Gray matter alterations and their atlas-based spatial associations with neurotransmitter distributions in isolated REM sleep behavior disorder
- 1Department of Neurology, Kyung Hee University Hospital at Gangdong, Kyung Hee University College of Medicine, Seoul, Korea
- 2Departments of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-Ro, Jongno-Gu, Seoul, 110-744 Korea
- 3Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-Ro, Jongno-Gu, Seoul, 110-744 Korea
Abstract
Purpose: Multiple neurotransmitter systems are implicated in the pathophysiology of isolated rapid eye movement sleep behavior disorder (iRBD) and its progression to α-synucleinopathy. This study aimed to identify baseline gray matter (GM) alterations in patients with iRBD compared with healthy controls and to examine their spatial correspondence with known neurotransmitter distributions. We further characterized GM patterns associated with future phenoconversion and their neurochemical context.
Methods: A total of 109 patients with iRBD who completed at least one follow-up evaluation and 24 age- and sex-matched healthy controls underwent structural magnetic resonance imaging. Gray matter volume (GMV) alterations were assessed using the CAT12 toolbox. Spatial correlations between group-level GMV difference maps and neurotransmitter atlases were evaluated using the JuSpace toolbox.
Results: At baseline, patients with iRBD showed reduced GMV in the right cerebellar cortex and vermis, along with increased GMV in the left putamen and pallidum. These GMV alterations demonstrated significant spatial correspondence with dopaminergic receptor and transporter maps, including dopamine D2 receptors and the dopamine transporter (DAT). Among patients with iRBD, those who subsequently phenoconverted exhibited lower baseline GMV in the right medial orbital gyrus compared with non-converters. This pattern showed significant spatial correlations with serotonergic (5-HT2A), glutamatergic (mGluR5), GABAergic (GABAa), and dopaminergic (FDOPA) neurotransmitter maps.
Conclusion: Patients with iRBD exhibit distinct patterns of GMV alteration that spatially align with dopaminergic neurotransmitter distribution maps, while phenoconversion is associated with GM changes corresponding to multiple neurotransmitter systems, although the phenoconversion findings are exploratory.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s11325-026-03845-2.
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BibTeX
@article{byun2026gray,
title = {{Gray matter alterations and their atlas-based spatial associations with neurotransmitter distributions in isolated REM sleep behavior disorder}},
author = {Jung-Ick Byun and Huijin Song and Jung Hwan Shin and Han-Joon Kim and Won Chul Shin and Chul-Ho Sohn and Ki-Young Jung},
journal = {Sleep \& Breathing = Schlaf \& Atmung},
year = {2026},
month = oct,
doi = {10.1007/s11325-026-03845-2},
url = {https://doi.org/10.1007/s11325-026-03845-2},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Gray matter alterations and their atlas-based spatial associations with neurotransmitter distributions in isolated REM sleep behavior disorder
AU - Jung-Ick Byun
AU - Huijin Song
AU - Jung Hwan Shin
AU - Han-Joon Kim
AU - Won Chul Shin
AU - Chul-Ho Sohn
AU - Ki-Young Jung
PY - 2026
DA - 2026/10/29
JO - Sleep & Breathing = Schlaf & Atmung
DO - 10.1007/s11325-026-03845-2
UR - https://doi.org/10.1007/s11325-026-03845-2
AB - Purpose: Multiple neurotransmitter systems are implicated in the pathophysiology of isolated rapid eye movement sleep behavior disorder (iRBD) and its progression to α-synucleinopathy. This study aimed to identify baseline gray matter (GM) alterations in patients with iRBD compared with healthy controls and to examine their spatial correspondence with known neurotransmitter distributions. We further characterized GM patterns associated with future phenoconversion and their neurochemical context. Methods: A total of 109 patients with iRBD who completed at least one follow-up evaluation and 24 age- and sex-matched healthy controls underwent structural magnetic resonance imaging. Gray matter volume (GMV) alterations were assessed using the CAT12 toolbox. Spatial correlations between group-level GMV difference maps and neurotransmitter atlases were evaluated using the JuSpace toolbox. Results: At baseline, patients with iRBD showed reduced GMV in the right cerebellar cortex and vermis, along with increased GMV in the left putamen and pallidum. These GMV alterations demonstrated significant spatial correspondence with dopaminergic receptor and transporter maps, including dopamine D2 receptors and the dopamine transporter (DAT). Among patients with iRBD, those who subsequently phenoconverted exhibited lower baseline GMV in the right medial orbital gyrus compared with non-converters. This pattern showed significant spatial correlations with serotonergic (5-HT2A), glutamatergic (mGluR5), GABAergic (GABAa), and dopaminergic (FDOPA) neurotransmitter maps. Conclusion: Patients with iRBD exhibit distinct patterns of GMV alteration that spatially align with dopaminergic neurotransmitter distribution maps, while phenoconversion is associated with GM changes corresponding to multiple neurotransmitter systems, although the phenoconversion findings are exploratory. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s11325-026-03845-2.
SN - 1520-9512
SN - 1522-1709
ER -