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 process
2-4, 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
stroke
5. 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 Ameli
5 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
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