Paul Fletcher

Attempts to understand psychosis—the experience of profoundly altered perceptions and beliefs—raise questions about how the brain models the world. Standard predictive coding approaches suggest that it does so by minimising mismatches between incoming sensory evidence and predictions. By adjusting predictions, we converge iteratively on a best guess of the nature of the reality. Recent arguments have shown that a modified version of this framework—hybrid predictive coding—provides a better model of how healthy agents make inferences about external reality. We suggest that this more comprehensive model gives us a richer understanding of psychosis compared with standard predictive coding accounts. In this Personal View, we briefly describe the hybrid predictive coding model and show how it offers a more comprehensive account of the phenomenology of delusions, thereby providing a potentially …

BackgroundAltered neural responses to sweet flavours are reported in eating and weight-related disorders. The mechanism underlying these observations remains unknown partly due to the complex reinforcing effects of sugar. Sugar has both hedonic and nutritive value, which are encoded by largely distinct neural circuits, and neural activation is further modulated by a flavour’s expected value. We sought to delineate these effects by manipulating the effect of expectation on brain responses to sugar and non-nutritive sweetener.MethodsTwenty-seven healthy volunteers (n= 19 female, Mage= 24.3 years) who poorly discriminated between sugar and non-nutritive sweetener underwent 3T fMRI scanning, during which they performed probabilistic and deterministic gustatory conditioning tasks. During the probabilistic task, participants were shown a cue, indicating the probability of receiving either sugar or sweetener …

“The name of the LORD is a strong tower: the righteous runneth into it, and is safe.”-Proverbs 18: 10 KJV My book is trying convey the fact that God is in complete control; that a man’s heart plans his way, but the Lord directs his steps; that God has shown and continues to show me that He has His hands in and on my life in a magnificent way; that God has given me unusual foresight; that we should trust in the Lord with all of our hearts and do not lean on our own understanding.

BackgroundPatients with major depressive disorder (MDD) can present with altered brain structure and deficits in cognitive function similar to aging. Yet, the interaction between age-related brain changes and brain development in MDD remains understudied. In a cohort of adolescents and adults with and without MDD, we assessed brain aging differences and associations through a newly developed tool quantifying normative neurodevelopmental trajectories.Methods304 MDD participants and 236 non-depressed controls were recruited and scanned from three studies under the Canadian Biomarker Integration Network for Depression. Volumetric data were used to generate brain centile scores, which were examined for: a) differences in MDD relative to controls; b) differences in individuals with versus without severe childhood maltreatment; and c) correlations with depressive symptom severity, neurocognitive …

Blanchard and Canteras (1) express concerns about our recent suggestion (2) that the influential distinction between fear and anxiety, though it has provided a useful and informative framework, is based on unreliable evidence and should be considered an oversimplification. We thank them for raising a number of points and we respond here. First, as they say, one part of our argument is that fear has been related to the central nucleus of the amygdala (CeA) while anxiety has been related to the bed nucleus of the stria terminalis, and the other part is that if the descriptive distinction is truly upheld at a neurobiological level, then we would expect a dissociation (preferably a double dissociation) between activity in these two regions under conditions deemed to provoke fear compared with those provoking anxiety. Blanchard and Canteras challenge this, suggesting that the small size of these two regions, coupled with …

BackgroundPrader–Willi syndrome (PWS) is a rare and complex neurodevelopmental disorder resulting from absent paternal expression of maternally imprinted genes at chromosomal locus 15q11-13. This absence of expression occurs as a consequence of a deletion on the chromosome 15 of paternal origin (ca. 70%), a chromosome 15 maternal uniparental disomy (mUPD; ca. 25%), or an imprinting centre defect (IC; ca. 1–3%). At birth, individuals with PWS are severely hypotonic and fail to thrive. Hyperphagia and characteristic physical and neuropsychiatric phenotypes become apparent during childhood. The risk for the development of a co-morbid psychotic illness increases during the teenage years, specifically in those with PWS due to the presence of an mUPD. The primary aim of this literature review is to inform clinical practice. To achieve this, we have undertaken a systematic analysis of the clinical …

Although mental effort is a frequently used term, it is poorly defined and understood. Consequently, its usage is frequently loose and potentially misleading. In neuroscience research, the term is used to mean both the cognitive ‘work’ that is done in meeting task demands, and the subjective experience of performing that work. We argue that conflating these two meanings hampers progress in understanding cognitive impairments in neuropsychiatric conditions, because cognitive work and the subjective experience of it have distinct underlying mechanisms. We suggest that the most coherent and clinically useful perspective on mental effort is that it is a subjective experience. This makes a clear distinction between cognitive impairments arising from changes in the cognitive apparatus, as in dementia and brain injury, and those arising from subjective difficulties in carrying out the cognitive work, as in attention deficit …

