Larger hypothalamic subfield volumes in patients with chronic insomnia disorder and relationships to levels of corticotropin-releasing hormone.

The hypothalamus is a well-established core structure in the sleep-wake cycle. While previous studies have not consistently found whole hypothalamus volume changes in chronic insomnia disorder (CID), differences may exist at the smaller substructural level of the hypothalamic nuclei. The study aimed to investigate the differences in total and subfield hypothalamic volumes, between CID patients and healthy controls (HCs) in vivo, through an advanced deep learning-based automated segmentation tool. A total of 150 patients with CID and 155 demographically matched HCs underwent T1-weighted structural magnetic resonance scanning. We utilized FreeSurfer v7.2 for automated segmentation of the hypothalamus and its five nuclei. Additionally, correlation and causal mediation analyses were performed to investigate the association between hypothalamic volume changes, insomnia symptom severity, and hypothalamus-pituitary-adrenal (HPA) axis-related blood biomarkers. CID patients exhibited larger volumes in the right anterior inferior, left anterior superior, and left posterior subunits of the hypothalamus compared to HCs. Moreover, we observed a positive association between blood corticotropin-releasing hormone (CRH) levels and insomnia severity, with anterior inferior hypothalamus (a-iHyp) hypertrophy mediating this relationship. In conclusion, we found significant volume increases in several hypothalamic subfield regions in CID patients, highlighting the central role of the HPA axis in the pathophysiology of insomnia.

Thalamic network under wakefulness after sleep onset and its coupling with daytime fatigue in insomnia disorder: An EEG-fMRI study.

BACKGROUND: Fatigue is the most common daytime impairment of insomnia disorder (ID). Thalamus is acknowledged as the key brain region closely associated with fatigue. However, the thalamus-based neurobiological mechanisms of fatigue in patients with ID remain unknown. METHODS: Forty-two ID patients and twenty-eight well-matched healthy controls (HCs) underwent simultaneous electroencephalography--functional magnetic resonance imaging. We calculated the functional connectivity (FC) between the thalamic seed and each voxel across the whole brain in two conditions of wakefulness--after sleep onset (WASO) and before sleep onset. A linear mixed effect model was used to determine the condition effect of the thalamic FC. The correlation between daytime fatigue and the thalamic connectivity was explored. RESULTS: After sleep onset, the connectivity with the bilateral thalamus was increased in the cerebellar and cortical regions. Compared with HCs, ID patients showed significantly lower FC between left thalamus and left cerebellum under the WASO condition. Furthermore, thalamic connectivity with cerebellum under the WASO condition was negatively correlated with Fatigue Severity Scale scores in the pooled sample. CONCLUSIONS: These findings contribute to an emerging framework that reveals the link between insomnia-related daytime fatigue and the altered thalamic network after sleep onset, further highlighting the possibility that this neural pathway is a therapeutic target for meaningfully mitigating fatigue.

Enhanced intrathalamic morphological connectivity in patients with chronic insomnia.

This study aimed to systematically investigate abnormal morphological connectivity in subregions of the thalamus and examine the clinical relevance of this connectivity in patients with chronic insomnia. One hundred and two patients with chronic insomnia (aged 45.50 [34.75 ~ 58.00] years; 24 men, 78 women) and one hundred and one healthy controls (aged 45.00 [34.00 ~ 55.00] years; 32 men, 69 women) were recruited. Intrathalamic and thalamocortical morphological connectivity in the thalamic subregions defined in the Human Brainnetome Atlas were computed and compared between the two groups. Spearman's correlation was used to estimate the association between thalamic morphological connectivity alterations and clinical variables. Compared with the control group, the insomnia group exhibited higher intrathalamic mean morphological connectivity than the control group, though no alterations in thalamocortical morphological connectivity were observed. However, no correlation was found between altered intrathalamic morphological connectivity and behavioral scales. In addition, alterations in morphological connectivity among thalamic subregions were found mainly in the left medial premotor thalamus, left medial prefrontal thalamus, and left sensory thalamus; however, these results were no longer significant after correction. Our findings suggest increased intrathalamic morphological connectivity in patients with chronic insomnia, thus enriching the understanding of morphological connectivity at the individual level and providing new perspectives for clinical interventions and diagnostic imaging.

Altered thalamic functional connectivity and cerebral blood flow in insomnia disorder: a resting-state functional magnetic resonance imaging study.

