Disconnection as a mechanism for social cognition impairment in multiple sclerosis

Neurology ◽  
2017 ◽  
Vol 89 (1) ◽  
pp. 38-45 ◽  
Author(s):  
Sonia Batista ◽  
Carolina Alves ◽  
Otília C. d’Almeida ◽  
Ana Afonso ◽  
Ricardo Félix-Morais ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Social Cognition ◽  
White Matter ◽  
Corpus Callosum ◽  
Diffusion Tensor ◽  
Brain Mri ◽  
Mean Diffusivity ◽  
Uncinate Fasciculus ◽  
Neural Basis ◽  
Cognition Impairment

Objective:To assess the contribution of microstructural normal-appearing white matter (NAWM) damage to social cognition impairment, specifically in the theory of mind (ToM), in multiple sclerosis (MS).Methods:We enrolled consecutively 60 patients with MS and 60 healthy controls (HC) matched on age, sex, and education level. All participants underwent ToM testing (Eyes Test, Videos Test) and 3T brain MRI including conventional and diffusion tensor imaging sequences. Tract-based spatial statistics (TBSS) were applied for whole-brain voxel-wise analysis of fractional anisotropy (FA) and mean diffusivity (MD) on NAWM.Results:Patients with MS performed worse on both tasks of ToM compared to HC (Eyes Test 58.7 ± 13.8 vs 81.9 ± 10.4, p < 0.001, Hedges g −1.886; Videos Test 75.3 ± 9.3 vs 88.1 ± 7.1, p < 0.001, Hedges g −1.537). Performance on ToM tests was correlated with higher values of FA and lower values of MD across widespread white matter tracts. The largest effects (≥90% of voxels with statistical significance) for the Eyes Test were body and genu of corpus callosum, fornix, tapetum, uncinate fasciculus, and left inferior cerebellar peduncle, and for the Videos Test genu and splenium of corpus callosum, fornix, uncinate fasciculus, left tapetum, and right superior fronto-occipital fasciculus.Conclusions:These results indicate that a diffuse pattern of NAWM damage in MS contributes to social cognition impairment in the ToM domain, probably due to a mechanism of disconnection within the social brain network. Gray matter pathology is also expected to have an important role; thus further research is required to clarify the neural basis of social cognition impairment in MS.

scholarly journals The neural basis of fatigue in multiple sclerosis

2018 ◽  
Vol 8 (6) ◽  
pp. 492-500 ◽  
Author(s):  
Ana Margarida Novo ◽  
Sonia Batista ◽  
Carolina Alves ◽  
Otília C. d’Almeida ◽  
Inês Brás Marques ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Diffusion Tensor ◽  
Brain Mri ◽  
Mean Diffusivity ◽  
Internal Capsule ◽  
Cerebral Peduncle ◽  
Neural Basis ◽  
Focal Lesions ◽  
External Capsule ◽  
Impact Scale

BackgroundFatigue is a frequent disabling symptom in multiple sclerosis (MS), but its pathophysiology remains incompletely understood. This study aimed to explore the underlying neural basis of fatigue in patients with MS.MethodsWe enrolled 60 consecutive patients with MS and 60 healthy controls (HC) matched on age, sex, and education. Fatigue was assessed using the Portuguese version of the Modified Fatigue Impact Scale (MFIS). All participants underwent 3T brain MRI (conventional and diffusion tensor imaging [DTI] sequences). White matter (WM) focal lesions were identified and T1/T2 lesion volumes were computed. Tract-based spatial statistics were applied for voxel-wise analysis of DTI metrics fractional anisotropy and mean diffusivity (MD) on normal-appearing WM (NAWM). Using Freesurfer software, total and regional volumes of cortical and subcortical gray matter (GM) were calculated.ResultsCompared to HC, patients with MS scored significantly higher on MFIS (33.8 ± 19.7 vs 16.5 ± 15.1, p < 0.001). MFIS scores were not significantly correlated with T1/T2 lesion volumes, total GM volume, or any regional volume of cortical and subcortical GM. Significant correlations were found between global scores of MFIS and MD increase of the NAWM skeleton, including corona radiata, internal capsule, external capsule, corticospinal tract, cingulum, corpus callosum, fornix, superior longitudinal fasciculus, superior fronto-occipital fasciculus, sagittal stratum, posterior thalamic radiation, cerebral peduncle, and uncinate fasciculus.ConclusionsIn this study, fatigue was associated with widespread NAWM damage but not with lesion load or GM atrophy. Functional disconnection, caused by diffuse microstructural WM damage, might be the main neural basis of fatigue in MS.