This service evaluation reviewed inclusion of Immersive Virtual Reality (iVR) relaxation activities as part of routine occupational therapy sensory sessions on a specialist dementia unit. Twenty-five sessions were completed over 13 wk with 14 participants. Nine participants chose to engage in multiple sessions. Feasibility was assessed through participant engagement and tolerability. Modal first session length was in the range 30 s to 2 min. This increased to over 2 min on second sessions. There was a lack of significant adverse effects measured by direct questioning, neuropsychiatric assessment before vs. after sessions and adverse incident reporting. Acceptability was assessed via structured review of user and staff feedback which noted positive experiences such as relaxation, openness to discussion, reminiscence, wider engagement and interest in future use. Further work is required to explore efficacy and …

Eating disorders often emerge during adolescence, and affected individuals frequently demonstrate high rates of psychiatric comorbidity, particularly with depressive and anxiety disorders. Although risk for eating disorders reflects both genetic and neurobiological factors, knowledge of how genetic risk for eating disorders relates to neurobiology and psychiatric symptoms during critical developmental periods remains limited. Here we simultaneously estimated associations between genetic risk, brain structure, and eating-disorder-related psychopathology symptoms in over 4,900 adolescents of European ancestry from the ABCD study (mean age (s.d.) = 9.94 (0.62) years). Polygenic scores for anorexia nervosa (AN PGS) and body mass index (BMI PGS) were related to three morphometric brain features—cortical thickness, surface area, and subcortical gray matter volume—and to latent psychopathology factors …

This pre-registration is part of a larger replication effort of the influential study by Lally et al.(2010)​​ in which they tracked the subjective automaticity of a novel, daily (eating or exercise-related) routine, using the Self-Report Habit Index across 12 consecutive weeks. The replication of the main finding (that it takes 66 days to form a new habit) has been addressed in a separate pre-registration (https://osf. io/bj9r2). In the current extension of this basic replication, we will investigate potential causes of interindividual variability, including the consistency and complexity of the habit, as well as individual differences in impulsivity, personal need for structure (PNS), conscientiousness, effort, intention, and reward. Consistency and complexity were already explored by Lally et al., but they could not draw strong conclusions due to their small sample size. Individual differences in impulsivity, PNS, and conscientiousness were not included in the original publication, but they were part of the original study protocol. In addition to addressing the research questions of the original study, we will also investigate how anticipated effort, intention, and reward influence habit formation.

Background To interact successfully with their environment, humans need to build a model to make sense of noisy and ambiguous inputs. An inaccurate model, as suggested to be the case for people with psychosis, disturbs optimal action selection. Recent computational models, such as active inference, have emphasized the importance of action selection, treating it as a key part of the inferential process. Based on an active inference framework, we sought to evaluate previous knowledge and belief precision in an action-based task, given that alterations in these parameters have been linked to the development of psychotic symptoms. We further sought to determine whether task performance and modelling parameters would be suitable for classification of patients and controls.Methods Twenty-three individuals with an at-risk mental state, 26 patients with first-episode psychosis and 31 controls completed a …

The increasing number of long-term survivors of pediatric brain tumors requires us to incorporate the most recent knowledge derived from cognitive neuroscience into their oncological treatment. As the lesion itself, as well as each treatment, can cause specific neural damage, the long-term neurocognitive outcomes are highly complex and challenging to assess. The number of neurocognitive studies in this population grows exponentially worldwide, motivating modern neuroscience to provide guidance in follow-up before, during and after treatment. In this review, we provide an overview of structural and functional brain connectomes and their role in the neuropsychological outcomes of specific brain tumor types. Based on this information, we propose a theoretical neuroscientific framework to apply appropriate neuropsychological and imaging follow-up for future clinical care and rehabilitation trials.

Although overconsumption of high-fat foods is a major driver of weight gain, the neural mechanisms that link the oral sensory properties of dietary fat to reward valuation and eating behavior remain unclear. Here we combine novel food-engineering approaches with functional neuroimaging to show that the human orbitofrontal cortex (OFC) translates oral sensations evoked by high-fat foods into subjective economic valuations that guide eating behavior. Male and female volunteers sampled and evaluated nutrient-controlled liquid foods that varied in fat and sugar (“milkshakes”). During oral food processing, OFC activity encoded a specific oral-sensory parameter that mediated the influence of the foods' fat content on reward value: the coefficient of sliding friction. Specifically, OFC responses to foods in the mouth reflected the smooth, oily texture (i.e., mouthfeel) produced by fatty liquids on oral surfaces. Distinct …

