Decreased functional connectivity in thalamic-cortex and default mode network in idiopathic generalized epilepsy

Idiopathic generalized epilepsy (IGE) is a common group of epilepsy syndromes associated with abnormalities in thalamo-cortical circuits and default mode network (DMN) connectivity. The thalamus and the DMN are key brain regions critical for sustaining normal cognitive functions. Alterations in the functionality of these regions may contribute indirectly to the cognitive impairments observed in IGE. In this study, we performed functional connectivity analysis to calculate the functional connectivity of the thalamo-cortical circuitry, intra-network of the DMN, and between the DMN and other brain networks. We evaluated the neuropsychological performance of patients with IGE and explored the correlation between abnormal network connectivity and neuropsychological assessment scores. Compared with healthy controls, IGE exhibited reduced functional connectivity between the thalamus and multiple regions including the cerebellum, motor-related cerebral cortex, basal ganglia, and cingulate cortex. Within the DMN, IGE exhibited widespread reductions in functional connectivity relative to healthy controls, predominantly involving the medial superior frontal gyrus, posterior cingulate cortex, anterior cingulate cortex, angular gyrus and precuneus. Regarding inter-network connectivity between the DMN and other brain networks, IGE showed enhanced functional connectivity of the DMN with the visual network, ventral attention network and sensorimotor network. By contrast, DMN connectivity was reduced with the cerebellar network, limbic network and dorsal attention network. Functional connectivity strength among key nodes of the DMN was negatively correlated with global cognitive level. This study identified reduced functional connectivity in both the DMN and thalamus, with pronounced reductions in functional connectivity between the cerebellum and each of these two brain structures. Such alterations may constitute an important feature of brain functional impairment in IGE. The role played by the cerebellum also warrants further attention. These findings contribute to a deeper understanding of the pathophysiological mechanisms of IGE.