Effects of insufficient sleep on sensorimotor processing in migraine: A randomised, blinded crossover study of event related beta oscillations.

BACKGROUND: Migraine has a largely unexplained connection with sleep and is possibly related to a dysfunction of thalamocortical systems and cortical inhibition. In this study we investigate the effect of insufficient sleep on cortical sensorimotor processing in migraine. METHODS: We recorded electroencephalography during a sensorimotor task from 46 interictal migraineurs and 28 controls after two nights of eight-hour habitual sleep and after two nights of four-hour restricted sleep. We compared changes in beta oscillations of the sensorimotor cortex after the two sleep conditions between migraineurs, controls and subgroups differentiating migraine subjects usually having attacks starting during sleep and not during sleep. We included preictal and postictal recordings in a secondary analysis of temporal changes in relation to attacks. RESULTS: Interictally, we discovered lower beta synchronisation after sleep restriction in sleep related migraine compared to non-sleep related migraine (p=0.006) and controls (p=0.01). No differences were seen between controls and the total migraine group in the interictal phase. After migraine attacks, we observed lower beta synchronisation (p<0.001) and higher beta desynchronisation (p=0.002) after sleep restriction closer to the end of the attack compared to later after the attack. CONCLUSION: The subgroup with sleep related migraine had lower sensorimotor beta synchronisation after sleep restriction, possibly related to dysfunctional GABAergic inhibitory systems. Sufficient sleep during or immediately after migraine attacks may be of importance for maintaining normal cortical excitability.

Insufficient sleep may alter cortical excitability near the migraine attack: A blinded TMS crossover study.

BACKGROUND: Migraine is a brain disorder with a multifaceted and unexplained association to sleep. Brain excitability likely changes periodically throughout the migraine cycle. In this study we examine the effect of insufficient sleep on neuronal excitability during the course of the migraine cycle. METHODS: We examined 54 migraine patients after two nights of eight-hour habitual sleep and two nights of four-hour restricted sleep in a randomised, blinded crossover study. We performed transcranial magnetic stimulation and measured cortical silent period, short- and long-interval intracortical inhibition, intracortical facilitation and short-latency afferent inhibition. We analysed how responses changed before and after attacks with linear mixed models. RESULTS: Short- interval intracortical inhibition was more reduced after sleep restriction compared to habitual sleep the shorter the time that had elapsed since the attack (p = 0.041), and specifically in the postictal phase (p = 0.013). Long-interval intracortical inhibition was more increased after sleep restriction with time closer before the attack (p = 0.006), and specifically in the preictal phase (p = 0.034). Short-latency afferent inhibition was more decreased after sleep restriction with time closer to the start of the attack (p = 0.026). CONCLUSION: Insufficient sleep in the period leading up to a migraine attack may cause dysfunction in cortical GABAergic inhibition. The results also suggest that migraine patients may have increased need for sufficient sleep during a migraine attack to maintain normal neurological function after the attack.

Retinal structure and visual pathway function at school age in children born extremely preterm: a population-based study.

BACKGROUND: Children born extremely preterm (gestational age < 28 weeks) show reduced visual function even without any cerebral or ophthalmological neonatal diagnosis. In this study, we aimed to assess the retinal structure with optical coherence tomography (OCT) and visual function with pattern-reversal visual evoked potentials (PR-VEPs) in a geographically defined population-based cohort of school-aged children born extremely preterm. Moreover, we aimed to explore the association between measures of retinal structure and visual pathway function in this cohort. METHODS: All children born extremely preterm from 2006-2011 (n = 65) in Central Norway were invited to participate. Thirty-six children (55%) with a median age of 13 years (range = 10-16) were examined with OCT, OCT-angiography (OCT-A), and PR-VEPs. The foveal avascular zone (FAZ) and circularity, central macular vascular density, and flow were measured on OCT-A images. Central retinal thickness, circumpapillary retinal nerve fibre layer (RNFL) and inner plexiform ganglion cell layer (IPGCL) thickness were measured on OCT images. The N70-P100 peak-to-peak amplitude and N70 and P100 latencies were assessed from PR-VEPs. RESULTS: Participants displayed abnormal retinal structure and P100 latencies (≥ 2 SD) compared to reference populations. Moreover, there was a negative correlation between P100 latency in large checks and RNFL (r = -.54, p = .003) and IPGCL (r = -.41, p = .003) thickness. The FAZ was smaller (p = .003), macular vascular density (p = .006) and flow were higher (p = .004), and RNFL (p = .006) and IPGCL (p = .014) were thinner in participants with ROP (n = 7). CONCLUSION: Children born extremely preterm without preterm brain injury sequelae have signs of persistent immaturity of retinal vasculature and neuroretinal layers. Thinner neuroretinal layers are associated with delayed P100 latency, prompting further exploration of the visual pathway development in preterms.