scholarly journals Multiple sclerosis and depressive manifestations: can diffusion tensor MR imaging help in the detection of microstructural white matter changes?

2019 ◽  
Vol 50 (1) ◽  
Author(s):  
Talaat A. Hassan ◽  
Shaima Fattouh Elkholy ◽  
Bahaa Eldin Mahmoud ◽  
Mona ElSherbiny
Keyword(s):  
Multiple Sclerosis ◽  
Depressive Symptoms ◽  
White Matter ◽  
Limbic System ◽  
Diffusion Tensor ◽  
Control Group ◽  
Uncinate Fasciculus ◽  
White Matter Tracts ◽  
Significant Difference ◽  
The Right

Abstract Background Multiple sclerosis is one of the commonest causes of neurological disability in middle-aged and young adults. Depression in MS patients can compromise cognitive functions, lead to suicide attempts, impair relationships and reduce compliance with disease-modifying treatments. The aim of this study was to investigate and compare the microstructural changes in the white matter tracts of the limbic system in MS patients with and those without depressive manifestations using a diffusion tensor imaging (DTI) technique. Methods This study included 40 patients who were divided into three groups. Group 1 comprised of 20 patients with relapsing-remitting MS with depressive symptoms and group 2 comprised 10 MS patients without symptoms of depression. The third group is a control group that included 10 age-matched healthy individuals. All patients underwent conventional MRI examinations and DTI to compare the fractional anisotropy (FA) values in the white matter tracts of the limbic system. Results We compared the DTI findings in MS patients with and those without depressive symptoms. It was found that patients with depression and MS exhibited a significant reduction in the FA values of the cingulum (P < 0.0111 on the right and P < 0.0142 on the left), uncinate fasciculus (P < 0.0001 on the right and P < 0.0076 on the left) and the fornix (P < 0.0001 on both sides). No significant difference was found between the FA values of the anterior thalamic radiations in both groups. Conclusion Patients with depression and MS showed more pronounced microstructural damage in the major white matter connections of the limbic pathway, namely, the uncinate fasciculus, cingulum and fornix. These changes can be detected by DTI as decreased FA values in depressed MS patients compared to those in non-depressed patients.

scholarly journals White matter abnormalities in the corpus callosum with cognitive impairment in Parkinson disease

Neurology ◽  
2018 ◽  
Vol 91 (24) ◽  
pp. e2244-e2255 ◽  
Author(s):  
Ian O. Bledsoe ◽  
Glenn T. Stebbins ◽  
Doug Merkitch ◽  
Jennifer G. Goldman
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
Corpus Callosum ◽  
Parkinson Disease ◽  
Information Transfer ◽  
Diffusion Tensor ◽  
Anterior Segment ◽  
Mean Diffusivity ◽  
Cognitive Domain ◽  
White Matter Abnormalities

