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Background: This is the first report of the pharmacodynamic (PD) effects of the selective, potent and brain-penetrant P2X7 receptor (P2X7R) antagonist JNJ-54175446. Activation of the P2X7R, an adenosine triphosphate-gated ion channel, leads to the production of pro-inflammatory cytokines, which have been linked to neuroinflammation and play a role in the pathogenesis of mood disorders. Previous clinical studies with JNJ-54175446 demonstrated peripheral target engagement of JNJ-54175446 by assessing ex vivo lipopolysaccharide (LPS)-stimulated cytokine production. Blood-brain barrier penetration and a clear dose-receptor occupancy relationship was demonstrated using positron emission tomography.Aims: The objectives of this double-blind, placebo-controlled, translational study were to assess the safety and tolerability of administering multiple doses of JNJ-54175446 and to explore its PD effects using a dexamphetamine challenge.Methods: Subjects (N = 64) were randomised to either JNJ-54175446 (50-450 mg; n = 48) or placebo (n = 16) and underwent a baseline oral 20 mg dexamphetamine challenge followed by 11 consecutive days q.d. dosing with JNJ-54175446/placebo and a randomised crossover dexamphetamine/placebo challenge.Results: At all doses tested, JNJ-54175446 was well tolerated and suppressed the ex vivo LPS-induced release of cytokines. At doses ⩾100 mg, JNJ-54175446 attenuated dexamphetamine-induced increases in locomotion and enhanced the mood-elevating effects of dexamphetamine, suggesting that a dose that is approximately twice as high is needed to obtain a central PD response compared to the dose needed for maximum peripheral occupancy.Conclusion: Overall, the observed pharmacological profile of JNJ-54175446 in the dexamphetamine challenge paradigm is compatible with a potential mood-modulating effect. [ABSTRACT FROM AUTHOR]

Abstract Numerous novel neuroscience-based drug targets have been identified in recent years. However, it remains unclear how these targets relate to the expression of symptoms in central nervous system (CNS) disorders in general and psychiatric disorders in particular. To discuss this issue, a New Frontiers Meetings of European College of Neuropsychopharmacology (ECNP) was organized to address the challenges in translational neuroscience research that are impeding the effective development of new treatments. The main aim of this meeting was to discuss scientific insights, concepts and methodologies in order to improve drug development for psychiatric disorders. The meeting was designed to bring together stakeholders from academia, pharmaceutical industry, and regulatory agencies. Here we provide a synopsis of the proceedings from the meeting entitled ‘New approaches to psychiatric drug development’. New views on psychiatric drug development were presented to address the challenges and pitfalls as identified by the different stakeholders. The general conclusion of the meeting was that drug discovery could be stimulated by designing new classification and sensitive assessment tools for psychiatric disorders, which bear closer relationships to neuropharmacological and neuroscientific developments. This is in line with the vision of precision psychiatry in which patients are clustered, not merely on symptoms, but primarily on biological phenotypes that represent pathophysiological relevant and ‘drugable’ processes. To achieve these goals, a closer collaboration between all stakeholders in early stages of development is essential to define the research criteria together and to reach consensus on new quantitative biological methodologies and etiology-directed treatments. [ABSTRACT FROM AUTHOR]

Pre-registration nursing and midwifery students are under considerable pressure to acquire the necessary information technology (IT) skills by the time they embark on a professional nursing career. There is a multitude of research findings detailing the use of computer-based learning materials, IT training initiatives and how such materials are beneficial to learners. There is, however, relatively little in terms of the extent to which students are given the opportunity to use such skills during study periods over an extended period of time. This paper explores related issues by presenting the results of a study into the extent to which a cohort of undergraduate nursing and midwifery students retained and applied IT knowledge six months after the initial training period. The results reveal an interesting disparity between the skills taught and their retention and use in practice. Concerns are raised over the risk of such skills being forgotten by the time students enter professional nursing careers. [ABSTRACT FROM AUTHOR]

