Graph-Theoretical Signature from Neural and Vascular Signals Reveals Spinal Cord Stimulation Frequency-Specific Brain...

Introdution: Spinal cord stimulation (SCS) has emerged as a promising neuromodulatory intervention for patients with disorders of consciousness (DoC). However, the identification of optimal stimulation frequencies remains a subject of ongoing debate. Although previous electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) studies have suggested the therapeutic efficacy of 5- and 70-Hz, respectively, the integrative neurovascular mechanisms and frequency-specific network dynamics underlying these effects remain to be elucidated. Objective and Impact Statement: This study aims to characterize frequency-dependent network reconfiguration in DoC using simultaneous EEG-fNIRS recordings and graph theoretical analysis. By delineating distinct neurophysiological and hemodynamic signatures, our findings establish a mechanistic framework for the optimization of SCS parameters, thereby advancing personalized neuromodulation strategies for the promotion of consciousness recovery. Methods: This prospective trial used simultaneous EEG-fNIRS and graph theory in 16 patients with DoC undergoing multifrequency SCS at 5, 20, 70, and 100 Hz to decode frequency-specific network dynamics. Our integrated EEG-fNIRS analysis revealed 3 principal advances. First, multimodal cortical mapping via a unified anatomical atlas quantified frequency-dependent network reconfiguration, generating graph-theoretical metrics (global and nodal efficiency, characteristic path length, and clustering coefficients) from source-localized EEG (delta-gamma bands) and fNIRS (oxyhemoglobin and deoxygenated) data. Second, we identified frequency-dependent neurophysiological profiles. Results: Five-hertz stimulation produced acute enhancement of theta-band global network efficiency coupled with elevated gamma-band nodal efficiency in the right cingulate motor area, indicating immediate frontolimbic engagement. Conversely, 70-Hz stimulation selectively evoked delayed hemodynamic responses in the visual cortices and increased occipital hemoglobin oxygenation without concomitant EEG alterations, suggesting preferential retinotopic pathway recruitment. Conclusion: Multimodal EEG-fNIRS analysis elucidates frequency-specific SCS mechanisms, where 5-Hz stimulation optimizes local information integration through theta and gamma modulation, while 70-Hz enhances long-range connectivity, exposing frequency-specific neural plasticity mechanisms.