Psilocybin Facilitates Fear Extinction: Importance of Dose, Context, and Serotonin Receptors.

A variety of classic psychedelics and MDMA have been shown to enhance fear extinction in rodent models. This has translational significance because a standard treatment for post-traumatic stress disorder (PTSD) is prolonged exposure therapy. However, few studies have investigated psilocybin's potential effect on fear learning paradigms. More specifically, the extents to which dose, timing of administration, and serotonin receptors may influence psilocybin's effect on fear extinction are not understood. In this study, we used a delay fear conditioning paradigm to determine the effects of psilocybin on fear extinction, extinction retention, and fear renewal in male and female mice. Psilocybin robustly enhances fear extinction when given acutely prior to testing for all doses tested. Psilocybin also exerts long-term effects to elevate extinction retention and suppress fear renewal in a novel context, although these changes were sensitive to dose. Analysis of sex differences showed that females may respond to a narrower range of doses than males. Administration of psilocybin prior to fear learning or immediately after extinction yielded no change in behavior, indicating that concurrent extinction experience is necessary for the drug's effects. Cotreatment with a 5-HT2A receptor antagonist blocked psilocybin's effects for extinction, extinction retention, and fear renewal, whereas 5-HT1A receptor antagonism attenuated only the effect on fear renewal. Collectively, these results highlight dose, context, and serotonin receptors as crucial factors in psilocybin's ability to facilitate fear extinction. The study provides preclinical evidence to support investigating psilocybin as a pharmacological adjunct for extinction-based therapy for PTSD.

Optogenetic inhibition of light-captured alcohol-taking striatal engrams facilitates extinction and suppresses reinstatement.

BACKGROUND: Alcohol use disorder (AUD) is a complex condition, and it remains unclear which specific neuronal substrates mediate alcohol-seeking and -taking behaviors. Engram cells and their related ensembles, which encode learning and memory, may play a role in this process. We aimed to assess the precise neural substrates underlying alcohol-seeking and -taking behaviors and determine how they may affect one another. METHODS: Using FLiCRE (Fast Light and Calcium-Regulated Expression; a newly developed technique which permits the trapping of acutely activated neuronal ensembles) and operant self-administration (OSA), we tagged striatal neurons activated during alcohol-taking behaviors. We used FLiCRE to express an inhibitory halorhodopsin in alcohol-taking neurons, permitting loss-of-function manipulations. RESULTS: We found that the inhibition of OSA-tagged alcohol-taking neurons decreased both alcohol-seeking and -taking behaviors in future OSA trials. In addition, optogenetic inhibition of these OSA-tagged alcohol-taking neurons during extinction training facilitated the extinction of alcohol-seeking behaviors. Furthermore, inhibition of these OSA-tagged alcohol-taking neurons suppressed the reinstatement of alcohol-seeking behaviors, but, interestingly, it did not significantly suppress alcohol-taking behaviors during reinstatement. CONCLUSIONS: Our findings suggest that alcohol-taking neurons are crucial for future alcohol-seeking behaviors during extinction and reinstatement. These results may help in the development of new therapeutic approaches to enhance extinction and suppress relapse in individuals with AUD.

Design and simulation of a compact polarization beam splitter based on dual-core photonic crystal fiber with elliptical gold layer.

For the polarization multiplexing requirements in all-optical networks, this work presents a compact all-fiber polarization beam splitter (PBS) based on dual-core photonic crystal fiber (PCF) and an elliptical gold layer. Numerical analysis using the finite element method (FEM) demonstrates that the mode modulation effect of the central gold layer effectively reduces the dimensions of the proposed PBS. By determining reasonable structural parameters of the proposed PCF, the coupling length ratio (CLR) between X- and Y-polarized super-modes can approach 2, achieving a minimal device length of 0.122 mm. The PBS exhibits a maximum extinction ratio (ER) of - 65 dB at 1.55 µm, with an operating bandwidth spanning 100 nm (1.5-1.6 µm) and a stable insertion loss (IL) of ~ 1.5 dB at 1.55 µm. Furthermore, the manufacture feasibility and performance verification scheme are also investigated. It is widely anticipated that the designed PBS will play a crucial role in the ongoing development process of miniaturization and integration of photonic devices.

