Propagation of a Solitary Fission Wave

Reaction-diffusion phenomena are encountered in an astonishing array of natural systems. Under the right conditions, self stabilizing reaction waves can arise that will propagate at constant velocity. Numerical studies have shown that fission waves of this type are also possible and that they exhibit soliton like properties. Here, we derive the conditions required for a solitary fission wave to propagate at constant velocity. The results place strict conditions on the shapes of the flux, diffusive, and reactive profiles that would be required for such a phenomenon to persist, and this condition would apply to other reaction diffusion phenomena as well. Numerical simulations are used to confirm the results and show that solitary fission waves fall into a bistable class of reaction diffusion phenomena. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4729927]United States Nuclear Regulatory Commission NRC-38-08-946Mechanical Engineerin

Neural correlates of experimental trauma memory retrieval

OBJECTIVES Traumatic memories such as intrusions and flashbacks play a major role in the development and maintenance of post-traumatic stress disorder (PTSD). A thorough understanding of the neural mechanisms underlying traumatic memories is indispensable for precise diagnosis, for personalized treatment and prevention. In particular, the identification of early neural predictor variables for intrusion development shortly after trauma exposure requires detailed investigation. EXPERIMENTAL DESIGN Here, we examined the neural correlates of early experimental trauma memory retrieval in a traumatic film paradigm in 42 young healthy females, using both implicit and explicit retrieval tasks. PRINCIPAL OBSERVATIONS We show that implicit experimental trauma retrieval specifically involved the retrosplenial cortex and the anterior cingulate cortex (ACC), while both retrieval tasks resulted in trauma-related activity in the posterior cingulate cortex (PCC) and the precuneus. Importantly, neural activity early after experimental trauma exposure predicted later intrusion development, with independent contributions from activity in the retrosplenial cortex (implicit retrieval) and the PCC (explicit retrieval). Additional analyses revealed a stronger connectivity between the bilateral amygdala and the supplementary motor area, precentral and paracentral lobule for the control group compared to the experimental trauma group. CONCLUSIONS Our study gives new insights in the neural correlates of experimental trauma memory retrieval and their predictive value for subsequent symptom development. Our results could provide the basis for personalized early treatment and prevention of PTSD. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc. Hum Brain Mapp 38:3592-3602, 2017. © 2017 Wiley Periodicals, Inc

Detailing the effects of polypharmacy in psychiatry: longitudinal study of 320 patients hospitalized for depression or schizophrenia

Current treatment standards in psychiatry are oriented towards polypharmacy, that is, patients receive combinations of several antidepressants, antipsychotics, mood stabilizers, anxiolytics, hypnotics, antihistamines, and anticholinergics, along with other somatic treatments. In tandem with the beneficial effects of psychopharmacological drug treatment, patients experience significant adverse reactions which appear to have become more frequent and more severe with the rise of ubiquitous polypharmacy. In this study, we aimed to assess today's acute inpatient treatment of depressive and schizophrenic disorders with focus on therapeutic strategies, medications, adverse side effects, time course of recovery, and efficacy of treatments. Of particular interest was the weighing of the benefits and drawbacks of polypharmacy regimens. We recruited a total of 320 patients hospitalized at three residential mental health treatment centers with a diagnosis of either schizophrenic (ICD-10: "F2x.x"; n = 94; "F2 patients") or depressive disorders (ICD-10: "F3x.x"; n = 226; "F3 patients"). The study protocol included (1) assessment of previous history by means of the SADS Syndrome Check List SSCL-16 (lifetime version); (2) repeated measurements over 5 weeks assessing the time course of improvement by the Hamilton Depression Scale HAM-D and the Positive and Negative Syndrome Scale PANSS, along with medications and adverse side effects through the Medication and Side Effects Inventory MEDIS; and (3) the collection of blood samples from which DNA and serum were extracted. Polypharmacy was by far the most common treatment regimen (85%) in this study. On average, patients received 4.50 ± 2.68 medications, consisting of 3.30 ± 1.84 psychotropic drugs, plus 0.79 ± 1.13 medications that alleviate adverse side effects, plus 0.41 ± 0.89 other somatic medications. The treating psychiatrists appeared to be the main determining factor in this context, while «previous history» and «severity at baseline» played a minor role, if at all. Adverse drug reactions were found to be an inherent component of polypharmacy and tended to have a 2-3 times higher incidence compared to monotherapy. Severe adverse reactions could not be attributed to a particular drug or drug combination. Rather, the empirical data suggested that severe side effects can be triggered by virtually all combinations of drugs, provided patients have a respective vulnerability. In terms of efficacy, there were no advantages of polypharmacy over monotherapy. The results of this study underlined the fact that polypharmacy regimens are not equally suited for every patient. Specifically, such regimens appeared to have a negative impact on treatment outcome and to obfuscate the "natural" time course of recovery through a multitude of interfering factors. Evidence clearly speaks against starting just every therapeutic intervention in psychiatry with a combination of psychopharmaceuticals. We think that it is time for psychiatry to reconsider its treatment strategies, which are far too one-sidedly fixated on psychopharmacology and pay far too little attention to alternative approaches, especially in mild cases where psychotherapy without concurrent medication should still be an option. Also, regular exercises and sports can definitely be an effective therapeutic means in a considerable number of cases. General practitioners (GPs) are particularly in demand here

