Inter-Strain Differences in Default Mode Network: A Resting State fMRI Study on Spontaneously Hypertensive Rat and Wistar Kyoto Rat

Abstract

Genetic divergences among mammalian strains are presented phenotypically in various aspects of physical appearance such as body shape and facial features. Yet how genetic diversity is expressed in brain function still remains unclear. Functional connectivity has been shown to be a valuable approach in characterizing the relationship between brain functions and behaviors. Alterations in the brain default mode network (DMN) have been found in human neuropsychological disorders. In this study we selected the spontaneously hypertensive rat (SHR) and the Wistar Kyoto rat (WKY), two inbred rat strains with close genetic origins, to investigate variations in the DMN. Our results showed that the major DMN differences are the activities in hippocampal area and caudate putamen region. This may be correlated to the hyperactive behavior of the SHR strain. Advanced animal model studies on variations in the DMN may have potential to shed new light on translational medicine, especially with regard to neuropsychological disorders.

Figure 1. The DMN maps derived from RSC seeds.

(Dash line ROI at Bregma −4.8 mm).The maps show the pixels with correlation coefficients significantly larger than 0.3 (p < 0.0056). The SHR rats presented clusters including the orbital cortex, cingulate cortex, posterior parietal cortex, auditory cortex, somatosensory cortex, and caudate putamen. On the other hand, the WKY rats showed a dissimilar pattern. The SHR rats showed widespread connection between the caudate putamen and RSC seed, while the WKY rats presented a pattern with hippocampal activity.

Figure 2. Comparison of the connective strength within the DMNs.

(a) Histograms of correlation coefficients within the DMNs of the SHR and WKY rats. The differences in the distributions can be visualized. A quantitative comparison of the connective strength within the DMNs for the two strains is shown in (b). Correlation coefficients were transformed to Fisher’s z-scores. The SHR rats presented with significantly higher DMN strength (p < 10⁻¹⁰). The error bar denotes the standard deviation between voxels.

Figure 3. Network analysis based on 25 a priori ROIs.

Lines were depicted in case the correlation coefficients between the two groups were significantly different (p < 0.0056). (a) Network analysis under normal-dose anesthesia. (b) Network analysis under high-dose anesthesia. The graphical visualizations demonstrate that the respective connective organizations in the SHR and WKY rats were unequal under both normal- and high-dose anesthesia.

Figure 4. The DMN map under high-dose anesthesia derived from RSC seed.

The map shows the pixels with correlation coefficients significantly larger than 0.3 (p < 0.0062). An obvious decrease of DMN was evident in the SHR group, while the DMN of the WKY group tended to be disrupted into a different organization. Note that activity in the caudate putamen region emerged in the WKY group.