Antoni Valero-Cabre - US grants

DESCRIPTION (provided by applicant): In the last three years, the biomedical community has seen an explosion in the use of invasive and non- invasive brain neuromodulation methods to increase recovery of function after localized brain damage. Such techniques operate on the principle that neural plasticity -the ability of a damaged brain to compensate for behavioral deficits- can be boosted and guided by techniques able to "sculpt" the functional patterns of excitability in spared or affected neural networks. Among the best known, Deep Brain Stimulation (DBS), Epidural Brain Stimulation (EDBS), and more recently Transcranial Magnetic Stimulation (TMS) have stood out in providing very encouraging preliminary results in chronic stroke patients. The mechanisms, real therapeutic potential, side effects and spectrum of neural "costs" of these stimulation methods remain to be fully explored in animal models and clinical applications. Nevertheless, they have provided behavioral neurology and psychiatry with new hopes of treatment in medical fields and conditions for which diagnosis was in many cases the ultimate and final step. In this emerging scenario, transcranial Direct Current Stimulation (tDCS), the effects of which were first studied during the early 1960s, has been recently "re-discovered" and is being re-evaluated for clinical and therapeutic use. Transcranial DC Stimulation provides a non-invasive, easy to apply and low cost method to stimulate or polarize brain tissue and has considerable potential to produce guided changes in neural activity and result in significant patterns of recovery after brain damage. Notwithstanding, not much is yet known on its ability to induce long lasting effects on intact and spared neural networks and particularly how such modulation can explain at the system's level the achievement of behavioral recovery. In order to fully assess its therapeutic potential and study its spatial network specificity we propose to test its effects in a well- studied feline model of unilateral parietal damage resulting into visual-spatial neglect. We plan on achieving long-lasting improvements in degraded visuo-spatial detection-localization abilities by means of two strategies both aimed at facilitating plastic take over of lost functions by spared cortical or subcortical regions. More importantly, by means of whole-brain metabolic glucose labeling techniques, we will try to develop a detailed understanding of the nature and extent of the mechanisms underlying such recovery, so that it can be optimally applied. PUBLIC HEALTH RELEVANCE: We will test the use of transcranial Direct Current Stimulation (tDCS) for improving function after chronic cerebral damage. We will study its underlying mechanisms of action and derive conclusions for future human therapeutic applications in clinical settings.