Gray matter alterations in sleep disorders lead to brain networks changes: A systematic review of cortical and subcortical points

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However, the effects on cortical thickness and gray matter volume can differ in children. This systematic review aims to explore the changes in gray matter and the cortex in children experiencing sleep disorders. Methods This systematic review was conducted based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, and the principle of non-bias was respected. All the articles from 2020-2022 were extracted from the Web of Science, PubMed, and Scopus databases. This study extracted sleep disorders, cortical and gray matter alterations, and alterations anatomy from children up to 18 years old. Results Eleven studies were identified with inclusion criteria that addressed breathing disorders, obstructive sleep apnea, and periodic sleep disorders. The mean age of the children involved was 3.22 ± 8.89 years, with a T-chart illustrating a predominance of boys over girls. An association was observed between rapid eye movement sleep behavioral disorder and rapid eye movement sleep behavioral disorder. Notably, the thickness of the cerebral cortex in the right anterior caudate cingulate and right cuneiform regions was significantly elevated following obstructive sleep-disordered breathing. The gray matter volume exhibited both increases in certain areas and decreases in others, a phenomenon that applies to all sleep disorders. Conclusion Sleep disorders change the thickness of the cerebral cortex and the volume of gray matter. Despite the difference in the articles' results, this study found a point change pattern in the brain anatomy, justifying the difference in the results of the previous systematic reviews. Sleep disorders Gray matter Cortical thickness Systematic review Brain network Figures Figure 1 Figure 2 Introduction Introduction Sleep disorders in pediatric populations have become an increasingly recognized concern among healthcare professionals and researchers (1). Defined as persistent difficulties in initiating or maintaining sleep, these disorders encompass a wide range of conditions, including insomnia, sleep apnea, restless legs syndrome, and parasomnias (2, 3). The prevalence of sleep disorders in children is alarming, with estimates suggesting that up to 25% of children experience some form of sleep disruption (4, 5); these disturbances can lead to a myriad of complications, particularly affecting the developing brain (6, 7). The critical stages of brain maturation, occurring during childhood, are susceptible to sleep quality (8). Insufficient or disrupted sleep can hinder cognitive development, leading to issues such as impaired attention, learning difficulties, and emotional regulation problems (4, 9). Accordingly, understanding the implications of sleep disorders on pediatric brain development is essential for early intervention and treatment. Research has increasingly focused on the structural alterations in the brain associated with sleep disorders in children. Previous studies have indicated that chronic sleep deprivation and disturbances can lead to significant morphological changes in brain structure(10, 11), particularly affecting white matter integrity(12). White matter, consisting of myelinated axons, facilitating communication between different brain regions(13), is crucial for cognitive functioning(14). Additionally, changes in specific brain components, such as the prefrontal cortex and hippocampus, have been assessed in children suffering from sleep disturbances (15, 16). These regions are vital for memory formation and emotional regulation, further underscoring the potential long-term consequences of inadequate sleep on a child's cognitive and emotional health(17, 18). Although the structural and morphological changes of the cortex and subcortex have been confirmed in sleep disorders, the concept of changes in this subject is tied with many ambiguities. Rostampour conducted a systematic review focusing on alterations in white matter; however, the studies incorporated in this review exhibited inconsistencies (12), just as Moghaddam found it challenging to make decisions on white matter changes (19). The current investigation addresses the lack of comprehensive studies on changes in gray matter. We systematically reviewed recent literature to form an impartial judgment regarding the alterations in gray matter thickness and volume. The Patient/Population, Intervention, Comparison, Outcomes (PICO) criteria guide this study, and it consolidates findings from research conducted over the last 10 years. Methods o Protocol and registration This systematic study was performed based on the accepted criteria of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). To comply with the principle of non-bias, this study used the Cochrane Manual for Systematic Reviewers 5.1.0 for clinical studies and reviewed the studies in terms of allocation concealment, blinding of participants, study personnel, and outcome assessors. The research question was based on PICO criteria o Eligibility criteria and search strategy This systematic review assessed published studies from January 2014 to 2024 in databases such as Web of Science, PubMed, and Scopus. Sleep disorders were defined according to the guidelines of the American Academy of Sleep Medicine (AASM) (2). This study's primary criterion for identifying cognitive impairment was the International Classification of Cognitive Impairment in Epilepsy (IC-CoDE). The studies that investigated the volume and morphological changes of the brain cortex in children with sleep disorders were included in the study. Studies with following characters were excluded: · Non-English studies. · Studies whose participant age range included cases above 18 years old . These studies only included children between the ages of one day and 18. · All studies included neuropsychiatric, neurodegenerative, neuroautoimmune diseases, and congenital cranial and spinal disorders. · Studies were included if cognitive disorders were part of the complications of sleep disorders. Those examined for the occurrence of sleep disorders in cognitive disorders were excluded. · Review studies, case reports, and letters to the editor. Original studies were merely included. Additionally, the studies were organized chronologically, with older comparable studies being substituted by more recent ones. This research involved a comprehensive assessment of published studies spanning from January 2014 to May 2024, utilizing databases such as Web of Science, PubMed, and Scopus. This study also reviewed the titles within the Cochrane Database to identify similarities and evaluate related systematic studies. The keywords were derived from searches conducted in the MeSH database. Two groups of two persons searched the database (first Web of Science, then PubMed and Scopus) separately according to the keywords sleep disorders and gray matter alterations. According to the PRISMA criteria, similar and non-English items were first removed, and then both groups screened titles and abstracts. The eligible articles were given to the co-author for aggregation. If there was an issue with accessing the articles, they were reviewed under the first author's supervision to resolve the problem. Ultimately, 11 studies were selected, and all their texts were evaluated. No