Brain structural correlates of subjective sleepiness and insomnia symptoms in shift workers.

Background: Studies 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. Methods: Shift 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). Results: No 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. Conclusion: Left motor cortex surface area and bilateral putamen volumes were unique structural correlates of subjective sleepiness and insomnia symptoms in shift workers, respectively.

The Influence of Life Stress and Sleep Disturbance on White Matter Integrity.

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.

Decreased resting-state functional connectivity of the habenula-cerebellar in a major depressive disorder.

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.

Cognitive Appraisal of Sleep and Brain Activation in Response to Sleep-Related Sounds in Healthy Adults.

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.

Evidence of White Matter Integrity Changes in the Anterior Cingulum Among Shift Workers: A Cross-Sectional Study.

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.

Gray Matter Volume of Thalamic Nuclei in Traumatized North Korean Refugees.

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.

Life stress, sleep disturbance and depressive symptoms: The moderating role of prefrontal activation during emotion regulation.

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.

Thalamocortical functional connectivity in patients with insomnia using resting-state fMRI.

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.

Thalamo-Habenular Connection Differences Between Patients With Major Depressive Disorder and Normal Controls.

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.

Neural correlates of emotional reactivity and regulation in traumatized North Korean refugees.

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.

Increased medial prefrontal cortical thickness and resilience to traumatic experiences in North Korean refugees.

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.

Effect of Cognitive Training in Fully Immersive Virtual Reality on Visuospatial Function and Frontal-Occipital Functional Connectivity in Predementia: Randomized Controlled Trial.

BACKGROUND: Cognitive training can potentially prevent cognitive decline. However, the results of recent studies using semi-immersive virtual reality (VR)-assisted cognitive training are inconsistent. OBJECTIVE: We 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. METHODS: Participants 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. RESULTS: After 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. CONCLUSIONS: Fully 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 REGISTRATION: Clinical Research Information Service KCT0005243; https://tinyurl.com/2a4kfasa.

Multitask fMRI and machine learning approach improve prediction of differential brain activity pattern in patients with insomnia disorder.

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.

Brain reactivity using fMRI to insomnia stimuli in insomnia patients with discrepancy between subjective and objective sleep.

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.

Resting State Functional Connectivity of the Thalamus in North Korean Refugees with and without Posttraumatic Stress Disorder.

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.

Alexithymia and frontal-amygdala functional connectivity in North Korean refugees.

BACKGROUND: Refugees commonly experience difficulties with emotional processing, such as alexithymia, due to stressful or traumatic experiences. However, the functional connectivity of the amygdala, which is central to emotional processing, has yet to be assessed in refugees. Thus, the present study investigated the resting-state functional connectivity of the amygdala and its association with emotional processing in North Korean (NK) refugees. METHODS: This study included 45 NK refugees and 40 native South Koreans (SK). All participants were administered the Toronto Alexithymia Scale (TAS), Beck Depression Inventory (BDI), and Clinician-administered PTSD Scale (CAPS), and differences between NK refugees and native SK in terms of resting-state functional connectivity of the amygdala were assessed. Additionally, the association between the strength of amygdala connectivity and the TAS score was examined. RESULTS: Resting-state connectivity values from the left amygdala to the bilateral dorsolateral prefrontal cortex (dlPFC) and dorsal anterior cingulate cortex (dACC) were higher in NK refugees than in native SK. Additionally, the strength of connectivity between the left amygdala and right dlPFC was positively associated with TAS score after controlling for the number of traumatic experiences and BDI and CAPS scores. CONCLUSIONS: The present study found that NK refugees exhibited heightened frontal-amygdala connectivity, and that this connectivity was correlated with alexithymia. The present results suggest that increased frontal-amygdala connectivity in refugees may represent frontal down-regulation of the amygdala, which in turn may produce alexithymia.

Decreased regional brain activity in response to sleep-related sounds after cognitive behavioral therapy for psychophysiological insomnia.

AIM: Patients with psychophysiological insomnia (PI) experience hyperarousal, especially as a reaction to sound stimuli. In the current study, we explored brain activity changes in response to sleep-related sounds (SS) in patients with insomnia after cognitive behavioral therapy for insomnia (CBT-I). METHODS: In 14 drug-free PI patients, regional brain activity in response to SS, and to white noise sound (NS) as neutral stimuli, was investigated before and after individual CBT-I using functional magnetic resonance imaging. Blood oxygen level-dependent (BOLD) signals to SS and NS were compared before and after CBT-I. In addition, the association between clinical improvement after CBT-I and changes in brain activity in response to SS and NS was analyzed. RESULTS: Compared with baseline, regional brain activity in response to SS after CBT-I decreased in the left middle temporal and left middle occipital gyrus. In regression analysis, a reduction in the Dysfunctional Beliefs and Attitudes about Sleep (DBAS) Scale score after CBT-I was associated with decrease in brain activity in response to SS in both thalami. However, brain activity in response to NS showed no BOLD signal changes and no association with DBAS change. CONCLUSION: Cortical hyperactivity, which may cause hyperarousal in PI, was found to decrease after CBT-I. CBT-I targeting changes in beliefs and attitudes about sleep may induce its therapeutic effects by reducing thalamic brain activity in response to sleep-related stimuli.

