scholarly journals Long-range connections are more severely damaged and relevant for cognition in multiple sclerosis

Brain ◽  
2019 ◽  
Vol 143 (1) ◽  
pp. 150-160 ◽  
Author(s):  
Kim A Meijer ◽  
Martijn D Steenwijk ◽  
Linda Douw ◽  
Menno M Schoonheim ◽  
Jeroen J G Geurts
Keyword(s):  
Multiple Sclerosis ◽  
Functional Connectivity ◽  
Fractional Anisotropy ◽  
Long Range ◽  
Short Range ◽  
Brain Regions ◽  
Healthy Controls ◽  
Network Efficiency ◽  
Structural Network ◽  
The Impact

Abstract An efficient network such as the human brain features a combination of global integration of information, driven by long-range connections, and local processing involving short-range connections. Whether these connections are equally damaged in multiple sclerosis is unknown, as is their relevance for cognitive impairment and brain function. Therefore, we cross-sectionally investigated the association between damage to short- and long-range connections with structural network efficiency, the functional connectome and cognition. From the Amsterdam multiple sclerosis cohort, 133 patients (age = 54.2 ± 9.6) with long-standing multiple sclerosis and 48 healthy controls (age = 50.8 ± 7.0) with neuropsychological testing and MRI were included. Structural connectivity was estimated from diffusion tensor images using probabilistic tractography (MRtrix 3.0) between pairs of brain regions. Structural connections were divided into short- (length < quartile 1) and long-range (length > quartile 3) connections, based on the mean distribution of tract lengths in healthy controls. To determine the severity of damage within these connections, (i) fractional anisotropy as a measure for integrity; (ii) total number of fibres; and (iii) percentage of tract affected by lesions were computed for each connecting tract and averaged for short- and long-range connections separately. To investigate the impact of damage in these connections for structural network efficiency, global efficiency was computed. Additionally, resting-state functional connectivity was computed between each pair of brain regions, after artefact removal with FMRIB’s ICA-based X-noiseifier. The functional connectivity similarity index was computed by correlating individual functional connectivity matrices with an average healthy control connectivity matrix. Our results showed that the structural network had a reduced efficiency and integrity in multiple sclerosis relative to healthy controls (both P < 0.05). The long-range connections showed the largest reduction in fractional anisotropy (z = −1.03, P < 0.001) and total number of fibres (z = −0.44, P < 0.01), whereas in the short-range connections only fractional anisotropy was affected (z = −0.34, P = 0.03). Long-range connections also demonstrated a higher percentage of tract affected by lesions than short-range connections, independent of tract length (P < 0.001). Damage to long-range connections was more strongly related to structural network efficiency and cognition (fractional anisotropy: r = 0.329 and r = 0.447. number of fibres r = 0.321 and r = 0.278. and percentage of lesions: r = −0.219; r = −0.426, respectively) than damage to short-range connections. Only damage to long-distance connections correlated with a more abnormal functional network (fractional anisotropy: r = 0.226). Our findings indicate that long-range connections are more severely affected by multiple sclerosis-specific damage than short-range connections. Moreover compared to short-range connections, damage to long-range connections better explains network efficiency and cognition.

Depletion of brain functional connectivity enhancement leads to disability progression in multiple sclerosis: A longitudinal resting-state fMRI study

2016 ◽  
Vol 22 (13) ◽  
pp. 1695-1708 ◽  
Author(s):  
Anthony Faivre ◽  
Emmanuelle Robinet ◽  
Maxime Guye ◽  
Celia Rousseau ◽  
Adil Maarouf ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Functional Connectivity ◽  
Long Range ◽  
Resting State ◽  
Short Range ◽  
Resting State Fmri ◽  
Disability Progression ◽  
Fmri Study ◽  
Brain Functional Connectivity

Background: The compensatory effect of brain functional connectivity enhancement in relapsing-remitting multiple sclerosis (RRMS) remains controversial. Objective: To characterize the relationships between brain functional connectivity changes and disability progression in RRMS. Methods: Long-range connectivity, short-range connectivity, and density of connections were assessed using graph theoretical analysis of resting-state functional magnetic resonance imaging (fMRI) data acquired in 38 RRMS patients (disease duration: 120 ± 32 months) and 24 controls. All subjects were explored at baseline and all patients and six controls 2 years later. Results: At baseline, levels of long-range and short-range brain functional connectivity were higher in patients compared to controls. During the follow-up, decrease in connections’ density was inversely correlated with disability progression. Post-hoc analysis evidenced differential evolution of brain functional connectivity metrics in patients according to their level of disability at baseline: while patients with lowest disability at baseline experienced an increase in all connectivity metrics during the follow-up, patients with higher disability at baseline showed a decrease in the connectivity metrics. In these patients, decrease in the connectivity metrics was associated with disability progression. Conclusion: The study provides two main findings: (1) brain functional connectivity enhancement decreases during the disease course after reaching a maximal level, and (2) decrease in brain functional connectivity enhancement participates in disability progression.