additional articles were found through manual citation searches. Data extraction, Study selection, and methodological quality assessment The corresponding and first author formed the summary table and reviewed the studies based on the Cochrane tool on the risk of bias 2 (Rob 2) (20) To extract the data, a group of three authors started extracting kind of sleep disorders, cortical and gray matter alterations, and alterations anatomy, related cognitive disorders, population age mean and sexuality, assessments procedures and tools from the articles separately and without communication, the results were under the supervision of the corresponding and first author, based on the Cochrane guidelines to minimize the bias error and ensure the accuracy of the information. o Statistical analysis To compare the ages and the number of available children, statistical indicators of frequency and mean were used of Artificial intelligence Chat-GPT version 4.0 for all statistical data. Results o Processing After removing all types of review studies, case reports, and letters to the editor mentioned in PubMed, Scopus, and Web of Science databases, a two-person team deleted similar titles and then screened their summaries. Initially, all studies that investigated gray matter and sleep disorders were selected, and the AIM and CONCLUSION of each article were examined. Approximately eighty-six studies were reviewed using this method to exclude studies from the statistical population mentioned in the method section (exclusion studies). Then, two authors separately conducted a comprehensive study of the studies and extracted the necessary information. In total, twenty-six studies available included full-text assessment (Figure 1). After reviewing the full text of the articles, eight studies with the effect of psychological disorders were excluded. Four studies without open access responded negatively to an email request to make detailed results available. After reviewing the studies based on Cochrane's non-biased guidelines for non-randomized clinical trial studies and Rob 2 analysis, three studies with a high risk of bias were excluded (21-23)(Figure 2). Eventually, eleven studies were included in this systematic review to answer the research question. o Demographic extraction The average age of all children under study was 7.03 ± 1.29 years in the lowest range and 15.54 ± 1.66 years in the highest range. The average of the available population (except for the above two studies) was 8.89±3.22. The number of girls (45%) in the available studies is less than the number of boys (55%), indicating that males suffer more from sleep disorders and changes in the brain cortex. o Gray matter alterations and sleep disorders assessment tools MRI in the form of T1-weighted images was the most crucial tool introduced to measure changes in cortical thickness. Polysomnography (PSG) was the main measurable tool for sleep disorders. For the anatomical examination of brain components, all studies referred to the Desikan-Killiany Atlas. o Sleep disorders and cortical alterations Obstructive sleep apnea (SDA) and obstructive sleep-disordered breathing (SDB) were the most reported sleep-breathing disorders. After that, sleep disturbances, including the duration and depth of sleep, were evident in the studies. Only one study dealt with isolated rapid eye movement sleep behavioral disorder (iRBD). · Gray matter alterations in rapid eye movement and sleep disturbance Voxel-based morphometry in iRBD shows that the gray cortex in the left supramarginal gyrus has become thinner (24); however, in this study, regional cortical thickness analyses did not show any difference between the control group and the patients. Shorter sleep duration is associated with a decrease in thickness in the superior middle temporal, right postcentral, and right frontal cortex and a smaller basolateral volume. However, this study violates the relationship between sleep duration and the amygdala (25, 26). Kocevska examines the decrease in gray matter volume at ages two, three, and six. This study showed that the reduction is still noticeable at these ages. However, the study challenges the link between reduced gray matter volume and shorter sleep periods at age seven (27). In other words, in 7-year-old children in this study, but not with white matter, subcortical gray matter volumes, hippocampal or thalamic volume, they are not related to shorter sleep periods. · Sleep breath disorders Breathing disorder during sleep is associated with changes in the thickness and volume of the brain cortex, specifically the gray matter. Subcortical components of gray matter show severe changes in sleep disorders. The thickness of the cerebral cortex in the right anterior caudate cingulate and right cuneiform regions is significantly increased after Obstructive Sleep-Disordered Breathing (28). However, Lee reports that the average thickness of the cerebral cortex is not significantly different between the obstructive sleep apnea group and the control group, although the right superior parietal area has decreased in Obstructive sleep apnea (OSA) (29). Another study using the same method refers to the thinning of the male cortical cortex to the left hemisphere and not the entire cerebral cortex (30). Eventually, the thickness of the cortex in respiratory disorders has been associated with two different results; this discrepancy in findings is also evident in the accounts regarding the volume of the cortex and gray matter. An increase in volume was observed in the middle caudal frontal, left caudal, bilateral, left, right, and bilateral frontal cingulate, left, right, and bilateral caudate brain regions in children with SDB (28), and the volume of the subiculum region on the right side of the hippocampus in adolescent children with OSA is larger than in the control group (31). On the other hand, two studies report a decrease in gray matter volume in the superior frontal, rostral, middle frontal, and caudal middle frontal regions (30, 32). Research consistently shows that respiratory disorders can lead to changes in the brain's structural network, affecting how different parts of the brain communicate with one another (24, 29). Lee reports that sleep breathing disorders increase the clustering coefficient in children and decrease the nodal betweenness centrality, meaning that the left caudal anterior cingulate, left caudal middle frontal, left fusiform, left transverse temporal, right pars opercularis, and right precentral regions They are associated with a decrease in network interaction resulting from hypoxia (33). Severe tissue changes are associated with a decrease in entropy in the areas of the prefrontal cortex, middle and posterior corpus callosum, thalamus, hippocampus, and cerebellum (34). Generally, children's breathing disorders during sleep are associated with changes in brain structure, volume, and thickness of the cortex and gray matter, which are associated with dysfunctions in the affected areas. The complications are variable depending on the affected area, and cognitive disorders are one of the most relevant among them. o Cognitive impairments in sleep disorders Regional and network structural changes of the brain in sleep disorders led to functional and cognitive changes. Children with OSA had a lower total intelligence score and verbal IQ than the control group in the Wechsler test. Furthermore, the volume