Impact of Insomnia Treatment on Brain Responses During Resting-state and Cognitive Tasks

N/AActive Not RecruitingNCT04024787

Concordia University, Montreal120 enrolled

Overview

Individuals with chronic insomnia have persistent difficulty falling and staying asleep, as well as complaints of altered daytime functioning that may be associated with cognitive impairments. The neural processes underlying these daytime complaints may involve abnormal activation of brain regions and neural networks involved in working memory, memory encoding and emotions. The goal of this study is to assess whether a psychological treatment for insomnia will reverse these abnormalities in brain responses to cognitive tasks and at rest. A secondary objective of the study is to characterize impairments in attentional processing and assess if the impairments can be reversed by the psychological treatment. We hypothesized that the psychological treatment for insomnia will lead to a normalization of the brain responses to working memory, declarative memory encoding, insomnia-related stimuli, and the functional connectivity within the default-mode and limbic networks.

Study hypothesis Brain responses associated with working memory task and declarative memory encoding will be decreased in chronic insomnia compared to good sleepers and, among individuals with chronic insomnia, cognitive-behavioral therapy for insomnia will lead to larger recovery in these brain responses, compared to a 3-month wait period. Brain responses to emotional stimulation, especially to insomnia-related stimuli, will be increased in chronic insomnia compared to good sleepers, and, among individuals with chronic insomnia, cognitive-behavioral therapy for insomnia will lead to larger reduction in these brain responses, compared to a 3-month wait period. Connectivity in the default-mode and limbic networks during resting-state will be increased in chronic insomnia compared to good sleepers, and, among individuals with chronic insomnia, cognitive-behavioral therapy for insomnia will lead to larger reduction in this connectivity, compared to a 3-month wait period.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Interventions

Cognitive-Behavioural therapy for insomnia (CBT-I)BEHAVIORAL

Participants with chronic primary insomnia are randomized into 2 groups with a 1:1 allocation ratio, after the completion of the pre-treatment assessment. Post-treatment and post-waitlist assessment occur after the 3-month treatment or waiting period. One group will receive the intervention immediately after the pre-treatment assessment and the other group will receive the intervention after a waiting period of 3 months. The intervention consists of manualized cognitive-behavioural therapy for insomnia. This treatment includes psychoeducation about sleep and circadian rhythms, stimulus control, sleep restriction, relaxation, and cognitive therapy. The therapy is administered individually. Participants meet for 8 sessions of 50 minutes spread over 12 weeks.

Eligibility

Sex: ALLMin age: 25 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: 80 participants with chronic primary insomnia (40 per group) 40 good sleepers Exclusion Criteria: 1. Older than 65 y.o. or younger than 25 y.o. 2. Contraindication to the MRI scanning 3. Current neurological disorder 4. Past history of brain lesion 5. Major surgery (i.e., requiring general anesthesia) in the past 3 months 6. Untreated thyroid disorder 7. Chronic pain syndrome self-reported as interfering with sleep 8. Recent and severe infection in the past 3 months 9. Active cancer, or remitted cancer with cancer treatment within the last 2 years 10. Stroke 11. Myocardial infarct 12. Arterial bypass or angioplasty 13. Pacemaker 14. Heart failure causing limitation of ordinary physical activity 15. Renal insufficiency 16. Sleep apnea with an apnea-hypopnea index \> 5/h 17. Restless legs syndrome with symptoms 3 days or more per week 18. Periodic limb movements during sleep with index \> 15/h 19. REM-sleep behavior disorder 20. Narcolepsy and other central disorders of hypersomnolence 21. Sleepwalking more than once/month 22. Having worked on night shifts or rotating shifts for more than 2 weeks in the last 3 months or expecting to do so during the study period 23. Severe mental disorders: bipolar disorder (Type I), schizophrenia, anxiety disorders, major depressive disorder, current substance use disorder, current post-traumatic stress disorder 24. Current suicidality 25. Frequent alcohol consumption (\>10 glasses/week) or use of cannabis (more than once a week) or illicit drugs (more than once a month) 26. Smoking cigarettes more than 10 cigarettes/day 27. Pregnant or breastfeeding women 28. Current psychotherapy or past cognitive-behavioural therapy for insomnia 29. Current use of medication for depression or anxiety 30. Unable to stop hypnosedative medications for at least 2 weeks prior to the first assessment 31. For good sleepers: insomnia symptoms more than 3 times/ week.

