A Comparison of Network Connectivity and Atrophy Patterns in Behavioral Variant Frontotemporal Dementia

Abstract

The relationship between the topography of atrophy and resting state networks in different neurodegenerative diseases is of current interest. We aimed to compare the distribution of atrophy and network connectivity in behavioral variant frontotemporal dementia (bvFTD). We identified 18 subjects with bvFTD and 22 age and gender-matched controls that had 3T task free functional MRI and volumetric MRI. Independent component analysis (ICA) was performed using controls. The salience network and default mode network (DMN) were identified from the ICA networks and used to select seed regions of interest for a voxel-wise connectivity analysis that was performed across all subjects. Seeds were placed in the left anterior cingulate (salience) and precuneus (DMN). Two sample t-tests were used to compare bvFTD and controls in voxel-wise connectivity maps, with age and gender entered as covariates. Voxel-based morphometry was used to assess patterns of grey matter loss in bvFTD compared to controls. Grey matter loss was observed predominantly in the medial frontal and bilateral temporal lobes in bvFTD (Figure). Resting state fMRI results will be reported in four categories (Figure). In bvFTD relative to controls, the magnitude of direct connectivity was: 1) Reduced in right anterior insula and inferior frontal lobes for the salience seed. Grey matter loss was observed in these same regions. 2) Increased in anterior dorsolateral frontal lobes for the salience seed. These regions are not typically considered a major salience hub, and no grey matter loss was observed in these regions. 3) Reduced in bilateral temporal lobe and medial prefrontal cortex for the DMN seed. Grey matter loss was observed in these regions. 4) Increased in precuneus and posterior cingulate for the DMN seed. These regions are considered to be part of the DMN, and did not show grey matter loss. Both the salience and DMN networks show functional reorganization in a similar way. Direct connectivity was reduced in areas of neurodegenerative grey matter loss, and new areas of connectivity were formed in areas of relatively healthy brain. The areas of new connectivity can occur either inside or outside the topographic distribution of the two networks.