Neurophysiological effects of high-frequency spinal cord stimulation on cortico-sensory areas in large ovine animal model.

Spinal Cord Stimulation (SCS) has been a cornerstone in managing chronic pain since the late 1960s. However, traditional SCS is often associated with variable efficacy and side effects, driving the development of advanced techniques like high-frequency SCS (hSCS). Previous studies have demonstrated that the power of high-frequency cerebral oscillations increases as a function of stimulus intensity and plays a critical role in local neural processing of peripheral sensory stimuli. Extending from the current body of literature, we hypothesized that hSCS could selectively influence stimulus-triggered neural oscillations involved in sensory processing and perception. Using electrocorticography (ECoG) in sheep (n = 4), we investigated the effects of 8.2 KHz hSCS on low-frequency (4-30 Hz) and high-frequency (70-150 Hz) oscillations in ovine somatosensory and association cortices. Neural signals were recorded before, and after hSCS application to assess frequency-specific modulation of cortical activity. Our findings reveal that hSCS induces broad suppression of high-frequency oscillations across both cortical regions. In contrast, low-frequency oscillations were selectively suppressed or enhanced in both cortices. Furthermore, a linear mixed model analysis revealed that low-frequency oscillations better predict high-frequency modulation in the association than the somatosensory cortex, highlighting a reciprocal low-/high-frequency relationship between cortices. These distinct effects on cortical oscillations suggest potential supraspinal mechanisms through which hSCS may exert its analgesic effects. Our findings provide new insights for optimizing neuromodulation strategies in pain management, emphasizing the role of frequency-specific modulation in sensory and cognitive pain processing. PERSPECTIVE: This study demonstrates that high-frequency spinal cord stimulation modulates cortical oscillations in a frequency- and region-specific manner, suggesting a supraspinal mechanism of pain. These findings advance our understanding of how neuromodulation influences sensory components of pain, with implications for optimizing stimulation protocols in chronic pain management.