No phenotypic or genotypic evidence for a link between sleep duration and brain atrophy.

Short sleep is held to cause poorer brain health, but is short sleep associated with higher rates of brain structural decline? Analysing 8,153 longitudinal MRIs from 3,893 healthy adults, we found no evidence for an association between sleep duration and brain atrophy. In contrast, cross-sectional analyses (51,295 observations) showed inverse U-shaped relationships, where a duration of 6.5 (95% confidence interval, (5.7, 7.3)) hours was associated with the thickest cortex and largest volumes relative to intracranial volume. This fits converging evidence from research on mortality, health and cognition that points to roughly seven hours being associated with good health. Genome-wide association analyses suggested that genes associated with longer sleep for below-average sleepers were linked to shorter sleep for above-average sleepers. Mendelian randomization did not yield evidence for causal impacts of sleep on brain structure. The combined results challenge the notion that habitual short sleep causes brain atrophy, suggesting that normal brains promote adequate sleep duration-which is shorter than current recommendations.

Alterations of functional connectivity in young people with depression mediate the relationship between sleep quality and cognitive function.

BACKGROUND: Sleep disturbances is common in young people with depression, and poor sleep quality affects the ability to learn. In this study, we examined possible resting-state functional connectivity abnormalities between regions of interest, and clarified the relationship with depressive symptoms, sleep quality, and cognitive function. METHODS: Resting-state functional magnetic resonance imaging (fMRI) was collected on 42 healthy controls (HCs), 82 youth depressive patients (44 without sleep disturbances (NSD), and 38 with sleep disturbances (SD)). Regions of interest were defined by using Brainnetome Atlas. Functional connectivity was calculated, and its associations with depressive symptoms, sleep quality, and cognitive function were examined using correlation analysis and mediation analysis. RESULTS: The left and right caudal of cingulate gyrus, tongue and larynx region of postcentral gyrus were significant brain regions in NSD versus SD. The average functional connectivity between these regions was associated with poor sleep quality (r = 0.368, p = 0.001) and worse working memory (r = -0.256, p = 0.023) and mediated the relationship between sleep quality and working memory (c = -0.738, c' = -0.500). LIMITATION: Data consistency in this study was not good enough. This study did not monitor sleep rhythms to provide objective sleep-related data. CONCLUSION: The functional connectivity between the left and right caudal of cingulate gyrus with tongue and larynx region of postcentral gyrus may be the neural mechanism by which sleep disturbances affect working memory. This provides an intervention target for clinically improving cognitive function in young people with depression.

Novel neuroelectrophysiological age index associated with imaging features of brain aging and sleep disorders.

Sleep architecture and microstructures alter with aging and sleep disorder-led accelerated aging. We proposed a sleep EEG based brain age prediction model using convolutional neural networks. We then associated the estimated brain age index with brain structural aging features, sleep disorders and various sleep parameters. Our model also showed a higher BAI (predicted brain age minus chronological age) is associated with cortical thinning in various functional areas. We found a higher BAI for sleep disorder groups compared to healthy sleepers, as well as significant differences in the spectral pattern of EEG among different sleep disorders (lower power in slow and ϑ waves for sleep apnea vs. higher power in ß and σ for insomnia), suggesting sleep disorder-dependent pathomechanisms of aging. Our results demonstrate that the new EEG-BAI can be a biomarker reflecting brain health in normal and various sleep disorder subjects, and may be used to assess treatment efficacy.

The association of amygdala-insula functional connectivity and adolescent e-cigarette use via sleep problems and depressive symptoms.