Illusory Body Ownership Affects the Cortical Response to Vicarious Somatosensation

Fundamental human feelings such as body ownership (“this” body is “my” body) and vicariousness (first-person-like experience of events occurring to others) are based on multisensory integration. Behavioral links between body ownership and vicariousness have been shown, but the neural underpinnings remain largely unexplored. To fill this gap, we investigated the neural effects of altered body ownership on vicarious somatosensation. While recording functional brain imaging data, first, we altered participants’ body ownership by robotically delivering tactile stimulations (“tactile” stroking) in synchrony or not with videos of a virtual hand being brushed (“visual” stroking). Then, we manipulated vicarious somatosensation by showing videos of the virtual hand being touched by a syringe’s plunger (touch) or needle (pain). Only after the alteration of body ownership (synchronous visuo-tactile stroking) and specifically during late epochs of vicarious somatosensation, vicarious pain was associated with lower activation in premotor and anterior cingulate cortices with respect to vicarious touch. At the methodological level, the present study highlights the importance of the neural response’s temporal evolution. At the theoretical level, it shows that the higher-level (cognitive) impact of a lower-level (sensory) body-related processing (visuo-tactile) is not limited to body ownership but also extends to other psychological body-related domains, such as vicarious somatosensation

Ketamine decreases resting state functional connectivity between networks via the dorsal nexus: implications for major depression

