Pub Date : 2026-01-26DOI: 10.1016/j.nbscr.2026.100144
Michael C. Tackenberg , Maria Luísa Jabbur , Vincent M. Cassone , Jeff R. Jones
A circadian clock enables an organism to occupy a particular temporal niche, and the evolutionary pressures associated with that temporal niche in turn shape the organization of the circadian network in which the clock is embedded. Although circadian organization has often been dichotomized into centralized and distributed systems, our modern understanding of circadian networks reveals a more complex organization that cannot be captured by this simple dichotomy. In this review, we examine how coupling between nodes of the circadian network (from cells, to tissues, to organs) gives rise to coherent circadian organization in mammals. We further highlight how comparative research on non-mammalian organisms reveals conserved and divergent strategies for circadian coupling that inform general principles of circadian network function across species.
{"title":"Reconsidering mammalian circadian organization","authors":"Michael C. Tackenberg , Maria Luísa Jabbur , Vincent M. Cassone , Jeff R. Jones","doi":"10.1016/j.nbscr.2026.100144","DOIUrl":"10.1016/j.nbscr.2026.100144","url":null,"abstract":"<div><div>A circadian clock enables an organism to occupy a particular temporal niche, and the evolutionary pressures associated with that temporal niche in turn shape the organization of the circadian network in which the clock is embedded. Although circadian organization has often been dichotomized into centralized and distributed systems, our modern understanding of circadian networks reveals a more complex organization that cannot be captured by this simple dichotomy. In this review, we examine how coupling between nodes of the circadian network (from cells, to tissues, to organs) gives rise to coherent circadian organization in mammals. We further highlight how comparative research on non-mammalian organisms reveals conserved and divergent strategies for circadian coupling that inform general principles of circadian network function across species.</div></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":"20 ","pages":"Article 100144"},"PeriodicalIF":0.0,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-21DOI: 10.1016/j.nbscr.2026.100143
Mariko Izumo , Kimberly H. Cox , Joseph S. Takahashi
The suprachiasmatic nucleus (SCN), a central clock in the hypothalamus of mammals, consists of heterogeneous populations of neurons. The SCN expresses various neurotransmitters/neuropeptides and hundreds of other genes as detected by cell census studies including transcriptomics. Nonetheless, the SCN can sustain a precise ∼24 h rhythm and acts as a central pacemaker to control daily rhythms of behavior and physiological processes throughout a lifespan. How does the SCN achieve this regularity in a network of ∼20,000 diverse cellular identities? Are there unique roles in individual SCN neurons or in subsets of SCN neurons? How are they classified, connected to sustain synchrony, and entrained to external light-dark cycles at the level of cell types? Only recently, the functional significance of individual oscillators in the SCN is beginning to be uncovered through the development and advancement of neurotechniques to target specific cell types for genetic manipulation and imaging. This review will summarize recent conditional knockout studies, focusing particularly on genetic drivers utilized in various experimental approaches. We will also discuss what questions lie ahead to disentangle the complexity of cellular components in the central pacemaker network.