BACKGROUND AND PURPOSE: The thalamus plays a crucial role in sleep regulation, but few studies have examined functional connectivity of the thalamus in insomnia disorder. This study aimed to investigate the connectivity patterns and perfusion of the thalamus in patients with insomnia disorder using resting-state functional connectivity and three-dimensional arterial spin labeling (3D ASL). MATERIALS AND METHODS: In total, 56 patients with insomnia disorder and 59 healthy control participants with a similar age-, gender-, and education lever distribution underwent resting-state functional magnetic resonance imaging (rs-fMRI) and 3D-ASL. The thalamus was selected as the seed region. Whole-brain connectivity was assessed using rs-fMRI. Cerebral blood flow (CBF) of the bilateral thalamus was measured with 3D-ASL using region-of-interest (ROI) analysis. All participants completed a series of neuropsychological assessments. Sleep parameters were assessed via polysomnography (PSG). The relationships between imaging parameters and clinical variables were assessed with Pearson correlation analysis. RESULTS: Compared with healthy controls, patients with insomnia disorder exhibited increased connectivity between the left thalamus and right precentral gyrus, and right thalamus and left middle frontal gyrus (MFG), right superior parietal lobule (SPL) and right superior frontal gyrus (SFG). Whereas decreased connectivity was noted between the right thalamus and left posterior cerebellar lobe including Crus I, Crus II, and VII b/VII. Connectivity between the right thalamus and left Crus I was positively correlated with MoCA scores (r = 0.286, P = 0.036) in insomnia disorder. CONCLUSIONS: Our findings illustrate functional abnormalities in brain connectivity and their relationship with cognitive impairments in insomnia disorder, providing novel insight into the neural mechanisms of insomnia disorder.

White matter alterations in heart-kidney imbalance insomnia and Jiao-Tai-Wan treatment: A diffusion-tensor imaging study.

Previous studies have reported changes in white matter microstructures in patients with insomnia. However, few neuroimaging studies have focused specifically on white matter tracts in insomnia patients after having received treatment. In this prospective study, diffusion-tensor imaging was used in two samples of heart-kidney imbalance insomnia patients who were treated with placebo or Jiao-Tai-Wan, a traditional Chinese medicine commonly used to treat heart-kidney imbalance insomnia, to assess the changes in white matter tracts. Tract-based spatial statistical analyses were first applied to compare the changes in mean diffusivity and fractional anisotropy of white matter between 75 heart-kidney imbalance insomnia patients and 41 healthy control participants. In subsequent randomized, double-blind, placebo-controlled trials, comparisons of mean diffusivity and fractional anisotropy were also performed in 24 heart-kidney imbalance insomnia patients (8 males; 16 females; 42.5 ± 10.4 years) with Jiao-Tai-Wan and 26 heart-kidney imbalance insomnia patients (11 males; 15 females; 39.7 ± 9.4 years) with a placebo, with age and sex as covariates. Fractional anisotropy values in left corticospinal tract were increased in heart-kidney imbalance insomnia patients. Heart-kidney imbalance insomnia patients showed lower mean diffusivity and fractional anisotropy values of several white matter tracts than healthy control participants, such as the bilateral anterior limb of internal capsule, bilateral superior longitudinal fasciculus and bilateral posterior corona radiata. After being treated with Jiao-Tai-Wan, heart-kidney imbalance insomnia patients showed a trend towards reduced fractional anisotropy values in the left corticospinal tract. Jiao-Tai-Wan may improve the sleep quality by reversing the structural changes of the left corticospinal tract caused by heart-kidney imbalance insomnia.

[Changes in the functional connectivity of the thalamus in insomniac ED patients with yin deficiency and fire syndrome: An exploration based on functional MRI findings].