Stroop Task-Related Brain Activity in Patients With Insomnia: Changes After Cognitive-Behavioral Therapy for Insomnia.

Objective/Background: In the present study, we compared differences in brain activity during the Stroop task between patients with chronic insomnia disorder (CID) and good sleepers (GS). Furthermore, we evaluated changes in Stroop task-related brain activity after cognitive-behavioral therapy for insomnia (CBT-I). Participants/Methods: The final analysis included 21 patients with CID and 25 GS. All participants underwent functional magnetic resonance imaging (fMRI) while performing the color-word Stroop task. CBT-I, consisting of 5 sessions, was administered to 14 patients with CID in the absence of medication. After CBT-I, fMRI was repeated in the patients with CID while performing the same task. Sleep-related questionnaires and sleep variables from a sleep diary were also obtained before and after CBT-I. Results: No significant differences in behavioral performance in the Stroop task or task-related brain activation were observed between the CID and GS groups. No changes in behavioral performance or brain activity were found after CBT-I. However, clinical improvement in the Insomnia Severity Index (ISI) score was significantly associated with changes in the Stroop task-related regional blood oxygen level-dependent signals in the left supramarginal gyrus. Conclusions: Our findings suggest that cognitive impairment in patients with CID was not detectable by the Stroop task or Stroop task-related brain activation on fMRI. Moreover, there was no altered brain activity during the Stroop task after CBT-I. However, the ISI score reflected changes in the neural correlates of cognitive processes in patients with CID after CBT-I.

Changes in subcortical resting-state functional connectivity in patients with psychophysiological insomnia after cognitive-behavioral therapy: Changes in resting-state FC after CBT for insomnia patients.

STUDY OBJECTIVES: To examine the resting-state functional connectivity (FC) between subcortical regions in relation to whole-brain activity in patients with psychophysiological insomnia (PI) and changes following cognitive-behavioral therapy for insomnia (CBTi). METHODS: The FC between subcortical seed regions (caudate, putamen, pallidum, amygdala, thalamus, and hippocampus) and whole-brain voxels were compared between the PI group (n = 13, mean age: 51.0 ± 10.2 years) and good sleepers (GS, n = 18, mean age: 42.7 ± 12.3 years). Also, in the PI group, FC was compared before and after 5 weeks of CBTi. RESULTS: Compared to the GS group, the PI group exhibited stronger FC between the thalamus and prefrontal cortex and between the pallidum and precuneus but weaker FC between the pallidum and angular gyrus, the caudate and orbitofrontal cortex, and the hippocampus and fusiform gyrus. After CBTi, the PI group exhibited decreased FC between the thalamus and parietal cortex, the putamen and motor cortices, and the amygdala and lingual gyrus, but increased FC between the caudate and supramarginal gyrus, the pallidum and orbitofrontal cortex, and the hippocampus and frontal/parietal gyri. CONCLUSIONS: The present findings demonstrate different FC in PI patients compared to GS and provide insight into the neurobiological rationale for CBTi.

Exploration of changes in the brain response to sleep-related pictures after cognitive-behavioral therapy for psychophysiological insomnia.

Psychophysiological insomnia (PI) includes arousal to sleep-related stimuli (SS), which can be treated by cognitive behavioral therapy for insomnia (CBT-I). The present study was an exploratory, prospective intervention study that aimed to explore brain response to visual SS in PI before and after CBT-I. Blood oxygen level dependent (BOLD) signal differences in response to SS and neutral stimuli (NS) were compared between 14 drug-free PI patients and 18 good sleepers (GS) using functional magnetic resonance imaging (fMRI). BOLD changes after CBT-I in patients were also examined. PI patients showed higher BOLD activation to SS in the precentral, prefrontal, fusiform, and posterior cingulate cortices before CBT-I. The increased responses to SS were reduced after CBT-I. The increased response to SS in the precentral cortex was associated with longer wake time after sleep onset (WASO), and its reduction after CBT-I was associated with improvements in WASO. Clinical improvements after CBT-I were correlated with BOLD reduction in the right insula and left paracentral cortex in response to SS. PI showed hyper-responses to SS in the precentral cortex, prefrontal cortex, and default mode network and these brain hyper-responses were normalized after CBT-I. CBT-I may exert its treatment effects on PI by reducing hyper-responses to SS in the precentral cortex and insula.