Older adults exercising ON TIME: protocol for a randomized controlled cross-over study to assess the effect of physical activity timing on insomnia severity.

BACKGROUND: There are increased indications that physical activity timing, irrespective of intensity, impacts insomnia and circadian clock function. Here, we describe the rationale and design of a randomized cross-over study, called ON TIME, to examine the effects of (changing) physical activity timing on insomnia severity and on multiple exploratory outcomes that are linked to circadian clock function. METHODS: We will conduct a randomized cross-over trial in 40 healthy older adults (aged 65 to 75 years) with subclinical or clinical insomnia (Insomnia Severity Index (ISI) scores of ≥ 10) from the Dutch municipality of Leiden and surroundings. Participants will undergo 3 intervention periods (14 days each) consecutively: one sedentary period and two periods of increased physical activity (one period with morning activity and one period with evening activity). The intervention periods are separated by a wash-out period of 1 week. In both active intervention arms, participants will follow coached or uncoached outdoor physical exercise sessions comprising endurance, strength, and flexibility exercises for 14 days. The primary outcome is change in insomnia severity as measured by the ISI. Additional exploratory outcomes include multiple components of objective sleep quality measured with tri-axial accelerometry and subjective sleep quality assessed by questionnaires as well as dim light melatonin onset and 24-h rhythms in heart rate, heart rate variability, breathing rate, oxygen saturation, mood, and objective emotional arousal and stress. Additionally, we will collect diary data on eating patterns (timing and composition). Finally, fasting blood samples will be collected at baseline and after each intervention period for measurements of biomarkers of metabolic and physiological functioning and expression of genes involved in regulation of the biological clock. DISCUSSION: We anticipate that this study will make a significant contribution to the limited knowledge on the effect of physical activity timing. Optimizing physical activity timing has the potential to augment the health benefits of increased physical exercise in the aging population. TRIAL REGISTRATION: Trial was approved by the Medical Ethics Committee Leiden, The Hague, Delft, The Netherlands (June, 2023). The trial was registered in the CCMO-register https://www.toetsingonline.nl/to/ccmo_search.nsf/Searchform?OpenForm under study ID NL82335.058.22 and named ("Ouderen op tijd in beweging" or in English "Older adults exercising on time"). At time of manuscript submission, the trial was additionally registered at ClinicalTrials.gov under study ID: NL82335.058.22 and is awaiting approval.

Enhanced cerebral blood flow similarity of the somatomotor network in chronic insomnia: Transcriptomic decoding, gut microbial signatures and phenotypic roles.

Chronic insomnia (CI) is a complex disease involving multiple factors including genetics, gut microbiota, and brain structure and function. However, there lacks a unified framework to elucidate how these factors interact in CI. By combining data of clinical assessment, sleep behavior recording, cognitive test, multimodal MRI (structural, functional, and perfusion), gene, and gut microbiota, this study demonstrated that enhanced cerebral blood flow (CBF) similarities of the somatomotor network (SMN) acted as a key mediator to link multiple factors in CI. Specifically, we first demonstrated that only CBF but not morphological or functional networks exhibited alterations in patients with CI, characterized by increases within the SMN and between the SMN and higher-order associative networks. Moreover, these findings were highly reproducible and the CBF similarity method was test-retest reliable. Further, we showed that transcriptional profiles explained 60.4 % variance of the pattern of the increased CBF similarities with the most correlated genes enriched in regulation of cellular and protein localization and material transport, and gut microbiota explained 69.7 % inter-individual variance in the increased CBF similarities with the most contributions from Negativicutes and Lactobacillales. Finally, we found that the increased CBF similarities were correlated with clinical variables, accounted for sleep behaviors and cognitive deficits, and contributed the most to the patient-control classification (accuracy = 84.4 %). Altogether, our findings have important implications for understanding the neuropathology of CI and may inform ways of developing new therapeutic strategies for the disease.

