Resting-state Functional Connectivity in Children and Adults with Spinal Muscular Atrophy
Emilie Groulx-Boivin1, Helen Carlson2, Andrea Oliveira-Carneiro3, Amalia Floer2, Adam Kirton4, Jean Mah4, Christine Saint-Martin5, Roberta La Piana6, Maryam Oskoui7
1Departments of Pediatrics and Neurology & Neurosurgery, Montreal Children’s Hospital, McGill University, 2Alberta Children's Hospital Research Institute, University of Calgary, 3Research Institute, McGill University Health Centre, 4Alberta Children's Hospital Research Institute, University of Calgary and Department of Pediatrics, Cumming School of Medicine, University of Calgary, 5Division of Pediatric Radiology, Department of Medical Imaging, Montreal Children's Hospital, McGill University, 6Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University, 7Departments of Pediatrics and Neurology & Neurosurgery, McGill University and Research Institute, McGill University Health Centre
Objective:
This study aimed to investigate resting-state functional connectivity in children and adults with spinal muscular atrophy (SMA).
Background:
Despite the use of disease-modifying therapies, many individuals with SMA have chronic motor impairments. Although neuromodulator therapies have been used successfully in other neurological disorders to augment motor learning, the effects of early motor unit dysfunction on brain connectivity in SMA remain largely unknown.
Design/Methods:
We conducted a multicenter cross-sectional case control study of individuals with 5q SMA and peer controls matched by age and sex. Blood oxygen level dependent (BOLD) fluctuations at rest were acquired on a 3T magnetic resonance imaging (MRI) scanner. Seed-based functional connectivity analyses were performed using CONN in SPM12, with site as a covariate. Connectivity between regions of interest identified on primary analysis, expressed as Fisher-transformed correlation coefficients, were then assessed for correlation with motor function scores and SMN2 copy number.
Results:
A total of 42 participants completed the study procedures, with a mean age of 17.4 years (range 7-40) and comprising 67% males. Compared to their peer controls, individuals with SMA demonstrated lower functional connectivity within the cerebellum and within salience network regions, alongside higher functional connectivity between the precentral gyri and the default mode network (corrected p<0.05). No association between the connectivity values and motor function or SMN2 copy number was observed in individuals with SMA when controlling for age at MRI and site.
Conclusions:
Differences in resting-state functional connectivity in individuals with SMA encompass various brain regions, extending beyond motor areas. Insights into the reorganization of brain networks in SMA may open new pathways for adjunctive therapies to augment motor and other types of learning in symptomatic patients, optimizing outcomes.