Individualized Responses to Ipsilesional High-Frequency and Contralesional Low-Frequency rTMS in Chronic Stroke: A Pilot Study to Support the Individualization of Neuromodulation for Rehabilitation

John Harvey Kindred; Elizabeth Carr Wonsetler; Charalambos Costas Charalambous; Shraddha Srivastava; Barbara Khalibinzwa Marebwa; Leonardo Bonilha; Steven A Kautz; Mark G Bowden

doi:10.3389/fnhum.2020.578127

Individualized Responses to Ipsilesional High-Frequency and Contralesional Low-Frequency rTMS in Chronic Stroke: A Pilot Study to Support the Individualization of Neuromodulation for Rehabilitation

Front Hum Neurosci. 2020 Nov 19:14:578127. doi: 10.3389/fnhum.2020.578127. eCollection 2020.

Authors

John Harvey Kindred^{1

2}, Elizabeth Carr Wonsetler³, Charalambos Costas Charalambous^{4

5}, Shraddha Srivastava⁶, Barbara Khalibinzwa Marebwa⁷, Leonardo Bonilha⁷, Steven A Kautz^{1

2

6}, Mark G Bowden^{1

2

6}

Affiliations

¹ Department of Research and Development, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC, United States.
² Division of Physical Therapy, College of Health Professions, Medical University of South Carolina, Charleston, SC, United States.
³ Department of Public Health and Community Medicine, School of Medicine, Tufts University, Boston, MA, United States.
⁴ Department of Basic and Clinical Sciences, Medical School, University of Nicosia, Nicosia, Cyprus.
⁵ Center for Neuroscience and Integrative Brain Research (CENIBRE), Medical School, University of Nicosia, Nicosia, Cyprus.
⁶ Department of Health Sciences and Research, College of Health Professions, Medical University of South Carolina, Charleston, SC, United States.
⁷ Department of Neurology, College of Medicine, Medical University of South Carolina, Charleston, SC, United States.

Abstract

Background: In this pilot study, we examined the effects of ipsilesional high-frequency rTMS (iHF-rTMS) and contralesional low-frequency rTMS (cLF-rTMS) applied via a double-cone coil on neurophysiological and gait variables in patients with chronic stroke. Objective/Hypothesis: To determine the group and individual level effects of two types of stimulation to better individualize neuromodulation for rehabilitation. Methods: Using a randomized, within-subject, double-blind, sham-controlled trial with 14 chronic stroke participants iHF-rTMS and cLF-rTMS were applied via a double-cone coil to the tibialis anterior cortical representation. Neurophysiological and gait variables were compared pre-post rTMS. Results: A small effect of cLF-rTMS indicated increased MEP amplitudes (Cohen's D; cLF-rTMS, d = -0.30). Group-level analysis via RMANOVA showed no significant group effects of stimulation (P > 0.099). However, secondary analyses of individual data showed a high degree of response variability to rTMS. Individual percent changes in resting motor threshold and normalized MEP latency correlated with changes in gait propulsive forces and walking speed (iHF-rTMS, nLAT:Pp, R = 0.632 P = 0.015; cLF-rTMS, rMT:SSWS, R = -0.557, P = 0.039; rMT:Pp, R = 0.718, P = 0.004). Conclusions: Changes in propulsive forces and walking speed were seen in some individuals that showed neurophysiological changes in response to rTMS. The neurological consequences of stroke are heterogeneous making a "one type fits all" approach to neuromodulation for rehabilitation unlikely. This pilot study suggests that an individual's unique response to rTMS should be considered before the application/selection of neuromodulatory therapies. Before neuromodulatory therapies can be incorporated into standard clinical practice, additional work is needed to identify biomarkers of response and how best to prescribe neuromodulation for rehabilitation for post-stroke gait.

Keywords: NM4R; brain stimulation; corticomotor response; gait rehabilitation; neuromodulation for rehabilitation; rTMS; rehabilitation; walking speed.

Abstract

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