The Complex Relationship between Neuromodulators, Circadian Rhythms, and Insomnia in Patients with Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) has been linked to disruptions in circadian rhythm and neurotrophin (NFT) signaling. This study explored the link between neuromodulators, chronotype, and insomnia in OSA. The participants (n = 166) underwent polysomnography (PSG) before being categorized into either the control or the OSA group. The following questionnaires were completed: Insomnia Severity Index (ISI), Epworth Sleepiness Scale, Chronotype Questionnaire (morningness-eveningness (ME), and subjective amplitude (AM). Blood samples were collected post-PSG for protein level assessment using ELISA kits for brain-derived neurotrophic factor (BDNF), proBDNF, glial-cell-line-derived neurotrophic factor, NFT3, and NFT4. Gene expression was analyzed utilizing qRT-PCR. No significant differences were found in neuromodulator levels between OSA patients and controls. The controls with insomnia exhibited elevated neuromodulator gene expression (p < 0.05). In the non-insomnia individuals, BDNF and NTF3 expression was increased in the OSA group compared to controls (p = 0.007 for both); there were no significant differences between the insomnia groups. The ISI scores positively correlated with all gene expressions in both groups, except for NTF4 in OSA (R = 0.127, p = 0.172). AM and ME were predicting factors for the ISI score and clinically significant insomnia (p < 0.05 for both groups). Compromised compensatory mechanisms in OSA may exacerbate insomnia. The correlation between chronotype and NFT expression highlights the role of circadian misalignments in sleep disruptions.

Exploration of effects of galvanic vestibular stimulation on circadian rhythms and its associations with sleep and spatial memory in patients with breast cancer: The ICANSLEEP-2 protocol.

BACKGROUND: Patients with breast cancer (BC) exhibit circadian rhythm disruptions, mainly of rest-activity rhythm (RAR), of which sleep is an essential component, and cortisol rhythm. Sleep complaints such as insomnia and cognitive impairments are prevalent in BC. In general population, sleep is known to contribute greatly to cognition. Thus, improving RAR (and particularly sleep) could help limiting cognitive impairments in BC patients. It has recently been suggested that, in addition to its essential role in spatial memory, the vestibular system contributes to RAR synchronization. Its stimulation could therefore limit both sleep disturbances and spatial memory deficits in BC. OBJECTIVES: The main aim of the ICANSLEEP-2 study is to assess the effects of galvanic vestibular stimulation (GVS) on circadian rhythms. The secondary aim is to assess whether GVS improves sleep and spatial memory in BC patients. METHODS: Two groups with insomnia complaints (Insomnia Severity Index > 7) will be included: a patients' group with BC (n = 50) and a healthy control group without history of cancer (n = 25). There will be two assessment sessions, before and after 2 weeks of GVS. Patients will be randomly assigned to either a GVS group or a sham group (noneffective stimulation). Controls will receive GVS. GVS effects will be quantified and compared between groups. Assessments will include actigraphy, salivary cortisol, polysomnography, a cognitive test battery (including a computer-based task for spatial memory) and validated questionnaires (for psychological functioning and sleep complaints). DISCUSSION: Current methods for improving sleep in BC have had controversial outcomes regarding sleep structure. We expect GVS to offer a new mean of directly targeting RAR disruptions in BC patients, with beneficial effects on sleep structure. Given the crucial impact of sleep on cognitive functioning, notably spatial memory, improving sleep of BC patients should enhance their cognitive functioning. ETHICS AND DISSEMINATION: This study received ethical approval from the Ile de France IV institutional review board on 19 April 2022 (no. ID-RCB: 2022-A00437-36). The findings yielded by this protocol will be presented at various conferences and in peer-reviewed journals. CLINICALTRIALS.GOV REGISTRATION NUMBER: NCT05414357.

[Clinical effect of acupuncture based on the specific response of jing-well point for intractable insomnia: a randomized controlled trial].