BACKGROUND: Adolescent electronic cigarette (e-cigarette) use remains high. Elucidating contributing factors may enhance prevention strategies. Neurobiologically, amygdala-insula resting-state functional connectivity (rsFC) has been linked with aspects of sleep, affect, and substance use (SU). As such, we hypothesized that amygdala's rsFC with the insula would be associated with e-cigarette use via sleep problems and/or depression levels. METHODS: An adolescent sample (N = 146) completed a rs-fMRI scan at time 1 and self-reports at time 2 (∼15 months later). Given consistent associations between mental health outcomes and the rsFC of the laterobasal amygdala (lbAMY) with the anterior insula, we utilized a seed region (lbAMY) to region of interest (ROI) analysis approach to characterize brain-behavior relationships. Two serial mediation models tested the interrelations between amygdala's rsFC with distinct anterior insula subregions (i.e., ventral insula [vI], dorsal insula [dI]), sleep problems, depression levels, and days of e-cigarette use. RESULTS: An indirect effect was observed when considering the lbAMY's rsFC with the vI. Greater rsFC predicted more sleep problems, more sleep problems were linked with greater depressive symptoms, and greater depressive symptoms were associated with more e-cigarette use (indirect effect = 0.08, CI [0.01,0.21]). Indicative of a neurobiological dissociation, a similar indirect effect linking these variables was not observed when considering the lbAMY's rsFC with the dI (indirect effect = 0.03, CI [-0.001,0.10]). CONCLUSIONS: These outcomes highlight functional interactions between the amygdala and insula as a neurobiological contributor to sleep problems, depressive symptoms, and ultimately SU thereby suggesting potential intervention points to reduce teen e-cigarette use.

Sleep Dysfunction and Grey Matter Volume.

PURPOSE OF REVIEW: With the voxel-based morphometry (VBM), structural imaging studies turned into new directions aiming to explore neurological disorders differently. This approach helps identify possible pathophysiological correlations between neuroanatomical grey matter (GM) structures in patients with sleep dysfunction. This article reviews recent findings on GM structure in various sleep disorders and possible causes of disturbed sleep and discusses the future perspectives. RECENT FINDINGS: At present, research on the effect of GM volume changes in specific brain areas on the pathogenesis of sleep disturbances is incomplete. It remains unknown if the GM thickness reduction in patients with REM sleep behaviour disorder, obstructive sleep apnea, restless legs syndrome, and insomnia is due to complex disease presentation or direct response to disturbed sleep. Additionally, many VBM studies have yielded inconsistent results showing either reduction or increase in GM. The spatiotemporal complexity of whole-brain networks and state transitions during sleep and the role of GM changes increase new debates. Having multimodal data from large sample studies can help model sleep network dynamics in different disorders and provide novel data for possible therapeutic interventions.

Neural correlates of sleep quality in children: Sex-specific associations shown by brain diffusion tractography.

BACKGROUND AND PURPOSE: Sleep quality is important for healthy growth and development of children. We aimed to identify associations between sleep disturbances in healthy children without clinical diagnosis of sleep disorders and brain white matter (WM) microstructure using an advanced diffusion-weighted magnetic resonance imaging (DW-MRI) based tractography analysis, and to explore whether there are sex differences in these associations. METHODS: Brain DW-MRI data were collected from sixty-two 8-year-old children (28 boys, 34 girls) whose parents also completed Children's Sleep Habits Questionnaire (CSHQ). Track-weighted imaging (TWI) measures were computed from the DW-MRI data for 37 WM tracts in each subject. Sex-specific partial correlation analyses were performed to evaluate correlations between TWI measures and a set of sleep disturbance scores derived from the CSHQ. RESULTS: Significant correlations (P < .05, FDR-corrected; r: .48-.67) were identified in 13 WM tracts between TWI and sleep disturbance scores. Sexually dimorphic differences in correlations between sleep disturbance scores and WM microstructure measurements were observed. Specifically, in boys, daytime sleepiness positively correlated with track-weighted mean or radial diffusivity in 10 WM tracts (bilateral arcuate fasciculus, left cingulum, right middle longitudinal fasciculus, and three bilateral segments of superior longitudinal fasciculus). In girls, total CSHQ score, night walking, or sleep onset delay negatively correlated with track-weighted fractional anisotropy or axial diffusivity in 4 WM tracts (bilateral inferior longitudinal fasciculus and uncinate fasciculus). CONCLUSIONS: The findings suggest that sleep disturbances without clinical diagnosis of sleep disorders are associated with lower WM microstructural integrity in children. Additionally, the associations possess unique patterns in boys and girls.