ObjectiveTo evaluate microstructural characteristics of the corpus callosum using diffusion tensor imaging (DTI) and their relationships to cognitive impairment in Parkinson disease (PD).MethodsSeventy-five participants with PD and 24 healthy control (HC) participants underwent structural MRI brain scans including DTI sequences and clinical and neuropsychological evaluations. Using Movement Disorder Society criteria, PD participants were classified as having normal cognition (PD-NC, n = 23), mild cognitive impairment (PD-MCI, n = 35), or dementia (PDD, n = 17). Cognitive domain (attention/working memory, executive function, language, memory, visuospatial function) z scores were calculated. DTI scalar values, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), were established for 5 callosal segments on a midsagittal plane, single slice using a topographically derived parcellation method. Scalar values were compared among participant groups. Regression analyses were performed on cognitive domain z scores and DTI metrics.ResultsParticipants with PD showed increased AD values in the anterior 3 callosal segments compared to healthy controls. Participants with PDD had significantly increased AD, MD, and RD in the anterior 2 segments compared to participants with PD-NC and most anterior segment compared to participants with PD-MCI. FA values did not differ significantly between participants with PD and participants with HC or among PD cognitive groups. The strongest associations for the DTI metrics and cognitive performance occurred in the most anterior and most posterior callosal segments, and also reflected fronto-striatal and posterior cortical type cognitive deficits, respectively.ConclusionsMicrostructural white matter abnormalities of the corpus callosum, as measured by DTI, may contribute to PD cognitive impairment by disrupting information transfer across interhemispheric and callosal–cortical projections.

scholarly journals 18F-AV1451 PET imaging and white matter changes in progressive supranuclear palsy

2019 ◽  
Author(s):  
Nicolas Nicastro ◽  
Patricia Vazquez Rodriguez ◽  
Maura Malpetti ◽  
William Richard Bevan-Jones ◽  
P. Simon Jones ◽  
...  
Keyword(s):  
White Matter ◽  
Progressive Supranuclear Palsy ◽  
Pet Imaging ◽  
Diffusion Tensor ◽  
Brain Mri ◽  
Mean Diffusivity ◽  
White Matter Integrity ◽  
Tau Pathology ◽  
Cross Sectional ◽  
White Matter Changes

ABSTRACTIntroductionProgressive supranuclear palsy (PSP) is characterized by deposition of straight filament tau aggregates in the grey matter of deep nuclei and cerebellum. White matter changes are increasingly documented as a feature of degenerative parkinsonism. We therefore examined the relationship between tau pathology (assessed via 18F-AV1451 positron emission tomography) and white matter integrity (using diffusion tensor imaging, DTI) in PSP.MethodsTwenty-three people with clinically probable PSP-Richardson’s syndrome (age 68.8 ± 5.8 years, 39% female) and 23 controls underwent structural 3T brain MRI including DTI. Twenty-one patients also underwent 18F-AV145 PET imaging. DTI group comparisons were performed using Fractional Anisotropy (FA), Mean Diffusivity (MD) and Radial Diffusivity (RD). Voxel-wise white matter integrity was correlated with 18F-AV1451 binding in typical subcortical PSP regions of interest (i.e. putamen, pallidum, thalamus and midbrain). DTI and 18F-AV1451 imaging measures were correlated with clinical impairment.ResultsWidespread DTI changes in PSP subjects relative to controls (family-wise error FWE p<0.01) were observed. In PSP, higher 18F-AV1451 binding correlated with reduced white matter integrity in the bilateral internal capsule, corona radiata, and superior longitudinal fasciculus (FWE p<0.05). Association between cognitive impairment (ACER score) and white matter deficits were found in the genu of corpus callosum and cingulum (p<0.005).ConclusionThis cross-sectional study demonstrates an association between in vivo proxy measures of tau pathology and white matter degeneration in PSP. Longitudinal studies and more specific PET probes for non-Alzheimer tauopathies are warranted to assess the complex interplay between microstructural changes and protein deposition in PSP.

scholarly journals Age-Related Variations in Regional White Matter Volumetry and Microstructure During the Post-adolescence Period: A Cross-Sectional Study of a Cohort of 1,713 University Students

2021 ◽  
Vol 15 ◽  
Author(s):  
Ami Tsuchida ◽  
Alexandre Laurent ◽  
Fabrice Crivello ◽  
Laurent Petit ◽  
Antonietta Pepe ◽  
...  
Keyword(s):  
White Matter ◽  
University Students ◽  
Diffusion Tensor ◽  
Brain Mri ◽  
Mean Diffusivity ◽  
High Angular Resolution ◽  
White Matter Volume ◽  
Matter Volume ◽  
Brain White Matter ◽  
Age Related

