Distributed causality in resting-state network connectivity in the acute and remitting phases of RRMS

Abstract Background: Although previous studies have shown that intranetwork abnormalities in brain functional networks are correlated with clinical/cognitive impairment in multiple sclerosis (MS), there is little information regarding the pattern of causal interactions among cognition-related resting-state networks (RSNs) in different disease stages of relapsing-remitting MS (RRMS) patients. We hypothesized that abnormalities of causal interactions among RSNs occurred in RRMS patients in the acute and remitting phases.Patients and methods: Seventeen patients in the acute phases of RRMS, 24 patients in the remitting phases of RRMS, and 23 appropriately matched healthy controls participated in this study. First, we used group independent component analysis to extract the time courses of the spatially independent components from all the subjects. Then, the Granger causality test was used to investigate the causal relationships among RSNs in the spectral domain and to identify correlations with clinical indices . Results: Compared with the patients in the acute phase of RRMS, patients in the remitting phase of RRMS showed a significantly lower expanded disability status scale, modified fatigue impact scale scores, and significantly higher paced auditory serial addition test (PASAT) scores. Compared with healthy subjects, during the acute phase, RRMS patients had significantly increased driving connectivity from the right executive control network (rECN) to the anterior salience network (aSN), and the causal coefficient was negatively correlated with the PASAT score. During the remitting phase, RRMS patients had significantly increased driving connectivity from the rECN to the aSN and from the rECN to the visuospatial network. Conclusion: Together with the disease duration (mean disease duration < 5 years) and relatively better clinical scores than those in the acute phase, abnormal connections, such as the information flow from the rECN to the aSN and the rECN to the visuospatial network, might provide adaptive compensation in the remitting phase of RRMS.

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Distributed causality in resting-state network connectivity in the acute and remitting phases of RRMS

10.21203/rs.3.rs-18415/v1 ◽

2020 ◽

Author(s):

Lin Wu ◽

Muhua Huang ◽

Fuqing Zhou ◽

Xianjun Zeng ◽

Honghan Gong

Keyword(s):

Acute Phase ◽

Resting State ◽

Disease Duration ◽

Network Connectivity ◽

Causality Test ◽

Impact Scale ◽

Scale Scores ◽

Time Courses ◽

Serial Addition ◽

The Right

Abstract Background Although previous studies have shown that intranetwork abnormalities in brain functional networks are correlated with clinical/cognitive impairment in multiple sclerosis (MS), there is little information regarding the pattern of causal interactions among cognition-related resting-state networks (RSNs) in different disease stages of relapsing-remitting MS (RRMS) patients. We hypothesized that abnormalities of causal interactions among RSNs occurred in RRMS patients in the acute and remitting phases. Patients and methods: Seventeen patients in the acute phases of RRMS, 24 patients in the remitting phases of RRMS, and 23 appropriately matched healthy controls participated in this study. First, we first used group independent component analysis to extract the time courses of the spatially independent components from all the subjects. Then, the Granger causality test was used to investigate the causal relationships among RSNs in the spectral domain and to identify correlations with clinical indexes. Results Compared with the patients in the acute phase of RRMS, patients in the remitting phase of RRMS showed a significantly lower expanded disability status scale, modified fatigue impact scale scores, and significantly higher paced auditory serial addition test (PASAT) scores. Compared with healthy subjects, during the acute phase, RRMS patients had significantly increased driving connectivity from the right executive control network (rECN) to the anterior salience network (aSN), and the causal coefficient was negatively correlated with the PASAT score. During the remitting phase, RRMS patients had significantly increased driving connectivity from the rECN to the aSN and from the rECN to the visuospatial network. Conclusion Together with the disease duration (mean disease duration < 5 years) and relatively better clinical scores than those in the acute phase, abnormal connections, such as the information flow from the rECN to the aSN and the rECN to the visuospatial network, might provide adaptive compensation in the remitting phase of RRMS.

