| Author: | Chen, Bo |
| Title: | Clinical effects and neurophysiological activities of repetitive transcranial magnetism stimulation (rTMS) on patients with severe upper limb dysfunction after stroke |
| Advisors: | Chan, Chi Chung Sam (RS) |
| Degree: | DHSc |
| Year: | 2024 |
| Department: | Faculty of Health and Social Sciences |
| Pages: | 194 pages : color illustrations |
| Language: | English |
| Abstract: | Background Patients with stroke often experience motor and non-motor deficits affecting both upper limb and lower limb function. The manifestation would adversely affect their independence in activities of daily living (ADL), limiting their social participation, thus leading to a heavy burden on society and families. Repeated transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation tool, has been shown to improve motor function on the stroke survivors. However, previous studies have not yet clarified the full brain neurophysiological activities by which rTMS improves clinical functioning in patients with stroke who have severe upper limb dysfunction. Thus, the aim of this study was to investigate the changes after rTMS treatment in clinical functions on the upper limbs (measured by Fugl-Meyer Motor Assessment upper extremity (FMA-UE), Modified Barthel Index (MBI), National Institutes of Health Stroke Scale (NIHSS)) and neurophysiological activities including the cortical activity level and brain networks level (measured by resting state electroencephalography (EEG)) on patients with severe upper limb dysfunction. This study also aimed to find out if there is any correlation between the changes of clinical functions and the neurophysiological activities after both high frequency (HF)- and low frequency (LF)-rTMS interventions. The objectives of this study including, 1. To investigate the changes of upper limb function after the HF-rTMS and LF-rTMS intervention measured by FMA-UE; 2. To investigate the changes of daily function after the HF-rTMS and LF-rTMS intervention measured by MBI; 3. To investigate the changes of stroke severity after the HF-rTMS and LF-rTMS measured by NIHSS; 4. To explore the cortical activities of the brain after the intervention measured by cortical oscillatory power and brain symmetry index (BSI); 5. To explore the brain network as measured by the functional connectivity, network path length and global efficiency of the brain after the HF-rTMS and LF-rTMS intervention; 6. To find out the relationships between the clinical outcomes and the neurophysiological activities (the cortical activities and of neuro-network the brain) of the participants after the intervention. Methods A total of 60 eligible patients with first onset of unilateral ischemic stroke were recruited in the study. They were randomly allocated into two groups, 32 in the HF-rTMS group and 28 into the LF-rTMS group. For the HF-rTMS group, rTMS was administered to the cortical motor areas of the affected hemisphere with a stimulus intensity of 90% resting motor threshold. Each treatment session including 30 trains, with 50 pulses per trains session which last for 25 seconds, leading to a total 1500 pulses a session. For the LF-rTMS group, 1 Hz was applied to the cortical motor area of the unaffected hemisphere with a stimulus intensity of 90% resting motor threshold and other parameters are the same as for the HF-rTMS group. All participants received a total of 10 daily session of rTMS in consecutive days. Assessments were performed before and after the intervention. Clinical outcomes assessments included stroke severity (NIHSS), upper extremity function (FMA-UE), ADL (MBI). The neurophysiological activities were detected via resting state EEG, including the cortical activity level (cortical oscillation power and pairwise derived brain symmetry index (pdBSI)) and brain networks level (functional connectivity, path length and global efficiency of brain network). Both participants and assessors were blinded to the group allocation. Differences in clinical outcomes and neurophysiological activities before and after intervention were compared by paired t-tests with false discovery rate (FDR) correction. Differences in clinical outcomes and neurophysiological changes after ten consecutive rTMS between the HF and LF groups were compared by independent t-tests with FDR correction. Correlation analysis was employed to examine relationships between clinical outcomes and neurophysiological activities. A significant level of p<0.05 was used to determine statistical significance. Results There were no significant differences in all demographic characteristics at baseline between the HF-rTMS (10 Hz) and the LF-rTMS (1 Hz) groups, except gender. First, changes of clinical outcomes. Paired t-tests with FDR correction revealed that ten sessions of rTMS led to significant improvements in FMA-UE scores in the LF-rTMS group but not in HF-rTMS group (t=2.32, d=0.26, *p=0.028). Both the HF-(t=-3.76, d=-0.54, *p<0.001) and LF-rTMS group (t=-4.36, d=-0.66, *p<0.001) showed significant improvements in stroke severity of participants in both groups measured by the NIHSS scores. Independent t-tests with FDR correction shown no significant differences were found between the HF and LF group in FMA-UE, NIHSS, or MBI scores post-rTMS. Secondly, changes in the neurophysiological activity of the brain at the cortical activity level. Significant cortical activity changes were noted only in the LF-rTMS group by paired t-tests with FDR correction, specifically, θpdBSI (t=2.23; d=-0.56; *p=0.04) in the frontal (F3-F4 electrode pairs) and αpdBSI (t=2.31; d=0.49; *p=0.03) in temporal (T5-T6 electrode pairs) lobes. Independent t-tests with FDR correction indicated significant differences between the HF and LF group in δpdBSI (t=-2.38; d=-0.70; *p=0.02) and (t=-2.04; d=-0.62; *p=0.04) and β1pdBSI (13-30 Hz) (t=2.22; d=0.64; *p=0.03) in the frontal lobes (F3-F4 and F7-F8 electrode pairs) post-rTMS. Regarding brain networks, only the HF group showed reduced path length (t=2.14; d=-0.46; *p=0.04) and increased global efficiency (t=2.25; d=0.47; *p=0.03) in the β2 (30-45 Hz) oscillation rhythm band post-rTMS, with significant differences noted between the HF and LF groups in this band (t=2.04; d=0.60; *p=0.04). Thirdly, Correlation analysis did not show a relationship between changes in FMA-UE, MBI scores and resting-state EEG markers (cortical activity and brain network) for both groups. However, improvements in NIHSS scores in the LF-rTMS group were correlated with the changes of cortical activities, specifically, a positive correlation with αpdBSI (r=0.46; *p=0.03) and a negative correlation with θpdBSI (r=-0.58; *p=0.046). Conversely, the improvements in NIHSS score in the HF-rTMS group were negatively correlated with the path length of the brain network in the β2 oscillation rhythm band (r=-0.405; *p=0.049). Conclusion In this study, the application of LF-rTMS on the unaffected brain appeared to improve the upper limb function and stroke severity among patients with severe upper limb dysfunction after stroke, while HF-rTMS could only reduce the stroke severity. No correlation was found between rTMS effects on upper limb function and neurophysiological activities of cortical activity or brain network changes. However, improvements in stroke severity appeared to correlate to the resting state EEG, providing insights into the brain mechanisms underlying rTMS clinical outcomes. |
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