Contributions
Abstract: P534
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Background: Lower Conscientiousness is associated with cognitive impairment in MS. The physiologic basis of this association is poorly understood, but may be due to a shared relationship with disruption of frontal cortical networks. Newer network-based analysis methods are well suited for discriminating between pathology associated with Conscientiousness and other neuropsychological impairments.
Objective: To identify structural brain networks whose disruption relates most significantly with low Conscientiousness and to compare these results with BICAMS (Brief International Cognitive Assessment for MS) associations.
Methods: Neuropsychological assessment and brain MRI was carried out for 131 people with MS and CIS. Severity of lesion-based disruption between pairwise gray matter regions was assessed using the Network Modification tool. Each lesion was used as a seed region in a high-resolution reference cohort, and normative diffusion streamlines were followed to specific atlas-based gray matter regions. Next, network-level analysis, controlling for disease group, age, sex, and normalized whole brain volume, was carried out with the Network-Based-Statistics (NBS) tool. Results were controlled for multiple comparisons at a level of p< 0.05.
Results: Two networks of disruption were significantly associated with low Conscientiousness (p = 0.040 & p = 0.041). The larger network, consisting of 9 region pairs, was entirely composed of left frontal cortical connections. Within this network, Conscientiousness was most robustly correlated with left superior frontal to left lateral orbitofrontal (t = 3.21) and left superior frontal to left pars triangularis
(t = 3.13). In comparison, the two networks significantly associated with processing speed were much larger, containing over 90 region pairs, but frontal cortex disruption was included in both. Other BICAMS measures were related to disconnection of networks including regions already known to be associated with those cognitive domains, e.g. decreased visual learning with hippocampus, thalamus, occipital cortex, and temporal cortex.
Conclusions: Our results suggest that low Conscientiousness in MS is explained by pathology in connections between frontal cortical regions, predominantly in the left hemisphere. This pattern of disruption overlaps with those related to processing speed, and may in part explain why decreased conscientiousness is associated with cognitive decline in MS.
Disclosure:
Tom Fuchs, Shumita Roy, Sanjeevani Choudhery, Patrick Rooney, Keith Carolus, Niels Bergsland, Deepa Ramasamy, and Dejan Jakimovski have nothing to disclose.
Ralph Benedict has acted as a consultant or scientific advisory board member for Bayer, Biogen Idec, Actelion, and Novartis. He receives royalties from Psychological Assessment Resources, Inc. He has received financial support for research activities from Shire Pharmaceuticals, Accorda and Biogen Idec
Bianca Weinstock-Guttman received honoraria as a speaker and as a consultant for Biogen Idec, Teva Pharmaceuticals, EMD Serono, Genzyme, Sanofi, Novartis and Acorda. Dr Weinstock-Guttman received research funds from Biogen Idec, Teva Pharmaceuticals, EMD Serono,Genzyme, Sanofi, Novartis, Acorda.
R Zivadinov received personal compensation from EMD Serono, Genzyme-Sanofi, Novartis, Claret-Medical, Celgene for speaking and consultant fees. He received financial support for research activities from Claret Medical, Genzyme-Sanofi, QuintilesIMS Health, Intekrin-Coherus, Novartis and Intekrin-Coherus.
Michael G. Dwyer has received consultant fees from Claret Medical and EMD Serono and research grant support from Novartis.
Abstract: P534
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Background: Lower Conscientiousness is associated with cognitive impairment in MS. The physiologic basis of this association is poorly understood, but may be due to a shared relationship with disruption of frontal cortical networks. Newer network-based analysis methods are well suited for discriminating between pathology associated with Conscientiousness and other neuropsychological impairments.
Objective: To identify structural brain networks whose disruption relates most significantly with low Conscientiousness and to compare these results with BICAMS (Brief International Cognitive Assessment for MS) associations.
Methods: Neuropsychological assessment and brain MRI was carried out for 131 people with MS and CIS. Severity of lesion-based disruption between pairwise gray matter regions was assessed using the Network Modification tool. Each lesion was used as a seed region in a high-resolution reference cohort, and normative diffusion streamlines were followed to specific atlas-based gray matter regions. Next, network-level analysis, controlling for disease group, age, sex, and normalized whole brain volume, was carried out with the Network-Based-Statistics (NBS) tool. Results were controlled for multiple comparisons at a level of p< 0.05.
Results: Two networks of disruption were significantly associated with low Conscientiousness (p = 0.040 & p = 0.041). The larger network, consisting of 9 region pairs, was entirely composed of left frontal cortical connections. Within this network, Conscientiousness was most robustly correlated with left superior frontal to left lateral orbitofrontal (t = 3.21) and left superior frontal to left pars triangularis
(t = 3.13). In comparison, the two networks significantly associated with processing speed were much larger, containing over 90 region pairs, but frontal cortex disruption was included in both. Other BICAMS measures were related to disconnection of networks including regions already known to be associated with those cognitive domains, e.g. decreased visual learning with hippocampus, thalamus, occipital cortex, and temporal cortex.
Conclusions: Our results suggest that low Conscientiousness in MS is explained by pathology in connections between frontal cortical regions, predominantly in the left hemisphere. This pattern of disruption overlaps with those related to processing speed, and may in part explain why decreased conscientiousness is associated with cognitive decline in MS.
Disclosure:
Tom Fuchs, Shumita Roy, Sanjeevani Choudhery, Patrick Rooney, Keith Carolus, Niels Bergsland, Deepa Ramasamy, and Dejan Jakimovski have nothing to disclose.
Ralph Benedict has acted as a consultant or scientific advisory board member for Bayer, Biogen Idec, Actelion, and Novartis. He receives royalties from Psychological Assessment Resources, Inc. He has received financial support for research activities from Shire Pharmaceuticals, Accorda and Biogen Idec
Bianca Weinstock-Guttman received honoraria as a speaker and as a consultant for Biogen Idec, Teva Pharmaceuticals, EMD Serono, Genzyme, Sanofi, Novartis and Acorda. Dr Weinstock-Guttman received research funds from Biogen Idec, Teva Pharmaceuticals, EMD Serono,Genzyme, Sanofi, Novartis, Acorda.
R Zivadinov received personal compensation from EMD Serono, Genzyme-Sanofi, Novartis, Claret-Medical, Celgene for speaking and consultant fees. He received financial support for research activities from Claret Medical, Genzyme-Sanofi, QuintilesIMS Health, Intekrin-Coherus, Novartis and Intekrin-Coherus.
Michael G. Dwyer has received consultant fees from Claret Medical and EMD Serono and research grant support from Novartis.