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

The importance of pro-social processing, and ameliorating dysfunction in schizophrenia. An FMRI study of oxytocin

Schizophrenia is often a severe and debilitating mental illness, frequently associated with impairments in social cognition that hinder individuals' abilities to relate to others and integrate effectively in society. Oxytocin has emerged as a putative therapeutic agent for treating social deficits in schizophrenia, but the mode of action remains unclear. This placebo-controlled crossover study aimed to elucidate the neural underpinnings of oxytocin administration in patients with schizophrenia. 20 patients with schizophrenia were examined using functional magnetic resonance imaging under oxytocin (40 IU) or placebo nasal spray. Participants performed a stochastically rewarded decision-making task that incorporated elements of social valence provided by different facial expressions, i.e. happy, angry and neutral. Oxytocin attenuated the normal bias in selecting the happy face accompanied by reduced activation in a network of brain regions that support mentalising, processing of facial emotion, salience, aversion, uncertainty and ambiguity in social stimuli, including amygdala, temporo-parietal junction, posterior cingulate cortex, precuneus and insula. These pro-social effects may contribute to the facilitation of social engagement and social interactions in patients with schizophrenia and warrant further investigation in future clinical trials for social cognitive impairments in schizophrenia

An evaluation of the variation and underuse of clozapine in the United Kingdom

Background Clozapine is the only licensed treatment for treatment refractory schizophrenia. Despite this, it remains grossly underused relative to the prevalence of refractory schizophrenia. The extent of underuse and the degree of regional variation in prescribing in the United Kingdom is unknown. It is also unclear, how the UK compares with other European countries in rates of clozapine prescribing. Methods We obtained data relating to all clozapine prescribing in the UK from the relevant clozapine registries. We examined regional variation in clozapine use across England, corrected for the known prevalence of severe mental illness (SMI). We also compared the UK rate of clozapine use per 100,000 population to that described in other European countries. Findings There is substantial variation in clozapine prescribing across different regions of England and only about a third of potentially eligible patients were prescribed the drug in the UK. Clozapine prescribing rate in the UK was lower than in several European countries. Interpretation There is clear regional inequity in access to the most effective treatment in refractory schizophrenia in England. Strategies to increase clozapine use, by overcoming both real and perceived barriers, are urgently necessary to reduce treatment inequity for patients with refractory schizophrenia

Mental Health Partnership NHS Trust, Epping, UK Summary

The functional anatomy of divided attentio

Girls-Boys: An Investigation of Gender Differences in the Behavioral and Neural Mechanisms of Trust and Reciprocity in Adolescence

Background: Trust and reciprocity toward others have often been found to increase from childhood to adulthood. Gender differences in these social behaviors have been reported in adults. While adolescence is a key-period of change in social behavior, gender differences in trust and reciprocity during this developmental stage have rarely been investigated. Methods: Here we investigate age-related gender differences in trust and reciprocity (n = 100, 51 female) and associated neural mechanisms (n = 44, 20 female) in adolescents between 13 and 19 years of age. Participants played two multi-round trust games with a pre-programmed cooperative and an unfair partner. Forty-four of 100 participants completed the trust game while undergoing functional brain imaging. Results: Participants’ investments were greater toward a cooperative than unfair game partner (p < 0.01), showing sensitivity to the degree of trustworthiness. There were no gender or age or related differences in baseline trust. In repeated cooperative interactions no gender differences were found, but younger adolescents showed slightly steeper increase of investments than older adolescents. In unfair interactions, younger males reacted with stronger decrease of investments than older males. Region of interest analysis of brain areas associated with in mentalizing, reward learning, conflict processing, and cognitive control revealed gender-by-age interactions on trusting behavior in the temporo-parietal junction (TPJ) and the caudate, showing stronger influence of age in males than in females during cooperation, and the reverse in unfair interactions. Additionally, main effects of gender were found in the TPJ, with higher activation in males, and in the caudate, with females showing greater activation. Conclusion: In first interactions and during repeated cooperative interactions, adolescent males and females showed similar trusting behavior. Younger males showed stronger responses to unfairness by others. Gender-by-age interactions in specific ROIs suggest differential development in mentalizing and reward related cognitive processes. In conjunction with previous research, our findings suggest the presence of subtle gender and age-related changes in trust and cooperation that are only detectable using larger age windows

Neural correlates of positive and negative symptoms through the illness course: an fMRI study in early psychosis and chronic schizophrenia

