IntroductionInsomnia in shift workers has distinctive features due to circadian rhythm disruption caused by reversed or unstable sleep-wake cycle work schedules. While previous studies have primarily focused on a limited number of predictors for insomnia severity in shift workers, there is a need to further explore key predictors, and develop a data-driven prediction model for insomnia in shift workers. This study aims to identify potential predictors of insomnia severity in shift workers using a machine learning (ML) approach and evaluate the accuracy of the resulting prediction model.MethodsWe assessed the predictors of insomnia severity in large samples of individuals (4,572 shift workers and 2,093 non-shift workers). The general linear model with the least absolute shrinkage and selection operator (LASSO) was used to determine an ML-based prediction model. Additional analyses were conducted to assess the interaction effects depending on the shift work schedule.ResultsThe ML algorithms identified 41 key predictors from 281 variables: 1 demographic, 7 physical health, 13 job characteristics, and 20 mental health factors. Compared to the non-shift workers, the shift workers showed a stronger association between insomnia severity and five predicting variables: passiveness at work, authoritarian work atmosphere, easiness to wake up, family and interpersonal stress, and medication. The prediction model demonstrated good performance with high accuracy and specificity overall despite a limited F1 score (classification effectiveness) and recall (sensitivity). Specifically, a prediction model for shift workers showed better balance in F1 scores and recall compared to that for non-shift workers.DiscussionThis ML algorithm provides an effective method for identifying key factors that predict insomnia severity in shift workers. Our findings align with the traditional insomnia model while also reflecting the distinctive features of shift work such as workplace conditions. Although the potential for immediate clinical application is limited, this study can serve as guidance for future research in improving a prediction model for shift workers. Constructing comprehensive ML-based prediction models that include our key predictors could be a crucial approach for clinical purposes.

BACKGROUND:Computerized cognitive training (CCT) has been proposed as a potential therapy for cognitive decline. One of the benefits of CCT is a transfer effect, but its mechanism on the memory domain is unclear. This study aimed to investigate the transfer effect of non-memory multidomain CCT on the memory domain and its neural basis in patients with mild cognitive impairment (MCI) through a randomized controlled trial. METHODS:Patients with MCI recruited from memory clinics were randomly assigned to either the CCT or the control group. The CCT group received multidomain CCT training excluding memory training, while the control group read educational books with learning-based quizzes twice a week for 8 weeks. Participants underwent memory tests yielding a composite score, other cognitive domain tests, non-cognitive scales, and resting-state functional magnetic resonance imaging (rsfMRI), at baseline and after intervention. Within- and between-group comparisons, group × time interactions, and seed-to-voxel analyses in memory-involving brain networks were performed. RESULTS:The CCT group showed improvement over the control group in memory domain (Group × time, F = 5.87, P = 0.03, η2 = 0.31), which was related with the increased connectivity in the hippocampal-frontal and fusiform-occipital network. No other cognitive and non-cognitive symptoms differed between groups after adjusting for covariates. CONCLUSION:Eight weeks of multidomain CCT without memory training improved memory function and restored functional network in the hippocampal and medial temporal region in MCI patients. These results can provide evidence for the transferring ability of CCT on memory functioning with its neural basis.

BackgroundStudies on the brain structures of shift workers are limited; thus, this cross-sectional study aimed to compare the brain structures and the brain structural correlates of subjective sleepiness and insomnia symptoms between shift workers and non-shift workers.MethodsShift workers (n = 63) and non-shift workers (n = 58) completed questionnaires assessing subjective sleepiness and insomnia symptoms. Cortical thickness, cortical surface area, and subcortical volumes were measured by magnetic resonance imaging. The brain morphometric measures were compared between the groups, and interaction analyses using the brain morphometric measures as the dependent variable were performed to test the interactions between the study group and measures of sleep disturbance (i.e., subjective sleepiness and insomnia symptoms).ResultsNo differences in cortical thickness, cortical surface area, or subcortical volumes were detected between shift workers and non-shift workers. A single cluster in the left motor cortex showed a significant interaction between the study group and subjective sleepiness in the cortical surface area. The correlation between the left motor cortex surface area and the subjective sleepiness level was negative in shift workers and positive in non-shift workers. Significant interaction between the study group and insomnia symptoms was present for the left/right putamen volumes. The correlation between the left/right putamen volumes and insomnia symptom levels was positive in shift workers and negative in non-shift workers.ConclusionLeft motor cortex surface area and bilateral putamen volumes were unique structural correlates of subjective sleepiness and insomnia symptoms in shift workers, respectively.

