Project Grant R01HD104637

MECHANISTIC AND NEUROANATOMIC BASES OF DISPARITY BETWEEN ARM CAPACITY AND USE IN STROKE - PROJECT SUMMARY MORE THAN 750,000 INDIVIDUALS IN THE U.S. HAVE A STROKE EACH YEAR, AND AS MANY AS 94% OF STROKE SURVIVORS EXHIBIT REDUCED USE OF ONE ARM, WITH ADVERSE CONSEQUENCES FOR DISABILITY, CAREGIVER BURDEN, AND QUALITY OF LIFE. APPROXIMATELY 40%-80% OF INDIVIDUALS WHO FAIL TO USE THE AFFECTED ARM IN DAILY LIFE POSSESS ADEQUATE SENSORY- MOTOR CAPACITY TO DO SO. THE DISPARITY BETWEEN ARM USE AND CAPACITY (I.E., USE/CAPACITY DISPARITY -- UCD) OCCURS ACROSS A BROAD SPECTRUM OF SENSORY-MOTOR SEVERITY AND IS A PERPLEXING AND URGENT PROBLEM IN NEURO- REHABILITATION. PERHAPS IN PART BECAUSE UCD LIES AT THE INTERFACE OF SENSORY-MOTOR PROCESSING AND COGNITIVE/AFFECTIVE PHENOMENA, NO PAST RESEARCH HAS ASSESSED ITS UNDERLYING MECHANISMS OR NEUROANATOMIC BIOMARKERS. GIVEN ITS PREVALENCE, AN UNDERSTANDING OF THE MECHANISMS OF UCD ACROSS A RANGE OF SEVERITY IS REQUIRED TO DEVELOP TARGETED TREATMENTS TO AMELIORATE THE DISORDER. MOREOVER, INDIVIDUALS WITH STROKE ARE RARELY ASSESSED FOR THE PRESENCE OF UCD, IN PART BECAUSE SUCH ASSESSMENT IS CHALLENGING. THE PROPOSED RESEARCH WILL ADDRESS THESE GAPS IN OUR KNOWLEDGE AND CAPACITY BY TESTING THE PREDICTIONS OF 3 HYPOTHESES OF THE MECHANISMS UNDERLYING UCD: THE SENSORIMOTOR, ATTENTION, AND APATHY/MOTIVATION ACCOUNTS. IN AIM 1 WE WILL ADMINISTER A TARGETED BATTERY OF SENSORIMOTOR AND NEUROPSYCHOLOGICAL TESTS TO TEST THE PREDICTIONS OF EACH OF THE 3 HYPOTHESES IN A SAMPLE OF 100 MILD TO MODERATE LEFT- AND RIGHT-HEMISPHERE CHRONIC STROKE PATIENTS. WE WILL DETERMINE THE ASSOCIATION OF THESE MEASURES AS WELL AS DEMOGRAPHIC AND STROKE-RELATED VARIABLES WITH UCD. AIM 2 WILL USE ADVANCED NEUROIMAGING METHODS WITH DATA FROM RESTING-STATE FUNCTIONAL MAGNETIC RESONANCE IMAGING TO DEVELOP IMAGING BIOMARKERS ASSOCIATED WITH UCD. IN AIM 3 WE WILL VALIDATE A NOVEL VIRTUAL REALITY ASSESSMENT TOOL TO RAPIDLY AND RELIABLY EVALUATE UCD. IN ADDITION TO ITS CLINICAL UTILITY, THE TASK ENABLES BUILT-IN ASSESSMENT OF THE ATTENTION HYPOTHESIS BY DETERMINING WHETHER UCD IS INFLUENCED BY ATTENTIONAL TASK DEMANDS. BY THE END OF THE GRANT PERIOD, WE WILL HAVE DETERMINED THE DEMOGRAPHIC, SENSORIMOTOR, NEUROPSYCHOLOGICAL, AND NEUROANATOMICAL FACTORS THAT PREDICT UCD AND VALIDATED A CLINICALLY-USEFUL VR ASSESSMENT TOOL. GIVEN THE LIMITED KNOWLEDGE BASE IN THIS AREA, THIS COMPREHENSIVE RESEARCH WILL PAVE THE WAY FOR DEVELOPMENT OF TREATMENTS TARGETED TO UNDERLYING MECHANISMS AND ENHANCED IDENTIFICATION OF AT-RISK INDIVIDUALS.