Project Summary Abstract Motor deficits after stroke produce long term disability. While contralesional motor deficits are most obvious, ipsilesional deficits are common & influence functioning even in chronic stroke patients, especially hemiplegics who rely on their ipsilesional limb. This grant is a renewal of Haaland's previous CSR&D grant, which established collaboration with Robert Sainburg, a kinesiologist at Penn State. The current proposal is designed to elucidate the underlying mechanisms for the hemispheric differences demonstrated in the first grant, which is critical for theories of hemispheric specialization & for designing more specific stroke rehabilitation. The previous grant supported a hybrid model that incorporated Haaland's view that hemispheric specialization for movement was associated with differential control of open & closed loop processing and Sainburg's hypothesis that the two hemispheres differed in their control of limb dynamics (e.g., joint torque interactions) and steady state positional control. However, this conclusion was not based on a direct comparison of the two hypotheses. Therefore, this proposal will extend our previous findings in three experiments to determine: 1) Whether both left & right hemisphere damage (LHD, RHD) produce deficits in on- line response modification, which would be inconsistent with the open loop/closed loop hypothesis; 2) Whether movement errors after LHD & RHD will be more common depending on whether the underlying motor control mechanism is specification of limb dynamics or steady state positional control in an experiment where each type of control is manipulated independently. 3) Whether these hemispheric asymmetries are associated with differences in utilizing visual & proprioceptive information during planning. We will also compare patients with & without hemiparesis to determine the importance of damage to the motor system on these hemispheric differences. And, finally the differential impact of frontocentral & posterior parietal damage will be assessed with the predictions that dynamic control will be more impaired after left frontocentral than posterior parietal damage, & steady state positional control will be equally impaired after right frontocentral or posterior parietal damage. Three kinematic reaching experiments will be performed by 60 right-handed stroke patients (30 RHD, 30 LHD) who are > 6 months post stroke, using their ipsilesional arm & by 60 demographically matched, right-handed healthy control subjects using either arm (30 right & 30 left hand). Lesion size & location will be measured using MRIcro & a program to normalize individual brains to Talairach space. Region of interest analyses & voxel-based lesion symptom mapping will be done to identify the role of frontocentral & posterior parietal lesions. PUBLIC HEALTH RELEVANCE: Relevance to the VA Patient Care Mission This project is an example of translational research that tests the utility of a theoretical model, the dynamic dominance hypothesis, for understanding hemispheric specialization of movement with the eventual goal of translating that understanding into better rehabilitation after stroke. Most studies of the neural basis of movement focus upon contralateral control. While many have demonstrated ipsilesional movement deficits and the functional implications of those deficits, few have examined if each hemisphere is dominant for a different aspect of limb control. If this is confirmed in the current grant, then rehabilitation strategies for patients with RHD or LHD may benefit from different therapeutic strategies. Our findings from the previous CSR&D showed there is hemispheric specialization for different aspects of reaching. The current grant will be the first to study the mechanisms of these hemispheric differences after brain damage and their intrahemispheric correlates. About 600,000 people suffer a stroke each year, and incidence doubles for each decade of life after age 55. The number of veterans over 55 is projected to be more than 14 million in 2010 with more than 90% having some disability, many of whom will have strokes. Therefore, the long term functional impact of stroke is a significant concern for the patient care mission of the VA system. Forty percent of stroke survivors in the United States have moderate functional limitations related to motor function, and 37% require assistance with basic activities of daily living. Recent experimental protocols designed to rehabilitate the hemiparetic upper extremity including, reduced gravity training, constraint induced movement therapy, robot-assisted therapy, and bilateral training, have shown substantial promise. However, regardless of improvements in contralesional arm function, longitudinal studies have estimated that a minority of hemiplegic stroke patients will demonstrate full functional recovery in the contralesional limbs. Bonifer et al. reported that even after engaging in a constraint induced movement therapy trial that improved active movement, the contralesional arm of moderately impaired patients continued to be used to assist with bimanual activities, rather than as the lead controller, even in the case of dominant arm paresis. Finally, one paper showed that chronic hemiparetic stroke patients used the ipsilesional limb three to six times more frequently than its hemiparetic counterpart. Thus, for many hemiparetic patients, functional recovery relies heavily on ipsilesional limb function. The chronic persistence of ipsilesional deficits suggests that this arm does not spontaneously improve coordination through practice, alone. While occupational therapy has often employed compensatory training of the ipsilesional limb to regain independence in ADL, we now suggest that better understanding the nature of ipsilesional deficits might facilitate more adaptive.