{"title":"Toward dissection of diverse neural components in the suprachiasmatic nucleus (SCN) pacemaker network","authors":"Mariko Izumo , Kimberly H. Cox , Joseph S. Takahashi","doi":"10.1016/j.nbscr.2026.100143","DOIUrl":"10.1016/j.nbscr.2026.100143","url":null,"abstract":"<div><div>The suprachiasmatic nucleus (SCN), a central clock in the hypothalamus of mammals, consists of heterogeneous populations of neurons. The SCN expresses various neurotransmitters/neuropeptides and hundreds of other genes as detected by cell census studies including transcriptomics. Nonetheless, the SCN can sustain a precise ∼24 h rhythm and acts as a central pacemaker to control daily rhythms of behavior and physiological processes throughout a lifespan. How does the SCN achieve this regularity in a network of ∼20,000 diverse cellular identities? Are there unique roles in individual SCN neurons or in subsets of SCN neurons? How are they classified, connected to sustain synchrony, and entrained to external light-dark cycles at the level of cell types? Only recently, the functional significance of individual oscillators in the SCN is beginning to be uncovered through the development and advancement of neurotechniques to target specific cell types for genetic manipulation and imaging. This review will summarize recent conditional knockout studies, focusing particularly on genetic drivers utilized in various experimental approaches. We will also discuss what questions lie ahead to disentangle the complexity of cellular components in the central pacemaker network.</div></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":"20 ","pages":"Article 100143"},"PeriodicalIF":0.0,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aging is a risk factor for various disorders, and age-dependent changes in sleep parameters are involved in the pathogenesis of many diseases. Senescence-accelerated mice-prone 8 (SAMP8) have a short lifespan and show a disrupted circadian rhythm. However, little is known about how sleep parameters change with age in SAMP8. In this study, we evaluated changes in sleep parameters with aging in SAMP8 compared with those in senescence-accelerated mouse resistant 1 (SAMR1) as the control. Sleep quantity and fragmentation of sleep were evaluated at 4, 36, and 56 weeks of age using a PiezoSleep® system. The average duration of sleep episodes, reflected as the sleep fragmentation, decreased in an age-dependent manner in both SAMR1 and SAMP8, especially under light phase conditions. Interestingly, while the difference between SAMR1 and SAMP8 was not evident at 4 weeks of age, it was significantly reduced in SAMP8 at 36 and 56 weeks of age. These results suggest that the reduction of average sleep episode duration associated with the aging process was accelerated in SAMP8. To explore the mechanisms underlying the accelerated sleep fragmentation in SAMP8, we performed RNA sequencing on hypothalamic specimens obtained from SAMR1 and SAMP8 at 49 weeks of age, which revealed upregulation of type I interferon (IFN)-responsive genes in the SAMP8 hypothalamus. Furthermore, serum IFN-α levels at 49 weeks of age were higher in SAMP8 compared with those in SAMR1, suggesting that elevated IFN-α production in SAMP8 could be associated with the sleep fragmentation.
{"title":"Sleep disruption with aging in senescence-accelerated mice-prone 8 (SAMP8) mice and analysis of factors associated with age-related sleep fragmentation using RNA sequencing of the hypothalamus","authors":"Kazuyuki Okamura , Rie Yanagisawa , Miyuki Sato , Takehiro Suzuki , Nobuyoshi Nakajima , Tin-Tin Win-shwe , Eiko Koike","doi":"10.1016/j.nbscr.2025.100142","DOIUrl":"10.1016/j.nbscr.2025.100142","url":null,"abstract":"<div><div>Aging is a risk factor for various disorders, and age-dependent changes in sleep parameters are involved in the pathogenesis of many diseases. Senescence-accelerated mice-prone 8 (SAMP8) have a short lifespan and show a disrupted circadian rhythm. However, little is known about how sleep parameters change with age in SAMP8. In this study, we evaluated changes in sleep parameters with aging in SAMP8 compared with those in senescence-accelerated mouse resistant 1 (SAMR1) as the control. Sleep quantity and fragmentation of sleep were evaluated at 4, 36, and 56 weeks of age using a PiezoSleep® system. The average duration of sleep episodes, reflected as the sleep fragmentation, decreased in an age-dependent manner in both SAMR1 and SAMP8, especially under light phase conditions. Interestingly, while the difference between SAMR1 and SAMP8 was not evident at 4 weeks of age, it was significantly reduced in SAMP8 at 36 and 56 weeks of age. These results suggest that the reduction of average sleep episode duration associated with the aging process was accelerated in SAMP8. To explore the mechanisms underlying the accelerated sleep fragmentation in SAMP8, we performed RNA sequencing on hypothalamic specimens obtained from SAMR1 and SAMP8 at 49 weeks of age, which revealed upregulation of type I interferon (IFN)-responsive genes in the SAMP8 hypothalamus. Furthermore, serum IFN-α levels at 49 weeks of age were higher in SAMP8 compared with those in SAMR1, suggesting that elevated IFN-α production in SAMP8 could be associated with the sleep fragmentation.</div></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":"20 ","pages":"Article 100142"},"PeriodicalIF":0.0,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145925064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-30DOI: 10.1016/j.nbscr.2025.100141
