Functional Reorganization of the Brain in Ischemic Stroke Patients after the Repetitive Transcranial Magnetic Stimulation: a fMRI Study
Jing Li1, Xuewei Zhang2, Jie Lu1, Zhentao Zuo3, Rong Xue3, Yong Fan4, Yuzhou Guan5, and Weihong Zhang1

1Department of Radiology, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China, People's Republic of, 2Department of Interventional Radiology, China Meitan General Hospital, Beijing, China, People's Republic of, 3State Key Laboratory of Brain and Cognitive Science, Beijing MR Center for Brain Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China, People's Republic of, 4Department of Radiology, School of Medicine, University of Pennsylvania, Philadelphia, PA, United States, 5Department of Neurology, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China, People's Republic of

Synopsis

It is a resting-state fMRI( rs-fMRI) study of patients with motor disturbance after acute ischemic stroke. We assessed the functional connectivity (FC) changes of the ipsilesional primary motor cortex (M1) within the brain before and after the repetitive transcranial magnetic stimulation (rTMS) by rs-fMRI. The research not only gave theoretical support of the rTMS treatment in stroke patients but also investigated the cerebral functional changes in motor recovery.

Purpose

To investigate the cerebral functional changes before and after the repetitive transcranial magnetic stimulation (rTMS) in ischemic stroke patients using the resting-state functional magnetic resonance imaging (rs-fMRI).

Methods

Thirteen patients with unilateral cerebral subcortex lesion in the middle cerebral artery territory detected by diffusion weighted image (DWI) were enrolled. Eight of them were included in the treatment group and received a ten-day rTMS beginning at about five days after onset. The stimulation involved 50 trains of 20 pulses each day over the ipsilesional M1 at a frenquency of 5HZ, with the stimulus intensity set at 120% of the resting motor threshold of the unaffected extremity. The sham group is consisted of the rest five patients with no rTMS. The treatment group were scanned with rs-fMRI prior to and after the rTMS and the sham received them at the same time point, namely at approximately four days and thirty-one days after onset. Motor functional scores were assessed before every fMRI and included: 1) National Institutes of Health Stroke Scale (NIHSS), 2) Barthel Index(BI), and 3) Fugl-Meyer assessment(FMA). (see Table 1) MRI including rs-fMRI and structural images were performed on a 3.0 Tesla MR imaging System (MAGNETOM Skyra System, Siemens, Erlangen, Germany) by using a twenty-channel phased-array head coil. Preprocessing of the fMRI data was carried out by using Data Processing Assistant for Resting-State fMRI (DPARSF)1. Pearson correlation analysis between the time course of the ipsilesional M1 and that of every voxel within the whole brain was performed for maps of correlation coefficients, which were Fisher’s z-transformed and called as z-functional connectivity (z-FC) maps. The contrast between the z-FC maps post- and pre- the rTMS treatment (for the sham group: at about thirty-one days and four days after onset) was calculated for each patient. The achieved differential contrast images (∆z-FC maps) were then used for a two-sample t test to compare the FC changes between the rTMS treatment group and the sham group. And it was the same with the statistical analysis of motor functional scores of the two groups.

Results

The NIHSS scores of the treatment group were decreased (P<0.05) after the rTMS, while the BI and FMA scores increased (P<0.05). And it was the same with the sham group, which indicated motor improvement. However, there is no significant difference between the treatment and the sham group. Compared with the sham group, the rTMS treatment group showed significantly increased functional connectivity between the ipsilesional M1 and the bilateral thalamus, the contralesional postcentral gyrus, the contralesional supplementary motor area (SMA), the contralesional middle occipital gyrus, the bilateral superior temporal gyrus, the ipsilesional pallidum and the contralesional Heschl gyrus. And decreased functional connectivity of the ipsilesional M1 was demonstrated in the ipsilesional inferior and middle temporal gyrus, the ipsilesional inferior and middle frontal gyrus, the contralesional superior temporal gyrus and the contralesional middle and superior frontal gyrus.(see Figure 1-2)

