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There are profound sex differences in the incidence of many psychiatric disorders. Although these disorders are frequently linked to social stress and to deficits in social engagement, little is known about sex differences in the neural mechanisms that underlie these phenomena. Phenotypes characterized by dominance, competitive aggression, and active coping strategies appear to be more resilient to psychiatric disorders such as posttraumatic stress disorder (PTSD) compared with those characterized by subordinate status and the lack of aggressiveness. Here, we report that serotonin (5-HT) and arginine–vasopressin (AVP) act in opposite ways in the hypothalamus to regulate dominance and aggression in females and males. Hypothalamic injection of a 5-HT1a agonist stimulated aggression in female hamsters and inhibited aggression in males, whereas injection of AVP inhibited aggression in females and stimulated aggression in males. Striking sex differences were also identified in the neural mechanisms regulating dominance. Acquisition of dominance was associated with activation of 5-HT neurons within the dorsal raphe in females and activation of hypothalamic AVP neurons in males. These data strongly indicate that there are fundamental sex differences in the neural regulation of dominance and aggression. Further, because systemically administered fluoxetine increased aggression in females and substantially reduced aggression in males, there may be substantial gender differences in the clinical efficacy of commonly prescribed 5-HT–active drugs such as selective 5-HT reuptake inhibitors. These data suggest that the treatment of psychiatric disorders such as PTSD may be more effective with the use of 5-HT–targeted drugs in females and AVP-targeted drugs in males.

•Classical and non-classical psychedelics induce common brain network changes.•Nitrous oxide, ketamine, and LSD all reduce within-network connectivity.•Nitrous oxide, ketamine, and LSD all enhance between-network connectivity.•Changes in temporoparietal junction are consistent across diverse psychedelics. The neurobiology of the psychedelic experience is not fully understood. Identifying common brain network changes induced by both classical (i.e., acting at the 5-HT2 receptor) and non-classical psychedelics would provide mechanistic insight into state-specific characteristics. We analyzed whole-brain functional connectivity based on resting-state fMRI data in humans, acquired before and during the administration of nitrous oxide, ketamine, and lysergic acid diethylamide. We report that, despite distinct molecular mechanisms and modes of delivery, all three psychedelics reduced within-network functional connectivity and enhanced between-network functional connectivity. More specifically, all three drugs increased connectivity between right temporoparietal junction and bilateral intraparietal sulcus as well as between precuneus and left intraparietal sulcus. These regions fall within the posterior cortical “hot zone,” posited to mediate the qualitative aspects of experience. Thus, both classical and non-classical psychedelics modulate networks within an area of known relevance for consciousness, identifying a biologically plausible candidate for their subjective effects.

Neuroimaging has enhanced our understanding of the neural correlates of pain. Yet, how neural circuits interact and contribute to persistent pain remain largely unknown. Here, we investigate the mesoscale organization of the brain through intrinsic functional communities generated from resting state functional MRI data from two independent datasets, a discovery cohort of 43 Fibromyalgia (FM) patients and 20 healthy controls (HC) as well as a replication sample of 34 FM patients and 21 HC. Using normalized mutual information, we found that the global network architecture in chronic pain patients is less stable (more variable). Subsequent analyses of node community assignment revealed the composition of the communities differed between FM and HC. Furthermore, differences in network organization were associated with the changes in the composition of communities between patients with varying levels of clinical pain. Together, this work demonstrates that intrinsic network communities differ substantially between patients with FM and controls. These differences may represent a novel aspect of the pathophysiology of chronic nociplastic pain.

Despite the longstanding use of nitrous oxide and descriptions of its psychological effects more than a century ago, there is a paucity of neurobiological investigation of associated psychedelic experiences. We measure the brain’s functional geometry (through analysis of cortical gradients) and temporal dynamics (through analysis of co-activation patterns) using human resting-state functional magnetic resonance imaging data acquired before and during administration of 35% nitrous oxide. Both analyses demonstrate that nitrous oxide reduces functional differentiation in frontoparietal and somatomotor networks. Importantly, the subjective psychedelic experience induced by nitrous oxide is inversely correlated with the degree of functional differentiation. Thus, like classical psychedelics acting on serotonin receptors, nitrous oxide flattens the functional geometry of the cortex and disrupts temporal dynamics in association with psychoactive effects. Like classical psychedelics, nitrous oxide reduces functional differentiation in human frontoparietal and somatomotor networks, flattening functional brain geometry and disrupting temporal dynamics in association with the psychedelic experience.

RationaleUnderstanding the neurobiological mechanisms mediating dominance and competitive aggression is essential to understanding the development and treatment of various psychiatric disorders. Previous research suggests that these mechanisms are both sexually differentiated and influenced substantially by social experience. In numerous species, GABAA receptors in the lateral septum have been shown to play a significant role in aggression in males. However, very little is known about the role of these GABAA receptors in female aggression, the role of social experience on GABAA receptor–mediated aggression, or the roles of different GABAA subtypes in regulating aggression.ObjectivesThus, in the following set of experiments, we determined the role of social experience in modulating GABAA receptor–induced aggression in both male and female Syrian hamsters, with a particular focus on the GABAA receptor subtype mediating these effects.ResultsActivation of GABAA receptors in the dorsal lateral septum increased aggression in both males and females. Social housing, however, significantly decreased the ability of GABAA receptor activation to induce aggression in males but not females. No significant differences were observed in the effects of GABAA receptor activation in dominant versus subordinate group-housed hamsters. Finally, examination of potential GABAA receptor subtype specificity revealed that social housing decreased the ratio of δ extrasynaptic to γ2 synaptic subunit GABAA receptor mRNA expression in the anterior dorsal lateral septum, while activation of δ extrasynaptic, but not γ2 synaptic, GABAA receptors in the dorsal lateral septum increased aggression.ConclusionsThese data suggest that social experience can have profound effects on the neuronal mechanisms mediating aggression, especially in males, and that δ extrasynaptic GABAA receptors may be an important therapeutic target in disorders characterized by high levels of aggression.