OBJECTIVE: To investigate the changes of nocturnal erectile function and functional connectivity (FC) of bilateral thalami in insomniac ED patients with yin deficiency and fire syndrome. METHODS: We enrolled 30 healthy controls and 87 ED patients with yin deficiency and fire syndrome, 41 with and the other 46 without insomnia. Using IIEF-5 and Pittsburgh Sleep Quality Index (PSQI), we evaluated the nocturnal erectile function and sleep quality of the patients and compared the clinical indicators between the two groups. Then we collected and preprocessed the MRI data on the cerebral function of the 15 ED patients with insomnia, another 15 without insomnia and the 30 healthy controls. With the thalamus as the region of interest (ROI), we calculated and compared the FC values of brain regions between the ED patients (with or without insomnia) and healthy controls, and corrected the results for multiple comparisons using the AlphaSim method. RESULTS: Compared with the patients without insomnia, those with insomnia had a lower duration of erectile episode and tumescence and rigidity activity units in the tip of the penis. With the left thalamus as the ROI, the right middle frontal gyrus and inferior parietal were shown to be the differential brain regions among the three groups. Compared with the healthy controls, the patients without insomnia showed decreased FC values between the left thalamus and left orbital part of the middle frontal gyrus, insula, putamen and right thalamus, while those with insomnia exhibited decreased FC values between the left thalamus and bilateral middle frontal gyri, inferior parietal, calcarine fissure, parahippocampal gyrus, left superior parietal gyrus, right precuneus and inferior temporal gyrus, and they also exhibited decreased FC values between the left thalamus and middle frontal gyrus in comparison with those without insomnia. With the right thalamus as the ROI, the left medial superior frontal gyrus, bilateral calcarine fissure and right thalamus were found to be the differential brain regions among the three groups. Compared with the healthy controls, the patients without insomnia showed decreased FC values between the right thalamus (including the right thalamus itself) and left medial orbital superior frontal gyrus, superior temporal gyrus (temporal pole), middle temporal gyrus, insula and right orbital part of the inferior frontal gyrus, while those with insomnia manifested decreased FC values between the right thalamus and middle frontal gyrus, inferior parietal, left superior parietal gyrus and calcarine fissure, and they also manifested increased FC values between the right thalamus and medial superior frontal gyrus, and decreased FC values between the right thalamus and left calcarine fissure in comparison with those without insomnia. CONCLUSION: ED patients with insomnia have more serious clinical symptoms, with FC changes in the thalamocortical loop, which might be the pathological mechanisms of ED with insomnia.

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.

The cerebral mechanism of acupuncture for chronic insomnia with gastrointestinal disorder: protocol for a randomized controlled trial.

BACKGROUND: Many patients with chronic insomnia disorder (CID) have gastrointestinal (GI) symptoms. First-line insomnia medications do not treat GI problems. Acupuncture has a comprehensive regulative action on both CID and GI disorder and is receiving increasing attention. Recent studies indicate that both CID and GI diseases may cause abnormal brain activity. However, the neurological mechanism underlying the effect of acupuncture on such diseases is still unclear. The aim of this study is to explore the pathological mechanisms of CID with GI discomfort, as well as the main response characteristics of acupuncture treatment from multiple perspectives using multimodal magnetic resonance imaging (MRI). METHODS: A total of 60 participants with CID and GI disorders will be randomly divided into two groups (real acupuncture group and sham acupuncture group; ratio of 1:1). Patients will receive 20 sessions (five sessions per week) of real acupuncture treatment or sham acupuncture treatment. The primary outcome is the aggregate score on the Pittsburgh Sleep Quality Index. Secondary outcomes are scores on the Gastrointestinal Symptom Rating Scale, Self-Rating Anxiety Scale, and Self-Rating Depression Scale. Multimodal MRI scans and clinical assessments will be performed both at baseline and post-treatment. Another 30 age-, sex-, and education-matched healthy subjects will be recruited as controls and will receive MRI scans and clinical evaluations. DISCUSSION: This study aims to provide scientific evidence for the mechanism of acupuncture in treating CID with GI disorder using multimodal MRI imaging data on brain structure, function, and metabolism. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800017092 (URL: http://www.chictr.org.cn/showproj.aspx?proj=27173 ). Registered on July 11, 2018.

Altered thalamic connectivity in insomnia disorder during wakefulness and sleep.

Insomnia disorder is the most common sleep disorder and has drawn increasing attention. Many studies have shown that hyperarousal plays a key role in the pathophysiology of insomnia disorder. However, the specific brain mechanisms underlying insomnia disorder remain unclear. To elucidate the neuropathophysiology of insomnia disorder, we investigated the brain functional networks of patients with insomnia disorder and healthy controls across the sleep-wake cycle. EEG-fMRI data from 33 patients with insomnia disorder and 31 well-matched healthy controls during wakefulness and nonrapid eye movement sleep, including N1, N2 and N3 stages, were analyzed. A medial and anterior thalamic region was selected as the seed considering its role in sleep-wake regulation. The functional connectivity between the thalamic seed and voxels across the brain was calculated. ANOVA with factors "group" and "stage" was performed on thalamus-based functional connectivity. Correlations between the misperception index and altered functional connectivity were explored. A group-by-stage interaction was observed at widespread cortical regions. Regarding the main effect of group, patients with insomnia disorder demonstrated decreased thalamic connectivity with the left amygdala, parahippocampal gyrus, putamen, pallidum and hippocampus across wakefulness and all three nonrapid eye movement sleep stages. The thalamic connectivity in the subcortical cluster and the right temporal cluster in N1 was significantly correlated with the misperception index. This study demonstrated the brain functional basis in insomnia disorder and illustrated its relationship with sleep misperception, shedding new light on the brain mechanisms of insomnia disorder and indicating potential therapeutic targets for its treatment.

