The Study Of Brain Structural And Functional Changes During The Early Stage Of SCI

Background and purposeSpinal cord injury(SCI) is a common cause of disability in the world, which often leads to motor and sensory dysfunction below the spinal injury site. During the past 20 years, although various therapies have been developed for restoring motor function in SCI, to date, there are no efficient and trustworthy clinical treatments available for SCI patients. Every year, there are tens of thousands of people around the world become unfortunate patients with SCI for all kinds of unexpected events, who will spend the rest of the life in a wheelchair. This not only caused great mental distress to the patients and their family, but also brought a long-term difficult to load the economic burden, which has been became one of the most serious social problem. Therefore, a better understanding of the physiopathology mechanism of motor dysfunction following SCI and then taking some effective clinical interventions in the early stages of disease to enable SCI patients better integrate to the society, have especially important social significance and economic value.How to maximize the recovery of motor function in patients with SCI has been one of the most hot-topics and difficult problems in the clinical research. In the past few decades, many researchers have tried various methods to repair spinal cord injuries, such as cell transplantation, neurotrophic drugs and tissue engineering technology, etc., but these methods in clinic did not obtain a satisfactory result. Now in the clinical there still have been lack of effective treatments for spinal cord injury, expect spinal cord decompression, reconstructing the spinal stability, and high-dose methylprednisolone therapy within 8 hours after injury. After analyzing the current difficulties of SCI therapies, we found most of the previous studies mainly focus on the local changes in the spinal injury site and neglect the intimate interconnection with the brain.Why the motor cortex plays an important role in the recovery of motor function following SCI? This is because, after axon injury the axon regeneration and repair mainly rely on the role of the neuron cell body. And the reason why the motor dysfunction after SCI is that the injuries cause the corticospinal tract partial or total disruption. Corticospinal tract is mainly composed of motor neuron axons, the cell body mainly in the pyramidal cell layer of the brain motor cortex. Therefore, treatment that prevent the damage of cerebral motor cortex neurons after SCI will play a vital role in the regeneration and repair of corticospinal tract. Based on this point, we speculated that the structure or function changes of the motor cortex will plays an important role in the recovery of motor function after SCI.Current therapeutic strategies generally assume intact brain motor system function for driving limb movements. However, there is increasing evidence from animal models that SCI may result in atrophic or apoptosis changes of neural sensorimotor systems. The animal experiments cannot be simulated conditions of human reality, whether the structural and functional changes of the cerebral cortex also exist in the human remain unclear. To address this question, in this study, we will use the multimodal MRI to investigate the structural and functional changes in the acute SCI patients, and further explore the relationships between the brain changes and the motor recovery in SCI patients.Material and methodThe present study were divided into three parts:1. The preliminary study of brain structural changes during the early stage of SCI.Twenty SCI patients and 30 matched healthy controls underwent structural MRI scans on a 3-T MR system. VBM8 was used to investigate the brain white matter and grey matter changes. Meanwhile, ROI based methods also was used to investigate the volume changes of the primary motor cortex(M1), primary sensory cortex(S1), supplementary motor cortex(SMA), premotor cortex(PMC), medial prefrontal cortex and thalamus. Pearson correlation analysis were used to explore the relationship between the brain structural changes and ASIA scores. Furthermore, the SCI patients were split into two sub-groups according to the ASIA injury severity including the complete SCI groups and incomplete SCI groups. Finally, the SCI patients were also split into two sub-groups according to the injury site, including the cervical SCI groups and thoracolumbar SCI groups. The difference of brain structural changes between the two sub-groups were investigated.2. The preliminary study of brain structural changes during the early stage of SCI.Twenty-five SCI patients and 25 matched healthy controls underwent resting state f MRI scans on a 3-T MR system. SPM8 and REST soft were used to preprocess the f MRI data, and the amplitude of low-frequency fluctuations(ALFF) method was used to analyze the regional brain functional changes, and the functional connectivity(FC) method was used to analyze the network level brain functional changes. The ALFF and FC values of the abnormal areas were extracted and correlated to the ASIA scores using Pearson correlation.3. The study of the relationships between brain structural and functional changes and motor recovery in SCITwenty-five patients with SCI including 10 good motor recoverers and 15 poor motor recoverers were studied, along with 25 matched healthy controls. All subjects underwent structural and functional MRI scans on a 3-T MR system. The differences of the cross-sectional spinal cord area at the C2/C3 level, brain cortical thickness, white matter microstructure, functional connectivity during the resting state were evaluated among the three groups. The associations between the structural and functional reorganizations and the rate of motor recovery were also evaluated.Results:1. The preliminary study of brain structural changes during the early stage of SCI.Using VBM method, we found the brain areas with grey matter atrophy mainly in the primary M1, S1, SMA, and thalamus, and brain white matter atrophy in the corticospinal tract at the site of bilateral cerebral peduncle. ROI analysis showed the same abnormal areas as the areas of whole-brain VBM analysis. The gray matter volume in the M1 was positively correlated with the total ASIA motor score in patients with SCI(left, r2 = 0.49, P<0.001; right, r2 = 0.38, P= 0.003).The gray matter volume of bilateral M1, S1, SMA and thalamus in complete SCI patients is lower than that of in incomplete SCI patients(P<0.05), suggesting the more serious of SCI, the more serious brain atrophy in SCI patients. The gray matter volume of bilateral M1, S1, SMA and thalamus in cervical SCI patients is lower than that of in thoracolumbar SCI patients(P<0.05), suggesting the injury closer to the brain, the more serious of brain atrophy in SCI patients.2. The preliminary study of brain functional changes during the early stage of SCI.Compared to healthy controls, SCI patients showed decreased ALFF in the bilateral M1, and increased ALFF in the bilateral cerebellum and right orbitofrontal cortex. The ALFF value in the left cerebellum was negatively correlated with the ASIA motor score in SCI patients(r2=0.56, P<0.001). Furthermore, SCI patients mainly showed decreased inter-hemispheric FC between the bilateral M1, as well as increased intra-hemispheric FC within the motor network, including the M1, PMC, SMA, thalamus and cerebellum. Subsequent correlation analyses revealed that increased FC within the M1, SMA, and cerebellum negatively correlated with the total ASIA motor score(r2=0.33, P=0.002; r2=0.21, P=0.01; respectively).3. The study of the relationships between brain structural and functional changes and motor recovery in SCI.After SCI, poor recoverers exhibited more serious and widespread structural atrophy(cross-sectional spinal cord area, cortical thickness, and white matter microstructure) at the spinal and brain levels than the good recoverers. Meanwhile, poor recoverers exhibited decreased function connectivity between the primary motor cortex and the higher order motor areas(SMA and PMC), while good recoverers showed increased functional connectivity among these regions. These structural and functional reorganizations at the spinal and brain levels were associated with the motor recovery rate in all SCI patients.Conclusion1. SCI causes significant structural atrophy in the human sensorimotor system in the early stage of disease. The extent of brain atrophy relate to the damaged severity and segments.2. The brain structural atrophy acts as an obstacle to achieving effective motor function recovery following SCI: the more the structural integrity was in the spinal cord and brain the faster and better the motor recovery.3. SCI can induce significant regional and network-level functional alterations in the early stage of the disease.4. SCI patients appears to be recruitment of additional motor areas(SMA and PMC) in order to compensate for reduced capacity of the primary sensorimotor cortex to generate sufficient motor output.5. Multimodal imaging approach at the spinal and brain levels hold promise to predict motor recovery, and to monitor the effects of therapeutic interventions.