scholarly journals Mechanisms of Network Changes in Cognitive Impairment in Multiple Sclerosis

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012834
Author(s):  
Danka Jandric ◽  
Ilona Lipp ◽  
David Paling ◽  
David Rog ◽  
Gloria Castellazzi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cognitive Impairment ◽  
Functional Connectivity ◽  
Resting State ◽  
Structural Connectivity ◽  
Cognitively Impaired ◽  
Anatomical Connectivity ◽  
Cross Sectional

Background and Objectives:Cognitive impairment in multiple sclerosis (MS) is associated with functional connectivity abnormalities. While there have been calls to use functional connectivity measures as biomarkers there remains to be a full understanding of why they are affected in MS. In this cross-sectional study we tested the hypothesis that functional network regions may be susceptible to disease-related ‘wear-and-tear’ and that this can be observable on co-occuring abnormalities on other MR metrics. We tested whether functional connectivity abnormalities in cognitively impaired MS patients co-occur with either 1) overlapping, 2) local, or 3) distal changes in anatomical connectivity and cerebral blood flow abnormalities.Methods:Multimodal 3T MRI and assessment with the Brief Repeatable Battery of Neuropsychological tests was performed in 102 relapsing-remitting MS patients and 27 healthy controls. MS patients were classified as cognitively impaired if they scored ≥1.5 standard deviations below the control mean on ≥2 tests (n=55), or else cognitively preserved (n=47). Functional connectivity was assessed with Independent Component Analysis and dual regression of resting-state fMRI images. Cerebral blood flow maps were estimated and anatomical connectivity was assessed with anatomical connectivity mapping and fractional anisotropy of diffusion-weighted MRI. Changes in cerebral blood flow and anatomical connectivity were assessed within resting state networks that showed functional connectivity abnormalities in cognitively impaired MS patients.Results:Functional connectivity was significantly decreased in the anterior and posterior default mode networks and significantly increased in the right and left frontoparietal networks in cognitively impaired relative to cognitively preserved MS patients (TFCE-corrected at p≤0.05, two-sided). Networks showing functional abnormalities showed altered cerebral blood flow and anatomical connectivity locally and distally but not in overlapping locations.Discussion:We provide the first evidence that FC abnormalities are accompanied with local cerebral blood flow and structural connectivity abnormalities but also demonstrate that these effects do not occur in exactly the same location. Our findings suggest a possibly shared pathological mechanism for altered functional connectivity in brain networks in MS.

scholarly journals Concurrent anatomical, physiological and network changes in cognitively impaired multiple sclerosis patients

2020 ◽  
Author(s):  
Danka Jandric ◽  
Ilona Lipp ◽  
David Paling ◽  
David Rog ◽  
Gloria Castellazzi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Functional Connectivity ◽  
Resting State ◽  
Metabolic Stress ◽  
Cognitively Impaired ◽  
Anatomical Connectivity ◽  
Resting State Network ◽  
Multiple Sclerosis Patients

AbstractCognitive impairment in multiple sclerosis is associated with functional connectivity abnormalities, but the pathological substrates of these abnormalities are not well understood. It has been proposed that resting-state network nodes that integrate information from disparate regions are susceptible to metabolic stress, which may impact functional connectivity. In multiple sclerosis, pathology could increase metabolic stress within axons, damaging the anatomical connections of network regions, and leading to functional connectivity changes. We tested this hypothesis by assessing whether resting state network regions that show functional connectivity abnormalities in people with cognitive impairment also show anatomical connectivity abnormalities.Multimodal MRI and neuropsychological assessments were performed in 102 relapsing remitting multiple sclerosis patients and 27 healthy controls. Patients were considered cognitively impaired if they obtained a z-score of ≤1.5 on ≥2 tests of the Brief Repeatable Battery of Neuropsychological Tests (n=55). Functional connectivity was assessed with Independent Component Analysis of resting state fMRI images, and anatomical connectivity with Anatomical Connectivity Mapping of diffusion-weighted MRI. Exploratory analyses of fractional anisotropy and cerebral blood flow changes were conducted to assess local tissue characteristics.We found significantly decreased functional connectivity in the anterior and posterior default mode networks and significant increases in the right and left frontoparietal networks in cognitively impaired relative to cognitively preserved patients. Networks showing functional abnormalities also showed reduced anatomical connectivity and white matter microstructure integrity as well as reduced local tissue cerebral blood flow.Our results identify key pathological correlates of functional connectivity abnormalities associated with impaired cognitive function in multiple sclerosis, consistent with metabolic dysfunction in functional network regions.

scholarly journals Altered Coupling Between Resting-State Cerebral Blood Flow and Functional Connectivity Strength in Cervical Spondylotic Myelopathy Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Wuzeng Wei ◽  
Tao Wang ◽  
Tuersong Abulizi ◽  
Bing Li ◽  
Jun Liu
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Functional Connectivity ◽  
Resting State ◽  
Cervical Spondylotic Myelopathy ◽  
Cortical Level ◽  
Functional Connectivity Strength ◽  
Visual Cortices ◽  
Connectivity Strength ◽  
Bilateral Thalamus