Background and Objective: Psilocybin is currently being extensively studied as a potential therapeutic agent for multiple psychiatric disorders. Here, a systematic literature review of all published pharmacokinetic data on the pharmacologically active metabolite of psilocybin, psilocin, is presented., Methods: The review includes clinical studies that reported pharmacokinetic data and/or parameters after psilocybin administration in humans. In addition, raw pharmacokinetic data from these studies was requested and/or extracted to further compare results across studies., Results: In total, 309 publications were identified, of which 19 publications were ultimately included, which covered 12 unique clinical datasets. Except for one study that investigated intravenous psilocybin, all included studies administered psilocybin orally. Psilocybin acts as a pro-drug and is rapidly absorbed and transformed to psilocin after oral administration. In the majority of studies, unconjugated psilocin was measured while some also measured conjugated and total concentrations. Psilocin's biphasic concentration-time profiles demonstrates fast and extensive disposition with an apparent distribution volume of 505-1267 L and a terminal half-life of 1.23-4.72 h. Only 1.5-3.4% of the dose is excreted as psilocin in urine. Psilocin is mainly transformed to 4-hydroxyindole-3-acetic acid and in less amounts to conjugated psilocin, where 4-hydroxyindole-3-acetic acid formation may occur prior to systemic psilocin absorption. Information on the absolute bioavailability of psilocin was limited, and estimated at 55% in one study. No covariates nor food effects have been reported, based on four studies with known fasting status., Conclusions: Overall, we found the pharmacokinetic parameters of psilocin to be consistent between studies. This review may guide the further clinical development of psilocybin-based therapies., Competing Interests: Declarations. Funding: No funding was received to conduct this study or prepare this article. Conflicts of Interest/Competing Interests: Marije E. Otto, Katelijne V. van der Heijden, Jan W. Schoones, Michiel J. van Esdonk, Laura G.J.M. Borghans, Gabriel E. Jacobs and Coen J.G. van Hasselt have no conflicts of interest that are directly relevant to the content of this article. Ethics Approval: Not applicable. Consent to Participate: Not applicable. Consent for Publication: Not applicable. Availability of Data and Material: Data presented in this study were acquired from authors upon request or extracted from published reports, which have been referenced. Gathered data therefore are not directly available from the authors, but may be available upon request of the referred authors. Code Availability: Code is available upon request. Authors’ Contributions: MEO and KVvH designed the study, searched, acquired and analysed the data, and drafted the manuscript. JWS designed the search strategy and searched the literature. JWS MJvE, LGJMB, GJ and JGCvH critically reviewed the manuscript. All authors read and approved the final version of the manuscript., (© 2025. The Author(s).)

Paired petrography and acid maceration has shown that preferential silicification of shelly faunas can bias recovery based on taxon and body size. Here, silicified fossils from the Upper Ordovician Edinburg Formation, Strasburg Junction, Virginia, USA, were analyzed using X-ray tomographic microscopy (μCT) in conjunction with recovered residues from acid maceration of the same materials to further examine sources of potential bias. Results reveal that very small (<~1 mm) fossils are poorly resolved in μCT when scanning at lower resolutions (~30 µm), underestimating abundance of taxa including ostracods and bryozoans. Acid maceration, meanwhile, fails to recover poorly silicified fossils prone to disarticulation and/or fragmentation during digestion. Tests for patterns of breakage, however, indicate no significant size or taxonomic bias during extraction. Comparisons of individual fossils from 3-D fossil renders and maceration residues reveal patterns of fragmentation that are taxon-specific and allow the differentiation of biostratinomic and preparational breakage. Multivariate ordinations and cluster analyses of μCT and residue data in general produce concordant results but indicate that the variation in taxonomic composition of our samples is compromised by the resolvability of small size classes in μCT imaging, limiting the utility of this method for addressing paleoecological questions in these specific samples. We suggest that comparability of results will depend strongly on the sample size, taphonomic history, textural, and compositional characteristics of the samples in question, as well as μCT scan parameters. Additionally, applying these methods to different deposits will test the general applicability of the conclusions drawn on the relative strengths and weaknesses of the methods., Competing Interests: The authors declare that they have no competing interests., (© 2024 Jacobs et al.)