of the hippocampus in OSA has increased compared to healthy people. Although the decrease in sleep period has been associated with a decrease in the volume of the amygdala, the changes in the volume of these two parts of the brain, which are central to the brain's cognitive network, have a significant impact on cognitive disorders. However, Kokdan with iRBD showed lower ability than the control group in memory, abstract reasoning, and visual-spatial deficits. Nevertheless, Tan violated the relationship between breathing disorders during sleep and cognitive disorders. Discussion The present study determined the changes in volume and thickness of gray matter caused by different sleep disorders. Additionally, this study reviewed the measurement tools in all studies and compared the age and gender of the children population in all studies. The frequency of boys with sleep disorders is higher than that of girls (55% for males), which can be concluded that males are more likely to have sleep disorders. Sleep disorders are linked to alterations in the cortex, with evidence suggesting that these disorders correlate with a reduction in cortical thickness. Notably, only a single study has reported an increase in thickness. The measurement method and MRI imaging data with the T1-weighted technique are the same in all studies. The volume of gray matter has decreased with a decrease in sleep duration and sleep quality. However, once again, sleep disorders cannot be generally related to a decrease in the volume of gray matter and even subcortical areas because one study reported an increase in the volume of OSA. It still needs to be possible to make a complete judgment based on the number of studies in favor of reducing the volume of gray matter. Although the changes in the structure and texture of the cerebral cortex are undeniable and most studies have reported a decrease in volume, it is not easy to judge due to the fact that the measurement tools are the same. These conflicting results may be related to environmental, genetic, and other factors. To make an accurate judgment, further research is necessary. However, it has been observed that more children have experienced a reduction in thickness using the same method. The volume of gray matter increases significantly in the elderly with sleep disorders, but the changes are not the same in all brain tissue. Kumar observed a decrease in brain volume in rostral, mid-dorsal, medial-caudal, and mid-ventral sites, while caudal, mid-dorsal, mid-ventral portions, and ventral sites showed increased volume(35). These results confirm the studies on volume increase in OSA that gray matter in areas of the brain will be associated with volume increase. Perhaps looking at regional changes in the brain in sleep disorders, specifically OSA, can resolve the conflict of results. The increase in the volume of the cerebellum following the increase in the volume of both gray and white matter confirms the increase in subcortical organs in the caudal regions (36). Although in childhood, this difference between different parts of the brain may vary until the final growth and development, the child's growth can increase or decrease these differences. The present findings showed the reduction of gray matter volume in the lower period of sleep at the age of six, and these changes have decreased in seven-year-old children; timely management and treatment of sleep can prevent or aggravate further injuries. The child's development may be influenced by genetic factors that alter the brain's structure, particularly in relation to sleep disorders, potentially resulting in distinct volumetric abnormalities in both the cortex and subcortical regions (3, 37). These changes can involve the cerebellum, hippocampus, amygdala, and thalamus, putting the child's essential responses at risk (38, 39). The cognitive and functional network of the brain forms the response between thousands of neurons in order to coordinate communication with the external environment and the appropriate functional response (40, 41). The center of the cognitive network is the hippocampus, which, in connection with the amygdala, provides a person's knowledge of the environment in order to respond appropriately(42). The volume of the cortex and gray matter in different parts of the brain will change in sleep disorders, as the obtained results show volume changes in the subcortical components, such as the hippocampus. OSA reduces the volume of the hippocampus in the right posterior areas, while in the area’s subiculum and uncus, the increase in the volume of the hippocampus is measured (43, 44). Related to brain regions in sleep disorders, especially OSA, the hippocampus also benefits from the pattern of regional changes, confirming the current results obtained from the articles. However, the obtained results indicate that changes in amygdala volume may not be related to the hippocampus and other members of the cognitive network. Disruption in one of the members of the brain network can lead to disruption, prolongation and disruption of the neuronal responses to the function of another. The volume of gray matter from its standard in each point of the network disrupts the entire brain network. Although these changes may vary in different sleep disorders, they are also related to the severity and pattern of sleep disorders. Although the present results confirm that changes in the cerebral cortex and gray matter are related to sleep disorders, there are still studies that deny this relationship altogether (45). The gray matter and cortex of the brain are the site of vital information processing in the neural network of the brain, which supports the communication of subcortical components for better coordination and more appropriate response (46). Sleep disorders include the coordination of these networks with each other to create and maintain the sleep cycle, along with supporting vital organs such as the heart and lungs (47). Irregular sleep rhythm, irregular breathing rhythm, and even short or long sleep periods mean the brain's neural network cannot coordinate the different components of this network(48, 49). Undoubtedly, many pathological influences that result in changes to the tissue, volume, or structure of the brain network's components disrupt the usual responses required to sustain a stable state of the body during sleep. These changes can permanently change brain structures in children during neural development and cause tissue necrosis or even tissue inflammations in different places that lead to cognitive disorders, memory, learning, and coordination. Early detection of these tissue damage can lead to better prevention and management of these disorders in children. Brain development may resolve the changes, but the damages, such as cognitive disorders after inflammation or severe tissue damage of the hippocampus, threaten the child's life for a long time. In summary, the present study confirms changes in gray matter and cerebral cortex. In response to the different results of past studies, the model suggests regional brain changes in changes in the volume and thickness of the cortex. According to the obtained results, different areas of the brain may show an increase or decrease in thickness and volume of a sleep disorder, and in order to effectively manage sleep disorders, it is necessary to obtain a detailed brain scan from all possible areas. In