Disorders of consciousness, including vegetative state/unresponsive wakefulness syndrome and minimally conscious state, remain extremely challenging to treat because reliable and effective interventions are still limited. In this context, spinal cord stimulation has emerged as a promising neuromodulation strategy. Previous studies have suggested that spinal cord stimulation may improve arousal, functional connectivity, and some clinical scores, but the stimulation frequencies used across studies vary widely, ranging from 5 to 100 Hz, and there is still no clear consensus on which frequency is most effective. More importantly, most earlier work has relied on only a single modality, such as EEG or fNIRS, to assess stimulation effects. "Although these studies have separately suggested potential benefits of 5 Hz and 70 Hz, they still leave key questions unresolved, including why these frequencies may work, which brain networks they preferentially engage, and how electrophysiological and hemodynamic responses evolve together during stimulation." said the author Nan Wang, a researcher at Beijing Tiantan Hospital, "As a result, a more systematic multimodal investigation of frequency-specific brain network reconfiguration has become an important step toward optimizing spinal cord stimulation parameters and advancing personalized treatment for patients with disorders of consciousness."
This prospective study enrolled 16 patients with disorders of consciousness and systematically compared brain network responses to spinal cord stimulation at 4 frequencies: 5, 20, 70, and 100 Hz. During treatment, simultaneous EEG–fNIRS recordings were acquired, and both electrophysiological and hemodynamic brain activity were reconstructed in source space under a unified anatomical atlas and mapped onto a shared set of cortical regions. Functional connectivity analysis and graph-theoretical methods were then applied to extract both global- and nodal-level network features, including global efficiency, characteristic path length, clustering coefficient, and nodal efficiency, in order to characterize how brain networks were reconfigured before, during, and after stimulation at each frequency. In parallel, the patients' levels of consciousness were evaluated using CRS-R scores before surgery, during the initial stimulation stage, and at 1-month follow-up, allowing the multimodal network changes to be related to clinical recovery and helping clarify the neural mechanisms associated with different stimulation frequencies.
The study showed that different spinal cord stimulation frequencies triggered clearly distinct brain network responses in patients with disorders of consciousness, with 5 Hz and 70 Hz producing the most prominent effects, whereas 20 Hz and 100 Hz did not lead to obvious network improvement. More specifically, 5 Hz mainly induced a rapid electrophysiological reconfiguration of brain networks: it increased theta-band global network efficiency and enhanced gamma-band nodal efficiency in the right cingulate motor area, suggesting that this frequency more effectively promotes fast local information integration within frontolimbic-related circuits. In contrast, 70 Hz was characterized more by delayed hemodynamic responses, with its effects concentrated in the visual cortex and occipital regions, where local oxygenation, nodal clustering, and nodal efficiency increased without corresponding EEG changes. This indicates that 70 Hz may act more through long-range connectivity and vascular/metabolic recruitment. Overall, the findings suggest that there is no single universal optimal frequency for spinal cord stimulation in disorders of consciousness; instead, different frequencies appear to influence consciousness-related networks through distinct neural and vascular pathways, with 5 Hz favoring immediate electrophysiological integration and 70 Hz favoring delayed hemodynamic and long-range network modulation.
The importance of this work lies in moving the discussion of spinal cord stimulation in disorders of consciousness beyond whether it works to how different stimulation frequencies work. By combining simultaneous EEG–fNIRS with graph-theoretical analysis, the study shows that 5 Hz and 70 Hz are not simply different in strength, but instead correspond to 2 distinct modes of brain network modulation: the former is more associated with rapid electrophysiological integration, whereas the latter is more related to delayed hemodynamic recruitment and long-range network reorganization. This not only helps explain why previous studies have disagreed on the optimal stimulation frequency, but also suggests that parameter optimization should not aim for a single universally "best" frequency. Instead, stimulation settings may need to be matched to the preserved network state and the regulatory pathway most likely to benefit in each patient. In this sense, the value of the study lies not only in adding multimodal evidence, but also in providing a more mechanistically grounded direction for personalized neuromodulation in disorders of consciousness. "At the same time, the current sample size remains limited, and differences across etiologies were not fully resolved, so larger multicenter studies with longer follow-up will be needed to further validate these frequency-specific network markers and move spinal cord stimulation from empirical use toward more precise mechanism-guided therapy." said Nan Wang.
Authors of the paper include Nan Wang, Xiaoke Chai, Yifang He, Jiuxiang Song, Tianqing Cao, Qiheng He, Sipeng Zhu, Yitong Jia, Juanning Si, Yi Yang, and Jizong Zhao.
This work was partially supported by the National High Level Hospital Clinical Research Funding (2025-PUMCH-D-004), Science and Technology Innovation 2030 (2022ZD0205300), National Natural Science Foundation of China (82501457), Chinese Institute for Brain Research Youth Scholar Program (2022-NKX-XM-02), Natural Science Foundation of Beijing Municipality (7252004), and International (Hong Kong, Macao, and Taiwan) Science and Technology Cooperation Project (Z221100002722014).
The paper, "Graph-Theoretical Signature from Neural and Vascular Signals Reveals Spinal Cord Stimulation Frequency-Specific Brain Network in Disorders of Consciousness Patients" was published in the journal Cyborg and Bionic Systems on Apr 23, 2026, at DOI: 10.34133/cbsystems.0539.
