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Abstract
Objective: To investigate whether brain functional network connectivity is disrupted in patients with the behavioral variant of frontotemporal dementia (bvFTD).
Methods: Graph theoretical analysis was applied to resting state functional MRI data from 18 patients with probable bvFTD and 50 healthy individuals. Functional connectivity between 90 cortical and subcortical brain regions was estimated using bivariate correlation analysis and thresholded to construct a set of undirected graphs. Correlations between network properties and cognitive variables were tested.
Results: Global topologic organization of the functional brain network in bvFTD was significantly disrupted as indicated by reduced mean network degree, clustering coefficient, and global efficiency and increased characteristic path length and assortativity relative to normal subjects. Compared to controls, bvFTD data showed retention of major “hub” regions in the medial parietal, temporal, and occipital lobes, but cortical hubs were not noted in the frontal lobes. Medial and dorsal frontal regions, left caudate nucleus, left insular cortices, and some regions of the temporal, parietal, and occipital lobes showed decreased nodal centrality. BvFTD patients showed the greatest decrease in inter-regional connectivity between the frontal and occipital regions, and the insular cortices and occipital, temporal, subcortical, and frontal regions. In bvFTD, altered global network properties correlated with executive dysfunction.
Conclusions: Global and local functional networks are altered in bvFTD, suggesting a loss of efficiency in information exchange between both distant and close brain areas. Altered brain regions are located in structures that are closely associated with neuropathologic changes in bvFTD. Aberrant topology of the functional brain networks in bvFTD appears to underlie cognitive deficits in these patients.
GLOSSARY
- AAL=
- automated anatomical labeling;
- ACC=
- anterior cingulate cortex;
- AD=
- Alzheimer disease;
- bvFTD=
- behavioral variant of frontotemporal dementia;
- CDR-SB=
- Clinical Dementia Rating scale–sum of boxes;
- FDR=
- false discovery rate;
- fMRI=
- functional MRI;
- FTLD=
- frontotemporal lobar degeneration;
- GM=
- gray matter;
- ITG=
- inferior temporal gyrus;
- MMSE=
- Mini-Mental State Examination;
- pFDR=
- positive FDR;
- RS=
- resting state;
- SFG=
- superior frontal gyrus
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at www.neurology.org
Editorial, page 104
- Received November 28, 2012.
- Accepted in final form March 7, 2013.
- © 2013 American Academy of Neurology
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