Identifying the bioimaging features of Alzheimer's disease based on pupillary light response-driven brain-wide fMRI in awake mice.

Liu, X; Hike, D; Choi, S; Man, W; Ran, C; Zhou, XA; Jiang, Y; Yu, X

Identifying the bioimaging features of Alzheimer's disease based on pupillary light response-driven brain-wide fMRI in awake mice.

Liu, X Hike, D Choi, S Man, W Ran, C Zhou, XA Jiang, Y Yu, X

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Publisher:: Springer Nature
Publication Type:: Journal Article
Citation:: Nat Commun, 2024, 15, (1), pp. 9657
Issue Date:: 2024-11-07

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Field	Value	Language
dc.contributor.author	Liu, X
dc.contributor.author	Hike, D
dc.contributor.author	Choi, S
dc.contributor.author	Man, W
dc.contributor.author	Ran, C
dc.contributor.author	Zhou, XA
dc.contributor.author	Jiang, Y
dc.contributor.author	Yu, X https://orcid.org/0000-0002-0269-5649
dc.date.accessioned	2024-12-02T01:18:01Z
dc.date.available	2024-10-23
dc.date.available	2024-12-02T01:18:01Z
dc.date.issued	2024-11-07
dc.identifier.citation	Nat Commun, 2024, 15, (1), pp. 9657
dc.identifier.issn	2041-1723
dc.identifier.issn	2041-1723
dc.identifier.uri	http://hdl.handle.net/10453/182226
dc.description.abstract	Pupil dynamics has emerged as a critical non-invasive indicator of brain state changes. In particular, pupillary-light-responses (PLR) in Alzheimer's disease (AD) patients show potential as biomarkers for brain degeneration. To investigate AD-specific PLR and its underlying neuromodulatory sources, we combine high-resolution awake mouse fMRI with real-time pupillometry to map brain-wide event-related correlation patterns based on illumination-driven pupil constriction ( P c ) and post-illumination pupil dilation recovery (amplitude, P d , and time, T). The P c -driven differential analysis reveals altered visual signal processing and reduced thalamocortical activation in AD mice in comparison with wild-type (WT) control mice. In contrast, the post-illumination pupil dilation recovery-based fMRI highlights multiple brain areas associated with AD brain degeneration, including the cingulate cortex, hippocampus, septal area of the basal forebrain, medial raphe nucleus, and pontine reticular nuclei (PRN). Additionally, the brain-wide functional connectivity analysis highlights the most significant changes in PRN of AD mice, which serves as the major subcortical relay nuclei underlying oculomotor function. This work integrates non-invasive pupil-fMRI measurements in preclinical models to identify pupillary biomarkers based on brain-wide functional changes, including neuromodulatory dysfunction coupled with AD brain degeneration.
dc.format	Electronic
dc.language	eng
dc.publisher	Springer Nature
dc.relation	National Institute of Neurological Disorders and StrokeR21NS121642
dc.relation	National Institute of Neurological Disorders and StrokeR01NS122904
dc.relation	Directorate for Engineering2123970
dc.relation	National Institute of Neurological Disorders and StrokeR01NS120594
dc.relation	National Institute of Mental HealthS10MH124733
dc.relation	National Institute of Neurological Disorders and StrokeRF1NS113278
dc.relation	Office of the DirectorS10OD036211
dc.relation	National Institute of Neurological Disorders and StrokeRF1NS124778
dc.relation.ispartof	Nat Commun
dc.relation.isbasedon	10.1038/s41467-024-53878-y
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.mesh	Animals
dc.subject.mesh	Alzheimer Disease
dc.subject.mesh	Magnetic Resonance Imaging
dc.subject.mesh	Pupil
dc.subject.mesh	Mice
dc.subject.mesh	Brain
dc.subject.mesh	Disease Models, Animal
dc.subject.mesh	Male
dc.subject.mesh	Reflex, Pupillary
dc.subject.mesh	Mice, Inbred C57BL
dc.subject.mesh	Wakefulness
dc.subject.mesh	Mice, Transgenic
dc.subject.mesh	Humans
dc.subject.mesh	Light
dc.subject.mesh	Brain Mapping
dc.subject.mesh	Brain
dc.subject.mesh	Pupil
dc.subject.mesh	Animals
dc.subject.mesh	Mice, Inbred C57BL
dc.subject.mesh	Mice, Transgenic
dc.subject.mesh	Humans
dc.subject.mesh	Mice
dc.subject.mesh	Alzheimer Disease
dc.subject.mesh	Disease Models, Animal
dc.subject.mesh	Magnetic Resonance Imaging
dc.subject.mesh	Reflex, Pupillary
dc.subject.mesh	Brain Mapping
dc.subject.mesh	Wakefulness
dc.subject.mesh	Light
dc.subject.mesh	Male
dc.subject.mesh	Animals
dc.subject.mesh	Alzheimer Disease
dc.subject.mesh	Magnetic Resonance Imaging
dc.subject.mesh	Pupil
dc.subject.mesh	Mice
dc.subject.mesh	Brain
dc.subject.mesh	Disease Models, Animal
dc.subject.mesh	Male
dc.subject.mesh	Reflex, Pupillary
dc.subject.mesh	Mice, Inbred C57BL
dc.subject.mesh	Wakefulness
dc.subject.mesh	Mice, Transgenic
dc.subject.mesh	Humans
dc.subject.mesh	Light
dc.subject.mesh	Brain Mapping
dc.title	Identifying the bioimaging features of Alzheimer's disease based on pupillary light response-driven brain-wide fMRI in awake mice.
dc.type	Journal Article
utslib.citation.volume	15
utslib.location.activity	England
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Engineering and Information Technology
utslib.copyright.status	open_access	*
dc.rights.license	This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.date.updated	2024-12-02T01:17:54Z
pubs.issue	1
pubs.publication-status	Published online
pubs.volume	15
utslib.citation.issue	1

Abstract:

Pupil dynamics has emerged as a critical non-invasive indicator of brain state changes. In particular, pupillary-light-responses (PLR) in Alzheimer's disease (AD) patients show potential as biomarkers for brain degeneration. To investigate AD-specific PLR and its underlying neuromodulatory sources, we combine high-resolution awake mouse fMRI with real-time pupillometry to map brain-wide event-related correlation patterns based on illumination-driven pupil constriction ( P c ) and post-illumination pupil dilation recovery (amplitude, P d , and time, T). The P c -driven differential analysis reveals altered visual signal processing and reduced thalamocortical activation in AD mice in comparison with wild-type (WT) control mice. In contrast, the post-illumination pupil dilation recovery-based fMRI highlights multiple brain areas associated with AD brain degeneration, including the cingulate cortex, hippocampus, septal area of the basal forebrain, medial raphe nucleus, and pontine reticular nuclei (PRN). Additionally, the brain-wide functional connectivity analysis highlights the most significant changes in PRN of AD mice, which serves as the major subcortical relay nuclei underlying oculomotor function. This work integrates non-invasive pupil-fMRI measurements in preclinical models to identify pupillary biomarkers based on brain-wide functional changes, including neuromodulatory dysfunction coupled with AD brain degeneration.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/182226