OBJECTIVE: To evaluate clinical effect and safety on the basis of detecting the specific response of jing-well point in treatment of intractable insomnia with acupuncture by meridian differentiation. METHODS: Sixty-four patients with intractable insomnia were randomized into an observation group (32 cases, 1 case dropped out and 1 case was eliminated) and a control group (32 cases, 1 case was eliminated). In the observation group, the meridian imbalance value detected at the jing-well point was taken as the evidence so that the corresponding yuan-source and back-shu points were stimulated with acupuncture. In the control group, the routine acupuncture was operated at Baihui (GV 20), Sishencong (EX-HN 1), and bilateral Shenmen (HT 7), Sanyinjiao (SP 6), Shenmai (BL 62) and Zhaohai (KI 6). Besides, the detection at jing-well point was performed for blindness in the control group. In the two groups, the interventions were delivered once daily, 5 times a weeks and for consecutive 4 weeks. In the two groups, the scores of Pittsburgh sleep quality index (PSQI), insomnia severity index (ISI) and the TCM symptom scale were observed before treatment and after 2 and 4 weeks of treatment; the clinical effect and safety were evaluated after treatment; the changes of meridian imbalance value were observed before and after treatment and the correlation analysis with the total score of PSQI was conducted. RESULTS: After 2 and 4 weeks of treatment, except the scores for hypnotic drug in the two groups and sleep disorder after 2 weeks of treatment in the control group, the scores of the other factors and the total scores of PSQI were all reduced when compared with those before treatment in the two groups (P<0.05). After 4 weeks of treatment, except the scores for hypnotic drug in the two groups and sleep disorder in the control group, the scores of the other factors and the total scores of PSQI were lower than those after 2 weeks of treatment in the two groups (P<0.05). After 2 weeks of treatment, the scores for time to fall asleep, sleep efficiency and daytime dysfunction in the observation group were lower than those of the control group (P<0.05); and after 4 weeks of treatment, except the scores for sleep disorder and hypnotic drug, the scores of the other factors and the total score of PSQI in the observation group were all lower than those of the control group (P<0.05). After 2 and 4 weeks of treatment, ISI scores and the scores of TCM symptom scale decreased when compared with those before treatment (P<0.05), and the scores of these two scales after 4 weeks of treatment were lower than those after 2 weeks of treatment (P<0.05) in the two groups; and the scores in the observation group were lower than thoese in the control group (P<0.05). The total effective rate was 93.3% (28/30) in the observation group, higher than that (90.3% [28/31]) in the control group (P<0.05). Of 64 cases, there was only 1 case of mild hematoma in the control group; and no any other adverse events occurred. Among 64 cases, the meridians, with the imbalance frequency ≥30 times, included the pericardium meridian of hand-jueyin and the heart meridian of hand-shaoyin; those with the imbalance frequency ≥20 times, were the kidney meridian of foot-shaoyin, the triple energizers meridian of hand-shaoyang, the gallbladder meridian of foot-shaoyang, the spleen meridian of foot-taiyin and the stomach meridian of foot-yangming. Except the lung meridian of hand-taiyin in the control group, the imbalance value of each meridian was reduced after treatment (P<0.05, P<0.001, P<0.01), and the meridian imbalance value presented a linear positive correlation with the total score of PSQI in the two groups . CONCLUSION: Meridian differentiation acupuncture based on detecting the specific response of jing-well point can significantly improve the sleep quality and reduce the related symptoms in the patients with intractable insomnia. This therapy promotes the conversion of the meridians from the imbalance to the balance and is satisfactory in its safe operation.

[Clinical effect of the warm acupuncture of Mongolian medicine on insomnia in the elderly and its brain-gut peptide mechanism: a randomized controlled trial].