order to reduce the ambiguity in the discussion of changes in the cerebral cortex, this review suggests more studies on children, which in this way suggests the use of newer tools to clarify the results. Conclusion Changes in the thickness of the cortex and gray matter occur in sleep disorders, varying across different brain regions. While some studies suggest these changes are unrelated to sleep disorders, more research using alternative measurement methods is needed to understand these variations fully. Findings Unlike previous systematic reviews that exclusively dealt with white matter changes, this study determined the nature of gray matter changes. Moreover, previous studies only expressed the differences, so the results were not divided into regional changes in the brain. This review divided the studies into different parts of the brain, leading to the puzzle of different results. Among other things, most of the studies measured the thickness of the cortex only with white matter, and this study aimed to investigate the thickness of the cortex based on gray matter. Inevitably, these studies were excluded, which may be needed for judgment in the general discussion of the thickness of the cortex. The studies also failed to provide detailed results regarding their imaging, merely indicating an increase in volume in broad regions. Consequently, it remains unclear which specific areas of the brain network have undergone changes. Declarations Ethics approval and consent to participate All procedures performed in this study involving human participants studies, were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors. Consent for publication Not applicable. Availability of data and materials The datasets used or analyzed during the current study available from the corresponding author on reasonable request. Competing interests The authors declare no competing interests. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Author contribution H.T.A. the study design and protocol development; oversaw the clinical trial implementation; contributed to data interpretation and manuscript writing. M.S. and N.P.A. Managed participant recruitment and retention; performed statistical analysis; drafted sections of the results and discussion. M.S.H. Conducted literature review and provided expertise in clinical methodology; assisted in data collection and quality assurance; contributed to manuscript revisions. Y.G. Supervised the overall project and ensured compliance with ethical standards; reviewed and approved the final manuscript. Acknowledgment We are sincerely thankful to our counsellors in the Clinical Research Development Center of Amir Kabir Children’s Hospital. 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Cite Share Download PDF Status: Published Journal Publication published 26 Sep, 2025 Read the published version in Sleep Science and Practice → Version 1 posted Editorial decision: Revision requested 03 Jun, 2025 Reviews received at journal 25 May, 2025 Reviews received at journal 17 May, 2025 Reviewers agreed at journal 15 May, 2025 Reviewers agreed at journal 15 May, 2025 Reviewers agreed at journal 13 May, 2025 Reviewers invited by journal 13 May, 2025 Editor assigned by journal 05 May, 2025 Submission checks completed at journal 05 May, 2025 First submitted to journal 30 Apr, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6566964","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":457270202,"identity":"c7e9e538-e732-49da-ac94-1024c67b5201","order_by":0,"name":"Hassan Taherahmadi","email":"","orcid":"","institution":"Arak University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Hassan","middleName":"","lastName":"Taherahmadi","suffix":""},{"id":457270204,"identity":"3939b7fa-6d9b-453c-8a02-7dcb7f58c0cb","order_by":1,"name":"Yazdan Ghandi","email":"","orcid":"","institution":"Arak University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Yazdan","middleName":"","lastName":"Ghandi","suffix":""},{"id":457270208,"identity":"469e421a-1b6b-4f39-8d37-e0692e4ec394","order_by":2,"name":"Negar Poor Ahmadian","email":"","orcid":"","institution":"Arak University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Negar","middleName":"Poor","lastName":"Ahmadian","suffix":""},{"id":457270210,"identity":"401fa47f-d85a-41fa-a30e-43f536f8ccb9","order_by":3,"name":"Mahbod Soltani","email":"","orcid":"","institution":"Arak University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Mahbod","middleName":"","lastName":"Soltani","suffix":""},{"id":457270212,"identity":"589c7c80-1a30-4206-a82b-d80f3599f5ec","order_by":4,"name":"Mohammad Satarzadeh","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/ElEQVRIiWNgGAWjYHCDBDbmPxU2QAZj4wGCig9AtTDwnEkDaWkgQQtv22EkARxAt4H94ecPNffs+duTjz2QOHPebm37YaAtNTbRuLSYHeAxljhwrJhZ4syzdAODitvJ284kArUcS8ttwK2FQeIAG9BRN3LMJBLO3E42OwDUwthwGI8W9sc/DvxL4JG/kf9N4mDbuWSz8w8JaWEwA6pMkDC4kcMm2dh2wM7sBiFbDvOYWZztSzAwPPPMTJrhTHKC2Q2gLQn4/HK8/fGNim8J9nLHk59JM1TY2ZudT3/44EONDU4tDMxo/ESwygRcyrEBe1IUj4JRMApGwcgAAHbEZ1ZjwpdFAAAAAElFTkSuQmCC","orcid":"","institution":"Hormozgan University of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"Mohammad","middleName":"","lastName":"Satarzadeh","suffix":""}],"badges":[],"createdAt":"2025-04-30 17:23:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6566964/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6566964/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s41606-025-00152-9","type":"published","date":"2025-09-26T15:58:14+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":82898649,"identity":"e2b73c7f-de70-49d8-b8ad-31c792f82c5b","added_by":"auto","created_at":"2025-05-16 13:12:29","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":109210,"visible":true,"origin":"","legend":"\u003cp\u003ePRISMA 2020 flow diagram for systematic reviews\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6566964/v1/f9c162c396899b553007fea9.png"},{"id":82901240,"identity":"6c80a612-1a7b-4561-89b8-9ea6ad217488","added_by":"auto","created_at":"2025-05-16 13:28:30","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":599092,"visible":true,"origin":"","legend":"\u003cp\u003eRob 2 plot for our article. High and very high overall marks were removed.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6566964/v1/ebde1592c43ea0ab85faac18.png"},{"id":92431547,"identity":"443893c5-b53e-4e48-8906-51927ab26f5d","added_by":"auto","created_at":"2025-09-29 16:09:52","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1238054,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6566964/v1/bf31e0b7-29d7-42d8-b2cd-e5cfee849d13.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Gray matter alterations in sleep disorders lead to brain networks changes: A systematic review of cortical and subcortical points","fulltext":[{"header":"Introduction","content":"\u003cp\u003eIntroduction Sleep disorders in pediatric populations have become an increasingly recognized concern among healthcare professionals and researchers\u0026nbsp;(1). Defined as persistent difficulties in initiating or maintaining sleep, these disorders encompass a wide range of conditions, including insomnia, sleep apnea, restless legs syndrome, and parasomnias (2, 3). The prevalence of sleep disorders in children is alarming, with estimates suggesting that up to 25% of children experience some form of sleep disruption (4, 5); these disturbances can lead to a myriad of complications, particularly affecting the developing brain (6, 7). The critical stages of brain maturation, occurring during childhood, are susceptible to sleep quality (8). Insufficient or disrupted sleep can hinder cognitive development, leading to issues such as impaired attention, learning difficulties, and emotional regulation problems (4, 9). Accordingly, understanding the implications of sleep disorders on pediatric brain development is essential for early intervention and treatment. Research has increasingly focused on the structural alterations in the brain associated with sleep disorders in children.