Danny Camfferman

Eczema and sleep and its relationship to daytime functioning in children

Chronic childhood eczema has significant morbidity characterised by physical discomfort, emotional distress, reduced child and family quality-of-life and, of particular note, disturbed sleep characterised by frequent and prolonged arousals. Sleep disturbance affects up to 60% of children with eczema, increasing to 83% during exacerbation. Even when in clinical remission, children with eczema demonstrate more sleep disturbance than healthy children. Notably, disturbed sleep in otherwise healthy children is associated with behavioural and neurocognitive deficits. Preliminary evidence suggests that disturbed sleep in children with eczema is also associated with behavioural deficits while the impact on neuropsychological functioning remains unexplored. In conclusion, a disease which affects up to 20% of children in some countries and may produce long-term behavioural and neurocognitive deficits merits further evaluation using standardised tests of sleep, behaviour and neurocognition.

Prader Willi Syndrome and excessive daytime sleepiness

Prader Willi Syndrome (PWS) is a rare genetic disorder characterized by a range of physical, psychological and physiological abnormalities. PWS patients may also demonstrate a range of abnormalities of sleep architecture and of breathing during sleep, and excessive daytime sleepiness (EDS). In the general population EDS is associated with Obstructive Sleep Apnea Syndrome (OSAS). In PWS, by contrast, OSAS is unlikely to fully explain EDS and other factors, including hypothalamic dysfunction are likely to contribute. The present review examines OSAS and hypothalamic dysfunction and other contributing factors to EDS in PWS.

Sleep and neurocognitive functioning in children with eczema

Sleep disruption in childhood is associated with clearly defined deficits in neurocognition and behaviour. Childhood eczema is also a potent cause of sleep disruption though it is unknown whether it too results in neurocognitive deficits. To test this hypothesis, neurocognitive (WISC-IV), parental-reported sleep quality (Sleep Disturbance Scale of Children (SDSC)) and overnight polysomnographic (PSG) data were collected in 21 children with eczema and 20 healthy controls (age range 6-16 years). Children with eczema had worse sleep quality on both PSG (notably increased nocturnal wakefulness, a higher number of stage shifts and a longer latency to REM onset) and parental report. In addition, they demonstrated significant neurocognitive deficits (especially verbal comprehension, perceptual reasoning and to a lesser extent working memory) with a composite Full Scale IQ 16 points lower than controls. Parental reported sleep problems but not PSG parameters were correlated with reduced neurocognitive performance. However, hierarchical regression analyses revealed that eczema status was predictive while sleep fragmentation (parental or PSG) was not predictive of neurocognitive performance. As this is the first study to systematically examine neurocognitive functioning in children with eczema and given the finding of significant deficits it merits replication especially given the prevalence of the condition. The unanswered question is whether these cognitive deficits normalise with effective eczema treatment and if this is mediated by improvements in sleep architecture.

Identifying adolescent sleep problems

Objectives To examine the efficacy of self-report and parental report of adolescent sleep problems and compare these findings to the incidence of adolescents who fulfill clinical criteria for a sleep problem. Sleep and daytime functioning factors that predict adolescents’ self-identification of a sleep problem will also be examined. Method 308 adolescents (aged 13–17 years) from eight socioeconomically diverse South Australian high schools participated in this study. Participants completed a survey battery during class time, followed by a 7-day Sleep Diary and the Flinders Fatigue Scale completed on the final day of the study. Parents completed a Sleep, Medical, Education and Family History Survey. Results The percentage of adolescents fulfilling one or more of the criteria for a sleep problem was inordinately high at 66%. Adolescent self-reporting a sleep problem was significantly lower than the adolescents who had one or more of the clinical criteria for a sleep problem (23.1% vs. 66.6%; χ2 = 17.46, p<.001). Parental report of their adolescent having a sleep problem was significantly lower than adolescent self-report (14.3% vs. 21.1%, p<.001). Adolescents who reported unrefreshing sleep were 4.81 times more likely to report a sleep problem. For every hour that bedtime was delayed, the odds of self-reporting a sleep problem increased by 1.91 times, while each additional 10 minutes taken to fall asleep increased the odds 1.40 times. Conclusion While many adolescents were found to have sleep patterns indicative of a sleep problem, only a third of this number self-identify having a sleep problem, while only a sixth of this number are indicated by parental report. This study highlights important features to target in future sleep education and intervention strategies for both adolescents and parents.