OBJECTIVE: To observe the clinical effect and safety of the warm acupuncture of Mongolian medicine in treatment of insomnia in the elderly, and to explore its underlying brain-gut peptide mechanism. METHODS: Sixty elderly patients with insomnia were randomly divided into a warm acupuncture group and a western medication group, 30 cases in each group. In the warm acupuncture group, the warm acupuncture of Mongolian medicine was operated at Dinghuixue (at the center of the vertex, the crossing site of the anterior midline and the line connected the upper edges of two ear apexes), Heyixue (at the depression of the spinous process of the 7th cervical vertebra) or Xinxue (at the depression of the spinous process of the 6th thoracic vertebra) in each treatment. Only one of the above points was selected and stimulated for 20 min one treatment and the three points were used alternatively. The treatment was given once every day or every other day, 3 times a week, and for a total of 3 weeks. In the western medication group, estazolam tablets were administered orally, once a day, 1 mg before bedtime, consecutively for 3 weeks. Before and after treatment, as well as in 1-month follow-up visit after the treatment completion, the scores of the Pittsburgh sleep quality index (PSQI) and the insomnia severity index (ISI) were observed in the two groups. The serum brain-related peptide markers (substance P [SP], neuropeptide Y [NPY], 5-hydroxytryptamine 1A [5-HT1A] and 5-hydroxytryptamine 2A [5-HT2A]) were measured before and after treatment, and the clinical efficacy and safety was evaluated in the two groups. RESULTS: After treatment and in follow-up, the scores of sleep quality, sleep latency, sleep duration, sleep efficiency, sleep disturbance and daytime dysfunction, as well as the total scores of PSQI, and ISI scores were all reduced in the two groups (P<0.05, P<0.01); and the scores in the warm acupuncture group were lower than those of the western medication group (P<0.05, P<0.01). After treatment, the levels of serum SP and 5-HT2A were decreased (P<0.01) and the levels of serum NPY and 5-HT1A were increased (P<0.01) when compared with those before treatment in the two groups. The levels of serum SP and 5-HT2A in the warm acupuncture group were lower than those of the western medication group (P<0.05), and the levels of serum NPY and 5-HT1A were higher than those of the western medication group (P<0.05). After treatment, the total effective rate was 93.3% (28/30) in the warm acupuncture group, which was higher than 83.3% (25/30) of the western medication group (P<0.05). No serious adverse reactions were found in the two groups. CONCLUSION: Warm acupuncture of Mongolian medicine can effectively improve the sleep quality of the elderly patients with insomnia, and its mechanism may be related to the regulation of the levels of serum SP, NPY, 5-HT1A and 5-HT2A.

The association between insomnia symptoms and cognitive flexibility among undergraduates: An event-related potential study.

OBJECTIVE: To explore the association between insomnia symptoms and cognitive flexibility among undergraduates, along with its potential neural mechanisms. METHOD: A total of 102 participants were divided into insomnia (n = 55) and control (n = 47) groups based on sleep status. Cognitive flexibility was assessed using the Cognitive Flexibility Inventory (CFI) and the Number-Letter Task (N-L task). EEG data were recorded during the N-L task. RESULTS: The insomnia group exhibited lower CFI scores and higher switch costs in reaction time and accuracy compared to the control group. ERP analysis showed differences in P2, N2, and P3 component amplitudes between the two groups, with reduced N2 amplitude in the insomnia group under repeat trials. Time-frequency analysis revealed larger theta band event related synchronization in the frontal region and smaller theta band ERS in the parietal region under switch trials in the control group; the alpha band event-related desynchronization in the parietal region under repeat trials was significantly smaller in the control group compared to switch trials. CONCLUSION: Compared to undergraduates with normal sleep, those with insomnia symptoms exhibited reduced cognitive flexibility, which may be associated with some alterations in brain electrophysiological activities.

Predicting response to stepped-care cognitive behavioral therapy for insomnia using pre-treatment heart rate variability in cancer patients.

OBJECTIVE: This study examined whether high frequency heart-rate variability (HF-HRV) and HF-HRV reactivity to worry moderate response to cognitive behavioural therapy for insomnia (CBT-I) within both a standard and stepped-care framework among cancer patients with comorbid insomnia. Biomarkers such as HF-HRV may predict response to CBT-I, a finding which could potentially inform patient allocation to different treatment intensities within a stepped-care framework. METHODS: 177 participants (86.3 % female; Mage = 55.3, SD = 10.4) were randomized to receive either stepped-care or standard CBT-I. 145 participants had their HRV assessed at pre-treatment during a rest and worry period. Insomnia symptoms were assessed using the Insomnia Severity Index (ISI) and daily sleep diary across five timepoints from pre-treatment to a 12-month post-treatment follow-up. RESULTS: Resting HF-HRV was significantly associated with pre-treatment sleep efficiency and sleep onset latency but not ISI score. However, resting HF-HRV did not predict overall changes in insomnia across treatment and follow-up. Similarly, resting HF-HRV did not differentially predict changes in sleep diary parameters across standard or stepped-care groups. HRV reactivity was not related to any of the assessed outcome measures in both cross-sectional and longitudinal analyses. CONCLUSION: Although resting HF-HRV was related to initial daily sleep parameters, HF-HRV measures did not significantly predict longitudinal responses to CBT-I. These findings suggest that HF-HRV does not predict treatment responsiveness to CBT-I interventions of different intensity in cancer patients.

