Hemiparesis (loss of motor control and strength in the arm and leg on one side of the body) is the most common problem after stroke, the leading cause of adult disability. Most recovery of strength and control occurs in the first 3 months post stroke. Subsequent recovery is mainly the result of learning to compensate with residual capacities. Animal models suggest that the early recovery occurs as the result of interactions between up-regulated repair processes around the region of the stroke (heightened plasticity) and training regimens. There has been very little study of the early period of stroke recovery in humans. In this proposal we will use two principal approaches to determine what distinguishes the state of the brain in the first 3 months after stroke compared to the next 6 months. The first approach uses non-invasive brain stimulation methods to test the hypothesis that the human brain has heightened excitability and plasticity in the first 3 months after stroke compared both to later after stroke and to age-matched controls. The second approach tests the hypothesis that patients are more responsive to motor training in the first 3 months after stroke compared to subsequent months. That is to say, patients early after stroke may be particularly good learners. Conformation of our two hypotheses about a time window of heightened plasticity and increased responsiveness to training will have important implications for future innovations in neuro-rehabilitation. First, if it is possible to detect the state of heightened plasticity in any given atient then it could be used to devise an algorithm for how to plan rehabilitation. For example, if heightened plasticity were still present then rehabilitation of impairment would be emphasized rather than teaching compensatory strategies that rely on spared capacities. If plasticity were seen to have returned to normal levels then compensation would be emphasized. Second, having assays of heightened plasticity will allow assessment of pharmacological and other approaches that attempt to prolong, augment or re-open this critical time window of recovery.

Public Health Relevance

Although we know that patients recovering from stroke change rapidly early after stroke, we do not know why is this, and whether people are more sensitive to training during that time. Thus, we propose to investigate the relationship between recovery of motor abilities with brain plasticity and responsiveness to physical training. The findings of our study will inform the best way to plan and deliver motor training exercises to rehabilitate patients with stroke.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD053793-12
Application #
9534709
Study Section
Motor Function, Speech and Rehabilitation Study Section (MFSR)
Program Officer
Cruz, Theresa
Project Start
2007-07-27
Project End
2020-05-31
Budget Start
2018-06-01
Budget End
2019-05-31
Support Year
12
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Physical Medicine & Rehab
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205
Ejaz, Naveed; Xu, Jing; Branscheidt, Meret et al. (2018) Evidence for a subcortical origin of mirror movements after stroke: a longitudinal study. Brain :
Spampinato, D; Celnik, P (2017) Temporal dynamics of cerebellar and motor cortex physiological processes during motor skill learning. Sci Rep 7:40715
Hallett, Mark; Di Iorio, Riccardo; Rossini, Paolo Maria et al. (2017) Contribution of transcranial magnetic stimulation to assessment of brain connectivity and networks. Clin Neurophysiol 128:2125-2139
Mawase, Firas; Uehara, Shintaro; Bastian, Amy J et al. (2017) Motor Learning Enhances Use-Dependent Plasticity. J Neurosci 37:2673-2685
Spampinato, Danny A; Block, Hannah J; Celnik, Pablo A (2017) Cerebellar-M1 Connectivity Changes Associated with Motor Learning Are Somatotopic Specific. J Neurosci 37:2377-2386
Grimaldi, Giuliana; Argyropoulos, Georgios P; Bastian, Amy et al. (2016) Cerebellar Transcranial Direct Current Stimulation (ctDCS): A Novel Approach to Understanding Cerebellar Function in Health and Disease. Neuroscientist 22:83-97
Mawase, Firas; Wymbs, Nicholas; Uehara, Shintaro et al. (2016) Reward gain model describes cortical use-dependent plasticity. Conf Proc IEEE Eng Med Biol Soc 2016:5-8
Cantarero, Gabriela; Spampinato, Danny; Reis, Janine et al. (2015) Cerebellar direct current stimulation enhances on-line motor skill acquisition through an effect on accuracy. J Neurosci 35:3285-90
Schlerf, John E; Galea, Joseph M; Spampinato, Danny et al. (2015) Laterality Differences in Cerebellar-Motor Cortex Connectivity. Cereb Cortex 25:1827-34
Celnik, Pablo (2015) Understanding and modulating motor learning with cerebellar stimulation. Cerebellum 14:171-4

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