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Zhou F.,Nanchang University | Zhou F.,Jiangxi Province Medical Imaging Research Institute | Zhuang Y.,Second Hospital of Nanchang | Gong H.,Nanchang University | And 6 more authors.
PLoS ONE | Year: 2016

Brain entropy (BEN) mapping provides a novel approach to characterize brain temporal dynamics, a key feature of human brain. Using resting state functional magnetic resonance imaging (rsfMRI), reliable and spatially distributed BEN patterns have been identified in normal brain, suggesting a potential use in clinical populations since temporal brain dynamics and entropy may be altered in disease conditions. The purpose of this study was to characterize BEN in multiple sclerosis (MS), a neurodegenerative disease that affects millions of people. Since currently there is no cure for MS, developing treatment or medication that can slow down its progression represents a high research priority, for which validating a brain marker sensitive to disease and the related functional impairments is essential. Because MS can start long time before any measurable symptoms and structural deficits, assessing the dynamic brain activity and correspondingly BEN may provide a critical way to study MS and its progression. Because BEN is new to MS, we aimed to assess BEN alterations in the relapsing-remitting MS (RRMS) patients using a patient versus control design, to examine the correlation of BEN to clinical measurements, and to check the correlation of BEN to structural brain measures which have been more often used inMS studies. As compared to controls, RRMS patients showed increased BEN in motor areas, executive control area, spatial coordinating area, and memory system. Increased BEN was related to greater disease severity as measured by the expanded disability status scale (EDSS) and greater tissue damage as indicated by the mean diffusivity. Patients also showed decreased BEN in other places, which was associated with less disability or fatigue, indicating a disease-related BEN re-distribution. Our results suggest BEN as a novel and useful tool for characterizing RRMS. © 2016 Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Zhou F.,Nanchang University | Zhou F.,Jiangxi Province Medical Imaging Research Institute | Zhuang Y.,The Second Hospital of Nanchang | Wang L.,Sun Yat Sen University | And 7 more authors.
Neuropsychiatric Disease and Treatment | Year: 2015

Background and purpose: Little is known about the functional and structural connectivity (FC and SC) of the hippocampus and amygdala, which are two important structures involved in cognitive processes, or their involvement in relapsing-remitting multiple sclerosis (RRMS). In this study, we aimed to examine the connectivity of white-matter (WM) tracts and the synchrony of intrinsic neuronal activity in outer regions connected with the hippocampus or amygdala in RRMS patients. Patients and methods: Twenty-three RRMS patients and 23 healthy subjects participated in this study. Diffusion tensor probabilistic tractography was used to examine the SC, the FC correlation coefficient (FC-CC) and combined FC strength (FCS), which was derived from the resting-state functional magnetic resonance imaging used to examine the FC, of the connection between the hippocampus or the amygdala and other regions, and the correlations of these connections with clinical markers. Results: Compared with healthy subjects, the RRMS patients showed significantly decreased SC and increased FCS of the bilateral hippocampus, and left amygdala. Their slightly increased FC-CC was positively correlated with WM tract damage in the right hippocampus (ρ=0.57, P=0.005); an increased FCS was also positively correlated with WM tract damage in the right amygdala. A relationship was observed between the WM lesion load and SC alterations, including the lg(N tracts) of the right hippocampus (ρ=-0.68, P,0.05), lg(N tracts) (ρ=-0.69, P,0.05), and fractional anisotropy (ρ=-0.68, P,0.05) and radial diffusivity of the left hippocampus (ρ=0.45, P,0.05). A relationship between WM lesion load and FCS of the left amygdale was also observed. Conclusion: The concurrent increased functional connections and demyelination-related structural disconnectivity between the hippocampus or amygdala and other regions in RRMS suggest that the functional-structural relationships require further investigation. © 2015 Zhou et al.


