This study will evaluate the effect of a well-defined physical intervention (constraint-induced movement therapy (CIMT)) on cortical motor reorganization following stroke using transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI). The primary objectives are 1) to determine whether TMS motor maps or fMRI activation predictably change following CIMT, 2) to assess whether this change correlates with motor recovery, and 3) to identify possible mechanisms underlying that change. Eighty patients participating in a randomized multicenter trial (EXCITE) of CIMT administered either immediately or one year later will be studied. Clinical assessment, TMS and fMRI will be obtained prior to randomization into the treatment arms, and repeated within three days of completing CIMT (or at the equivalent time for patients randomized to delayed treatment), and one year later. The primary focus of the study will be changes in the primary motor cortices (FMC's) of each hemisphere in response to CIMT, but we will also qualitatively evaluate activation changes in other motor regions. Outcome measures for TMS will include indices of cortical map area and center of gravity to evaluate changes in size and directional shift of motor maps over time. Functional MRI outcome measures will be generated from a volume of interest (VOI) analysis of activation in the PMC during a motor task, and will parallel TMS measures. In addition, a """"""""laterality index"""""""" will measure the relative activation in the PMC's contralateral and ipsilateral to hand movement. Clinical outcome measures will be obtained as part of the EXCITE trial, and will include the laboratory-based Wolf Motor Function Test and a measure of real life use of the stroke-affected arm: the Motor Activity Log. Nonparametric statistical analyses will be used to examine the relationship between changes in TMS maps, fMRI activation and clinical outcome for each group of patients. The study is a unique opportunity to use non-invasive methods to study cortical plasticity in subjects receiving a specific therapy intervention, compared to a control group. We expect to identify specific patterns of change in TMS motor maps and fMRI activation patterns in response to the CIMT intervention. The project will validate the concept that physiological cortical motor changes after stroke are closely correlated with motor improvement and are influenced by a physical intervention. This could lead to the development of new rehabilitative strategies based on the interaction between therapeutic interventions and the physiology and anatomy of recovery.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD040984-02
Application #
6625760
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Ansel, Beth
Project Start
2002-05-02
Project End
2006-03-31
Budget Start
2003-04-01
Budget End
2004-03-31
Support Year
2
Fiscal Year
2003
Total Cost
$600,816
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Neurology
Type
Schools of Medicine
DUNS #
937727907
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157
Sawaki, Lumy; Butler, Andrew J; Leng, Xiaoyan et al. (2014) Differential patterns of cortical reorganization following constraint-induced movement therapy during early and late period after stroke: A preliminary study. NeuroRehabilitation 35:415-26
Wittenberg, George F (2010) Experience, cortical remapping, and recovery in brain disease. Neurobiol Dis 37:252-8
Sawaki, Lumy; Butler, Andrew J; Leng, Xiaoyan et al. (2008) Constraint-induced movement therapy results in increased motor map area in subjects 3 to 9 months after stroke. Neurorehabil Neural Repair 22:505-13
Zhang, Luduan; Butler, Andrew J; Sun, Chang-Kai et al. (2008) Fractal dimension assessment of brain white matter structural complexity post stroke in relation to upper-extremity motor function. Brain Res 1228:229-40
Morales, Pedro J; Pace, Judith L; Platt, Jeralyn Sue et al. (2007) Synthesis of beta(2)-microglobulin-free, disulphide-linked HLA-G5 homodimers in human placental villous cytotrophoblast cells. Immunology 122:179-88
Corneal, Scott F; Butler, Andrew J; Wolf, Steven L (2005) Intra- and intersubject reliability of abductor pollicis brevis muscle motor map characteristics with transcranial magnetic stimulation. Arch Phys Med Rehabil 86:1670-5
Niyazov, D M; Butler, A J; Kadah, Y M et al. (2005) Functional magnetic resonance imaging and transcranial magnetic stimulation: effects of motor imagery, movement and coil orientation. Clin Neurophysiol 116:1601-10
Sawaki, Lumy (2005) Use-dependent plasticity of the human motor cortex in health and disease. IEEE Eng Med Biol Mag 24:36-9
Wolf, Steven L; Butler, Andrew J; Alberts, Jay L et al. (2005) Contemporary linkages between EMG, kinetics and stroke rehabilitation. J Electromyogr Kinesiol 15:229-39
Wolf, Steven L; Butler, Andrew J; Campana, Georgette I et al. (2004) Intra-subject reliability of parameters contributing to maps generated by transcranial magnetic stimulation in able-bodied adults. Clin Neurophysiol 115:1740-7

Showing the most recent 10 out of 11 publications