Contributions
Abstract: P496
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Imaging
Background: The primary motor cortex - Brodmann area 4 (BA4) - has two cytoarchitectonically distinct sub-regions: anterior (BA4a) and posterior (BA4p). Recently, in healthy subjects (HS), it has been shown that these two sub-regions possess unique BOLD-grip-force (GF) relationships during a grip task. Here, we aimed to assess whether, in multiple sclerosis (MS), the BOLD-GF relationship is altered in BA4 and shows regional differences between BA4a and BA4p.
Methods: 14 right-handed (RH) HS (9F; aged 31 (±4.64) years) and 14 RH relapsing-remitting (RR) MS patients (10F; aged 35 (±5.36) years; median (range) EDSS 3.5 (1.5-6.5)) were assessed with a 3T fMRI whilst performing a visuomotor power-grip task using a squeezeball with their RH. The paradigm comprised 75 trials divided into 5 GFs (20, 30, 40, 50, and 60% of maximum strength). Signal changes were fitted with higher-order polynomial expansions using a parametric design to assess linear and non-linear BOLD-GF effects. Significant voxels were defined using P< 0.05, corrected (FWE). In addition, to better understand the effect of disability, we divided the MS group based on their EDSS score into two sub-groups of low (EDSS≤3) and high (EDSS>3) disability.
Results: We report four major findings:
1) Main effect of movement: RRMS patients showed increased and greater activation extent compared with HS in both BA4a and BA4p (P=0.0001). RRMS patients also showed increased activations as their EDSS increased within BA4p only (P=0.001);
2) Mean BOLD-GF in BA4p: In patients with low EDSS, the BOLD-GF relationship was very similar to HS, whereas at higher EDSS, the regression of BOLD on GF deviated from the HS pattern or patients with low disability;
3) Mean BOLD-GF in BA4a: No differences were detected between MS subjects and HS;
4) Response profile comparison at subject level: The profile was very similar across subjects, when comparing responses of subjects at similar stages of the disease.
Conclusion: We have shown altered relationships in BA4 between BOLD and GF in patients with MS. The observation that the BOLD response to GF in patients with low EDSS was similar to that of HS, while it was consistently altered at higher EDSS (within BA4p but not BA4a) poses interesting mechanistic questions, suggesting differences not only in cytoarchitecture but also in myeloarchitecture of these two sub-regions, translating into differences in susceptibility and adaptive responses to MS pathology.
Disclosure:
Adnan Alahmadi, Matteo Pardini, Rebecca Samson, Egidio D´Angelo and Karl Friston have nothing to disclose.
Ahmed Toosy has received speaker honoraria from Biomedia, Sereno Symposia International Foundation, Bayer and meeting expenses from Biogen Idec.
Claudia GWK is on the editorial board of Functional Neurology and receives research grants (PI and co-applicant) from ISRT, EPSRC, Wings for Life, UK MS Society, Horizon2020, Biogen and Novartis.
Abstract: P496
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Imaging
Background: The primary motor cortex - Brodmann area 4 (BA4) - has two cytoarchitectonically distinct sub-regions: anterior (BA4a) and posterior (BA4p). Recently, in healthy subjects (HS), it has been shown that these two sub-regions possess unique BOLD-grip-force (GF) relationships during a grip task. Here, we aimed to assess whether, in multiple sclerosis (MS), the BOLD-GF relationship is altered in BA4 and shows regional differences between BA4a and BA4p.
Methods: 14 right-handed (RH) HS (9F; aged 31 (±4.64) years) and 14 RH relapsing-remitting (RR) MS patients (10F; aged 35 (±5.36) years; median (range) EDSS 3.5 (1.5-6.5)) were assessed with a 3T fMRI whilst performing a visuomotor power-grip task using a squeezeball with their RH. The paradigm comprised 75 trials divided into 5 GFs (20, 30, 40, 50, and 60% of maximum strength). Signal changes were fitted with higher-order polynomial expansions using a parametric design to assess linear and non-linear BOLD-GF effects. Significant voxels were defined using P< 0.05, corrected (FWE). In addition, to better understand the effect of disability, we divided the MS group based on their EDSS score into two sub-groups of low (EDSS≤3) and high (EDSS>3) disability.
Results: We report four major findings:
1) Main effect of movement: RRMS patients showed increased and greater activation extent compared with HS in both BA4a and BA4p (P=0.0001). RRMS patients also showed increased activations as their EDSS increased within BA4p only (P=0.001);
2) Mean BOLD-GF in BA4p: In patients with low EDSS, the BOLD-GF relationship was very similar to HS, whereas at higher EDSS, the regression of BOLD on GF deviated from the HS pattern or patients with low disability;
3) Mean BOLD-GF in BA4a: No differences were detected between MS subjects and HS;
4) Response profile comparison at subject level: The profile was very similar across subjects, when comparing responses of subjects at similar stages of the disease.
Conclusion: We have shown altered relationships in BA4 between BOLD and GF in patients with MS. The observation that the BOLD response to GF in patients with low EDSS was similar to that of HS, while it was consistently altered at higher EDSS (within BA4p but not BA4a) poses interesting mechanistic questions, suggesting differences not only in cytoarchitecture but also in myeloarchitecture of these two sub-regions, translating into differences in susceptibility and adaptive responses to MS pathology.
Disclosure:
Adnan Alahmadi, Matteo Pardini, Rebecca Samson, Egidio D´Angelo and Karl Friston have nothing to disclose.
Ahmed Toosy has received speaker honoraria from Biomedia, Sereno Symposia International Foundation, Bayer and meeting expenses from Biogen Idec.
Claudia GWK is on the editorial board of Functional Neurology and receives research grants (PI and co-applicant) from ISRT, EPSRC, Wings for Life, UK MS Society, Horizon2020, Biogen and Novartis.