Functional connectome mediates the association between sleep disturbance and mental health in preadolescence: A longitudinal mediation study.

Sleep disturbance is known to be associated with various mental disorders and often precedes the onset of mental disorders in youth. Given the increasingly acknowledged bidirectional influence between sleep disturbance and mental disorders, we aim to identify a shared neural mechanism that underlies sleep disturbance and mental disorders in preadolescents. We analyzed a dataset of 9,350 9-10 year-old children, among whom 8,845 had 1-year follow-up data, from the Adolescent Brain Cognitive Development (ABCD) study. Linear mixed-effects models, mediation analysis, and longitudinal mediation analysis were used to investigate the relationship between sleep disturbance, mental disorders, and resting-state network connectivity. Out of 186 unique connectivities, the effect of total sleep disturbance (TSP, from Sleep Disturbance Scale) and mental problems (MP, from Child Behavior Checklist) converged in the default mode network (DMN) and the dorsal attention network (DAN). Within- and between-network connectivities (DMN-DAN, DMN-DMN, DAN-DAN) mediated the relationship between baseline TSD and MP at 1-year follow-up and the relationship between baseline MP and TSD at 1-year follow-up. The pathway model in which sleep disturbance and mental problems affect each other through two anticorrelated brain networks (DMN and DAN) suggests a common neural mechanism between them. Longitudinally, a less segregated DMN and DAN is associated with negative outcomes on mental well-being and sleep disturbance a year later. These findings have important implications for the design of prevention and neurofeedback intervention for mental disorders and sleep problems.

Sleep duration, sleep problems, and perceived stress are associated with hippocampal subfield volumes in later life: findings from The Irish Longitudinal Study on Ageing.

STUDY OBJECTIVES: This study examines the cross-sectional and 2-year follow-up relationships between sleep and stress and total hippocampal volume and hippocampal subfield volumes among older adults. METHODS: Four hundred seventeen adults (aged 68.8 ± 7.3; 54% women) from the Irish Longitudinal Study on Ageing completed an interview, a questionnaire, and multiparametric brain magnetic resonance imaging. The relationships between self-reported sleep duration, sleep problems, perceived stress, and total hippocampal volume were examined by using ordinary least squares regressions. Linear mixed-effects models were used to investigate the relationships between sleep duration, sleep problems, perceived stress, changes in these measures over 2-years, and hippocampal subfield volumes. RESULTS: No cross-sectional and follow-up associations between sleep and total hippocampal volume and between stress and total hippocampal volume were found. By contrast, Long sleep (≥9-10 h/night) was associated with smaller volumes of molecular layer, hippocampal tail, presubiculum, and subiculum. The co-occurrence of Short sleep (≤6 h) and perceived stress was associated with smaller cornu ammonis 1, molecular layer, subiculum, and tail. Sleep problems independently and in conjunction with higher stress, and increase in sleep problems over 2 years were associated with smaller volumes of these same subfields. CONCLUSION: Our study highlights the importance of concurrently assessing suboptimal sleep and stress for phenotyping individuals at risk of hippocampal subfield atrophy.

Alcohol use severity and the neural correlates of the effects of sleep disturbance on sustained visual attention.

Alcohol misuse is associated with sleep disturbance and cognitive dysfunction. However, the neural processes inter-relating the severity of alcohol use, sleep disturbance and cognitive performance remain under-investigated. We addressed this issue with a dataset of 964 subjects (504 women) curated from the Human Connectome Project. Participants were assessed with the Pittsburgh Sleep Quality Index (PSQI) and fMRI while identifying relational dimension pictures and matching dimension pictures (as a control) in alternating blocks. Imaging data were analyzed with published routines and the results were evaluated at a corrected threshold. Subjects showed lower accuracy rate and longer reaction time (RT) in relational than control blocks. The difference in RT between the two blocks (RTRel-Con) was driven primarily by the RT and correlated positively with performance accuracy of relational trials, suggesting that a more cautious response (i.e., longer RTRel-Con) improved accuracy. The severity of alcohol use, identified from principal component analysis of drinking metrics, was positively correlated with sleep disturbance. Further, whole-brain regression identified activity of the superior colliculus (SC) during relational vs. control blocks in positive and negative correlation with RTRel-Con and PSQI score, respectively. Mediation and path analyses demonstrated a significant model: more severe alcohol use → greater sleep disturbance → diminished SC activity → impaired performance. These findings support the influences of alcohol misuse on sleep and suggest neural correlates that mediate the relationship between sleep disturbance and altered sustained attention in young adults.

