Altered Brain Volume, Microstructure Metrics and Functional Connectivity Features in Multiple System Atrophy.

In order to deeply understand the specific patterns of volume, microstructure, and functional changes in Multiple System Atrophy patients with cerebellar ataxia syndrome (MSA-c), we perform the current study by simultaneously applying structural (T1-weighted imaging), Diffusion tensor imaging (DTI), functional (BOLD fMRI) and extended Network-Based Statistics (extended-NBS) analysis. Twenty-nine MSA-c type patients and twenty-seven healthy controls (HCs) were involved in this study. First, we analyzed the whole brain changes of volume, microstructure, and functional connectivity (FC) in MSA-c patients. Then, we explored the correlations between significant multimodal MRI features and the total Unified Multiple System Atrophy Rating Scale (UMSARS) scores. Finally, we searched for sensitive imaging biomarkers for the diagnosis of MSA-c using support vector machine (SVM) classifier. Results showed significant grey matter atrophy in cerebellum and white matter microstructural abnormalities in cerebellum, left fusiform gyrus, right precentral gyrus and lingual gyrus. Extended-NBS analysis found two significant different connected components, featuring altered functional connectivity related to left and right cerebellar sub-regions, respectively. Moreover, the reduced fiber bundle counts at right Cerebellum_3 (Cbe3) and decreased fractional anisotropy (FA) values at bilateral Cbe9 were negatively associated with total UMSARS scores. Finally, the significant features at left Cbe9, Cbe1, and Cbe7b were found to be useful as sensitive biomarkers to differentiate MSA-c from HCs according to the SVM analysis. These findings advanced our understanding of the neural pathophysiological mechanisms of MSA from the perspective of multimodal neuroimaging.

Impact of injury duration on a sensorimotor functional network in complete spinal cord injury.

Connectivity changes after spinal cord injury (SCI) appear as dynamic post-injury procedures. The present study aimed to investigate the alterations in the functional connectivity (FC) in different injury duration in complete SCI using resting-state functional magnetic resonance imaging (fMRI). A total of 30 healthy controls (HCs) and 27 complete SCI patients were recruited in this study. A seed-based connectivity analysis compared FC differences between HCs and SCI and among SCI subgroups (SCI patients with post-injury within 6 months (early stage, n = 13) vs. those with post-injury beyond 6 months (late stage, n = 14)). Compared to HCs, SCI patients showed an increase in FC between sensorimotor cortex and cognitive, visual, and auditory cortices. The FC between motor cortex and cognitive cortex increased over time after injury. The FC between sensory cortex and visual cortex increased within 6 months after SCI, while FC between the sensory cortex and auditory cortex increased beyond 6 months after injury. The FC between sensorimotor cortex and cognitive, visual, auditory regions increased in complete SCI patients. The brain FC changed dynamically, and rehabilitation might be adapted over time after SCI.

Analysis of Prognostic Risk Factors Determining Poor Functional Recovery After Comprehensive Rehabilitation Including Motor-Imagery Brain-Computer Interface Training in Stroke Patients: A Prospective Study.

