Use of Virtual Reality as Therapeutic Tool for Behavioural Exposure in the Ambit of Social

We hereby present a study whose aim is to evaluate the efficiency and flexibility of virtual reality as a therapeutic tool in the confines of a social phobia behavioural therapeutic program. Our research protocol, accepted by the ethical commission of the cantonal hospices’ psychiatry service, is identical in content and structure for each patient. This study’s second goal is to use the confines of virtual exposure to objectively evaluate a specific parameter present in social phobia, namely eye contact avoidance, by using an eyetracking system. Analysis of our results shows that there is a tendency to improvement in both the questionnaires and eye contact avoidance

A Femtosecond Neutron Source

The possibility to use the ultrashort ion bunches produced by circularly polarized laser pulses to drive a source of fusion neutrons with sub-optical cycle duration is discussed. A two-side irradiation of a thin foil deuterated target produces two countermoving ion bunches, whose collision leads to an ultrashort neutron burst. Using particle-in-cell simulations and analytical modeling, it is evaluated that, for intensities of a few $10^{19} W cm^{-2}$, more than $10^3$ neutrons per Joule may be produced within a time shorter than one femtosecond. Another scheme based on a layered deuterium-tritium target is outlined.Comment: 15 pages, 3 figure

Verbal instructions override the meaning of facial expressions

Psychological research has long acknowledged that facial expressions can implicitly trigger affective psychophysiological responses. However, whether verbal information can alter the meaning of facial emotions and corresponding response patterns has not been tested. This study examined emotional facial expressions as cues for instructed threat-of-shock or safety, with a focus on defensive responding. In addition, reversal instructions were introduced to test the impact of explicit safety instructions on fear extinction. Forty participants were instructed that they would receive unpleasant electric shocks, for instance, when viewing happy but not angry faces. In a second block, instructions were reversed (e.g., now angry faces cued shock). Happy, neutral, and angry faces were repeatedly presented, and auditory startle probes were delivered in half of the trials. The defensive startle reflex was potentiated for threat compared to safety cues. Importantly, this effect occurred regardless of whether threat was cued by happy or angry expressions. Although the typical pattern of response habituation was observed, defense activation to newly instructed threat cues remained significantly enhanced in the second part of the experiment, and it was more pronounced in more socially anxious participants. Thus, anxious individuals did not exhibit more pronounced defense activation compared to less anxious participants, but their defense activation was more persistent

Movement of environmental threats modifies the relevance of the defensive eye-blink in a spatially-tuned manner.

Subcortical reflexive motor responses are under continuous cortical control to produce the most effective behaviour. For example, the excitability of brainstem circuitry subserving the defensive hand-blink reflex (HBR), a response elicited by intense somatosensory stimuli to the wrist, depends on a number of properties of the eliciting stimulus. These include face-hand proximity, which has allowed the description of an HBR response field around the face (commonly referred to as a defensive peripersonal space, DPPS), as well as stimulus movement and probability of stimulus occurrence. However, the effect of stimulus-independent movements of objects in the environment has not been explored. Here we used virtual reality to test whether and how the HBR-derived DPPS is affected by the presence and movement of threatening objects in the environment. In two experiments conducted on 40 healthy volunteers, we observed that threatening arrows flying towards the participant result in DPPS expansion, an effect directionally-tuned towards the source of the arrows. These results indicate that the excitability of brainstem circuitry subserving the HBR is continuously adjusted, taking into account the movement of environmental objects. Such adjustments fit in a framework where the relevance of defensive actions is continually evaluated, to maximise their survival value

Differential Effects of Bartonella henselae on Human and Feline Macro- and Micro-Vascular Endothelial Cells

Bartonella henselae, a zoonotic agent, induces tumors of endothelial cells (ECs), namely bacillary angiomatosis and peliosis in immunosuppressed humans but not in cats. In vitro studies on ECs represent to date the only way to explore the interactions between Bartonella henselae and vascular endothelium. However, no comparative study of the interactions between Bartonella henselae and human (incidental host) ECs vs feline (reservoir host) ECs has been carried out because of the absence of any available feline endothelial cell lines

Predictive modeling of indoor dust lead concentrations: Sources, risks, and benefits of intervention

Lead (Pb) contamination continues to contribute to world-wide morbidity in all countries, particularly low- and middle-income countries. Despite its continued widespread adverse effects on global populations, particularly children, accurate prediction of elevated household dust Pb and the potential implications of simple, low-cost household interventions at national and global scales have been lacking. A global dataset (∼40 countries, n = 1951) of community sourced household dust samples were used to predict whether indoor dust was elevated in Pb, expanding on recent work in the United States (U.S.). Binned housing age category alone was a significant (p < 0.01) predictor of elevated dust Pb, but only generated effective predictive accuracy for England and Australia (sensitivity of ∼80%), similar to previous results in the U.S. This likely reflects comparable Pb pollution legacies between these three countries, particularly with residential Pb paint. The heterogeneity associated with Pb pollution at a global scale complicates the predictive accuracy of our model, which is lower for countries outside England, the U.S., and Australia. This is likely due to differing environmental Pb regulations, sources, and the paucity of dust samples available outside of these three countries. In England, the U.S., and Australia, simple, low-cost household intervention strategies such as vacuuming and wet mopping could conservatively save 70 billion USD within a four-year period based on our model. Globally, up to 1.68 trillion USD could be saved with improved predictive modeling and primary intervention to reduce harmful exposure to Pb dust sources