Human brain white matter undergoes a protracted maturation that continues well into adulthood. Recent advances in diffusion-weighted imaging (DWI) methods allow detailed characterizations of the microstructural architecture of white matter, and they are increasingly utilized to study white matter changes during development and aging. However, relatively little is known about the late maturational changes in the microstructural architecture of white matter during post-adolescence. Here we report on regional changes in white matter volume and microstructure in young adults undergoing university-level education. As part of the MRi-Share multi-modal brain MRI database, multi-shell, high angular resolution DWI data were acquired in a unique sample of 1,713 university students aged 18–26. We assessed the age and sex dependence of diffusion metrics derived from diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) in the white matter regions as defined in the John Hopkins University (JHU) white matter labels atlas. We demonstrate that while regional white matter volume is relatively stable over the age range of our sample, the white matter microstructural properties show clear age-related variations. Globally, it is characterized by a robust increase in neurite density index (NDI), and to a lesser extent, orientation dispersion index (ODI). These changes are accompanied by a decrease in diffusivity. In contrast, there is minimal age-related variation in fractional anisotropy. There are regional variations in these microstructural changes: some tracts, most notably cingulum bundles, show a strong age-related increase in NDI coupled with decreases in radial and mean diffusivity, while others, mainly cortico-spinal projection tracts, primarily show an ODI increase and axial diffusivity decrease. These age-related variations are not different between males and females, but males show higher NDI and ODI and lower diffusivity than females across many tracts. These findings emphasize the complexity of changes in white matter structure occurring in this critical period of late maturation in early adulthood.

Abstract P64: Longitudinal Brain Structural Changes After Stroke

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Kyle C Kern ◽  
Clinton B Wright ◽  
Richard Leigh
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Stroke Volume ◽  
Brain Atrophy ◽  
Structural Changes ◽  
Diffusion Tensor ◽  
Brain Mri ◽  
Mean Diffusivity ◽  
Intracranial Volume ◽  
Post Stroke

Background: Stroke causes focal and diffuse structural brain changes that may contribute to subsequent cognitive decline and dementia. We hypothesize that MRI structural measures can detect continued cerebral degeneration over the first year after stroke. We identify predictors for progression of brain atrophy, leukoaraiosis and diffusion tensor imaging (DTI) metrics. Methods: Patients with ischemic stroke were enrolled prospectively in an observational study that included serial brain MRI. Patients underwent MRI FLAIR and DTI at the time of acute stroke and were followed for at least 9 months with multiple MRIs between 30 days and 15 months post-stroke. We used FLAIR to measure brain atrophy as the percent brain parenchymal fraction (BPF) of the total intracranial volume (TICV) and white matter hyperintensity volume (WMHV) as a percentage of TICV. DTI was used to calculate Peak Skeletonized Mean Diffusivity (PSMD), a global measure of white matter integrity previously validated in cerebral small vessel disease. Longitudinal changes in BPF, WMHV or PSMD were measured from 30 days post-stroke onward using linear regression models that included age, stroke volume, baseline BPF and WMHV as predictors. Results: Twenty-six patients had a median of 4 follow-ups over 9-15 months. Median age was 74 years (range 51-84) and 38% were women. Mean stroke volume was 4.5cc (0 - 30cc). Mean BPF was 78% (72 - 86%) and mean baseline WMHV was 1.1% (0.1 - 3.9%). BPF was associated with age and declined by 0.7% per year (t(111) = 2.7, p = 0.007). Progression was associated with baseline BPF (t(111) = -3.4, p < 0.001). WMHV in the non-stroke hemisphere was associated with age and increased by 0.10% per year (t(87) = -5.8, p < 0.001). Accumulation was associated with age (t(87) = 5.8, p < 0.001). PSMD was associated with baseline WMHV and had a relative increase of 1.9% per year in the non-stroke hemisphere and 4.5% in the stroke hemisphere (t(174) = -2.1, p = 0.03). Progression was associated with age (t(174) = 2.3, p = 0.03) and stroke volume (t(174) = 2.4, p = 0.02). Conclusions: During the months after ischemic stroke, BPF, WMHV and PSMD can detect persistent structural changes that may reflect later phases of stroke injury or ongoing contributions of aging, silent ischemia, or neurodegeneration.