Question: Increasing preclinical and clinical evidence underscores the strong and rapid antidepressant properties of the glutamate modulating NMDA receptor antagonist ketamine [1, 2]. Targeting the glutamatergic system might thus provide a novel therapeutic strategy for antidepressant drug treatment [3]. Since glutamate is the most abundand and major excitatory neurotransmitter in the human brain, pathophysiological changes in glutamatergic signalling are likely to affect neurobehavioural plasticity, information processing and large-scale changes in functional brain connectivity underlying certain symptoms of major depressive disorder (MDD) [4]. Using resting state functional MRI (rsfMRI), the „dorsal nexus“ (DN) was recently identified as a bilateral dorsal medial prefrontal cortex (DMPFC) region showing dramatically increased depression-associated fMRI connectivity with large portions of the cognitive control network (CCN), the default mode network (DMN), and the affective network (AN) [5]. Hence, Sheline and colleagues [5] proposed that reducing increased connectivity of the DN might play a critical role in reducing depressive symptomatology and thus represent a potential therapeutic target for affective disorders. Since little is known about how ketamine affects large-scale neural network dynamics in the human brain, we aimed to test the hypothesis that ketamine as an antidepressant glutamatergic agent decreases resting state connectivties via the DN. Methods: Study design: 17 healthy subjects (mean age, 40.5 +/- 7.5 [SD]; 9 males) completed four resting state fMRI sessions in a double-blind, randomized, crossover study design (s. Fig 1). The baseline scan was followed by an intravenous infusion (45 mins) of either S-ketamine (0.25 mg/kg) or placebo (saline) outside the scanner. Since the antidepressant effect of ketamine is most prominent after one day [1], the followup scans were scheduled 24 hours after the ketamine or placebo infusion in order to assess the mid-term effects on neuronal network dynamics that might contribute to its antidepressant efficacy. To avoid a possible carry-over effect, the time lag between the two baseline measurements was set to at least 10 days. rsfMRI data acquisition and analysis: Measurements were performed on a Philips Achieva TX 3-T whole-body MR unit equipped with an 8-channel SENSE head coil. During each session a total of 200 functional images were collected in 10 minute runs (eyes closed) using the following acquisition parameters: TE = 35 ms, TR = 3000 ms (θ = 82°), FOV = 22 cm, acquisition matrix = 80 x 80 interpolated to 128 x 128, voxel size = 2.75 x 2.75 x 4 mm, 32 contiguous axial slices (placed along the anterior-posterior commissure plane), and sensitivity-encoded acceleration factor R = 2.0. A 3-dimensional T1-weighted anatomical scan was obtained for structural reference. Data were analyzed using the SPM8 (Wellcome Trust Center for Neuroimaging, London, England) based data processing assistant for resting state fMRI (DPARSF, by Yan Chao-Gan et al.) which includes a resting state fMRI data analysis toolkit (REST, by Song Xiao-Wei et al.). The postprocessing steps followed the standard protocol described by Yan and Zang (2010) [6]. Results: To test our hypothesis, we created a seed region of interest in the left and right DMPFC (10 mm sphere at ± 6 51 24) representing the DN. 24 h following ketamine administration, functional connectivity was exclusively reduced to the posterior cingulate cortex (PCC), to the subgenual anterior cingulate cortex (sgACC), and to anterior and mediodorsal parts of the thalamus (compared to placebo). The backprojection from a seed in the PCC confirmed these results and revealed an additional significant reduction of functional connectivity to the pregenual ACC (PACC) and medioprefrontal cortex (MPFC). For details, see Fig. 2 A, B and bar diagrams (functional connectivity change, paired t tests). Conclusion: While pharmacological effects of ketamine on task induced fMRI BOLD signals have been studied extensively, this is the first randomized, placebo-controlled, double-blind, crossover study demonstrating changes in resting state functional connectivity in response to ketamine administration in healthy subjects. Here, we report a significant decrease in functional connectivity of the sgACC (AN) and the PCC (DMN) via the DN 24 hours following ketamine administration, thus reflecting a neuronal pattern of normalization with regard to MDD where increased connectivities of the AN and DMN via the DN have been observed [5]. As critical hub of the AN, the sgACC plays an important role in mood regulation. Subgenual cortical activity was shown to be elevated in MDD and effective antidepressant treatment was associated with a reduction in sgACC activity [for review see ref. 7]. In addition, the observed reduction in functional connectivity between anterior (PACC/MPFC) and posterior parts of the DMN (PCC) may partially reverse the disrupted neurobehavioral homeostasis in MDD where a failure to normally down-regulate activity within the DMN during emotional stimulation was found [8], with increasing levels of DMN dominance being associated with higher levels of maladaptive, depressive rumination and lower levels of adaptive, reflective rumination [9]. Finally, reductions in cortico-thalamic connectivity may reflect functional alterations in thalamocortical loops via the prefrontal cortex. Based on the fact that the antidepressant effect of ketamine peaks one day after a single intravenous administration [1], we conclude that pharmacologically reducing the hyperconnectivity via the DN may play a critical role in reducing depressive symptomatology and in representing a systems level mechanism of treatment response for major depression

Cerebral mGluR5 availability contributes to elevated sleep need and behavioral adjustment after sleep deprivation.

Increased sleep time and intensity quantified as low-frequency brain electrical activity after sleep loss demonstrate that sleep need is homeostatically regulated, yet the underlying molecular mechanisms remain elusive. We here demonstrate that metabotropic glutamate receptors of subtype 5 (mGluR5) contribute to the molecular machinery governing sleep-wake homeostasis. Using positron emission tomography, magnetic resonance spectroscopy, and electroencephalography in humans, we find that increased mGluR5 availability after sleep loss tightly correlates with behavioral and electroencephalographic biomarkers of elevated sleep need. These changes are associated with altered cortical myo-inositol and glycine levels, suggesting sleep loss-induced modifications downstream of mGluR5 signaling. Knock-out mice without functional mGluR5 exhibit severe dysregulation of sleep-wake homeostasis, including lack of recovery sleep and impaired behavioral adjustment to a novel task after sleep deprivation. The data suggest that mGluR5 contribute to the brain's coping mechanisms with sleep deprivation and point to a novel target to improve disturbed wakefulness and sleep