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Distributed causality in resting-state network connectivity in the acute and remitting phases of RRMS

BMC Neuroscience ◽

10.1186/s12868-020-00590-4 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Lin Wu ◽

Muhua Huang ◽

Fuqing Zhou ◽

Xianjun Zeng ◽

Honghan Gong

Keyword(s):

Acute Phase ◽

Resting State ◽

Disease Duration ◽

Network Connectivity ◽

Causality Analysis ◽

Impact Scale ◽

Scale Scores ◽

Time Courses ◽

Serial Addition ◽

The Right

Abstract Background Although previous studies have shown that intra-network abnormalities in brain functional networks are correlated with clinical/cognitive impairment in multiple sclerosis (MS), there is little information regarding the pattern of causal interactions among cognition-related resting-state networks (RSNs) in different disease stages of relapsing–remitting MS (RRMS) patients. We hypothesized that abnormalities of causal interactions among RSNs occurred in RRMS patients in the acute and remitting phases. Methods Seventeen patients in the acute phases of RRMS, 24 patients in the remitting phases of RRMS, and 23 appropriately matched healthy controls participated in this study. First, we used group independent component analysis to extract the time courses of the spatially independent components from all the subjects. Then, the Granger causality analysis was used to investigate the causal relationships among RSNs in the spectral domain and to identify correlations with clinical indices. Results Compared with the patients in the acute phase of RRMS, patients in the remitting phase of RRMS showed a significantly lower expanded disability status scale, modified fatigue impact scale scores, and significantly higher paced auditory serial addition test (PASAT) scores. Compared with healthy subjects, during the acute phase, RRMS patients had significantly increased driving connectivity from the right executive control network (rECN) to the anterior salience network (aSN), and the causal coefficient was negatively correlated with the PASAT score. During the remitting phase, RRMS patients had significantly increased driving connectivity from the rECN to the aSN and from the rECN to the visuospatial network. Conclusions Together with the disease duration (mean disease duration < 5 years) and relatively better clinical scores than those in the acute phase, abnormal connections, such as the information flow from the rECN to the aSN and the rECN to the visuospatial network, might provide adaptive compensation in the remitting phase of RRMS.

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Distributed causality in resting-state network connectivity in the acute and remitting phases of RRMS

10.21203/rs.3.rs-18415/v3 ◽

2020 ◽

Author(s):

Lin Wu ◽

Muhua Huang ◽

Fuqing Zhou ◽

Xianjun Zeng ◽

Honghan Gong

Keyword(s):

Acute Phase ◽

Resting State ◽

Disease Duration ◽

Network Connectivity ◽

Causality Analysis ◽

Impact Scale ◽

Scale Scores ◽

Time Courses ◽

Serial Addition ◽

The Right

Abstract Background: Although previous studies have shown that intra-network abnormalities in brain functional networks are correlated with clinical/cognitive impairment in multiple sclerosis (MS), there is little information regarding the pattern of causal interactions among cognition-related resting-state networks (RSNs) in different disease stages of relapsing-remitting MS (RRMS) patients. We hypothesized that abnormalities of causal interactions among RSNs occurred in RRMS patients in the acute and remitting phases.Patients and methods: Seventeen patients in the acute phases of RRMS, 24 patients in the remitting phases of RRMS, and 23 appropriately matched healthy controls participated in this study. First, we used group independent component analysis to extract the time courses of the spatially independent components from all the subjects. Then, the Granger causality analysis was used to investigate the causal relationships among RSNs in the spectral domain and to identify correlations with clinical indices. Results: Compared with the patients in the acute phase of RRMS, patients in the remitting phase of RRMS showed a significantly lower expanded disability status scale, modified fatigue impact scale scores, and significantly higher paced auditory serial addition test (PASAT) scores. Compared with healthy subjects, during the acute phase, RRMS patients had significantly increased driving connectivity from the right executive control network (rECN) to the anterior salience network (aSN), and the causal coefficient was negatively correlated with the PASAT score. During the remitting phase, RRMS patients had significantly increased driving connectivity from the rECN to the aSN and from the rECN to the visuospatial network. Conclusion: Together with the disease duration (mean disease duration < 5 years) and relatively better clinical scores than those in the acute phase, abnormal connections, such as the information flow from the rECN to the aSN and the rECN to the visuospatial network, might provide adaptive compensation in the remitting phase of RRMS.