Sleep disturbances are associated with cortical and subcortical atrophy in alcohol use disorder.

Sleep disturbances are prominent in patients with alcohol use disorder (AUD) and predict relapse. So far, the mechanisms underlying sleep disruptions in AUD are poorly understood. Because sleep-related regions vastly overlap with regions, where patients with AUD showed pronounced grey matter (GM) reduction; we hypothesized that GM structure could contribute to sleep disturbances associated with chronic alcohol use. We combined sleep EEG recording and high-resolution structural brain imaging to examine the GM-sleep associations in 36 AUD vs. 26 healthy controls (HC). The patterns of GM-sleep associations differed for N3 vs. REM sleep and for AUD vs. HC. For cortical thickness (CT), CT-sleep associations were significant in AUD but not in HC and were lateralized such that lower CT in right hemisphere was associated with shorter N3, whereas in left hemisphere was associated with shorter REM sleep. For the GM density (GMD), we observed a more extensive positive GMD-N3 association in AUD (right orbitofrontal cortex, cerebellum, dorsal cingulate and occipital cortex) than in HC (right orbitofrontal cortex), and the GMD-REM association was positive in AUD (midline, motor and paralimbic regions) whereas negative in HC (the left supramarginal gyrus). GM structure mediated the effect of chronic alcohol use on the duration of N3 and the age by alcohol effect on REM sleep. Our findings provide evidence that sleep disturbances in AUD were associated with GM reductions. Targeting sleep-related regions might improve sleep in AUD and enhance sleep-induced benefits in cognition and emotional regulation for recovery.

The brain mechanism of awakening dysfunction in children with primary nocturnal enuresis based on PVT-NAc neural pathway: a resting-state fMRI study.

Primary nocturnal enuresis (PNE) affects children's physical and mental health with a high rate. However, its neural mechanism is still unclear. Studies have found that the paraventricular thalamus (PVT) is among the key brain regions implicated with awakening regulation and its control of the transition between sleep and wakening is dependent on signaling through the PVT-nucleus accumbens (NAc) pathway. So this study analyzed the function of brain regions and their connectivity of PVT and NAc. A total of twenty-six PNE and typically developing (TD) children were involved in the study and the methods of amplitude of low frequency fluctuation (ALFF), degree centrality (DC) and functional connectivity (FC) based on resting-state functional magnetic resonance imaging (rs-fMRI) were used to analyze the brain functions. Results showed that there was no statistical significant difference in ALFF and DC between PNE and TD children in bilateral PVT and NAc. And there was statistical significant difference of the comparison of the FC of left PVT (lPVT) and left NAc (lNAc) between PNE and TD children. Meanwhile, there was negative correlation between awakening score and the FC of rPVT and lNAc, and no obvious correlation between awakening score and the FC of lPVT and lNAc in PNE children. Meanwhile, there was both negative correlation between awakening score and the FC of lPVT, rPTV and lNAc in TD children. Therefore, the FC between rPVT and lNAc was more reliable in assessing the degree of awakening ability in PNE children. This finding could help establish the evaluation index of PNE.

Altered intrinsic brain activity in mild Alzheimer's disease patients with sleep disturbances.