Pain thresholds and suprathreshold pain after sleep restriction in migraine - A blinded crossover study.

OBJECTIVE: There is an unexplained association between disturbed sleep and migraine. In this blinded crossover study, we investigate if experimental sleep restriction has a different effect on pain thresholds and suprathreshold pain in interictal migraineurs and controls. METHODS: Forearm heat pain thresholds and tolerance thresholds, and trapezius pressure pain thresholds and suprathreshold pain were measured in 39 interictal migraineurs and 31 healthy controls after two consecutive nights of partial sleep restriction and after habitual sleep. RESULTS: The effect of sleep restriction was not significantly different between interictal migraineurs and controls in the primary analyses. Pressure pain thresholds tended to be lower (i.e., increased pain sensitivity) after sleep restriction in interictal migraineurs compared to controls with a 48-hour preictal-interictal cut-off (p = 0.061). We found decreased pain thresholds after sleep restriction in two of seven migraine subgroup comparisons: heat pain thresholds decreased in migraineurs with lower pain intensity during attacks (p = 0.005) and pressure pain thresholds decreased in migraineurs with higher severity of photophobia during attacks (p = 0.031). Heat pain thresholds tended to decrease after sleep restriction in sleep-related migraine (p = 0.060). Sleep restriction did not affect suprathreshold pain measurements in either group. CONCLUSION: This study could not provide strong evidence for an increased effect of sleep restriction on pain sensitivity in migraineurs compared to healthy controls. There might be a slightly increased effect of sleep restriction in migraineurs, detectable using large samples or more pronounced in certain migraine subgroups.

Validation of questionnaires for restless legs syndrome in the general population: the Trøndelag Health Study (HUNT).

Questionnaires for restless legs syndrome have rarely been validated against face-to-face interviews in the general population. We aimed to validate the modified Norwegian, seven-item Cambridge-Hopkins restless legs syndrome questionnaire and a single diagnostic question for restless legs syndrome. We also aimed to stratify validity at 65 years of age. Among a random sample of 1,201 participants from the fourth wave of the Trøndelag Health Study, 232 (19%) agreed to participate, out of whom 221 had complete data for analyses. Participants completed the questionnaires for restless legs syndrome immediately before attending a face-to-face interview using the latest diagnostic criteria. We calculated sensitivity, specificity, and Cohen's kappa statistic (κ) of questionnaire- versus interview-based diagnoses. We found acceptable validity of the seven-item modified Cambridge-Hopkins diagnostic questionnaire for restless legs syndrome (κ = 0.37, 95% confidence interval [CI] 0.23-0.51) and good validity of the single diagnostic question (κ = 0.47, 95% CI 0.35-0.58). We also found good validity through the combination of modified Cambridge-Hopkins diagnostic questionnaire for restless legs syndrome items 2 and 5, while item 1 or 2 alone showed only acceptable validity. The single diagnostic question was significantly more valid among those aged <65 years (κ = 0.60 versus κ = 0.26). Both single- and two-item questionnaire-based diagnoses overestimated interview-based restless legs syndrome prevalence. The seven-item modified Cambridge-Hopkins diagnostic questionnaire for restless legs syndrome will be useful for epidemiological studies although low sensitivity may cause underestimation of true restless legs syndrome prevalence in the general population, especially among elderly. Brief questionnaire-based diagnoses of up to three items seem best utilised as an initial screen. Future studies should identify brief and even more valid questionnaire-based diagnoses for restless legs syndrome in order to estimate prevalence accurately in large epidemiological studies.

Validation of insomnia questionnaires in the general population: The Nord-Trøndelag Health Study (HUNT).

The primary aim was to validate questionnaire-based insomnia diagnoses from a modified Karolinska Sleep Questionnaire (KSQ) and the Insomnia Severity Index (ISI), by age category (< or >65 years), against a semi-structured face-to-face interview. Secondary aims were to split validity by diagnostic certainty of the interview and to compare prevalence estimates of questionnaire- and interview-based diagnoses. A total of 232 out of 1,200 invited (19.3%) from the fourth Nord-Trøndelag Health Study (HUNT4) completed questionnaires, including the KSQ and ISI, shortly before attending a face-to-face diagnostic interview for insomnia based on the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Both a tentative (DSM-5 criteria A-E) and a definite (criteria A-H) interview diagnosis was evaluated. Cohen's kappa statistic quantified questionnaire validity. In all, 33% (95% confidence interval 27-39%) of participants had definite insomnia: 40% of women and 21% of men. The ISI (cut-off 12) and several KSQ-based diagnoses showed very good validity (κ ≤0.74) against the tentative, versus good validity (κ ≤0.61) against the definite interview diagnosis. Short questionnaires, requiring a daytime symptom at least three times a week, may underestimate insomnia prevalence. Validity was consistently higher for persons aged below versus above 65 years (definite insomnia: κ ≤0.64 vs. κ ≤0.56). Our results have implications for epidemiological population-based studies utilising insomnia questionnaires.