Elizaveta Kadukhina , Siqi Jia , Linda M. Villa , Xiao Yi , Daniel G.S. Capelluto , Jonathan S. Briganti , Anne M. Brown , Carla V. Finkielstein
The circadian clock component PER2 coordinates daily oscillations in gene expression across multiple tissues, yet its role in assembling multi-protein regulatory complexes remains incompletely understood. Here, we report that PER2 nucleates a ternary complex with the tumor suppressor BRCA1 and the transcription factor POU2F1(OCT-1) to impose circadian control on target gene promoters. Using bacterial two-hybrid screening, we identified BRCA1 as a novel PER2-interacting protein. Biochemical mapping revealed that PER2 engages BRCA1 through multiple discrete binding interfaces: PER2 spanning residues 356–574 and 683–872 interact with both the N-terminal (1–400) and C-terminal BRCT (1670–1863) domains of BRCA1. Structural modeling predicted 361 residue contacts between PER2 and BRCA1, substantially more than the 74 contacts predicted for PER2:POU2F1(OCT-1), indicating differential affinities that enable ordered complex assembly. Sequential pull-down assays demonstrated that PER2, BRCA1, and POU domain form a stable ternary complex in vitro, with POU2F1(OCT-1) serving as the DNA-binding platform. Electrophoretic mobility shift assays revealed that pre-assembly of PER2 with POU domain inhibits DNA binding, while BRCA1 is essential for stabilizing PER2 recruitment to DNA-bound POU2F1(OCT-1). Using ESR1 as a functional readout, we demonstrated that this ternary complex directly regulates promoter activity. Circadian transcriptome analysis revealed that Esr1 exhibits robust clock-dependent oscillations that are abolished in Per1/2 double-knockout mice, while Pou2f1 and Brca1 maintain constitutive expression. These findings establish PER2 as a circadian scaffold that assembles multivalent protein complexes to temporally gate transcription, providing mechanistic insight into how circadian disruption can influence target gene expression.
{"title":"The PER2:BRCA1:POU2F1(OCT-1) ternary complex represents a multi-component scaffold model for circadian gene regulation","authors":"Elizaveta Kadukhina , Siqi Jia , Linda M. Villa , Xiao Yi , Daniel G.S. Capelluto , Jonathan S. Briganti , Anne M. Brown , Carla V. Finkielstein","doi":"10.1016/j.nbscr.2025.100141","DOIUrl":"10.1016/j.nbscr.2025.100141","url":null,"abstract":"<div><div>The circadian clock component PER2 coordinates daily oscillations in gene expression across multiple tissues, yet its role in assembling multi-protein regulatory complexes remains incompletely understood. Here, we report that PER2 nucleates a ternary complex with the tumor suppressor BRCA1 and the transcription factor POU2F1(OCT-1) to impose circadian control on target gene promoters. Using bacterial two-hybrid screening, we identified BRCA1 as a novel PER2-interacting protein. Biochemical mapping revealed that PER2 engages BRCA1 through multiple discrete binding interfaces: PER2 spanning residues 356–574 and 683–872 interact with both the N-terminal (1–400) and C-terminal BRCT (1670–1863) domains of BRCA1. Structural modeling predicted 361 residue contacts between PER2 and BRCA1, substantially more than the 74 contacts predicted for PER2:POU2F1(OCT-1), indicating differential affinities that enable ordered complex assembly. Sequential pull-down assays demonstrated that PER2, BRCA1, and POU domain form a stable ternary complex <em>in vitro</em>, with POU2F1(OCT-1) serving as the DNA-binding platform. Electrophoretic mobility shift assays revealed that pre-assembly of PER2 with POU domain inhibits DNA binding, while BRCA1 is essential for stabilizing PER2 recruitment to DNA-bound POU2F1(OCT-1). Using <em>ESR1</em> as a functional readout, we demonstrated that this ternary complex directly regulates promoter activity. Circadian transcriptome analysis revealed that <em>Esr1</em> exhibits robust clock-dependent oscillations that are abolished in <em>Per1/2</em> double-knockout mice, while <em>Pou2f1</em> and <em>Brca1</em> maintain constitutive expression. These findings establish PER2 as a circadian scaffold that assembles multivalent protein complexes to temporally gate transcription, providing mechanistic insight into how circadian disruption can influence target gene expression.</div></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":"20 ","pages":"Article 100141"},"PeriodicalIF":0.0,"publicationDate":"2025-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145692402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-24DOI: 10.1016/j.nbscr.2025.100140
Mohammadreza Iravani, Sadaf Moharreri