Functional MRI-based biomarkers of insomnia with objective short sleep duration phenotype.

BACKGROUND: Insomnia disorder with objective short sleep duration (ISS) phenotype is a more serious biological subtype than insomnia with objective normal sleep duration (INS) phenotype, and the neuroimaging data is helpful to understand the pathophysiology of the ISS phenotype. This study was to compare the amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and functional connectivity (FC) between the ISS phenotype and the INS phenotype. METHODS: In this cross-sectional study, 55 patients with insomnia disorder were recruited, and 22 of them were defined as the ISS phenotype by the objective cardiopulmonary coupling (CPC) technique. The blood oxygen level-dependent (BOLD) sequences of all participants were obtained using the 3.0 T magnetic resonance imaging system. We analyzed and compared the ALFF, ReHo, and FC between the ISS phenotype and the INS phenotype. We also conducted Pearson's correlation analysis between significant neuroimaging biomarkers and the CPC parameters. RESULTS: The differences were not significant in ALFF (PFWE-corr＞0.05) or ReHo (PFWE-corr＞0.05) between the ISS phenotype and the INS phenotype. For the FC analysis, the ISS phenotype had a Hub-node of the left inferior occipital gyrus (IOG.L), with significantly decreased connections (p＜0.001) in the bilateral occipital, parietal, and temporal regions. The significant FCs were closely related to sleep parameters. CONCLUSION: The left inferior occipital gyrus (IOG.L), as a Hub-node with decreased functional connections, may be a potential fMRI-based biomarker of the ISS phenotype.

Effectiveness of repetitive transcranial magnetic stimulation for insomnia disorder on fear memory extinction: study protocol for a randomised controlled trial.

BACKGROUND: Fear memory extinction is closely related to insomnia. Repetitive transcranial magnetic stimulation (rTMS) is safe and effective for treating insomnia disorder (ID), and it has been shown to be an efficient method for modulating fear extinction. However, whether rTMS can improve fear extinction memory in ID patients remains to be studied. In this study, we specifically aim to (1) show that 1 Hz rTMS stimulation could improve fear extinction memory in ID patients and (2) examine whether changes in sleep mediate this impact. METHODS AND DESIGN: We propose a parallel group randomised controlled trial of 62 ID participants who meet the inclusion criteria. Participants will be assigned to a real rTMS group or a sham rTMS group. The allocation ratio will be 1:1, with 31 subjects in each group. Interventions will be administered five times per week over a 4-week period. The assessments will take place at baseline (week 0), post-intervention (week 4), and 8-week follow-up (week 8). The primary outcome measure of this study will be the mean change in the Pittsburgh Sleep Quality Index (PSQI) scores from baseline to post-intervention at week 4. The secondary outcome measures include the mean change in skin conductance response (SCR), fear expectation during fear extinction, Insomnia Severity Index (ISI), Zung Self-Rating Anxiety Scale (SAS), and the Zung Self-Rating Depression Scale (SDS). DISCUSSION: This study will be the first examination of the impact of rTMS on fear memory extinction in ID patients. TRIAL REGISTRATION: Chinese Clinical Trials Register ChiCTR2300076097. Registered on 25 September 2021.

A randomized controlled trial of alpha phase-locked auditory stimulation to treat symptoms of sleep onset insomnia.