\u003c/p\u003e\n\u003cp\u003ePrevious studies have indicated that chronic sleep deprivation and disturbances can lead to significant morphological changes in brain structure(10, 11), particularly affecting white matter integrity(12). White matter, consisting of myelinated axons, facilitating communication between different brain regions(13), is crucial for cognitive functioning(14).\u0026nbsp;Additionally, changes in specific brain components, such as the prefrontal cortex and hippocampus, have been assessed in children suffering from sleep disturbances\u0026nbsp;(15, 16). These regions are vital for memory formation and emotional regulation, further underscoring the potential long-term consequences of inadequate sleep on a child's cognitive and emotional health(17, 18).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAlthough the structural and morphological changes of the cortex and subcortex have been confirmed in sleep disorders, the concept of changes in this subject is tied with many ambiguities. Rostampour conducted a systematic review focusing on alterations in white matter; however, the studies incorporated in this review exhibited inconsistencies (12), just as Moghaddam found it challenging to make decisions on white matter changes (19). The current investigation addresses the lack of comprehensive studies on changes in gray matter. We systematically reviewed recent literature to form an impartial judgment regarding the alterations in gray matter thickness and volume. The Patient/Population, Intervention, Comparison, Outcomes (PICO) criteria guide this study, and it consolidates findings from research conducted over the last 10 years.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eo \u003cem\u003eProtocol and registration\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis systematic study was performed based on the accepted criteria of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). To comply with the principle of non-bias, this study used the Cochrane Manual for Systematic Reviewers 5.1.0 for clinical studies and reviewed the studies in terms of allocation concealment, blinding of participants, study personnel, and outcome assessors. The research question was based on PICO criteria\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eo \u003cem\u003eEligibility criteria\u0026nbsp;and search strategy\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis systematic review assessed published studies from January 2014 to 2024 in databases such as Web of Science, PubMed, and Scopus.\u0026nbsp;Sleep disorders were defined according to the guidelines of the American Academy of Sleep Medicine (AASM) (2). This study's primary criterion for identifying cognitive impairment was the International Classification of Cognitive Impairment in Epilepsy (IC-CoDE).\u0026nbsp;The studies that investigated the volume and morphological changes of the brain cortex in children with sleep disorders were included in the study.\u0026nbsp;Studies with following characters were excluded:\u003c/p\u003e\n\u003cp\u003e· Non-English studies.\u003c/p\u003e\n\u003cp\u003e· Studies whose participant age range included cases above 18 years old . These studies only included children between the ages of one day and 18.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e· All studies included neuropsychiatric, neurodegenerative, neuroautoimmune diseases, and congenital cranial and spinal disorders.\u003c/p\u003e\n\u003cp\u003e· Studies were included if cognitive disorders were part of the complications of sleep disorders. Those examined for the occurrence of sleep disorders in cognitive disorders were excluded.\u003c/p\u003e\n\u003cp\u003e· Review studies, case reports, and letters to the editor. Original studies were merely included.\u003c/p\u003e\n\u003cp\u003eAdditionally, the studies were organized chronologically, with older comparable studies being substituted by more recent ones. This research involved a comprehensive assessment of published studies spanning from January 2014 to May 2024, utilizing databases such as Web of Science, PubMed, and Scopus. This study also reviewed the titles within the Cochrane Database to identify similarities and evaluate related systematic studies. The keywords were derived from searches conducted in the MeSH database. \u0026nbsp;Two groups of two persons searched the database (first Web of Science, then PubMed and Scopus) separately according to the keywords sleep disorders and gray matter alterations.\u0026nbsp;According to the PRISMA criteria, similar and non-English items were first removed, and then both groups screened titles and abstracts. The eligible articles were given to the co-author for aggregation. If there was an issue with accessing the articles, they were reviewed under the first author's supervision to resolve the problem. Ultimately, 11 studies were selected, and all their texts were evaluated. No additional articles were found through manual citation searches.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eData extraction, Study selection, and methodological quality assessment\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe corresponding and first author formed the summary table and reviewed the studies based on the Cochrane tool on the risk of bias 2 (Rob 2) (20) To extract the data, a group of three authors started extracting kind of sleep disorders, cortical and gray matter alterations, and alterations anatomy, related cognitive disorders, population age mean and sexuality, assessments procedures and tools from the articles separately and without communication, the results were under the supervision of the corresponding and first author, based on the Cochrane guidelines to minimize the bias error and ensure the accuracy of the information.\u003c/p\u003e\n\u003cp\u003eo \u003cem\u003eStatistical analysis\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eTo compare the ages and the number of available children, statistical indicators of frequency and mean were used of Artificial intelligence Chat-GPT version 4.0 for all statistical data.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eo \u003cstrong\u003eProcessing\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAfter removing all types of review studies, case reports, and letters to the editor mentioned in PubMed, Scopus, and Web of Science databases, a two-person team deleted similar titles and then screened their summaries.\u003c/p\u003e\n\u003cp\u003eInitially, all studies that investigated gray matter and sleep disorders were selected, and the AIM and CONCLUSION of each article were examined. Approximately eighty-six studies were reviewed using this method to exclude studies from the statistical population mentioned in the method section (exclusion studies). Then, two authors separately conducted a comprehensive study of the studies and extracted the necessary information. In total, twenty-six studies available included full-text assessment (Figure 1).