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Distributed causality in resting-state network connectivity in the acute and remitting phases of RRMS

10.21203/rs.3.rs-18415/v4 ◽

2020 ◽

Author(s):

Lin Wu ◽

Muhua Huang ◽

Fuqing Zhou ◽

Xianjun Zeng ◽

Honghan Gong

Keyword(s):

Acute Phase ◽

Resting State ◽

Disease Duration ◽

Network Connectivity ◽

Causality Analysis ◽

Impact Scale ◽

Scale Scores ◽

Time Courses ◽

Serial Addition ◽

The Right

Abstract Background: Although previous studies have shown that intra-network abnormalities in brain functional networks are correlated with clinical/cognitive impairment in multiple sclerosis (MS), there is little information regarding the pattern of causal interactions among cognition-related resting-state networks (RSNs) in different disease stages of relapsing-remitting MS (RRMS) patients. We hypothesized that abnormalities of causal interactions among RSNs occurred in RRMS patients in the acute and remitting phases.Methods: Seventeen patients in the acute phases of RRMS, 24 patients in the remitting phases of RRMS, and 23 appropriately matched healthy controls participated in this study. First, we used group independent component analysis to extract the time courses of the spatially independent components from all the subjects. Then, the Granger causality analysis was used to investigate the causal relationships among RSNs in the spectral domain and to identify correlations with clinical indices. Results: Compared with the patients in the acute phase of RRMS, patients in the remitting phase of RRMS showed a significantly lower expanded disability status scale, modified fatigue impact scale scores, and significantly higher paced auditory serial addition test (PASAT) scores. Compared with healthy subjects, during the acute phase, RRMS patients had significantly increased driving connectivity from the right executive control network (rECN) to the anterior salience network (aSN), and the causal coefficient was negatively correlated with the PASAT score. During the remitting phase, RRMS patients had significantly increased driving connectivity from the rECN to the aSN and from the rECN to the visuospatial network. Conclusions: Together with the disease duration (mean disease duration < 5 years) and relatively better clinical scores than those in the acute phase, abnormal connections, such as the information flow from the rECN to the aSN and the rECN to the visuospatial network, might provide adaptive compensation in the remitting phase of RRMS.

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Impaired intrinsic functional connectivity between the thalamus and visual cortex in migraine without aura

The Journal of Headache and Pain ◽

10.1186/s10194-019-1065-1 ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 6

Author(s):

Heng-Le Wei ◽

Xin Zhou ◽

Yu-Chen Chen ◽

Yu-Sheng Yu ◽

Xi Guo ◽

...

Keyword(s):

Functional Connectivity ◽

Resting State ◽

Migraine Without Aura ◽

Network Connectivity ◽

Resting State Fmri ◽

Neural Activation ◽

Scale Scores ◽

The Right ◽

Complex Scenario ◽

Visual Network

Abstract Background Resting-state functional magnetic resonance imaging (fMRI) has confirmed disrupted visual network connectivity in migraine without aura (MwoA). The thalamus plays a pivotal role in a number of pain conditions, including migraine. However, the significance of altered thalamo-visual functional connectivity (FC) in migraine remains unknown. The goal of this study was to explore thalamo-visual FC integrity in patients with MwoA and investigate its clinical significance. Methods Resting-state fMRI data were acquired from 33 patients with MwoA and 22 well-matched healthy controls. After identifying the visual network by independent component analysis, we compared neural activation in the visual network and thalamo-visual FC and assessed whether these changes were linked to clinical characteristics. We used voxel-based morphometry to determine whether functional differences were dependent on structural differences. Results The visual network exhibited significant differences in regions (bilateral cunei, right lingual gyrus and left calcarine sulcus) by inter-group comparison. The patients with MwoA showed significantly increased FC between the left thalami and bilateral cunei and between the right thalamus and the contralateral calcarine sulcus and right cuneus. Furthermore, the neural activation of the left calcarine sulcus was positively correlated with visual analogue scale scores (r = 0.319, p = 0.043), and enhanced FC between the left thalamus and right cuneus in migraine patients was negatively correlated with Generalized Anxiety Disorder scores (r = − 0.617, p = 0.005). Conclusion Our data suggest that migraine distress is exacerbated by aberrant feedback projections to the visual network, playing a crucial role in migraine physiological mechanisms. The current study provides further insights into the complex scenario of migraine mechanisms.