Sleep onset insomnia is a pervasive problem that contributes significantly to the poor health outcomes associated with insufficient sleep. Auditory stimuli phase-locked to slow-wave sleep oscillations have been shown to augment deep sleep, but it is unknown whether a similar approach can be used to accelerate sleep onset. The present randomized controlled crossover trial enrolled adults with objectively verified sleep onset latencies (SOLs) greater than 30 min to test the effect of auditory stimuli delivered at specific phases of participants' alpha oscillations prior to sleep onset. During the intervention week, participants wore an electroencephalogram (EEG)-enabled headband that delivered acoustic pulses timed to arrive anti-phase with alpha for 30 min (Stimulation). During the Sham week, the headband silently recorded EEG. The primary outcome was SOL determined by blinded scoring of EEG records. For the 21 subjects included in the analyses, stimulation had a significant effect on SOL according to a linear mixed effects model (p = 0.0019), and weekly average SOL decreased by 10.5 ± 15.9 min (29.3 ± 44.4%). These data suggest that phase-locked acoustic stimulation can be a viable alternative to pharmaceuticals to accelerate sleep onset in individuals with prolonged sleep onset latencies. Trial Registration: This trial was first registered on clinicaltrials.gov on 24/02/2023 under the name Sounds Locked to ElectroEncephalogram Phase For the Acceleration of Sleep Onset Time (SLEEPFAST), and assigned registry number NCT05743114.

Waking qEEG in older adults with insomnia and its associations with sleep reactivity and dysfunctional beliefs about sleep.

Sleep quality often deteriorates with age, and insomnia among the elderly increases the risks of both physical and psychiatric disorders. To elucidate the mechanisms and identify useful diagnostic biomarkers for insomnia in the elderly, the current study investigated the associations of waking brain activity patterns with susceptibility to stress-induced insomnia (sleep reactivity) and dysfunctional beliefs about sleep, major factors precipitating and maintaining insomnia, respectively. Forty-five participants aged 60 years or older with insomnia completed self-reported measures assessing depression, anxiety, sleep quality, dysfunctional beliefs about sleep, and sleep reactivity. Participants were then examined by quantitative electroencephalography (qEEG) during wakefulness, and spectral analysis was conducted to examine associations of regional frequency band power with these insomnia-precipitating and -maintaining factors. Dysfunctional beliefs about sleep were significantly correlated with higher beta/high-beta frequency band powers, while sleep reactivity was correlated with higher theta and delta frequency band powers. These findings suggest that sleep reactivity of older adults is associated with widespread cortical deactivation leading to poor stress coping, while their dysfunctional beliefs about sleep are associated with hyperactivation which is related to cognitive processes. These associations suggest that cognitive inflexibility and maladaptive stress-coping contribute to insomnia among the elderly.

Association between sleep state misperception and bedtime behavior in patients with chronic insomnia.

Previous studies on sleep state misperception have objectively evaluated sleep status in special environments using polysomnography. There is a paucity of data from studies that evaluated habitual sleep status in home environments. The present study aimed to investigate sleep state misperception in the home environment of patients with chronic insomnia using a lumbar-worn actigraphy to identify sleep habits associated with sleep state misperception severity. Thirty-one patients and 42 healthy volunteers were included in the insomnia and non-insomnia group, respectively. Participants recorded subjective assessments in sleep diaries, objective assessments with an actigraphy worn for 14 days, and self-assessments using questionnaires. Both groups had similar objective sleep ratings; however, insomnia group had significantly worse subjective ratings (total sleep time, wake after sleep onset, and sleep onset latency). A significant correlation was found between subjective and objective total sleep time scores in non-insomnia group but not in insomnia group. Insomnia group had earlier bedtimes, significantly longer bedtimes, and impaired daytime functioning (Sheehan Disability Scale score); additionally, they underestimated their total sleep time, particularly with earlier bedtimes and longer laying durations. Monitoring the sleep status and habits of individuals in home environments could be instrumental in identifying key points for targeted interventions on sleep hygiene and cognitive behavioral therapy for insomnia.

Sleep health primary care clinical resource.

