UC Irvine

Stroke is a leading cause of long-term adult disability and many therapies are under study aiming to improve post-stroke motor function. Unfortunately, patient response to therapy is highly variable and the reasons for this are unknown. Clinical assessments are typically used to guide therapeutic decision-making after stroke. However, neuroimaging research over the last 15 years suggests that probes of neural injury and neural function provide crucial insight into post-stroke motor status. Limited research has examined how such measures could predict the likelihood of therapy-induced motor recovery and serve as biomarkers of treatment gains. Therefore, the current dissertation examined several neuroimaging measures of neural injury and neural function, as well as clinical and demographic variables, to 1) characterize our patient sample and understand the factors related to pre-therapy motor impairment and disability; 2) identify predictors of motor gains from a 3-week course of robotic arm therapy; and 3) elucidate potential biomarkers of motor gains from therapy. At baseline, reduced corticospinal tract (CST) integrity and neurophysiology (no motor evoked potential from transcranial magnetic stimulation) were correlated with greater pre-therapy motor impairment. Among less impaired patients, greater contralesional primary motor cortex (M1) and dorsal premotor cortex (PMd) activation correlated with greater motor impairment. The factors related to greater disability were reduced CST integrity and poorer cognitive status. The baseline measures predictive of greater motor gains from therapy were smaller CST injury (CST-lesion overlap) and greater interhemispheric functional connectivity. A notable finding was that predictors of gains varied according to lacunar stroke subtype: greater ipsilesional M1 activation and intrahemispheric functional connectivity predicted larger motor gains. Lastly, functional connectivity measures proved stronger biomarker candidates of treatment gains than changes in regional measures of motor cortex activation or an exploratory susceptibility-weighted imaging measure of peri-infarct tissue perfusion/angiogenesis. Furthermore, biomarkers differed according to stroke severity. Among less impaired patients, reductions in intra- and interhemispheric functional connectivity with therapy correlated with greater motor gains whereas in more impaired patients decreases in interhemispheric functional connectivity correlated with smaller gains. The current findings illustrate that measures of neural injury and neural function provide great insight into motor status after stroke, the likelihood of gains from therapy, and the heterogeneity of patient response to therapy. Ultimately, these measures should be incorporated into clinical trials of restorative stroke therapies to stratify patients to appropriate therapies and guide therapeutic decision-making for maximal patient gains.