Dataset Information

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.

SUBMITTER: Quarantelli M

PROVIDER: S-EPMC3747049 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Default-mode network changes in Huntington's disease: an integrated MRI study of functional connectivity and morphometry.

Quarantelli Mario M Salvatore Elena E Giorgio Sara Maria Delle Acque SM Filla Alessandro A Cervo Amedeo A Russo Cinzia Valeria CV Cocozza Sirio S Massarelli Marco M Brunetti Arturo A De Michele Giuseppe G

PloS one 20130819 8

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 volun ...[more]

PMID: 23977239

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Project description:BackgroundFunctional magnetic resonance imaging research suggests that major depressive disorder (MDD) in both adults and adolescents is marked by aberrant connectivity of the default mode network (DMN) during resting state. However, emotional dysregulation is also a key feature of MDD. No studies to date have examined emotion-related DMN pathology in adolescent depression. Comprehensively understanding the dynamics of DMN connectivity across brain states in individuals with depression with short disease histories could provide insight into the etiology of MDD.MethodsWe collected functional magnetic resonance imaging data during an emotion identification task and during resting state from 26 medication-free adolescents (13-17 years old) with MDD and 37 well-matched healthy control subjects. We examined between-group differences in blood oxygenation level-dependent task responses and emotion-dependent and resting-state functional connectivity of the two primary nodes of the DMN: medial prefrontal cortex and posterior cingulate cortex (PCC). Additionally, we examined between-group differences in DMN functional connectivity and its relationship to depression severity and onset.ResultsRelative to healthy control subjects, unmedicated adolescents with MDD demonstrated reduced medial prefrontal cortex and PCC emotion-related deactivation and greater medial prefrontal cortex and PCC emotion-dependent functional connectivity with precuneus, cingulate gyrus, and striatum/subcallosal cingulate gyrus. The PCC-subcallosal cingulate connectivity remained inflexibly elevated in the subjects with MDD versus healthy control subjects during resting state. Stronger PCC emotion-dependent functional connectivity was associated with greater depression severity and an earlier age of depression onset.ConclusionsAdolescent depression is associated with inflexibly elevated DMN connections. Given more recent evidence of DMN maturation throughout adolescence, our findings suggest that early-onset depression adversely affects normal development of functional brain networks.

Project description:BackgroundAt present, clinical use of MRI in Alzheimer's disease (AD) is mostly focused on the assessment of brain atrophy, namely in the hippocampal region. Despite this, multiple biomarkers reflecting structural and functional brain connectivity changes have shown promising results in the assessment of AD. To help identify the most relevant ones that may stand a chance of being used in clinical practice, we compared multiple biomarker in terms of their value to discriminate AD from healthy controls and analyzed their age dependency.Methods20 AD patients and 20 matched controls underwent MRI-scanning (3T GE), including T1-weighted, diffusion-MRI, and resting-state-fMRI (rsfMRI). Whole brain, white matter, gray matter, cortical gray matter and hippocampi volumes were measured using icobrain. rsfMRI between regions of the default-mode-network (DMN) was assessed using group independent-component-analysis. Median diffusivity and kurtosis were determined in gray and white-matter. DTI data was used to evaluate pairwise structural connectivity between lobar regions and the hippocampi.Logistic-Regression and Random-Forest models were trained to classify AD-status based on, respectively different isolated features and age, and feature-groups combined with age.ResultsHippocampal features, features reflecting the functional connectivity between the medial-Pre-Frontal-Cortex (mPFC) and the posterior regions of the DMN, and structural interhemispheric frontal connectivity showed the strongest differences between AD-patients and controls. Structural interhemispheric parietal connectivity, structural connectivity between the parietal lobe and hippocampus in the right hemisphere, and mPFC-DMN-features, showed only an association with AD-status (p < 0.05) but not with age. Hippocampi volumes showed an association both with age and AD-status (p < 0.05).Smallest-hippocampus-volume was the most discriminative feature. The best performance (accuracy:0.74, sensitivity:0.74, specificity:0.74) was obtained with an RF-model combining the best feature from each feature-group (smallest hippocampus volume, WM volume, median GM MD, lTPJ-mPFC connectivity and structural interhemispheric frontal connectivity) and age.ConclusionsBrain connectivity changes caused by AD are reflected in multiple MRI-biomarkers. Decline in both the functional DMN-connectivity and the parietal interhemispheric structural connectivity may assist sepparating healthy-aging driven changes from AD, complementing hippocampal volumes which are affected by both aging and AD.

Dataset Information

Default-mode network changes in Huntington's disease: an integrated MRI study of functional connectivity and morphometry.

Publications

Default-mode network changes in Huntington's disease: an integrated MRI study of functional connectivity and morphometry.

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