A New Analysis of Resting State Connectivity and Graph Theory Reveals Distinctive Short-Term Modulations due to Whisker Stimulation in Rats

Silke Kreitz, Benito de Celis Alonso, Michael Uder, Andreas Hess

Resting state (RS) connectivity has been increasingly studied in healthy and diseased brains in humans and animals. This paper presents a new method to analyze RS data from fMRI that combines multiple seed correlation analysis with graph-theory (MSRA). We characterize and evaluate this new method in relation to two other graph-theoretical methods and ICA. The graph-theoretical methods calculate cross-correlations of regional average time-courses, one using seed regions of the same size (SRCC) and the other using whole brain structure regions (RCCA). We evaluated the reproducibility, power, and capacity of these methods to characterize short-term RS modulation to unilateral physiological whisker stimulation in rats. Graph-theoretical networks found with the MSRA approach were highly reproducible, and their communities showed large overlaps with ICA components. Additionally, MSRA was the only one of all tested methods that had the power to detect significant RS modulations induced by whisker stimulation that are controlled by family-wise error rate (FWE). Compared to the reduced resting state network connectivity during task performance, these modulations implied decreased connectivity strength in the bilateral sensorimotor and entorhinal cortex. Additionally, the contralateral ventromedial thalamus (part of the barrel field related lemniscal pathway) and the hypothalamus showed reduced connectivity. Enhanced connectivity was observed in the amygdala, especially the contralateral basolateral amygdala (involved in emotional learning processes). In conclusion, MSRA is a powerful analytical approach that can reliably detect tiny modulations of RS connectivity. It shows a great promise as a method for studying RS dynamics in healthy and pathological conditions.