\u003c/p\u003e\n\u003cp\u003eAfter reviewing the full text of the articles, eight studies with the effect of psychological disorders were excluded. Four studies without open access responded negatively to an email request to make detailed results available. After reviewing the studies based on Cochrane's non-biased guidelines for non-randomized clinical trial studies and Rob 2 analysis, three studies with a high risk of bias were excluded (21-23)(Figure 2). Eventually, eleven studies were included in this systematic review to answer the research question.\u003c/p\u003e\n\u003cp\u003eo \u003cstrong\u003eDemographic extraction\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe average age of all children under study was 7.03 ± 1.29 years in the lowest range and 15.54 ± 1.66 years in the highest range. The average of the available population (except for the above two studies) was 8.89±3.22. The number of girls (45%) in the available studies is less than the number of boys (55%), indicating that males suffer more from sleep disorders and changes in the brain cortex.\u003c/p\u003e\n\u003cp\u003eo \u003cstrong\u003eGray matter alterations and sleep disorders assessment tools\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMRI in the form of T1-weighted images was the most crucial tool introduced to measure changes in cortical thickness. Polysomnography (PSG) was the main measurable tool for sleep disorders. For the anatomical examination of brain components, all studies referred to the Desikan-Killiany Atlas.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eo \u003cstrong\u003eSleep disorders and cortical alterations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eObstructive sleep apnea (SDA) and obstructive sleep-disordered breathing (SDB) were the most reported sleep-breathing disorders. After that, sleep disturbances, including the duration and depth of sleep, were evident in the studies. Only one study dealt with isolated rapid eye movement sleep behavioral disorder (iRBD).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e· \u003cstrong\u003e\u003cem\u003eGray matter alterations in rapid eye movement and sleep disturbance \u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eVoxel-based morphometry in iRBD shows that the gray cortex in the left supramarginal gyrus has become thinner (24); however, in this study, regional cortical thickness analyses did not show any difference between the control group and the patients. Shorter sleep duration is associated with a decrease in thickness in the superior middle temporal, right postcentral, and right frontal cortex and a smaller basolateral volume. However, this study violates the relationship between sleep duration and the amygdala (25, 26).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Kocevska examines the decrease in gray matter volume at ages two, three, and six. This study showed that the reduction is still noticeable at these ages. However, the study challenges the link between reduced gray matter volume and shorter sleep periods at age seven (27). In other words, in 7-year-old children in this study, but not with white matter, subcortical gray matter volumes, hippocampal or thalamic volume, they are not related to shorter sleep periods.\u003c/p\u003e\n\u003cp\u003e· \u003cstrong\u003e\u003cem\u003eSleep breath disorders\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBreathing disorder during sleep is associated with changes in the thickness and volume of the brain cortex, specifically the gray matter. Subcortical components of gray matter show severe changes in sleep disorders. The thickness of the cerebral cortex in the right anterior caudate cingulate and right cuneiform regions is significantly increased after Obstructive Sleep-Disordered Breathing (28). However, Lee reports that the average thickness of the cerebral cortex is not significantly different between the obstructive sleep apnea group and the control group, although the right superior parietal area has decreased in Obstructive sleep apnea (OSA) (29). Another study using the same method refers to the thinning of the male cortical cortex to the left hemisphere and not the entire cerebral cortex (30). Eventually, the thickness of the cortex in respiratory disorders has been associated with two different results; this discrepancy in findings is also evident in the accounts regarding the volume of the cortex and gray matter.\u003c/p\u003e\n\u003cp\u003eAn increase in volume was observed in the middle caudal frontal, left caudal, bilateral, left, right, and bilateral frontal cingulate, left, right, and bilateral caudate brain regions in children with SDB (28), and the volume of the subiculum region on the right side of the hippocampus in adolescent children with OSA is larger than in the control group (31). On the other hand, two studies report a decrease in gray matter volume in the superior frontal, rostral, middle frontal, and caudal middle frontal regions (30, 32).\u003c/p\u003e\n\u003cp\u003eResearch consistently shows that respiratory disorders can lead to changes in the brain's structural network, affecting how different parts of the brain communicate with one another (24, 29). Lee reports that sleep breathing disorders increase the clustering coefficient in children and decrease the nodal betweenness centrality, meaning that the left caudal anterior cingulate, left caudal middle frontal, left fusiform, left transverse temporal, right pars opercularis, and right precentral regions They are associated with a decrease in network interaction resulting from hypoxia (33). Severe tissue changes are associated with a decrease in entropy in the areas of the prefrontal cortex, middle and posterior corpus callosum, thalamus, hippocampus, and cerebellum (34).\u003c/p\u003e\n\u003cp\u003eGenerally, children's breathing disorders during sleep are associated with changes in brain structure, volume, and thickness of the cortex and gray matter, which are associated with dysfunctions in the affected areas. The complications are variable depending on the affected area, and cognitive disorders are one of the most relevant among them.\u003c/p\u003e\n\u003cp\u003eo \u003cstrong\u003eCognitive impairments in sleep disorders\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRegional and network structural changes of the brain in sleep disorders led to functional and cognitive changes. Children with OSA had a lower total intelligence score and verbal IQ than the control group in the Wechsler test. Furthermore, the volume of the hippocampus in OSA has increased compared to healthy people. Although the decrease in sleep period has been associated with a decrease in the volume of the amygdala, the changes in the volume of these two parts of the brain, which are central to the brain's cognitive network, have a significant impact on cognitive disorders. However, Kokdan with iRBD showed lower ability than the control group in memory, abstract reasoning, and visual-spatial deficits. Nevertheless, Tan violated the relationship between breathing disorders during sleep and cognitive disorders.