Figure 1.
After the pre-processing steps, all rsfMRI data were analysed using the REST-toolbox. 1) Whole brain seed correlation analysis: The smoothed data and masks for every seed region were loaded and the filter was set between 0.01 and 0.1 Hz. Time courses of the low frequency fluctuations of the BOLD-signal were computed for each seed region from each subject. The functional correlation between the time courses of each seed region was calculated and the correlation coefficients were z-transformed, resulting in functional connectivity (FC) matrices for each subject. Then, the mean z-transformed FC matrices were calculated for the WT and TG groups. 2) Pairwise seed correlation analyses: Interhemispheric FC (hatched regions) was assessed between each seed region in the left hemisphere (yellow) and the corresponding region in the right hemisphere. Then, mean z-transformed FC maps of the WT and TG groups were computed in SPM.
Figure 2.
Results of the whole brain seed correlation analysis for the WT and TG groups.
A) The FC matrices representing the mean correlation values between each seed region for the WT group and the TG group (FDR-corrected p < 0.05). The last figure of panel A shows the functional correlations that are significantly different between the WT and TG groups (p <0.05). The colour scale on the right represents the strength of the correlation. The functional correlation coefficients were calculated between the cingulate cortex (Cg), the motor cortex (MC), the somatosensory cortex (SC), the thalamus (T), the hippocampus (Hc), the temporal auditory cortex (AU), the visual cortex (VC) and the retrosplenial cortex (Rs) for the left (l) and the right (r) hemisphere. B) Grey lines represent correlation strength between seed regions (red dots). The thickness of the line is proportionate to the strength of the correlation: The thickest lines represent correlation coefficients > 0.35, the intermediate lines represent correlation coefficients 0.15–0.35, and the thinnest lines represent correlation coefficients < 0.15.
Figure 3.
Results of the pairwise seed correlation analysis for the WT and TG groups.
A = the motor cortex (MC), B = the somatosensory cortex (SC), C = the hippocampus (Hc). The left figure shows the location of the seed region (yellow) and the regions that were selected to assess interhemispheric FC (hatched) on the Franklin and Paxinos anatomical mouse brain atlas. The middle figure shows the mean statistical interhemispheric FC map of the WT group and the right figure shows the mean statistical FC map of the TG group. The mean FC maps for both groups are overlaid on an EPI image. The colour bar on the right represents the t-value, i.e., a measure of the strength of the functional correlation. The interhemispheric FC of the MC was similar in WT and TG groups. The interhemispheric FC of the SC and the Hc was lower in the TG group (FWE-corrected p < 0.05) than in the WT group (indicated by the green arrows).
Figure 4.
Results of immunofluorescence staining of the left sensory cortex for a representative WT and TG animal.
A) The synapses (red) and amyloid plaques (green) for the WT group and TG group. Scale bar indicates 200 µm. The third column shows a close-up of an amyloid plaque and the surrounding synapses (scale bar indicates 50 µm). B) Astrocytes (red) and amyloid plaques (green) for the WT group and TG group. Scale bar indicates 200 µm. The third column shows a close-up of a plaque and the surrounding astrocytes (scale bar indicates 50 µm). C) Microglia (red) and amyloid plaques (green) for the WT group and TG group. Scale bar indicates 200 µm. The third column shows a close-up of a plaque and the surrounding microglia (scale bar indicates 50 µm), in which the cell nuclei are shown in blue.