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Resting-state neural network disturbances that underpin the emergence of emotional symptoms in adolescent girls: resting-state fMRI study

The British Journal of Psychiatry ◽

10.1192/bjp.2019.10 ◽

2019 ◽

Vol 215 (3) ◽

pp. 545-551 ◽

Cited By ~ 3

Author(s):

Gin S. Malhi ◽

Pritha Das ◽

Tim Outhred ◽

Richard A. Bryant ◽

Vince Calhoun

Keyword(s):

Emotional Disorders ◽

Adolescent Girls ◽

Resting State ◽

Early Adulthood ◽

Network Connectivity ◽

Resting State Fmri ◽

Imaging Data ◽

Emotional Symptoms ◽

Fmri Study ◽

The Right

BackgroundSubsyndromal emotional symptoms in adolescence may represent precursors for full-blown emotional disorders in early adulthood. Understanding the neurobiological mechanisms that drive this development is essential for prevention.AimsSelf-referential processing and emotion regulation are remodelled substantively during adolescence, therefore this study examined integration of key neural networks involved in these processes.MethodAt baseline, clinical and resting-state functional magnetic resonance imaging data were collected for 88 adolescent girls (mean age 15 years), and 71 of these girls underwent repeat clinical assessment after 2 years. These 71 girls were then partitioned into two groups depending on the presence (ES+) or absence (ES−) of emotional symptoms, and differences in dynamic functional network connectivity were determined and correlated with clinical variables.ResultsThe two groups displayed a differential pattern of functional connectivity involving the left lateral prefrontal network (LPFN). Specifically, in the ES+ group this network displayed positive coupling with the right LPFN but negative coupling with the default mode network, and the inverse of this pattern was found in the ES− group. Furthermore, the coupling strengths between left and right LPFN at the irst time point predicted follow-up depression and state anxiety scores.ConclusionsOur findings suggest that in adolescent girls, emotional symptoms may emerge as a result of impaired integration between networks involved in self-referential information processing and approach-avoidance behaviours. These impairments can compromise the pursuit of important goals and have an impact on emotion processing and finally may lead to the development of emotional disorders, such as anxiety and depression in adulthood.Declaration of interestNone.

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White-Matter Hyperintensity Load and Differences in Resting-State Network Connectivity Based on Mild Cognitive Impairment Subtype

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.737359 ◽

2021 ◽

Vol 13 ◽

Author(s):