Sleep disturbances are one of the preventive factors to delay the onset and progression of Alzheimer's disease. Early identification of Alzheimer's disease patients prone to develop sleep disturbances to offer early medical intervention is important. Resting-state functional MRI is a widely used method to investigate the neural mechanisms and find neuroimaging biomarkers in neuropsychiatric diseases. In this study, we applied percent amplitude of fluctuation (PerAF) and mPerAF (divided by global mean PerAF) to test the strength of intrinsic brain activity in 38 mild Alzheimer's disease patients with sleep disturbances (ADSD) and 21 mild Alzheimer's disease patients without sleep disturbances (ADNSD). Compared with ADNSD, we found decreased intrinsic brain activity in the calcarine gyrus, the lingual gyrus, the fusiform gyrus extending to the parahippocampal gyrus, the precentral gyrus, the postcentral gyrus (all in the left hemisphere) and the left brainstem. Conclusively, ADSD exhibited reduced neural activity in specific brain regions related to the sensorimotor network and the visual network, which indicated the contribution of sleep disturbances to the progression of Alzheimer's disease. Especially, the ventral visual pathway to the hippocampus might serve for the memory impaired by sleep disturbances in Alzheimer's disease, and the brainstem might be critical in the initiation of sleep disturbances in Alzheimer's disease. These findings further elucidate the interactions between Alzheimer's disease and sleep disturbances and could help with the early recognition of Alzheimer's disease patients who tend to develop sleep disturbances.

Link between Mild Traumatic Brain Injury, Poor Sleep, and Magnetic Resonance Imaging: Visible Perivascular Spaces in Veterans.

Impaired clearance of perivascular waste in the brain may play a critical role in morbidity after mild traumatic brain injury (mTBI). We aimed to determine the effect of mTBI on the burden of magnetic resonance imaging (MRI)-visible perivascular spaces (PVSs) in a cohort of U.S. military veterans and whether sleep modulates this effect. We also investigated the correlation between PVS burden and severity of persistent post-concussive symptoms. Fifty-six Iraq/Afghanistan veterans received 3 Tesla MRI as part of a prospective cohort study on military blast mTBI. White matter PVS burden (i.e., number and volume) was calculated using an established automated segmentation algorithm. Multi-variate regression was used to establish the association between mTBIs sustained in the military and PVS burden. Covariates included age, blood pressure, number of impact mTBIs outside the military, and blast exposures. Correlation coefficients were calculated between PVS burden and severity of persistent post-concussive symptoms. There was a significant positive relationship between the number of mTBIs sustained in the military and both PVS number and volume (p = 0.04). A significant interaction was found between mTBI and poor sleep on PVS volume (p = 0.04). A correlation was found between PVS number and volume, as well as severity of postconcussive symptoms (p = 0.03). Further analysis revealed a moderate correlation between PVS number and volume, as well as balance problems (p < 0.001). In Iraq/Afghanistan veterans, mTBI is associated with an increase in PVS burden. Further, an interaction exists between mTBI and poor sleep on PVS burden. Increased PVS burden, which may indicate waste clearance dysfunction, is associated with persistent post-concussive symptom severity.

Slow-Wave Sleep and MRI Markers of Brain Aging in a Community-Based Sample.

OBJECTIVE: To test the hypothesis that reduced slow-wave sleep, or N3 sleep, which is thought to underlie the restorative functions of sleep, is associated with MRI markers of brain aging, we evaluated this relationship in the community-based Framingham Heart Study Offspring cohort using polysomnography and brain MRI. METHODS: We studied 492 participants (age 58.8 ± 8.8 years, 49.4% male) free of neurological diseases who completed a brain MRI scan and in-home overnight polysomnography to assess slow-wave sleep (absolute duration and percentage of total sleep). Volumes of total brain, total cortical, frontal cortical, subcortical gray matter, hippocampus, and white matter hyperintensities were investigated as a percentage of intracranial volume, and the presence of covert brain infarcts was evaluated. Linear and logistic regression models were adjusted for age, age squared, sex, time interval between polysomnography and MRI (3.3 ± 1.0 years), APOE ε4 carrier status, stroke risk factors, sleeping pill use, body mass index, and depression. RESULTS: Less slow-wave sleep was associated with lower cortical brain volume (absolute duration, ß [standard error] = 0.20 [0.08], p = 0.015; percentage, 0.16 [0.08], p = 0.044), lower subcortical brain volume (percentage, 0.03 [0.02], p = 0.034), and higher white matter hyperintensities volume (absolute duration, -0.12 [0.05], p = 0.010; percentage, -0.10 [0.04], p = 0.033). Slow-wave sleep duration was not associated with hippocampal volume or the presence of covert brain infarcts. CONCLUSION: Loss of slow-wave sleep might facilitate accelerated brain aging, as evidence by its association with MRI markers suggestive of brain atrophy and injury. Alternatively, subtle injuries and accelerated aging might reduce the ability of the brain to produce slow-wave sleep.