scholarly journals Retrospective analysis of hemispheric structural network change as a function of location and size of glioma

2020 ◽  
Author(s):  
Shawn D’Souza ◽  
Lisa Hirt ◽  
David R Ormond ◽  
John A Thompson
Keyword(s):  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Temporal Lobe ◽  
Diffusion Tensor ◽  
Brain Regions ◽  
Structural Network ◽  
Tumour Location ◽  
The Impact ◽  
Tractography Data ◽  
Diffusion Tensor Imaging Tractography

Abstract Gliomas are neoplasms that arise from glial cell origin and represent the largest fraction of primary malignant brain tumours (77%). These highly infiltrative malignant cell clusters modify brain structure and function through expansion, invasion and intratumoral modification. Depending on the growth rate of the tumour, location and degree of expansion, functional reorganization may not lead to overt changes in behaviour despite significant cerebral adaptation. Studies in simulated lesion models and in patients with stroke reveal both local and distal functional disturbances, using measures of anatomical brain networks. Investigations over the last two decades have sought to use diffusion tensor imaging tractography data in the context of intracranial tumours to improve surgical planning, intraoperative functional localization, and post-operative interpretation of functional change. In this study, we used diffusion tensor imaging tractography to assess the impact of tumour location on the white matter structural network. To better understand how various lobe localized gliomas impact the topology underlying efficiency of information transfer between brain regions, we identified the major alterations in brain network connectivity patterns between the ipsilesional versus contralesional hemispheres in patients with gliomas localized to the frontal, parietal or temporal lobe. Results were indicative of altered network efficiency and the role of specific brain regions unique to different lobe localized gliomas. This work draws attention to connections and brain regions which have shared structural susceptibility in frontal, parietal and temporal lobe glioma cases. This study also provides a preliminary anatomical basis for understanding which affected white matter pathways may contribute to preoperative patient symptomology.

scholarly journals Altered Long- and Short-Range Functional Connectivity in Patients with Betel Quid Dependence: A Resting-State Functional MRI Study

2016 ◽  
Vol 40 (6) ◽  
pp. 1626-1636 ◽  
Author(s):  
Tao Liu ◽  
Jianjun Li ◽  
Zhiqiang Zhang ◽  
Qiang Xu ◽  
Guangming Lu ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Long Range ◽  
Short Range ◽  
Anterior Cingulate ◽  
Betel Quid ◽  
Posterior Lobe ◽  
Functional Connectivity Density ◽  
Dorsolateral Prefrontal ◽  
The Right ◽  
Mri Study

Objective: Addiction is a chronic relapsing brain disease. Brain structural abnormalities may constitute an abnormal neural network that underlies the risk of drug dependence. We hypothesized that individuals with Betel Quid Dependence (BQD) have functional connectivity alterations that can be described by long- and short-range functional connectivity density(FCD) maps. Methods: We tested this hypothesis using functional magnetic resonance imaging (fMRI) data from subjects of the Han ethnic group in Hainan, China. Here, we examined BQD individuals (n = 33) and age-, sex-, and education-matched healthy controls (HCs) (n = 32) in a rs-fMRI study to observe FCD alterations associated with the severity of BQD. Results: Compared with HCs, long-range FCD was decreased in the right anterior cingulate cortex (ACC) and increased in the left cerebellum posterior lobe (CPL) and bilateral inferior parietal lobule (IPL) in the BQD group. Short-range FCD was reduced in the right ACC and left dorsolateral prefrontal cortex (dlPFC), and increased in the left CPL. The short-range FCD alteration in the right ACC displayed a negative correlation with the Betel Quid Dependence Scale (BQDS) (r=-0.432, P=0.012), and the long-range FCD alteration of left IPL showed a positive correlation with the duration of BQD(r=0.519, P=0.002) in BQD individuals. Conclusions: fMRI revealed differences in long- and short- range FCD in BQD individuals, and these alterations might be due to BQ chewing, BQ dependency, or risk factors for developing BQD.

