The influence of trial-by-trial feedback on trust in health, first-episode and chronic psychosis

Trust is crucial to establishing reciprocal, positive social interactions and seems to be compromised in psychosis. The trust game offers methods to assess an individual’s trust responses to trust-reciprocating, positive feedback. Various computational techniques have been implemented to measure trust responsiveness, mostly based on investments. Here, we propose a new method, focusing on feedback response. Psychosis patients show social dysfunction and reduced trust during early and more progressed illness stages. The present study inspects differences in feedback responsiveness of 102 first-episode psychosis patients (FEPs), 43 chronic psychosis patients (CPs), and 39 healthy controls (HCs) by adopting a novel assessment approach. Additionally, baseline trust, the trust exerted without any prior knowledge of the partner’s trustworthiness, and mean trust were examined. Participants performed a multi-round trust game, playing the investor role, and were paired with a computer, programmed to return at least the invested amount, representing a trustworthy partner. The new method detected group differences, more distinguished than the former methods. Contrary to our expectations, baseline trust was intact in patients. Relative to HCs, patients were less responsive to feedback, failing to integrate the positive information into their decision-making process. The magnitude of returns was not associated with increases in trust. This novel method showed promising results and confirmed patients’ deficits within the social interactional domain

A systematic review of TMS and neurophysiological biometrics in patients with schizophrenia

Transcranial magnetic stimulation can be combined with electromyography (TMS-EMG) and electroencephalography (TMS-EEG) to evaluate the excitatory and inhibitory functions of the cerebral cortex in a standardized manner. It has been postulated that schizophrenia is a disorder of functional neural connectivity underpinned by a relative imbalance of excitation and inhibition. The aim of this review was to provide a comprehensive overview of TMS-EMG and TMS-EEG research in schizophrenia, focused on excitation or inhibition, connectivity, motor cortical plasticity and the effect of antipsychotic medications, symptom severity and illness duration on TMS-EMG and TMS-EEG indices. We searched PsycINFO, Embase and Medline, from database inception to April 2020, for studies that included TMS outcomes in patients with schizophrenia. We used the following combination of search terms: transcranial magnetic stimulation OR tms AND interneurons OR glutamic acid OR gamma aminobutyric acid OR neural inhibition OR pyramidal neurons OR excita* OR inhibit* OR GABA* OR glutam* OR E-I balance OR excitation-inhibition balance AND schizoaffective disorder* OR Schizophrenia OR schizophreni*. TMS-EMG and TMS-EEG measurements revealed deficits in excitation or inhibition, functional connectivity and motor cortical plasticity in patients with schizophrenia. Increased duration of the cortical silent period (a TMS-EMG marker of γ-aminobutyric acid B receptor activity) with clozapine was a relatively consistent finding. Most of the studies used patients with chronic schizophrenia and medicated patients, employed cross-sectional group comparisons and had small sample sizes. TMS-EMG and TMS-EEG offer an opportunity to develop a novel and improved understanding of the physiologic processes that underlie schizophrenia and to assess the therapeutic effect of antipsychotic medications. In the future, these techniques may also help predict disease progression and further our understanding of the excitatory/inhibitory balance and its implications for mechanisms that underlie treatment-resistant schizophrenia. [Abstract copyright: © 2021 CMA Joule Inc. or its licensors.

Stimulating learning: A functional MRI and behavioral investigation of the effects of transcranial direct current stimulation on stochastic learning in schizophrenia

Transcranial direct current stimulation (tDCS) of the medial prefrontal cortex (mPFC) is under clinical investigation as a treatment for cognitive deficits. We investigate the effects of tDCS over the mPFC on performance SSLT in individuals with schizophrenia, and the underlying neurophysiological effect in regions associated with learning values and stimulus-outcome relationships. In this parallel-design double-blind pilot study, 49 individuals with schizophrenia, of whom 28 completed a fMRI, were randomized into active or sham tDCS stimulation groups. Subjects participated in 4 days of SSLT training (days 1, 2, 14, 56) with tDCS applied at day-1, and during a concurrent MRI scan at day-14. The SSLT demonstrated a significant mean difference in performance in the tDCS treatment group: at day-2 and at day-56. Active tDCS was associated with increased insular activity, and reduced amygdala activation. tDCS may offer an important novel approach to modulating brain networks to ameliorate cognitive deficits in schizophrenia, with this study being the first to show a longer-term effect on SSLT

Neuroimaging oxytocin modulation of social reward learning in schizophrenia.