Martina Vettore ◽

Matteo De Marco ◽

Claudia Pallucca ◽

Matteo Bendini ◽

Maurizio Gallucci ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

White Matter ◽

Resting State ◽

Large Scale ◽

Network Connectivity ◽

Functional Networks ◽

Frontoparietal Network ◽

Definition Of ◽

The Right

“Mild cognitive impairment” (MCI) is a diagnosis characterised by deficits in episodic memory (aMCI) or in other non-memory domains (naMCI). Although the definition of subtypes is helpful in clinical classification, it provides little insight on the variability of neurofunctional mechanisms (i.e., resting-state brain networks) at the basis of symptoms. In particular, it is unknown whether the presence of a high load of white-matter hyperintensities (WMHs) has a comparable effect on these functional networks in aMCI and naMCI patients. This question was addressed in a cohort of 123 MCI patients who had completed an MRI protocol inclusive of T1-weighted, fluid-attenuated inversion recovery (FLAIR) and resting-state fMRI sequences. T1-weighted and FLAIR images were processed with the Lesion Segmentation Toolbox to quantify whole-brain WMH volumes. The CONN toolbox was used to preprocess all fMRI images and to run an independent component analysis for the identification of four large-scale haemodynamic networks of cognitive relevance (i.e., default-mode, salience, left frontoparietal, and right frontoparietal networks) and one control network (i.e., visual network). Patients were classified based on MCI subtype (i.e., aMCI vs. naMCI) and WMH burden (i.e., low vs. high). Maps of large-scale networks were then modelled as a function of the MCI subtype-by-WMH burden interaction. Beyond the main effects of MCI subtype and WMH burden, a significant interaction was found in the salience and left frontoparietal networks. Having a low WMH burden was significantly more associated with stronger salience-network connectivity in aMCI (than in naMCI) in the right insula, and with stronger left frontoparietal-network connectivity in the right frontoinsular cortex. Vice versa, having a low WMH burden was significantly more associated with left-frontoparietal network connectivity in naMCI (than in aMCI) in the left mediotemporal lobe. The association between WMH burden and strength of connectivity of resting-state functional networks differs between aMCI and naMCI patients. Although exploratory in nature, these findings indicate that clinical profiles reflect mechanistic interactions that may play a central role in the definition of diagnostic and prognostic statuses.

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Altered thalamic connectivity during spontaneous attacks of migraine without aura: A resting-state fMRI study

Cephalalgia ◽

10.1177/0333102417729113 ◽

2017 ◽

Vol 38 (7) ◽

pp. 1237-1244 ◽

Cited By ~ 22

Author(s):

Faisal Mohammad Amin ◽

Anders Hougaard ◽

Stefano Magon ◽

Till Sprenger ◽

Frauke Wolfram ◽

...

Keyword(s):

Functional Connectivity ◽

Resting State ◽

Migraine Without Aura ◽

Primary Motor Cortex ◽

Premotor Cortex ◽

Network Connectivity ◽

Insular Cortex ◽

Resting State Fmri ◽

Brain Regions ◽

The Right

Background Functional connectivity of brain networks may be altered in migraine without aura patients. Functional magnetic resonance imaging (fMRI) studies have demonstrated changed activity in the thalamus, pons and cerebellum in migraineurs. Here, we investigated the thalamic, pontine and cerebellar network connectivity during spontaneous migraine attacks. Methods Seventeen patients with episodic migraine without aura underwent resting-state fMRI scan during and outside of a spontaneous migraine attack. Primary endpoint was a difference in functional connectivity between the attack and the headache-free days. Functional connectivity was assessed in four different networks using seed-based analysis. The chosen seeds were in the thalamus (MNI coordinates x,y,z: right, 22,–24,0 and left, –22,–28,6), pons (right, 8,–24,–32 and left, –8,–24,–32), cerebellum crus I (right, 46,–58,–30 and left, –46,–58,–30) and cerebellum lobule VI (right, 34,–42,–36 and left, –32,–42,–36). Results We found increased functional connectivity between the right thalamus and several contralateral brain regions (superior parietal lobule, insular cortex, primary motor cortex, supplementary motor area and orbitofrontal cortex). There was decreased functional connectivity between the right thalamus and three ipsilateral brain areas (primary somatosensory cortex and premotor cortex). We found no change in functional connectivity in the pontine or the cerebellar networks. Conclusions The study indicates that network connectivity between thalamus and pain modulating as well as pain encoding cortical areas are affected during spontaneous migraine attacks.

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Reduced resting-state brain functional network connectivity and poor regional homogeneity in patients with CADASIL

The Journal of Headache and Pain ◽

10.1186/s10194-019-1052-6 ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 1

Author(s):

Jingjing Su ◽

Shiyu Ban ◽

Mengxing Wang ◽

Fengchun Hua ◽

Liang Wang ◽

...