Poor Self-Reported Sleep is Related to Regional Cortical Thinning in Aging but not Memory Decline-Results From the Lifebrain Consortium.

We examined whether sleep quality and quantity are associated with cortical and memory changes in cognitively healthy participants across the adult lifespan. Associations between self-reported sleep parameters (Pittsburgh Sleep Quality Index, PSQI) and longitudinal cortical change were tested using five samples from the Lifebrain consortium (n = 2205, 4363 MRIs, 18-92 years). In additional analyses, we tested coherence with cell-specific gene expression maps from the Allen Human Brain Atlas, and relations to changes in memory performance. "PSQI # 1 Subjective sleep quality" and "PSQI #5 Sleep disturbances" were related to thinning of the right lateral temporal cortex, with lower quality and more disturbances being associated with faster thinning. The association with "PSQI #5 Sleep disturbances" emerged after 60 years, especially in regions with high expression of genes related to oligodendrocytes and S1 pyramidal neurons. None of the sleep scales were related to a longitudinal change in episodic memory function, suggesting that sleep-related cortical changes were independent of cognitive decline. The relationship to cortical brain change suggests that self-reported sleep parameters are relevant in lifespan studies, but small effect sizes indicate that self-reported sleep is not a good biomarker of general cortical degeneration in healthy older adults.

Sleep Disturbance of Evacuees in Minamisanriku Town after Great East Japan Earthquake: Risk Factors and Treatment.

In 2011, Minamisanriku Town lost all of its medical facilities during the Great East Japan Earthquake. Using 10,459 anonymized disaster medical records of affected people in Minamisanriku Town, we assessed the prevalence and risk factors of sleep disturbance, which is known to exacerbate non-communicable diseases (NCDs) and anxiety disorder. Because sleep disturbance is a part of mental health issues, we divided the patients into two groups: patients (n = 492) with mental health issues other than sleep disturbance and the remaining (n = 9,967) with other comorbidities. Out of 492 patients with mental health issues, 295 patients (60.0%, 114 male, 158 female and 23 unknown) had sleep disturbance who might have required specific treatments. Out of the remaining 9,967 patients, 1,203 patients (12.1%, 361 male and 769 female and 73 unknown) had sleep disturbance. Univariate and multivariate analyses of the 9,967 patients revealed that the odds ratio (OR) of sleep disturbance was higher for female (OR 1.95), elderly persons over 60 (OR 16.15) and residing in evacuation centers (OR 1.36). Patients with two or more NCD had higher risk (OR 1.42). Importantly, sleep disturbance affects younger patients without NCD residing in evacuation center. Emergency medical teams most frequently prescribed benzodiazepines both for sleep induction and anxiolysis. In addition to high risk groups (female, older, with other mental health issues, residing in evacuation center), it is important to survey sleep disturbance in younger and healthier populations especially in evacuation centers and to provide psychosocial and medical support for them.

The Role of Polysomnography in Identifying Sleep Disorders in Children with Migraine.

Migraine pathophysiology and sleep share common neural pathways, and there are clinical as well as paraclinical observations, which lead to the hypothesis of an association between migraine and sleep disorders. The objective of this study consisted of the evaluation of a possible correlation between migraine and sleep disorders in children, as reflected by sleep architecture and electroencephalographic patterns. Eighteen patients aged five to seventeen were recruited for the migraine group, and sixteen age-matched patients with no criteria for migraine or any underlying organic disorder, diagnosed with emotional disorders, were enrolled in the control group. All patients underwent inpatient full night polysomnographic recordings, the results of which were analyzed using appropriate statistical methods. Patients in the migraine group had decreased REM sleep (p = 0.049) and increased N1 sleep (p = 0.018) percentages, compared to the control group. Also, more arousals (p = 0.011) and lower sleep latency (p = 0.029) were noted in the migraine group. A statistically significant association was observed between migraine and sleep disorders when the latter was defined with respect to normal values of polysomnographic parameters published in studies conducted on healthy children. Polysomnography can be a useful tool for studying sleep in pediatric migraine patients. The results of this study can be regarded as a starting point for a better understanding of the complex role of sleep in the developing brain and of eventual intricacies with migraine pathophysiological mechanisms.