scholarly journals Disrupted white matter integrity is associated with cognitive deficits in patients with amnestic mild cognitive impairment: An atlas-based study

2016 ◽  
Vol 4 ◽  
pp. 205031211664881 ◽  
Author(s):  
Duan Liu ◽  
Zan Wang ◽  
Hao Shu ◽  
Zhijun Zhang
Keyword(s):  
Cognitive Impairment ◽  
Diffusion Tensor Imaging ◽  
Mild Cognitive Impairment ◽  
White Matter ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Amnestic Mild Cognitive Impairment ◽  
Uncinate Fasciculus ◽  
Radial Diffusivity ◽  
Mild Cognitive Impairment Group

Objective: This study investigated white matter integrity in patients with amnestic mild cognitive impairment by diffusion tensor imaging. Methods: A total of 83 patients with amnestic mild cognitive impairment and 85 elderly healthy controls underwent neuropsychological testing and a diffusion tensor imaging scan. Whole-brain white matter data were parcellated into 50 regions based on the anatomical ICBM-DTI-81 atlas, and regional diffusion metrics consisting of fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity were calculated for each region. Diffusion tensor imaging indices were compared between groups, and it was determined that between-group differences were significantly correlated with neurocognitive performance. Results: Relative to the healthy controls group, the amnestic mild cognitive impairment group exhibited poorer cognitive performance in all neuropsychological tests except the complex figure test ( p = 0.083) and showed decreased mean fractional anisotropy in the fornix, increased mean diffusivity in the fornix and bilateral uncinate fasciculus, elevated axial diffusivity in the fornix and genu of corpus callosum, and elevated radial diffusivity in the fornix and bilateral uncinate fasciculus ( p < 0.05). Behaviorally, integrity of the bilateral uncinate fasciculus was correlated positively with episodic memory function, while left uncinate fasciculus integrity was positively associated with language function in the amnestic mild cognitive impairment group ( p < 0.05). Conclusion: White matter abnormalities in neural pathways associated with memory were correlated with neurocognitive deficiencies in amnestic mild cognitive impairment. Given that amnestic mild cognitive impairment is putatively a prodromal syndrome for Alzheimer’s disease, this study furthers our understanding of the white matter changes associated with Alzheimer’s disease pathogenesis in the predementia stage.

scholarly journals Cortical axonal loss is associated with both gray matter demyelination and white matter tract pathology in progressive multiple sclerosis: Evidence from a combined MRI-histopathology study

2020 ◽  
pp. 135245852091897 ◽  
Author(s):  
Svenja Kiljan ◽  
Paolo Preziosa ◽  
Laura E Jonkman ◽  
Wilma DJ van de Berg ◽  
Jos Twisk ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
White Matter Lesions ◽  
Progressive Multiple Sclerosis ◽  
Axonal Loss ◽  
Normal Appearing White Matter ◽  
Axonal Density ◽  
Neuroaxonal Degeneration

Background: Neuroaxonal degeneration is one of the hallmarks of clinical deterioration in progressive multiple sclerosis (PMS). Objective: To elucidate the association between neuroaxonal degeneration and both local cortical and connected white matter (WM) tract pathology in PMS. Methods: Post-mortem in situ 3T magnetic resonance imaging (MRI) and cortical tissue blocks were collected from 16 PMS donors and 10 controls. Cortical neuroaxonal, myelin, and microglia densities were quantified histopathologically. From diffusion tensor MRI, fractional anisotropy, axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) were quantified in normal-appearing white matter (NAWM) and white matter lesions (WML) of WM tracts connected to dissected cortical regions. Between-group differences and within-group associations were investigated through linear mixed models. Results: The PMS donors displayed significant axonal loss in both demyelinated and normal-appearing (NA) cortices ( p < 0.001 and p = 0.02) compared with controls. In PMS, cortical axonal density was associated with WML MD and AD ( p = 0.003; p = 0.02, respectively), and NAWM MD and AD ( p = 0.04; p = 0.049, respectively). NAWM AD and WML AD explained 12.6% and 22.6%, respectively, of axonal density variance in NA cortex. Additional axonal loss in demyelinated cortex was associated with cortical demyelination severity ( p = 0.002), explaining 34.4% of axonal loss variance. Conclusion: Reduced integrity of connected WM tracts and cortical demyelination both contribute to cortical axonal loss in PMS.