Sleep stage flagging is critical for diagnosing conditions like insomnia, sleep apnea, and narcolepsy. Traditional methods rely on time-intensive manual scoring by experts, limiting scalability and accessibility, especially in resource-limited settings. Automating sleep stage classification through signal processing and machine learning could improve diagnostic efficiency and reduce healthcare burdens. While prior studies have utilized multiple signals such as electroencephalogram (EEG), electromyogram (EMG), and electrocardiogram (ECG), this study focuses solely on ECG to provide a simpler, more accessible solution. By simplifying signal input, the approach enhances feasibility in resource-constrained environments. Features based on heart rate variability (HRV) and Poincaré plot descriptors were extracted and used to train machine learning models for five-stage sleep classification. The approach was evaluated using two publicly available datasets, the Haaglanden Medisch Centrum Sleep Staging Database and the MIT-BIH Polysomnographic Database, which were chosen for their varied recording environments and subject diversity. Neural Networks, K-Nearest Neighbors (KNN), XGBoost, and Random Forest were employed to assess performance. The highest classification accuracy of 67 % was achieved with long-duration ECG recordings, outperforming models trained on shorter segments by 12 %. These findings emphasize the impact of signal duration on classification performance and suggest opportunities to refine sleep stage prediction. The study demonstrates the feasibility of ECG-only systems for portable, low-cost, and scalable sleep monitoring. The insights gained may facilitate the development of more accessible and efficient sleep disorder detection, particularly in low-resource settings.
{"title":"Sleep stage classification from ECG using machine learning: Evaluating the impact of signal duration","authors":"Mohammadreza Iravani, Sadaf Moharreri","doi":"10.1016/j.nbscr.2025.100140","DOIUrl":"10.1016/j.nbscr.2025.100140","url":null,"abstract":"<div><div>Sleep stage flagging is critical for diagnosing conditions like insomnia, sleep apnea, and narcolepsy. Traditional methods rely on time-intensive manual scoring by experts, limiting scalability and accessibility, especially in resource-limited settings. Automating sleep stage classification through signal processing and machine learning could improve diagnostic efficiency and reduce healthcare burdens. While prior studies have utilized multiple signals such as electroencephalogram (EEG), electromyogram (EMG), and electrocardiogram (ECG), this study focuses solely on ECG to provide a simpler, more accessible solution. By simplifying signal input, the approach enhances feasibility in resource-constrained environments. Features based on heart rate variability (HRV) and Poincaré plot descriptors were extracted and used to train machine learning models for five-stage sleep classification. The approach was evaluated using two publicly available datasets, the Haaglanden Medisch Centrum Sleep Staging Database and the MIT-BIH Polysomnographic Database, which were chosen for their varied recording environments and subject diversity. Neural Networks, K-Nearest Neighbors (KNN), XGBoost, and Random Forest were employed to assess performance. The highest classification accuracy of 67 % was achieved with long-duration ECG recordings, outperforming models trained on shorter segments by 12 %. These findings emphasize the impact of signal duration on classification performance and suggest opportunities to refine sleep stage prediction. The study demonstrates the feasibility of ECG-only systems for portable, low-cost, and scalable sleep monitoring. The insights gained may facilitate the development of more accessible and efficient sleep disorder detection, particularly in low-resource settings.</div></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":"20 ","pages":"Article 100140"},"PeriodicalIF":0.0,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145624875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Light, particularly blue-wavelength light exerts a broad range of non-image forming (NIF) effects including the stimulation of cognition and alertness and the regulation of mood, sleep and circadian rhythms. However, its underlying brain mechanisms are not fully elucidated. Likewise, whether adolescents show a different NIF sensitivity to light compared to adults is not established. Here, we investigated whether cortical excitability, a basic aspect of brain function that depends on sleep-wake regulation, is affected by blue light and whether the effect is similar in young adults and adolescents. We used transcranial magnetic stimulation coupled to high-density electroencephalography (TMS–EEG) in healthy young adults (N = 13, 24.2 ± 3.4 y) and in adolescents (N = 15, 16.9 ± 1.1 y). Our results showed that, in young adults, blue light affected cortical excitability following an apparent inverted-U relationship, while adolescents' cortical excitability was not significantly different under blue light compared to orange light. In addition, although light did not affect performance on a visuomotor vigilance task completed during the TMS-EEG recordings, cortical excitability was positively correlated to task performance in both age groups. This study provides valuable insights into the complex interplay between light, cortical excitability, and behavior. Our findings highlight the role of age in NIF effects of light, suggesting that brain responses to light differ during developmental periods.
