Dynamic functional abnormalities in generalized anxiety disorders and their increased network segregation of a hyperarousal brain state modulated by insomnia.

Abstract

Insomnia is frequently accompanied by the generalized anxiety disorder (GAD) but mostly fMRI studies investigated their aberrant functional connectivity (FC) without this issue. Recently, dynamic FC approach is prevailing to capture the time-varying fluctuations of spontaneous brain activities. Nevertheless, it is unclear how the dynamic FC characteristics are altered by insomnia in GAD. We acquired resting state fMRI and neuropsychological tests for the 17 comorbid GAD with insomnia (GAD/IS), 15 GAD and 24 healthy controls (HC). Then, based on the sliding window correlations, we estimated distinct brain states and statistically compared their dynamic properties. Further combining with graph theory, their network properties of each state among groups were accessed. Lastly, we examined associations between abnormal parameters and neuropsychological tests. We identified four brain states but did not observe significance on the state transitions. The mean dwell time and fraction of one globally hypoactive state accounted for high proportion of brain activities were significantly different (GAD > HC > GAD/IS). Meanwhile, we found gradual decreases in a brain state representing slight sleep/drowsiness (HC > GAD/IS > GAD). Additionally, we observed the GAD/IS patients had significantly increased network segregation and posterior cingulate cortex in a hyperarousal state, as well as significant associations with anxiety and insomnia severity. The influences of depression on dynamic FC properties in GAD are unclear yet and more subjects should be recruited. These results provide new insights about the temporal features in GAD and offer potential biomarkers to evaluate the impacts of insomnia.