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Peripheral neuromuscular stimulation modulates low-frequency cerebrovascular oscillations in subacute ischaemic stroke
ABSTRACT
Background:
Impaired cerebrovascular regulation is a hallmark of subacute ischaemic stroke yet bedside methods to quantify low-frequency vascular dynamics remain limited. Functional near-infrared spectroscopy (fNIRS) captures slow haemodynamic fluctuations, and operational modal analysis (OMA) can characterize these as intrinsic dynamic modes defined by frequency and damping.
Objective:
To determine whether bilateral common peroneal nerve neuromuscular electrical stimulation (NMES), delivered for venous thromboembolism prophylaxis, modulates low-frequency brain-like haemodynamic modes in subacute ischaemic stroke.
Methods:
Cortical haemodynamics were recorded with fNIRS during NMES in participants from the RETRAIN Phase 1 study. Total haemoglobin signals were pre-processed, and one brain-like mode per segment-file was selected using stability, frequency, damping, and classifier-margin criteria. The final dataset included 462 observations from 51 subject-condition units from 18 participants. Linear mixed-effects models assessed associations of stimulation segment (INIT vs LAST), posture group, and stimulation level with modal frequency and damping. Cluster bootstrap resampling (2000 iterations) evaluated robustness.
Results:
Modal frequency was lower in LAST versus INIT (β=−0.0267, 95% CI −0.0452 to −0.0082; p=0.005) with additional effects of protocol group (p=0.001) and stimulation level (p<0.001). A monotonic decrease in frequency with increasing stimulation level was observed (β=−0.00446 Hz/level; p=0.015). Bootstrap resampling confirmed robustness (Segment 85.7%, Group 90.6%, Stimulation Level 97.0% significant). Damping increased modestly in LAST (β=0.0948; P=.045) but effects were less robust.
Conclusions:
Common peroneal nerve NMES modulates low-frequency brain-like haemodynamic dynamics in subacute stroke primarily through reduced modal frequency with increased stimulation exposure. fNIRS-derived modal metrics may provide bedside physiological markers of cerebrovascular regulation. Clinical Trial: ClinicalTrials.gov Identifier: NCT06614400
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