Neuromodulation and Disorders of Consciousness: Systematic Review and Pathophysiology

Introduction: Disorders of consciousness represent a range of clinical states, affect hundreds of thousands of people in the United States, and have relatively poor outcomes despite some pharmacological treatments. Neuromodulation technologies, particularly deep brain stimulation, spinal cord stimulation, low-intensity focused ultrasound, and median nerve stimulation were systematically reviewed as potential novel treatments for disorders of consciousness.

Methods: Adhering to the PRIMSA guidelines for systematic literature review, the PubMed, Scopus, and Web of Science databases were queried to identify articles published between 1990 and 2023 in which neuromodulation was used to treat or reverse disorders of consciousness in humans and animals. Records were excluded if disorders of consciousness (e.g., unresponsive wakefulness syndrome, minimally conscious state, etc.) were not the primary clinical target.

Results: Thirty-six studies (26 human, 10 animal) met inclusion criteria for the systematic review. Most human studies investigated deep brain stimulation (n = 15), usually of the central thalamus, and spinal cord stimulation (n = 7) of the dorsal column. A few studies investigated low-intensity focused ultrasound (n = 1) and median nerve stimulation (n = 3). Animal studies included primate and murine models, mostly of deep brain stimulation (n = 9), and one of ultrasound.

Conclusion : The identified studies lend insight into the pathophysiology of disorders of consciousness, namely the deficiencies in functional connectivity including neocortical and thalamic neurons. While clinical outcomes were mixed and possibly confounded by natural recovery from disordered states, deep brain stimulation appeared to facilitate greater improvement in disorders of consciousness than other modalities, suggested both by biomarkers and clinical evaluation.