Barbara J Sahakian

(1) Background: Traumatic brain injury (TBI) often results in cognitive impairments, including in visuospatial planning and executive function. Methylphenidate (MPh) demonstrates potential improvements in several cognitive domains in patients with TBI. The Tower of London (TOL) is a visuospatial planning task used to assess executive function.(2) Methods: Volunteers with a history of TBI (n= 16) participated in a randomised, double-blinded, placebo-controlled, fMRI study to investigate the neurobiological correlates of visuospatial planning and executive function, on and off MPh.(3) Results: Healthy controls (HCs)(n= 18) and patients on placebo (TBI-placebo) differed significantly in reaction time (p< 0.0005) and accuracy (p< 0.0001) when considering all task loads, but especially for high cognitive loads for reaction time (p< 0.001) and accuracy (p< 0.005). Across all task loads, TBI-MPh were more accurate than TBI-placebo (p< 0.05) but remained less accurate than HCs (p< 0.005). TBI-placebo substantially improved in accuracy with MPh administration (TBI-MPh) to a level statistically comparable to HCs at low (p= 0.443) and high (p= 0.175) cognitive loads. Further, individual patients that performed slower on placebo at low cognitive loads were faster with MPh (p< 0.05), while individual patients that performed less accurately on placebo were more accurate with MPh at both high and low cognitive loads (p< 0.005). TBI-placebo showed reduced activity in the bilateral inferior frontal gyri (IFG) and insulae versus HCs. MPh normalised these regional differences. MPh enhanced within-network connectivity (between parietal, striatal, insula, and …

BackgroundCOVID-19 lockdowns increased the risk of mental health problems, especially for children with autism spectrum disorder (ASD). However, despite its importance, little is known about the protective factors for ASD children during the lockdowns.MethodsBased on the Shanghai Autism Early Developmental Cohort, 188 ASD children with two visits before and after the strict Omicron lockdown were included; 85 children were lockdown-free, while 52 and 51 children were under the longer and the shorter durations of strict lockdown, respectively. We tested the association of the lockdown group with the clinical improvement and also the modulation effects of parent/family-related factors on this association by linear regression/mixed-effect models. Within the social brain structures, we examined the voxel-wise interaction between the grey matter volume and the identified modulation effects.ResultsCompared …

Serotonin is critical for adapting behavior flexibly to meet changing environmental demands. Cognitive flexibility is important for successful attainment of goals, as well as for social interactions, and is frequently impaired in neuropsychiatric disorders, including obsessive–compulsive disorder. However, a unifying mechanistic framework accounting for the role of serotonin in behavioral flexibility has remained elusive. Here, we demonstrate common effects of manipulating serotonin function across two species (rats and humans) on latent processes supporting choice behavior during probabilistic reversal learning, using computational modelling. The findings support a role of serotonin in behavioral flexibility and plasticity, indicated, respectively, by increases or decreases in choice repetition (‘stickiness’) or reinforcement learning rates following manipulations intended to increase or decrease serotonin function. More …

Eugene Stern Paykel was born on 9 September 1934 in Auckland, New Zealand. His research work focused on affective disorders in which he made significant and far-reaching contributions to the study of both causes and treatments of depression, spanning the fields of epidemiology, community psychiatry, psychological therapy, and psychopharmacology. He was the sole editor of the influential ‘Handbook of Affective Disorders’(editions 1 and 2) which brought together these disparate areas of study as an early example of the biopsychosocial framework for understanding mental illness. Overall, he published approximately 400 papers, with over 32,000 citations, and authored, co-authored, or edited eight books. As a reflection of his research interest in psychopharmacology, he served as President of The British Association for Psychopharmacology (BAP) and The Collegium Internationale …

BACKGROUNDIrritable bowel syndrome (IBS) interacts with psychopathology in a complex way, yet little is known about the underlying brain, biochemical and genetic mechanisms.METHODSTo clarify the phenotypic and genetic associations between IBS and brain health, we performed a comprehensive retrospective cohort study on a large population. Our study included 171,104 participants from the UK Biobank who underwent a thorough assessment of the IBS syndrome, with the majority also providing neuroimaging, behavioral, biochemical, and genetic information. Multistage linked analyses were conducted, including phenome-wide association analysis, polygenic risk score calculation, and two-sample Mendelian Randomization (MR) analysis.RESULTSThe phenome-wide association analysis showed that IBS is linked to brain health problems, including anxiety and depression, and poor cognitive …

Subregions of the medial temporal lobe (MTL) undergo substantial changes during the female menopause. How the decline in MTL volumes during menopause affects cognitive function is still unknown. In this study, we aim to validate previous results of decreased MTL grey matter (GM) volumes in post-menopausal women and investigate how diffusion imaging measures are affected by it. We relate this to changes in cognition, specifically focussing on learning and memory changes. Furthermore, we investigate whether hormone replacement therapy can slow the progression of decline in cognition and MTL volumes. We use data from approximately 13,000 participants from the UK Biobank cohort that were either pre-or post-menopausal. We investigate the effect of spontaneous menopause, HRT, and duration of HRT use on GM volumes, fractional anisotropy (FA) and mean diffusivity (MD).

BackgroundThe nature of cognitive flexibility deficits in obsessive-compulsive disorder (OCD), which historically have been tested with probabilistic reversal learning tasks, remains elusive. Here, a novel deterministic reversal task and inclusion of unmedicated patients in the study sample illuminated the role of fixed versus uncertain rules/contingencies and of serotonergic medication. Additionally, our understanding of probabilistic reversal was enhanced through theoretical computational modeling of cognitive flexibility in OCD.MethodsWe recruited 49 patients with OCD, 21 of whom were unmedicated, and 43 healthy control participants matched for age, IQ, and gender. Participants were tested on 2 tasks: a novel visuomotor deterministic reversal learning task with 3 reversals (feedback rewarding/punishing/neutral) measuring accuracy/perseveration and a 2-choice visual probabilistic reversal learning task with …

The present project is part of a larger project aimed at examining cognitive flexibility, other executive functions, and learning in healthy adults (Melani et al., 2022; Sam et al., 2022; Tong et al., 2021) in Singapore. The current pre-registration form primarily aims to examining specific hypotheses related to the association between socio-cognitive variables and career development/transitional behaviours and outcomes, which might not be described in the main studies (https://osf. io/ay9gr; https://osf. io/n352u; https://osf. io/6rc9h) in detail. Changes in the workplace over the past decades have spawned an increase in research investigating contemporary career types, which are characterized by increased self-directedness, flexibility, and the aim of subjective career success. Living in a dynamic and complex environment necessitates that all living organisms be flexible and adaptive to survive (Powell & Ragozzino, 2017). Humans are required to proactively equip themselves with the ability to shift their strategies and update their beliefs and actions in response to changing environmental demands (Diamond, 2006; Garcia-Garcia et al., 2010; Geurts et al., 2009; Herrmann et al., 2015). For instance, the increasing volatility in the 21st-century workforce, particularly during the unprecedented COVID-19 pandemic, has served as a timely reminder of the urgency of cultivating the flexibility to respond to unforeseen changes and uncertainties more adaptively in order to stay competitive in turbulent job markets. The view of a linear career path (whereby workers are only trained to perform and master one job) that dominated the mainstream workplace system …