Fluctuations of sensorimotor processing in migraine: a controlled longitudinal study of beta event related desynchronization.

BACKGROUND: The migraine brain seems to undergo cyclic fluctuations of sensory processing. For instance, during the preictal phase, migraineurs experience symptoms and signs of altered pain perception as well as other well-known premonitory CNS-symptoms. In the present study we measured EEG-activation to non-painful motor and sensorimotor tasks in the different phases of the migraine cycle by longitudinal measurements of beta event related desynchronization (beta-ERD). METHODS: We recorded electroencephalography (EEG) of 41 migraine patients and 31 healthy controls. Each subject underwent three EEG recordings on three different days with classification of each EEG recording according to the actual migraine phase. During each recording, subjects performed one motor and one sensorimotor task with the flexion-extension movement of the right wrist. RESULTS: Migraine patients had significantly increased beta-ERD and higher baseline beta power at the contralateral C3 electrode overlying the primary sensorimotor cortex in the preictal phase compared to the interictal phase. We found no significant differences in beta-ERD or baseline beta power between interictal migraineurs and controls. CONCLUSION: Increased preictal baseline beta activity may reflect a decrease in pre-activation in the sensorimotor cortex. Altered pre-activation may lead to changes in thresholds for inhibitory responses and increased beta-ERD response, possibly reflecting a generally increased preictal cortical responsivity in migraine. Cyclic fluctuations in the activity of second- and third-order afferent somatosensory neurons, and their associated cortical and/or thalamic interneurons, may accordingly also be a central part of the migraine pathophysiology.

Does pain sensitivity change by migraine phase? A blinded longitudinal study.

Objective Studies suggest that pain thresholds may be altered before and during migraine headaches, but it is still debated if a central or peripheral dysfunction is responsible for the onset of pain in migraine. The present blinded longitudinal study explores alterations in thermal pain thresholds and suprathreshold heat pain scores before, during, and after headache. Methods We measured pain thresholds to cold and heat, and pain scores to 30 seconds of suprathreshold heat four times in 49 migraineurs and once in 31 controls. Sessions in migraineurs were categorized by migraine diaries as interictal, preictal (≤one day before attack), ictal or postictal (≤one day after attack). Results Trigeminal cold pain thresholds were decreased ( p = 0.014) and pain scores increased ( p = 0.031) in the ictal compared to the interictal phase. Initial pain scores were decreased ( p < 0.029), and the temporal profile showed less adaptation ( p < 0.020) in the preictal compared to the interictal phase. Hand cold pain thresholds were decreased in interictal migraineurs compared to controls ( p < 0.019). Conclusion Preictal heat hypoalgesia and reduced adaptation was followed by ictal trigeminal cold suballodynia and heat hyperalgesia. Our results support that cyclic alterations of pain perception occur late in the prodromal phase before headache. Further longitudinal investigation of how pain physiology changes within the migraine cycle is important to gain a more complete understanding of the pathogenic mechanisms behind the migraine attack.

Habituation of laser-evoked potentials by migraine phase: a blinded longitudinal study.

BACKGROUND: Migraineurs seem to have cyclic variations in cortical excitability in several neurophysiological modalities. Laser-evoked potentials (LEP) are of particular interest in migraine because LEP specifically targets pain pathways, and studies have reported different LEP-changes both between and during headaches. Our primary aim was to explore potential cyclic variations in LEP amplitude and habituation in more detail with a blinded longitudinal study design. METHODS: We compared N1 and N2P2 amplitudes and habituation between two blocks of laser stimulations to the dorsal hand, obtained from 49 migraineurs with four sessions each. We used migraine diaries to categorize sessions as interictal (> one day from previous and to next attack), preictal (< one day before the attack), ictal or postictal (< one day after the attack). Also, we compared 29 interictal recordings from the first session to 30 controls. RESULTS: N1 and N2P2 amplitudes and habituation did not differ between preictal, interictal and postictal phase sessions, except for a post hoc contrast that showed deficient ictal habituation of N1. Habituation is present and similar in migraineurs in the interictal phase and controls. CONCLUSIONS: Hand-evoked LEP amplitudes and habituation were mainly invariable between migraine phases, but this matter needs further study. Because hand-evoked LEP-habituation was similar in migraineurs and controls, the present findings contradict several previous LEP studies. Pain-evoked cerebral responses are normal and show normal habituation in migraine.

Validation of Trøndelag Apnoea Score Proxy for Obstructive Sleep Apnoea in the General Population of Norway: The HUNT Study.

