Cristina Sánchez-Castañeda1,2, Francesco de Pasquale2,3, Chiara Falletta Caravasso2, Massimo Marano4, Sabrina Maffi4, Simone Migliore4,5, Umberto Sabatini2,6, Ferdinando Squitieri4. 1. Department of Medicine, School of Medicine and Health Sciences, IDIBAPS, Neuroscience Institute, University of Barcelona, Barcelona, Spain. 2. Radiology Department, IRCCS Santa Lucia Foundation, Rome, Italy. 3. Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy. 4. Huntington and Rare Diseases Unit, IRCSS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy. 5. LIRH Foundation, Rome, Italy. 6. Neuroradiology Department, Magna Graecia University, Catanzaro, Italy.
Abstract
AIMS: To analyze brain functional connectivity in the somatomotor and default-mode networks (DMNs) of patients with Huntington disease (HD), its relationship with gray matter (GM) volume loss, and functional changes after pridopidine treatment. METHODS: Ten patients and ten untreated controls underwent T1-weighted imaging and resting-state functional magnetic resonance imaging (fMRI); four patients were also assessed after 3 months of pridopidine treatment (90 mg/d). The seed-based functional connectivity patterns from the posterior cingulate cortex and the supplementary motor area (SMA), considered cortical hubs of the DMN and somatomotor networks, respectively, were computed. FMRIB Software Library voxel-based morphometry measured GM volume. RESULTS: Patients had GM volume decrease in all cortical and subcortical areas of the somatomotor network with preservation of the SMA, and increased somatomotor and DMN connectivity. In DMN structures, functional connectivity impairment preceded volume loss. Pridopidine reduced the intensity of these aberrant connections. CONCLUSION: The abnormal connectivity of the somatomotor and DMN observed in HD patients may represent an early dysfunction marker, as it preceded volume loss in DMN. Pridopidine reduced connectivity of these networks in all four treated patients, suggesting that connectivity is sensitive to treatment response.
AIMS: To analyze brain functional connectivity in the somatomotor and default-mode networks (DMNs) of patients with Huntington disease (HD), its relationship with gray matter (GM) volume loss, and functional changes after pridopidine treatment. METHODS: Ten patients and ten untreated controls underwent T1-weighted imaging and resting-state functional magnetic resonance imaging (fMRI); four patients were also assessed after 3 months of pridopidine treatment (90 mg/d). The seed-based functional connectivity patterns from the posterior cingulate cortex and the supplementary motor area (SMA), considered cortical hubs of the DMN and somatomotor networks, respectively, were computed. FMRIB Software Library voxel-based morphometry measured GM volume. RESULTS:Patients had GM volume decrease in all cortical and subcortical areas of the somatomotor network with preservation of the SMA, and increased somatomotor and DMN connectivity. In DMN structures, functional connectivity impairment preceded volume loss. Pridopidine reduced the intensity of these aberrant connections. CONCLUSION: The abnormal connectivity of the somatomotor and DMN observed in HDpatients may represent an early dysfunction marker, as it preceded volume loss in DMN. Pridopidine reduced connectivity of these networks in all four treated patients, suggesting that connectivity is sensitive to treatment response.
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