JNJ-54175446 is a selective purine P2X7 receptor (P2X7R) antagonist that attenuates microglial IL-1β/IL-18 release. In healthy volunteers, JNJ-54175446 suppressed peripheral interleukin (IL)-1β release, and attenuated dexamphetamine-induced improvements of mood and (visuo)motor performance in a human dexamphetamine-challenge paradigm. In depression, P2X7R inhibition may dampen immune-related dysregulation of mood. These results suggest that the impact of P2X7R inhibition is most prominent in situations where mood regulation is disrupted. Total sleep deprivation (TSD) results in an acute emotional perturbation, which yields a transient antidepressant effect. In the current study, TSD was applied as a behavioral challenge to investigate whether such effects could be modulated by JNJ-54175446. This was a double-blind, placebo-controlled, randomized study to assess the safety and pharmacokinetics of JNJ-54175446 and explore its effects in patients with single episode and recurrent major depressive disorder (MDD) (N = 69) and baseline total Inventory of Depressive Symptomatology Clinician Rated (IDS-C) > 30. Patients were randomized to receive JNJ-54175446 throughout the 10-day treatment period, placebo for days 1-3 followed by JNJ-54175446 or placebo throughout. All patients underwent 36 h of TSD starting on day three until the evening of day four. The early start group was hypothesized to experience a reduced effect from TSD whilst the late starting group was hypothesized to experience prolonged effects from the TSD. JNJ-54175446 was well-tolerated and adverse events were mild to moderate. JNJ-54175446 reduced IL-1β release by LPS-stimulated peripheral white blood cells in the presence of the P2X receptor agonist benzyl adenosine triphosphate (BzATP). JNJ-54175446 did not have a significant effect on mood as assessed using the Hamilton Depression Rating Scale, 17 items (HDRS17) and the Self-rated Quick Inventory of Depressive Symptoms (QIDS-SR). However, JNJ-54175446 blunted an acute reduction of anhedonia that occurred as a result of TSD, assessed by the Snaith-Hamilton Pleasure Scale (SHAPS) and the Probabilistic Instrumental Learning Task (PILT)., (© 2023. The Author(s).)

Major depressive disorder (MDD) is a multifactorial psychiatric disorder with obscure pathophysiology. A biomarker-based approach in combination with standardized interview-based instruments is needed to identify MDD subtypes and novel therapeutic targets. Recent findings support the impairment of the mammalian target of rapamycin complex 1 (mTORC1) in MDD. No well-established biomarkers of mTORC1 disease- and treatment-modulated activity are currently available for use in early phase antidepressant drug (AD) development. This review aims to summarize biomarkers of mTORC1 activity in MDD and to suggest how these could be implemented in future early clinical trials on mTORC1 modulating ADs. Therefore, a PubMed-based narrative literature review of the mTORC1 involvement in MDD was performed. We have summarized recent pre-clinical and clinical findings linking the MDD to the impaired activity of several key biomarkers related to mTORC1. Also, cases of restoration of these impairments by classical ADs and novel fast-acting investigational ADs are summarized. The presented biomarkers may be used to monitor pharmacological effects by novel rapid-acting mTORC1-targeting ADs. Based on findings in the peripheral blood mononuclear cells, we argue that those may serve as an ex vivo model for evaluation of mTORC1 activity and propose the use of the summarized biomarkers for this purpose. This could both facilitate the selection of a pharmacodynamically active dose and guide future early clinical efficacy studies in MDD. In conclusion, this review provides a blueprint for the rational development of rapid-acting mTORC1-targeting ADs., Competing Interests: Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2021.)

TAK-653 is a novel α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-positive allosteric modulator being developed as a potential therapeutic for major depressive disorder (MDD). Currently, there are no translational biomarkers that evaluate physiological responses to the activation of glutamatergic brain circuits available. Here, we tested whether noninvasive neurostimulation, specifically single-pulse or paired-pulse motor cortex transcranial magnetic stimulation (spTMS and ppTMS, respectively), coupled with measures of evoked motor response captures the pharmacodynamic effects of TAK-653 in rats and healthy humans. In the rat study, five escalating TAK-653 doses (0.1-50 mg/kg) or vehicle were administered to 31 adult male rats, while measures of cortical excitability were obtained by spTMS coupled with mechanomyography. Twenty additional rats were used to measure brain and plasma TAK-653 concentrations. The human study was conducted in 24 healthy volunteers (23 males, 1 female) to assess the impact on cortical excitability of 0.5 and 6 mg TAK-653 compared with placebo, measured by spTMS and ppTMS coupled with electromyography in a double-blind crossover design. Plasma TAK-653 levels were also measured. TAK-653 increased both the mechanomyographic response to spTMS in rats and the amplitude of motor-evoked potentials in humans at doses yielding similar plasma concentrations. TAK-653 did not affect resting motor threshold or paired-pulse responses in humans. This is the first report of a translational functional biomarker for AMPA receptor potentiation and indicates that TMS may be a useful translational platform to assess the pharmacodynamic profile of glutamate receptor modulators.