The hypothalamus is an important neuroendocrine hub for the control of appetite and satiety. In animal studies it has been established that hypothalamic lesioning or stimulation causes alteration to feeding behaviour and consequently body mass, and exposure to high calorie diets induces hypothalamic inflammation. These findings suggest that alterations in hypothalamic structure and function are both a cause and a consequence of changes to food intake. However, there is limited in vivo human data relating the hypothalamus to obesity or eating disorders, in part due to technical problems relating to its small size. Here, we used a novel automated segmentation algorithm to exploratorily investigate the relationship between hypothalamic volume, normalised to intracranial volume, and body mass index (BMI). The analysis was applied across four independent datasets comprising of young adults (total n = 1,351 …

Health warning labels (HWLs) show promise in reducing motivation towards energy-dense snack foods. Understanding the underlying mechanisms could optimise their effectiveness. In two experimental studies in general population samples (Study 1 n = 90; Study 2 n = 1382), we compared the effects of HWLs and irrelevant aversive labels (IALs) on implicit (approach) motivation towards unhealthy snacks, using an approach-avoidance task (Study 1), and a manikin task (Study 2). We also assessed explicit motivation towards unhealthy snacks using food selection tasks. We examined whether labelling effects on motivation arose from the creation of outcome-dependent associations between the food and its health consequences or from simple, non-specific aversive associations. Both label types reduced motivation towards snack foods but only when the label was physically present. HWLs and IALs showed …

Neuroanatomical abnormalities have been reported along a continuum from at-risk stages, including high schizotypy, to early and chronic psychosis. However, a comprehensive neuroanatomical mapping of schizotypy remains to be established. The authors conducted the first large-scale meta-analyses of cortical and subcortical morphometric patterns of schizotypy in healthy individuals, and compared these patterns with neuroanatomical abnormalities observed in major psychiatric disorders. The sample comprised 3004 unmedicated healthy individuals (12–68 years, 46.5% male) from 29 cohorts of the worldwide ENIGMA Schizotypy working group. Cortical and subcortical effect size maps with schizotypy scores were generated using standardized methods. Pattern similarities were assessed between the schizotypy-related cortical and subcortical maps and effect size maps from comparisons of schizophrenia (SZ …

The predictive processing framework encourages us to consider perception as arising from the integration of preexisting knowledge with current sensory input (1). It formulates hallucinations—percepts without accompanying stimuli—in terms of increased weighting of predicted over actual input and thereby suggests an explanation of the computational mechanisms underlying such experiences. Several studies of individuals with or prone to hallucinations have exploited this framework and have suggested ways in which the balance between prediction and input may be altered. In the current issue of Biological Psychiatry, Kafadar et al.(2) elegantly extend this work in 3 ways: 1) they replicate a previous observation (3) that individuals experiencing auditory-verbal hallucinations show a greater influence of prediction on auditory experience; 2) they show that this tendency reflects individuals’ current levels of auditory …

BackgroundPsychotic experiences emerge from abnormalities in perception and belief formation, and occur more commonly in those experiencing childhood trauma. Yet, which precise aspects of belief formation are atypical in psychosis is not well understood. We used a computational modelling approach to characterise belief-updating in young adults in the general population, examine their relationship with psychotic outcomes and trauma, and the extent to which they mediate the trauma-psychosis relationship.MethodsWe used data from 3,360 individuals from the Avon Longitudinal Study of Parents and Children birth cohort who completed assessments for psychotic outcomes, depression, anxiety, and two belief-updating tasks at age 24, and had data available on traumatic events assessed from birth to late adolescence. Unadjusted and adjusted regression and counterfactual mediation methods were used for …

BigBrain is a publicly available 3D model of the human brain at 20 micron isotropic resolution, reconstructed from 7404 histological tissue sections that have been stained for cell bodies. This dataset contains profiles of the staining intensities, sampled at surface positions across the complete isocortex, ranging from the pial surface to the gray/white matter boundary. Since BigBrain's staining is sensitive to cell bodies, profiles are an approximate local measure of cortical cell density.

In the version of this article initially published, there were errors in the affiliations for K. Im (missing affiliation, Division of Newborn Medicine and Neuroradiology, Fetal Neonatal Neuroimaging and Developmental Science Center, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA), J. Lerch (missing affiliation, Mouse Imaging Centre, Toronto, Ontario, Canada), S. Villeneuve and XN Zuo (incorrect affiliation numbers listed), H. Yun (missing affiliation, Division of Newborn Medicine and Neuroradiology, Fetal Neonatal Neuroimaging and Developmental Science Center, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA), and HJ Zar (extra affiliation shown). In addition, the affiliation numbers for all authors listed in the consortium membership section were incorrect by 1–3 digits. The errors have been corrected in the HTML and PDF versions of the article.