Enhanced superconductivity in spin-orbit proximitized bilayer graphene.

In the presence of a large perpendicular electric field, Bernal-stacked bilayer graphene (BLG) features several broken-symmetry metallic phases1-3 as well as magnetic-field-induced superconductivity1. The superconducting state is quite fragile, however, appearing only in a narrow window of density and with a maximum critical temperature Tc ≈ 30 mK. Here we show that placing monolayer tungsten diselenide (WSe2) on BLG promotes Cooper pairing to an extraordinary degree: superconductivity appears at zero magnetic field, exhibits an order of magnitude enhancement in Tc and occurs over a density range that is wider by a factor of eight. By mapping quantum oscillations in BLG-WSe2 as a function of electric field and doping, we establish that superconductivity emerges throughout a region for which the normal state is polarized, with two out of four spin-valley flavours predominantly populated. In-plane magnetic field measurements further reveal that superconductivity in BLG-WSe2 can exhibit striking dependence of the critical field on doping, with the Chandrasekhar-Clogston (Pauli) limit roughly obeyed on one end of the superconducting dome, yet sharply violated on the other. Moreover, the superconductivity arises only for perpendicular electric fields that push BLG hole wavefunctions towards WSe2, indicating that proximity-induced (Ising) spin-orbit coupling plays a key role in stabilizing the pairing. Our results pave the way for engineering robust, highly tunable and ultra-clean graphene-based superconductors.

Imaging inter-valley coherent order in magic-angle twisted trilayer graphene.

Magic-angle twisted trilayer graphene (MATTG) exhibits a range of strongly correlated electronic phases that spontaneously break its underlying symmetries1,2. Here we investigate the correlated phases of MATTG using scanning tunnelling microscopy and identify marked signatures of interaction-driven spatial symmetry breaking. In low-strain samples, over a filling range of about two to three electrons or holes per moiré unit cell, we observe atomic-scale reconstruction of the graphene lattice that accompanies a correlated gap in the tunnelling spectrum. This short-scale restructuring appears as a Kekulé supercell-implying spontaneous inter-valley coherence between electrons-and persists in a wide range of magnetic fields and temperatures that coincide with the development of the gap. Large-scale maps covering several moiré unit cells further reveal a slow evolution of the Kekulé pattern, indicating that atomic-scale reconstruction coexists with translation symmetry breaking at a much longer moiré scale. We use auto-correlation and Fourier analyses to extract the intrinsic periodicity of these phases and find that they are consistent with the theoretically proposed incommensurate Kekulé spiral order3,4. Moreover, we find that the wavelength characterizing moiré-scale modulations monotonically decreases with hole doping away from half-filling of the bands and depends weakly on the magnetic field. Our results provide essential insights into the nature of the correlated phases of MATTG in the presence of strain and indicate that superconductivity can emerge from an inter-valley coherent parent state.

Evidence for unconventional superconductivity in twisted trilayer graphene.

Magic-angle twisted trilayer graphene (MATTG) has emerged as a moiré material that exhibits strong electronic correlations and unconventional superconductivity1,2. However, local spectroscopic studies of this system are still lacking. Here we perform high-resolution scanning tunnelling microscopy and spectroscopy of MATTG that reveal extensive regions of atomic reconstruction favouring mirror-symmetric stacking. In these regions, we observe symmetry-breaking electronic transitions and doping-dependent band-structure deformations similar to those in magic-angle bilayers, as expected theoretically given the commonality of flat bands3,4. Most notably in a density window spanning two to three holes per moiré unit cell, the spectroscopic signatures of superconductivity are manifest as pronounced dips in the tunnelling conductance at the Fermi level accompanied by coherence peaks that become gradually suppressed at elevated temperatures and magnetic fields. The observed evolution of the conductance with doping is consistent with a gate-tunable transition from a gapped superconductor to a nodal superconductor, which is theoretically compatible with a sharp transition from a Bardeen-Cooper-Schrieffer superconductor to a Bose-Einstein-condensation superconductor with a nodal order parameter. Within this doping window, we also detect peak-dip-hump structures that suggest that superconductivity is driven by strong coupling to bosonic modes of MATTG. Our results will enable further understanding of superconductivity and correlated states in graphene-based moiré structures beyond twisted bilayers5.