The neurobiology of the psychedelic experience is not fully elucidated. Identifying common brain network changes induced by both canonical (i.e., acting at the 5-HT2 receptor) and non-canonical psychedelics would provide mechanistic insight into state-specific characteristics. We analyzed whole-brain functional connectivity based on resting-state fMRI data in humans, acquired before and during the administration of nitrous oxide, ketamine, and lysergic acid diethylamide. We report that, despite distinct molecular mechanisms and modes of delivery, all three psychedelics reduced within-network functional connectivity and enhanced between-network functional connectivity. More specifically, all drugs tested increased connectivity between right temporoparietal junction and bilateral intraparietal sulcus as well as between precuneus and left intraparietal sulcus. These regions fall within the posterior cortical hot zone, posited to mediate the content of consciousness. Thus, both canonical and non-canonical psychedelics modulate networks within an area of known relevance for conscious experience, identifying a biologically plausible candidate for their subjective effects. Competing Interest Statement The authors have declared no competing interest.

Despite the longstanding use of nitrous oxide and descriptions of its psychological effects more than a century ago, there is a paucity of neurobiological investigation of associated psychedelic experiences. Identifying the impact of nitrous oxide on functional brain networks would advance understanding and contribute to the growing body of research in psychedelic neuroscience. Based on human resting-state fMRI data acquired before and during the administration of 35% nitrous oxide, we measured the brain’s functional geometry (through analysis of cortical gradients) and temporal dynamics (through analysis of co-activation patterns). Both analyses show that nitrous oxide reduces functional differentiation in frontoparietal and somatomotor networks. Importantly, the subjective psychedelic experience induced by nitrous oxide is inversely correlated with the degree of functional differentiation. Thus, like classical psychedelics acting on 5-HT2 receptors, nitrous oxide flattens the functional geometry of the cortex and disrupts temporal dynamics in association with psychoactive effects.

It is unknown how chronic inflammation impacts the brain. Here, we examined whether higher levels of peripheral inflammation were associated with brain connectivity and structure in 54 rheumatoid arthritis patients using functional and structural MRI. We show that higher levels of inflammation are associated with more positive connections between the inferior parietal lobule (IPL), medial prefrontal cortex, and multiple brain networks, as well as reduced IPL grey matter, and that these patterns of connectivity predicted fatigue, pain and cognitive dysfunction. At a second scan 6 months later, some of the same patterns of connectivity were again associated with higher peripheral inflammation. A graph theoretical analysis of whole-brain functional connectivity revealed a pattern of connections spanning 49 regions, including the IPL and medial frontal cortex, that are associated with peripheral inflammation. These regions may play a critical role in transducing peripheral inflammatory signals to the central changes seen in rheumatoid arthritis. Many diseases, such as rheumatoid arthritis, are characterized by a chronic inflammatory state, but it is not clear whether or how this affects the brain. Here, the authors show that the severity of on-going inflammation predicts altered functional brain connectivity in people with rheumatoid arthritis.

The James Webb Space Telescope (JWST) is a large, infrared space telescope that has recently started its science program which will enable breakthroughs in astrophysics and planetary science. Notably, JWST will provide the very first observations of the earliest luminous objects in the universe and start a new era of exoplanet atmospheric characterization. This transformative science is enabled by a 6.6 m telescope that is passively cooled with a 5 layer sunshield. The primary mirror is comprised of 18 controllable, low areal density hexagonal segments, that were aligned and phased relative to each other in orbit using innovative image-based wave front sensing and control algorithms. This revolutionary telescope took more than two decades to develop with a widely distributed team across engineering disciplines. We present an overview of the telescope requirements, architecture, development, superb on-orbit performance, and lessons learned. JWST successfully demonstrates a segmented aperture space telescope and establishes a path to building even larger space telescopes.

ObjectivesThe English Bowel Cancer Screening Programme invites 55 year olds for a sigmoidoscopy (Bowel Scope Screening (BSS)), aiming to resect premalignant polyps, thus reducing cancer incidence. A national patient survey indicated higher procedural pain than anticipated, potentially impacting on screening compliance and effectiveness. We aimed to assess whether water-assisted sigmoidoscopy (WAS), as opposed to standard CO2 technique, improved procedural pain and detection of adenomatous polyps.DesignThe WASh (Water-Assisted Sigmoidoscopy) trial was a multicentre, single-blind, randomised control trial for people undergoing BSS. Participants were randomised to either receive WAS or CO2 from five sites across England. The primary outcome measure was patient-reported moderate/severe pain, as assessed by patients on a standard Likert scale post procedure prior to discharge. The key secondary outcome was adenoma detection rate (ADR). The costs of each technique were also measured.Results1123 participants (50% women, mean age 55) were randomised (561 WAS, 562 CO2). We found no difference in patient-reported moderate/severe pain between WAS and CO2 (14% in WAS, 15% in CO2; p=0.47). ADR was 15% in the CO2 arm and 11% in the WAS arm (p=0.03); however, it remained above the minimum national performance standard in both arms. There was no statistical difference in mean number of adenomas nor overall polyp detection rate. There was negligible cost difference between the two techniques.ConclusionIn the context of enema-prepared unsedated screening sigmoidoscopies performed by screening-accredited endoscopists, no difference in patient-reported pain was seen when using either a CO2 or WAS intubation technique.Trial registration number ISRCTN81466870.