The impact of the left inferior frontal gyrus on fear extinction: A transcranial direct current stimulation study.

INTRODUCTION: Fear extinction is a fundamental component of exposure-based therapies for anxiety-related disorders. The renewal of fear in a different context after extinction highlights the importance of contextual factors. In this study, we aimed to investigate the causal role of the left inferior frontal gyrus (LiFG) in the context-dependency of fear extinction learning via administration of transcranial direct current stimulation (tDCS) over this area. METHODS: 180 healthy subjects were assigned to 9 groups: 3 tDCS conditions (anodal, cathodal, and sham) × 3 context combinations (AAA, ABA, and ABB). The fear conditioning/extinction task was conducted over three consecutive days: acquisition, extinction learning, and extinction recall. tDCS (2 mA, 10min) was administered during the extinction learning phase over the LiFG via a 4-electrode montage. Skin conductance response (SCR) data and self-report assessments were collected. RESULTS: During the extinction learning phase, groups with excitability-enhancing anodal tDCS showed a significantly higher fear response to the threat cues compared to cathodal and sham stimulation conditions, irrespective of contextual factors. This effect was stable until the extinction recall phase. Additionally, excitability-reducing cathodal tDCS caused a significant decrease of the response difference between the threat and safety cues during the extinction recall phase. The self-report assessments showed no significant differences between the conditions throughout the experiment. CONCLUSION: Independent of the context, excitability enhancement of the LiFG did impair fear extinction, and led to preservation of fear memory. In contrast, excitability reduction of this area enhanced fear extinction retention. These findings imply that the LiFG plays a role in the fear extinction network, which seems to be however context-independent.

Reducing FKBP51 Expression in the Ventral Hippocampus Decreases Auditory Fear Conditioning in Male Rats.

Fear conditioning evokes a physiologic release of glucocorticoids that assists learning. As a cochaperone in the glucocorticoid receptor complex, FKBP51 modulates stress-induced glucocorticoid signaling and may influence conditioned fear responses. This study combines molecular and behavioral approaches to examine whether locally reducing FKBP51 expression in the ventral hippocampus is sufficient to affect fear-related behaviors. We hypothesized that reducing FKBP51 expression in the VH would increase glucocorticoid signaling to alter auditory fear conditioning. Adult male rats were injected with an adeno-associated virus (AAV) vector expressing short hairpin - RNAs (shRNA) targeting FKBP5 into the ventral hippocampus to reduce FKBP5 levels or a control AAV. Infusion of FKBP5-shRNA into the ventral hippocampus decreased auditory fear acquisition and recall. Although animals injected with FKBP5-shRNA showed less freezing during extinction recall, the difference was due to a reduced fear recall rather than improved extinction. Reducing ventral hippocampus FKBP51 did not affect exploratory behavior in either the open field test or the elevated zero maze test but did increase passive behavior in the forced swim test, suggesting that the reduction in auditory fear recall was not due to more active responses to acute stress. Furthermore, lower ventral hippocampus FKBP51 levels did not alter corticosterone release in response to restraint stress, suggesting that the reduced fear recall was not due to lower corticosterone release. Our findings suggest FKBP51 in the ventral hippocampus plays a selective role in modulating fear-learning processes and passive behavioral responses to acute stress rather than hypothalamic-pituitary-adrenal axis reactivity or exploratory responses.

Ursus spelaeus (Rosenmüller, 1794) during the MIS 3: new evidence from the Cioclovina Uscata Cave and radiocarbon age overview for the Carpathians.

