D13 Modulation of resting state brain connectivity highlights potentiality for functional mri biomarkers. (13th September 2016) - Sánchez-Castañeda, Cristina
Abstract : Background: The spatial pattern of atrophy of a disease is related to its functional connectivity structure, mapped by resting-state functional magnetic resonance imaging (fMRI). Increased somatomotor and default mode resting-state networks play key roles in Huntington's disease pathophysiology. Objectives: To analyse brain functional connectivity in the somatomotor and default mode networks in patients with different Huntington's disease stages and HTT gene mutation sizes, its relationship with grey matter volume loss, and functional changes after pridopidine treatment. Methods: Ten patients and 10 controls without treatment underwent T1-weighted imaging and resting-state fMRI; four patients were also assessed after 3 months of pridopidine treatment (90 mg/day). The seed-based functional connectivity patterns from the posterior cingulate cortex and the supplementary motor area (SMA), considered cortical hubs of the somatomotor and default mode networks, respectively, were computed. Grey matter volume was measured by FSL voxel-based morphometry. Results: There was decreased grey matter volume in all cortical and subcortical areas involved in the somatomotor network in patients, with preservation of the SMA. Increased somatomotor and default mode network connectivity was seen in patients compared with controls. The volume of the SMA may be dependent on its connectivity. Pridopidine reduced the intensity of these aberrant connexions. Conclusions: Abnormal functional connectivity of the somatomotor and default mode networks was observed in patients with Huntington's disease, independent of brain atrophy, which may represent a marker of early dysfunction. Pridopidine modulates these netwoks by reducing connectivity. Results suggest that network connectivity may be used to measure response to experimental therapies.