Paired Associative Stimulation as a Tool to Assess Plasticity Enhancers in Chronic Stroke

Frontiers in Neuroscience

Marco Iacoboni¹  Allan Wu²  Bruce Dobkin³  Dylan J. Edwards⁵  Linda M. Gerber⁷  Clara Oromendia⁷  Tomoko Kitago⁸  Mar Cortes^1,10  Rajiv R. Ratan^1,11  Joshua Silverstein^1,12  Katherine Zoe Tsagaris^1,12  Pasquale Fonzetti^1,13  Alejandra Climent^1,14 

[1] 0Ahmanson-Lovelace Brain Mapping Center, University of California, Los Angeles, Los Angeles, CA, United States;1Department of Neurology, University of California, Los Angeles, Los Angeles, CA, United States;2Department of Neurology, Geffen School of Medicine, Reed Neurologic Research Center, University of California, Los Angeles, Los Angeles, CA, United States;3Moss Rehabilitation Research Institute, Elkins Park, PA, United States;4School of Medical and Health Sciences, Edith Cowan University, Perth, WA, Australia;Burke Neurological Institute, White Plains, NY, United States;Department of Healthcare Policy and Research, Weill Cornell Medical College, New York, NY, United States;Department of Neurology, Weill Cornell Medical College, New York, NY, United States;Department of Psychiatry and Biobehavioral Sciences, UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA, United States;Department of Rehabilitation and Human Performance, Icahn School of Medicine at Mount Sinai, New York, NY, United States;Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, NY, United States;Human Motor Recovery Laboratory, Burke Neurological Institute, White Plains, NY, United States;Memory Evaluation and Treatment Service, Burke Rehabilitation Hospital, White Plains, NY, United States;Sant Joan de Deu Hospital, Department of Neurology, University of Barcelona, Barcelona, Spain;

关键词: paired associative stimulation;    stroke;    memantine;    neurorehabilitation;    TMS;   

DOI  :  10.3389/fnins.2019.00792

来源: DOAJ

【 摘 要 】

Background and PurposeThe potential for adaptive plasticity in the post-stroke brain is difficult to estimate, as is the demonstration of central nervous system (CNS) target engagement of drugs that show promise in facilitating stroke recovery. We set out to determine if paired associative stimulation (PAS) can be used (a) as an assay of CNS plasticity in patients with chronic stroke, and (b) to demonstrate CNS engagement by memantine, a drug which has potential plasticity-modulating effects for use in motor recovery following stroke.MethodsWe examined the effect of PAS in fourteen participants with chronic hemiparetic stroke at five time-points in a within-subjects repeated measures design study: baseline off-drug, and following a week of orally administered memantine at doses of 5, 10, 15, and 20 mg, comprising a total of seventy sessions. Each week, MEP amplitude pre and post-PAS was assessed in the contralesional hemisphere as a marker of enhanced or diminished plasticity. Strength and dexterity were recorded each week to monitor motor-specific clinical status across the study period.ResultsWe found that MEP amplitude was significantly larger after PAS in baseline sessions off-drug, and responsiveness to PAS in these sessions was associated with increased clinical severity. There was no observed increase in MEP amplitude after PAS with memantine at any dose. Motor threshold (MT), strength, and dexterity remained unchanged during the study.ConclusionPaired associative stimulation successfully induced corticospinal excitability enhancement in chronic stroke subjects at the group level. However, this response did not occur in all participants, and was associated with increased clinical severity. This could be an important way to stratify patients for future PAS-drug studies. PAS was suppressed by memantine at all doses, regardless of responsiveness to PAS off-drug, indicating CNS engagement.

【 授权许可】

Unknown