PURPOSE: Exercise can reduce postprandial hyperglycemia by increasing contraction-mediated glucose uptake in skeletal muscles. However, postprandial exercise does not always have similar effects in all patients. This study aimed to analyze the factors influencing glucose response to exercise following oral glucose load.METHODS: We enrolled 169 adults with impaired glucose tolerance (IGT, n = 64) and type 2 diabetes (T2D, n = 105). We measured fingertip capillary blood glucose level at 30-minute intervals over 2-hour after the 75-g oral glucose ingestion. In addition, a single bout of moderate-intensity aerobic exercise was conducted at 30 minutes after 75-g oral glucose ingestion. We also measured glycated hemoglobin (HbA1c), insulin, insulin resistance (HOMA-IR), β-cell function (HOMA-β), physical activity level questionnaire and anthropometrics.RESULTS: There was a significant difference in glucose concentration between the IGT and T2D groups (p <.001). Additionally, we found that patients with short diabetes duration (≤1 year) had significantly more decrease in glucose concentration than long diabetes duration (≥10 years) (p <.001). A regression analysis showed that waist circumference, visceral fat area, fasting glucose, HbA1c, and HOMA-IR affected glucose response to exercise following oral glucose load in patients with T2D.CONCLUSIONS: Higher volumes of exercise following an oral glucose load may be necessary for individuals with Type 2 Diabetes (T2D) who have a longer disease duration, larger waist circumference, increased visceral fat area, higher HbA1c levels, and elevated HOMA-IR values in order to prevent hyperglycemia.

OBJECTIVE:This study investigated whether sleep and stress mutually interact to induce changes in white matter integrity.METHODS:Diffusion tensor imaging (DTI) was conducted on 36 participants (male=22, female=14; mean age=38.33±12.78 years). Participants were divided into three groups depending on their sleep quality and stress levels: poor sleepers with stress, poor sleepers without stress, and good sleepers. Sleep quality and stress level were evaluated using the Pittsburgh Sleep Quality Index and the Life Experiences Survey, respectively. Fractional anisotropy (FA) values were calculated employing DTI tractography.RESULTS:After controlling for age and sex, poor sleepers with stress exhibited a lower FA of the left inferior cerebellar peduncle (ICP) than did poor sleepers without stress (t=2.81, p=0.02). Poor sleepers without stress showed a higher FA of the right middle longitudinal fasciculus (MdLF) than did good sleepers (t=3.35, p=0.006).CONCLUSION:The current study reports the effects of sleep, stress, and their interaction on the white matter integrities of the ICP and MdLF. ICP change seems to be associated with sleep disturbances related to stress, while MdLF change would be associated with sleep disturbances unrelated to stress.

Purpose:Sounds play important roles in promoting and disrupting sleep. How our brain processes sleep-related sounds and individual differences in processing sleep-related sounds must be determined to understand the role of sound in sleep. We investigated neural responses to sleep-related sounds and their associations with cognitive appraisals of sleep.Participants and Methods:Forty-four healthy adults heard sleep-related and neutral sounds during functional magnetic resonance imaging using a 3T scanner. They also completed the Dysfunctional Beliefs and Attitudes about Sleep (DBAS) questionnaire, which was used to assess cognitive appraisals of sleep. We conducted a voxel-wise whole-brain analysis to compare brain activation in response to sleep-related and neutral sounds. We also examined the association between the DBAS score and brain activity in response to sleep-related sounds (vs neutral sounds) using region of interest (ROI) and whole-brain correlation analyses. The ROIs included the anterior cingulate cortex (ACC), anterior insula (AI), and amygdala.Results:The whole-brain analysis revealed increased activation in the temporal regions and decreased activation in the ACC in response to sleep-related sounds compared to neutral sounds. The ROI and whole-brain correlation analyses showed that higher DBAS scores, indicating a negative appraisal of sleep, were significantly correlated with increased activation of the ACC, right medial prefrontal cortex, and brainstem in response to sleep-related sounds.Conclusion:These results indicate that the temporal cortex and ACC, which are implicated in affective sound processing, may play important roles in the processing of sleep-related sounds. The positive association between the neural responses to sleep-related sounds and DBAS scores suggest that negative and dysfunctional appraisals of sleep may be an important factor in individual differences in the processing of sleep-related sounds.