Ursus spelaeus, the Late Pleistocene a cave bear is known from numerous accumulations found in the fossil sector of caves situated in the Carpathian and Apuseni Mountains. In this study, we present new radiocarbon data along a profile of the Cioclovina Uscata Cave, which is situated in the South Carpathians. The data suggest that, during the entire Marine Isotope Stage 3 (MIS 3) interval, the cave was serving as a shelter for U. spelaeus, with the oldest dated bone indicating an age of > 47,710 and the youngest one, an age of 31,820 ± 400 years cal BP. Histogram plots of 110 radiocarbon data from different caves of the Carpathian and Apuseni Mountains as Cioclovina Uscata, Peștera (Cave) cu Oase, Peștera Muierii, or Peștera Urșilor, respectively, show a maximum expansion of the cave bear population between 50,000 and 40,000, a decline between 40,000 and 35,000 and a partial recovery from 35,000-30,000 years cal BP. Radiocarbon data of Homo sapiens remains, younger than 35,000 years cal BP, support the fact that H. sapiens accessed the same caves where the cave bear persisted to hibernate. Besides general cool conditions and restricted food sources, the presence of H. sapiens constituted an additional stress factor driving the cave bear to extinction.

The temperate marine Peruvian Province: How history accounts for its unusual biota.

The Peruvian Province, from 6° S in Peru to 42° S in Chile, is a highly productive coastal marine region whose biology and fossil record have long been studied separately but never integrated. To understand how past events and conditions affected today's species composition and interactions, we examined the role of extinction, colonization, geologic changes to explain previously unrecognized peculiar features of the biota and to compare the Peruvian Province's history to that of other climatically similar temperate coasts. We synthesized all available data on the benthic (or benthically feeding) biota, with emphasis on fossilizable taxa, for the interval from the Miocene (23-5.4 Ma) and Pliocene (5.4-2.5 Ma) to the present. We outline the history of ecological guilds including primary producers, herbivores, predators, and suspension-feeders and document patterns of extinction, colonization, and geographic restriction. We identify twelve unusual attributes of the biota, most of which are the result of repeated episodes of extinction. Several guilds present during the Miocene and Pliocene are not represented in the province today, while groups such as kelps and perhaps intertidal predatory sea stars are relative newcomers. Guilds on soft bottoms and in sheltered habitats were severely affected by extinction, whereas those on hard bottoms were most affected by colonists and held their own in diversity. The Peruvian Province has not served as a biogeographic refuge, in contrast to the coasts of Australasia and Argentina, where lineages no longer present in the Peruvian Province survive. The loss of sheltered habitats since the Pliocene explains many of the present-day peculiarities of the biota. The history of the province's biota explains its unique attributes. High productivity, a rich Southern Hemisphere heritage, and colonization from the north account for the present-day composition and unusual characteristics of the biota.

Stochastic two-strain epidemic model with saturated incidence rates driven by Lévy noise.

In this paper, we introduce a stochastic two-strain epidemic model driven by Lévy noise describing the interaction between four compartments; susceptible, infected individuals by the first strain, infected ones by the second strain and the recovered individuals. The forces of infection, for both strains, are represented by saturated incidence rates. Our study begins with the investigation of unique global solution of the suggested mathematical model. Then, it moves to the determination of sufficient conditions of extinction and persistence in mean of the two-strain disease. In order to illustrate the theoretical findings, we give some numerical simulations.

High levels of species' extirpation in an urban environment-A case study from Berlin, Germany, covering 1700-2023.

Species loss is highly scale-dependent, following the species-area relationship. We analysed spatio-temporal patterns of species' extirpation on a multitaxonomic level using Berlin, the capital city of Germany. Berlin is one of the largest cities in Europe and has experienced a strong urbanisation trend since the late nineteenth century. We expected species' extirpation to be exceptionally high due to the long history of urbanisation. Analysing 37 regional Red Lists of Threatened Plants, Animals and Fungi of Berlin (covering 9498 species), we found that 16% of species were extirpated, a rate 5.9 times higher than at the German scale and 47.1 times higher than at the European scale. Species' extirpation in Berlin is comparable to that of another German city with a similarly broad taxonomic coverage, but much higher than in regional areas with less human impact. The documentation of species' extirpation started in the eighteenth century and is well documented for the nineteenth and twentieth centuries. We found an average annual extirpation of 3.6 species in the nineteenth century, 9.6 species in the twentieth century and the same number of extirpated species as in the nineteenth century were documented in the twenty-first century, despite the much shorter time period. Our results showed that species' extirpation is higher at small than on large spatial scales, and might be negatively influenced by urbanisation, with different effects on different taxonomic groups and habitats. Over time, we found that species' extirpation is highest during periods of high human alterations and is negatively affected by the number of people living in the city. But, there is still a lack of data to decouple the size of the area and the human impact of urbanisation. However, cities might be suitable systems for studying species' extirpation processes due to their small scale and human impact.