Gender-related difference in altered fractional amplitude of low-frequency fluctuations after electroacupuncture on primary insomnia patients: A resting-state fMRI study.

BACKGROUND: Primary insomnia (PI) is defined as a sleep disorder with no definite cause or inducement. Electroacupuncture, a treatment of inserting needles into specific points on the body surface and applying electrical stimulation, has been proved effective in treating PI with minimal adverse effects. However, the influence of gender difference on the clinical treatment efficacy of electroacupuncture for PI patients remains unclear. Therefore, we designed a clinical trial to compare the clinical treatment efficacy of electroacupuncture for PI patients with different genders. The research on the mechanism of electroacupuncture suggested it could modulate the sleep and wakefulness by activating or deactivating brain regions via a needling/tactile somatosensory specific stimulus. Therefore, we also designed a resting-state functional magnetic resonance imaging (rs-fMRI) study to detect the spontaneous brain activity of PI patients before and after the electroacupuncture treatment. METHOD: Thirty PI patients were recruited to accept 5-week electroacupuncture treatment on HT-7. Athens Insomnia Scale (AIS) and Pittsburgh sleep quality index (PSQI) questionnaires were used to evaluate the clinical treatment efficacy. Rs-fMRI was employed to observe the spontaneous brain activity in the resting state at the baseline and after 5 weeks of electroacupuncture treatment, which was measured by the fractional amplitude of low-frequency fluctuations (fALFF). RESULT: The AIS and PSQI scores were significantly decreased both in the female PI group and the male PI group after treatment. The decreased PSQI of female patients was significantly more than that of male patients (p < .05). The gender-related difference in the cerebral response to electroacupuncture was mainly in posterior cingulate and supramarginal gyrus. CONCLUSION: There is a gender-related difference in the clinical treatment efficacy of electroacupuncture for PI patients, and female patients may benefit more from electroacupuncture. Gender-related differences in the cerebral response to electroacupuncture may be one of the factors affecting clinical treatment efficacy.

Effectiveness and cerebral responses of multi-points acupuncture for primary insomnia: a preliminary randomized clinical trial and fMRI study.

BACKGROUND: Primary insomnia (PI) is characterized by difficulties in initiating sleep or maintaining sleep, which lead to many serious diseases. Acupuncture for PI has drawn attention with its effectiveness and safety. However, the operation of choosing acupoints lacks scientific suggestion. Our trial aims to provide reference and scientific basis for the selection of acupoints and to explore its possible mechanism. METHODS: A patient-assessor-blinded, randomized and sham controlled trial was designed to compare the efficacy of 5-weeks acupuncture at a single acupoint, the combination of multi-acupoints, and a sham point. The Pittsburgh sleep quality index and Athens Insomnia Scale questionnaire were used for the primary clinical outcomes, while polysomnography was performed for the secondary clinical outcomes. The resting state functional MRI was employed to detect the cerebral responses to acupuncture. The brain activity in resting state was measured by calculating the fractional amplitude of low-frequency fluctuations (fALFF), which reflected the idiopathic activity level of neurons in the resting state. These results were analyzed by two factorial ANOVA test and post-hoc t-tests. RESULTS: The clinical outcomes suggest that acupuncture could improve clinical symptoms, and the combination of multi-acupoints might lead to a better clinical efficacy. The rs-fMRI results suggested that the brain activity of certain regions was related to the sleep experience, and acupuncture could regulate the activity of these regions. Furthermore, the combination of multi-acupoints could impact more regions which were influenced by the sleep experience. CONCLUSIONS: Acupuncture has been proven to be beneficial for PI patients, and the combination of multi-acupoints might improve its efficacy. TRIAL REGISTRATION: This trial has been registered on the U.S. National Library of Medicine (https://clinicaltrials.gov) ClinicalTrials.gov Identifier: NCT02448602 . Registered date: 14/04/2015.

Sleep Onset Problems and Subcortical Development in Infants Later Diagnosed With Autism Spectrum Disorder.