Discussion

To the best of our knowledge, this is the first study to evaluate the cerebral functional changes after rTMS in ischemic stroke patients using the rs-fMRI. Our research is a longitudinal study instead of a cross-sectional one. As we all know, stroke develops over a certain time course and the motor recovery is a dynamic process2-4, from which aspect the longitudinal study is better. What’s more, our research includes stroke patients in the acute stage only, which can minimize the bias caused by the course of the disease. In addition, former study demonstrated that high-frequency rTMS over ipsilesional M1 improved movement kinematics in most of the patients with subcortical stroke, but not in patients with cortical stroke5. Only subcortical stroke patients are included in our research, which on one side improved the effectiveness of rTMS and on the other hand excluded the probable influence of the cerebral cortex to motor function. Motor function of the rTMS group approved after the treatment, assessed by the behavioral testing. However, there is no significant difference of motor recovery between the treatment and the sham group. We thought that it may be due to the small sample size of our research to some degree. The previous study of Mitra Ameli5 showed that facilitary rTMS over ipsilesional M1 caused a significant motor improvement of the affected hand in patients with subcortical stroke. They conceived that the high-frequency (10HZ) rTMS reduced the neural activity in the contralesional hemisphere for movements of the affected hand in subcortical stroke.

Conclusion

Changes of functional connectivity pre- and post- rTMS provide us with a new approach for revealing its mechanism in improving motor function in stroke patients.

Acknowledgements

My deepest gratitude goes first and foremost to Professor Zhang , my supervisor, for her constant encouragement and guidance. She has walked me through all the stages of doing the research and writing the paper. Second, I would like to express my heartfelt thanks to Professor Guan, who has given me a lot help and guidance in the neurological part of the research. I am also greatly indebted to the professors and teachers of the Institute of Automation of Chinese Academy of Sciences, who have instructed and helped me a lot in the data processing. Last my thanks would go to my friends who gave me their help and time in listening to me and helping me work out my problems during the difficult course of the research.

References

1. Chao-Gan Y, Yu-Feng Z. DPARSF: A MATLAB Toolbox for "Pipeline" Data Analysis of Resting-State fMRI. Frontiers in systems neuroscience 2010; 4: 13.

2. Park CH, Chang WH, Ohn SH, et al. Longitudinal changes of resting-state functional connectivity during motor recovery after stroke. Stroke; a journal of cerebral circulation 2011; 42(5): 1357-62.

3. Wang L, Yu C, Chen H, et al. Dynamic functional reorganization of the motor execution network after stroke. Brain : a journal of neurology 2010; 133(Pt 4): 1224-38.

4. Feydy A, Carlier R, Roby-Brami A, et al. Longitudinal Study of Motor Recovery After Stroke: Recruitment and Focusing of Brain Activation. Stroke; a journal of cerebral circulation 2002; 33(6): 1610-7.

5. MD MAMCG. Differential effects of high-frequency repetitive transcranial magnetic stimulation over ipsilesional primary motor cortex in cortical and subcortical middle cerebral artery stroke. Annals of neurology 2009; 66(3): 298-309.

Figures

The FC of the right (ipsilesional) M1 within the brain of the rTMS treatment group comparing with the sham group. PreCG: Precentral gyrus; SFG: Superior frontal gyrus, dorsolateral; MFG: Middle frontal gyrus; IFGtriang: Inferior frontal gyrus, triangular part; SMA: Supplementary motor area; MOG: Middle occipital gyrus; PoCG: Postcentral gyrus; PAL: Lenticular nucleus, pallidum; THA: Thalamus; HES: Heschl gyrus; STG: Superior temporal gyrus; TPOsup: Temporal pole, superior temporal gyrus.

The increased and decreased FC of the right (ipsilesional) primary motor cortex (M1) within the brain of the rTMS treatment group comparing with the sham group.

Motor functional assessment pre- and post- the rTMS treatment.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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