threshold, 1,000 pulses per session (20 trains of 5 seconds), 20 minutes per session, five days per week for two weeks (10 sessions total). Motor outcomes were assessed using the Fugl-Meyer Assessment (FMA; upper and lower extremities), Modified Barthel Index (MBI), and Brunnstrom stages. Resting-state functional near-infrared spectroscopy (fNIRS) was used to evaluate cortical activity and functional connectivity before and after the intervention. Primary analyses were conducted in the intention-to-treat (ITT) population (n = 50), with completer analyses (n = 43) performed as sensitivity analyses. RESULTS: Both groups showed significant within-group improvements in FMA and MBI after the intervention (all p < 0.001), and changes in Brunnstrom stages were also uniformly significant. No statistically significant between-group differences were observed in post-intervention FMA, MBI, or Brunnstrom stages (all p > 0.05), and completer analyses yielded consistent between-group conclusions. In contrast, change-from-baseline analyses demonstrated greater improvements in FMA scores in the LIFU group compared with the rTMS group (ΔFMA upper limb: median 7 [IQR 3-10.5] vs. 2 [1-3], p = 0.001; lower limb: 3 [1-4.5] vs. 1 [0-1.5], p < 0.001). Exploratory fNIRS analyses revealed modality-specific patterns: prefrontal fractional amplitude of low-frequency fluctuations (fALFF) increased significantly in the LIFU group (p = 0.002) but not in the rTMS group, while functional connectivity changes did not remain significant after correction for multiple comparisons. CONCLUSION: LIFU and rTMS were associated with comparable short-term motor outcomes in subacute stroke. Differences observed in change-from-baseline motor improvements and exploratory neuroimaging measures suggest potential divergence in recovery dynamics and cortical modulation, warranting further investigation in larger, longitudinal studies. TRIAL REGISTRATION: This study was derived from a prospectively registered, three-arm randomized controlled trial in the Chinese Clinical Trial Registry (ChiCTR2500114687). The present manuscript reports a secondary head-to-head comparison between the two neuromodulation intervention arms.

References

1. 1.Zheng, S., Bian, R., Song, H., Liao, Z., Gao, T., Yan, M., Huang, H., Lou, Z., Wu, F., & Li, J. (2026). A secondary head-to-head comparison of low-intensity focused ultrasound and repetitive transcranial magnetic stimulation for motor recovery after stroke. PLoS One. https://doi.org/10.1371/journal.pone.0348030