Objective: Upper limb (UL) motor function recovery, especially distal function, is one of the main goals of stroke rehabilitation as this function is important to perform activities of daily living (ADL). The efficacy of the motor-imagery brain-computer interface (MI-BCI) has been demonstrated in patients with stroke. Most patients with stroke receive comprehensive rehabilitation, including MI-BCI and routine training. However, most aspects of MI-BCI training for patients with subacute stroke are based on routine training. Risk factors for inadequate distal UL functional recovery in these patients remain unclear; therefore, it is more realistic to explore the prognostic factors of this comprehensive treatment based on clinical practice. The present study aims to investigate the independent risk factors that might lead to inadequate distal UL functional recovery in patients with stroke after comprehensive rehabilitation including MI-BCI (CRIMI-BCI). Methods: This prospective study recruited 82 patients with stroke who underwent CRIMI-BCI. Motor-imagery brain-computer interface training was performed for 60 min per day, 5 days per week for 4 weeks. The primary outcome was improvement of the wrist and hand dimensionality of Fugl-Meyer Assessment (δFMA-WH). According to the improvement score, the patients were classified into the efficient group (EG, δFMA-WH > 2) and the inefficient group (IG, δFMA-WH ≤ 2). Binary logistic regression was used to analyze clinical and demographic data, including aphasia, spasticity of the affected hand [assessed by Modified Ashworth Scale (MAS-H)], initial UL function, age, gender, time since stroke (TSS), lesion hemisphere, and lesion location. Results: Seventy-three patients completed the study. After training, all patients showed significant improvement in FMA-UL (Z = 7.381, p = 0.000**), FMA-SE (Z = 7.336, p = 0.000**), and FMA-WH (Z = 6.568, p = 0.000**). There were 35 patients (47.9%) in the IG group and 38 patients (52.1%) in the EG group. Multivariate analysis revealed that presence of aphasia [odds ratio (OR) 4.617, 95% confidence interval (CI) 1.435-14.860; p < 0.05], initial FMA-UL score ≤ 30 (OR 5.158, 95% CI 1.150-23.132; p < 0.05), and MAS-H ≥ level I+ (OR 3.810, 95% CI 1.231-11.790; p < 0.05) were the risk factors for inadequate distal UL functional recovery in patients with stroke after CRIMI-BCI. Conclusion: We concluded that CRIMI-BCI improved UL function in stroke patients with varying effectiveness. Inferior initial UL function, significant hand spasticity, and presence of aphasia were identified as independent risk factors for inadequate distal UL functional recovery in stroke patients after CRIMI-BCI.

Abnormal static and dynamic functional connectivity of resting-state fMRI in multiple system atrophy.

In order to explore the topological alterations in functional brain networks between multiple system atrophy (MSA) patients and healthy controls (HC), a new joint analysis method of static and dynamic functional connectivity (FC) is proposed in this paper. Twenty-four MSA patients and twenty HCs were enrolled in this study. We constructed static and dynamic brain networks from resting-state fMRI data and calculated four graph theory attributes. Statistical comparisons and correlation analysis were carried out for static and dynamic FC separately before combining both cases. We found decreased local efficiency (LE) and weighted degree (WD) in cerebellum from both static and dynamic graph attributes. For static FC alone, we identified increased betweenness centrality (BC) at left dorsolateral prefrontal cortex, left Cerebellum_Crus9 and decreased WD at Vermis_6. For dynamic FC alone, decreased BC, clustering coefficients and LE at several cortical regions and cerebellum were identified. All the features had significant correlation with total UMSARS scores. Receiver operating characteristic analysis showed that dynamic features had the highest area under the curve value. Our work not only added new evidence for the underlying neurobiology and disrupted dynamic disconnection syndrome of MSA, but also proved the possibility of disease diagnosis and progression tracking using rs-fMRI.

A Distance-Based Neurorehabilitation Evaluation Method Using Linear SVM and Resting-State fMRI.

During neurorehabilitation, clinical measurements are widely adopted to evaluate behavioral improvements after treatment. However, it is not able to identify or monitor the change of central nervous system (CNS) of each individual patient. Resting-state functional magnetic resonance imaging (rs-fMRI) has been widely used to investigate brain functions in healthy controls (HCs) and patients with neurological diseases, which could find functional changes following neurorehabilitation. In this paper, a distance-based rehabilitation evaluation method based on rs-fMRI was proposed. Specifically, we posit that in the functional connectivity (FC) space, patients and HCs distribute separately. Linear support vector machines (SVM) were trained on the brain networks to firstly separate patients from HCs. Second, the FC similarity between patients and HCs was measured by the L2 distance of each subject's feature vector to the separating hyperplane. Finally, statistical analysis of the distance revealed rehabilitation program induced improvements in patients and predicted rehabilitation outcomes. An rs-fMRI dataset with 22 HCs and 18 spinal cord injury (SCI) patients was utilized to validate our method. We built whole-brain networks using five atlases to test the robustness of the method and search for features under different node resolutions. The classifier successfully separated patients and HCs. Significant improvements in FC after treatment were found for the patients for all five atlases using the proposed method, which was consistent with clinical measurements. Furthermore, distance obtained from individual patient's longitudinal data showed a similar trend with each one's clinical scores, implying the possibility of individual rehabilitation outcome tracking and prediction. Our method not only provides a novel perspective of applying rs-fMRI to neurorehabilitation monitoring but also proves the potential in individualized rehabilitation prediction.