Background: Changes in regional neural activity and functional connectivity in cervical spondylotic myelopathy (CSM) patients have been reported. However, resting-state cerebral blood flow (CBF) changes and coupling between CBF and functional connectivity in CSM patients are largely unknown.Methods: Twenty-seven CSM patients and 24 sex/age-matched healthy participants underwent resting-state functional MRI and arterial spin labeling imaging to compare functional connectivity strength (FCS) and CBF between the two groups. The CBF–FCS coupling of the whole gray matter and specific regions of interest was also compared between the groups.Results: Compared with healthy individuals, CBF–FCS coupling was significantly lower in CSM patients. The decrease in CBF–FCS coupling in CSM patients was observed in the superior frontal gyrus, bilateral thalamus, and right calcarine cortex, whereas the increase in CBF–FCS coupling was observed in the middle frontal gyrus. Moreover, low CBF and high FCS were observed in sensorimotor cortices and visual cortices, respectively.Conclusion: In general, neurovascular decoupling at cortical level may be a potential neuropathological mechanism of CSM.

scholarly journals Structural and Functional Connectivity Substrates of Cognitive Impairment in Multiple Sclerosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Jian Zhang ◽  
Rosa Cortese ◽  
Nicola De Stefano ◽  
Antonio Giorgio
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Impairment ◽  
Functional Connectivity ◽  
Diffusion Tensor ◽  
Structural Connectivity ◽  
Diffusion Kurtosis Imaging ◽  
High Angular Resolution ◽  
Diffusion Spectrum Imaging ◽  
Analysis Methods ◽  
Scan Time

Cognitive impairment (CI) occurs in 43 to 70% of multiple sclerosis (MS) patients at both early and later disease stages. Cognitive domains typically involved in MS include attention, information processing speed, memory, and executive control. The growing use of advanced magnetic resonance imaging (MRI) techniques is furthering our understanding on the altered structural connectivity (SC) and functional connectivity (FC) substrates of CI in MS. Regarding SC, different diffusion tensor imaging (DTI) measures (e.g., fractional anisotropy, diffusivities) along tractography-derived white matter (WM) tracts showed relevance toward CI. Novel diffusion MRI techniques, including diffusion kurtosis imaging, diffusion spectrum imaging, high angular resolution diffusion imaging, and neurite orientation dispersion and density imaging, showed more pathological specificity compared to the traditional DTI but require longer scan time and mathematical complexities for their interpretation. As for FC, task-based functional MRI (fMRI) has been traditionally used in MS to brain mapping the neural activity during various cognitive tasks. Analysis methods of resting fMRI (seed-based, independent component analysis, graph analysis) have been applied to uncover the functional substrates of CI in MS by revealing adaptive or maladaptive mechanisms of functional reorganization. The relevance for CI in MS of SC–FC relationships, reflecting common pathogenic mechanisms in WM and gray matter, has been recently explored by novel MRI analysis methods. This review summarizes recent advances on MRI techniques of SC and FC and their potential to provide a deeper understanding of the pathological substrates of CI in MS.

scholarly journals Cognitive correlates of cerebellar resting-state functional connectivity in Parkinson disease

Neurology ◽  
2019 ◽  
Vol 94 (4) ◽  
pp. e384-e396 ◽  
Author(s):  
Baijayanta Maiti ◽  
Jonathan M. Koller ◽  
Abraham Z. Snyder ◽  
Aaron B. Tanenbaum ◽  
Scott A. Norris ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Functional Connectivity ◽  
Parkinson Disease ◽  
Resting State ◽  
Cognitive Status ◽  
Association Cortex ◽  
Resting State Functional Connectivity ◽  
Clinical Dementia Rating ◽  
Cross Sectional ◽  
Global Cognition

ObjectiveTo investigate in a cross-sectional study the contributions of altered cerebellar resting-state functional connectivity (FC) to cognitive impairment in Parkinson disease (PD).MethodsWe conducted morphometric and resting-state FC-MRI analyses contrasting 81 participants with PD and 43 age-matched healthy controls using rigorous quality assurance measures. To investigate the relationship of cerebellar FC to cognitive status, we compared participants with PD without cognitive impairment (Clinical Dementia Rating [CDR] scale score 0, n = 47) to participants with PD with impaired cognition (CDR score ≥0.5, n = 34). Comprehensive measures of cognition across the 5 cognitive domains were assessed for behavioral correlations.ResultsThe participants with PD had significantly weaker FC between the vermis and peristriate visual association cortex compared to controls, and the strength of this FC correlated with visuospatial function and global cognition. In contrast, weaker FC between the vermis and dorsolateral prefrontal cortex was found in the cognitively impaired PD group compared to participants with PD without cognitive impairment. This effect correlated with deficits in attention, executive functions, and global cognition. No group differences in cerebellar lobular volumes or regional cortical thickness of the significant cortical clusters were observed.ConclusionThese results demonstrate a correlation between cerebellar vermal FC and cognitive impairment in PD. The absence of significant atrophy in cerebellum or relevant cortical areas suggests that this could be related to local pathophysiology such as neurotransmitter dysfunction.