Obstructive Sleep Apnea Syndrome in Prader-Willi Syndrome: An Unrecognized and Untreated Cause of Cognitive and Behavioral Deficits?

Prader-Willi Syndrome (PWS) is a rare genetic disorder characterized by a range of physical, psychological, and physiological abnormalities. It is also distinguished by the high prevalence of obstructive sleep apnea syndrome (OSAS), i.e., repetitive upper airway collapse during sleep resulting in hypoxia and sleep fragmentation. In non-PWS populations, OSAS is associated with a range of neurocognitive and psychosocial deficits. Importantly, these deficits are at least partly reversible following treatment. Given the findings in non-PWS populations, it is possible that OSAS may contribute to neurocognitive and psychosocial deficits in PWS. The present review examines this possibility. While acknowledging a primary contribution from the primary genetic abnormality to central neural dysfunction in PWS, we conclude that OSAS may be an important secondary contributing factor to reduced neurocognitive and psychosocial performance. Treatment of OSAS may have potential benefits in improving neurocognitive performance and behavior in PWS, but this awaits confirmatory investigation.

The blink reflex magnitude is continuously adjusted according to both current and predicted stimulus position with respect to the face

The magnitude of the hand-blink reflex (HBR), a subcortical defensive reflex elicited by the electrical stimulation of the median nerve, is increased when the stimulated hand is close to the face (‘far–near effect’). This enhancement occurs through a cortico-bulbar facilitation of the polysynaptic medullary pathways subserving the reflex. Here, in two experiments, we investigated the temporal characteristics of this facilitation, and its adjustment during voluntary movement of the stimulated hand. Given that individuals navigate in a fast changing environment, one would expect the cortico-bulbar modulation of this response to adjust rapidly, and as a function of the predicted spatial position of external threats. We observed two main results. First, the HBR modulation occurs without a temporal delay between when the hand has reached the stimulation position and when the stimulus happens (Experiments 1 and 2). Second, the voluntary movement of the hand interacts with the ‘far–near effect’: stimuli delivered when the hand is far from the face elicit an enhanced HBR if the hand is being moved towards the face, whereas stimuli delivered when the hand is near the face elicit an enhanced HBR regardless of the direction of the hand movement (Experiment 2). These results indicate that the top-down modulation of this subcortical defensive reflex occurs continuously, and takes into account both the current and the predicted position of potential threats with respect to the body. The continuous control of the excitability of subcortical reflex circuits ensures appropriate adjustment of defensive responses in a rapidly-changing sensory environment.

Pain by Association? Experimental Modulation of Human Pain Thresholds Using Classical Conditioning

UNLABELLED A classical conditioning framework is often used for clinical reasoning about pain that persists after tissue healing. However, experimental studies demonstrating classically conditioned pain in humans are lacking. The current study tested whether non-nociceptive somatosensory stimuli can come to modulate pain thresholds after being paired with painful nociceptive stimuli in healthy humans. We used a differential simultaneous conditioning paradigm in which one nonpainful vibrotactile conditioned stimulus (CS(+)) was simultaneously paired with an unconditioned painful laser stimulus, and another vibrotactile stimulus (CS(-)) was paired with a nonpainful laser stimulus. After acquisition, at-pain-threshold laser stimuli were delivered simultaneously with a CS(+) or CS(-) vibrotactile stimulus. The primary outcome was the percentage of at-threshold laser stimuli that were reported as painful. The results were as expected: after conditioning, at-threshold laser trials paired with the CS(+) were reported as painful more often, as more intense, and as more unpleasant than those paired with the CS(-). This study provides new evidence that pain thresholds can be modulated via classical conditioning, even when the stimulus used to test the threshold cannot be anticipated. As such, it lays a critical foundation for further investigations of classical conditioning as a possible driver of persistent pain. PERSPECTIVE This study provides new evidence that human pain thresholds can be influenced by non-nociceptive somatosensory stimuli, via a classical conditioning effect. As such, it lays a critical foundation for further investigations of classical conditioning as a possible driver of persistent pain.

