Functional Connectivity From Disease Epicenters in Frontotemporal Dementia

Area of Science:

• Neuroimaging
• Neuroscience
• Connectomics

Background:

• Frontotemporal dementia (FTD) spectrum disorders involve neurodegeneration.
• Understanding pathologic propagation requires network-based models.
• MRI connectomics can map functional connectivity changes.

Purpose of the Study:

• To explore functional connectivity reorganization in FTD using a novel graph theory-based MRI paradigm.
• To discern direct and indirect connections from disease epicenters.
• To relate connectivity patterns to neurodegeneration across FTD subtypes (bvFTD, nfvPPA, svPPA).

Main Methods:

• Defined disease epicenters (atrophy peaks) in FTD patients.
• Used stepwise functional connectivity (SFC) analyses in an independent FTD cohort.
• Assessed connectivity of regions directly and indirectly linked to epicenters.
• Correlated SFC architecture with atrophy patterns.

Main Results:

• Identified specific disease epicenters for bvFTD, nfvPPA, and svPPA.
• Observed widespread decreased SFC in bvFTD and nfvPPA, with increased SFC in connected regions.
• svPPA showed decreased SFC within temporal lobes and increased SFC in cerebellar regions.
• Topological distance from the left ITG correlated with gray matter volume in svPPA.

Conclusions:

• Each FTD syndrome displays a unique pattern of altered functional connectivity with its epicenter.
• SFC analysis provides novel insights into functional disconnection topology in FTD.
• These findings may inform future longitudinal studies modeling FTD progression.