A biomarker for personalized care in post-stroke spatial neglect

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This SPiRE provides the opportunity to raise the technical expertise of the PI (Barrett), and provide a critical missing element for personalized rehabilitation care in spatial neglect (SN), a disabling cognitive deficit causing asymmetric 3-D spatial action, movement, perception and awareness. For more than 10 years, the PI and colleagues addressed SN by extensively characterizing neuropsychological deficits, documenting the adverse impact on function and freedom, and developing feasible SN rehabilitation protocols. Their research reported ~80% SN underdiagnosis and undertreatment; improving this care delivery gap is certain to reduce the devastating personal and social losses associated with SN. Here, the PI moves from her past work advancing dissemination, implementation, and rehabilitation to gain neuroimaging skills and pursue a new, biological approach to improving SN care delivery. The PI and colleagues discovered that the Aiming SN subtype, associated with motor-intentional deficits, predicts rapid improvement of daily life function with early rehabilitation. However, Aiming SN is difficult to identify on typical behavioral screening. Unlike other SN subtypes, however, Aiming SN is strongly associated with specific neuroanatomic features: frontal lobe disconnection. In this study, supported by experts in studying white matter disruption in SN (Carter), white matter disruption as a predictor of stroke rehabilitation outcomes (Cramer), and novel brain imaging (Qiu), the PI will develop a new process of SN diagnosis based on brain imaging biomarkers. The team will develop brain imaging biomarkers associated with Aiming SN, using 4 advanced imaging procedures, and demonstrate that these biomarkers can predict daily life function improvement at 3 months and 6 months post-stroke (Aim 1). The experts supporting the PI have experience with rapidly translating biomarker analyses to clinical imaging data, and thus the SPiRE will also include a direct comparison of advanced imaging (high-resolution and diffusivity) versus clinically-acquired data (Aim 2). The team will directly compare the biomarkers derived from research imaging, with those derived from clinical imaging, to identify Aiming SN. They will also test the relative ability of research versus clinical biomarkers to predict functional independence at 3 and 6 months. At the next research step, armed with a potential biomarker for Aiming SN and for functional gains with SN rehabilitation, our team will propose a larger, multi-site study for biomarker validation. Our long-term goal is to lead SN research toward routinely identifying affected veterans, and rapidly providing personalized cognitive rehabilitation, to improve functional outcomes for veterans with stroke in the community.