Zhuang Y.,Nanchang University | Zhuang Y.,Second Hospital of Nanchang | Zhou F.,Nanchang University | Zhou F.,Jiangxi Province Medical Imaging Research Institute | And 2 more authors.
PLoS ONE | Year: 2015

Background and Purpose: Advanced MRI studies have revealed regional alterations in the sensorimotor cortex of patients with relapsing-remitting multiple sclerosis (RRMS). However, the organizational features underlying the relapsing phase and the subsequent remitting phase have not been directly shown at the functional network or the connectome level. Therefore, this study aimed to characterize MS-related centrality disturbances of the sensorimotor network (SMN) and to assess network integrity and connectedness. Methods: Thirty-four patients with clinically definite RRMS and well-matched healthy controls participated in the study. Twenty-three patients in the remitting phase underwent one resting-state functional MRI, and 11 patients in the relapsing-remitting phase underwent two different MRIs. We measured voxel-wise centrality metrics to determine direct (degree centrality, DC) and global (eigenvector centrality, EC) functional relationships across the entire SMN. Results: In the relapsing phase, DC was significantly decreased in the bilateral primary motor and somatosensory cortex (M1/S1), left dorsal premotor (PMd), and operculum-integrated regions. However, DC was increased in the peripheral SMN areas. The decrease in DC in the bilateral M1/S1 was associated with the expanded disability status scale (EDSS) and total white matter lesion loads (TWMLLs), suggesting that this adaptive response is related to the extent of brain damage in the rapid-onset attack stage. During the remission process, these alterations in centrality were restored in the bilateral M1/S1 and peripheral SMN areas. In the remitting phase, DC was reduced in the premotor, supplementary motor, and operculum-integrated regions, reflecting an adaptive response due to brain atrophy. However, DC was enhanced in the right M1 and left parietal-integrated regions, indicating chronic reorganization. In both the relapsing and remitting phases, the changes in EC and DC were similar. Conclusions: The alterations in centrality within the SMN indicate rapid plasticity and chronic reorganization with a biased impairment of specific functional areas in RRMS patients. © 2015 Zhuang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Wu L.,Nanchang University | Wu L.,Jiangxi Province Medical Imaging Research Institute | Zhang Y.,Jiangxi University of Traditional Chinese Medicine | Zhou F.,Nanchang University | And 8 more authors.
Neuropsychiatric Disease and Treatment | Year: 2016

Background and purpose: Neuroimaging studies of relapsing–remitting multiple sclerosis (RRMS) have found structural disconnection and large-scale neural network dysfunction. However, few studies have explored the local brain activity of RRMS patients in the resting state. Patients and methods: In this study, regional homogeneity (ReHo) and resting-state functional connectivity (FC) were used to investigate intra-and interregional synchronized activity in 22 patients with RRMS and 22 matched healthy controls (HCs). Results: Compared with HCs, patients with RRMS showed significantly decreased ReHo in the left insula and right caudate. Through further seed-based FC analysis, we found decreased FC between the left insula and left precentral gyrus in patients with RRMS compared with HCs, as well as increased FC between the right caudate and right dorsolateral prefrontal cortex. Pearson’s correlation analysis showed that a decreased ReHo value in the left insula was associated with an increased total white matter lesion loads (TWMLL) score (r=−0.594, P=0.004) or a worsened paced auditory serial addition test score (r=0.536, P=0.010). No other significant correlations were observed between the FC value (left insula − left precentral gyrus) and clinical scores (P=0.246–0.982). The ReHo value of the right caudate was negatively correlated with disease duration (r=−0.526, P=0.012) and with the TWMLL score (r=−0.596, P=0.003). Moreover, a positive correlation was observed between the FC value (right caudate − right dorsolateral prefrontal cortex) and the TWMLL score (r=0.523, P=0.012) or the modified fatigue impact scale-5 score (r=0.608, P=0.003). Conclusion: Together, these findings suggest that the insula with regional dysfunction involves disconnection with sensorimotor regions, and demyelinating lesion-related intra-and interregional dysfunction in the caudate is associated with the impact of fatigue on cognitive control functions. Abnormal synchronization of intra-and interregional activity in the insula and caudate may play important roles in the pathology of RRMS. © 2016 Wu et al.