Outcomes

Primary Outcomes

Functional magnetic resonance imaging (fMRI) to examine brain responses to working memory with increasing task difficulty

Functional magnetic resonance imaging (fMRI) will be used to look at changes in brain activations to working memory in individuals with chronic insomnia compared to good sleepers, as well as the modifications in these brain activations after cognitive-behavioral therapy for insomnia.

Time frame: 3 months

Functional magnetic resonance imaging (fMRI) to examine brain responses to declarative memory encoding

Functional magnetic resonance imaging (fMRI) will be used to look at changes in brain activations to declarative memory encoding in individuals with chronic insomnia compared to good sleepers, as well as the modifications in these brain activations after cognitive-behavioral therapy for insomnia.

Time frame: 3 months

Functional magnetic resonance imaging (fMRI) to examine brain responses to insomnia-related stimuli

Functional magnetic resonance imaging (fMRI) will be used to look at changes in brain activations to insomnia-related pictures in individuals with chronic insomnia compared to good sleepers, as well as the modifications in these brain activations after cognitive-behavioral therapy for insomnia.

Time frame: 3 months

Functional magnetic resonance imaging (fMRI) to examine functional connectivity within the default-mode and limbic networks at rest

Functional magnetic resonance imaging (fMRI) will be used to look at changes in resting state functional connectivity in individuals with chronic insomnia compared to good sleepers, as well as the modifications in this functional connectivity after cognitive-behavioral therapy for insomnia, with a focus on the default-mode and limbic networks.

Time frame: 3 months

Secondary Outcomes

Insomnia Severity Index (ISI)

Self-reported insomnia severity

Time frame: 3 months and 1 year

Pittsburgh Sleep Quality Index (PSQI)

Self-reported sleep quality

Time frame: 3 months and 1 year

Total sleep time

Self-reported total sleep time from 14-day sleep diary

Time frame: 3 months and 1 year

Total sleep time

Total sleep time from 14-day actigraphy

Time frame: 3 months

Sleep latency

Self-reported sleep latency from 14-day sleep diary

Time frame: 3 months and 1 year

Sleep latency

Sleep latency from 14-day actigraphy

Time frame: 3 months

Wake-after-sleep-onset (WASO)

Self-reported duration of wake-after-sleep-onset from 14-day sleep diary

Time frame: 3 months and 1 year

Wake-after-sleep-onset (WASO)

Duration of wake-after-sleep-onset from 14-day actigraphy

Time frame: 3 months

Sleep efficiency

Self-reported sleep efficiency from 14-day sleep diary

Time frame: 3 months and 1 year

Sleep efficiency

Sleep efficiency from 14-day actigraphy

Time frame: 3 months

Diagnosis of insomnia disorder

A trained interviewer evaluates the presence of an insomnia disorder using the SCID-V

Time frame: 3 months and 1 year

PSG total sleep time

Total sleep time from overnight polysomnography

Time frame: 3 months

PSG sleep latency

Sleep latency from overnight polysomnography

Time frame: 3 months

PSG wake-after-sleep-onset (WASO)

Duration of wake-after-sleep-onset from overnight polysomnography

Time frame: 3 months

PSG sleep efficiency

Sleep efficiency from overnight polysomnography

Time frame: 3 months

Sleep stage durations (N1, N2, N3, REM)

