Graph-Theoretical Signature from Neural and Vascular Signals Reveals Spinal Cord Stimulation Frequency-Specific Brain Network in Disorders of Consciousness Patients

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.

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.

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.

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.

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.