Background: Digital technologies have the potential to provide objective and precise tools to detect depression-related symptoms. Deployment of digital technologies in clinical research can enable collection of large volumes of clinically relevant data that may not be captured using conventional psychometric questionnaires and patient-reported outcomes. Rigorous methodology studies to develop novel digital endpoints in depression are warranted. Objective: We conducted an exploratory, cross-sectional study to evaluate several digital technologies in subjects with major depressive disorder (MDD) and persistent depressive disorder (PDD), and healthy controls. The study aimed at assessing utility and accuracy of the digital technologies as potential diagnostic tools for unipolar depression, as well as correlating digital biomarkers to clinically validated psychometric questionnaires in depression. Methods: A cross-sectional, non-interventional study of 20 participants with unipolar depression (MDD and PDD/dysthymia) and 20 healthy controls was conducted at the Centre for Human Drug Research (CHDR), the Netherlands. Eligible participants attended three in-clinic visits (days 1, 7, and 14), at which they underwent a series of assessments, including conventional clinical psychometric questionnaires and digital technologies. Between the visits, there was at-home collection of data through mobile applications. In all, seven digital technologies were evaluated in this study. Three technologies were administered via mobile applications: an interactive tool for the self-assessment of mood, and a cognitive test; a passive behavioral monitor to assess social interactions and global mobility; and a platform to perform voice recordings and obtain vocal biomarkers. Four technologies were evaluated in the clinic: a neuropsychological test battery; an eye motor tracking system; a standard high-density electroencephalogram (EEG)-based technology to analyze the brain network activity during cognitive testing; and a task quantifying bias in emotion perception. Results: Our data analysis was organized by technology - to better understand individual features of various technologies. In many cases, we obtained simple, parsimonious models that have reasonably high diagnostic accuracy and potential to predict standard clinical outcome in depression. Conclusion: This study generated many useful insights for future methodology studies of digital technologies and proof-of-concept clinical trials in depression and possibly other indications., Competing Interests: OS, JC, KH, LG, VD, FA, JP, VV, AD, BG-M, KB, MD, and J-HC were employed by Novartis. FC was employed by Cambridge Cognition. JA was employed by Neurotrack Technologies, Inc. ZP, GI, and OL were employed by ElMindA, Ltd. DJ was employed by Sonde Health, Inc. AZ, RZ, KR, ZZ, and GJ were employed by CHDR. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sverdlov, Curcic, Hannesdottir, Gou, De Luca, Ambrosetti, Zhang, Praestgaard, Vallejo, Dolman, Gomez-Mancilla, Biliouris, Deurinck, Cormack, Anderson, Bott, Peremen, Issachar, Laufer, Joachim, Jagesar, Jongs, Kas, Zhuparris, Zuiker, Recourt, Zuilhof, Cha and Jacobs.)

Orexin neurons originating in the perifornical and lateral hypothalamic area project to anxiety- and panic-associated neural circuitry, and are highly reactive to anxiogenic stimuli. Preclinical evidence suggests that the orexin system, and particularly the orexin-1 receptor (OX1R), may be involved in the pathophysiology of panic and anxiety. Selective OX1R antagonists thus may constitute a potential new treatment strategy for panic- and anxiety-related disorders. Here, we characterized a novel selective OX1R antagonist, JNJ-61393215, and determined its affinity and potency for human and rat OX1R in vitro. We also evaluated the safety, pharmacokinetic, and pharmacodynamic properties of JNJ-61393215 in first-in-human single- and multiple-ascending dose studies conducted. Finally, the potential anxiolytic effects of JNJ-61393215 were evaluated both in rats and in healthy men using 35% CO 2 inhalation challenge to induce panic symptoms. In the rat CO 2 model of panic anxiety, JNJ-61393215 demonstrated dose-dependent attenuation of CO 2 -induced panic-like behavior without altering baseline locomotor or autonomic activity, and had minimal effect on spontaneous sleep. In phase-1 human studies, JNJ-61393215 at 90 mg demonstrated significant reduction (P < 0.02) in CO 2 -induced fear and anxiety symptoms that were comparable to those obtained using alprazolam. The most frequently reported adverse events were somnolence and headache, and all events were mild in severity. These results support the safety, tolerability, and anxiolytic effects of JNJ-61393215, and validate CO 2 exposure as a translational cross-species experimental model to evaluate the therapeutic potential of novel anxiolytic drugs.

