Disrupted brainstem-parahippocampal connectivity identified as a biomarker for delirium


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Background and objectives

Delirium, commonly observed in critically ill patients following intracerebral hemorrhage (ICH), is an acute neuropsychiatric disorder characterized by disturbances in attention, consciousness, and cognition. The underlying brain network mechanisms remain poorly understood. This study aimed to explore the functional connectivity (FC) of the ascending reticular activating system (ARAS) in delirium patients with basal ganglia ICH and to identify potential biomarkers for predicting delirium onset.

Methods

In this cross-sectional study, brain networkomics techniques were used to examine the FC within the ARAS in ICH patients with and without delirium. A two-sample t-test compared differences in ARAS connectivity between delirium and non-delirium groups, identifying abnormal brain regions and their corresponding FC values. Receiver operating characteristic curve analysis was then performed to evaluate the predictive value of FC for delirium onset.

Results

A significant disruption in FC between the brainstem ARAS nuclei and the left parahippocampal gyrus was observed in ICH patients with delirium. The FC strength between these regions was a reliable predictor of delirium occurrence, with an area under the curve of 0.893, indicating high predictive accuracy.

Conclusions

Disruption of FC between the brainstem ARAS nuclei and the left parahippocampal gyrus may underlie the pathogenesis of delirium. The corresponding FC strength could serve as an effective biomarker for predicting delirium onset. Restoring normal connectivity between these regions holds potential as a strategy for early reversal of delirium and represents a key focus for future research.

Source:

Journal reference:

Zhang, J., et al. (2025). Disrupted Connectivity of the Brainstem Ascending Reticular Activating System Nuclei-left Parahippocampal Gyrus Could Reveal Mechanisms of Delirium Following Basal Ganglia Intracerebral Hemorrhage. Neurosurgical Subspecialties. doi.org/10.14218/nsss.2025.00030


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