DESCRIPTION (provided by applicant): The central objective of this application is to explore trans- cranial magnetic stimulation (TMS) as a potential tool for assessing neuroplasticity in the language system, and to explore the utility of this technology as a biomarker for functional recovery in patients with aphasia after stroke. Aphasia affects approximately one third of acute stroke patients and is a common and often devastating source of persistent disability. Long-term aphasia recovery is highly variable and is understood to depend largely on the brain's potential for plastic reorganization of language processing. However, to date, no physiologic measures of neuroplasticity have been incorporated into the assessment of patients with post- stroke aphasia. TMS is a form of noninvasive brain stimulation that has been used to induce focal reversible changes in neural function, including language processing. The behavioral and neurophysiologic effects of TMS reflect the responsiveness of the cortex and are driven by well-recognized mechanisms of plasticity. These effects could therefore potentially be employed as indices of the neuroplastic capacity in the brain. The first specific aim of the proposed project i to determine whether TMS-induced changes in naming performance correlate with long-term recovery from chronic aphasia. Having developed a statistical model that predicts chronic aphasia severity, we will operationally define differences in language plasticity in terms of whether patients perform better than accounted for by the model (high plasticity) or worse (low plasticity). Using a TMS protocol similar to one that we have already shown can transiently facilitate naming ability in patients with chronic nonfluent aphasia; we predict that the degree of transient TMS-induced enhancement in naming will be greater in the high plasticity group of subjects than in the low plasticity group. The second specific aim of the proposed project is to determine whether a sensitive TMS measure of motor physiology can be employed to assess plasticity in patients with chronic nonfluent aphasia. To achieve this aim, we will again employ our statistical model of aphasia recovery to determine whether patients with high language plasticity exhibit a greater effect of TMS on measures of motor physiology than low plasticity patients. The final aim will explore of the feasibility of employing these TMS measures in patients with sub-acute stroke and aphasia, and will determine whether these measures are robust and reliable in this patient population. Achievement of the aims of this project will greatl expand knowledge about the nature of plasticity in language systems. Importantly, development of a marker of language plasticity will also lay the foundation for improved prognostication of aphasia outcomes, more appropriate stratification of therapeutic language interventions, and the further development of treatments aimed at facilitating adaptive change in language systems.

PUBLIC HEALTH RELEVANCE: Aphasia after stroke affects approximately 1 million patients in the US and has a highly unpredictable course of recovery. Because this variability represents a critical barrier to the refinement of language therapies, the main objective of this project is to develop a biological marker of neuroplasticity that can be used to predict the recovery of language systems after stroke. Achievement of this objective will allow for improved prognostication of aphasia outcomes, better stratification and utilization of existing language therapies, and advancement of treatments aimed at promoting language plasticity.