Objectives: Evidence suggests that emotion regulation difficulty may play an important role in the association between life stress, sleep disturbance and depressive symptoms. We proposed two models depicting the possible moderating roles of prefrontal cortex activation during emotion regulation in the associations among these variables and tested them. We hypothesized that (1) the association between stress and sleep disturbance would differ across prefrontal cortex activation during emotion regulation (moderation model) and (2) the indirect effects of stress on depressive symptoms through sleep disturbance would depend on prefrontal cortex activation during emotion regulation (moderated mediation model). Methods: Forty-eight healthy adults without sleep disorders based on nocturnal polysomnography participated in this study. They received functional magnetic resonance imaging scans while performing an emotion regulation task. They also completed questionnaires assessing life stress, sleep disturbance and depressive symptoms. The proposed models were tested using the PROCESS macro for SPSS. Results: As hypothesized, there was a significant moderating effect of prefrontal cortex activation during emotion regulation on the association between life stress and sleep disturbance. Furthermore, right lateral prefrontal cortex activation had a moderating role in the indirect effect of life stress on depressive symptoms through sleep disturbance. Conclusion: These findings highlight the important role of prefrontal cortex function during emotion regulation in the associations between stress, sleep disturbance and depressive symptoms. Increasing lateral prefrontal cortex recruitment when regulating the emotional response to negative life events may be critical for the prevention and intervention of depression as well as sleep problems.

Background In animal experiments, the habenula and septal nuclei are known as the key brain areas of depression. However, there are few magnetic resonance imaging (MRI) studies on the functional connectivity between these areas and the subcortical areas in humans with major depression. We aimed to investigate the difference in resting-state functional connectivity (RSFC) among the major regions of interest (ROI) in the subcortical areas, including both the habenula and septal nuclei. Methods We performed the seed-to-voxel analysis to investigate the RSFC between both the habenula and septal nucleus, as well as other subcortical regions. Furthermore, ROI-to-ROI analysis was performed among the combinations of ROI pairs in the subcortical areas. Results The seed-to-voxel analysis showed a lower RSFC between the left habenula and the cerebellum in major depressive disorder (MDD) than in healthy controls (HCs). As a result of ROI-to-ROI analysis in subcortical areas, a total of 31 pairs of FCs in the MDD group showed a lower RSFC than in the HCs group. Conclusion This study revealed a lower RSFC between the left habenula and cerebellum in patients with MDD and reduced RSFC among numerous subcortical areas. These new findings on the neural circuitry of MDD might contribute to an in-depth understanding of depression.

The current study investigated differences in the regional gray matter (GM) volume of specific thalamic nuclei between North Korean (NK) refugees and South Korean (SK) residents. It also investigated associations between thalamic GM volume changes and psychological symptoms. Psychological evaluations and magnetic resonance imaging were conducted on 50 traumatized NK refugees and 55 non-traumatized SK residents. The regional GM volume ratios in the bilateral thalami were calculated for all participants using voxel-based morphometry. NK refugees showed greater GM volume ratios in the right medial-posterior nuclei and left medial nuclei compared with SK residents. NK refugees also exhibited more depressive symptoms than SK residents. However, increased GM volume ratios in both right medial-posterior nuclei and left medial nuclei were correlated with fewer depressive symptoms in NK refugees, but not in SK residents. The findings indicate that traumatized NK refugees had increased GM volumes in the right medial-posterior nuclei and left medial nuclei, which were associated with fewer depressive symptoms. The enlarged specific thalamic nuclei presented among refugees in the current study might be associated with a neurobiological compensatory mechanism that prevents the development or progression of depression in refugees after repetitive traumatic experiences.