OBJECTIVE: Sleep patterns in children with autism spectrum disorder (ASD) appear to diverge from typical development in the second or third year of life. Little is known, however, about the occurrence of sleep problems in infants who later develop ASD and possible effects on early brain development. In a longitudinal neuroimaging study of infants at familial high or low risk for ASD, parent-reported sleep onset problems were examined in relation to subcortical brain volumes in the first 2 years of life. METHODS: A total of 432 infants were included across three study groups: infants at high risk who developed ASD (N=71), infants at high risk who did not develop ASD (N=234), and infants at low risk (N=127). Sleep onset problem scores (derived from an infant temperament measure) were evaluated in relation to longitudinal high-resolution T1 and T2 structural imaging data acquired at 6, 12, and 24 months of age. RESULTS: Sleep onset problems were more common at 6-12 months among infants who later developed ASD. Infant sleep onset problems were related to hippocampal volume trajectories from 6 to 24 months only for infants at high risk who developed ASD. Brain-sleep relationships were specific to the hippocampus; no significant relationships were found with volume trajectories of other subcortical structures examined (the amygdala, caudate, globus pallidus, putamen, and thalamus). CONCLUSIONS: These findings provide initial evidence that sleep onset problems in the first year of life precede ASD diagnosis and are associated with altered neurodevelopmental trajectories in infants at high familial risk who go on to develop ASD. If replicated, these findings could provide new insights into a potential role of sleep difficulties in the development of ASD.

Acupuncture for patients with insomnia disorder using resting-state functional magnetic resonance imaging: a protocol for a randomized controlled trial.

BACKGROUND: Insomnia is among the most prevalent of the sleep-related disorders. Insomnia disorder is associated with a brain hyperarousal state manifested by abnormal regional brain activity and resting state functional connectivity. Acupuncture improves sleep quality and modulates the hyperarousal state; however, the underlying neurobiological basis for improved sleep quality is poorly understood. The purpose of this clinical trial is to study the efficacy of acupuncture in the treatment of insomnia disorder. In addition, the neural mechanism by which acupuncture affects insomnia disorder will be explored using resting-state functional magnetic resonance imaging (rs-fMRI) and neuropsychological parameters. METHODS AND DESIGN: A randomized, patient- and assessor-blinded trial will be conducted. We will randomize (in a 1:1 ratio) 60 eligible patients with insomnia disorder into a real acupuncture group or a sham acupuncture group. Interventions will be administered three times per week over a 4-week period, with an 8-week follow-up period. The healthy control group will consist of 30 age- and sex-matched healthy individuals who sleep well without any treatment intervention. All participants will undergo neuropsychological and rs-fMRI evaluations. The change in Pittsburgh Sleep Quality Index (PSQI) scores is the primary outcome parameter. The secondary outcome parameters include the Hyperarousal scale (HAS), rs-fMRI measurements, the Fatigue scale-14 (FS-14), the Hamilton depression scale (HAMD), the Hamilton anxiety scale (HAMA), a sleep diary, and an actigraph. Assessment of all parameters will be performed at baseline, post-treatment, and during follow-up. Analyses will be implemented based on intention-to-treat. DISCUSSION: The study results will be used to clarify the effectiveness and elucidate the mechanism by which acupuncture improves sleep quality in patients with insomnia disorder. TRIAL REGISTRATION: Chinese Clinical Trials Register, ChiCTR1800015282. Registered on 20 March 2018.

Non-pharmacological and pharmacological interventions relieve insomnia symptoms by modulating a shared network: A controlled longitudinal study.

BACKGROUND: Primary insomnia (PI) is one of the most common complaints among the general population. Both non-pharmacological and pharmacological therapies have proven effective in treating primary insomnia. However, the underlying mechanism of treatment remains unclear, and no studies have compared the underlying mechanisms of different treatments. METHODS: In this study, we investigated gray matter volume (GMV) and resting-state functional connectivity (rsFC) changes following both pharmacological and non-pharmacological treatments in patients with PI. A total of 67 PI patients were randomized into benzodiazepine treatment, cupping treatment, or a wait-list control group for 4 weeks. The Pittsburgh Sleep Quality Index (PSQI), gray matter volume (GMV), and resting-state functional connectivity (rsFC) of the hippocampus were measured at the beginning and end of the experiment. RESULTS: We found 1) significantly decreased PSQI scores in the cupping and benzodiazepine treatment groups compared to the control group with no significant differences between the two treatment groups; 2) significant GMV increases in the cupping group compared to the control group at the right hippocampus after 4 weeks of treatment; 3) significantly increased rsFC between the right hippocampus and left rostral anterior cingulate cortex/medial prefrontal cortex (rACC/mPFC) in the two treatment groups, which was significantly associated with PSQI score decreases. DISCUSSION: Our findings suggest that benzodiazepine and cupping may share a common mechanism to relieve the symptoms of patients with PI.

