Cerebral perfusion during pharmacologically induced sleep: Cortical and subcortical changes quantified by ASL MRI

Örzsik, Balázs, Asllani, Iris, Dijk, Derk-Jan, Harrison, Neil A and Cercignani, Mara ORCID: https://orcid.org/0000-0002-4550-2456 2025. Cerebral perfusion during pharmacologically induced sleep: Cortical and subcortical changes quantified by ASL MRI. NeuroImage 323 , 121611. 10.1016/j.neuroimage.2025.121611

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Abstract

Introduction Cerebral blood flow (CBF) reductions during non-REM sleep have been consistently demonstrated in positron emission tomography (PET) studies, but PET’s limitations restrict its use. Arterial spin labeling (ASL) MRI allows repeated, noninvasive CBF measurement but has rarely been applied to sleep. This study examined global and regional CBF changes during wakefulness and pharmacologically induced sleep after sleep deprivation, with an exploratory focus on the ascending arousal network (AAN). Methods Twenty-one healthy participants (13 male, 8 female; mean age = 22.4 ± 3.1 years) underwent ASL MRI during wake and sleep. Sleep was facilitated with 10 mg Zolpidem following sleep deprivation and verified through reduced button-press responses and increased high-frequency heart rate variability (HF-HRV). Pseudo-continuous ASL was acquired with a labeling duration of 1.9 s and post-labeling delay of 1.8 s. Results Sleep was confirmed in 19 participants; one was excluded for excessive head displacement, resulting in a final sample of 18. Grey matter CBF decreased from 59.7 ± 9.0 to 49.5 ± 8.1 ml/100g/min (p < 0.0001), and white matter CBF from 28.7 ± 4.9 to 25.1 ± 3.0 ml/100g/min (p < 0.001). Voxelwise analysis revealed reductions in cingulate, medial prefrontal cortex, precuneus, insula, thalamus, and caudate. ROI analysis indicated decreases in AAN regions including the Locus Coeruleus (−29.3 %, p = 0.0019), Medial Reticular Formation (−22.8 %, p = 0.0010), Pontis Oralis (−23.4 %, p = 0.0044), and Pedunculopontine Nucleus (−20.8 %, p = 0.0023). Discussion and Conclusion Observed perfusion decreases are consistent with PET evidence of cortical and thalamic downregulation during sleep and indicate suppression of brainstem arousal nuclei. These findings provide a detailed ASL characterization of cortical and brainstem perfusion changes during pharmacologically induced sleep, extending PET work and offering new insight into sleep-related arousal systems.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Psychology
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by/4.0/, Start Date: 2025-11-22
Publisher:	Elsevier
ISSN:	1053-8119
Date of First Compliant Deposit:	1 December 2025
Date of Acceptance:	22 November 2025
Last Modified:	01 Dec 2025 16:45
URI:	https://orca.cardiff.ac.uk/id/eprint/182789

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