BACKGROUND: Obstructive sleep apnoea (OSA) and insomnia are the two most common sleep disorders and are frequent reasons for presentation in Australian general practice. OBJECTIVE: This article describes the development, content and suggested uses of the online sleep health primary care clinical resource, which provides general practitioners and other primary healthcare professionals with evidence-based information on the aetiology, assessment, management, referral and ongoing care for OSA and chronic insomnia. DISCUSSION: The Royal Australian College of General Practitioners-accepted clinical resource for the management of OSA and chronic insomnia in primary care was developed by the Australian National Centre for Sleep Health Services Research. The resource is designed to be used during consultations (eg following the steps in assessment and management and the use of online questionnaires for the assessment of OSA [Epworth Sleepiness Scale/OSA50/STOP-Bang] and insomnia [Sleep Condition Indicator/and Insomnia Severity Index]) and as an education/training tool (eg evidence on the role of continuous positive airway pressure/mandibular advancement splints for management of OSA and brief behavioural therapy for insomnia/cognitive behavioural therapy for insomnia for the management of insomnia).

Insomnia symptoms and neurofunctional correlates among adults receiving buprenorphine for opioid use disorder.

OBJECTIVES: Insomnia symptoms are negatively related to opioid use disorder (OUD) treatment outcomes, possibly reflecting the influence of sleep on neurofunctional domains implicated in addiction. Moreover, the intersection between OUD recovery and sleep represents an area well-suited for the development of novel, personalized treatment strategies. This study assessed the prevalence of clinically significant insomnia symptoms and characterized its neurofunctional correlates among a clinical sample of adults with OUD receiving buprenorphine. METHODS: Adults (N = 129) receiving buprenorphine for OUD from an outpatient clinic participated in a cross-sectional survey. Participants completed an abbreviated version of NIDA's Phenotyping Assessment Battery, which assessed 6 neurofunctional domains: sleep, negative emotionality, metacognition, interoception, cognition, and reward. Bivariate descriptive statistics compared those with evidence of clinically significant insomnia symptoms (Insomnia Severity Index [ISI] score of ≥11) to those with minimal evidence of clinically significant insomnia symptoms (ISI score of ≤10) across each of the neurofunctional domains. RESULTS: Roughly 60% of participants reported clinically significant insomnia symptoms (ISI score of ≥11). Experiencing clinically significant insomnia symptoms was associated with reporting greater levels of depression, anxiety, post-traumatic stress, stress intolerance, unhelpful metacognition, and interoceptive awareness (ps<0.05). Participants with evidence of clinically significant insomnia were more likely to report that poor sleep was interfering with their OUD treatment and that improved sleep would assist with their treatment (ps<0.05). CONCLUSIONS: Insomnia was prevalent among adults receiving buprenorphine for OUD. Insomnia was associated with neurofunctional performance, which may impact OUD treatment trajectories. Our findings indicate potential targets in the development of personalized treatment plans for patients with co-morbid insomnia and OUD. To inform the development of novel treatment strategies, more research is needed to understand the potential mechanistic links between sleep disturbances and substance use.

Activity-Based Prospective Memory in Insomniacs.

OBJECTIVE: To investigate the activity-based prospective memory performance in patients with insomnia, divided, on the basis of actigraphic evaluation, into sleep onset, maintenance, mixed and negative misperception insomnia. METHODS: A total of 153 patients with insomnia (I, 83 females, mean age + SD = 41.37 + 16.19 years) and 121 healthy controls (HC, 78 females, mean age + SD = 36.99 + 14.91 years) wore an actigraph for one week. Insomnia was classified into sleep onset insomnia (SOI), maintenance insomnia (MaI), mixed insomnia (MixI) and negative misperception insomnia (NMI). To study their activity-based prospective memory performance, all the participants were required to push the actigraph event marker button twice, at bedtime (task 1) and at get-up time (task 2). RESULTS: Only patients with maintenance and mixed insomnia had a significantly lower accuracy in the activity-based prospective memory task at get-up time compared with the healthy controls. CONCLUSION: The results show that maintenance and mixed insomnia involve an impaired activity-based prospective memory performance, while sleep onset and negative misperception insomnia do not seem to be affected. This pattern of results suggests that the fragmentation of sleep may play a role in activity-based prospective memory efficiency at wake-up in the morning.

Sleep Symptoms in Migraine.