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe present study determined the changes in volume and thickness of gray matter caused by different sleep disorders. Additionally, this study reviewed the measurement tools in all studies and compared the age and gender of the children population in all studies. The frequency of boys with sleep disorders is higher than that of girls (55% for males), which can be concluded that males are more likely to have sleep disorders.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; Sleep disorders are linked to alterations in the cortex, with evidence suggesting that these disorders correlate with a reduction in cortical thickness. Notably, only a single study has reported an increase in thickness. The measurement method and MRI imaging data with the T1-weighted technique are the same in all studies.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe volume of gray matter has decreased with a decrease in sleep duration and sleep quality. However, once again, sleep disorders cannot be generally related to a decrease in the volume of gray matter and even subcortical areas because one study reported an increase in the volume of OSA. It still needs to be possible to make a complete judgment based on the number of studies in favor of reducing the volume of gray matter. Although the changes in the structure and texture of the cerebral cortex are undeniable and most studies have reported a decrease in volume, it is not easy to judge due to the fact that the measurement tools are the same. These conflicting results may be related to environmental, genetic, and other factors. To make an accurate judgment, further research is necessary. However, it has been observed that more children have experienced a reduction in thickness using the same method. The volume of gray matter increases significantly in the elderly with sleep disorders, but the changes are not the same in all brain tissue. Kumar observed a decrease in brain volume in rostral, mid-dorsal, medial-caudal, and mid-ventral sites, while caudal, mid-dorsal, mid-ventral portions, and ventral sites showed increased volume(35). These results confirm the studies on volume increase in OSA that gray matter in areas of the brain will be associated with volume increase. Perhaps looking at regional changes in the brain in sleep disorders, specifically OSA, can resolve the conflict of results. The increase in the volume of the cerebellum following the increase in the volume of both gray and white matter confirms the increase in subcortical organs in the caudal regions (36). Although in childhood, this difference between different parts of the brain may vary until the final growth and development, the child's growth can increase or decrease these differences. The present findings showed the reduction of gray matter volume in the lower period of sleep at the age of six, and these changes have decreased in seven-year-old children; timely management and treatment of sleep can prevent or aggravate further injuries. The child's development may be influenced by genetic factors that alter the brain's structure, particularly in relation to sleep disorders, potentially resulting in distinct volumetric abnormalities in both the cortex and subcortical regions (3, 37). These changes can involve the cerebellum, hippocampus, amygdala, and thalamus, putting the child's essential responses at risk (38, 39).\u003c/p\u003e\n\u003cp\u003eThe cognitive and functional network of the brain forms the response between thousands of neurons in order to coordinate communication with the external environment and the appropriate functional response (40, 41). The center of the cognitive network is the hippocampus, which, in connection with the amygdala, provides a person's knowledge of the environment in order to respond appropriately(42). The volume of the cortex and gray matter in different parts of the brain will change in sleep disorders, as the obtained results show volume changes in the subcortical components, such as the hippocampus. OSA reduces the volume of the hippocampus in the right posterior areas, while in the area’s subiculum and uncus, the increase in the volume of the hippocampus is measured (43, 44). Related to brain regions in sleep disorders, especially OSA, the hippocampus also benefits from the pattern of regional changes, confirming the current results obtained from the articles. However, the obtained results indicate that changes in amygdala volume may not be related to the hippocampus and other members of the cognitive network. Disruption in one of the members of the brain network can lead to disruption, prolongation and disruption of the neuronal responses to the function of another. The volume of gray matter from its standard in each point of the network disrupts the entire brain network. Although these changes may vary in different sleep disorders, they are also related to the severity and pattern of sleep disorders.\u003c/p\u003e\n\u003cp\u003eAlthough the present results confirm that changes in the cerebral cortex and gray matter are related to sleep disorders, there are still studies that deny this relationship altogether (45). The gray matter and cortex of the brain are the site of vital information processing in the neural network of the brain, which supports the communication of subcortical components for better coordination and more appropriate response (46). Sleep disorders include the coordination of these networks with each other to create and maintain the sleep cycle, along with supporting vital organs such as the heart and lungs (47). Irregular sleep rhythm, irregular breathing rhythm, and even short or long sleep periods mean the brain's neural network cannot coordinate the different components of this network(48, 49). Undoubtedly, many pathological influences that result in changes to the tissue, volume, or structure of the brain network's components disrupt the usual responses required to sustain a stable state of the body during sleep. These changes can permanently change brain structures in children during neural development and cause tissue necrosis or even tissue inflammations in different places that lead to cognitive disorders, memory, learning, and coordination. Early detection of these tissue damage can lead to better prevention and management of these disorders in children. Brain development may resolve the changes, but the damages, such as cognitive disorders after inflammation or severe tissue damage of the hippocampus, threaten the child's life for a long time.\u003c/p\u003e\n\u003cp\u003eIn summary, the present study confirms changes in gray matter and cerebral cortex. In response to the different results of past studies, the model suggests regional brain changes in changes in the volume and thickness of the cortex. According to the obtained results, different areas of the brain may show an increase or decrease in thickness and volume of a sleep disorder, and in order to effectively manage sleep disorders, it is necessary to obtain a detailed brain scan from all possible areas. In order to reduce the ambiguity in the discussion of changes in the cerebral cortex, this review suggests more studies on children, which in this way suggests the use of newer tools to clarify the results.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eChanges in the thickness of the cortex and gray matter occur in sleep disorders, varying across different brain regions. While some studies suggest these changes are unrelated to sleep disorders, more research using alternative measurement methods is needed to understand these variations fully.