Trauma Disrupts Reinforcement Learning in Rats-A Novel Animal Model of Chronic Stress Exposure.

Trauma, as well as chronic stress that characterizes a modern fast-paced lifestyle, contributes to numerous psychopathologies and psychological problems. Psychiatric patients with traumas, as well as healthy individuals who experienced traumas in the past, are often characterized by diminished cognitive abilities. In our protocol, we used an animal model to explore the influence of chronic trauma on cognitive abilities and behavior in the group of 20 rats (Rattus norvegicus). The experimental group was introduced to chronic (12 consecutive days) exposure to predator odor (bobcat urine). We measured the reinforcement learning of each individual before and after the exposition via the Probabilistic Selection Task (PST) and we used Social Interaction Test (SIT) to assess the behavioral changes of each individual before and after the trauma. In the experimental group, there was a significant decrease in reinforcement learning after exposure to a single trauma (Wilcoxon Test, p = 0.034) as well as after 11 days of chronic trauma (Wilcoxon-test, p = 0.01) in comparison to pre-trauma performance. The control group, which was not exposed to predator odor but underwent the same testing protocol, did not present significant deterioration in reinforcement learning. In cross-group comparisons, there was no difference between the experimental and control group in PST before odor protocol (U Mann-Whitney two-sided, p = 0.909). After exposure to chronic trauma, the experimental group deteriorated in PST performance compared to control (U Mann-Whitney Two-sided, p = 0.0005). In SIT, the experimental group spent less time in an Interaction Zone with an unfamiliar rat after trauma protocol (Wilcoxon two-sided test, p = 0.019). Major strengths of our models are: (1) protocol allows investigating reinforcement learning before and after exposition to chronic trauma, with the same group of rats, (2) translational scope, as the PST is displayed on touchscreen, similarly to human studies, (3) protocol delivers chronic trauma that impairs reward learning, but behaviorally does not induce full-blown anhedonia, thus rats performed voluntarily throughout all the procedures.

Coarse-Grained Neural Network Model of the Basal Ganglia to Simulate Reinforcement Learning Tasks.

Computational models of the basal ganglia (BG) provide a mechanistic account of different phenomena observed during reinforcement learning tasks performed by healthy individuals, as well as by patients with various nervous or mental disorders. The aim of the present work was to develop a BG model that could represent a good compromise between simplicity and completeness. Based on more complex (fine-grained neural network, FGNN) models, we developed a new (coarse-grained neural network, CGNN) model by replacing layers of neurons with single nodes that represent the collective behavior of a given layer while preserving the fundamental anatomical structures of BG. We then compared the functionality of both the FGNN and CGNN models with respect to several reinforcement learning tasks that are based on BG circuitry, such as the Probabilistic Selection Task, Probabilistic Reversal Learning Task and Instructed Probabilistic Selection Task. We showed that CGNN still has a functionality that mirrors the behavior of the most often used reinforcement learning tasks in human studies. The simplification of the CGNN model reduces its flexibility but improves the readability of the signal flow in comparison to more detailed FGNN models and, thus, can help to a greater extent in the translation between clinical neuroscience and computational modeling.

Confirmation Bias in the Course of Instructed Reinforcement Learning in Schizophrenia-Spectrum Disorders.

A large body of research attributes learning deficits in schizophrenia (SZ) to the systems involved in value representation (prefrontal cortex, PFC) and reinforcement learning (basal ganglia, BG) as well as to the compromised connectivity of these regions. In this study, we employed learning tasks hypothesized to probe the function and interaction of the PFC and BG in patients with SZ-spectrum disorders in comparison to healthy control (HC) subjects. In the Instructed Probabilistic Selection task (IPST), participants received false instruction about one of the stimuli used in the course of probabilistic learning which creates confirmation bias, whereby the instructed stimulus is overvalued in comparison to its real experienced value. The IPST was administered to 102 patients with SZ and 120 HC subjects. We have shown that SZ patients and HC subjects were equally influenced by false instruction in reinforcement learning (RL) probabilistic task (IPST) (p-value = 0.441); however, HC subjects had significantly higher learning rates associated with the process of overcoming cognitive bias in comparison to SZ patients (p-value = 0.018). The behavioral results of our study could be hypothesized to provide further evidence for impairments in the SZ-BG circuitry; however, this should be verified by neurofunctional imaging studies.

