Deconstructing Post-Stroke Hemiparesis for Precision Neurorehabilitation

PROJECT SUMMARY / ABSTRACT Dr. David Lin is a Neurocritical Care and Neurorehabilitation specialized Neurologist at VA Providence Health Care System whose career goal is to conduct mechanistic clinical trials of neurorehabilitation technologies, to maximize neuroplastic potential and functional recovery for Veterans with motor deficits after stroke. A critical

step towards this goal is for Dr. Lin to perform research and acquire training in the phenotype of upper extremity stroke hemiparesis as well as its neuroanatomic and neurophysiologic underpinnings. Dr. Lin currently leads a natural history study of upper extremity stroke motor recovery in which he has demonstrated the feasibility of

recruiting over 180 acute stroke patients with arm weakness into a research study and tracking their upper extremity impairments from the acute to chronic stages of recovery. Dr. Lin is completing an analysis of patterns of EEG cortical connectivity change after stroke in his VA CDA-1 project. In this Career Development Award-2

(CDA-2) project, Dr. Lin proposes to test specific systems neuroscience, model-driven hypothesis about the relationship between the phenotype of post-stroke upper extremity hemiparesis with anatomy (assessed by diffusion magnetic resonance imaging) and physiology (assessed by transcranial magnetic stimulation) of

specific descending motor pathways (corticospinal and corticoreticulospinal). Specifically, he will (1) Deconstruct post-stroke hemiparesis into its individual components (2) Map descending motor tract anatomy onto distinct components of post-stroke hemiparesis and (3) Map descending motor tract physiology onto

distinct components of post-stroke hemiparesis. To achieve these aims, Dr. Lin plans to conduct a new and dedicated cross-sectional study at Providence VA of N = 75 Veterans with chronic hemiparesis after stroke. The proposed CDA-2 project will provide Dr. Lin with fundamental training in motor control, structural

neuroimaging, motor systems neurophysiology, and applied biostatistics for neurorehabilitation research as well as further experience with research skills necessary to lead an independent VA laboratory and clinical trials. Dr. Lin will achieve the science and training proposed with the support of a world-class and

multidisciplinary mentorship team. Dr. Leigh Hochberg (primary mentor) and Dr. John Krakauer (primary co- mentor) will coordinate a panel of content mentors (neuroimaging- Dr. Jennifer Barredo, neurophysiology- Dr. Noah Philip, and kinematics and motor control - Dr. Steven Kautz) and subject advisors (neuroimaging- Dr.

Sanes, motor systems physiology- Dr. Monica Perez, neurotechnology- Dr. Karunesh Ganguly, applied biostatistics- Dr. Jeff Goldsmith). Dr. Lin has developed a systematic mentoring and didactic plan to complement the scientific activities in his proposed project. All of these activities will leverage the extensive

resources and world-class environment of VA RR&D Center for Neurorestoration and Neurotechnology (CfNN) at Providence VA and research affiliate, Massachusetts General Hospital, Harvard Medical School. Thus, the proposed VA patient-oriented research project, in concert with the mentorship and training plan, will provide

Dr. Lin with the scientific insights and skills that are essential for him to develop into an independent VA physician-scientist career at the cutting edge of stroke neurorehabilitation and systems neuroscience.