Effects of high- and low-frequency repetitive transcranial magnetic stimulation on motor recovery in early stroke patients: Evidence from a randomized controlled trial with clinical, neurophysiological and functional imaging assessments

Abstract

BackgroundRepetitive transcranial magnetic stimulation (rTMS) can modulate cortical excitability, and may be beneficial for motor recovery after stroke. However, the neuroplasticity effects of rTMS have not been thoroughly investigated in the early stage after stroke.ObjectiveTo comprehensively assess the effects of high- and low-frequency repetitive transcranial magnetic stimulations on motor recovery in early stroke patients, using a randomized controlled trial based on clinical, neurophysiological and functional imaging assessments.MethodsSixty hospitalized, first-ever ischemic stroke patients (within 2 weeks after stroke) with motor deficits were randomly allocated to receive, in addition to standard physical therapy, five consecutive sessions of either: (1) High-frequency (HF) rTMS at 10 Hz over the ipsilesional primary motor cortex (M1); (2) Low-frequency (LF) rTMS at 1 Hz over the contralesional M1; (3) sham rTMS. The primary outcome measure was a motor impairment score (Upper Extremity Fugl-Meyer) evaluated at baseline, after rTMS intervention, and at 3-month follow-up. Cortical excitability and functional magnetic resonance imaging (fMRI) data were obtained within 24 h before and after rTMS intervention. Analyses of variance were conducted to compare the recovery effects among the three rTMS groups, assessed using clinical, neurophysiological and fMRI tests.ResultsMotor improvement was significantly larger in the two rTMS groups than in the control group. The HF-rTMS group showed significantly increased cortical excitability and motor-evoked fMRI activation in ipsilesional motor areas, whereas the LF-rTMS group had significantly decreased cortical excitability and motor-evoked fMRI activation in contralesional motor areas. Activity in ipsilesional motor cortex significantly correlated with motor function, after intervention as well as at 3-month follow-up.ConclusionHF- and LF-rTMS can both improve motor function by modulating motor cortical activation in the early phase of stroke.

Altered Topological Organization in the Sensorimotor Network After Application of Different Frequency rTMS

“…Specifically, decreased degree centrality was positively associated with decreased ALFF in the left PCL. These findings were consistent with the inhibitory effect of low-frequency rTMS on ipsilateral cortical excitability (Khedr et al, 2009;Corti et al, 2012;Du et al, 2018). The PCL, a U-shaped convolution on the medial hemispheric surface, connects medial portions of the precentral and postcentral gyrus and is involved in motor control and sensory innervations of the limbs (Johns, 2014).…”

“…Transcranial magnetic stimulation (TMS) is a focal and noninvasive technique that utilizes short, rapidly changing magnetic field pulses to induce electrical currents in underlying cortical tissue (Hallett, 2007;Fox et al, 2012). Repetitive TMS (rTMS) at different frequencies could induce distinct effects: high-frequency rTMS (>1 Hz) has been indicated to facilitate the cortical excitability of the ipsilateral hemisphere (Peinemann et al, 2004;Pascual-Leone et al, 2005;Khedr et al, 2009;Corti et al, 2012;Du et al, 2018), while low-frequency rTMS (≤1 Hz) could induce decreased cortical excitability in the ipsilateral side and increased excitability in the contralateral hemisphere (Muellbacher et al, 2000;Ziemann, 2004;Khedr et al, 2009;Corti et al, 2012;Du et al, 2018).…”

Evidence of Neuroplasticity: A Robotic Hand Exoskeleton Study for Post-Stroke Rehabilitation

“…However, (signi cant) changes in CG were found to be limited only to the clinical-scales, and the changes in brain was speci cally found only in the RG. An increase in corticalexcitability in the ipsilesional-hemisphere along with interhemispheric-normalization of RMT asymm could point towards the recruitment of perilesional areas in ipsilesional-hemisphere or exploitation of the preserved functional recovery reservoir in the ipsilesional-hemisphere (35), (39), (40), (41). The decrease of RMT and change in RMT asymmetry from distal-muscle was also accompanied by functional markers-FMW/H evidencing sensorimotor-plasticity, functional recovery along with task-dependent rehabilitation.…”

“…Cortical-excitability and corticospinal-tract integrity have also been shown to be correlated with functional recovery potential in patients with chronic stroke (31) and exoskeleton-training appears to be bene cial in activating the ipsilesional-hemisphere for chronic patients (13.8 ± 9.1 months). Activation of ipsilesional-hemisphere could indicate either vicariation of the loss of neural circuits or unmasking of pre-existing synapses or recruitment of perilesional areas in ipsilesional-hemisphere or exploitation of the preserved functional recovery reservoir in ipsilesional-hemisphere (35),(39),(40), (41). Further, a ~ 30% decrease in MEP-amplitude in contralesional-hemisphere over the duration of intervention might indicate a decrease in cortical-excitability, evidencing a trend towards restoring the Inter-Hemisphere Inhibition (IHI) balance in the motor-network between the two hemispheres(39),(40), however, it needs to be further evaluated in a larger cohort.…”

“…∆RMTasymm-ratio showed a mean increase of 0.12 ± 0.14 in RG and CG an increase of mean 0.011 ± 0.1 ( Table-3). Normalization might indicate the recruitment of peri-lesional areas in the ipsilesionalhemisphere or exploitation of the preserved functional-recovery reservoir in the ipsilesional-hemisphere (35), (39), (40), (41). Normalization in response to therapy, in terms of TMS measures on the ipsilesional-side, has been shown to have a greater recovery of arm and hand function in acute, sub-acute and chronic stages (35).…”