The Role of Dopaminergic Genes in Probabilistic Reinforcement Learning in Schizophrenia Spectrum Disorders.

Schizophrenia spectrum disorders (SZ) are characterized by impairments in probabilistic reinforcement learning (RL), which is associated with dopaminergic circuitry encompassing the prefrontal cortex and basal ganglia. However, there are no studies examining dopaminergic genes with respect to probabilistic RL in SZ. Thus, the aim of our study was to examine the impact of dopaminergic genes on performance assessed by the Probabilistic Selection Task (PST) in patients with SZ in comparison to healthy control (HC) subjects. In our study, we included 138 SZ patients and 188 HC participants. Genetic analysis was performed with respect to the following genetic polymorphisms: rs4680 in COMT, rs907094 in DARP-32, rs2734839, rs936461, rs1800497, and rs6277 in DRD2, rs747302 and rs1800955 in DRD4 and rs28363170 and rs2975226 in DAT1 genes. The probabilistic RL task was completed by 59 SZ patients and 95 HC subjects. SZ patients performed significantly worse in acquiring reinforcement contingencies during the task in comparison to HCs. We found no significant association between genetic polymorphisms and RL among SZ patients; however, among HC participants with respect to the DAT1 rs28363170 polymorphism, individuals with 10-allele repeat genotypes performed better in comparison to 9-allele repeat carriers. The present study indicates the relevance of the DAT1 rs28363170 polymorphism in RL in HC participants.

Induction of Phage-Specific Antibodies by Two Therapeutic Staphylococcal Bacteriophages Administered per os.

In therapeutic phage applications oral administration is a common and well-accepted delivery route. Phages applied per os may elicit a specific humoral response, which may in turn affect phage activity. We present specific anti-phage antibody induction in mice receiving therapeutic staphylococcal bacteriophage A3R or 676Z in drinking water. The schedule comprised: (1) primary exposure to phages for 100 days, followed by (2) diet without phage for 120 days, and (3) secondary exposure to the same phage for 44 days. Both phages induced specific antibodies in blood (IgM, IgG, IgA), even though poor to ineffective translocation of the phages to blood was observed. IgM reached a maximum on day 22, IgG increased from day 22 until the end of the experiment. Specific IgA in the blood and in the gut were induced simultaneously within about 2 months; the IgA level gradually decreased when phage was removed from the diet. Importantly, phage-specific IgA was the limiting factor for phage activity in the gastrointestinal tract. Multicopy proteins (major capsid protein and tail morphogenetic protein H) contributed significantly to phage immunogenicity (IgG), while the baseplate protein gpORF096 did not induce a significant response. Microbiome composition assessment by next-generation sequencing (NGS) revealed that no important changes correlated with phage treatment.

Mammalian Host-Versus-Phage immune response determines phage fate in vivo.

Emerging bacterial antibiotic resistance draws attention to bacteriophages as a therapeutic alternative to treat bacterial infection. Examples of phage that combat bacteria abound. However, despite careful testing of antibacterial activity in vitro, failures nevertheless commonly occur. We investigated immunological response of phage antibacterial potency in vivo. Anti-phage activity of phagocytes, antibodies, and serum complement were identified by direct testing and by high-resolution fluorescent microscopy. We accommodated the experimental data into a mathematical model. We propose a universal schema of innate and adaptive immunity impact on phage pharmacokinetics, based on the results of our numerical simulations. We found that the mammalian-host response to infecting bacteria causes the concomitant removal of phage from the system. We propose the notion that this effect as an indirect pathway of phage inhibition by bacteria with significant relevance for the clinical outcome of phage therapy.

Impairments of working memory in schizophrenia and bipolar disorder: the effect of history of psychotic symptoms and different aspects of cognitive task demands.

