Disruption of functional connectivity among subcortical arousal system and cortical networks in temporal lobe epilepsy
Growing evidence has demonstrated widespread brain network alterations in temporal lobe epilepsy (TLE). However, the relatively accurate portrait of the subcortical-cortical relationship for impaired consciousness in TLE remains unclear. We proposed that consciousness-impairing seizures may invade subcortical arousal system and corresponding cortical regions, resulting in functional abnormalities and information flow disturbances between subcortical and cortical networks. We performed resting-state fMRI in 26 patients with TLE and 30 matched healthy controls. All included patients were diagnosed with impaired awareness during focal temporal lobe seizures. Functional connectivity density was adopted to determine whether local or distant network alterations occurred in TLE, and Granger causality analysis (GCA) was utilized to assess the direction and magnitude of causal influence among these altered brain networks further. Patients showed increased local functional connectivity in several arousal structures, such as the midbrain, thalamus, and cortical regions including bilateral prefrontal cortex (PFC), left superior temporal pole, left posterior insula, and cerebellum (P < 0.05, FDR corrected). GCA analysis revealed that the casual effects among these regions in patients were significantly sparser than those in controls (P < 0.05, uncorrected), including decreased excitatory and inhibitory effects among the midbrain, thalamus and PFC, and decreased inhibitory effect from the cerebellum to PFC. These findings suggested that consciousness-impairing seizures in TLE are associated with functional alterations and disruption of information process between the subcortical arousal system and cortical network. Understanding the functional networks and innervation pathway involved in TLE can provide insights into the mechanism underlying seizure-related loss of consciousness.
KeywordsConsciousness Functional connectivity Granger causality analysis Subcortical arousal system Midbrain
We would like to express our gratitude to the patients and volunteers for participating in this study. This work was supported by the National Natural Science Foundation of China (81771407, 61533006, and 81471653).
Compliance with ethical standards
Conflict of interest
Rong Li, Chongyu Hu, Liangcheng Wang, Ding Liu, Dingyang Liu, Wei Liao, Bo Xiao, Huafu Chen and Li Feng declare that they have no conflict of interest.
All procedures followed were in accordance with the ethnical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinksi Declaration of 1975, and the applicable revisions at the time of the investigation. Informed consent was obtained from all patients for being included in the study.
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