Central thalamic deep brain stimulation for cognitive neuromodulation - a review of proposed mechanisms and investigational studies.

We review the history of efforts to apply central thalamic deep brain stimulation (CT/DBS) to restore consciousness in patients in a coma or vegetative state by changing the arousal state. Early experimental and clinical studies, and the results of a recent single-subject human study that demonstrated both immediate behavioral facilitation and carry-over effects of CT/DBS are reviewed. We consider possible mechanisms underlying CT/DBS effects on cognitively-mediated behaviors in conscious patients in light of the anatomical connectivity and physiological specializations of the central thalamus. Immediate and carry-over effects of CT/DBS are discussed within the context of possible effects on neuronal plasticity and gene expression. We conclude that CT/DBS should be studied as a therapeutic intervention to improve impaired cognitive function in severely brain-injured patients who, in addition to demonstrating clinical evidence of consciousness and goal-directed behavior, retain sufficient preservation of large-scale cerebral networks within the anterior forebrain. Although available data provide evidence for proof-of-concept, very significant challenges for study design and development of CT/DBS for clinical use are identified.