Correlation-driven topological phases in magic-angle twisted bilayer graphene.

Magic-angle twisted bilayer graphene (MATBG) exhibits a range of correlated phenomena that originate from strong electron-electron interactions. These interactions make the Fermi surface highly susceptible to reconstruction when ±1, ±2 and ±3 electrons occupy each moiré unit cell, and lead to the formation of various correlated phases1-4. Although some phases have been shown to have a non-zero Chern number5,6, the local microscopic properties and topological character of many other phases have not yet been determined. Here we introduce a set of techniques that use scanning tunnelling microscopy to map the topological phases that emerge in MATBG in a finite magnetic field. By following the evolution of the local density of states at the Fermi level with electrostatic doping and magnetic field, we create a local Landau fan diagram that enables us to assign Chern numbers directly to all observed phases. We uncover the existence of six topological phases that arise from integer fillings in finite fields and that originate from a cascade of symmetry-breaking transitions driven by correlations7,8. These topological phases can form only for a small range of twist angles around the magic angle, which further differentiates them from the Landau levels observed near charge neutrality. Moreover, we observe that even the charge-neutrality Landau spectrum taken at low fields is considerably modified by interactions, exhibits prominent electron-hole asymmetry, and features an unexpectedly large splitting between zero Landau levels (about 3 to 5 millielectronvolts). Our results show how strong electronic interactions affect the MATBG band structure and lead to correlation-enabled topological phases.

Superconductivity in metallic twisted bilayer graphene stabilized by WSe2.

Magic-angle twisted bilayer graphene (TBG), with rotational misalignment close to 1.1 degrees, features isolated flat electronic bands that host a rich phase diagram of correlated insulating, superconducting, ferromagnetic and topological phases1-6. Correlated insulators and superconductivity have been previously observed only for angles within 0.1 degree of the magic angle and occur in adjacent or overlapping electron-density ranges; nevertheless, the origins of these states and the relation between them remain unclear, owing to their sensitivity to microscopic details. Beyond twist angle and strain, the dependence of the TBG phase diagram on the alignment4,6 and thickness of the insulating hexagonal boron nitride (hBN)7,8 used to encapsulate the graphene sheets indicates the importance of the microscopic dielectric environment. Here we show that adding an insulating tungsten diselenide (WSe2) monolayer between the hBN and the TBG stabilizes superconductivity at twist angles much smaller than the magic angle. For the smallest twist angle of 0.79 degrees, superconductivity is still observed despite the TBG exhibiting metallic behaviour across the whole range of electron densities. Finite-magnetic-field measurements further reveal weak antilocalization signatures as well as breaking of fourfold spin-valley symmetry, consistent with spin-orbit coupling induced in the TBG via its proximity to WSe2. Our results constrain theoretical explanations for the emergence of superconductivity in TBG and open up avenues towards engineering quantum phases in moiré systems.

New guidance for self-harm: an opportunity not to be missed.

In this editorial we, as members of the 2022 NICE Guideline Committee, highlight and discuss what, in our view, are the key guideline recommendations (generated through evidence synthesis and consensus) for mental health professionals when caring for people after self-harm, and we consider some of the implementation challenges.

Criminal sanctions for suicidality in the 21st Century UK.

Criminal sanctions including court orders, prosecution and imprisonment persist as responses to suicidality in the UK even where there is no public danger. Their prevalence, the level of clinical involvement and outcomes are unclear. There is an urgent need to examine the national picture of harms, benefits and the responsibilities of mental health professionals.

Data-driven integration of hippocampal CA1 synaptic physiology in silico.

The anatomy and physiology of monosynaptic connections in rodent hippocampal CA1 have been extensively studied in recent decades. Yet, the resulting knowledge remains disparate and difficult to reconcile. Here, we present a data-driven approach to integrate the current state-of-the-art knowledge on the synaptic anatomy and physiology of rodent hippocampal CA1, including axo-dendritic innervation patterns, number of synapses per connection, quantal conductances, neurotransmitter release probability, and short-term plasticity into a single coherent resource. First, we undertook an extensive literature review of paired recordings of hippocampal neurons and compiled experimental data on their synaptic anatomy and physiology. The data collected in this manner is sparse and inhomogeneous due to the diversity of experimental techniques used by different groups, which necessitates the need for an integrative framework to unify these data. To this end, we extended a previously developed workflow for the neocortex to constrain a unifying in silico reconstruction of the synaptic physiology of CA1 connections. Our work identifies gaps in the existing knowledge and provides a complementary resource toward a more complete quantification of synaptic anatomy and physiology in the rodent hippocampal CA1 region.

