Motor Cortex and Motor Cortical Interhemispheric Communication in Walking After Stroke: The Roles of Transcranial Magnetic Stimulation and Animal Models in Our Current and Future Understanding

Abstract

Despite the plethora of human neurophysiological research, the bilateral involvement of the leg motor cortical areas and their interhemispheric interaction during both normal and impaired human walking is poorly understood. Using transcranial magnetic stimulation (TMS), we have expanded our understanding of the role upper-extremity motor cortical areas play in normal movements and how stroke alters this role, and probed the efficacy of interventions to improve post-stroke arm function. However, similar investigations of the legs have lagged behind, in part, due to the anatomical difficulty in using TMS to stimulate the leg motor cortical areas. Additionally, leg movements are predominately bilaterally controlled and require interlimb coordination that may involve both hemispheres. The sensitive, but invasive, tools used in animal models of locomotion hold great potential for increasing our understanding of the bihemispheric motor cortical control of walking. In this review, we discuss 3 themes associated with the bihemispheric motor cortical control of walking after stroke: (a) what is known about the role of the bihemispheric motor cortical control in healthy and poststroke leg movements, (b) how the neural remodeling of the contralesional hemisphere can affect walking recovery after a stroke, and (c) what is the effect of behavioral rehabilitation training of walking on the neural remodeling of the motor cortical areas bilaterally. For each theme, we discuss how rodent models can enhance the present knowledge on human walking by testing hypotheses that cannot be investigated in humans, and how these findings can then be back-translated into the neurorehabilitation of poststroke walking.

Keywords: interhemispheric motor cortical communication; rehabilitation; rodent models; stroke; translational science; walking.

Figure 1

TMS-based optimal motor cortical locations and variations of the left and right abductor pollicis brevis and tibialis anterior in human healthy brains. Black dots denote the normalized hot spots while colored areas represent the 95% confidence intervals areas for the abductor pollicis brevis (left: red; right: dark blue) and tibialis anterior (left: green; right: light blue). (Used with permission from Niskanen E, Julkunen P, Saisanen L, Vanninen R, Karjalainen P, Kononen M. Group-level variations in motor representation areas of thenar and anterior tibial muscles: Navigated Transcranial Magnetic Stimulation Study. Human brain mapping. 2010; 31(8):1272–1280.)

Figure 2

Motor organization of rat’s brain using ICMS. A. The orientation of the location for the motor representations of the face, forelimb, and hindlimb on the dorsolateral part of the rat brain. B. ICMS-based hindlimb motor area in the left motor cortex of a representative rat. C. Individual ICMS-based hindlimb motor areas in 5 rats. (Used with permission from Frost SB, Iliakova M, Dunham C, Barbay S, Arnold P, Nudo RJ. Reliability in the location of hindlimb motor representations in Fischer-344 rats. Journal of neurosurgery. Spine. 2013; 19 (2):248–255.).