Conventional pharmacological approaches have limited effectiveness for schizophrenia. There is interest in the application of oxytocin, which is involved in social cognition. Clinical trials have yielded mixed results, with a gap in understanding neural mechanisms. To evaluate the behavioural impact of oxytocin administration on a social learning task in individuals with schizophrenia, and elucidate any differential neural activity produced. We recruited 20 clinically stable right-handed men diagnosed with schizophrenia or schizoaffective disorder. In a double-blind cross-over randomised controlled study, 40 IU of oxytocin or placebo were administered before functional magnetic resonance imaging of participants playing a multi-round economic exchange game of trust. Participants had the role of investors (investment trials) receiving repayment on their investments (repayment trials), playing one session against a computer and a second against a player believed to be human. During investment trials, oxytocin increased neural signalling in the right lateral parietal cortex for both human and computer player trials, and attenuated signalling in the right insula for human player trials. For repayment trials, oxytocin elicited signal increases in left insula and left ventral caudate, and a signal decrease in right amygdala during the human player trials; conversely it resulted in right dorsal caudate activation during the computer player trials. We did not find a significant change in behavioural performance associated with oxytocin administration, or any associations with symptoms. During a social learning task oxytocin modulates cortical and limbic substrates of the reward-processing network. These perturbations can be putatively linked to the pathoaetiology of schizophrenia

Real-world effectiveness of admissions to a tertiary treatment-resistant psychosis service: 2-year mirror-image study

Background Treatment-resistant schizophrenia is a major disabling illness which often proves challenging to manage in a secondary care setting. The National Psychosis Unit (NPU) is a specialised tertiary in-patient facility that provides evidence-based, personalised, multidisciplinary interventions for complex treatment-resistant psychosis, in order to reduce the risk of readmission and long-term care costs. Aims This study aimed to assess the long-term effectiveness of treatment at the NPU by considering naturalistic outcome measures. Method Using a mirror image design, we compared the numbers of psychiatric and general hospital admissions, in-patient days, acuity of placement, number of psychotropic medications and dose of antipsychotic medication prescribed before and following NPU admission. Data were obtained from the Clinical Records Interactive Search system, an anonymised database sourced from the South London and Maudsley NHS Trust electronic records, and by means of anonymous linkage to the Hospital Episode Statistics system. Results Compared with the 2 years before NPU admission, patients had fewer mental health admissions (1.65 ± 1.44 v. 0.87 ± 0.99, z = 5.594, P < 0.0001) and less mental health bed usage (335.31 ± 272.67 v. 199.42 ± 261.96, z = 5.195 P < 0.0001) after NPU admission. Total in-patient days in physical health hospitals and total number of in-patient days were also significantly reduced (16.51 ± 85.77 v. 2.83 ± 17.38, z = 2.046, P = 0.0408; 351.82 ± 269.09 v. 202.25 ± 261.05, z = 5.621, P < 0.0001). The reduction in level of support required after treatment at the NPU was statistically significant (z = −8.099, P < 0.0001). Conclusions This study demonstrates the long-term effectiveness of a tertiary service specialising in treatment-resistant psychosis

The effect of training intensity on implicit learning rates in schizophrenia

Cognitive impairments in learning and memory are core symptoms of schizophrenia, associated with reduced self-reported quality of life. The most effective treatment of cognitive impairments is drill and practice cognitive training. Still, to date no study has investigated the effect of varying the frequency of training on cognitive outcomes. Here we utilized a verbal memory based language learning task, tapping into implicit cognitive processes, to investigate the role of training intensity on learning rates in individuals with schizophrenia. Data from 47 participants across two studies was utilized, one with a daily training regimen over 5 days and the other with a more intensive schedule of 5 sessions delivered over 2 days. The primary outcome measure was the change in implicit learning performance across five sessions, quantified with the Matthews Correlation Coefficient (MCC). Participants in the daily training group showed improved performance compared to the intensive group only at session 4. This is the first study to show that implicit learning rates are influenced by training intensity, with daily sessions outperforming a more intensive regimen; a period of consolidation overnight may be necessary to optimize cognitive training for individuals with schizophrenia

VStore: Feasibility and acceptability of a novel virtual reality functional cognition task

Virtual reality (VR) is becoming an increasingly popular tool in neuroscience and mental health research. In recent years, efforts have been made to virtualise neuropsychological testing with the intent to increase the ecological validity of cognitive assessments. However, there are some limitations in the current literature—feasibility and acceptability data are often not reported or available and sample sizes have generally been small. In this study, we describe the development and establish the feasibility and acceptability of use of a novel functional cognition VR shopping task, VStore, in three separate samples with data from a total of 210 participants. Two samples include healthy volunteers between the ages of 20 and 79 and there is one clinical cohort of patients with psychosis. Main VStore outcomes were: 1) verbal recall of 12 grocery items, 2) time to collect items, 3) time to select items on a self-checkout machine, 4) time to make the payment, 5) time to order hot drink, and 6) total time. Feasibility and acceptability were assessed by the completion rate across the three studies. VR induced adverse effects were assessed preand post-VStore administration to establish tolerability. Finally, as an exploratory objective, VStore’s ability to differentiate between younger and older age groups, and between patients and matched healthy controls was examined as preliminary indication of its potential utility. The overall completion rate across the studies was exceptionally high (99.95%), and VStore did not induce any adverse effects. Additionally, there was a clear difference in VStore performance metrics between both the patients and controls and between younger and older age groups, suggesting potential clinical utility of this VR assessment. These findings demonstrate that VStore is a promising neuropsychological tool that is well-tolerated and feasible to administer to both healthy and clinical populations. We discuss the implications for future research involving neuropsychological testing based on our experience and the contemporary literature

