Author: Bai, Zhongfei
Title: Modulation of the inter and intracortical neural networks for hemiparetic upper extremity functions after stroke
Advisors: Fong, N. K. Kenneth (RS)
Degree: Ph.D.
Year: 2022
Subject: Cerebrovascular disease -- Patients -- Rehabilitation
Hong Kong Polytechnic University -- Dissertations
Department: Department of Rehabilitation Sciences
Pages: xxv, 302 pages : color illustrations
Language: English
Abstract: Chapter 1 presents an introduction to this these. Stroke is a leading cause of long-term disability in adults worldwide, and approximately 90% of stroke survivors experience motor impairment immediately after disease onset. Although previous studies have provided evidence of the characteristics of poststroke cortical activity using neuroimaging techniques, thorough understanding regarding the underlying mechanisms of motor recovery has not yet been achieved. In addition to conventional motor evoked potential (MEP)-based measures for intracortical and interhemispheric excitation/inhibition, concurrent transcranial magnetic stimulation and electroencephalography recording (TMS-EEG) is a novel technique to directly probe the activity of the brain cortex without any contamination from the spinal cord, and the recorded signals are termed TMS-evoked potentials (TEPs). Therefore, TMS-EEG is an optimal investigation tool for patients with stroke regardless of the severity of motor impairment. Repetitive TMS (rTMS) in the form of intermittent theta burst stimulation (iTBS) has been shown to be effective in inducing long-term potentiation-like neuroplastic changes within the cortex in healthy people, but limited number of studies have investigated its utility in patients with stroke, especially using the TMS-EEG approach. Therefore, the overall objective of this thesis is to advance our understanding on the neurophysiology and neuroplasticity of the primary motor cortex (M1) using TMS-EEG approach in patients with chronic stroke.
Chapter 2 presents a systematic review and meta-analysis aimed at summarizing the effects of four rTMS protocols, namely, low frequency rTMS applied to the contralesional M1, high frequency rTMS applied to the ipsilesional M1, continuous theta burst stimulation applied to the contralesional M1 and iTBS applied to the ipsilesional M1, in modulating corticospinal excitability in patients with stroke. Finally, a total of 61 studies were included in the current review. Except for continuous theta burst stimulation, it is evident that these protocols are effective in enhancing the corticospinal excitability of the ipsilesional M1 in stroke, shown by an increase on the amplitude of MEPs and/or a decrease on resting motor threshold.
Prior to the main study with stroke, a pilot study was conducted in young healthy people (Chapter 3). Using TMS-EEG, the modulatory effects of iTBS applied to the M1 was compared to a control condition of targeting the primary visual cortex (V1). Simultaneously, another condition of iTBS targeting the supplementary motor area (SMA) was employed, because a facilitatory connection from the SMA and the M1 has been shown in previous studies. Eighteen young adults (12 males) were enrolled in this study. The results showed that iTBS to the M1, but not the SMA or the V1, significantly reduced the N100 amplitude of TEPs in bilateral hemispheres, confirming the local and remote after-effects of iTBS in reducing intracortical inhibition within the M1.
To deal with the objective of this thesis, the main study (Chapter 4) recruited 23 patients with chronic stroke and 21 age-matched healthy controls. A battery of MEP-based measures and TMS-EEG were cross-sectionally compared between the two populations. The results (Part 1 of the main study) confirmed that the ipsilesional M1 demonstrated a reduction of corticospinal excitability and prolonged cortical silent period. The reduced amplitude of N100 indicated an impairment of intracortical inhibition, primarily mediated by GABA-B receptors. Two control conditions were completed in healthy participants to verify whether our TMS-EEG setups were appropriate for eliminating the contamination of auditory-evoked potentials from TEPs. The results showed that our TMS-EEG setups were useful for eliminating the contamination of auditory-evoked potentials from TEPs, particularly in the early and middle stage following TMS pulses.
Interhemispheric signal propagation is a novel measure which is believed to represent interhemispheric inhibition in healthy people. However, recent studies indicated that there are different mechanisms underlying interhemispheric signal propagation and interhemispheric inhibition in healthy participants and patients with stroke. The data from the main study was used to reveal the functional correlates of interhemispheric signal propagate in stroke, and the results (Part 2 of the main study) are presented in Chapter 5. It was found that interhemispheric signal propagation was negatively correlated with TEPs of the stimulated M1 in both healthy participants and patients with stroke, irrespective of which hemisphere was stimulated, whereas TEPs of the non-stimulated side was not. Therefore, the data showed that interhemispheric signal propagation may not represent the process of interhemispheric inhibition.
The patients recruited in the main study also participated in a pseudo-randomized, sham-controlled, crossover study (Chapter 6) to evaluate the immediate effects of a single-session iTBS in modulating the neurophysiology of patients with stroke (Part 3 of the main study). Following a single-session stimulation, iTBS, but not sham iTBS, was effective in enhancing the amplitude of P30 and MEPs of the ipsilesional M1 in patients with stroke without effects on other network-related meaures.
Chapter 7 presents conclusions of this thesis.
Chapter 8 presents appendices of this thesis
Regarding the implications of this thesis, patients with stroke show a complex change of GABA-B receptor-mediated intracortical inhibition (i.e., prolonged duration but reduced magnitude), which is a new insight into the neurophysiology of patients with stroke. Our study supports the effects of iTBS in enhancing ipsilesional corticospinal excitability not only from a perspective of MEP-based measures but also from TEPs. The N100 appears to be a useful biomarker to represent the overall excitatory and inhibitory functioning within the ipsilesional M1 in patients after stroke, and it may be useful as a pronostic biomaker to evaluate patients' neurophysiological state and their rehabilitation potentials.
Rights: All rights reserved
Access: open access

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