Despite the promise of intranasal oxytocin (OT) for modulating social behavior, recent work has provided mixed results. This may relate to suboptimal drug deposition achieved with conventional nasal sprays, inter-individual differences in nasal physiology and a poor understanding of how intranasal OT is delivered to the brain in humans. Delivering OT using a novel ‘Breath Powered' nasal device previously shown to enhance deposition in intranasal sites targeted for nose-to-brain transport, we evaluated dose-dependent effects on social cognition, compared response with intravenous (IV) administration of OT, and assessed nasal cavity dimensions using acoustic rhinometry. We adopted a randomized, double-blind, double-dummy, crossover design, with 16 healthy male adults completing four single-dose treatments (intranasal 8 IU (international units) or 24 IU OT, 1 IU OT IV and placebo). The primary outcome was social cognition measured by emotional ratings of facial images. Secondary outcomes included the pharmacokinetics of OT, vasopressin and cortisol in blood and the association between nasal cavity dimensions and emotional ratings. Despite the fact that all the treatments produced similar plasma OT increases compared with placebo, there was a main effect of treatment on anger ratings of emotionally ambiguous faces. Pairwise comparisons revealed decreased ratings after 8 IU OT in comparison to both placebo and 24 IU OT. In addition, there was an inverse relationship between nasal valve dimensions and anger ratings of ambiguous faces after 8-IU OT treatment. These findings provide support for a direct nose-to-brain effect, independent of blood absorption, of low-dose OT delivered from a Breath Powered device.

Neuroimaging and genetics studies have advanced our understanding of the neurobiology of sleep and its disorders. However, individual studies usually have limitations to identifying consistent and reproducible effects, including modest sample sizes, heterogeneous clinical characteristics and varied methodologies. These issues call for a large-scale multi-centre effort in sleep research, in order to increase the number of samples, and harmonize the methods of data collection, preprocessing and analysis using pre-registered well-established protocols. The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium provides a powerful col-How to cite this article: Tahmasian M, Aleman A, Andreassen OA, et al. ENIGMA-Sleep: Challenges, opportunities, and the road map.

This study investigated how proactive and reactive cognitive control processing in the brain was associated with habitual sleep health. BOLD fMRI data were acquired from 81 healthy adults with normal sleep (41 females, age 20.96–39.58 years) during a test of cognitive control (Not-X-CPT). Sleep health was assessed in the week before MRI scanning, using both objective (actigraphy) and self-report measures. Multiple measures indicating poorer sleep health—including later/more variable sleep timing, later chronotype preference, more insomnia symptoms, and lower sleep efficiency—were associated with stronger and more widespread BOLD activations in fronto-parietal and subcortical brain regions during cognitive control processing (adjusted for age, sex, education, and fMRI task performance). Most associations were found for reactive cognitive control activation, indicating that poorer sleep health is linked to a “hyper-reactive” brain state. Analysis of time-on-task effects showed that, with longer time on task, poorer sleep health was predominantly associated with increased proactive cognitive control activation, indicating recruitment of additional neural resources over time. Finally, shorter objective sleep duration was associated with lower BOLD activation with time on task and poorer task performance. In conclusion, even in “normal sleepers,” relatively poorer sleep health is associated with altered cognitive control processing, possibly reflecting compensatory mechanisms and/or inefficient neural processing.