This research was planned to build a Pharmacokinetic/Pharmacodynamic (PK/PD) model of 5-hydroxytryptophan (5-HTP) challenge study including a circadian rhythm component of cortisol and to predict serum cortisol based on saliva cortisol. Data from three 5-HTP challenge studies in healthy volunteers were collected. Serum 5-HTP, saliva, and serum cortisol were sampled as PK and PD marker. The population PK/PD modeling approach was applied. A baseline model of serum cortisol was built to assess the circadian rhythm before a pharmacodynamic model was used to evaluate the drug effect of the 5-HTP on cortisol. Finally, linear and power function relationships were tested to predict serum cortisol based on saliva cortisol. The PK of 5-HTP could be described using a one-compartment model with a transit compartment. The typical value for clearance was 20.40 L h -1 and showed inter-study variability. A cosine function was chosen and properly described the circadian rhythm of serum cortisol. A linear approximation model was applied to fit the 5-HTP PD effect on cortisol data with a slope of 4.16 ng mL -1  h. A power function provided a better description than a linear function to relate the saliva and serum cortisol. In conclusion, a circadian rhythm component was built in the PK/PD model of the 5-HTP challenge test which could better improve the understanding of the stimulating effect on HPA with cortisol change. After the 5-HTP challenge, saliva cortisol correlated well with serum cortisol and was predictable by a population PK-PD model., (© 2020 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.)

Excessive arousal has a role in the pathophysiology of major depressive disorder (MDD). Seltorexant (JNJ-42847922/MIN-202) is a selective antagonist of the human orexin-2 receptor (OX2R) that may normalize excessive arousal and thereby attenuate depressive symptoms. In this study, the effects of night-time arousal suppression on depressive symptoms were investigated. 47 MDD patients with a total Inventory of Depressive Symptomatology (IDS) score of ≥30 at screening were included in a randomized, double-blind, diphenhydramine-, and placebo-controlled multicentre study. Symptoms of depression were rated using the 17-item Hamilton Depression Rating Scale (HDRS 17 ). Effects on sleep were evaluated by polysomnography and by the Leeds Sleep Evaluation Questionnaire (LSEQ). To investigate the safety and tolerability of seltorexant, vital signs, suicidal ideation and adverse events were monitored. At baseline the severity of depressive symptoms correlated with sleep efficiency (SE), wake after sleep onset (WASO), duration of stage 2 sleep, and ruminations. Ten days of treatment with seltorexant (and not diphenhydramine) resulted in a significant improvement of core depressive symptoms compared to placebo; the antidepressant efficacy of seltorexant was maintained with continued treatment up to 28 days. Compared to placebo, the antidepressant efficacy of seltorexant coincided with an overall increase in (left posterior) EEG power and a relative increase in delta- and decrease in theta-, alpha- and beta power during stage 2 sleep. Treatment with seltorexant was associated with mild, self-limiting adverse drug reactions. Seltorexant affected core symptoms of depression in the absence of overt changes in the hypnogram; in contrast, diphenhydramine was not efficacious.

Anxiety disorders arise from disruptions among the highly interconnected circuits that normally serve to process the streams of potentially threatening stimuli. The resulting imbalance among these circuits can cause a fundamental misinterpretation of neural sensory information as threatening and can lead to the inappropriate emotional and behavioral responses observed in anxiety disorders. There is considerable preclinical evidence that the GABAergic system, in general, and its α2- and/or α5-subunit-containing GABA(A) receptor subtypes, in particular, are involved in the pathophysiology of anxiety disorders. However, the clinical efficacy of GABA-A α2-selective agonists for the treatment of anxiety disorders has not been unequivocally demonstrated. In this review, we present several human pharmacological studies that have been performed with the aim of identifying the pharmacologically active doses/exposure levels of several GABA-A subtype-selective novel compounds with potential anxiolytic effects. The pharmacological selectivity of novel α2-subtype-selective GABA(A) receptor partial agonists has been demonstrated by their distinct effect profiles on the neurophysiological and neuropsychological measurements that reflect the functions of multiple CNS domains compared with those of benzodiazepines, which are nonselective, full GABA(A) agonists. Normalizing the undesired pharmacodynamic side effects against the desired on-target effects on the saccadic peak velocity is a useful approach for presenting the pharmacological features of GABA(A)-ergic modulators. Moreover, combining the anxiogenic symptom provocation paradigm with validated neurophysiological and neuropsychological biomarkers may provide further construct validity for the clinical effects of novel anxiolytic agents. In addition, the observed drug effects on serum prolactin levels support the use of serum prolactin levels as a complementary neuroendocrine biomarker to further validate the pharmacodynamic measurements used during the clinical pharmacological study of novel anxiolytic agents.

