Orexins and primary headaches: an overview of the neurobiology and clinical impact.

INTRODUCTION: Primary headaches, including migraines and cluster headaches, are highly prevalent disorders that significantly impact quality of life. Several factors suggest a key role for the hypothalamus, including neuroimaging studies, attack periodicity, and the presence of altered homeostatic regulation. The orexins are two neuropeptides synthesized almost exclusively in the lateral hypothalamus with widespread projections across the central nervous system. They are involved in an array of functions including homeostatic regulation and nociception, suggesting a potential role in primary headaches. AREAS COVERED: This review summarizes current knowledge of the neurobiology of orexins, their involvement in sleep-wake regulation, nociception, and functions relevant to the associated symptomology of headache disorders. Preclinical reports of the antinociceptive effects of orexin-A in preclinical models are discussed, as well as clinical evidence for the potential involvement of the orexinergic system in headache. EXPERT OPINION: Several lines of evidence support the targeted modulation of orexinergic signaling in primary headaches. Critically, orexins A and B, acting differentially via the orexin 1 and 2 receptors, respectively, demonstrate differential effects on trigeminal pain processing, indicating why dual-receptor antagonists failed to show clinical efficacy. The authors propose that orexin 1 receptor agonists or positive allosteric modulators should be the focus of future research.

Investigating the relationship between sleep and migraine in a global sample: a Bayesian cross-sectional approach.

BACKGROUND: There is a bidirectional link between sleep and migraine, however causality is difficult to determine. This study aimed to investigate this relationship using data collected from a smartphone application. METHODS: Self-reported data from 11,166 global users (aged 18-81 years, mean: 41.21, standard deviation: 11.49) were collected from the Migraine Buddy application (Healint Pte. Ltd.). Measures included: start and end times of sleep and migraine attacks, and pain intensity. Bayesian regression models were used to predict occurrence of a migraine attack the next day based on users' deviations from average sleep, number of sleep interruptions, and hours slept the night before in those reporting ≥ 8 and < 25 migraine attacks on average per month. Conversely, we modelled whether attack occurrence and pain intensity predicted hours slept that night. RESULTS: There were 724 users (129 males, 412 females, 183 unknown, mean age = 41.88 years, SD = 11.63), with a mean monthly attack frequency of 9.94. More sleep interruptions (95% Highest Density Interval (95%HDI [0.11 - 0.21]) and deviation from a user's mean sleep (95%HDI [0.04 - 0.08]) were significant predictors of a next day attack. Total hours slept was not a significant predictor (95%HDI [-0.04 - 0.04]). Pain intensity, but not attack occurrence was a positive predictor of hours slept. CONCLUSIONS: Sleep fragmentation and deviation from typical sleep are the main drivers of the relationship between sleep and migraine. Having a migraine attack does not predict sleep duration, yet the pain associated with it does. This study highlights sleep as crucial in migraine management.

The impact of acoustic stimulation during sleep on memory and sleep architecture: A meta-analysis.

The relationship between sleep and cognition has long been recognized, with slow-wave sleep thought to play a critical role in long-term memory consolidation. Recent research has presented the possibility that non-invasive acoustic stimulation during sleep could enhance memory consolidation. Herein, we report a random-effects model meta-analysis examining the impact of this intervention on memory and sleep architecture in healthy adults. Sixteen studies were identified through a systematic search. We found a medium significant effect of acoustic stimulation on memory task performance (g = 0.68, p = .031) in young adults <35 years of age, but no statistically significant effect in adults >35 years of age (g = -0.83, p = .223). In young adults, there was a large statistically significant effect for declarative memory tasks (g = 0.87, p = .014) but no effect for non-declarative tasks (g = -0.25, p = .357). There were no statistically significant differences in polysomnography-derived sleep architecture values between sham and stimulation conditions in either young or older adults. Based on these results, it appears that acoustic stimulation during sleep may only be an effective intervention for declarative memory consolidation in young adults. However, the small number of studies in this area, their small sample sizes, the short-term nature of most investigations and the high between-studies heterogeneity highlight a need for high-powered and long-term experiments to better elucidate, and subsequently maximise, any potential benefits of this novel approach.

Brain-computer interface robotics for hand rehabilitation after stroke: a systematic review.

BACKGROUND: Hand rehabilitation is core to helping stroke survivors regain activities of daily living. Recent studies have suggested that the use of electroencephalography-based brain-computer interfaces (BCI) can promote this process. Here, we report the first systematic examination of the literature on the use of BCI-robot systems for the rehabilitation of fine motor skills associated with hand movement and profile these systems from a technical and clinical perspective. METHODS: A search for January 2010-October 2019 articles using Ovid MEDLINE, Embase, PEDro, PsycINFO, IEEE Xplore and Cochrane Library databases was performed. The selection criteria included BCI-hand robotic systems for rehabilitation at different stages of development involving tests on healthy participants or people who have had a stroke. Data fields include those related to study design, participant characteristics, technical specifications of the system, and clinical outcome measures. RESULTS: 30 studies were identified as eligible for qualitative review and among these, 11 studies involved testing a BCI-hand robot on chronic and subacute stroke patients. Statistically significant improvements in motor assessment scores relative to controls were observed for three BCI-hand robot interventions. The degree of robot control for the majority of studies was limited to triggering the device to perform grasping or pinching movements using motor imagery. Most employed a combination of kinaesthetic and visual response via the robotic device and display screen, respectively, to match feedback to motor imagery. CONCLUSION: 19 out of 30 studies on BCI-robotic systems for hand rehabilitation report systems at prototype or pre-clinical stages of development. We identified large heterogeneity in reporting and emphasise the need to develop a standard protocol for assessing technical and clinical outcomes so that the necessary evidence base on efficiency and efficacy can be developed.