Distinct alterations in probabilistic reversal learning across at-risk mental state, first episode psychosis and persistent schizophrenia.

We used a probabilistic reversal learning task to examine prediction error-driven belief updating in three clinical groups with psychosis or psychosis-like symptoms. Study 1 compared people with at-risk mental state and first episode psychosis (FEP) to matched controls. Study 2 compared people diagnosed with treatment-resistant schizophrenia (TRS) to matched controls. The design replicated our previous work showing ketamine-related perturbations in how meta-level confidence maintained behavioural policy. We applied the same computational modelling analysis here, in order to compare the pharmacological model to three groups at different stages of psychosis. Accuracy was reduced in FEP, reflecting increased tendencies to shift strategy following probabilistic errors. The TRS group also showed a greater tendency to shift choice strategies though accuracy levels were not significantly reduced. Applying the previously-used computational modelling approach, we observed that only the TRS group showed altered confidence-based modulation of responding, previously observed under ketamine administration. Overall, our behavioural findings demonstrated resemblance between clinical groups (FEP and TRS) and ketamine in terms of a reduction in stabilisation of responding in a noisy environment. The computational analysis suggested that TRS, but not FEP, replicates ketamine effects but we consider the computational findings preliminary given limitations in performance of the model.

Negative symptoms and cognitive impairment are associated with distinct motivational deficits in treatment resistant schizophrenia.

BACKGROUND: Motivational deficits are a central feature of the negative syndrome in schizophrenia. They have consistently been associated with reduced willingness to expend physical effort in return for monetary rewards on effort based decision making (EBDM) paradigms. Nevertheless, the mechanisms underlying such altered performance are not well characterised, and it remains unclear if they are driven purely by negative symptoms, or also in part by cognitive impairment, antipsychotic treatment or even positive symptoms. Here we investigated the impact of all these factors using a paradigm that has not previously been used to measure EBDM in schizophrenia. METHODS: Forty treatment resistant schizophrenia (TRS) patients on clozapine and matched controls (N = 80) completed a well validated EBDM task which offers monetary rewards in return for physical effort. Choice and reaction time data was analysed using logistic regressions, as well as Bayesian hierarchical drift diffusion modelling (HDDM). Behavioural parameters were compared between groups and their association with negative symptoms, cognitive function and serum clozapine levels were assessed. RESULTS: Overall, TRS patients accepted significantly less offers than controls during effort-based decision making, suggesting they were less motivated. They demonstrated reduced sensitivity to increasing rewards, but surprisingly were also less averse to increasing effort. Despite a positive correlation between negative symptoms and cognitive function in TRS, reward sensitivity was associated only with cognitive performance. In contrast, reduced effort aversion correlated with negative symptom severity. Clozapine levels and positive symptoms were not associated with either behavioural parameter. CONCLUSION: Motivational deficits in TRS are characterised by both diminished reward sensitivity and reduced effort aversion during EBDM. Cognitive dysfunction and negative symptom severity account for distinct aspects of these behavioural changes, despite positive associations between themselves. Overall, these findings demonstrate that negative symptoms and cognitive impairment have significant independent contributions to EBDM in TRS, thereby opening the possibility of individualised treatment targeting these mechanisms to improve motivation.

Surgical interventions in adult upper limb spasticity management: a systematic review.

Upper limb spasticity following upper motor neuron lesion is a key cause of long-term disability in adults, causing functional loss, pain, and reduced quality of life. Surgical management is an under-utilized intervention, and little work has been performed to collate and evaluate the evidence for these interventions. We undertake the first, PRISMA-compliant systematic review synthesizing the evidence for surgical management of spasticity in adults. Three databases were searched using pre-specified search strings over a 20-year window (September 2001-2021). Only primary research papers featuring an entirely adult sample were included. Case reports were excluded. Quality assessment was performed using the Oxford Centre for Evidence-Based Medicine Scale and the Methodological Index for Non-Randomized Studies. We identified 19 eligible studies, all of which were poor quality. Significant benefit of surgery was identified in 15 of the 16 studies conducting significance testing. Detailed analysis of the surgical procedures used was prevented by poor reporting. Studies reported low rates of serious postoperative complication, and relatively high rates of postoperative deformity recurrence. Studies' approaches to patient assessment and management varied significantly, reflecting a lack of standardization in this field. This review suggests that higher-quality, more standardized evidence is required to demonstrate the safety and efficacy of these surgical procedures. Future work should focus on improved reporting of surgical procedures and development of consensus assessment tools focusing on assessment of patient functionality and quality of life.