Introduction:We investigated the white matter integrity in shift and non-shift workers and its associations with sleep and activity. Methods:Diffusion tensor imaging (DTI) was performed on 61 shift workers and 31 non-shift workers. Their sleep and activity profiles were assessed using the Pittsburgh Sleep Quality Index (PSQI), sleep diaries, and actigraphy. Fractional anisotropy (FA) (a measure of white matter integrity) was calculated using DTI tractography. Results:Shift workers exhibited higher FA values in the bilateral anterior cingulum than did non-shift workers. An increased FA in the right anterior cingulum was correlated with poor sleep quality (ie, a high PSQI score) in shift workers. An increased FA in the right anterior cingulum was also correlated with higher actigraphic activity indices (the mesor and M10 indices) in shift workers. Discussion:The white matter integrity of the anterior cingulum was altered in shift workers, perhaps in association with sleep and activity disturbances.

We investigated the differential spatial covariance pattern of blood oxygen level-dependent (BOLD) responses to single-task and multitask functional magnetic resonance imaging (fMRI) between patients with psychophysiological insomnia (PI) and healthy controls (HCs), and evaluated features generated by principal component analysis (PCA) for discrimination of PI from HC, compared to features generated from BOLD responses to single-task fMRI using machine learning methods. In 19 patients with PI and 21 HCs, the mean beta value for each region of interest (ROIbval) was calculated with three contrast images (i.e., sleep-related picture, sleep-related sound, and Stroop stimuli). We performed discrimination analysis and compared with features generated from BOLD responses to single-task fMRI. We applied support vector machine analysis with a least absolute shrinkage and selection operator to evaluate five performance metrics: accuracy, recall, precision, specificity, and F2. Principal component features showed the best classification performance in all aspects of metrics compared to BOLD response to single-task fMRI. Bilateral inferior frontal gyrus (orbital), right calcarine cortex, right lingual gyrus, left inferior occipital gyrus, and left inferior temporal gyrus were identified as the most salient areas by feature selection. Our approach showed better performance in discriminating patients with PI from HCs, compared to single-task fMRI.

Refugees often report heightened emotional reactivity and emotion regulation difficulties and are at high risk for mental health problems. Given that refugees are repeatedly exposed to traumatic events that may cause changes in the brain, the present study examined neural correlates of emotional reactivity and regulation and their associations with refugee features (e.g., cumulative trauma) and the severity of psychiatric symptoms (e.g., post-traumatic stress disorder [PTSD]) in North Korean (NK) refugees. Forty NK refugees with trauma exposure and varying levels of psychopathology and 41 healthy South Korean (SK) controls without trauma exposure participated in this study. They performed an emotion regulation task during a functional magnetic resonance imaging (fMRI) assessment. Region of interest (ROI), whole brain, and generalized psychophysiological interaction (gPPI) analyses were conducted. NK refugees with trauma exposure and varying levels of psychopathology showed increased activation in response to negative socio-affective pictures in regions involved in affective processing, including the amygdala and hippocampus, relative to healthy SK controls without trauma exposure. They also exhibited greater prefrontal cortex (PFC) activation, amygdala–PFC functional connectivity (FC), and hippocampal–PFC FC during emotion regulation. More severe PTSD symptoms were associated with greater hippocampal response to negative pictures (vs. neutral pictures) in NK refugees. This study provides neuroscientific evidence for neural alterations in association with emotional reactivity and regulation in traumatized refugees. These findings may contribute to a better mechanistic understanding of emotional reactivity and regulation in refugees and suggest potential ways to address the emotional and mental problems of traumatized refugees.

