The main aim of the proposed study is to assess the feasibility of combining lower limb motor cortical plasticity with symmetrical walking training to enhance walking recovery in stroke survivors. The study will determine if repetitive transcranial magnetic stimulation (rTMS) delivered at 1 Hz to the contralesional motor cortex during symmetrical walking training induces functionally relevant plasticity of impaired motor pathways. Low frequency (1 Hz) rTMS suppresses motor cortex excitability. Reducing contralesional motor cortex excitability has been shown to enhance paretic upper limb function. The proposed study is designed as a prelude to a future preclinical trial. Evidence from the present study and from subsequent trials could lead to a breakthrough in stroke rehabilitation, providing major sociological and financial benefits to this large group of neurologically impaired individuals. Chronic subcortical stroke subjects will be recruited who have a moderate degree of asymmetry in their gait variables. Three groups (n = 10) will be stratified into an """"""""rTMS during symmetrical walking group,"""""""" a """"""""symmetrical walking only group,"""""""" and an """"""""rTMS during asymmetrical (hemiparetic) walking."""""""" Symmetrical walking will be constrained by the use of a split belt treadmill. The intervention will consist of 30 minutes of walking (symmetrical or hemiparetic depending on the group) during which 900 pulses of 1 Hz rTMS at an intensity that is above active threshold will be delivered in the first 15 minutes using a double cone coil offset 2 cm lateral to vertex to preferentially stimulate the target contralesional motor cortex. Twelve sessions will be conducted over a 4-week period. Gait and excitability measures will be taken prior to the 4-week training period, immediately following training, and again one-month later. Measures will include a lower limb clinical rating, walking speed, gait symmetry, contra-and ipsi-lesional motor system excitability, and H-reflex excitability. Prior to acceptance into the study, high quality anatomical MR imaging and tractography will be conducted to determine the ratio of contralesional to ipsilesional fiber numbers in the region of the corona radiate and internal capsule. Data will be examined for correlations between the initial between-hemisphere asymmetry in cortical excitability and the intervention-induced change in gait variables. Traditional therapies for impaired movement following neural insult to human motor systems involve voluntary and/or passive limb movement, usually guided by a therapist. In recent years no important advances in single rehabilitative treatments have occurred, although a few promising novel upper limb rehabilitation procedures have been examined in selected groups of chronic hemiparetic subjects. The proposed study will assess a novel therapy which involves increasing subject's motor cortex plasticity with repetitive magnetic stimulation and concurrently engaging the subject in unassisted symmetrical walking. A permanent improvement in gait symmetry is expected to enhance postural stability especially when the individual is negotiating uneven surfaces, and increase their general walking speed. These gains would enhance stroke survivor's physical and social well being.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21HD059287-02
Application #
7564798
Study Section
Clinical Neuroscience and Disease Study Section (CND)
Program Officer
Ansel, Beth
Project Start
2008-02-05
Project End
2010-11-30
Budget Start
2009-02-01
Budget End
2010-11-30
Support Year
2
Fiscal Year
2009
Total Cost
$105,451
Indirect Cost
Name
Rehabilitation Institute of Chicago
Department
Type
DUNS #
068477546
City
Chicago
State
IL
Country
United States
Zip Code
60611
Madhavan, Sangeetha; Krishnan, Chandramouli; Jayaraman, Arun et al. (2011) Corticospinal tract integrity correlates with knee extensor weakness in chronic stroke survivors. Clin Neurophysiol 122:1588-94
Madhavan, Sangeetha; Weber 2nd, Kenneth A; Stinear, James W (2011) Non-invasive brain stimulation enhances fine motor control of the hemiparetic ankle: implications for rehabilitation. Exp Brain Res 209:9-17
Madhavan, Sangeetha; Rogers, Lynn M; Stinear, James W (2010) A paradox: after stroke, the non-lesioned lower limb motor cortex may be maladaptive. Eur J Neurosci 32:1032-9
Madhavan, Sangeetha; Stinear, James W (2010) Focal and bi-directional modulation of lower limb motor cortex using anodal transcranial direct current stimulation. Brain Stimul 3:42