{"title":"Cortical excitability is affected by light exposure – Distinct effects in adolescents and young adults","authors":"Roya Sharifpour , Fermin Balda , Ilenia Paparella , John Read , Zoé Leysens , Sara Letot , Islay Campbell , Elise Beckers , Fabienne Collette , Christophe Phillips , Mikhail Zubkov , Gilles Vandewalle","doi":"10.1016/j.nbscr.2025.100138","DOIUrl":"10.1016/j.nbscr.2025.100138","url":null,"abstract":"<div><div>Light, particularly blue-wavelength light exerts a broad range of non-image forming (NIF) effects including the stimulation of cognition and alertness and the regulation of mood, sleep and circadian rhythms. However, its underlying brain mechanisms are not fully elucidated. Likewise, whether adolescents show a different NIF sensitivity to light compared to adults is not established. Here, we investigated whether cortical excitability, a basic aspect of brain function that depends on sleep-wake regulation, is affected by blue light and whether the effect is similar in young adults and adolescents. We used transcranial magnetic stimulation coupled to high-density electroencephalography (TMS–EEG) in healthy young adults (N = 13, 24.2 ± 3.4 y) and in adolescents (N = 15, 16.9 ± 1.1 y). Our results showed that, in young adults, blue light affected cortical excitability following an apparent inverted-U relationship, while adolescents' cortical excitability was not significantly different under blue light compared to orange light. In addition, although light did not affect performance on a visuomotor vigilance task completed during the TMS-EEG recordings, cortical excitability was positively correlated to task performance in both age groups. This study provides valuable insights into the complex interplay between light, cortical excitability, and behavior. Our findings highlight the role of age in NIF effects of light, suggesting that brain responses to light differ during developmental periods.</div></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":"20 ","pages":"Article 100138"},"PeriodicalIF":0.0,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145595088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-03DOI: 10.1016/j.nbscr.2025.100137
Ali Kavehee , Fatemeh Kashaninasab , Mir Farhad Ghalehbandi , Mahboobeh Khoozan
Objective
Sleep disorders including insomnia, obstructive sleep apnea (OSA), narcolepsy and REM sleep behavior disorder (RBD), significantly impair cognition, emotional wellbeing and physical health. This review synthesizes Neuroimaging evidence across major sleep disorders. It also documents knowledge gaps in the literature and provides clear next steps towards better diagnostic and therapeutic steps for sleep disorders.
Methods
PRISMA 2020 guidelines were followed for the systematic review of Neuroimaging studies on sleep disorders, with a comprehensive search of PubMed, Scopus and Google Scholar between 1997 and 2024.
Results
A total of 93 Neuroimaging studies published between 1997 and 2024 were systematically reviewed. Insomnia is characterized by reduced gray matter volume in the prefrontal cortex and hippocampus, increased beta activity in EEG, and decreased frontal lobe metabolism, supporting the hyperarousal model. OSA is associated with cortical thinning, hippocampal atrophy, and disrupted Default Mode Network (DMN) connectivity, correlating with cognitive deficits. Narcolepsy exhibits hypothalamic atrophy, reduced orexin signaling, and abnormal thalamocortical connectivity, explaining excessive daytime sleepiness and cataplexy. Parasomnias, particularly REM sleep behavior disorder (RBD), show neurodegenerative changes in the brainstem and basal ganglia, serving as early markers for synucleinopathies like Parkinson's disease.