Dynamical analysis of a stochastic maize streak virus epidemic model with logarithmic Ornstein-Uhlenbeck process.

To describe the transmission dynamics of maize streak virus infection, in the paper, we first formulate a stochastic maize streak virus infection model, in which the stochastic fluctuations are depicted by a logarithmic Ornstein-Uhlenbeck process. This approach is reasonable to simulate the random impacts of main parameters both from the biological significance and the mathematical perspective. Then we investigate the detailed dynamics of the stochastic system, including the existence and uniqueness of the global solution, the existence of a stationary distribution, the exponential extinction of the infected maize and infected leafhopper vector. Especially, by solving the five-dimensional algebraic equations corresponding to the stochastic system, we obtain the specific expression of the probability density function near the quasi-endemic equilibrium of the stochastic system, which provides valuable insights into the stationary distribution. Finally, the model is discretized using the Milstein higher-order numerical method to illustrate our theoretical results numerically. Our findings provide a groundwork for better methods of preventing the spread of this type of virus.

Chronic chemogenetic activation of hippocampal progenitors enhances adult neurogenesis and modulates anxiety-like behavior and fear extinction learning.

Adult hippocampal neurogenesis is a lifelong process that involves the integration of newborn neurons into the hippocampal network, and plays a role in cognitive function and the modulation of mood-related behavior. Here, we sought to address the impact of chemogenetic activation of adult hippocampal progenitors on distinct stages of progenitor development, including quiescent stem cell activation, progenitor turnover, differentiation and morphological maturation. We find that hM3Dq-DREADD-mediated activation of nestin-positive adult hippocampal progenitors recruits quiescent stem cells, enhances progenitor proliferation, increases doublecortin-positive newborn neuron number, accompanied by an acceleration of differentiation and morphological maturation, associated with increased dendritic complexity. Behavioral analysis indicated anxiolytic behavioral responses in transgenic mice subjected to chemogenetic activation of adult hippocampal progenitors at timepoints when newborn neurons are predicted to integrate into the mature hippocampal network. Furthermore, we noted an enhanced fear memory extinction on a contextual fear memory learning task in transgenic mice subjected to chemogenetic activation of adult hippocampal progenitors. Our findings indicate that hM3Dq-DREAD-mediated chemogenetic activation of adult hippocampal progenitors impacts distinct aspects of hippocampal neurogenesis, associated with the regulation of anxiety-like behavior and fear memory extinction.

Future climate warming threatens coral reef function on World Heritage reefs.

Climate change is the most significant threat to natural World Heritage (WH) sites, especially in the oceans. Warming has devastated marine faunas, including reef corals, kelp, and seagrass. Here, we project future declines in species and ecosystem functions across Australia's four WH coral reef regions. Model simulations estimating species-level abundances and probabilities of ecological persistence were combined with trait space reconstructions at "present," 2050 (+1.5°C of warming), and 2100 (+2°C) to explore biogeographical overlaps and identify key functional differences and forecast changes in function through time. Future climates varied by region, with Shark Bay projected to warm the most (>1.29°C), followed by Lord Howe, when standardized to marine park size. By 2050, ~40% of the Great Barrier Reef will exceed critical thresholds set by the warmest summer month (mean monthly maximum [MMM]), triggering mortality. Functional diversity was greatest at Ningaloo. At +1.5°C of warming, species and regions varied drastically in their functional responses, declined 20.2% in species richness (~70 extinctions) and lost functions across all reefs. At +2°C, models predicted a complete collapse of functions, consistent with IPCC forecasts. This variability suggests a bespoke management approach is needed for each region and is critical for understanding WH vulnerability to climate change, identifying thresholds, and quantifying uncertainty of impacts. This knowledge will aid in focusing management, policy and conservation actions to direct resources, rapid action, and set biodiversity targets for these reefs of global priority. As reefs reassemble into novel or different configurations, determining the winners and losers of functional space will be critical for meeting global landmark biodiversity goals.