In vivo gradients of thalamic damage in paediatric multiple sclerosis: a window into pathology

Brain ◽  
2020 ◽  
Author(s):  
Ermelinda De Meo ◽  
Loredana Storelli ◽  
Lucia Moiola ◽  
Angelo Ghezzi ◽  
Pierangelo Veggiotti ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Magnetic Resonance ◽  
Fractional Anisotropy ◽  
Mean Diffusivity ◽  
White Matter Lesions ◽  
Healthy Controls ◽  
Paediatric Multiple Sclerosis ◽  
Multiple Sclerosis Patients

Abstract The thalamus represents one of the first structures affected by neurodegenerative processes in multiple sclerosis. A greater thalamic volume reduction over time, on its CSF side, has been described in paediatric multiple sclerosis patients. However, its determinants and the underlying pathological changes, likely occurring before this phenomenon becomes measurable, have never been explored. Using a multiparametric magnetic resonance approach, we quantified, in vivo, the different processes that can involve the thalamus in terms of focal lesions, microstructural damage and atrophy in paediatric multiple sclerosis patients and their distribution according to the distance from CSF/thalamus interface and thalamus/white matter interface. In 70 paediatric multiple sclerosis patients and 26 age- and sex-matched healthy controls, we tested for differences in thalamic volume and quantitative MRI metrics—including fractional anisotropy, mean diffusivity and T1/T2-weighted ratio—in the whole thalamus and in thalamic white matter, globally and within concentric bands originating from CSF/thalamus interface. In paediatric multiple sclerosis patients, the relationship of thalamic abnormalities with cortical thickness and white matter lesions was also investigated. Compared to healthy controls, patients had significantly increased fractional anisotropy in whole thalamus (f2 = 0.145; P = 0.03), reduced fractional anisotropy (f2 = 0.219; P = 0.006) and increased mean diffusivity (f2 = 0.178; P = 0.009) in thalamic white matter and a trend towards a reduced thalamic volume (f2 = 0.027; P = 0.058). By segmenting the whole thalamus and thalamic white matter into concentric bands, in paediatric multiple sclerosis we detected significant fractional anisotropy abnormalities in bands nearest to CSF (f2 = 0.208; P = 0.002) and in those closest to white matter (f2 range = 0.183–0.369; P range = 0.010–0.046), while we found significant mean diffusivity (f2 range = 0.101–0.369; P range = 0.018–0.042) and T1/T2-weighted ratio (f2 = 0.773; P = 0.001) abnormalities in thalamic bands closest to CSF. The increase in fractional anisotropy and decrease in mean diffusivity detected at the CSF/thalamus interface correlated with cortical thickness reduction (r range = −0.27–0.34; P range = 0.004–0.028), whereas the increase in fractional anisotropy detected at the thalamus/white matter interface correlated with white matter lesion volumes (r range = 0.24–0.27; P range = 0.006–0.050). Globally, our results support the hypothesis of heterogeneous pathological processes, including retrograde degeneration from white matter lesions and CSF-mediated damage, leading to thalamic microstructural abnormalities, likely preceding macroscopic tissue loss. Assessing thalamic microstructural changes using a multiparametric magnetic resonance approach may represent a target to monitor the efficacy of neuroprotective strategies early in the disease course.

Discriminative Analysis of Symptom Severity and Ultra-High Risk of Schizophrenia Using Intrinsic Functional Connectivity

2020 ◽  
Vol 30 (09) ◽  
pp. 2050047
Author(s):  
Lubin Wang ◽  
Xianbin Li ◽  
Yuyang Zhu ◽  
Bei Lin ◽  
Qijing Bo ◽  
...  
Keyword(s):  
High Risk ◽  
Functional Connectivity ◽  
Symptom Severity ◽  
Large Scale ◽  
Brain Networks ◽  
Brain Regions ◽  
Support Vector ◽  
Healthy Controls ◽  
Intrinsic Functional Connectivity ◽  
Ultra High Risk