The physiological variability of channel density in hippocampal CA1 pyramidal cells and interneurons explored using a unified data-driven modeling workflow.

Every neuron is part of a network, exerting its function by transforming multiple spatiotemporal synaptic input patterns into a single spiking output. This function is specified by the particular shape and passive electrical properties of the neuronal membrane, and the composition and spatial distribution of ion channels across its processes. For a variety of physiological or pathological reasons, the intrinsic input/output function may change during a neuron's lifetime. This process results in high variability in the peak specific conductance of ion channels in individual neurons. The mechanisms responsible for this variability are not well understood, although there are clear indications from experiments and modeling that degeneracy and correlation among multiple channels may be involved. Here, we studied this issue in biophysical models of hippocampal CA1 pyramidal neurons and interneurons. Using a unified data-driven simulation workflow and starting from a set of experimental recordings and morphological reconstructions obtained from rats, we built and analyzed several ensembles of morphologically and biophysically accurate single cell models with intrinsic electrophysiological properties consistent with experimental findings. The results suggest that the set of conductances expressed in any given hippocampal neuron may be considered as belonging to two groups: one subset is responsible for the major characteristics of the firing behavior in each population and the other is responsible for a robust degeneracy. Analysis of the model neurons suggests several experimentally testable predictions related to the combination and relative proportion of the different conductances that should be expressed on the membrane of different types of neurons for them to fulfill their role in the hippocampus circuitry.

New insights into the classification and nomenclature of cortical GABAergic interneurons.

A systematic classification and accepted nomenclature of neuron types is much needed but is currently lacking. This article describes a possible taxonomical solution for classifying GABAergic interneurons of the cerebral cortex based on a novel, web-based interactive system that allows experts to classify neurons with pre-determined criteria. Using Bayesian analysis and clustering algorithms on the resulting data, we investigated the suitability of several anatomical terms and neuron names for cortical GABAergic interneurons. Moreover, we show that supervised classification models could automatically categorize interneurons in agreement with experts' assignments. These results demonstrate a practical and objective approach to the naming, characterization and classification of neurons based on community consensus.

γ-Aminobutyric Acid Type A (GABAA) Receptor Subunits Play a Direct Structural Role in Synaptic Contact Formation via Their N-terminal Extracellular Domains.

The establishment of cell-cell contacts between presynaptic GABAergic neurons and their postsynaptic targets initiates the process of GABAergic synapse formation. GABAA receptors (GABAARs), the main postsynaptic receptors for GABA, have been recently demonstrated to act as synaptogenic proteins that can single-handedly induce the formation and functional maturation of inhibitory synapses. To establish how the subunit composition of GABAARs influences their ability to induce synaptogenesis, a co-culture model system incorporating GABAergic medium spiny neurons and the HEK293 cells, stably expressing different combinations of receptor subunits, was developed. Analyses of HEK293 cell innervation by medium spiny neuron axons using immunocytochemistry, activity-dependent labeling, and electrophysiology have indicated that the γ2 subunit is required for the formation of active synapses and that its effects are influenced by the type of α/ß subunits incorporated into the functional receptor. To further characterize this process, the large N-terminal extracellular domains (ECDs) of α1, α2, ß2, and γ2 subunits were purified using the baculovirus/Sf9 cell system. When these proteins were applied to the co-cultures of MSNs and α1/ß2/γ2-expressing HEK293 cells, the α1, ß2, or γ2 ECD each caused a significant reduction in contact formation, in contrast to the α2 ECD, which had no effect. Together, our experiments indicate that the structural role of GABAARs in synaptic contact formation is determined by their subunit composition, with the N-terminal ECDs of each of the subunits directly participating in interactions between the presynaptic and postsynaptic elements, suggesting the these interactions are multivalent and specific.

GABA(A) receptors can initiate the formation of functional inhibitory GABAergic synapses.