Background: The thalamus and habenula are thought to be key brain regions in the etiology of major depressive disorder (MDD); however, few studies have investigated the structural connection between them. We compared the number of white matter tracts between the thalamus and habenula between patient with MDD and normal controls (NCs). Methods: The habenula and thalamus region of interest masks were extracted from brain magnetic resonance imaging data and individual tractography analysis was performed. First, we compared the number of fiber connections from the habenula to the thalamus between the MDD (n = 34) and NC (n = 37) groups and also compared hemispherical differences to investigate possible asymmetries. Results: There was a significant difference in the number of tracts in the right habenula-left mediodorsal thalamus pair between the two groups. For hemispherical fiber connections, the waytotal ratio of the right ipsilateral tract between the thalamus and habenula was significantly higher than that of the left ipsilateral tract in both groups. Conclusion: The number of right habenula-left mediodorsal thalamus tracts was higher in patients with MDD than in NCs. These results indicate that MDD is related to the disintegration of the left thalamus-right habenula tract function with an increased number of tracts as a compensational mechanism.

BackgroundCognitive training can potentially prevent cognitive decline. However, the results of recent studies using semi-immersive virtual reality (VR)-assisted cognitive training are inconsistent. ObjectiveWe aimed to examine the hypothesis that cognitive training using fully immersive VR, which may facilitate visuospatial processes, could improve visuospatial functioning, comprehensive neuropsychological functioning, psychiatric symptoms, and functional connectivity in the visual brain network in predementia. MethodsParticipants over 60 years old with subjective cognitive decline or mild cognitive impairment from a memory clinic were randomly allocated to the VR (n=23) or the control (n=18) group. The VR group participants received multidomain and neuropsychologist-assisted cognitive training in a fully immersive VR environment twice a week for 1 month. The control group participants did not undergo any additional intervention except for their usual therapy such as pharmacotherapy. Participants of both groups were evaluated for cognitive function using face-to-face comprehensive neuropsychological tests, including the Rey-Osterrieth Complex Figure Test (RCFT) copy task; for psychiatric symptoms such as depression, apathy, affect, and quality of life; as well as resting-state functional magnetic resonance imaging (rsfMRI) at baseline and after training. Repeated-measures analysis of variance was used to compare the effect of cognitive training between groups. Seed-to-voxel–based analyses were used to identify the cognitive improvement–related functional connectivity in the visual network of the brain. ResultsAfter VR cognitive training, significant improvement was found in the total score (F1,39=14.69, P=.001) and basic components score of the RCFT copy task (F1,39=9.27, P=.005) compared with those of the control group. The VR group also showed improvements, albeit not significant, in naming ability (F1,39=3.55, P=.07), verbal memory delayed recall (F1,39=3.03, P=.09), and phonemic fluency (F1,39=3.08, P=.09). Improvements in psychiatric symptoms such as apathy (F1,39=7.02, P=.01), affect (F1,39=14.40, P=.001 for positive affect; F1,39=4.23, P=.047 for negative affect), and quality of life (F1,39=4.49, P=.04) were found in the VR group compared to the control group. Improvement in the RCFT copy task was associated with a frontal-occipital functional connectivity increase revealed by rsfMRI in the VR group compared to the control group. ConclusionsFully immersive VR cognitive training had positive effects on the visuospatial function, apathy, affect, quality of life, and increased frontal-occipital functional connectivity in older people in a predementia state. Future trials using VR cognitive training with larger sample sizes and more sophisticated designs over a longer duration may reveal greater improvements in cognition, psychiatric symptoms, and brain functional connectivity. Trial RegistrationClinical Research Information Service KCT0005243; https://tinyurl.com/2a4kfasa

Little is known regarding structural brain changes in traumatized refugees and the association with psychopathology. In the present study, the cortical thickness in North Korean refugees and the association with psychological symptoms were explored. North Korean refugees with lifetime post-traumatic stress disorder (PTSD group, n = 27), trauma-exposed North Korean refugees without lifetime PTSD (trauma-exposed control (TEC) group, n = 23), and healthy South Korean controls without traumatic experiences (HC group, n = 51) completed questionnaires assessing depression, anxiety, somatization, and PTSD symptoms. The cortical thickness was measured by magnetic resonance imaging (MRI) using FreeSurfer. Age- and sex-adjusted cortical thickness of the right medial prefrontal cortex (mPFC) was greater in the TEC group than in the HC group. However, significant differences were not observed between the PTSD and HC groups. Increased right mPFC thickness was significantly correlated with less anxiety and somatization after controlling for age and sex in the TEC group, but not in the PTSD or HC groups. North Korean refugees who did not develop PTSD after trauma showed increased right mPFC thickness, which was associated with less severe psychiatric symptoms. These findings indicate that increased mPFC thickness might have helped to reduce PTSD and psychiatric symptoms after trauma, and likely reflects resilience achieved by potentially enhancing emotional regulation in the mPFC.

