439 Optimal Targets, Connectivity, and Tissue Integrity for Deep Brain Stimulation in Patients With Disorders of Consciousness

INTRODUCTION: Disorders of consciousness (DOC) are characterized by alterations in arousal and/or awareness resulting from brain injuries. Deep brain stimulation (DBS) is an emerging treatment to restore arousal/awareness in DOC. However, little is known about optimal targets and whether outcomes depend on brain connectivity, tissue integrity, or reorganization potential. METHODS: Retrospective analysis of 38 patients with DOC who underwent unilateral DBS targeting thalamic centromedian nucleus (ages = 12-65 years). DOC resulted from anoxic (n = 26) or traumatic (n = 12) injuries. Patients were classified as ‘responders’ or ‘non-responders’ using Coma/Near Coma and Coma Recovery Scales. Volumes of tissue activated (VTAs) assessed DBS locations associated with favorable response. Correlations were also performed with age, regional brain volumes from pre-operative MRI, and structural connectivity calculated from patients’ VTAs using normative diffusion MRI. RESULTS: 8/38 patients were responders and 24/38 non-responders; outcomes are pending in 6/38 patients due to <3 months follow-up. Favorable response was associated with younger age (median age = 19 years in responders, 42 years in non-responders) and greater volumes of whole-brain grey matter and subcortical regions including putamen, pallidum, caudate, and cerebellum. Responders also tended to have deeper and more medial implantations, with VTAs engaging parafascicular nucleus, reticular nucleus, and peri-midbrain red nucleus. In responders, VTA connectivity was higher with superior frontal gyrus, caudate, pallidum, and cerebellum, and lower with sensorimotor and occipital cortex. CONCLUSIONS: Efficacious DBS for DOC is linked to younger age, greater preservation of whole-brain grey-matter, greater volumes of and connectivity with select subcortical areas (pallidum, caudate, cerebellum), stronger connectivity with superior frontal gyrus, and stimulation of locations inferomedial to the centromedian nucleus. Findings may assist with optimizing patient selection, DBS targeting, and post-implantation programming.