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eFindings\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUnlike previous systematic reviews that exclusively dealt with white matter changes, this study determined the nature of gray matter changes. Moreover, previous studies only expressed the differences, so the results were not divided into regional changes in the brain. This review divided the studies into different parts of the brain, leading to the puzzle of different results. Among other things, most of the studies measured the thickness of the cortex only with white matter, and this study aimed to investigate the thickness of the cortex based on gray matter. Inevitably, these studies were excluded, which may be needed for judgment in the general discussion of the thickness of the cortex. The studies also failed to provide detailed results regarding their imaging, merely indicating an increase in volume in broad regions. Consequently, it remains unclear which specific areas of the brain network have undergone changes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll procedures performed in this study involving human participants studies, were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used or analyzed during the current study available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contribution\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eH.T.A. the study design and protocol development; oversaw the clinical trial implementation; contributed to data interpretation and manuscript writing. M.S. and N.P.A. Managed participant recruitment and retention; performed statistical analysis; drafted sections of the results and discussion. M.S.H. Conducted literature review and provided expertise in clinical methodology; assisted in data collection and quality assurance; contributed to manuscript revisions. Y.G. Supervised the overall project and ensured compliance with ethical standards; reviewed and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe are sincerely thankful to our counsellors in the Clinical Research Development Center of Amir Kabir Children’s Hospital.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere is no conflict of interest for this investigation.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAltevogt BM, Colten HR. 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Olfactory Epithelium Stimulation Using Rhythmic Nasal Air-Puffs Improves the Cognitive Performance of Individuals with Acute Sleep Deprivation. Brain Sci. 2024;14(4):378.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"sleep-science-and-practice","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ssap","sideBox":"Learn more about [Sleep Science and Practice](http://sleep.biomedcentral.com)","snPcode":"41606","submissionUrl":"https://submission.nature.com/new-submission/41606/3","title":"Sleep Science and Practice","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Sleep disorders, Gray matter, Cortical thickness, Systematic review, Brain network","lastPublishedDoi":"10.21203/rs.3.rs-6566964/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6566964/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDisorders are a common issue among children of various ages, often linked to alterations in the thickness and volume of the cortex in adults. However, the effects on cortical thickness and gray matter volume can differ in children. This systematic review aims to explore the changes in gray matter and the cortex in children experiencing sleep disorders.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis systematic review was conducted based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, and the principle of non-bias was respected. All the articles from 2020-2022 were extracted from the Web of Science, PubMed, and Scopus databases. This study extracted sleep disorders, cortical and gray matter alterations, and alterations anatomy from children up to 18 years old.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEleven studies were identified with inclusion criteria that addressed breathing disorders, obstructive sleep apnea, and periodic sleep disorders. The mean age of the children involved was 3.22 ± 8.89 years, with a T-chart illustrating a predominance of boys over girls. An association was observed between rapid eye movement sleep behavioral disorder and rapid eye movement sleep behavioral disorder. Notably, the thickness of the cerebral cortex in the right anterior caudate cingulate and right cuneiform regions was significantly elevated following obstructive sleep-disordered breathing. The gray matter volume exhibited both increases in certain areas and decreases in others, a phenomenon that applies to all sleep disorders.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSleep disorders change the thickness of the cerebral cortex and the volume of gray matter. Despite the difference in the articles' results, this study found a point change pattern in the brain anatomy, justifying the difference in the results of the previous systematic reviews.\u003c/p\u003e","manuscriptTitle":"Gray matter alterations in sleep disorders lead to brain networks changes: A systematic review of cortical and subcortical points","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-16 13:12:25","doi":"10.21203/rs.3.rs-6566964/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-06-03T16:32:44+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-25T17:25:04+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-17T15:46:29+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"338085960031816606570420447941463599067","date":"2025-05-15T18:49:25+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"313324855250416305631233760077871523685","date":"2025-05-15T14:59:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"327212316124397078074496408177213307712","date":"2025-05-13T20:03:49+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-05-13T17:14:39+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-05T23:33:05+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-05T23:30:11+00:00","index":"","fulltext":""},{"type":"submitted","content":"Sleep Science and Practice","date":"2025-04-30T17:13:45+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"sleep-science-and-practice","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ssap","sideBox":"Learn more about [Sleep Science and Practice](http://sleep.biomedcentral.com)","snPcode":"41606","submissionUrl":"https://submission.nature.com/new-submission/41606/3","title":"Sleep Science and Practice","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"315f14df-836f-4dfe-b328-f25696258cba","owner":[],"postedDate":"May 16th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-09-29T16:08:35+00:00","versionOfRecord":{"articleIdentity":"rs-6566964","link":"https://doi.org/10.1186/s41606-025-00152-9","journal":{"identity":"sleep-science-and-practice","isVorOnly":false,"title":"Sleep Science and Practice"},"publishedOn":"2025-09-26 15:58:14","publishedOnDateReadable":"September 26th, 2025"},"versionCreatedAt":"2025-05-16 13:12:25","video":"","vorDoi":"10.1186/s41606-025-00152-9","vorDoiUrl":"https://doi.org/10.1186/s41606-025-00152-9","workflowStages":[]},"version":"v1","identity":"rs-6566964","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6566964","identity":"rs-6566964","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}