scholarly journals Altered Coupling Between Resting-State Cerebral Blood Flow and Functional Connectivity in Schizophrenia

2017 ◽  
Vol 43 (6) ◽  
pp. 1363-1374 ◽  
Author(s):  
Jiajia Zhu ◽  
Chuanjun Zhuo ◽  
Lixue Xu ◽  
Feng Liu ◽  
Wen Qin ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Functional Connectivity ◽  
Resting State

scholarly journals Disruptions in Resting State Functional Connectivity and Cerebral Blood Flow in Mild Traumatic Brain Injury Patients

PLoS ONE ◽  
2015 ◽  
Vol 10 (8) ◽  
pp. e0134019 ◽  
Author(s):  
Chandler Sours ◽  
Jiachen Zhuo ◽  
Steven Roys ◽  
Kathirkamanthan Shanmuganathan ◽  
Rao P. Gullapalli
Keyword(s):  
Traumatic Brain Injury ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Brain Injury ◽  
Functional Connectivity ◽  
Mild Traumatic Brain Injury ◽  
Resting State ◽  
Resting State Functional Connectivity

scholarly journals The cerebellum and its network: Disrupted static and dynamic functional connectivity patterns and cognitive impairment in multiple sclerosis

2021 ◽  
pp. 135245852199927
Author(s):  
Menno M Schoonheim ◽  
Linda Douw ◽  
Tommy AA Broeders ◽  
Anand JC Eijlers ◽  
Kim A Meijer ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Impairment ◽  
Functional Connectivity ◽  
Resting State ◽  
Structural Damage ◽  
Grey Matter ◽  
Grey Matter Volume ◽  
Default Mode ◽  
Cerebellar Damage ◽  
The Impact

Background: The impact of cerebellar damage and (dys)function on cognition remains understudied in multiple sclerosis. Objective: To assess the cognitive relevance of cerebellar structural damage and functional connectivity (FC) in relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS). Methods: This study included 149 patients with early RRMS, 81 late RRMS, 48 SPMS and 82 controls. Cerebellar cortical imaging included fractional anisotropy, grey matter volume and resting-state functional magnetic resonance imaging (MRI). Cerebellar FC was assessed with literature-based resting-state networks, using static connectivity (that is, conventional correlations), and dynamic connectivity (that is, fluctuations in FC strength). Measures were compared between groups and related to disability and cognition. Results: Cognitive impairment (CI) and cerebellar damage were worst in SPMS. Only SPMS showed cerebellar connectivity changes, compared to early RRMS and controls. Lower static FC was seen in fronto-parietal and default-mode networks. Higher dynamic FC was seen in dorsal and ventral attention, default-mode and deep grey matter networks. Cerebellar atrophy and higher dynamic FC together explained 32% of disability and 24% of cognitive variance. Higher dynamic FC was related to working and verbal memory and to information processing speed. Conclusion: Cerebellar damage and cerebellar connectivity changes were most prominent in SPMS and related to worse CI.

scholarly journals Reduced dynamics of functional connectivity and cognitive impairment in multiple sclerosis

2019 ◽  
Vol 26 (4) ◽  
pp. 476-488 ◽  
Author(s):  
Alessandro d’Ambrosio ◽  
Paola Valsasina ◽  
Antonio Gallo ◽  
Nicola De Stefano ◽  
Deborah Pareto ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Impairment ◽  
Functional Connectivity ◽  
Network Connectivity ◽  
Brain Network ◽  
Cognitively Impaired ◽  
Healthy Controls ◽  
Correlation Matrices ◽  
Relapsing Remitting ◽  
Frequent Switching

Background: In multiple sclerosis (MS), abnormalities of brain network dynamics and their relevance for cognitive impairment have never been investigated. Objectives: The aim of this study was to assess the dynamic resting state (RS) functional connectivity (FC) on 62 relapsing-remitting MS patients and 65 sex-matched healthy controls enrolled at 7 European sites. Methods: MS patients underwent clinical and cognitive evaluation. Between-group network FC differences were evaluated using a dynamic approach (based on sliding-window correlation analysis) and grouping correlation matrices into recurrent FC states. Results: Dynamic FC analysis revealed, in healthy controls and MS patients, three recurrent FC states: two characterized by strong intra- and inter-network connectivity and one characterized by weak inter-network connectivity (State 3). A total of 23 MS patients were cognitively impaired (CI). Compared to cognitively preserved (CP), CI-MS patients had reduced RS-FC between subcortical and default-mode networks in the low-connectivity State 3 and lower dwell time (i.e. time spent in a given state) in the high-connectivity State 2. CI-MS patients also exhibited a lower number and a less frequent switching between meta-states, as well as a smaller distance traveled through connectivity states. Conclusion: Time-varying RS-FC was markedly less dynamic in CI- versus CP-MS patients, suggesting that slow inter-network connectivity contributes to cognitive dysfunction in MS.

Sign in / Sign up

Export Citation Format

Share Document