Brain Functional Networks Study of Subacute Stroke Patients With Upper Limb Dysfunction After Comprehensive Rehabilitation Including BCI Training.

Brain computer interface (BCI)-based training is promising for the treatment of stroke patients with upper limb (UL) paralysis. However, most stroke patients receive comprehensive treatment that not only includes BCI, but also routine training. The purpose of this study was to investigate the topological alterations in brain functional networks following comprehensive treatment, including BCI training, in the subacute stage of stroke. Twenty-five hospitalized subacute stroke patients with moderate to severe UL paralysis were assigned to one of two groups: 4-week comprehensive treatment, including routine and BCI training (BCI group, BG, n = 14) and 4-week routine training without BCI support (control group, CG, n = 11). Functional UL assessments were performed before and after training, including, Fugl-Meyer Assessment-UL (FMA-UL), Action Research Arm Test (ARAT), and Wolf Motor Function Test (WMFT). Neuroimaging assessment of functional connectivity (FC) in the BG was performed by resting state functional magnetic resonance imaging. After training, as compared with baseline, all clinical assessments (FMA-UL, ARAT, and WMFT) improved significantly (p < 0.05) in both groups. Meanwhile, better functional improvements were observed in FMA-UL (p < 0.05), ARAT (p < 0.05), and WMFT (p < 0.05) in the BG. Meanwhile, FC of the BG increased across the whole brain, including the temporal, parietal, and occipital lobes and subcortical regions. More importantly, increased inter-hemispheric FC between the somatosensory association cortex and putamen was strongly positively associated with UL motor function after training. Our findings demonstrate that comprehensive rehabilitation, including BCI training, can enhance UL motor function better than routine training for subacute stroke patients. The reorganization of brain functional networks topology in subacute stroke patients allows for increased coordination between the multi-sensory and motor-related cortex and the extrapyramidal system. Future long-term, longitudinal, controlled neuroimaging studies are needed to assess the effectiveness of BCI training as an approach to promote brain plasticity during the subacute stage of stroke.

Non-concomitant cortical structural and functional alterations in sensorimotor areas following incomplete spinal cord injury.

Brain plasticity, including anatomical changes and functional reorganization, is the physiological basis of functional recovery after spinal cord injury (SCI). The correlation between brain anatomical changes and functional reorganization after SCI is unclear. This study aimed to explore whether alterations of cortical structure and network function are concomitant in sensorimotor areas after incomplete SCI. Eighteen patients with incomplete SCI (mean age 40.94 ± 14.10 years old; male:female, 7:11) and 18 healthy subjects (37.33 ± 11.79 years old; male:female, 7:11) were studied by resting state functional magnetic resonance imaging. Gray matter volume (GMV) and functional connectivity were used to evaluate cortical structure and network function, respectively. There was no significant alteration of GMV in sensorimotor areas in patients with incomplete SCI compared with healthy subjects. Intra-hemispheric functional connectivity between left primary somatosensory cortex (BA1) and left primary motor cortex (BA4), and left BA1 and left somatosensory association cortex (BA5) was decreased, as well as inter-hemispheric functional connectivity between left BA1 and right BA4, left BA1 and right BA5, and left BA4 and right BA5 in patients with SCI. Functional connectivity between both BA4 areas was also decreased. The decreased functional connectivity between the left BA1 and the right BA4 positively correlated with American Spinal Injury Association sensory score in SCI patients. The results indicate that alterations of cortical anatomical structure and network functional connectivity in sensorimotor areas were non-concomitant in patients with incomplete SCI, indicating the network functional changes in sensorimotor areas may not be dependent on anatomic structure. The strength of functional connectivity within sensorimotor areas could serve as a potential imaging biomarker for assessment and prediction of sensory function in patients with incomplete SCI. This trial was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR-ROC-17013566).