The mechanisms that underlie the selection of an inhibitory GABAergic axon's postsynaptic targets and the formation of the first contacts are currently unknown. To determine whether expression of GABAA receptors (GABAA Rs) themselves--the essential functional postsynaptic components of GABAergic synapses--can be sufficient to initiate formation of synaptic contacts, a novel co-culture system was devised. In this system, the presynaptic GABAergic axons originated from embryonic rat basal ganglia medium spiny neurones, whereas their most prevalent postsynaptic targets, i.e., α1/ß2/γ2-GABAA Rs, were expressed constitutively in a stably transfected human embryonic kidney 293 (HEK293) cell line. The first synapse-like contacts in these co-cultures were detected by colocalization of presynaptic and postsynaptic markers within 2 h. The number of contacts reached a plateau at 24 h. These contacts were stable, as assessed by live cell imaging; they were active, as determined by uptake of a fluorescently labelled synaptotagmin vesicle-luminal domain-specific antibody; and they supported spontaneous and action potential-driven postsynaptic GABAergic currents. Ultrastructural analysis confirmed the presence of characteristics typical of active synapses. Synapse formation was not observed with control or N-methyl-d-aspartate receptor-expressing HEK293 cells. A prominent increase in synapse formation and strength was observed when neuroligin-2 was co-expressed with GABAA Rs, suggesting a cooperative relationship between these proteins. Thus, in addition to fulfilling an essential functional role, postsynaptic GABAA Rs can promote the adhesion of inhibitory axons and the development of functional synapses.

Petilla terminology: nomenclature of features of GABAergic interneurons of the cerebral cortex.

Neuroscience produces a vast amount of data from an enormous diversity of neurons. A neuronal classification system is essential to organize such data and the knowledge that is derived from them. Classification depends on the unequivocal identification of the features that distinguish one type of neuron from another. The problems inherent in this are particularly acute when studying cortical interneurons. To tackle this, we convened a representative group of researchers to agree on a set of terms to describe the anatomical, physiological and molecular features of GABAergic interneurons of the cerebral cortex. The resulting terminology might provide a stepping stone towards a future classification of these complex and heterogeneous cells. Consistent adoption will be important for the success of such an initiative, and we also encourage the active involvement of the broader scientific community in the dynamic evolution of this project.

How we developed an emergency psychiatry training course for new residents using principles of high-fidelity simulation.

New psychiatry residents must rapidly acquire new clinical skills and learn to work effectively with new colleagues. In medical and surgical specialties, high-fidelity simulation with structured debriefing is widely used, but so far this has not been applied to psychiatry. We have developed a one-day simulation-based training course for emergency psychiatry which incorporates clinical and team-working skills training. Five scenarios covering key psychiatric emergencies are delivered in a purpose-built simulation facility. Patients are played by an actor or a high-fidelity manikin. Each scenario is followed by a 45-minute group debrief. Evaluation of a pilot group found that the course was well received and improved participants' workplace confidence. We are now planning to expand the course, provide it to all new residents and conduct further evaluation.

No safety without emotional safety.

This Personal View highlights how emotional safety is required for a person to keep themselves physically safe. We explain how trying to control behaviour to increase physical safety in the short term can carry the unintended consequence of reducing emotional safety, which might in turn result in higher levels of stress and hopelessness. We use examples from institutions with psychiatric inpatients to describe these processes. We argue that emotional and physical safety cannot be separated, and therefore that the absence of emotional safety compromises basic care either in an acute crisis or in the long term. Staff who fear being criticised, and so feel driven to take autonomy and responsibility away from patients, unwittingly undermine patients' experience of being empathically understood and supported, adding to patients' sense of emotional turmoil and lack of safety. We suggest that a change in culture and regulatory reform is required to bring psychiatric care more in line with the psychological needs of patients to achieve both physical and emotional safety.

'Medical clearance' and referral to liaison psychiatry: a national service evaluation.

AIMS AND METHOD: The prevalence of delaying psychiatric care until the patient has received 'medical clearance', and the definitions and understanding of 'medical clearance' terminology by relevant clinicians, are largely unknown. In a service evaluation of adult liaison psychiatry services across England, we explore the prevalence, definitions and understanding of 'medical clearance' terminology in three parallel studies: (a) an analysis of trust policies, (b) a survey of liaison psychiatry services and (c) a survey of referring junior doctors. Content and thematic analyses were performed. RESULTS: 'Medical clearance' terminology was used in the majority of trust policies, reported as a referral criterion by many liaison psychiatry services and had been encountered by most referring doctors. 'Medical clearance' was identified as a common barrier to liaison psychiatry referral. Terms were inconsistently used and poorly defined. CLINICAL IMPLICATIONS: Many liaison psychiatry services seem not to comply with guidance promoting parallel assessment. This may affect parity of physical and mental healthcare provision.

