Default-Mode Network Changes in Huntington’s Disease: An Integrated MRI Study of Functional Connectivity and Morphometry

Abstract

Previous MRI studies of functional connectivity in pre-symptomatic mutation carriers of Huntington’s disease (HD) have shown dysfunction of the Default-Mode Network (DMN). No data however are currently available on the DMN alterations in the symptomatic stages of the disease, which are characterized by cortical atrophy involving several DMN nodes. We assessed DMN integrity and its possible correlations with motor and cognitive symptoms in 26 symptomatic HD patients as compared to 22 normal volunteers, by analyzing resting state functional MRI data, using the Precuneal Cortex/Posterior Cingulate Cortices (PC/PCC) as seed, controlling at voxel level for the effect of atrophy by co-varying for gray matter volume. Direct correlation with PC/PCC was decreased, without correlation with atrophy, in the ventral medial prefrontal cortex (including anterior cingulate and subgenual cortex), right dorso-medial prefrontal cortex, and in the right inferior parietal cortex (mainly involving the angular gyrus). Negative correlations with PC/PCC were decreased bilaterally in the inferior parietal cortices, while a cluster in the right middle occipital gyrus presented increased correlation with PC/PCC. DMN changes in the ventral medial prefrontal cortex significantly correlated with the performance at the Stroop test (p = .0002). Widespread DMN changes, not correlating with the atrophy of the involved nodes, are present in symptomatic HD patients, and correlate with cognitive disturbances.

Abnormal resting-state connectivity of motor and cognitive networks in early manifest Huntington's disease

“…This indicates that striatal and extra-striatal functional connectivity changes can occur simply because of regional brain volume loss and thus may not reflect activity changes independent from atrophy. This notion is in line with a recent study using BPM in early HD (Quarantelli et al 2013), which demonstrated that connectivity changes in the caudate nucleus and other cortical regions can be explained by regional atrophy. On the other hand, in patients BPM analyses also revealed areas of aberrant activity that were not apparent without atrophy correction.…”

Visual system integrity and cognition in early Huntington's disease

“…Recent functional neuroimaging data obtained from patients with manifest HD indicate that some activity changes, e.g. in the caudate nucleus or in cortical regions, can be explained by regional atrophy (Quarantelli et al ., ). In line with previous studies (e.g.…”

Brain connectivity in neurodegenerative diseases—from phenotype to proteinopathy

“…Given the strong motor component in this disease, sensorimotor and basal ganglia-thalamocortical networks might be preferentially affected, although studies assessing these networks have provided mixed findings, some reporting reduced connectivity 91,92 and others reporting increased connectivity or mixed patterns. 93,94 These observations are not easy to interpret in view of the clear-cut and selective localization of HD pathology in the caudate nucleus, and the established role of this nucleus in large and well-defined corticostriatal loops (oculomotor, dorsolateral and ventral-orbital circuits). 95 Structural connectivity studies in HD have been more consistent.…”