Blocking human fear memory with the matrix metalloproteinase inhibitor doxycycline

Learning to predict threat is a fundamental ability of many biological organisms, and a laboratory model for anxiety disorders. Interfering with such memories in humans would be of high clinical relevance. On the basis of studies in cell cultures and slice preparations, it is hypothesised that synaptic remodelling required for threat learning involves the extracellular enzyme matrix metalloproteinase (MMP) 9. However, in vivo evidence for this proposal is lacking. Here we investigate human Pavlovian fear conditioning under the blood-brain barrier crossing MMP inhibitor doxycyline in a pre-registered, randomised, double-blind, placebo-controlled trial. We find that recall of threat memory, measured with fear-potentiated startle 7 days after acquisition, is attenuated by ~60% in individuals who were under doxycycline during acquisition. This threat memory impairment is also reflected in increased behavioural surprise signals to the conditioned stimulus during subsequent re-learning, and already late during initial acquisition. Our findings support an emerging view that extracellular signalling pathways are crucially required for threat memory formation. Furthermore, they suggest novel pharmacological methods for primary prevention and treatment of posttraumatic stress disorder.Molecular Psychiatry advance online publication, 4 April 2017; doi:10.1038/mp.2017.65

Novel Primate Model of Serotonin Transporter Genetic Polymorphisms Associated with Gene Expression, Anxiety and Sensitivity to Antidepressants

This is the final version of the article. It first appeared from Nature Publishing Group via https://dx.doi.org/10.1038/npp.2016.41Genetic polymorphisms in the repeat upstream region of the serotonin transporter gene (SLC6A4) are associated with individual differences in stress reactivity, vulnerability to affective disorders and response to pharmacotherapy. However, the molecular, neurodevelopmental and psychopharmacological mechanisms underlying the link between SLC6A4 polymorphisms and the emotionally vulnerable phenotype are not fully understood. Thus, using the marmoset monkey Callithrix jacchus we characterize here a new neurobiological model to help to address these questions. We first sequenced the marmoset SLC6A4 promoter and identified a double nucleotide polymorphism (−2053AC/CT) and two single nucleotide polymorphisms (−2022C/T and −1592G/C) within the repeat upstream region. We showed their association with gene expression using in vivo quantitative PCR and with affective behavior using a primate test of anxiety (human intruder test). The low-expressing haplotype (AC/C/G) was linked with high anxiety whilst the high-expressing one (CT/T/C) was associated with an active coping strategy in response to threat. Pharmacological challenge with an acute dose of the selective serotonin reuptake inhibitor (SSRI), citalopram, revealed a genotype-dependent behavioral response. Whilst individuals homozygous for the high anxiety-related haplotype AC/C/G exhibited a dose-dependent, anxiogenic response, individuals homozygous for the low anxiety-related haplotype CT/T/C showed an opposing, dose-dependent anxiolytic effect. These findings provide a novel genetic and behavioral primate model to study the molecular, neurodevelopmental and psychopharmacological mechanisms that underlie genetic variation-associated complex behaviors, with specific implications for the understanding of normal and abnormal serotonin actions and the development of personalized pharmacological treatments for psychiatric disorders.Work was supported by an MRC Programme (ACR; G0901884) and performed within the Behavioural and Clinical Neuroscience Institute, University of Cambridge, funded jointly by the Wellcome Trust and MRC. AMS was supported by a McDonnell Foundation grant (PI’s: E. Phelps, T.W. Robbins; Co-Investigators: ACR and J. LeDoux; 22002015501) and currently supported by MRC; YS supported by the Long Term Student Support Program provided by Osaka University and the Ministry of Education, Culture, Sports, Science and Technology of Japan; HC supported by MRC Career Development Award and ACFS/MI supported by grants from the MRC and Wellcome Trust. GC supported by the Behavioural and Clinical Neuroscience Institute, Cambridge, United Kingdom. EHSS was self-funded

Effect of Citalopram on Emotion Processing in Humans:A Combined 5-HT [C]CUMI-101 PET and Functional MRI Study

A subset of patients started on a selective serotonin reuptake inhibitor (SSRI) initially experience increased anxiety, which can lead to early discontinuation before therapeutic effects are manifest. The neural basis of this early SSRI effect is not known. Presynaptic dorsal raphe neuron (DRN) 5-HT1A receptors are known to play a critical role in affect processing. Thus we investigated the effect of acute citalopram on emotional processing and the relationship between DRN 5-HT1A receptor availability and amygdala reactivity. Thirteen (mean age 48±9 years) healthy male subjects received either a saline or citalopram infusion intravenously (10 mg over 30 min) on separate occasions in a single-blind, random order, cross-over design. On each occasion, participants underwent a block design face-emotion processing task during fMRI known to activate the amygdala. Ten subjects also completed a positron emission tomography (PET) scan to quantify DRN 5-HT1A availability using [(11)C]CUMI-101.Citalopram infusion when compared to saline resulted in a significantly increased bilateral amygdala responses to fearful vs. neutral faces (Left p=0.025; Right p=0.038 FWE-corrected). DRN [(11)C]CUMI-101availability significantly positively correlated with the effect of citalopram on the left amygdala response to fearful faces (Z=2.51, p=0.027) and right amygdala response to happy faces (Z=2.33, p=0.032). Our findings indicate that the initial effect of SSRI treatment is to alter processing of aversive stimuli, and that this is linked to DRN 5-HT1A receptors in line with evidence that 5-HT1A receptors have a role in mediating emotional processing