Past studies have consistently shown functional dysconnectivity of large-scale brain networks in schizophrenia. In this study, we aimed to further assess whether multivariate pattern analysis (MVPA) could yield a sensitive predictor of patient symptoms, as well as identify ultra-high risk (UHR) stage of schizophrenia from intrinsic functional connectivity of whole-brain networks. We first combined rank-based feature selection and support vector machine methods to distinguish between 43 schizophrenia patients and 52 healthy controls. The constructed classifier was then applied to examine functional connectivity profiles of 18 UHR individuals. The classifier indicated reliable relationship between MVPA measures and symptom severity, with higher classification accuracy in more severely affected schizophrenia patients. The UHR subjects had classification scores falling between those of healthy controls and patients, suggesting an intermediate level of functional brain abnormalities. Moreover, UHR individuals with schizophrenia-like connectivity profiles at baseline presented higher rate of conversion to full-blown illness in the follow-up visits. Spatial maps of discriminative brain regions implicated increases of functional connectivity in the default mode network, whereas decreases of functional connectivity in the cerebellum, thalamus and visual areas in schizophrenia. The findings may have potential utility in the early diagnosis and intervention of schizophrenia.

Mapping white matter damage distribution in neuromyelitis optica spectrum disorders with a multimodal MRI approach

2020 ◽  
pp. 135245852094149
Author(s):  
Laura Cacciaguerra ◽  
Maria A Rocca ◽  
Loredana Storelli ◽  
Marta Radaelli ◽  
Massimo Filippi
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Fractional Anisotropy ◽  
Neuromyelitis Optica ◽  
Mean Diffusivity ◽  
Healthy Controls ◽  
Neuromyelitis Optica Spectrum Disorders ◽  
White Matter Damage ◽  
Axial Diffusivity ◽  
Spectrum Disorders

Background: The pathogenetic mechanisms sustaining neuroinflammatory disorders may originate from the cerebrospinal fluid. Objective: To evaluate white matter damage with diffusion tensor imaging and T1/T2-weighted ratio at progressive distances from the ventricular system in neuromyelitis optica spectrum disorders and multiple sclerosis. Methods: Fractional anisotropy, mean, axial, and radial diffusivity and T1/T2-weighted ratio maps were obtained from patients with seropositive neuromyelitis optica spectrum disorders, multiple sclerosis, and healthy controls ( n = 20 each group). White matter damage was assessed as function of ventricular distance within progressive concentric bands. Results: Compared to healthy controls, neuromyelitis optica spectrum disorders patients had similar fractional anisotropy, radial and axial diffusivity, increased mean diffusivity ( p = 0.009–0.013) and reduced T1/T2-weighted ratio ( p = 0.024–0.037) in all bands. In multiple sclerosis, gradient of percentage lesion volume and intra-lesional mean and axial diffusivity were higher in periventricular bands. Compared to healthy controls, multiple sclerosis patients had reduced fractional anisotropy ( p = 0.001–0.043) in periventricular bands, increased mean ( p < 0.001), radial ( p < 0.001–0.004), and axial diffusivity ( p = 0.002–0.008) and preserved T1/T2-weighted ratio in all bands. Conclusion: White matter damage is higher at periventricular level in multiple sclerosis and diffuse in neuromyelitis optica spectrum disorders. Fractional anisotropy preservation, associated with increased mean diffusivity and reduced T1/T2-weighted ratio may reflect astrocyte damage.

Altered effective connectivity during performance of an information processing speed task in multiple sclerosis

2011 ◽  
Vol 18 (4) ◽  
pp. 409-417 ◽  
Author(s):  
Victoria M Leavitt ◽  
Glenn Wylie ◽  
Helen M Genova ◽  
Nancy D Chiaravalloti ◽  
John DeLuca
Keyword(s):  
Multiple Sclerosis ◽  
Processing Speed ◽  
Effective Connectivity ◽  
A Priori ◽  
Brain Regions ◽  
Healthy Controls ◽  
Causality Analysis ◽  
Information Processing Speed ◽  
Neural Connections ◽  
Speed Task

Background: Functional magnetic resonance imaging (fMRI) studies of persons with multiple sclerosis (MS) reveal distinct patterns of activation during task performance. We were interested in determining whether distinct patterns of effective connectivity would be revealed with Granger causality analysis (GCA). Objective: To characterize directed neural connections in persons with MS during a processing speed task between brain regions known to be activated in healthy controls. Methods: fMRI and GCA were used to examine effective connectivity underlying performance of a processing speed task in persons with MS. In total, 16 individuals with MS and 17 healthy controls (HC) performed a modified version of the Symbol Digit Modality Task (mSDMT) in the MRI scanner. Eight seed regions were selected on the basis of a priori data showing areas involved in mSDMT performance of HC. Results: Behaviorally, the MS group attained a level of accuracy equivalent to the HC group, although they were significantly slower. While there was a great deal of overlap in the connections relied upon by both groups, the MS group showed significant differences in connectivity between critical brain regions. Specifically, the MS group had more connections from multiple regions to frontal cortices bilaterally relative to HCs. Conclusions: Greater neural recruitment by the MS group relative to HC is consistent with the neural efficiency hypothesis, and lends further support to the notion that more connections must be recruited to maintain performance in the presence of brain pathology.