Keyword(s):

Resting State ◽

Network Connectivity ◽

Functional Network ◽

Precentral Gyrus ◽

Functional Network Connectivity ◽

Brain Functional Network ◽

Z Scores ◽

The Mean ◽

The Right ◽

Local Brain

Abstract Background Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) manifests principally as a suite of cognitive impairments, particularly in the executive domain. Executive functioning requires the dynamic coordination of neural activity over large-scale networks. It remains unclear whether changes in resting-state brain functional network connectivity and regional homogeneities (ReHos) underly the mechanisms of executive dysfunction evident in CADASIL patients. Methods In this study, 22 CADASIL patients and 44 matched healthy controls underwent resting-state functional magnetic resonance imaging (fMRI). Independent component analysis (ICA) was used to measure functional brain network connectivity, and ReHos were calculated to evaluate local brain activities. We used seed-based functional connectivity (FC) analyses to determine whether dysfunctional areas (as defined by ReHos) exhibited abnormal FC with other brain areas. Relationships among the mean intra-network connectivity z-scores of dysfunctional areas within functional networks, and cognitive scores were evaluated using Pearson correlation analyses. Results Compared to the controls, CADASIL patients exhibited decreased intra-network connectivity within the bilateral lingual gyrus (LG) and the right cuneus (CU) (thus within the visual network [VIN)], and within the right precuneus (Pcu), inferior frontal gyrus (IFG), and precentral gyrus (thus within the frontal network [FRN]). Compared to the controls, patients also exhibited significantly lower ReHos in the right precuneus and cuneus (Pcu/CU), visual association cortex, calcarine gyri, posterior cingulate, limbic lobe, and weaker FC between the right Pcu/CU and the bilateral parahippocampal gyrus (PHG), and between the right Pcu/CU and the right postcentral gyrus. Notably, the mean connectivity z-scores of the bilateral LG and the right CU within the VIN were positively associated with compromised attention, calculation and delayed recall as revealed by tests of the various cognitive domains explored by the Mini-Mental State Examination. Conclusions The decreases in intra-network connectivity within the VIN and FRN and reduced local brain activity in the posterior parietal area suggest that patients with CADASIL may exhibit dysfunctional visuomotor behaviors (a hallmark of executive function), and that all visual information processing, visuomotor planning, and movement execution may be affected.

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Shared Characteristics of Intrinsic Connectivity Networks Underlying Interoceptive Awareness and Empathy

10.1101/2020.04.30.070490 ◽

2020 ◽

Author(s):

T. Stoica ◽

B.E. Depue

Keyword(s):

Resting State ◽

Network Connectivity ◽

Brain Regions ◽

Cognitive Empathy ◽

Autism Spectrum ◽

Neural Basis ◽

Strong Connectivity ◽

Increased Sensitivity ◽

Intrinsic Connectivity Networks ◽

The Right

AbstractAwareness of internal bodily sensations (interoception, IA) and its connection to complex socioemotional phenomena like empathy have been postulated, yet its neural basis remains poorly understood. The present fMRI study employs independent component analysis (ICA) to investigate whether the Cognitive or Affective facets of empathy and IA share resting state network connectivity and/or variability (SDBOLD). Healthy participants viewed an abstract movie demonstrated to evoke strong connectivity in resting state brain networks (InScapes), and resultant connectivity and variability data was correlated with self-reported empathy and IA questionnaires. We demonstrate a bidirectional behavioral and neurobiological relationship between empathy and IA, depending on the type of empathy interrogated: Affective empathy and IA share both connectivity and variability, while Cognitive empathy and IA only share variability. Specifically, increased connectivity in the right inferior frontal operculum (rIFO) of a larger attention network was associated with increased vicarious experience but decreased awareness of inner body sensations. Furthermore, increased variability between brain regions of an interoceptive network was related to increased sensitivity to internal sensations along with discomfort alleviation arising from witnessing another’s distress. Finally, increased variability between brain regions subserving a mentalizing network related to not only an improved ability to take someone’s perspective, but also a better sense of mind-body interconnectedness. Overall, these findings suggest that the awareness of one’s own internal body changes (IA) is related to the ability to feel and understand another’s emotional state (empathy) and critically, that this relationship is not task-dependent, but is reflected in the brain’s resting state neuroarchitecture. Methodologically, this work highlights the importance of utilizing network variability as a complementary window alongside functional connectivity to better understand neurological phenomena. Our results may be beneficial in aiding diagnosis in clinical populations such as autism spectrum disorder, where participants may be unable to complete tasks or questionnaires due to the severity of their socioemotional symptoms.

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