Psychotic illness is associated with cognitive control deficits and abnormal recruitment of neural circuits subserving cognitive control. It is unclear to what extent this dysfunction underlies the development and/or maintenance of positive and negative symptoms typically observed in schizophrenia. In this study we compared fMRI activation on a standard Stroop task and its relationship with positive and negative symptoms in early psychosis (EP, N = 88) and chronic schizophrenia (CHR-SZ, N = 38) patients. CHR-SZ patients showed reduced frontal, striatal, and parietal activation across incongruent and congruent trials compared to EP patients. Higher positive symptom severity was associated with reduced activation across both trial types in supplementary motor area (SMA), middle temporal gyrus and cerebellum in EP, but not CHR-SZ patients. Higher negative symptom severity was associated with reduced cerebellar activation in EP, but not in CHR-SZ patients. A negative correlation between negative symptoms and activation in SMA and precentral gyrus was observed in EP patients and in CHR-SZ patients. The results suggest that the neural substrate of positive symptoms changes with illness chronicity, and that cognitive control related neural circuits may be most relevant in the initial development phase of positive symptoms. These findings also highlight a changing role for the cerebellum in the development and later maintenance of both positive and negative symptoms

Investigating cortical excitability and inhibition in patients with schizophrenia: A TMS-EEG study.

Transcranial magnetic stimulation (TMS) combined with electromyography (EMG) has widely been used as a non-invasive brain stimulation tool to assess excitation/inhibition (E/I) balance. E/I imbalance is a putative mechanism underlying symptoms in patients with schizophrenia. Combined TMS-electroencephalography (TMS-EEG) provides a detailed examination of cortical excitability to assess the pathophysiology of schizophrenia. This study aimed to investigate differences in TMS-evoked potentials (TEPs), TMS-related spectral perturbations (TRSP) and intertrial coherence (ITC) between patients with schizophrenia and healthy controls. TMS was applied over the motor cortex during EEG recording. Differences in TEPs, TRSP and ITC between the patient and healthy subjects were analysed for all electrodes at each time point, by applying multiple independent sample t-tests with a cluster-based permutation analysis to correct for multiple comparisons. Patients demonstrated significantly reduced amplitudes of early and late TEP components compared to healthy controls. Patients also showed a significant reduction of early delta (50-160 ms) and theta TRSP (30-250ms),followed by a reduction in alpha and beta suppression (220-560 ms; 190-420 ms). Patients showed a reduction of both early (50-110 ms) gamma increase and later (180-230 ms) gamma suppression. Finally, the ITC was significantly lower in patients in the alpha band, from 30 to 260 ms. Our findings support the putative role of impaired GABA-receptor mediated inhibition in schizophrenia impacting excitatory neurotransmission. Further studies can usefully elucidate mechanisms underlying specific symptoms clusters using TMS-EEG biometrics. [Abstract copyright: Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

Sensory Attenuation Assessed by Sensory Evoked Potentials in Functional Movement Disorders.

BACKGROUND: Functional (psychogenic) movement disorders (FMD) have features associated with voluntary movement (e.g. distractibility) but patients report movements to be out of their control. One explanation for this phenomenon is that sense of agency for movement is impaired. The phenomenon of reduction in the intensity of sensory experience when movement is self-generated and a reduction in sensory evoked potentials (SEPs) amplitude at the onset of self-paced movement (sensory attenuation) have been linked to sense of agency for movement. METHODS: We compared amplitude of SEPs from median nerve stimulation at rest and at the onset of a self-paced movement of the thumb in 17 patients with FMD and 17 healthy controls. RESULTS: Patients showed lack of attenuation of SEPs at the onset of movement compared to reduction in amplitude of SEPs in controls. FMD patients had significantly different ratios of movement onset to rest SEPs than did healthy controls at each electrode: 0.79 in healthy controls and 1.35 in patients at F3 (t = -4.22, p<0.001), 0.78 in healthy controls and 1.12 at patients C3 (t = -3.15, p = 0.004) and 0.77 in healthy controls and 1.05 at patients P3 (t = -2.88, p = 0.007). CONCLUSIONS: Patients with FMD have reduced sensory attenuation as measured by SEPs at onset of self-paced movement. This finding can be plausibly linked to impairment of sense of agency for movement in these patients

Learning to trust: trust and attachment in early psychosis

Background Distrust and social dysfunction are characteristic in psychosis and may arise from attachment insecurity, which is elevated in the disorder. The relationship between trust and attachment in the early stages of psychosis is unknown, yet could help to understand interpersonal difficulties and disease progression. This study aimed to investigate whether trust is reduced in patients with early psychosis and whether this is accounted for by attachment avoidance and attachment anxiety. Method We used two trust games with a cooperative and unfair partner in a sample of 39 adolescents with early psychosis and 100 healthy controls. Results Patients had higher levels of attachment anxiety, but the groups did not differ in attachment avoidance. Basic trust was lower in patients than controls, as indicated by lower initial investments. During cooperation patients increased their trust towards levels of controls, i.e. they were able to learn and to override initial suspiciousness. Patients decreased their trust less than controls during unfair interactions. Anxious attachment was associated with higher basic trust and higher trust during unfair interactions and predicted trust independent of group status. Discussion Patients showed decreased basic trust but were able to learn from the trustworthy behaviour of their counterpart. Worries about the acceptance by others and low self-esteem are associated with psychosis and attachment anxiety and may explain behaviour that is focused on conciliation, rather than self-protection