Comparisons of cognitive impairments between schizophrenia (SZ) and bipolar disorder (BPD) have produced mixed results. We applied different working memory (WM) measures (Digit Span Forward and Backward, Short-delay and Long-delay CPT-AX, N-back) to patients with SZ (n = 23), psychotic BPD (n = 19) and non-psychotic BPD (n = 24), as well as to healthy controls (HC) (n = 18) in order to compare the level of WM impairments across the groups. With respect to the less demanding WM measures (Digit Span Forward and Backward, Short-delay CPT-AX), there were no between group differences in cognitive performance; however, with respect to the more demanding WM measures (Long-delay CPT-AX, N-back), we observed that the groups with psychosis (SZ, psychotic BPD) did not differ from one another, but performed poorer than the group without a history of psychosis (non-psychotic BPD). A history of psychotic symptoms may influence cognitive performance with respect to WM delay and load effects as measured by Long-delay CPT-AX and N-back tests, respectively. We observed a positive correlation of WM performance with antipsychotic treatment and a negative correlation with depressive symptoms in BPD and with negative symptoms in SZ subgroup. Our study suggests that WM dysfunctions are more closely related to a history of psychosis than to the diagnostic categories of SZ and BPD described by psychiatric classification systems.

Electromechanical delay of abdominal muscles is modified by low back pain prevention exercise.

The objective of the research was to assess the effect of a 4-week-long training program on selected parameters: electromechanical delay (EMD) and amplitude of electromyographic signal (EMG). Fourteen female students of the University School of Physical Education participated in the study. Torques and surface electromyography were evaluated under static conditions. Surface electrodes were glued to both sides of the rectus abdominis (RA), external oblique (EO), and erector spinae (ES) muscles. The 4-week-long program was aimed at strengthening the abdominal muscles and resulted in increased EMD during maximum torque production by flexors of the trunk, increased amplitudes of the signals of the erector spinae ( p = 0.005), and increased EMG amplitude asymmetry of the lower ( p = 0.013) and upper part ( p = 0.006) of the rectus abdominis muscle. In a training program composed of a large number of repetitions of strength exercises, in which the training person uses their own weight as the load (like in exercises such as curl-ups), the process of recruitment of motor units is similar to that found during fatiguing exercises and plyometric training.

Money matters: does the reimbursement policy for second generation antipsychotics influence the number of recorded schizophrenia patients and the burden of stigmatization?

PURPOSE: In Poland, non-compliance with the reimbursement policy for second-generation antipsychotics (SGA) manifested in prescribing SGA for patients with psychotic disorders other than schizophrenia may result in serious financial penalties. In this study, we aimed at investigating whether the implementation of the reimbursement policy for SGA contributed to increasing the number of patients with a diagnosis of schizophrenia relatively to the number of patients with a diagnosis of other psychotic disorders in outpatient clinics. METHODS: We analyzed data from Yearbooks of Mental Health that were published by the Institute of Psychiatry and Neurology, Warsaw, Poland in the years 1989­2009 registering the number of patients treated for various mental disorders in public facilities in Poland. Temporal trend analysis of the annual number of patients with a diagnosis of psychotic disorders, who were treated at outpatient clinics, was performed. RESULTS: We found a statistically significant increase in the total number of recorded schizophrenia patients treated at outpatient clinics, as well as in the number of patients treated for the first time at outpatient clinics for schizophrenia. These changes overlap with the implementation of the reimbursement policy for SGA. CONCLUSION: Our results suggest that the restricted reimbursement policy for SGA altered the diagnosing process in Poland. It seems that these alterations may have serious social consequences. Given that a diagnosis of schizophrenia is more stigmatizing than a diagnosis of other psychotic disorders, it might be assumed that schizophrenia over-diagnosing, possibly due to reimbursement reasons, add to the enormous burden associated with stigmatization.

Asymmetry of electromechanical delay (EMD) and torque in the muscles stabilizing spinal column.

Stabilization of the spinal column is ensured by the activity of trunk flexor and erector muscles, including rectus abdominis (RA) and erector spinae (ES). The goal of this study was to evaluate the symmetry of action potential and electromechanical delay (EMD) in RA and ES during generation of maximal muscle torque. In the present study, the symmetry of EMG activity in the right and left parts of RA and ES was tested under isometric conditions. The subjects (N = 13) were selected from the university population. Electromyographic signals and muscles torques were recorded with the sampling frequency of 1000 Hz. Lack of significant differences in EMD between left and right sides in both muscles studied and lack of correlation between EMD and maximal muscle torque were observed. Analysis aimed at assessing the symmetry of EMG signals amplitude revealed crossed laterality characterized by increased activity in the right side of RA muscle and left side of ES. The proportion of maximal muscle torque in ES to RA in the women examined amounted to 1.7:1.