Exercise and Fear and Safety Learning.

Fear conditioning paradigms have been studied for over 100 years and are of great interest to the behavioral and clinical sciences given that several safety learning processes (e.g., extinction learning and recall) are thought to be fundamental to the success of exposure-based therapies for anxiety and related disorders. This chapter provides an overview of preclinical and clinical investigations that examined the effects of exercise on initial fear acquisition, fear extinction learning and consolidation, and return of fear outcomes. This chapter highlights the collective body of evidence suggesting that exercise administered after extinction learning enhances the consolidation and subsequent recall of extinction memories to a greater extent than exercise administered prior to extinction learning. This suggests that the addition of exercise after exposure therapy sessions may improve treatment outcomes for people with anxiety and related disorders. Potential mechanisms are discussed in addition to suggestions for future research to improve our understanding of the effects of exercise on fear conditioning and extinction outcomes.

A Diffusion-Based Approach for Simulating Forward-in-Time State-Dependent Speciation and Extinction Dynamics.

We establish a general framework using a diffusion approximation to simulate forward-in-time state counts or frequencies for cladogenetic state-dependent speciation-extinction (ClaSSE) models. We apply the framework to various two- and three-region geographic-state speciation-extinction (GeoSSE) models. We show that the species range state dynamics simulated under tree-based and diffusion-based processes are comparable. We derive a method to infer rate parameters that are compatible with given observed stationary state frequencies and obtain an analytical result to compute stationary state frequencies for a given set of rate parameters. We also describe a procedure to find the time to reach the stationary frequencies of a ClaSSE model using our diffusion-based approach, which we demonstrate using a worked example for a two-region GeoSSE model. Finally, we discuss how the diffusion framework can be applied to formalize relationships between evolutionary patterns and processes under state-dependent diversification scenarios.

Thiol-polyethylene glycol-folic acid (HS-PEG-FA) induced aggregation of Au@Ag nanoparticles: A SERS and extinction UV-Vis spectroscopy combined study.

Plasmonic colloidal nanoparticles (NPs) functionalised with polymers are widely employed in diverse applications, offering advantages demonstrated over non-functionalised NPs such as enhanced colloidal stability or increased biocompatibility. However, functionalisation with polymers does not always increase the stability of the colloidal system. This work explores the intricate relationship between the functionalisation of plasmonic core@shell Au@Ag nanoparticles (NPs) with thiol-polyethylene glycol-folic acid (HS-PEG-FA) polymer chains and the resulting stability and spectral characteristics of Surface-Enhanced Raman Scattering (SERS) nanotags based on these NPs. We demonstrate that varying levels of HS-PEG-FA grafting influence nanotag stability, with a low level of grafting causing aggregation and subsequently affecting the spectral signature of Raman-reporter molecules attached to the surface of the NP. Electrostatic destabilisation is identified as the primary mechanism driving aggregation, impacting the SERS spectrum of Malachite Green isothiocyanate (MGITC) whose spectral shape is different between the aggregated and non-aggregated NPs. The findings provide valuable insights into NPs stability under different conditions, offering essential considerations for the design and optimisation of SERS nanotags in bio-analytical applications, particularly those involving data processing based on spectral shape, such as in multiplex approaches where experimental spectra are decomposed with several reference components.

Treatment Approaches for Posttraumatic Stress Disorder Derived from Basic Research on Fear Extinction.

