Abstract
SIGNIFICANCE: Disorders of consciousness (DOCs) pose significant challenges for therapeutic intervention. Spinal cord stimulation (SCS) has emerged as a promising neuromodulation technique for treating DOC patients. However, the selection of optimal SCS stimulation parameters, particularly intensity, lacks objective standards, and considerable variations in the configuration of stimulation intensity are evident among different research groups in previous studies. AIM: We aim to systematically evaluate the effects of different stimulation intensities of SCS using functional near-infrared spectroscopy (fNIRS) to further optimize the efficacy of SCS. APPROACH: Eleven DOC patients with implanted SCS devices were recruited. Four different stimulation intensities based on individual motor thresholds were used: low (50%), threshold (100%), medium (125%), and high (150%). Hemodynamic responses were recorded using fNIRS, and the mean, peak, and net area under the curve values of hemodynamics, as well as the activated channel count, were analyzed, mainly focusing on two regions of interest: the prefrontal cortex (PFC) and the temporo-parietal junction (TPJ). RESULTS: An inverted U-shaped dose-response curve was observed. The medium-intensity group triggered the most significant hemodynamic responses. The high-intensity group evoked less pronounced responses and showed negative responses post-stimulation. The threshold-intensity group exhibited positive responses but less pronounced than the medium- and high-intensity groups. Conversely, the low-intensity SCS evoked a decreased response. The medium-intensity SCS also resulted in the highest number of activated channels and maintained the highest total hemoglobin concentration level during the inter-stimulus interval. Differences in brain region responses to SCS intensity were observed, with the PFC tolerating higher intensities and the TPJ having a narrower therapeutic window. CONCLUSIONS: Our findings illustrate that the medium-intensity SCS provides the optimal hemodynamic effect. The observed inverted U-shaped dose-response curve underscores the importance of precise parameter adjustments in SCS for DOC patients to maximize efficacy and to avoid overstimulation or insufficient activation.