Contributions
Abstract: EP1549
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Introduction: Cognitive impairment in multiple sclerosis (MS) has been related to structural brain damage, but the mechanisms linking these two phenomena are unclear. Resting-state functional MRI (rsfMRI) is a promising method to evaluate this link, since abnormal functional connectivity (FC) patterns may reflect either maladaptive or compensatory mechanisms, favouring or limiting clinical consequences of structural brain damage even from early stages of MS. Independent component analysis (ICA) is a tool to study FC by decomposing within-voxel BOLD signal into different components. Voxel clusters with temporally correlated components form the specific resting-state functional networks (RSN), with clearly defined cognitive roles.
Aims: To characterise, in patients with a clinically isolated syndrome (CIS), the different RSN and the association between FC within the RSN and cognitive performance.
Methods: We included 19 CIS patients (9 female, mean age 36±9 years) and 12 healthy controls
(HC, 8 female, 35±8 years). All subjects were scanned (T1- and T2-weighted images, rsfMRI) in a 3T scanner. Patients underwent cognitive assessment (Symbol Digit Modalities Test, SDMT). CONN-FC toolbox was used to extract RSN with ICA and to perform statistical analyses: generalised linear models adjusted for age and gender. P-value thresholds to define significance were < 0.001 (uncorrected) at the voxel level and < 0.05 (FDR-corrected) at the cluster level.
Results: None of the RSN showed significant differences in within-network FC between groups. Yet using a more liberal threshold (p< 0.05 at voxel level), patients showed a trend towards higher FC in the default mode (b=0.82, p< 0.0001) and frontoparietal (b=0.54, p< 0.01) RSN, and lower FC in the dorsal-attention network (b=-0.73, p< 0.01) than controls. In patients, lower FC in several RSN (including frontoparietal and dorsal-attention RSN) was associated with worse cognitive performance (b=0.04, p=0.004). Instead, higher FC in the salience RSN (precuneus) was associated with lower cognitive performance
(b=-0.06; p=0.006).
Conclusions: In early CIS, FC within RSN is relatively intact. However, a trend towards altered FC in areas strongly associated with cognition was observed in patients. Longitudinal studies will address whether these findings indicate an incipient FC deterioration in the CIS, therefore reflecting both maladaptive and compensatory mechanisms leading to or limiting cognitive decline in MS.
Disclosure:
Marta Batlle has nothing to disclose
Adnan A.S. Alahmadi has nothing to disclose
Sara Collorone had a MAGNIMS-ECTRIMS fellowship
Ferran Prados has a Guarantor of Brain fellowship
Baris Kanber has nothing to disclose
Sebastien Ourselin has nothing to disclose
Ahmed Toosy has received speaker honoraria from Biomedia, Sereno Symposia International Foundation, Bayer and meeting expenses from Biogen Idec and is the UK-PI for two clinical trials sponsored by MEDDAY pharmaceutical company (MD1003 in optic neuropathy [MS-ON] and progressive MS [MS-SPI2]).
Claudia A.M. Gandini Wheeler-Kingshott receives research grants (PI and co-applicant) from Spinal Research, Craig H. Neilsen Foundation, EPSRC, Wings for Life, UK MS Society, Horizon2020, NIHR/MRC.
Olga Ciccarelli receives research funding from UK MS Society, National MS Society, Rosetrees trust and NIHR UCLH BRC. OC serves as a consultant for Biogen, Novartis, Roche, Genzyme, Teva and GE healthcare.
Carmen Tur has received an ECTRIMS post-doctoral research fellowship in 2015. She has also received honoraria and support for travelling from Bayer-Schering, Teva, Merck-Serono and Serono Foundation, Biogen, Sanofi-Aventis, Novartis, and Ismar Healthcare.
Abstract: EP1549
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Introduction: Cognitive impairment in multiple sclerosis (MS) has been related to structural brain damage, but the mechanisms linking these two phenomena are unclear. Resting-state functional MRI (rsfMRI) is a promising method to evaluate this link, since abnormal functional connectivity (FC) patterns may reflect either maladaptive or compensatory mechanisms, favouring or limiting clinical consequences of structural brain damage even from early stages of MS. Independent component analysis (ICA) is a tool to study FC by decomposing within-voxel BOLD signal into different components. Voxel clusters with temporally correlated components form the specific resting-state functional networks (RSN), with clearly defined cognitive roles.
Aims: To characterise, in patients with a clinically isolated syndrome (CIS), the different RSN and the association between FC within the RSN and cognitive performance.
Methods: We included 19 CIS patients (9 female, mean age 36±9 years) and 12 healthy controls
(HC, 8 female, 35±8 years). All subjects were scanned (T1- and T2-weighted images, rsfMRI) in a 3T scanner. Patients underwent cognitive assessment (Symbol Digit Modalities Test, SDMT). CONN-FC toolbox was used to extract RSN with ICA and to perform statistical analyses: generalised linear models adjusted for age and gender. P-value thresholds to define significance were < 0.001 (uncorrected) at the voxel level and < 0.05 (FDR-corrected) at the cluster level.
Results: None of the RSN showed significant differences in within-network FC between groups. Yet using a more liberal threshold (p< 0.05 at voxel level), patients showed a trend towards higher FC in the default mode (b=0.82, p< 0.0001) and frontoparietal (b=0.54, p< 0.01) RSN, and lower FC in the dorsal-attention network (b=-0.73, p< 0.01) than controls. In patients, lower FC in several RSN (including frontoparietal and dorsal-attention RSN) was associated with worse cognitive performance (b=0.04, p=0.004). Instead, higher FC in the salience RSN (precuneus) was associated with lower cognitive performance
(b=-0.06; p=0.006).
Conclusions: In early CIS, FC within RSN is relatively intact. However, a trend towards altered FC in areas strongly associated with cognition was observed in patients. Longitudinal studies will address whether these findings indicate an incipient FC deterioration in the CIS, therefore reflecting both maladaptive and compensatory mechanisms leading to or limiting cognitive decline in MS.
Disclosure:
Marta Batlle has nothing to disclose
Adnan A.S. Alahmadi has nothing to disclose
Sara Collorone had a MAGNIMS-ECTRIMS fellowship
Ferran Prados has a Guarantor of Brain fellowship
Baris Kanber has nothing to disclose
Sebastien Ourselin has nothing to disclose
Ahmed Toosy has received speaker honoraria from Biomedia, Sereno Symposia International Foundation, Bayer and meeting expenses from Biogen Idec and is the UK-PI for two clinical trials sponsored by MEDDAY pharmaceutical company (MD1003 in optic neuropathy [MS-ON] and progressive MS [MS-SPI2]).
Claudia A.M. Gandini Wheeler-Kingshott receives research grants (PI and co-applicant) from Spinal Research, Craig H. Neilsen Foundation, EPSRC, Wings for Life, UK MS Society, Horizon2020, NIHR/MRC.
Olga Ciccarelli receives research funding from UK MS Society, National MS Society, Rosetrees trust and NIHR UCLH BRC. OC serves as a consultant for Biogen, Novartis, Roche, Genzyme, Teva and GE healthcare.
Carmen Tur has received an ECTRIMS post-doctoral research fellowship in 2015. She has also received honoraria and support for travelling from Bayer-Schering, Teva, Merck-Serono and Serono Foundation, Biogen, Sanofi-Aventis, Novartis, and Ismar Healthcare.