Figure 2. Reduced functional connectivity (FC) in carriers compared to noncarriers, and the correlation between FC and memory performance.

The group comparisons (carriers versus noncarriers) of the ROI-to-ROI functional connectivity (FC) in the (A) left and (B) right hemisphere, respectively (each with nine ROIs). Bilateral ACC and bilateral PCC were each treated as one single ROI and were included in FC analyses in the left and right hemisphere. The pairwise ROI-to-ROI FC comparisons that reached significant difference (with FDR correction) were highlighted with a red square box. The colormap represented negative log p-values of group comparisons. ε4 carriers had significant lower FCs between CAUr and aHIPr, pHIPr, THAr, and PHCr than noncarriers. (C) Using the right caudate (CAUr) as the seed region, the seed-to-voxel analysis revealed that carriers had reduced FC between CAUr and a large cluster of brain regions in the right limbic system and the right occipital cortex. (D) By contrast, using the right anterior hippocampus (aHIPr) as the seed region, the seed-to-voxel analysis revealed that the reduced FC in carriers was largely limited to bilateral caudate nuclei. (E) After controlling for the BOLD timeseries in the aHIPr ROI, the seed-to-voxel analysis with CAUr as the seed region revealed that carriers had reduced FC between CAUr and a large cluster of brain regions in the right limbic system and the right occipital cortex. (F) By contrast, after controlling for the BOLD timeseries in the CAUr ROI, the seed-to-voxel analysis with aHIPr as the seed region did not found any significant cluster. All results showing here were controlled for age, for age, education, sex, and race. Seed-to-voxel analysis (C and D) were thresholded at voxel-wise p<0.001 (uncorrected) and cluster-wise p<0.05 (FDR corrected). Multivariate seed-to-voxel analysis (E and F) were thresholded at voxel-wise p<0.005 (uncorrected) and cluster-wise p<0.05 (FDR corrected). (G) Pearson correlation revealed a significant correlation (r=0.220, p=0.029, p_permutation=0.027 with 10000 permutations) between the adjusted FC_CAUr-aHIPr and adjusted HVLT-R retention (adjusted for age, education, sex, and race). Red crosses, carriers; blue circles, noncarriers. Abbreviations: ACC/PCC, anterior/posterior cingulate cortex; aHIP/pHIP, anterior/posterior hippocampus; CAU, caudate; FC, functional connectivity; FDR, false discovery rate; MB, mammillary body; OC, occipital cortex; ROI, region-of-interest; PUT, putamen. THA, thalamus; -l/-r: left/right (e.g., CAUl/CAUr, left and right caudate, respectively).