scholarly journals Corpus Callosum and Cingulum Tractography in Parkinson's Disease

2010 ◽  
Vol 37 (5) ◽  
pp. 595-600 ◽  
Author(s):  
Katie Wiltshire ◽  
Luis Concha ◽  
Myrlene Gee ◽  
Thomas Bouchard ◽  
Christian Beaulieu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
White Matter ◽  
Corpus Callosum ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Imaging Method ◽  
Motor Symptoms ◽  
Mri Scans

Background:In Parkinson's disease (PD) cell loss in the substantia nigra is known to result in motor symptoms; however widespread pathological changes occur and may be associated with non-motor symptoms such as cognitive impairment. Diffusion tensor imaging is a quantitative imaging method sensitive to the micro-structure of white matter tracts.Objective:To measure fractional anisotropy (FA) and mean diffusivity (MD) values in the corpus callosum and cingulum pathways, defined by diffusion tensor tractography, in patients with PD, PD with dementia (PDD) and controls and to determine if these measures correlate with Mini-Mental Status Examination (MMSE) scores in parkinsonian patients.Methods:Patients with PD (17 Males [M], 12 Females [F]), mild PDD (5 M, 1F) and controls (8 M, 7F) underwent cognitive testing and MRI scans. The corpus callosum was divided into four regions and the cingulum into two regions bilaterally to define tracts using the program DTIstudio (Johns Hopkins University) using the fiber assignment by continuous tracking algorithm. Volumetric MRI scans were used to measure white and gray matter volumes.Results:Groups did not differ in age or education. There were no overall FA or MD differences between groups in either the corpus callosum or cingulum pathways. In PD subjects the MMSE score correlated with MD within the corpus callosum. These findings were independent of age, sex and total white matter volume.Conclusions:The data suggest that the corpus callosum or its cortical connections are associated with cognitive impairment in PD patients.

Multiple sclerosis pathology in the normal and abnormal appearing white matter of the corpus callosum by diffusion tensor imaging

2004 ◽  
Vol 10 (4) ◽  
pp. 392-397 ◽  
Author(s):  
Bernard D Coombs ◽  
Alan Best ◽  
Mark S Brown ◽  
David E Miller ◽  
John Corboy ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Diffusion Coefficient ◽  
White Matter ◽  
Corpus Callosum ◽  
Diffusion Tensor ◽  
Age And Gender ◽  
Secondary Degeneration ◽  
Quantitative Mr ◽  
Normal Appearing White Matter ◽  
And Gender

Lesions in the corpus callosum in multiple sclerosis (MS) include those that are hyperintense on T2-weighted images, which can be either focal (isolated) or connected, but there is evidence that the corpus callosum, similar to other white matter regions, contains normal appearing white matter (NAWM) which is abnormal based on quantitative MR methodologies. In this pilot study, diffusion tensor based measures were determined in corpus callosum from 10 patients with MS and 12 age and gender matched controls. T2-hyperintense lesions were carefully segmented out from normal appearing corpus callosum to minimize contamination of the NAWM fraction with these lesions. The orientationally averaged diffusion coefficient was increased and the fractional anisotropy reduced in the NAWM fraction of the MS patients. These results confirm prior studies which suggest that pathology in the NAWM occurs independent of focal MS lesions, and are not likely the result of sample contamination through or across slices. This injury to the NAWM may be the result of focal, microscopic T2-invisible lesions and/or secondary degeneration related to distant lesions whose related fibres cross the corpus callosum.

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