Background: Valproic acid is one of the most widely prescribed drugs for the treatment of epilepsy and bipolar disorder. As only the unbound fraction of a medicinal product is pharmacologically active, in some strong protein-bound psychotropic drugs such as valproic acid and phenytoin, a rise in this fraction can lead to severe toxicity., Case Description: A 65-year-old male with a type 1 bipolar disorder developed a number of neurological symptoms including sluggishness, muscle weakness, difficulty in walking and disorders of micturition after his mood stabiliser was changed to valproic acid. Recognition of drug toxicity was delayed as his total plasma valproic acid levels were within the therapeutic range. Later it became apparent that the patient had toxic unbound valproic acid levels due to hypoalbuminaemia and impaired renal function., Conclusion: Clinicians should always consider drug toxicity in patients who show neurological symptoms and use highly protein-bound psychotropic drugs, even if the total plasma concentration of the drug is in the therapeutic range.

Cancer cell fusion was suggested as a mechanism of metastasis about a century ago. Since then, many additional modes of material transfer (i.e., tunneling nanotubes, and exosomes) to generate cell hybrids have been identified. However, studies documenting spontaneous tumor hybrid formation in vivo as a mechanism that enables metastasis are still lacking. Here, we tested whether spontaneous hybrid formation in vivo contributes to bona fide metastatic tumors. We first used single cell RNASeq to analyze the gene expression profile of spontaneously formed cancer cell-stromal hybrids, and results revealed that hybrids exhibit a clustering pattern that is distinct from either parental cell and suggestive of substantial diversity of individual hybrids. Despite the newly gained diversity, hybrids can retain expression of critical genes of each parental cell. To assess the biological impact of cancer cell hybrids in vivo , we transfected murine mammary tumor cells, isolated from FVB/N-Tg(MMTV-PyVT)634Mul/J mice (PyVT) with Cre recombinase prior to injection to the murine fat pad of FVB.129S6(B6)- Gt(ROSA)26Sor tm 1 (Luc)Kael /J mice such that luciferase expression is induced with hybrid formation; luciferase expression was tracked for up to four months. We observed that hybrid formation occurs spontaneously in vivo and that a significantly higher number of hybrids reside in metastases compared to the primary tumor, supporting the possibility that hybrids can emerge from the primary tumor and proliferate to help create a new tumor at a distant site. Additional studies are now warranted to delineate the mechanisms of cancer cell hybrid transit to metastases since drugs to inhibit hybrid formation might prevent metastatic spread.

Motor imagery-based brain-computer interface (BCI) using electroencephalography (EEG) has demonstrated promising applications by directly decoding users' movement related mental intention. The selection of control signals, e.g., the channel configuration and decoding algorithm, plays a vital role in the online performance and progressing of BCI control. While several offline analyses report the effect of these factors on BCI accuracy for a single session-performance increases asymptotically by increasing the number of channels, saturates, and then decreases-no online study, to the best of our knowledge, has yet been performed to compare for a single session or across training. The purpose of the current study is to assess, in a group of forty-five subjects, the effect of channel number and decoding method on the progression of BCI performance across multiple training sessions and the corresponding neurophysiological changes. The 45 subjects were divided into three groups using Laplacian Filtering (LAP/S) with nine channels, Common Spatial Pattern (CSP/L) with 40 channels and CSP (CSP/S) with nine channels for online decoding. At the first training session, subjects using CSP/L displayed no significant difference compared to CSP/S but a higher average BCI performance over those using LAP/S. Despite the average performance when using the LAP/S method was initially lower, but LAP/S displayed improvement over first three sessions, whereas the other two groups did not. Additionally, analysis of the recorded EEG during BCI control indicates that the LAP/S produces control signals that are more strongly correlated with the target location and a higher R-square value was shown at the fifth session. In the present study, we found that subjects' average online BCI performance using a large EEG montage does not show significantly better performance after the first session than a smaller montage comprised of a common subset of these electrodes. The LAP/S method with a small EEG montage allowed the subjects to improve their skills across sessions, but no improvement was shown for the CSP method.

