The principle aim of the proposed research is to assess the potential of rTMS as a candidate adjuvant to walking re-training post stroke, prior to the future conduct of a preclinical trial. A common concern for many chronic stroke patients is that their social health remains limited because they are unable to walk safely and efficiently despite current rehabilitative measures. Following stroke, an abnormally high interhemispheric inhibitory drive from the non-lesioned to the lesioned M1, has been shown to be functionally obstructive. The study's hypothesis predicts that hemiparetic walking asymmetries will be reduced by split belt treadmill walking (SBTW) to a greater extent when the asymmetry of between-hemisphere motor excitability is reduced, than SBTW alone. Split belt treadmill walking has been recently shown to induce robust kinematic symmetry in stroke patients, albeit short-lived, making it ideal for testing the effects of stimulation-induced neuralplasticity in the present proposal. The first specific aim is to evaluate the ability of varying dosages of inhibitory low-frequency repetitive transcranial magnetic stimulation (rTMS) to downregulate the motor excitability of the lower limb's cortical muscle representations to which it is applied, thereby upregulating the excitability of the muscle respresentations in the other hemisphere. The most efficient dosage determined, will be applied in the second specific aim, to subcortical stroke patients, in an attempt to downregulate the contralesional lower limb cortical representation and upregulate the ipsilesional lower limb representation. This inter-hemispheric effect of rTMS on lower limb motor cortices has not been previously reported. The third specific aim is to demonstrate stimulation-induced improvements in gait symmetry following 15 sessions of SBTW, each preceded by rTMS.
In aim 1 and 2, the motor excitability of the tibialis anterior (TA), rectus femoris (RF), medial hamstring (MH) and medial gastrocnemius (MG) will be measured using single-pulse TMS. Dependent measures will include TMS-derived corticomotor excitability, maximum overground walking speed, the 10 m speed test, the timed up and go test, and gait kinematics (swing time, stance time, step length, stride length, step time, double support time, single support time, and support base). If the present study's hypothesis is supported, the training effects could also be examined in cortical and subacute stroke, where stimulation enhanced SBTW may encourage symmetrical gait patterns to emerge during the early recovery period and prevent or minimize the development of a hemiparetic gait pattern.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31NS062503-02
Application #
7678368
Study Section
Special Emphasis Panel (ZRG1-F10-H (20))
Program Officer
Chen, Daofen
Project Start
2008-08-15
Project End
2011-08-14
Budget Start
2009-08-15
Budget End
2010-08-14
Support Year
2
Fiscal Year
2009
Total Cost
$28,228
Indirect Cost
Name
Johns Hopkins University
Department
Type
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Jayaram, Gowri; Tang, Byron; Pallegadda, Rani et al. (2012) Modulating locomotor adaptation with cerebellar stimulation. J Neurophysiol 107:2950-7
Jayaram, Gowri; Galea, Joseph M; Bastian, Amy J et al. (2011) Human locomotor adaptive learning is proportional to depression of cerebellar excitability. Cereb Cortex 21:1901-9