While there is evidence that reorganization in the motor cortex of the hemisphere contralateral to the stroke (contralesional M1) will impact motor function of the paretic limb in the acute and chronic phase post-stroke, the extent and the precise events that specifically influence it and how it relates to recovery of motor function remain to be defined. A better understanding of contralesional M1 reorganization is critical to the future development of optimal therapeutic strategies such as non-invasive stimulation protocols to improve functional recovery following stroke. The objectives in this application are to define the factors that influence contralesional M1 reorganization, determine the extent of contralesional M1 reorganization and its role in motor recovery in the acute and chronic post-stroke period. In a longitudinal study of stroke patients, contralesional M1 reorganization and stimulation will be assessed in two Specific Aims. In the first Specific Aim, we will determine the extent of functional and structural contralesional M1 reorganization using complementary techniques of transcranial magnetic stimulation (TMS), functional and structural MRI of the brain and behavioral measures. In the second Specific Aim, the contribution of contralesional M1 reorganization to the recovery of motor function will be studied. Repetitive TMS (rTMS) will be used to transiently disrupt contralesional M1 function, thereby determine its role for the motor performance of the paretic limb. RTMS related improvement of motor performance would identify a supportive role of contralesional M1 while deterioration of motor performance would indicate its detrimental role. In addition we will explore biomarkers that can determine the role contralesional M1 in the recovery process. At the completion of this project, it is our expectation that we will have identified the extent to which contralesional M1 activity determines motor performance during the acute and chronic phases of post-stroke recovery and can be targeted by interventions depending on its state (role) in the recovery process. This latter knowledge would be expected to have a substantial positive impact on the design of future evidence based treatment protocols for stroke patients that will significantly improve functional recovery.

Public Health Relevance

The research proposed in this longitudinal study of stroke patients links science to neurorehabilitation practice by identifying and establishing the extent t which the motor cortex of the non-affected hemisphere might serve as a new target for therapeutic interventions to improve motor performance. These data could then be used to design individualized, evidence-based, beneficial practice strategies, thereby reducing stroke morbidity and disability and, thus, dramatically reducing the costs for long-term ambulatory and nursing home care. The positive impact on the field of neurorehabilitation would be considerable.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS090677-01A1
Application #
8975027
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Chen, Daofen
Project Start
2015-08-01
Project End
2019-07-31
Budget Start
2015-08-01
Budget End
2016-07-31
Support Year
1
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Emory University
Department
Neurology
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Kesar, Trisha M; Belagaje, Samir R; Pergami, Paola et al. (2017) Effects of monoaminergic drugs on training-induced motor cortex plasticity in older adults. Brain Res 1670:106-117
Wischnewski, Miles; Kowalski, Greg M; Rink, Farrah et al. (2016) Demand on skillfulness modulates interhemispheric inhibition of motor cortices. J Neurophysiol 115:2803-13
Buetefisch, Cathrin M (2015) Role of the Contralesional Hemisphere in Post-Stroke Recovery of Upper Extremity Motor Function. Front Neurol 6:214