Music performance anxiety (MPA) is a specific condition for musicians. Although it can have a negative influence on their music careers, little attention is paid to this phenomenon both in the professional environment and in stress research. In the current pilot study, insight was gained into the physiology of the autonomic stress response related to anxiety in musicians when performing on stage by using a wearable biosensor patch for registration of a range of physiological parameters. Also, the validity of two different psychometric questionnaires in objectifying the stress response on stage to predict the individual stress response was explored. The autonomic physiological parameters (heart rate, respiratory rate, skin temperature) of 11 violists and violinists were collected while performing on stage and in resting state using the VitalConnect HealthPatch®. In addition, scores on validated questionnaires in research on MPA (State Anxiety Inventory, Kenny Music Performance Anxiety Inventory, Short Form Health Survey) were collected in order to try to objectify the magnitude of the subjective level of both MPA and experienced stress. The registration of the autonomic parameters showed a significant increase in heart rate, respiratory rate, and stress level from resting state measurements during stage performance. Analysis of heart rate variability showed a shift from indices of parasympathetic nervous system activity during baseline measurements towards indices of sympathetic nervous system activity during stress measurements. Surprisingly, none of the questionnaires was correlated to the physiological stress parameters on stage. In conclusion, the wearable biosensor patch proved to be an adequate tool to assess physiological stress parameters on stage. The different questionnaires did not contribute to the prediction of its occurrence in a group of musicians., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2018 by S. Karger AG, Basel.)

Despite efforts to develop more effective therapies, PTSD remains a difficult disorder to treat. Insight into the dynamic nature of memory formation and its required molecular machinery can provide an opportunity to target pathological memories for emotionally arousing events. As memories become labile upon retrieval, novel information can update the strength and course of these consolidated memories. Targeting the process of reconsolidation may offer a relevant approach to attenuate fearful and traumatic memories. Specific molecular mechanisms that are required for reconsolidation of arousing information include an intact functioning of the glutamatergic signaling pathways and, more specifically, the integrity of NMDA receptors. Ketamine, a noncompetitive NMDA-receptor antagonist, is receiving increasing interest for a variety of psychiatric indications. This compound can also be an interesting candidate for targeting emotional memories. We explore whether single intravenous infusion of a subanesthetic dose of ketamine can be considered as a viable augmentation strategy for trauma-focused psychotherapy in patients with PTSD. As a consequence, a systematic approach is needed to assess the pharmacodynamic effects of ketamine in relation to both psychotherapy and its pharmacokinetics prior to its application in patient populations. By using a "question-based drug development plan," we can explore such aspects for novel drugs, and we formulated five additional topics that need to be addressed concerning the psychotherapeutic approach and phase orientation of pharmacological assisted psychotherapy.

Background: Following remission of an anxiety disorder or a depressive disorder, antidepressants are frequently discontinued and in the case of symptom occurrence reinstated. Reinstatement of antidepressants seems less effective in some patients, but an overview is lacking. This systematic review aimed to provide insight into the magnitude and risk factors of response failure after reinstatement of antidepressants in patients with anxiety disorders, depressive disorders, obsessive-compulsive disorder (OCD), or posttraumatic stress disorder (PTSD)., Method: PubMed, Embase, and trial registers were systematically searched for studies in which patients: (1) had an anxiety disorder, a depressive disorder, OCD, or PTSD and (2) experienced failure to respond after reinstatement of a previously effective antidepressant., Results: Ten studies reported failure to respond following antidepressant reinstatement. The phenomenon was observed in 16.5% of patients with a depressive disorder, OCD, and social phobia and occurred in all common classes of antidepressants. The range of response failure was broad, varying between 3.8 and 42.9% across studies. No risk factors for failure to respond were investigated. The overall study quality was limited., Conclusion: Research investigating response failure is scarce and the study quality limited. Response failure occurred in a substantial minority of patients. Contributors to the relevance of this phenomenon are the prevalence of the investigated disorders, the number of patients being treated with antidepressants, and the occurrence of response failure for all common classes of antidepressants. This systematic review highlights the need for studies systematically investigating this phenomenon and associated risk factors., (© 2018 The Author(s) Published by S. Karger AG, Basel.)