GroupICA dual regression analysis of resting state networks in a behavioral variant of frontotemporal dementia

Abstract

Functional MRI studies have revealed changes in default-mode and salience networks in neurodegenerative dementias, especially in Alzheimer's disease (AD). The purpose of this study was to analyze the whole brain cortex resting state networks (RSNs) in patients with behavioral variant frontotemporal dementia (bvFTD) by using resting state functional MRI (rfMRI). The group specific RSNs were identified by high model order independent component analysis (ICA) and a dual regression technique was used to detect between-group differences in the RSNs with p < 0.05 threshold corrected for multiple comparisons. A y-concatenation method was used to correct for multiple comparisons for multiple independent components, gray matter differences as well as the voxel level. We found increased connectivity in several networks within patients with bvFTD compared to the control group. The most prominent enhancement was seen in the right frontotemporal area and insula. A significant increase in functional connectivity was also detected in the left dorsal attention network (DAN), in anterior paracingulate-a default mode sub-network as well as in the anterior parts of the frontal pole. Notably the increased patterns of connectivity were seen in areas around atrophic regions. The present results demonstrate abnormal increased connectivity in several important brain networks including the DAN and default-mode network (DMN) in patients with bvFTD. These changes may be associated with decline in executive functions and attention as well as apathy, which are the major cognitive and neuropsychiatric defects in patients with frontotemporal dementia.

Keywords: default; dorsal attention network; frontotemporal dementia; functional MRI; resting state.

Figure 1

Resting-state networks from the control group identified as anatomically and functionally classical RNSs and which were used for the dual regression analysis. The normal resting-state networks are shown in FSL red-yellow color encoding using a 3 < z-score < 9 threshold.

Figure 2

Independent components (IC) with significant increase in functional connectivity in patients with bvFTD. The differences in resting state networks corrected for multiple comparison at voxel level in green and for y-concatenation correction for including all RSNs in lilac-blue, threshold p < 0.05. The differences between groups are also adjusted for gray matter differences. The involved RSN is presented in red-yellow color encoding with (3.6 < z-score < 6) threshold. Arrows in ICs 3, 17, and 33 indicate the y-concatenated results.

Figure 3

Regional atrophy was detected in several frontal and temporal regions and also in the posterior cingulate cortex, occipital cortex, and occipital poles. Increased connectivity was constantly placed around the atrophied area. Atrophic regions are in red, difference in the RSNs are in yellow (bvFTD > controls) and overlapping areas are in orange color. Arrows in ICs 3, 17, and 33 indicate the difference in the RSN.