Contributions
Abstract: 96
Type: Scientific Session
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Introduction: An efficient network, like the human brain, features a combination of signal integration driven by long-range connections and local processing involving short-range connections. It is unknown, however, whether these connections are equally damaged in multiple sclerosis (MS) and how this relates to cognition. Therefore, we investigated the impact of structural damage to short- and long-range connections on both the functional connectome and cognitive function in MS.
Methods: From the Amsterdam MS cohort, 133 MS patients (age=54.2 (9.6)) and 48 healthy controls (HC; age=50.8 (7.0)) were included with neuropsychological testing and MRI. Structural connectivity was estimated from diffusion tensor images (DTI) using probabilistic tractography (MRtrix 3.0). The average fractional anisotropy (FA) as well as the average fiber length was determined in each tract between connecting pairs of brain regions based on the automated anatomical labelling (AAL) atlas. Connections were divided into short (< Q1), middle (Q1-Q3) and long (>Q3) range, based on the mean distribution of tract lengths in HC. Functional connectivity was computed between each pair of AAL regions, after artefact removal with FMRIB's ICA-based X-noisefier (FIX). The correspondence between individual functional connectivity matrices and the average connectivity matrix (based on all HC) was quantified. Statistical analyses were corrected for age, sex and education (p< 0.05; FDR-corrected).
Results: In general, the MS structural network showed connections with a reduced integrity and shorter distance compared to HC. In MS, the longest connections showed the largest reduction in integrity (z(FA)=-1.14; p< 0.001), whereas shorter connections were less severely affected (z(FA)=-0.29; p=0.03). In MS, integrity of long-range connections was more strongly related to cognitive performance than integrity of short-range connections (r=0.411; p< 0.001 and r=0.176; p=0.04, respectively). In addition, integrity loss of long-range connections was associated with a more abnormal functional network (r=0.204; p< 0.001), whereas damage to short-range connections did not relate to functional changes.
Conclusions: Our findings indicate that long-range connections are more vulnerable to MS-specific damage than short-range connections. Moreover, compared to short-range connections, damage to long-range connections has a larger impact on the functional network and cognitive performance.
Disclosure: Kim A Meijer receives funding from a research grant of Biogen. Menno M Schoonheim serves on the editorial board of Frontiers of Neurology, receives research support from the Dutch MS Research Foundation, grant number 13-820, and has received compensation for consulting services or speaker honoraria from ExceMed, Genzyme and Biogen. Linda Douw receives research support from Society in Science (Branco Weiss Fellowship). Martijn D Steenwijk has nothing to disclose. Jeroen JG Geurts is an editor of MS journal and serves on the editorial boards of Neurology and Frontiers of Neurology and is president of the Netherlands organization for health research and innovation. He has served as a consultant for Merck-Serono, Biogen, Novartis, Genzyme and Teva Pharmaceuticals.
Abstract: 96
Type: Scientific Session
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Introduction: An efficient network, like the human brain, features a combination of signal integration driven by long-range connections and local processing involving short-range connections. It is unknown, however, whether these connections are equally damaged in multiple sclerosis (MS) and how this relates to cognition. Therefore, we investigated the impact of structural damage to short- and long-range connections on both the functional connectome and cognitive function in MS.
Methods: From the Amsterdam MS cohort, 133 MS patients (age=54.2 (9.6)) and 48 healthy controls (HC; age=50.8 (7.0)) were included with neuropsychological testing and MRI. Structural connectivity was estimated from diffusion tensor images (DTI) using probabilistic tractography (MRtrix 3.0). The average fractional anisotropy (FA) as well as the average fiber length was determined in each tract between connecting pairs of brain regions based on the automated anatomical labelling (AAL) atlas. Connections were divided into short (< Q1), middle (Q1-Q3) and long (>Q3) range, based on the mean distribution of tract lengths in HC. Functional connectivity was computed between each pair of AAL regions, after artefact removal with FMRIB's ICA-based X-noisefier (FIX). The correspondence between individual functional connectivity matrices and the average connectivity matrix (based on all HC) was quantified. Statistical analyses were corrected for age, sex and education (p< 0.05; FDR-corrected).
Results: In general, the MS structural network showed connections with a reduced integrity and shorter distance compared to HC. In MS, the longest connections showed the largest reduction in integrity (z(FA)=-1.14; p< 0.001), whereas shorter connections were less severely affected (z(FA)=-0.29; p=0.03). In MS, integrity of long-range connections was more strongly related to cognitive performance than integrity of short-range connections (r=0.411; p< 0.001 and r=0.176; p=0.04, respectively). In addition, integrity loss of long-range connections was associated with a more abnormal functional network (r=0.204; p< 0.001), whereas damage to short-range connections did not relate to functional changes.
Conclusions: Our findings indicate that long-range connections are more vulnerable to MS-specific damage than short-range connections. Moreover, compared to short-range connections, damage to long-range connections has a larger impact on the functional network and cognitive performance.
Disclosure: Kim A Meijer receives funding from a research grant of Biogen. Menno M Schoonheim serves on the editorial board of Frontiers of Neurology, receives research support from the Dutch MS Research Foundation, grant number 13-820, and has received compensation for consulting services or speaker honoraria from ExceMed, Genzyme and Biogen. Linda Douw receives research support from Society in Science (Branco Weiss Fellowship). Martijn D Steenwijk has nothing to disclose. Jeroen JG Geurts is an editor of MS journal and serves on the editorial boards of Neurology and Frontiers of Neurology and is president of the Netherlands organization for health research and innovation. He has served as a consultant for Merck-Serono, Biogen, Novartis, Genzyme and Teva Pharmaceuticals.