Conclusion
Multimodal Neuroimaging and electrophysiological findings provide critical insights into the pathophysiology of sleep disorders, highlighting distinct neural patterns that enhance diagnostic precision and guide targeted interventions. Multimodal imaging approaches are essential for advancing precision medicine in sleep disorder management.
{"title":"Neuroimaging findings in sleep disorders: A review article","authors":"Ali Kavehee , Fatemeh Kashaninasab , Mir Farhad Ghalehbandi , Mahboobeh Khoozan","doi":"10.1016/j.nbscr.2025.100137","DOIUrl":"10.1016/j.nbscr.2025.100137","url":null,"abstract":"<div><h3>Objective</h3><div>Sleep disorders including insomnia, obstructive sleep apnea (OSA), narcolepsy and REM sleep behavior disorder (RBD), significantly impair cognition, emotional wellbeing and physical health. This review synthesizes Neuroimaging evidence across major sleep disorders. It also documents knowledge gaps in the literature and provides clear next steps towards better diagnostic and therapeutic steps for sleep disorders.</div></div><div><h3>Methods</h3><div>PRISMA 2020 guidelines were followed for the systematic review of Neuroimaging studies on sleep disorders, with a comprehensive search of PubMed, Scopus and Google Scholar between 1997 and 2024.</div></div><div><h3>Results</h3><div>A total of 93 Neuroimaging studies published between 1997 and 2024 were systematically reviewed. Insomnia is characterized by reduced gray matter volume in the prefrontal cortex and hippocampus, increased beta activity in EEG, and decreased frontal lobe metabolism, supporting the hyperarousal model. OSA is associated with cortical thinning, hippocampal atrophy, and disrupted Default Mode Network (DMN) connectivity, correlating with cognitive deficits. Narcolepsy exhibits hypothalamic atrophy, reduced orexin signaling, and abnormal thalamocortical connectivity, explaining excessive daytime sleepiness and cataplexy. Parasomnias, particularly REM sleep behavior disorder (RBD), show neurodegenerative changes in the brainstem and basal ganglia, serving as early markers for synucleinopathies like Parkinson's disease.</div></div><div><h3>Conclusion</h3><div>Multimodal Neuroimaging and electrophysiological findings provide critical insights into the pathophysiology of sleep disorders, highlighting distinct neural patterns that enhance diagnostic precision and guide targeted interventions. Multimodal imaging approaches are essential for advancing precision medicine in sleep disorder management.</div></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":"20 ","pages":"Article 100137"},"PeriodicalIF":0.0,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145595089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.nbscr.2025.100136
Peppi Schulz , Heiko I. Stecher , Christoph S. Herrmann
Transcranial alternating current stimulation (tACS) is a promising tool for research on oscillatory brain activity, yet both behavioral and electrophysiological outcome measures show high variability across studies. One source for this variability might be chronotype and an incidental mismatch between chronotype and the time of the measurement.
14 evening type and 14 morning type participants performed a sustained attention task — once at their chronotypically optimal and once at a non-optimal time of day. TACS was applied for 20 min at the individual alpha frequency over two electrodes located at Cz and Oz. EEG was recorded for 10 min prior to and after stimulation. Sleep timing and quality were assessed with a sleep questionnaire. While planned analyses failed to find effects of stimulation and session timing on alpha power, exploratory analyses revealed that below average sleep quality in evening types in the morning was associated with no changes or unexpected decreases in alpha power after stimulation. Effects of sleep quality were present in the morning for evening types, but neither in the evening session nor in morning types. It is suggested that this effect of sleep quality reflects increased sleepiness, which could impede expected aftereffects of tACS. It is likely that effects of sleepiness might be especially relevant when people are stimulated at a chronotypically non-optimal time. Due to the exploratory nature of these sleep effects and their presence in only a small subgroup leading to low power and confidence, future systematic sham-controlled studies are needed to clarify the relationship between sleep, time of day and chronotype in -tACS proposed here.
