Anatomical brain connectivity can assess cognitive dysfunction in multiple sclerosis

Bozzali, Marco; Spanò, Barbara; Parker, Geoffrey; Giulietti, Giovanni; Castelli, Maura; Basile, Barbara; Rossi, Silvia; Serra, Laura; Magnani, Giuseppe; Nocentini, Ugo; Caltagirone, Carlo; Centonze, Diego; Cercignani, Mara

doi:10.1177/1352458512474088

Cited by 32 publications

(32 citation statements)

References 34 publications

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“…This is in contrast with a previous study where ACM has been investigated in patients with RR-MS [14]. In that study, ACM changes were found in the subcortical GM nuclei of the thalami and caudate nuclei but not in WM.…”

Section: Discussioncontrasting

confidence: 98%

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Secondary Progressive and Relapsing Remitting Multiple Sclerosis Leads to Motor-Related Decreased Anatomical Connectivity

et al. 2014

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Multiple sclerosis (MS) damages central white matter pathways which has considerable impact on disease-related disability. To identify disease-related alterations in anatomical connectivity, 34 patients (19 with relapsing remitting MS (RR-MS), 15 with secondary progressive MS (SP-MS) and 20 healthy subjects underwent diffusion magnetic resonance imaging (dMRI) of the brain. Based on the dMRI, anatomical connectivity mapping (ACM) yielded a voxel-based metric reflecting the connectivity shared between each individual voxel and all other brain voxels. To avoid biases caused by inter-individual brain-shape differences, they were estimated in a spatially normalized space. Voxel-based statistical analyses using ACM were compared with analyses based on the localized microstructural indices of fractional anisotropy (FA). In both RR-MS and SP-MS patients, considerable portions of the motor-related white matter revealed decreases in ACM and FA when compared with healthy subjects. Patients with SP-MS exhibited reduced ACM values relative to RR-MS in the motor-related tracts, whereas there were no consistent decreases in FA between SP-MS and RR-MS patients. Regional ACM statistics exhibited moderate correlation with clinical disability as reflected by the expanded disability status scale (EDSS). The correlation between these statistics and EDSS was either similar to or stronger than the correlation between FA statistics and the EDSS. Together, the results reveal an improved relationship between ACM, the clinical phenotype, and impairment. This highlights the potential of the ACM connectivity indices to be used as a marker which can identify disease related-alterations due to MS which may not be seen using localized microstructural indices.

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Section: Discussioncontrasting

confidence: 98%

“…Another issue that may impact the reliability of the ACMs is the number of streamlines used in its estimation. This is one of the methodological differences that may have caused discrepancy with respects to a previous ACM-based MS study of [14]. We used a conservatively large number of streamlines (500) for this study.…”

Section: Discussionmentioning

confidence: 99%

Secondary Progressive and Relapsing Remitting Multiple Sclerosis Leads to Motor-Related Decreased Anatomical Connectivity

et al. 2014

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“…105,112 Interestingly, by means of a newly developed diffusion-weighted MRI tractography approach, reduced anatomical connectivity of the thalamus and the caudate nuclei was found in MS which was mainly located in areas spared by lesions. 113 A strong association of damage to strategically crucial deep gray matter nuclei such as thalamus or putamen with impaired cognitive processing has been demonstrated by multiple studies. 50,[114][115][116][117][118][119][120][121] Moreover, gray matter damage of the hippocampus which is especially relevant for memory performance has been revealed by various imaging techniques and was shown to be related to memory-related aspects of cognitive performance in MS.…”

Section: Deep Gray Matter Damagementioning

confidence: 99%

Pathology and MRI: exploring cognitive impairment in MS

Paul

2016

Acta Neurol Scand

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“…The Paced Auditory Serial Addition Test (PASAT) and the Symbol Digit Modalities Test (SDMT) are sensitive tools to examine different components of attention, executive functions and information processing speed and are widely used in neuropsychological evaluation of patients with MS (Boringa et al, 2001, Cutter et al, 1999). Cognitive dysfunction in MS has been associated with disconnection mechanisms related to focal lesions and diffuse microstructural damage in strategic white matter (WM) tracts involved in cognitive performance, in addition to gray matter (GM) impairment (Bozzali et al, 2013, Calabrese et al, 2009, Harrison et al, 2015, Llufriu et al, 2014, Preziosa et al, 2016). Moreover, brain functional modifications in task-based studies seem to drive compensatory mechanisms at the earliest stages of disease, when structural damage is low, with increased cortical recruitment probably contributing to the maintenance of a normal level of cognitive performance.…”

Section: Introductionmentioning

confidence: 99%

Structural networks involved in attention and executive functions in multiple sclerosis

Llufriú

Martínez‐Heras

Solana

et al. 2017

NeuroImage: Clinical

107

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Attention and executive deficits are disabling symptoms in multiple sclerosis (MS) that have been related to disconnection mechanisms. We aimed to investigate changes in structural connectivity in MS and their association with attention and executive performance applying an improved framework that combines high order probabilistic tractography and anatomical exclusion criteria postprocessing. We compared graph theory metrics of structural networks and fractional anisotropy (FA) of white matter (WM) connections or edges between 72 MS subjects and 38 healthy volunteers (HV) and assessed their correlation with cognition. Patients displayed decreased network transitivity, global efficiency and increased path length compared with HV (p < 0.05, corrected). Also, nodal strength was decreased in 26 of 84 gray matter regions. The distribution of nodes with stronger connections or hubs of the network was similar among groups except for the right pallidum and left insula, which became hubs in patients. MS subjects presented reduced edge FA widespread in the network, while FA was increased in 24 connections (p < 0.05, corrected). Decreased integrity of frontoparietal networks, deep gray nuclei and insula correlated with worse attention and executive performance (r between 0.38 and 0.55, p < 0.05, corrected). Contrarily, higher strength in the right transverse temporal cortex and increased FA of several connections (mainly from cingulate, frontal and occipital cortices) were associated with worse functioning (r between − 0.40 and − 0.47, p < 0.05 corrected). In conclusion, structural brain connectivity is disturbed in MS due to widespread impairment of WM connections and gray matter structures. The increased edge connectivity suggests the presence of reorganization mechanisms at the structural level. Importantly, attention and executive performance relates to frontoparietal networks, deep gray nuclei and insula. These results support the relevance of network integrity to maintain optimal cognitive skills.

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Anatomical brain connectivity can assess cognitive dysfunction in multiple sclerosis

Abstract: ACM opens a new perspective, clarifying the contribution of anatomical brain disconnection to clinical disabilities in MS.

Cited by 32 publications

References 34 publications

Secondary Progressive and Relapsing Remitting Multiple Sclerosis Leads to Motor-Related Decreased Anatomical Connectivity

Secondary Progressive and Relapsing Remitting Multiple Sclerosis Leads to Motor-Related Decreased Anatomical Connectivity

Pathology and MRI: exploring cognitive impairment in MS

Structural networks involved in attention and executive functions in multiple sclerosis

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