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.

Abnormalities of thalamus volume and resting state functional connectivity in primary insomnia patients.

Primary insomnia (PI) is associated with deteriorating attention, memory, physical and mood complaints. Based on the extensive literature demonstrating the critical roles of the thalamus in sleep regulation, we hypothesized that insomnia would be associated with functional and structural changes of the thalamus. This information is needed to better understand the neural mechanisms of insomnia, and would be useful for informing future attempts to alleviate or treat insomnia symptoms. Twenty-seven PI patients and 39 matched healthy controls were included in the present study. Subcortical volume and resting state functional connectivity (RSFC) of thalamus were compared between groups, and the relationships between neuroimaging differences and clinical features, including the Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index Scale (ISI), the Self-Rating Anxiety Scale (SAS) and the Self-Rating Depression Scale (SDS), also be explored. Compared with the control group, the PI group showed significantly reduced volume of thalamus. In addition, several brain regions showed reduced RSFC with thalamus in PI patients, such as anterior cingulate cortex (ACC), orbitofrontal cortex, hippocampus, caudate and putamen. Correlation analyses revealed that, several of these RSFC patterns were negatively correlated with PSQI score among PI patients, including thalamic connections with the putamen, caudate, hippocampus. Negative correlation was also observed between the RSFC strength of right thalamus-right ACC and SDS score in PI patients. This work demonstrates the structural and functional abnormalities of the thalamus in PI patients that were associated with key clinical features of insomnia. These data further highlight the important role of the thalamus in sleep and PI.

Low white-matter integrity between the left thalamus and inferior frontal gyrus in patients with insomnia disorder

Background: Previous studies have reported functional and structural abnormalities in the thalamus and the pars triangularis of the inferior frontal gyrus in patients with insomnia disorder. However, no studies have been conducted on the white-matter tracts between these 2 brain regions. We aimed to compare the white-matter integrity and structure of the left thalamus­pars triangularis tracts between patients with insomnia and controls, and to characterize the relationship between white-matter integrity and clinical features in patients with insomnia. Methods: In total, 22 participants with insomnia disorder and 27 controls underwent overnight polysomnography and brain magnetic resonance imaging, and then completed self-report clinical questionnaires and neurocognitive tests for spatial planning. Structural and diffusion measures such as fractional anisotropy, axial diffusivity, radial diffusivity and trace were analyzed in group comparison and correlation analyses. Results: The insomnia group showed significantly lower fractional anisotropy (F = 8.647, p = 0.02) and axial diffusivity (F = 5.895, p = 0.038) in the left thalamus­pars triangularis tracts than controls. In patients with insomnia, fractional anisotropy in the tracts was correlated with the results of the Stockings of Cambridge test (r = 0.451, p = 0.034), and radial diffusivity was correlated with Epworth Sleepiness Scale score (r = 0.437, p = 0.042). Limitations: Limitations included analyses of limited brain regions and the cross-sectional design. Conclusion: The insomnia group showed decreased integrity in the left thalamus­pars triangularis tracts, and integrity was correlated with cognition and daytime sleepiness. These results may imply that insomnia is characterized by disintegration of the white-matter tract between the left thalamus and inferior frontal gyrus.

[18F]FDG PET in fatal familial insomnia: the functional effects of thalamic lesions.

We used [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) and positron emission tomography (PET) to study regional cerebral glucose utilization (rCMRglc) in four patients with fatal familial insomnia (FFI), a prion disease with a mutation at codon 178 of the prion protein gene. Two patients, presenting only with insomnia and dysautonomia, had a prominent and, in one case, selective thalamic hypometabolism. The remaining two cases presented a more complex clinical picture with multiple neurologic deficits, with both thalamic and widespread brain hypometabolism involving the majority of cortical structures, basal ganglia, and the cerebellum. This widespread pattern was present in the early stage of the disease and showed significant worsening as the disease progressed in one patient examined twice. The thalamic hypometabolism, consistently found with PET in FFI patients, is in agreement with the neuropathologic findings and is a hallmark of the disease.