{"title":"Chronotype in alpha-tACS: Preliminary evidence hints at sleep quality modulation of aftereffects in evening types in the morning","authors":"Peppi Schulz , Heiko I. Stecher , Christoph S. Herrmann","doi":"10.1016/j.nbscr.2025.100136","DOIUrl":"10.1016/j.nbscr.2025.100136","url":null,"abstract":"<div><div>Transcranial alternating current stimulation (tACS) is a promising tool for research on oscillatory brain activity, yet both behavioral and electrophysiological outcome measures show high variability across studies. One source for this variability might be chronotype and an incidental mismatch between chronotype and the time of the measurement.</div><div>14 evening type and 14 morning type participants performed a sustained attention task — once at their chronotypically optimal and once at a non-optimal time of day. TACS was applied for 20 min at the individual alpha frequency over two electrodes located at Cz and Oz. EEG was recorded for 10 min prior to and after stimulation. Sleep timing and quality were assessed with a sleep questionnaire. While planned analyses failed to find effects of stimulation and session timing on alpha power, exploratory analyses revealed that below average sleep quality in evening types in the morning was associated with no changes or unexpected decreases in alpha power after stimulation. Effects of sleep quality were present in the morning for evening types, but neither in the evening session nor in morning types. It is suggested that this effect of sleep quality reflects increased sleepiness, which could impede expected aftereffects of tACS. It is likely that effects of sleepiness might be especially relevant when people are stimulated at a chronotypically non-optimal time. Due to the exploratory nature of these sleep effects and their presence in only a small subgroup leading to low power and confidence, future systematic sham-controlled studies are needed to clarify the relationship between sleep, time of day and chronotype in <span><math><mi>α</mi></math></span>-tACS proposed here.</div></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":"19 ","pages":"Article 100136"},"PeriodicalIF":0.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145518970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-17DOI: 10.1016/j.nbscr.2025.100135
Beimnet B. Kassaye , Alexis N. Jameson , Katherine Moore , Douglas G. McMahon , Brad A. Grueter
Photoperiod is the primary environmental cue that regulates changes in behavior across seasons. Previously, we have shown that photoperiod has sex-specific effects on synaptic dopamine dynamics in the nucleus accumbens (NAc). Further, evidence suggests that the dopamine transporter (DAT) is a potential locus of action for the sex-specific effects of photoperiod on NAc dopamine. The NAc is a critical node within the reward circuit that brings motivation to action, and changes to NAc dopamine dynamics at the synapse can result in robust changes in behaviors. Cocaine is a psychostimulant that targets monoamine transporters, including DAT, and generates robust behavioral effects. Thus, using cocaine-mediated behavior, we can determine whether photoperiod impacts DAT function and dopamine physiology. Here, using male and female mice we examined the effect of seasonally relevant photoperiods on DAT function in the NAc and dopamine-dependent behavior. We found that females raised in Short, winter-like photoperiod have blunted cocaine-induced hyperlocomotion. Conversely, females raised in Long, summer-like photoperiod exhibit greater DA release and cocaine-mediated DAT inhibition while we observe decreased sensitivity to cocaine-associated learning. The combined work presented here provides evidence that photoperiod has differential, female-specific effects on NAc DAT function and DAT-mediated behaviors.