Waking EEG Cortical Markers of Chronic Pain and Sleepiness

Objective Spectral power analyses of EEG recordings are reported to distinguish the cortical activity of individuals with chronic pain from those of controls. Further study of these spectral patterns may provide a greater understanding of the processes associated with chronic pain, in addition to providing potential biometric markers of chronic pain for use in both clinical and research settings. However, sleep deprived groups have demonstrated similar characteristics in their spectral power characteristics, particularly in alpha bandwidth power activity. Methods 103 individuals with chronic pain provided resting awake EEG data in addition to ratings of pain and sleep quality. Two Principal Axis Factor analyses using Promax rotation produced one pain and one sleep factor from relevant questionnaire data provided by participants. These factors were then used to test hypothesized relationships with alpha and theta bandwidth power at the frontal and parietal areas of the cortex. Results Our findings suggest that reductions in alpha bandwidth power are independently associated with both chronic pain intensity ratings and measures of sleep deficits. Conversely, theta bandwidth power was not found to be associated with either chronic pain or sleep quality measures. Conclusions This studys findings support that chronic pain intensity and sleep deficits are related to the Alpha spectral bandwidth activity in individuals with chronic pain.

Thermoregulation, scratch, itch and sleep deficits in children with eczema

Successful sleep onset and maintenance is associated with a reduction in core temperature, facilitated by heat loss at the distal periphery. Problems with initiating and maintaining sleep in children with eczema may relate to impaired thermoregulatory mechanisms, which also contribute to itching and scratching. Our hypothesis was that nocturnal distal skin temperature in eczematous children would be lower than controls, and would also be related to poor sleep quality. We compared overnight polysomnography and distal (finger) and proximal (clavicle) skin temperature in 18 children with eczema and 15 controls (6-16 years). Children with eczema had longer periods of nocturnal wakefulness (mean [SD] = 88.8 [25.8] vs. 44.3 [35.6] min) and lower distal temperatures (34.1 [0.6] °C vs. 34.7 [0.4] °C) than controls, whereas proximal temperature and the distal-proximal gradient were not significantly different. In children with eczema, a higher distal temperature was associated with indicators of poor sleep quality, whereas lower distal temperature was related to more scratching events during sleep. In conclusion, our findings indicate complex interrelationships among eczema, thermoregulation and sleep, and further, that deficits in thermoregulatory mechanisms may contribute to sleep disturbances in children with eczema.

Selectivity of conditioned fear of touch is modulated by somatosensory precision

Learning to initiate defenses in response to specific signals of danger is adaptive. Some chronic pain conditions, however, are characterized by widespread anxiety, avoidance, and pain consistent with a loss of defensive response specificity. Response specificity depends on ability to discriminate between safe and threatening stimuli; therefore, specificity might depend on sensory precision. This would help explain the high prevalence of chronic pain in body areas of low tactile acuity, such as the lower back, and clarify why improving sensory precision may reduce chronic pain. We compared the acquisition and generalization of fear of pain-associated vibrotactile stimuli delivered to either the hand (high tactile acuity) or the back (low tactile acuity). During acquisition, tactile stimulation at one location (CS+) predicted the noxious electrocutaneous stimulation (US), while tactile stimulation at another location (CS-) did not. Responses to three stimuli with decreasing spatial proximity to the CS+ (generalizing stimuli; GS1-3) were tested. Differential learning and generalization were compared between groups. The main outcome of fear-potentiated startle responses showed differential learning only in the hand group. Self-reported fear and expectancy confirmed differential learning and limited generalization in the hand group, and suggested undifferentiated fear and expectancy in the back group. Differences in generalization could not be inferred from the startle data. Specificity of fear responses appears to be affected by somatosensory precision. This has implications for our understanding of the role of sensory imprecision in the development of chronic pain.