Abstract
AIM: Disorders of consciousness (DOC) remain a major clinical challenge, and the efficacy of currently available neuromodulation strategies remains limited. The brainstem reticular formation is central to arousal regulation, but approaches directly targeting it remain technically demanding. This feasibility study aimed to explore whether epidural electrical stimulation applied via a transnasal clival approach could induce arousal and the electrocorticographic (ECoG) changes. METHODS: Three anesthetized sheep were implanted with epidural stimulating electrodes placed over the ventral brainstem via a transnasal clival approach and cortical recording electrodes on the fronto-parietal lobes. During the stimulation period, continuous behavioral monitoring was performed, and ECoG was recorded and later processed with spectral analysis. RESULTS: All three sheep successfully underwent electrode implantation without intraoperative complications, including cerebrospinal fluid leakage or neurovascular injury. Short-term stimulation reliably elicited behavioral signs of arousal. Concurrently, spectral analysis of ECoG revealed a reduction in low-frequency power (δ, θ) and an increase in high-frequency power (β, γ). CONCLUSIONS: Transnasal clival epidural stimulation is technically feasible and capable of modulating arousal-related neural activity. Further investigations with optimized electrode design and larger cohorts are required to validate its safety and efficacy.