Normalizing effect of heroin maintenance treatment on stress-induced brain connectivity

A single dose of heroin can reduce stress responses in heroin-dependent patients. Schmidt et al. report that increased amygdala-related functional connectivity during fearful face processing in heroin-dependent patients transiently normalises after a single dose of heroin. This measure may help to assess the efficacy of maintenance treatments in drug addictio

The Impact of COVID-19 on Mental Healthcare Utilization in Switzerland Was Strongest Among Young Females—Retrospective Study in 2018–2020

Objectives: To provide a thorough assessment of the impact of the COVID-19 pandemic on the utilization of inpatient and outpatient mental healthcare in Switzerland. Methods: Retrospective cohort study using nationwide hospital data (n > 8 million) and claims data from a large Swiss health insurer (n > 1 million) in 2018–2020. Incidence proportions of different types of psychiatric inpatient admissions, psychiatric consultations, and psychotropic medication claims were analyzed using interrupted time series models for the general population and for the vulnerable subgroup of young people. Results: Inpatient psychiatric admissions in the general population decreased by 16.2% (95% confidence interval: −19.2% to −13.2%) during the first and by 3.9% (−6.7% to −0.2%) during the second pandemic shutdown, whereas outpatient mental healthcare utilization was not substantially affected. We observed distinct patterns for young people, most strikingly, an increase in mental healthcare utilization among females aged <20 years. Conclusion: Mental healthcare provision for the majority of the population was largely maintained, but special attention should be paid to young people. Our findings highlight the importance of monitoring mental healthcare utilization among different populations

Sex differences in neurodevelopmental and common mental disorders examined from three epidemiological perspectives.

Sex differences in neurodevelopmental and common mental disorders are a ubiquitous, well-known, though poorly understood phenomenon. This study examined the issue from three epidemiological perspectives: congruence in age of onset, distribution of sex-ratios with respect to age of onset and similarity of comorbidity and risk factor patterns. The analysis was based on data from the population-based PsyCoLaus study (N = 4874, age 35-82 y). Congruence in age of onset and distribution of sex-ratios were examined with the Mann-Whitney test and cluster analysis. The similarity of comorbidity and risk factor patterns, which were represented by 35 variables, was assessed with the Jaccard coefficient and, after factor analysis, with Tucker's congruence coefficient. While age of onset parameters differed little by sex, the sex ratio varied markedly both in early and in late onset disorders. Moreover, the Jaccard coefficients for most disorders indicated that the similarity of comorbidity and further association patterns was low. Similarly, Tucker's congruence coefficient remained below the range of fair similarity in all factor combinations. In sum, sex differences in common mental disorders were impressively reflected by diverging sex ratios and comorbidity / risk factor patterns. This outcome supports the notion that most mental disorders need a sex-specific etiopathogenetic understanding

Urinary concentrations of GHB and its novel amino acid and carnitine conjugates following controlled GHB administration to humans

Gamma-hydroxybutyrate (GHB) remains a challenging clinical/forensic toxicology drug. Its rapid elimination to endogenous levels mainly causes this. Especially in drug-facilitated sexual assaults, sample collection often occurs later than the detection window for GHB. We aimed to investigate new GHB conjugates with amino acids (AA), fatty acids, and its organic acid metabolites for their suitability as ingestion/application markers in urine following controlled GHB administration to humans. We used LC–MS/MS for validated quantification of human urine samples collected within two randomized, double-blinded, placebo-controlled crossover studies (GHB 50 mg/kg, 79 participants) at approximately 4.5, 8, 11, and 28 h after intake. We found significant differences (placebo vs. GHB) for all but two analytes at 4.5 h. Eleven hours post GHB administration, GHB, GHB-AAs, 3,4-dihydroxybutyric acid, and glycolic acid still showed significantly higher concentrations; at 28 h only GHB-glycine. Three different discrimination strategies were evaluated: (a) GHB-glycine cut-off concentration (1 µg/mL), (b) metabolite ratios of GHB-glycine/GHB (2.5), and (c) elevation threshold between two urine samples (> 5). Sensitivities were 0.1, 0.3, or 0.5, respectively. Only GHB-glycine showed prolonged detection over GHB, mainly when compared to a second time- and subject-matched urine sample (strategy c)