This brief review article will describe treatment approaches for posttraumatic stress disorder (PTSD) based on findings from basic research. The focus of this review will be fear conditioning and extinction models, which provide a translational model of PTSD that can help translate basic research in non-human animals through well-controlled trials confirming the efficacy of treatment approaches in humans with PTSD such as prolonged exposure therapy. Specific cognitive aspects of fear extinction processes, including consolidation and reconsolidation, are reviewed along with behavioral and pharmacological treatment strategies based on basic research in these areas including attempts to prevent the development of PTSD as well as the treatment of chronic PTSD. Pharmacological, behavioral, and device-based augmentation strategies of PTSD treatment based in basic science findings are reviewed, including those that disrupt noradrenergic receptor processes, medications that act on NMDA receptors, physical exercise, cannabinoids, estradiol, dexamethasone, yohimbine, losartan, dopamine, and MDMA, along with the evidence for their efficacy in human clinical samples. While fear extinction provides an exciting translational opportunity to improve PTSD based on basic science findings, we review limitations and challenges of the extant literature as well as future directions.

Degradation of perineuronal nets in the medial prefrontal cortex promotes extinction and reduces reinstatement of methamphetamine-induced conditioned place preference in female mice.

The high rate of relapse to compulsive methamphetamine (MA)-taking and seeking behaviors after abstinence constitutes a major obstacle to the treatment of MA addiction. Perineuronal nets (PNNs), essential components of the extracellular matrix, play a critical role in synaptic function, learning, and memory. Abnormalities in PNNs have been closely linked to a series of neurological diseases, such as addiction. However, the exact role of PNNs in MA-induced related behaviors remains elusive. Here, we established a MA-induced conditioned place preference (CPP) paradigm in female mice and found that the number and average optical density of PNNs increased significantly in the medial prefrontal cortex (mPFC) of mice during the acquisition, extinction, and reinstatement stages of CPP. Notably, the removal of PNNs in the mPFC via chondroitinase ABC (ChABC) before extinction training not only facilitated the extinction of MA-induced CPP and attenuated the relapse of extinguished MA preference but also significantly reduced the activation of c-Fos in the mPFC. Similarly, the ablation of PNNs in the mPFC before reinstatement markedly lessened the reinstatement of MA-induced CPP, which was accompanied by the decreased expression of c-Fos in the mPFC. Collectively, our results provide more evidence for the implication of degradation of PNNs in facilitating extinction and preventing relapse of MA-induced CPP, which indicate that targeting PNNs may be an effective therapeutic option for MA-induced CPP memories.

Humidity modifies species-specific and age-dependent heat stress effects in an insect host-parasitoid interaction.

Climate change is projected to increase the frequency and intensity of extreme heat events, and may increase humidity levels, leading to coupled thermal and hydric stress. However, how humidity modulates the impacts of heat stress on species and their interactions is currently unknown. Using an insect host-parasitoid interaction: the Indian meal moth, Plodia interpunctella, and its endoparasitoid wasp, Venturia canescens, we investigated how humidity interacted with heat stress duration, applied at different host developmental stages, to affect life history traits. Hosts parasitized as 4th instar larvae and unparasitized hosts were maintained in high- (60.8% RH) or low-humidity (32.5% RH) at constant 28°C. They were then exposed to a 38°C thermal stress with a duration of 0 (no heat stress), 6 or 72 h in either the 4th or 5th host instar. Neither humidity nor heat stress duration affected emergence of unparasitized hosts, but increasing heat stress duration during the 4th instar decreased parasitoid emergence irrespective of humidity. When applied during the 5th instar, increasing heat duration decreased parasitoid emergence under low humidity, but no effect of heat stress was found under high humidity. Moreover, experiencing longer heat stress in the 4th instar increased host larval development time and decreased body size under high humidity, but this effect differed under low humidity; increasing heat duration in the 5th instar decreased parasitoid body sizes only under low humidity. Larval stage and heat stress duration directly affected parasitized host survival time, with a concomitant indirect reduction of parasitoid sizes. We show that humidity modifies key life history responses of hosts and parasitoids to heat stress in species-specific ways, highlighting the potential importance of humidity in regulating host-parasitoid interactions and their population dynamics. Finally, we emphasize that interactions between environmental stressors need to be considered in climate change research.

