Direct serotonin release in humans shapes aversive learning and inhibition.

The role of serotonin in human behaviour is informed by approaches which allow in vivo modification of synaptic serotonin. However, characterising the effects of increased serotonin signalling in human models of behaviour is challenging given the limitations of available experimental probes, notably selective serotonin reuptake inhibitors. Here we use a now-accessible approach to directly increase synaptic serotonin in humans (a selective serotonin releasing agent) and examine its influence on domains of behaviour historically considered core functions of serotonin. Computational techniques, including reinforcement learning and drift diffusion modelling, explain participant behaviour at baseline and after week-long intervention. Reinforcement learning models reveal that increasing synaptic serotonin reduces sensitivity for outcomes in aversive contexts. Furthermore, increasing synaptic serotonin enhances behavioural inhibition, and shifts bias towards impulse control during exposure to aversive emotional probes. These effects are seen in the context of overall improvements in memory for neutral verbal information. Our findings highlight the direct effects of increasing synaptic serotonin on human behaviour, underlining its role in guiding decision-making within aversive and more neutral contexts, and offering implications for longstanding theories of central serotonin function.

Pharmacological targeting of cognitive impairment in depression: recent developments and challenges in human clinical research.

Impaired cognition is often overlooked in the clinical management of depression, despite its association with poor psychosocial functioning and reduced clinical engagement. There is an outstanding need for new treatments to address this unmet clinical need, highlighted by our consultations with individuals with lived experience of depression. Here we consider the evidence to support different pharmacological approaches for the treatment of impaired cognition in individuals with depression, including treatments that influence primary neurotransmission directly as well as novel targets such as neurosteroid modulation. We also consider potential methodological challenges in establishing a strong evidence base in this area, including the need to disentangle direct effects of treatment on cognition from more generalised symptomatic improvement and the identification of sensitive, reliable and objective measures of cognition.

Visual perceptual deficit screening in stroke survivors: evaluation of current practice in the United Kingdom and Republic of Ireland.

PURPOSE: Visual perceptual deficits are frequently underdiagnosed in stroke survivors compared to sensory vision deficits or visual neglect. To better understand this imparity, we evaluated current practice for screening post-stroke visual perceptual deficits. METHODS: We conducted a survey targeted at professionals working with stroke survivors involved in screening visual perceptual deficits across the United Kingdom and the Republic of Ireland. RESULTS: Forty orthoptists and 174 occupational therapists responded to the survey. Visual perceptual deficit screening was primarily conducted by occupational therapists (94%), with 75∼100% of stroke survivors screened per month. Respondents lacked consensus on whether several common post-stroke visual deficits were perceptual or not. During the screening, respondents primarily relied on self-reports and observation (94%), while assessment batteries (58%) and screening tools were underutilised (56%) and selected inappropriately (66%). Respondents reported lack of training in visual perception screening (20%) and physical/cognitive condition of stroke survivors (19%) as extremely challenging during screening. CONCLUSIONS: Visual perceptual deficits are screened post-stroke at a similar rate to sensory vision or visual neglect. Underdiagnosis of visual perceptual deficits may stem from both reliance on subjective and non-standardised screening approaches, and conflicting definitions of visual perception held among clinicians. We recommend increased training provision and use of brief performance-based screening tools.IMPLICATIONS FOR REHABILITATIONLack of agreement among clinicians on what constitutes as visual perceptual or sensory vision deficits may prove problematic, as precise and exact language is often required for clinical decision-making (e.g., referrals).Biases for more familiar visual (perceptual) deficits held among clinicians during the screening process may lead to other visual deficits being missed.To avoid problems being missed, clinicians should aim to use standardised assessments rather than stroke survivor self-report and observations of function when screening for visual perceptual difficulties.

Current practice and challenges in screening for visual perception deficits after stroke: a qualitative study.

PURPOSE: We document current clinical practice and needs in screening for visual perception problems after stroke to inform development of new screening tools. MATERIALS AND METHODS: We interviewed 12 occupational therapists and 13 orthoptists. Interviews were thematically analysed using the Value Proposition Canvas, a model which establishes challenges and facilitators in what people want to achieve. RESULTS: Participants' understanding of visual perception varied and often included sensory and cognitive deficits. Occupational therapists commonly screened for visual field deficits and hemispatial neglect, while other aspects of visual cognition were rarely assessed. A positive screening result triggered an orthoptic referral. Screening generally occurred during functional assessments and/or with in-house developed tools. Challenges to practice were: lack of time, lack of training, environmental and stroke survivor factors (e.g., aphasia), insufficient continuation of care, and test characteristics (e.g., not evidence-based). Facilitators were: quick and practical tools, experienced staff or tools with minimal training requirements, a streamlined care pathway. CONCLUSIONS: Screening employs non-standardised assessments and rarely covers higher visual perceptual deficits. We demonstrates the need for an evidence-based visual perception screen, which should ideally be 15 min or less, be portable, and require minimal equipment. The screen should be suitable for bedside testing and aphasia-friendly.Implications for rehabilitationThere is a high demand for training on what visual perception deficits are and how to screen for them.Building local relationships between orthoptists and occupational therapists is perceived as highly beneficial for providing good vision and visual perception care for stroke survivors.Occupational therapists should be alert for visual perceptual deficits in their patients preferably through systematic screening with standardised assessments such as the shortened version of the Rivermead Perceptual Assessment Battery or Occupational Therapy Adult Perceptual Screening Test.