Subjective–objective discrepancy of sleep (SODS) might be related to the distorted perception of sleep deficit and hypersensitivity to insomnia-related stimuli. We investigated differences in brain activation to insomnia-related stimuli among insomnia patients with SODS (SODS group), insomnia patients without SODS (NOSODS group), and healthy controls (HC). Participants were evaluated for subjective and objective sleep using sleep diary and polysomnography. Functional magnetic resonance imaging was conducted during the presentation of insomnia-related ( Ins ), general anxiety-inducing ( Gen ), and neutral ( Neu ) stimuli. Brain reactivity to the contrast of Ins vs. Neu and Gen vs. Neu was compared among the SODS (n = 13), NOSODS (n = 15), and HC (n = 16) groups. In the SODS group compared to other groups, brain areas including the left fusiform, bilateral precuneus, right superior frontal gyrus, genu of corpus callosum, and bilateral anterior corona radiata showed significantly increased blood oxygen level dependent (BOLD) signal in the contrast of Ins vs. Neu . There was no brain region with significantly increased BOLD signal in the Gen vs. Neu contrast in the group comparisons. Increased brain activity to insomnia-related stimuli in several brain regions of the SODS group is likely due to these individuals being more sensitive to sleep-related threat and negative cognitive distortion toward insomnia.

BACKGROUND:Insomnia is a common disorder that affects a vast number of patients; the hyperarousal theory of insomnia postulates that patients with insomnia are physiologically activated not only at nighttime but also during the daytime. We aimed to investigate the differences in the resting-state functional connectivity (RSFC) of the thalamus with cortical areas between patients with insomnia disorder and healthy controls.METHODS:All participants completed clinical questionnaires and underwent portable polysomnography and resting-state fMRI.RESULTS:Patients in the insomnia group (n = 50) showed increased RSFC between the thalamus and right medial superior frontal area, bilateral middle temporal areas, left rectus and right parahippocampal areas compared with controls (n = 42) after controlling for age, sex and education level. Among the pairs that showed increased connectivity, several functional connections were negatively correlated with sleep efficiency, measured by polysomnography.Limitations: We used a small sample size.CONCLUSION:We consider these results on increased thalamocortical hyperactivity in brain areas related to sensory functions as providing evidence for the hyperarousal theory of insomnia.

In posttraumatic stress disorder (PTSD), functional connectivity (FC) between the thalamus and other brain areas has yet to be comprehensively investigated. The present study explored resting state FC (rsFC) of thalamus and its associations with trauma-related features. The included subjects were North Korean refugees with PTSD (n = 23), trauma-exposed North Korean refugees without PTSD (trauma-exposed control [TEC] group, n = 22), and South Korean healthy controls (HCs) without traumatic experiences (HC group, n = 40). All participants underwent psychiatric evaluation and functional magnetic resonance imaging (fMRI) procedures using the bilateral thalamus as seeds. In the TEC group, the negative rsFC between each thalamus and its contralateral postcentral cortex was stronger relative to the PTSD and HC groups, while positive rsFC between the left thalamus and left precentral cortex was stronger in the HC group compared to the PTSD and TEC groups. Thalamo-postcentral rsFC was positively correlated with the CAPS total score in the TEC group, and with the number of traumatic experiences in the PTSD group. The present study identified the difference of thalamic rsFC alterations among traumatized refugees and HCs. Negative rsFC between the thalamus and somatosensory cortices might be compensatory changes after multiple traumatic events in refugees.