Gender-related differences in functional connectivity in multiple sclerosis

2011 ◽  
Vol 18 (2) ◽  
pp. 164-173 ◽  
Author(s):  
Menno M Schoonheim ◽  
Hanneke E Hulst ◽  
Doriana Landi ◽  
Olga Ciccarelli ◽  
Stefan D Roosendaal ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Functional Connectivity ◽  
Gender Effects ◽  
Control Group ◽  
Visuospatial Memory ◽  
Information Processing Speed ◽  
Network Efficiency ◽  
Functional Changes ◽  
Female Patients ◽  
Male Patients

Background: Gender effects are strong in multiple sclerosis (MS), with male patients showing a worse clinical outcome than female patients. Functional reorganization of neural activity may contribute to limit disability, and possible gender differences in this process may have important clinical implications. Objectives: The aim of this study was to explore gender-related changes in functional connectivity and network efficiency in MS patients. Additionally, we explored the association of functional changes with cognitive function. Methods: Sixty subjects were included in the study, matched for age, education level and intelligence quotient (IQ). Male and female patients were matched for disability, disease duration and white matter lesion load. Two cognitive domains often impaired in MS, i.e. visuospatial memory and information processing speed, were evaluated in all subjects. Functional connectivity between brain regions and network efficiency was explored using resting-state functional magnetic resonance imaging and graph analysis. Differences in cognitive and functional characteristics between groups, and correlations with cognitive performance, were examined. Results: Male patients showed worse performance on cognitive tests than female and male controls, while female patients were cognitively normal. Decreases in functional connectivity and network efficiency, observed in male patients, correlated with reduced visuospatial memory ( r = −0.6 and r = −0.5, respectively). In the control group, no cognitive differences were found between genders, despite differences in functional connectivity between healthy men and women. Conclusions: Functional connectivity differences were found in male patients only and were related to impaired visuospatial memory. These results underline the importance of gender in MS and require further investigation in larger and longitudinal studies.

Altered functional connectivity and performance variability in relapsing–remitting multiple sclerosis

2014 ◽  
Vol 20 (11) ◽  
pp. 1453-1463 ◽  
Author(s):  
Magdalena Wojtowicz ◽  
Erin L Mazerolle ◽  
Virender Bhan ◽  
John D Fisk
Keyword(s):  
Multiple Sclerosis ◽  
Information Processing ◽  
Functional Connectivity ◽  
Processing Speed ◽  
Resting State ◽  
Healthy Controls ◽  
Information Processing Speed ◽  
Frontal Pole ◽  
Performance Variability ◽  
Relapsing Remitting

Background: Patients with multiple sclerosis (MS) demonstrate slower and more variable performance on attention and information processing speed tasks. Greater variability in cognitive task performance has been shown to be an important predictor of neurologic status and provides a unique measure of cognitive performance in MS patients. Objectives: This study investigated alterations in resting-state functional connectivity associated with within-person performance variability in MS patients. Methods: Relapsing–remitting MS patients and matched healthy controls completed structural MRI and resting-state fMRI (rsfMRI) scans, as well as tests of information processing speed. Performance variability was calculated from reaction time tests of processing speed. rsfMRI connectivity was investigated within regions associated with the default mode network (DMN). Relations between performance variability and functional connectivity in the DMN within MS patients were evaluated. Results: MS patients demonstrated greater reaction time performance variability compared to healthy controls ( p<0.05). For MS patients, more stable performance on a complex processing speed task was associated with greater resting-state connectivity between the ventral medial prefrontal cortex and the frontal pole. Conclusions: Among MS patients, greater functional connectivity between medial prefrontal and frontal pole regions appears to facilitate performance stability on complex speed-dependent information processing tasks.

Increased short-range and long-range functional connectivity in first-episode, medication-naive schizophrenia at rest

2015 ◽  
Vol 166 (1-3) ◽  
pp. 144-150 ◽  
Author(s):  
Wenbin Guo ◽  
Feng Liu ◽  
Changqing Xiao ◽  
Jianrong Liu ◽  
Miaoyu Yu ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Long Range ◽  
Short Range ◽  
First Episode
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