The aim was to validate a new seven-item "TASC" (Trøndelag Apnoea Score) proxy for obstructive sleep apnoea (OSA) against polysomnography in the general population. Objectives included validation against different polysomnographic criteria, stratification by age and gender, and estimation of OSA prevalence. From the fourth wave of the Trøndelag Health Study (HUNT4), 1,201 participants were randomly invited to a substudy focusing on sleep and headaches, of whom 232 accepted and 84 (64% women, mean age 55.0 years, and standard deviation 11.5 years) underwent polysomnography. The TASC proxy sums seven binary items for snoring, observed breathing pauses, restricted daytime activities, hypertension, body mass index (≥30 kg/m2), age (≥50 years), and gender (male). A single night of ambulatory (home) polysomnography was analysed using both the recommended and optional hypopnoea criteria of the American Academy of Sleep Medicine (AASM). We found 65% sensitivity and 87% specificity (Cohen's κ = 0.53, 95% confidence interval 0.34-0.72) for TASC ≥ 3 against AHI ≥ 15 (recommended AASM criteria). Validity was similar against AHI ≥ 30 but lower against AHI ≥ 5 and against the optional AASM criteria. Sensitivity and overall validity were higher among men and those above 50 years of age. The prevalence of an apnoea-hypopnoea index (AHI) of at least 5, 15, or 30 using the recommended (and optional) AASM criteria was 73% (46%), 37% (18%), or 15% (5%). A seven-item TASC proxy for OSA showed good validity and may be useful in screening and epidemiological settings. Sensitivity, specificity, and validity vary considerably by cut-off, by polysomnographic scoring criteria, and by gender and age strata.

Sleep restriction alters cortical inhibition in migraine: A transcranial magnetic stimulation study.

OBJECTIVE: Migraine is a primary headache disorder with a well-known association with insufficient sleep. However, both the underlying pathophysiology of the disease and the relationship with sleep is still unexplained. In this study, we apply transcranial magnetic stimulation to investigate possible mechanisms of insufficient sleep in migraine. METHODS: We used a randomised, blinded crossover design to examine 46 subjects with migraine during the interictal period and 29 healthy controls. Each subject underwent recordings of cortical silent period, short- and long-interval intracortical inhibition, intracortical facilitation and short-latency afferent inhibition after both two nights of habitual eight-hour sleep and two nights of restricted four-hour sleep. RESULTS: We found reduced cortical silent period duration after sleep restriction in interictal migraineurs compared to controls (p = 0.046). This effect was more pronounced for non-sleep related migraine (p = 0.002) and migraine with aura (p = 0.017). The sleep restriction effect was associated with ictal symptoms of hypersensitivity such as photophobia (p = 0.017) and overall silent period was associated with premonitory dopaminergic symptoms such as yawning (p = 0.034). CONCLUSIONS: Sleep restriction reduces GABAergic cortical inhibition during the interictal period in individuals with migraine. SIGNIFICANCE: Sleep related mechanisms appear to affect the pathophysiology of migraine and may differentiate between migraine subgroups.

The effect of sleep restriction on laser evoked potentials, thermal sensory and pain thresholds and suprathreshold pain in healthy subjects.

OBJECTIVE: Sleep restriction seems to change our experience of pain and reduce laser evoked potential (LEP) amplitudes. However, although LEP-habituation abnormalities have been described in painful conditions with comorbid sleep impairment, no study has previously measured the effect of sleep restriction on LEP-habituation, pain thresholds, and suprathreshold pain. METHOD: Sixteen males and seventeen females (aged 18-31years) were randomly assigned to either two nights of delayed bedtime and four hours sleep (partial sleep deprivation) or nine hours sleep. The study subjects slept at home, and the sleep was measured with actigraphy both nights and polysomnography the last night. LEP, thermal thresholds and suprathreshold pain ratings were obtained the day before and the day after intervention. The investigator was blinded. ANOVA was used to evaluate the interaction between sleep restriction and day for each pain-related variable. RESULTS: LEP-amplitude decreased after sleep restriction (interaction p=0.02) compared to subjects randomized to nine hours sleep. LEP-habituation was similar in both groups. Thenar cold pain threshold decreased after sleep restriction (interaction p=0.009). Supra-threshold heat pain rating increased temporarily 10s after stimulus onset after sleep restriction (interaction p=0.01), while it did not change after nine hours sleep. CONCLUSION: Sleep restriction reduced the CNS response to pain, while some of the subjective pain measures indicated hyperalgesia. SIGNIFICANCE: Since LEP-amplitude is known to reflect both CNS-pain-specific processing and cognitive attentive processing, our results suggest that hyperalgesia after sleep restriction might partly be caused by a reduction in cortical cognitive or perceptual mechanisms, rather than sensory amplification.