Functional Connectivity Alterations Associated with Gray Matter Atrophy in Spinocerebellar Ataxia 10
Poster No:
241
Submission Type:
Abstract Submission
Authors:
Gustavo Padron-Rivera1, Amanda Chirino2, Angel Omar Romero-Molina3, Omar Rodriguez-Mendoza2, Diana-Laura Torres2, Gabriel Ramirez‐Garcia2, Erick-Humberto Pasaye-Alcara4, Juan Fernandez‐Ruiz2
Institutions:
1Universidad Nacional Autonoma de Mexico, Mexico City, CDMX, 2Universidad Nacional Autónoma de Mexico, Mexico City, Mexico, 3Universidad Nacional Autónoma de Mexico, Mexico City, Mexico City, 4Instituto de Neurobiología UNAM, Juriquilla, Queretaro
First Author:
Co-Author(s):
Introduction:
Spinocerebellar ataxia 10 (SCA10) is a rare form of an autosomal dominant neurodegenerative disorder characterized by cerebellar ataxia and epilepsy, that is caused by an expansion of the pentanucleotide (ATTCT) repeat in ATXN10 gene on 22q13.31 [Leonardi et al.,2014;Matsuura et al.,2000]. Previous volumetric analysis showed extensive grey matter degeneration in the cerebellum, brainstem, thalamus, putamen and pallidum [Hernandez-Castillo et al.,2019;Arruda et al.,2020]. However, there is no information regarding the possible functional connectivity alterations caused by the brain degeneration in SCA10.
Methods:
Twenty-six patients with SCA10 (15 female;age 50.38±9.91) and twenty-six age, and gender matched healthy subjects (HS) (15 female;age 50.65±9.28) were enrolled. All procedures were approved by the ethics committee of the UNAM in accordance with the Helsinki Declaration. Clinical assessments,including Scale for the Assessment and Rating of Ataxia (SARA) scores [Schmitz-Hübsch et al.,2006],and Montreal Cognitive Assessment (MoCA) scores [Larner,2016],were obtained for 21 patients.Functional and structural magnetic resonance imaging data were acquired at the Instituto de Neurobiologia of the UNAM,using a 3T GE MR750 Discovery with a 32-channel head coil.Voxel-based morphometry (VBM) for whole-brain volume analysis was conducted using FSL-VBM [Ashburner and Friston,2000].A two-sample t-test,with 10,000 permutations and age as a covariate, was employed to compare SCA10 patients with HS.The resulting significant clusters were identified,and their peak maxima were utilized as the center of 12-mm spheres.These spheres served as seed regions for subsequent functional analysis related to atrophy.Functional MRI were preprocessed and a voxel-wise seed-based analysis was conducted to determine Functional Connectivity (FC) between each atrophy-related seed and the bold signal of the entire brain for both groups.Finally,the functional maps obtained for each seed were compared between groups using a two-sample t-test (10,000 permutations),controlling for age.
Results:
VBM analysis revealed GM decrease in SCA10 patients including right:cerebellar VIIIb,cerebellar VI, cerebellar V, cerebellar crus II, occipital fusiform gyrus and precentral gyrus.Left:precentral gyrus, occipital fusiform gyrus, temporal pole, superior frontal gyrus. Seed-based FC showed significant differences (p < 0.05).Seed located at the right occipital fusiform gyrus right,occipital fusiform gyrus left,and temporal pole left showed a higher FC in SCA10 patients (Fig.1-C).On the other side,seed located at the occipital fusiform gyrus right,cerebellar VI right and occipital fusiform gyrus left showed higher FC in control subjects (Fig.2-C).Finally,the analysis did not show significant correlations between the FC obtained from any seed with the SARA,or MoCA scores.
·Fig.1 Functional connectivity maps (threshold P < 0.05) per each Seeds-ROIs and their voxelwise analysis results that showed the significant differences SCA10 > HS
·Fig.2 Functional connectivity maps (threshold P < 0.05) per each Seeds-ROIs and their voxelwise analysis results that showed the significant differences HS > SCA10
Conclusions:
These results confirm the cerebellar volume decrease in SCA10,and show the significant changes in FC associated to the degeneration.The FC changes clearly show the impact of the cerebellar degeneration beyond this structure,and highlight its relationships from seed-ROIs with the rest of the brain,e.g.,seed located in cerebellar VI right showed significant FC with precentral gyrus right by HS compared to patients signifies a functional disconnection between the cerebellum and motor cortices.Notably,our results showed both increases and decreases in FC as a consequence of the neurodegeneration.Also,some FC changes were ipsilateral,and other were contralateral.Further analyses are needed to fully understand these changes and its possible consequences in the motor and cognitive performance of the patients.These findings provide valuable insights into the neural mechanisms underlying motor impairments associated with SCA10,suggesting a disrupted interplay between the cerebellum and motor-related brain regions.Support:CONAHCYT Estancias Posdoctorales por Mexico to GPR CVU 273410,PAPIIT IN220019 and CONACYT A1-S-10669 to JFR.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Genetics:
Neurogenetic Syndromes
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural) 2
Neuroinformatics and Data Sharing:
Brain Atlases
Novel Imaging Acquisition Methods:
Anatomical MRI
Keywords:
Degenerative Disease
fMRI CONTRAST MECHANISMS
FUNCTIONAL MRI
MRI
1|2Indicates the priority used for review
Provide references using author date format
Ashburner J, Friston KJ (2000): Voxel-Based Morphometry — The Methods 821:805–821.
Hernandez-Castillo CR, Diaz R, Vaca-Palomares I, Torres DL, Chirino A, Campos-Romo A, Ochoa A, Rasmussen A, Fernandez-Ruiz J (2019): Extensive cerebellar and thalamic degeneration in spinocerebellar ataxia type 10. Park Relat Disord 66:182–188. https://doi.org/10.1016/j.parkreldis.2019.08.011.
Larner AJ (2016): Cognitive screening instruments: A practical approach. Cognitive Screening Instruments: A Practical Approach.
Leonardi L, Marcotulli C, McFarland KN, Tessa A, DiFabio R, Santorelli FM, Pierelli F, Ashizawa T, Casali C (2014): Spinocerebellar ataxia type 10 in Peru: the missing link in the Amerindian origin of the disease. J Neurol 261:1691–1694.
Matsuura T, Yamagata T, Burgess DL, Rasmussen A, Grewal RP, Watase K, Khajavi M, McCall AE, Davis CF, Zu L, Achari M, Pulst SM, Alonso E, Noebels JL, Nelson DL, Zoghbi HY, Ashizawa T (2000): Large expansion of the ATTCT pentanucleotide repeat in spinocerebellar ataxia type 10. Nat Genet 26:191–194.
Schmitz-Hübsch T, Du Montcel ST, Baliko L, Berciano J, Boesch S, Depondt C, Giunti P, Globas C, Infante J, Kang JS, Kremer B, Mariotti C, Melegh B, Pandolfo M, Rakowicz M, Ribai P, Rola R, Schöls L, Szymanski S, Van De Warrenburg BP, Dürr A, Klockgether T, Fancellu R (2006): Scale for the assessment and rating of ataxia: Development of a new clinical scale. Neurology 66:1717–1720.