Identifying, understanding and responding to domestic abuse in the perinatal period.

Domestic abuse often begins or escalates during the perinatal period, increasing the risk of adverse pregnancy outcomes and death of the woman and infant. The hidden nature of domestic abuse, compounded by barriers to disclosure, means many clinicians are likely to have unknowingly encountered a patient who is being abused and missed a vital opportunity for intervention. This educational article presents the experience of a woman who was abused during pregnancy. It describes how to facilitate a disclosure and conduct an assessment and illustrates safeguarding duties alongside interventions.

A comprehensive neuroanatomical survey of the Drosophila Lobula Plate Tangential Neurons with predictions for their optic flow sensitivity.

Flying insects exhibit remarkable navigational abilities controlled by their compact nervous systems. Optic flow, the pattern of changes in the visual scene induced by locomotion, is a crucial sensory cue for robust self-motion estimation, especially during rapid flight. Neurons that respond to specific, large-field optic flow patterns have been studied for decades, primarily in large flies, such as houseflies, blowflies, and hover flies. The best-known optic-flow sensitive neurons are the large tangential cells of the dipteran lobula plate, whose visual-motion responses, and to a lesser extent, their morphology, have been explored using single-neuron neurophysiology. Most of these studies have focused on the large, Horizontal and Vertical System neurons, yet the lobula plate houses a much larger set of 'optic-flow' sensitive neurons, many of which have been challenging to unambiguously identify or to reliably target for functional studies. Here we report the comprehensive reconstruction and identification of the Lobula Plate Tangential Neurons in an Electron Microscopy (EM) volume of a whole Drosophila brain. This catalog of 58 LPT neurons (per brain hemisphere) contains many neurons that are described here for the first time and provides a basis for systematic investigation of the circuitry linking self-motion to locomotion control. Leveraging computational anatomy methods, we estimated the visual motion receptive fields of these neurons and compared their tuning to the visual consequence of body rotations and translational movements. We also matched these neurons, in most cases on a one-for-one basis, to stochastically labeled cells in genetic driver lines, to the mirror-symmetric neurons in the same EM brain volume, and to neurons in an additional EM data set. Using cell matches across data sets, we analyzed the integration of optic flow patterns by neurons downstream of the LPTs and find that most central brain neurons establish sharper selectivity for global optic flow patterns than their input neurons. Furthermore, we found that self-motion information extracted from optic flow is processed in distinct regions of the central brain, pointing to diverse foci for the generation of visual behaviors.

Mapping infant brain myelination with magnetic resonance imaging.

Myelination, the elaboration of myelin surrounding neuronal axons, is essential for normal brain function. The development of the myelin sheath enables rapid synchronized communication across the neural systems responsible for higher order cognitive functioning. Despite this critical role, quantitative visualization of myelination in vivo is not possible with current neuroimaging techniques including diffusion tensor and structural magnetic resonance imaging (MRI). Although these techniques offer insight into structural maturation, they reflect several different facets of development, e.g., changes in axonal size, density, coherence, and membrane structure; lipid, protein, and macromolecule content; and water compartmentalization. Consequently, observed signal changes are ambiguous, hindering meaningful inferences between imaging findings and metrics of learning, behavior or cognition. Here we present the first quantitative study of myelination in healthy human infants, from 3 to 11 months of age. Using a new myelin-specific MRI technique, we report a spatiotemporal pattern beginning in the cerebellum, pons, and internal capsule; proceeding caudocranially from the splenium of the corpus callosum and optic radiations (at 3-4 months); to the occipital and parietal lobes (at 4-6 months); and then to the genu of the corpus callosum and frontal and temporal lobes (at 6-8 months). Our results also offer preliminary evidence of hemispheric myelination rate differences. This work represents a significant step forward in our ability to appreciate the fundamental process of myelination, and provides the first ever in vivo visualization of myelin maturation in healthy human infancy.