Exogenous glucocorticoids to improve extinction learning for post-traumatic stress disorder patients with hypothalamic-pituitary-adrenal-axis dysregulation: a study protocol description.

Background: Trauma-focused treatments for post-traumatic stress disorder (PTSD) are effective for many patients. However, relapse may occur when acquired extinction memories fail to generalize beyond treatment contexts. A subgroup of PTSD patients - potentially with substantial exposure to early-life adversity (ELA) - show dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, which results in lower cortisol levels. Glucocorticoids, including cortisol, appear to facilitate strength and generalization of emotional memories.Objective: We describe the protocol of an integrated PTSD study. We investigate (A) associations between HPA-axis dysregulation, ELA, epigenetic markers, and PTSD treatment outcome (observational study); and (B) effects of exogenous glucocorticoids on strength and generalization of extinction memories and associated neural mechanisms [pharmacological intervention study with functional magnetic resonance imaging (fMRI)]. The objective is to provide proof of concept that PTSD patients with HPA-axis dysregulation often experienced ELA and may show improved strength and generalization of extinction learning after glucocorticoid administration.Method: The observational study (n = 160 PTSD group, n = 30 control group) assesses ELA, follow-up PTSD symptoms, epigenetic markers, and HPA-axis characteristics (salivary cortisol levels during low-dose dexamethasone suppression test and socially evaluated cold-pressor test). The pharmacological intervention study (n = 80 PTSD group, with and without HPA-axis dysregulation) is a placebo-controlled fMRI study with a crossover design. To investigate strength and generalization of extinction memories, we use a differential fear acquisition, extinction, and extinction recall task with spatial contexts within a virtual environment. Prior to extinction learning, 20 mg hydrocortisone or placebo is administered. During next-day recall, strength of the extinction memory is determined by recovery of skin conductance and pupil dilation differential responding, whereas generalization is assessed by comparing responses between different spatial contexts.Conclusion: The integrated study described in the current protocol paper could inform a personalized treatment approach in which these PTSD patients may receive glucocorticoids as a treatment enhancer in trauma-focused therapies.Trial registration: The research project is registered in the European Union Drug Regulating Authorities Clinical Trials (EudraCT) database, https://eudract.ema.europa.eu/, EudraCT number 2020-000712-30.

This protocol reports a proof-of-concept study for glucocorticoids as an enhancer for PTSD treatment.The study examines whether glucocorticoids enhance the strength and generalization of extinction memory.A further aim is to identify HPA-axis-related PTSD subgroups that may particularly benefit.

Climate change vulnerability of Arctic char across Scandinavia.

Climate change is anticipated to cause species to shift their ranges upward and poleward, yet space for tracking suitable habitat conditions may be limited for range-restricted species at the highest elevations and latitudes of the globe. Consequently, range-restricted species inhabiting Arctic freshwater ecosystems, where global warming is most pronounced, face the challenge of coping with changing abiotic and biotic conditions or risk extinction. Here, we use an extensive fish community and environmental dataset for 1762 lakes sampled across Scandinavia (mid-1990s) to evaluate the climate vulnerability of Arctic char (Salvelinus alpinus), the world's most cold-adapted and northernly distributed freshwater fish. Machine learning models show that abiotic and biotic factors strongly predict the occurrence of Arctic char across the region with an overall accuracy of 89 percent. Arctic char is less likely to occur in lakes with warm summer temperatures, high dissolved organic carbon levels (i.e., browning), and presence of northern pike (Esox lucius). Importantly, climate warming impacts are moderated by habitat (i.e., lake area) and amplified by the presence of competitors and/or predators (i.e., northern pike). Climate warming projections under the RCP8.5 emission scenario indicate that 81% of extant populations are at high risk of extirpation by 2080. Highly vulnerable populations occur across their range, particularly near the southern range limit and at lower elevations, with potential refugia found in some mountainous and coastal regions. Our findings highlight that range shifts may give way to range contractions for this cold-water specialist, indicating the need for pro-active conservation and mitigation efforts to avoid the loss of Arctic freshwater biodiversity.