Ying Zhuang

Altered Inter-Subregion Connectivity of the Default Mode Network in Relapsing Remitting Multiple Sclerosis: A Functional and Structural Connectivity Study

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 inter-subregion 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 networks function.

Altered motor network functional connectivity in amyotrophic lateral sclerosis: a resting-state functional magnetic resonance imaging study.

Resting-state functional MRI provides a viable tool for assessing brain dysfunctions in amyotrophic lateral sclerosis (ALS) without using explicit tasks. Altered resting brain functional connectivity (FC) in ALS has been reported in several studies but with large discrepancies in terms of the alteration directions. The purpose of this study was to provide new evidence for the resting FC disruptions in ALS. We focused on FC in the motor network as motor dysfunctions are a hallmark of ALS pathology. To test the hypothesis that ALS is associated with intermotor network FC changes, we compared FC of the key nodes of motor network between 12 ALS patients and 12 matched controls, and found both decreased and increased within-motor network FC in ALS patients. Increased FC between the bilateral superior parietal lobule and the right anterior inferior cerebellum was found to be correlated with disease severity, with higher FC related to more severe disease. The decreased motor network FC may be a result of motor function degradation in ALS, whereas the increased FC and its correlation to disease severity might suggest a brain mechanism to compensate the loss of the normal motor functionality in ALS. Our results also showed that the within-motor cortex FC except the within premotor area FC did not change in these early disease stage patients.

Frequency-dependent changes in local intrinsic oscillations in chronic primary insomnia: A study of the amplitude of low-frequency fluctuations in the resting state

New neuroimaging techniques have led to significant advancements in our understanding of cerebral mechanisms of primary insomnia. However, the neuronal low-frequency oscillation remains largely uncharacterized in chronic primary insomnia (CPI). In this study, the amplitude of low-frequency fluctuation (ALFF), a data-driven method based on resting-state functional MRI, was used to examine local intrinsic activity in 27 patients with CPI and 27 age-, sex-, and education-matched healthy controls. We examined neural activity in two frequency bands, slow-4 (between 0.027 and 0.073 Hz) and slow-5 (0.010–0.027 Hz), because blood-oxygen level dependent (BOLD) fluctuations in different low-frequency bands may present different neurophysiological manifestations that pertain to a spatiotemporal organization. The ALFF associated with the primary disease effect was widely distributed in the cerebellum posterior lobe (CPL), dorsal and ventral prefrontal cortex, anterior cingulate cortex, precuneus, somatosensory cortex, and several default-mode sub-regions. Several brain regions (i.e., the right cerebellum, anterior lobe, and left putamen) exhibited an interaction between the frequency band and patient group. In the slow-5 band, increased ALFF of the right postcentral gyrus/inferior parietal lobule (PoCG/IPL) was enhanced in association with the sleep quality (ρ = 0.414, P = 0.044) and anxiety index (ρ = 0.406, P = 0.049) of the CPI patients. These findings suggest that during chronic insomnia, the intrinsic functional plasticity primarily responds to the hyperarousal state, which is the loss of inhibition in sensory-informational processing. Our findings regarding an abnormal sensory input and intrinsic processing mechanism might provide novel insight into the pathophysiology of CPI. Furthermore, the frequency factor should be taken into consideration when exploring ALFF-related clinical manifestations.

Resting State Brain Entropy Alterations in Relapsing Remitting Multiple Sclerosis

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 in MS 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.

Intrinsic Functional Plasticity of the Sensorimotor Network in Relapsing-Remitting Multiple Sclerosis: Evidence from a Centrality Analysis

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.

Temporal regularity of intrinsic cerebral activity in patients with chronic primary insomnia: a brain entropy study using resting-state fMRI.

Several neuroimaging studies have suggested that patients with chronic primary insomnia (CPI) exhibit anatomical and functional alterations of the brain, but the temporal regularity in spontaneous neuronal activity remains unknown. Here, brain entropy (BEN), a data‐driven method used to measure the signal regularity of a time series, was applied for the first time to investigate changes in the entire brain at the voxel level.

Increased thalamic intrinsic oscillation amplitude in relapsing–remitting multiple sclerosis associated with the slowed cognitive processing ☆

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.

Intrinsic Functional Plasticity of the Thalamocortical System in Minimally Disabled Patients with Relapsing-Remitting Multiple Sclerosis

The thalamus plays a crucial role in sensorimotor, cognitive, and attentional circuit functions. Disruptions in thalamic connectivity are believed to underlie the symptoms of multiple sclerosis (MS). Therefore, assessing thalamocortical structural connectivity (SC) and functional connectivity (FC) may provide new insights into the mechanism of intrinsic functional plasticity in a large-scale neural network. We used resting-state FC measurement and diffusion tensor imaging probabilistic tractography to study the functional and structural integrity of the thalamocortical system in patients with relapsing-remitting MS (RRMS) and matched healthy controls. In the thalamocortical connections of RRMS patients, we found lesion load-related regional FC in the right temporal pole, which reflected compensatory hyperconnectivity related to lesion-related demyelination. We also found significant correlations between increased diffusivity and slowed cognitive processing (PASAT) or the impact of fatigue (MFIS-5), as well as between connective fiber loss and disease duration. Taken together, the evidence from SC and FC analysis of the thalamocortical system suggests that minimally disabled RRMS patients exhibit a dissociated SC–FC pattern and limited regional functional plasticity to compensate for the chronic demyelination-related loss of long-distance SC. These results also provide further evidence supporting the notion that MS is a disorder of anatomical disconnection.

Disconnection of the hippocampus and amygdala associated with lesion load in relapsing–remitting multiple sclerosis: a structural and functional connectivity study

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.

Density abnormalities in normal-appearing gray matter in the middle-aged brain with white matter hyperintense lesions: a DARTEL-enhanced voxel-based morphometry study

Background and purpose Little is known about the structural alterations within gray matter (GM) in middle-aged subjects with white matter hyperintense (WMH) lesions. Here, we aimed to examine the anatomical changes within the GM and their relationship to WMH lesion loads in middle-aged subjects. Participants and methods Twenty-three middle-aged subjects with WMH lesions (WMH group) and 23 demographically matched healthy control subjects participated in the study. A Diffeomorphic Anatomical Registration Through Exponentiated Liealgebra-enhanced voxel-based morphometry was used to measure the GM density, and the correlations between WMH lesion volume and extracted GM values in abnormal regions were identified by voxel-based morphometry analysis. Results Compared with the healthy control subjects, the WMH group had a significantly decreased GM density in the left middle frontal gyrus, bilateral anterior cingulate cortex, left and right premotor cortex, and left and right middle cingulate cortex and an increased GM density in the bilateral cerebellum anterior lobe, left middle temporal gyrus, right temporoparietal junction, left and right prefrontal cortex (PFC), and left inferior parietal lobule. A relationship was observed between the normalized WMH lesion volume and the decreased GM density, including the left middle frontal gyrus (ρ=−0.629, P=0.002), bilateral anterior cingulate cortex (ρ=−0.507, P=0.019), right middle cingulate cortex (ρ=−0.484, P=0.026), and right premotor cortex (ρ=−0.438, P=0.047). The WMH lesion loads also negatively correlated with increased GM density in the right temporoparietal junction (ρ=−0.484, P=0.026), left PFC (ρ=−0.469, P=0.032), and right PFC (ρ=−0.438, P=0.047). Conclusion We observed that lesion load-associated structural plasticity corresponds to bidirectional changes in regional GM density in the WMH group.