Thalamic network under wakefulness after sleep onset and its coupling with daytime fatigue in insomnia disorder: An EEG-fMRI study

Background: Fatigue is the most common daytime impairment of insomnia disorder (ID). Thalamus is acknowledged as the key brain region closely associated with fatigue. However, the thalamus-based neurobio-logical mechanisms of fatigue in patients with ID remain unknown.Methods: Forty-two ID patients and twenty-eight well-matched healthy controls (HCs) underwent simultaneous electroencephalography--functional magnetic resonance imaging. We calculated the functional connectivity (FC) between the thalamic seed and each voxel across the whole brain in two conditions of wakefulness--after sleep onset (WASO) and before sleep onset. A linear mixed effect model was used to determine the condition effect of the thalamic FC. The correlation between daytime fatigue and the thalamic connectivity was explored.Results: After sleep onset, the connectivity with the bilateral thalamus was increased in the cerebellar and cortical regions. Compared with HCs, ID patients showed significantly lower FC between left thalamus and left cere-bellum under the WASO condition. Furthermore, thalamic connectivity with cerebellum under the WASO con-dition was negatively correlated with Fatigue Severity Scale scores in the pooled sample.Conclusions: These findings contribute to an emerging framework that reveals the link between insomnia-related daytime fatigue and the altered thalamic network after sleep onset, further highlighting the possibility that this neural pathway is a therapeutic target for meaningfully mitigating fatigue.

Automated summary

This study found that there was a decreased connectivity between the left thalamus and the left cerebellum in patients with insomnia disorder (ID) during the wakefulness after sleep onset (WASO) condition, compared to healthy controls. Furthermore, the thalamic connectivity with the cerebellum was negatively correlated with Fatigue Severity Scale scores. These findings highlight the link between insomnia-related daytime fatigue and the altered thalamic network after sleep onset and suggest the potential of targeting this neural pathway for fatigue mitigation.