Structural Alterations in Large-scale Brain Networks and Their Relationship with Sleep Disturbances in the Adolescent Population.

Although sleep disturbances are highly prevalent in adolescents, neuroimaging evidence on the effects of sleep disturbances on their developing brains remains limited. Therefore, we explored gray matter volumes (GMVs) at the whole-brain level and investigated their relationship to sleep disturbances in a sample of Korean adolescents in the general population. We recruited participants from one middle school and high school. All participants and their legal guardians gave informed consent before participating in our study. We used component 5 of the Pittsburgh Sleep Quality Index to measure sleep disturbances and conducted a voxel-based morphometry-DARTEL procedure to measure GMVs. We performed partial correlation analyses to examine whether the GMVs were associated with sleep disturbances. A total of 56 adolescents participated in this study. Our results revealed that GMVs in multiple global regions were negatively correlated with sleep disturbances. Moreover, most of these identified regions belong to large-scale brain networks categorized by functional neuroimaging studies. We found an association between regional GMVs in multiple global regions involved in large-scale networks and the severity of sleep disturbances in the adolescent population. Based on this evidence and previous neuroimaging evidence, we suggest that structural alterations in the networks may be linked to sleep disturbances.

Self-reported Sleep Problems Related to Amyloid Deposition in Cortical Regions with High HOMER1 Gene Expression.

Sleep problems are related to the elevated levels of the Alzheimer's disease (AD) biomarker ß-amyloid (Aß). Hypotheses about the causes of this relationship can be generated from molecular markers of sleep problems identified in rodents. A major marker of sleep deprivation is Homer1a, a neural protein coded by the HOMER1 gene, which has also been implicated in brain Aß accumulation. Here, we tested whether the relationship between cortical Aß accumulation and self-reported sleep quality, as well as changes in sleep quality over 3 years, was stronger in cortical regions with high HOMER1 mRNA expression levels. In a sample of 154 cognitively healthy older adults, Aß correlated with poorer sleep quality cross-sectionally and longitudinally (n = 62), but more strongly in the younger than in older individuals. Effects were mainly found in regions with high expression of HOMER1. The anatomical distribution of the sleep-Aß relationship followed closely the Aß accumulation pattern in 69 patients with mild cognitive impairment or AD. Thus, the results indicate that the relationship between sleep problems and Aß accumulation may involve Homer1 activity in the cortical regions, where harbor Aß deposits in AD. The findings may advance our understanding of the relationship between sleep problems and AD risk.

Integrating sleep, neuroimaging, and computational approaches for precision psychiatry.

In advancing precision psychiatry, we focus on what imaging technology and computational approaches offer for the future of diagnostic subtyping and personalized tailoring of interventions for sleep impairment in mood and anxiety disorders. Current diagnostic criteria for mood and anxiety tend to lump different forms of sleep disturbance together. Parsing the biological features of sleep impairment and brain circuit dysfunction is one approach to identifying subtypes within these disorders that are mechanistically coherent and offer targets for intervention. We focus on two large-scale neural circuits implicated in sleep impairment and in mood and anxiety disorders: the default mode network and negative affective network. Through a synthesis of existing knowledge about these networks, we pose a testable framework for understanding how hyper- versus hypo-engagement of these networks may underlie distinct features of mood and sleep impairment. Within this framework we consider whether poor sleep quality may have an explanatory role in previously observed associations between network dysfunction and mood symptoms. We expand this framework to future directions including the potential for connecting circuit-defined subtypes to more distal features derived from digital phenotyping and wearable technologies, and how new discovery may be advanced through machine learning approaches.