Poster No:
2167
Submission Type:
Abstract Submission
Authors:
Isabella Orlando1, Joshua Tan2, Natasha Taylor3, Brandon Munn1, James Shine4, Claire O'Callaghan5
Institutions:
1University of Sydney, Sydney, NSW, 2The University of Sydney, Sydney, New South Wales, 3The University of Sydney, Camperdown, NSW, 4University of Sydney, Sydney, NA, 5University of Sydney, Sydney, New South Wales
First Author:
Co-Author(s):
Joshua Tan
The University of Sydney
Sydney, New South Wales
Introduction:
The locus coeruleus (LC) gives rise to highly diffuse noradrenergic projections targeting most brain regions, modulating brain states and arousal. Mammalian sleep studies have established an integral role for the LC in sleep: precise timing of LC firing during non-REM sleep is required for the coupling of spindles to slow wave oscillations and hippocampal sharp wave ripples (Eschenko et al., 2012; Osorio-Forero et al., 2021; Swift et al., 2018). In humans, these diverse rhythms and temporal couplings involving the LC remain relatively unexplored. Here we aim to uncover LC specific signatures during human non-REM sleep and how its activity modulates the coupling between sleep oscillations and transitions between brain states.
Methods:
Simultaneous electroencephalogram (EEG) and functional MRI (fMRI) were collected in thirty-three individuals (mean age = 22.1) at resting-state and across several sleep sessions (Gu et al., 2023, 2022). fMRI scans were pre-processed using fMRIprep. In addition, regression of head motion artifacts, the average combined signal of CSF and white matter, and low-pass filtering (0.1) was carried out. Time-series signal was extracted and z-scored from a parcellation of 456 regions (400 cortical regions (Schaefer et al., 2018), 54 subcortical regions (Tian et al., 2020), the noradrenergic LC (Ye et al., 2021) and the cholinergic nucleus basalis of Meynert (Zaborszky et al., 2008)). Individual sleep scans were time locked to 30-sec epochs of sleep stage scoring from EEG which was completed by registered polysomnographic technicians. Activity and complexity patterns of the LC was measured and compared across sleep stages.
Results:
We used simultaneous EEG and fMRI to identify patterns in subcortical and cortical activity, and their coupling, across wake and non-REM sleep stages 1 and 2. We found significant differences in activation patterns of the LC across the states of sleep, with activity during stage 2 significantly different to stage 1 sleep and more closely resembling awake activity (p = 0.03). Increased LC activity in stage 2 sleep, relative to stage 1 was associated with decreased recruitment of the default mode and frontoparietal control networks (p <0.05).
Conclusions:
Our results demonstrate a prominent difference in LC activity patterns between wake and non-REM sleep stages in human simultaneous EEG-fMRI analysis. These results substantiate a role for noradrenergic modulation of large-scale brain state organisation and oscillations during sleep. Ongoing analyses will calculate time-varying functional connectivity dynamics between the LC and other regions of interest across states and explore transitions between wake and sleep states in relation to LC phasic activity using low-dimensional energy landscapes (Munn et al., 2021). Given that non-REM sleep rhythms, as well as the LC itself, undergo profound alterations across neurodegenerative diseases of ageing, understanding the intricacies and specific profiles of sleep-wake circuitry in healthy humans is crucial for improving sleep treatment and probing the bidirectional relationships between altered sleep and neurodegenerative diseases of ageing.
Modeling and Analysis Methods:
fMRI Connectivity and Network Modeling 2
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Subcortical Structures
Transmitter Systems 1
Physiology, Metabolism and Neurotransmission :
Neurophysiology of Imaging Signals
Keywords:
Acetylcholine
Brainstem
Electroencephaolography (EEG)
FUNCTIONAL MRI
Noradrenaline
Sleep
Systems
Thalamus
1|2Indicates the priority used for review
Provide references using author date format
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