Durations of each sleep stage from overnight polysomnography

Time frame: 3 months

Arousal index

Number of EEG arousals per hour from overnight polysomnography

Time frame: 3 months

Spindle density

Number of sleep spindles per minute of stage N2-N3 sleep from overnight polysomnography

Time frame: 3 months

Dim light melatonin onset (DLMO)

Objective measure of central circadian timing (dim light melatonin onset; DLMO) will be obtained from hourly evening saliva samples

Time frame: 3 months

Cortisol

Cortisol will be assessed using salivary samples collected at bedtime, awakening and 45 minutes after awakening

Time frame: 3 months

Heart rate variability

Heart rate variability will be measured using the electrocardiogram leads during the overnight assessments

Time frame: 3 months

Blood pressure

Blood pressure is assessed using an oscillometer measurement of systolic and diastolic blood pressure in the morning following the overnight assessments

Time frame: 3 months

Circulating interleukin-6

Markers will be quantified using blood sample during the overnight assessments

Time frame: 3 months

Circulating tumor necrosis factor-alpha

Markers will be quantified using blood sample during the overnight assessments

Time frame: 3 months

Circulating C-reactive protein

Markers will be quantified using blood sample during the overnight assessments

Time frame: 3 months

Circulating neurotrophic factor BDNF

Markers will be quantified using blood sample during the overnight assessments

Time frame: 3 months

Beck Depression Inventory (BDI)

Time frame: 3 months and 1 year

State-Trait Inventory for Cognitive and Somatic Anxiety (STICSA)

Time frame: 3 months and 1 year

Sahlgrenska Academy Self-reported Cognitive Impairment Questionnaire (SASCI-Q, adapted version)

Questionnaire assessing self-reported (subjective) memory complaints. Total score ranges from 29 to 203 (higher score reflects more self-reported cognitive complaints).

Time frame: 3 months and 1 year

Work and Social Adjustment Scale (WSAS)

Self-reported measure assessing perceived functional impairment associated with insomnia. Total score ranges from 0 to 40 (lower score reflects less impairment).

Time frame: 3 months and 1 year

The Implicit Positive and Negative Affect Test (IPANAT)

Time frame: 3 months and 1 year

Beliefs and Attitudes about Sleep (DBAS)

Time frame: 3 months and 1 year

Daytime Insomnia Symptom Response Scale (DISRS)

Self-report measures assessing sleep-related rumination

Time frame: 3 months and 1 year

Attention

Attention will be assessed using computerized divided attention and multitasking tasks assessed in the evening and morning of the overnight assessments

Time frame: 3 months

Gray matter volume (GMV)

Brain morphometric measure from MRI

Time frame: 3 months

Cortical thickness

Brain morphometric measure from MRI

Time frame: 3 months

White matter integrity (fractional anisotropy, mean diffusivity)

Brain measure from MRI

Time frame: 3 months

GABA

GABA concentration from Magnetic Resonance Spectroscopy (in the anterior cingulate cortex)

Time frame: 3 months

Trier Inventory for Chronic Stress - short form

Time frame: 3 months and 1 year

Subjective happiness scale

Self-reported measure of global subjective happiness. Total score ranges from 4 to 28 (higher score reflects greater happiness).

Time frame: 3 months and 1 year

Temporal experience of pleasure scale (adapted version)

Self-reported measure of anticipatory and consummatory facets of pleasure. Total score ranges from 18 to 52 (higher score reflects greater pleasure).

Time frame: 3 months and 1 year

Fatigue symptom inventory

Time frame: 3 months and 1 year

Positive and Negative Affect Schedule

Time frame: 3 months and 1 year

Munich Chronotype Questionnaire (MCTQ)

Questionnaire on self-reported sleep habits, assessing individual chronotype (e.g., early type, normal type late type).

Time frame: 3 months and 1 year

Impact of Insomnia Treatment on Brain Responses During Resting-state and Cognitive Tasks

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes