It may soon be possible to adapt the use of deep brain stimulation (DBS) technologies developed to treat movement disorders to improve the general cognitive function of brain-injured patients. We outline neurophysiological foundations for novel neuromodulation strategies to address these goals. Emphasis is placed on developing a rationale for targeting the intralaminar and related nuclei of the human thalamus for electrical stimulation. Recent anatomical and physiological studies are compared with original neurophysiological recordings obtained in an alert non-human primate. In this context we consider neuronal mechanisms that may underlie both clinical observations and cognitive rehabilitation maneuvers that provide theoretical support for open and closed-loop strategies to remediate acquired cognitive disability (ACD).