Zhou F.,Nanchang University | Zhou F.,Jiangxi Province Medical Imaging Research Institute | Zhuang Y.,The Second Hospital of NanChang | Wu L.,Nanchang University | And 7 more authors.
Clinical Imaging | Year: 2014

Objective: To investigate the relationship between the amplitude of thalamic intrinsic neuronal activity, structural imaging indices, and the clinical neurological scales in relapsing-remitting multiple sclerosis (RRMS). Methods: Twenty-three patients with RRMS and 23 healthy controls were examined by resting-state fMRI (rs-fMRI) scan. Thalamic intrinsic oscillation amplitude was calculated by amplitude of low frequency fluctuation (ALFF) of rs-fMRI, as well as its correlations with clinical and structural imaging indices. Results: Compared with the healthy controls, RRMS patients showed significantly increased ALFF values in bilateral thalami (P<. .05, corrected). In the patient group, positive correlation was found between bilateral ALFF values and paced auditory serial addition test (left: P= .033; right: P= .016). Significant correlation was detected between the ALFF values and fractional anisotropy (FA) values in the left thalamus (r= 0.550, P= .007); only tendency increased correlation was detected between the ALFF values and FA values in the right thalamus (P= .114). No correlation was observed between bilateral thalamic ALFF values and disease duration, expanded disability status scale score, brain parenchymal fraction, or total white matter lesion loads (P>. .05). Conclusion: The increased thalamic intrinsic oscillation amplitude as an ineffective reorganization was responded to microstructural damage in the RRMS patients, as well as it was associated with the slowed cognitive processing in relatively minimally disabled stage. © 2014 Elsevier Inc.


Zhou F.,Nanchang University | Zhou F.,Jiangxi Province Medical Imaging Research Institute | Zhuang Y.,Second Hospital of Nanchang | Gong H.,Nanchang University | And 6 more authors.
PLoS ONE | Year: 2014

Background and Purpose: Little is known about the interactions between the default mode network (DMN) subregions in relapsing-remitting multiple sclerosis (RRMS). This study used diffusion tensor imaging (DTI) and resting-state functional MRI (rs-fMRI) to examine alterations of long white matter tracts in paired DMN subregions and their functional connectivity in RRMS patients. Methods: Twenty-four RRMS patients and 24 healthy subjects participated in this study. The fiber connections derived from DTI tractography and the temporal correlation coefficient derived from rs-fMRI were combined to examine the intersubregion structural-functional connectivity (SC-FC) within the DMN and its correlations with clinical markers. Results: Compared with healthy subjects, the RRMS patients showed the following: 1) significantly decreased SC and increased FC in the pair-wise subregions; 2) two significant correlations in SC-FC coupling patterns, including the positive correlation between slightly increased FC value and long white matter tract damage in the PCC/PCUN-MPFC connection, and the negative correlations between significantly increased FC values and long white matter tract damage in the PCC/ PCUN-bilateral mTL connections; 3) SC alterations [log(N track) of the PCC/PCUN-left IPL, RD value of the MPFC-left IPL, FA value of the PCC/PCUN-left mTL connections] correlated with EDSS, increases in the RD value of MPFC-left IPL connection was positively correlated to the MFIS; and decreases in the FA value of PCC/PCUN-right IPL connection was negatively correlated with the PASAT; 4) decreased SC (FA value of the MPFC-left IPL, track volume of the PCC/PCUN-MPFC, and log(N track) of PCC/PCUN-left mTL connections) was positively correlated with brain atrophy. Conclusions: In the connections of paired DMN subregions, we observed decreased SC and increased FC in RRMS patients. The relationship between MS-related structural abnormalities and clinical markers suggests that the disruption of this long-distance "inter-subregion" connectivity (white matter) may significantly impact the integrity of the network's function. © 2014 Zhou et al.

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