Contributions
Abstract: EP1526
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Background: Cytoarchitectonically, Brodmann area 4 (BA4) has been subdivided into two sub-regions: Anterior (BA4a) and posterior (BA4p). FMRI studies have shown that each sub-region contributes to different functions: BA4p activity is modulated by attention, fine forces, and imagined forces, whereas BA4a is related to force production. What are the healthy functional connectivity (FC) rsfMRI network of BA4a and BA4p, and how are these networks modulated by pathologies such as MS?
Methods: 26 subjects (10 HS: 5F; mean (std) age 30 (3.65) yrs and 16 relapsing-remitting MS (RRMS) patients: 8F; mean (std) age 34 (2.13) yrs; median (range) 9-hole peg test (9-HPT)=20.8 (14.7-33.1) were assessed with fMRI whilst resting. Region of interest (ROI)-to-ROI connectivity matrices were calculated for each subject. The left (dominant) hemisphere BA4 sub-divisions were defined according to a cytoarchitectonic probability atlas. The whole brain grey-matter areas were used as target regions. At the second level, FC measures were calculated and compared at group level using ANOVA, one or two sample t-tests, as appropriate. ROIs' FC measures were then correlated with the 9-HPT. Results were corrected with an FDR (p< 0.05).
Results:
1.Individual groups: Both sub-regions in both groups display different rsfMRI connectivity networks. In MS, the BA4p network includes additional areas (e.g. posterior cerebellum, visual and inferior frontal regions).
2.A direct comparison of the networks in both groups shows that both BA4a/p sub-regions in MS have reduced FC to the right hemisphere. In the left hemisphere, MS exhibit higher FC than HS in motor and associative areas.
3.In MS, exploring correlations of the FC with the 9-HPT showed: i) worse performance in the 9-HPT was associated with reduced FC of BA4a with the right anterior cerebellum and the thalamus; ii) worse 9-HPT performance was also associated with greater FC of BA4a/p with the right hemisphere.
Discussion: The observation that BA4p is mainly connected to associative and higher order functional areas while BA4a is connected to motor-related areas supports previous findings. Also, the correlation of the FC with the 9-HPT indicates that the increased FC may be either an unsuccessful compensatory attempt or even a maladaptive mechanism of disease. Multi-modal protocols may enable the investigation of the pathophysiology of these changes, which could derive from axonal loss and demyelination, but also perfusion or synaptic activity impairment.
Disclosure:
A.A, M.T, K.F, E.D have nothing to disclose;
R.S.S. is funded by the UK MS Society and INSPIRED (a spinal cord imaging grant jointly funded by the Spinal Research, Wings for Life and the Craig Nielsen Foundation);
A.T.T 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]);
C.G.W.K. receives research grants (PI and co-applicant) from Spinal Research, Craig H. Neilsen Foundation, EPSRC, Wings for Life, UK MS Society, Horizon2020, NIHR/MRC;
Abstract: EP1526
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Background: Cytoarchitectonically, Brodmann area 4 (BA4) has been subdivided into two sub-regions: Anterior (BA4a) and posterior (BA4p). FMRI studies have shown that each sub-region contributes to different functions: BA4p activity is modulated by attention, fine forces, and imagined forces, whereas BA4a is related to force production. What are the healthy functional connectivity (FC) rsfMRI network of BA4a and BA4p, and how are these networks modulated by pathologies such as MS?
Methods: 26 subjects (10 HS: 5F; mean (std) age 30 (3.65) yrs and 16 relapsing-remitting MS (RRMS) patients: 8F; mean (std) age 34 (2.13) yrs; median (range) 9-hole peg test (9-HPT)=20.8 (14.7-33.1) were assessed with fMRI whilst resting. Region of interest (ROI)-to-ROI connectivity matrices were calculated for each subject. The left (dominant) hemisphere BA4 sub-divisions were defined according to a cytoarchitectonic probability atlas. The whole brain grey-matter areas were used as target regions. At the second level, FC measures were calculated and compared at group level using ANOVA, one or two sample t-tests, as appropriate. ROIs' FC measures were then correlated with the 9-HPT. Results were corrected with an FDR (p< 0.05).
Results:
1.Individual groups: Both sub-regions in both groups display different rsfMRI connectivity networks. In MS, the BA4p network includes additional areas (e.g. posterior cerebellum, visual and inferior frontal regions).
2.A direct comparison of the networks in both groups shows that both BA4a/p sub-regions in MS have reduced FC to the right hemisphere. In the left hemisphere, MS exhibit higher FC than HS in motor and associative areas.
3.In MS, exploring correlations of the FC with the 9-HPT showed: i) worse performance in the 9-HPT was associated with reduced FC of BA4a with the right anterior cerebellum and the thalamus; ii) worse 9-HPT performance was also associated with greater FC of BA4a/p with the right hemisphere.
Discussion: The observation that BA4p is mainly connected to associative and higher order functional areas while BA4a is connected to motor-related areas supports previous findings. Also, the correlation of the FC with the 9-HPT indicates that the increased FC may be either an unsuccessful compensatory attempt or even a maladaptive mechanism of disease. Multi-modal protocols may enable the investigation of the pathophysiology of these changes, which could derive from axonal loss and demyelination, but also perfusion or synaptic activity impairment.
Disclosure:
A.A, M.T, K.F, E.D have nothing to disclose;
R.S.S. is funded by the UK MS Society and INSPIRED (a spinal cord imaging grant jointly funded by the Spinal Research, Wings for Life and the Craig Nielsen Foundation);
A.T.T 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]);
C.G.W.K. receives research grants (PI and co-applicant) from Spinal Research, Craig H. Neilsen Foundation, EPSRC, Wings for Life, UK MS Society, Horizon2020, NIHR/MRC;