{"title":"Identification of photoperiod as a regulator of dopamine-mediated behavior in female mice","authors":"Beimnet B. Kassaye , Alexis N. Jameson , Katherine Moore , Douglas G. McMahon , Brad A. Grueter","doi":"10.1016/j.nbscr.2025.100135","DOIUrl":"10.1016/j.nbscr.2025.100135","url":null,"abstract":"<div><div>Photoperiod is the primary environmental cue that regulates changes in behavior across seasons. Previously, we have shown that photoperiod has sex-specific effects on synaptic dopamine dynamics in the nucleus accumbens (NAc). Further, evidence suggests that the dopamine transporter (DAT) is a potential locus of action for the sex-specific effects of photoperiod on NAc dopamine. The NAc is a critical node within the reward circuit that brings motivation to action, and changes to NAc dopamine dynamics at the synapse can result in robust changes in behaviors. Cocaine is a psychostimulant that targets monoamine transporters, including DAT, and generates robust behavioral effects. Thus, using cocaine-mediated behavior, we can determine whether photoperiod impacts DAT function and dopamine physiology. Here, using male and female mice we examined the effect of seasonally relevant photoperiods on DAT function in the NAc and dopamine-dependent behavior. We found that females raised in Short, winter-like photoperiod have blunted cocaine-induced hyperlocomotion. Conversely, females raised in Long, summer-like photoperiod exhibit greater DA release and cocaine-mediated DAT inhibition while we observe decreased sensitivity to cocaine-associated learning. The combined work presented here provides evidence that photoperiod has differential, female-specific effects on NAc DAT function and DAT-mediated behaviors.</div></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":"19 ","pages":"Article 100135"},"PeriodicalIF":0.0,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145048830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-13DOI: 10.1016/j.nbscr.2025.100134
Suil Kim , Douglas G. McMahon
The suprachiasmatic nucleus (SCN) of the hypothalamus is a principal light-responsive circadian clock that adjusts circadian rhythms in mammalian physiology and behavior to changes in external light signals. Although mechanisms underlying how light acutely resets the timing of circadian rhythms have been characterized, it remains elusive how light signals induce lasting changes in circadian period, known as period after-effects. Here we have found that the period after-effects on circadian behavior of changing photoperiods are blocked by application of the DNA methyltransferase inhibitor RG108 near the SCN. At the level of single light pulses acting as clock-resetting stimulations, RG108 significantly attenuates period after-effects following acute phase shifts in behavioral rhythms in vivo, and blocks period after-effects on clock gene rhythms following phase resetting by the vasoactive intestinal peptide in the isolated ex vivo SCN. In addition, the DNA methyltransferase inhibitor SGI-1027 blocked period after-effects of optogenetic neuronal stimulation on ex vivo SCN rhythms. Acute clock resetting shifts themselves, however, do not appear to require DNA methylation at the SCN and behavioral levels, in contrast to subsequent period plasticity. Our results demonstrate that DNA methylation inhibitors block light-induced period after-effects in response to photoperiods and single light pulses. Together with previous studies showing that DNA methylation in the SCN is essential for period after-effects of non-24hr light cycles (T-cycles), this suggests that DNA methylation in the SCN may be a widespread mechanism of light-induced circadian period plasticity.
{"title":"Effects of DNA methylation inhibitors on light-induced circadian clock plasticity","authors":"Suil Kim , Douglas G. McMahon","doi":"10.1016/j.nbscr.2025.100134","DOIUrl":"10.1016/j.nbscr.2025.100134","url":null,"abstract":"<div><div>The suprachiasmatic nucleus (SCN) of the hypothalamus is a principal light-responsive circadian clock that adjusts circadian rhythms in mammalian physiology and behavior to changes in external light signals. Although mechanisms underlying how light acutely resets the timing of circadian rhythms have been characterized, it remains elusive how light signals induce lasting changes in circadian period, known as period after-effects. Here we have found that the period after-effects on circadian behavior of changing photoperiods are blocked by application of the DNA methyltransferase inhibitor RG108 near the SCN. At the level of single light pulses acting as clock-resetting stimulations, RG108 significantly attenuates period after-effects following acute phase shifts in behavioral rhythms <em>in vivo</em>, and blocks period after-effects on clock gene rhythms following phase resetting by the vasoactive intestinal peptide in the isolated <em>ex vivo</em> SCN. In addition, the DNA methyltransferase inhibitor SGI-1027 blocked period after-effects of optogenetic neuronal stimulation on <em>ex vivo</em> SCN rhythms. Acute clock resetting shifts themselves, however, do not appear to require DNA methylation at the SCN and behavioral levels, in contrast to subsequent period plasticity. Our results demonstrate that DNA methylation inhibitors block light-induced period after-effects in response to photoperiods and single light pulses. Together with previous studies showing that DNA methylation in the SCN is essential for period after-effects of non-24hr light cycles (T-cycles), this suggests that DNA methylation in the SCN may be a widespread mechanism of light-induced circadian period plasticity.</div></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":"19 ","pages":"Article 100134"},"PeriodicalIF":0.0,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144864651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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