Contextual perception under active inference

Human social interactions depend on the ability to resolve uncertainty about the mental states of others. The context in which social interactions take place is crucial for mental state attribution as sensory inputs may be perceived differently depending on the context. In this paper, we introduce a mental state attribution task where a target-face with either an ambiguous or an unambiguous emotion is embedded in different social contexts. The social context is determined by the emotions conveyed by other faces in the scene. This task involves mental state attribution to a target-face (either happy or sad) depending on the social context. Using active inference models, we provide a proof of concept that an agent’s perception of sensory stimuli may be altered by social context. We show with simulations that context congruency and facial expression coherency improve behavioural performance in terms of decision times. Furthermore, we show through simulations that the abnormal viewing strategies employed by patients with schizophrenia may be due to i) an imbalance between the precisions of local and global features in the scene and ii) a failure to modulate the sensory precision to contextualise emotions

A systematic review of TMS and neurophysiological biometrics in patients with schizophrenia

Background: Transcranial magnetic stimulation can be combined with electromyography (TMS-EMG) and electroencephalography (TMS-EEG) to evaluate excitatory and inhibitory functions of the cerebral cortex in a standardised manner. Schizophrenia has been postulated to be a disorder of functional neural connectivity underpinned by relative excitation/inhibition imbalance. The aim of this review is to provide a comprehensive overview of TMS-EMG and -EEG research in schizophrenia focused on excitation/inhibition, connectivity, motor cortical plasticity, and the impact of antipsychotic medications, symptom severity and illness duration on TMS-EMG and -EEG indices.Methods: We searched PsycInfo, Embase and Medline, from inception to April 2020, for studies including TMS outcomes in patients with schizophrenia. The following combination of search terms was used: (transcranial magnetic stimulation OR tms) AND (interneurons OR glutamic acid OR gamma aminobutyric acid OR neural inhibition OR pyramidal neurons OR excita* OR inhibit* OR GABA* OR glutam* OR E-I balance OR excitation-inhibition balance) AND (schizoaffective disorder* OR Schizophrenia OR schizophreni*).Results: TMS-EMG and TMS-EEG measurements revealed deficits in excitation/inhibition, functional connectivity and motor cortical plasticity in schizophrenia. Additionally, increased duration of cortical silent period, a TMS-EMG marker of GABAB receptor activity, by clozapine was a relatively consistent finding.Limitations: Most of the studies used chronic and medicated patients, employed cross-sectional group comparisons and had a small patient sample size. Conclusion: TMS-EMG and TMS-EEG offers an opportunity to develop a novel and improved understanding of the physiological processes underlying schizophrenia and assess the therapeutic effect of antipsychotic medications. In the future, the techniques may also help predict disease progression and further our understanding of the excitatory-inhibitory balance and its implications for mechanisms underlying treatment resistant schizophrenia

Influencia de los signos y síntomas de esquizofrenia en la teoría de la mente

La teoría de la mente propone que los signos y síntomas de la esquizofrenia reflejan una disfunción en el sistema cognitivo dedicado al reconocimiento y control de nuestras propias intenciones y a la atribuci6n de intenciones a otras personas. Nuestra pretensi6n es analizar si' los deficits metarepresentacionales observados en esquizofrénicos se asocian a su sintomatología. 47 sujetos se seleccionaron para el estudio: 27 esquizofrénicos y 20 sujetos control. Las pruebas utilizadas fueron: Test de factor "gn, escala PANSS y tarea extensiva de verbos mentales. Los enfermos se reunieron, según sus signos y síntomas, en los grupos de: signos conductuales, síntomas paranoides, fenómenos de pasividad y otros síntomas menos típicos! remisión. Se encontraron dificultades en TM en pacientes con signos conductuales negativos y positivos. con delirios paranoides y con características de pa$lvidad; dificultades que se plasmarán en su discurso. Asimismo. los pacientes con signos conductuales ejecutaron la tarea peor que los pacientes con delirios paranoides. El grupo con otros síntomas menos típicos y en remisión realizaron la tarea de mentalización normalmente.The theory of mind proposes that the signs and symptoms of schizophrenia reflect. the precise nature of the dysfunction within a cognitive system devoted to the recognition and monitoring of one 's own intentions and the attribution of intentions to others. This study examines the hypothesis that metarepresentational deficits seen in patients with schizophrenia are associated with their symptomatology. Forty- seven people were assessed during this study: twenty- seven patients with a diagnosis of schizophrenia and twenty non-psychiatric controls. Measures: Factor -g" test, PANSS scale and mental verbs extension task. The patients were al/ocated to one of four groups according to their current signs and symptoms: behavioural signs, paranoid symptoms. passivity phenomena and other symptoms! remission. We found metarepresentational problems in patients with negative and positive behavioural signs, paranoid delusions and passivity features and associated with speech disorder. Al so, our psychiatric participants with behavioural signs performed the task significan tI Y more poorly than do patients with paranoid delusions; while the group with other symptoms and those in remission performed the task normally