PURPOSE OF REVIEW: To review replicated and highlight novel studies of sleep in children and adults with episodic and chronic migraine. RECENT FINDINGS: Attack-related sleep symptoms are most common in the prodrome and may represent early activation of the hypothalamus rather than migraine triggers. Interictally, patients with migraine report poor sleep quality and high rates of insomnia symptoms. Cognitive behavioral therapy for insomnia in adults and adolescents with chronic migraine and comorbid insomnia results in significant improvement on their headache burden. Thus far, objective studies report that migraine per se is a not associated with sleep apnea. At the present time, there is minimal evidence that migraine is under circadian influence. The current body of evidence suggests that the insomnia symptoms and poor sleep quality commonly reported by patients with migraine are not attack-related but occur interictally and are a marker of worsening disease. The development of clinical guidelines to approach sleep symptoms and expansion of CBT-I trials in those with episodic migraine would be clinically valuable.

Altered morphometric similarity networks in insomnia disorder.

Previous studies on structural covariance network (SCN) suggested that patients with insomnia disorder (ID) show abnormal structural connectivity, primarily affecting the somatomotor network (SMN) and default mode network (DMN). However, evaluating a single structural index in SCN can only reveal direct covariance relationship between two brain regions, failing to uncover synergistic changes in multiple structural features. To cover this research gap, the present study utilized novel morphometric similarity networks (MSN) to examine the morphometric similarity between cortical areas in terms of multiple sMRI parameters measured at each area. With seven T1-weighted imaging morphometric features from the Desikan-Killiany atlas, individual MSN was constructed for patients with ID (N = 87) and healthy control groups (HCs, N = 84). Two-sample t-test revealed differences in MSN between patients with ID and HCs. Correlation analyses examined associations between MSNs and sleep quality, insomnia symptom severity, and depressive symptoms severity in patients with ID. The right paracentral lobule (PCL) exhibited decreased morphometric similarity in patients with ID compared to HCs, mainly manifested by its de-differentiation (meaning loss of distinctiveness) with the SMN, DMN, and ventral attention network (VAN), as well as its decoupling with the visual network (VN). Greater PCL-based de-differentiation correlated with less severe insomnia and fewer depressive symptoms in the patients group. Additionally, patients with less depressive symptoms showed greater PCL de-differentiation from the SMN. As an important pilot step in revealing the underlying morphometric similarity alterations in insomnia disorder, the present study identified the right PCL as a hub region that is de-differentiated with other high-order networks. Our study also revealed that MSN has an important potential to capture clinical significance related to insomnia disorder.

Analysis of functional connectivity changes in attention networks and default mode networks in patients with depression and insomnia.

PURPOSE: Major Depressive Disorder (MDD) and Insomnia Disorder (ID) are prevalent psychiatric conditions often occurring concurrently, leading to substantial impairment in daily functioning. Understanding the neurobiological underpinnings of these disorders and their comorbidity is crucial for developing effective interventions. This study aims to analyze changes in functional connectivity within attention networks and default mode networks in patients with depression and insomnia. METHODS: The functional connectivity alterations in individuals with MDD, ID, comorbid MDD and insomnia (iMDD), and healthy controls (HC) were assessed from a cohort of 174 participants. They underwent rs-fMRI scans, demographic assessments, and scale evaluations for depression and sleep quality. Functional connectivity analysis was conducted using region-of-interest (ROI) and whole-brain methods. RESULTS: The MDD and iMDD groups exhibited higher Hamilton Depression Scale (HAMD) scores compared to HC and ID groups (P < 0.001). Both ID and MDD groups displayed enhanced connectivity between the left and right orbital frontal cortex compared to HC (P < 0.05), while the iMDD group showed reduced connectivity compared to HC and ID groups (P < 0.05). In the left insula, reduced connectivity with the right medial superior frontal gyrus was observed across patient groups compared to HC (P < 0.05), with the iMDD group showing increased connectivity compared to MDD (P < 0.05). Moreover, alterations in functional connectivity between the left thalamus and left temporal pole were found in iMDD compared to HC and MDD (P < 0.05). Correlation analyses revealed associations between abnormal connectivity and symptom severity in MDD and ID groups. CONCLUSIONS: Our findings demonstrate distinct patterns of altered functional connectivity in individuals with MDD, ID, and iMDD compared to healthy controls. These findings contribute to a better understanding of the pathophysiology of depression and insomnia, which could be used as a reference for the diagnosis and treatments of these patients.