Forms of prediction in the nervous system.

The idea that predictions shape how we perceive and comprehend the world has become increasingly influential in the field of systems neuroscience. It also forms an important framework for understanding neuropsychiatric disorders, which are proposed to be the result of disturbances in the mechanisms through which prior information influences perception and belief, leading to the production of suboptimal models of the world. There is a widespread tendency to conceptualize the influence of predictions exclusively in terms of 'top-down' processes, whereby predictions generated in higher-level areas exert their influence on lower-level areas within an information processing hierarchy. However, this excludes from consideration the predictive information embedded in the 'bottom-up' stream of information processing. We describe evidence for the importance of this distinction and argue that it is critical for the development of the predictive processing framework and, ultimately, for an understanding of the perturbations that drive the emergence of neuropsychiatric symptoms and experiences.

Publisher Correction: Forms of prediction in the nervous system.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A Neural Mechanism in the Human Orbitofrontal Cortex for Preferring High-Fat Foods Based on Oral Texture.

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 activity patterns in OFC encoded the economic values associated with particular foods, which reflected the subjective integration of sliding friction with other food properties (sugar, fat, viscosity). Critically, neural sensitivity of OFC to oral texture predicted individuals' fat preferences in a naturalistic eating test: individuals whose OFC was more sensitive to fat-related oral texture consumed more fat during ad libitum eating. Our findings suggest that reward systems of the human brain sense dietary fat from oral sliding friction, a mechanical food parameter that likely governs our daily eating experiences by mediating interactions between foods and oral surfaces. These findings identify a specific role for the human OFC in evaluating oral food textures to mediate preference for high-fat foods.SIGNIFICANCE STATEMENT Fat and sugar enhance the reward value of food by imparting a sweet taste and rich mouthfeel but also contribute to overeating and obesity. Here we used a novel food-engineering approach to realistically quantify the physical-mechanical properties of high-fat liquid foods on oral surfaces and used functional neuroimaging while volunteers sampled these foods and placed monetary bids to consume them. We found that a specific area of the brain's reward system, the orbitofrontal cortex, detects the smooth texture of fatty foods in the mouth and links these sensory inputs to economic valuations that guide eating behavior. These findings can inform the design of low-calorie fat-replacement foods that mimic the impact of dietary fat on oral surfaces and neural reward systems.

The Use of Immersive Virtual Reality in Sensory Sessions on a Specialist Dementia Unit: Service Evaluation of Feasibility and Acceptability.

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 use in other settings.

Cortical and subcortical neuroanatomical signatures of schizotypy in 3004 individuals assessed in a worldwide ENIGMA study.

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), bipolar disorder (BD) and major depression (MDD) patients with controls. Thicker right medial orbitofrontal/ventromedial prefrontal cortex (mOFC/vmPFC) was associated with higher schizotypy scores (r = 0.067, pFDR = 0.02). The cortical thickness profile in schizotypy was positively correlated with cortical abnormalities in SZ (r = 0.285, pspin = 0.024), but not BD (r = 0.166, pspin = 0.205) or MDD (r = -0.274, pspin = 0.073). The schizotypy-related subcortical volume pattern was negatively correlated with subcortical abnormalities in SZ (rho = -0.690, pspin = 0.006), BD (rho = -0.672, pspin = 0.009), and MDD (rho = -0.692, pspin = 0.004). Comprehensive mapping of schizotypy-related brain morphometry in the general population revealed a significant relationship between higher schizotypy and thicker mOFC/vmPFC, in the absence of confounding effects due to antipsychotic medication or disease chronicity. The cortical pattern similarity between schizotypy and schizophrenia yields new insights into a dimensional neurobiological continuity across the extended psychosis phenotype.

BigBrain 3D atlas of cortical layers: Cortical and laminar thickness gradients diverge in sensory and motor cortices.

Histological atlases of the cerebral cortex, such as those made famous by Brodmann and von Economo, are invaluable for understanding human brain microstructure and its relationship with functional organization in the brain. However, these existing atlases are limited to small numbers of manually annotated samples from a single cerebral hemisphere, measured from 2D histological sections. We present the first whole-brain quantitative 3D laminar atlas of the human cerebral cortex. It was derived from a 3D histological atlas of the human brain at 20-micrometer isotropic resolution (BigBrain), using a convolutional neural network to segment, automatically, the cortical layers in both hemispheres. Our approach overcomes many of the historical challenges with measurement of histological thickness in 2D, and the resultant laminar atlas provides an unprecedented level of precision and detail. We utilized this BigBrain cortical atlas to test whether previously reported thickness gradients, as measured by MRI in sensory and motor processing cortices, were present in a histological atlas of cortical thickness and which cortical layers were contributing to these gradients. Cortical thickness increased across sensory processing hierarchies, primarily driven by layers III, V, and VI. In contrast, motor-frontal cortices showed the opposite pattern, with decreases in total and pyramidal layer thickness from motor to frontal association cortices. These findings illustrate how this laminar atlas will provide a link between single-neuron morphology, mesoscale cortical layering, macroscopic cortical thickness, and, ultimately, functional neuroanatomy.

Action selection in early stages of psychosis: an active inference approach.

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 probabilistic task in which action choice (go/no-go) was dissociated from outcome valence (gain or loss). We evaluated group differences in performance and active inference model parameters and performed receiver operating characteristic (ROC) analyses to assess group classification. RESULTS: We found reduced overall performance in patients with psychosis. Active inference modelling revealed that patients showed increased forgetting, reduced confidence in policy selection and less optimal general choice behaviour, with poorer action-state associations. Importantly, ROC analysis showed fair-to-good classification performance for all groups, when combining modelling parameters and performance measures. LIMITATIONS: The sample size is moderate. CONCLUSION: Active inference modelling of this task provides further explanation for dysfunctional mechanisms underlying decision-making in psychosis and may be relevant for future research on the development of biomarkers for early identification of psychosis.

Down, then up: non-parallel genome size changes and a descending chromosome series in a recent radiation of the Australian allotetraploid plant species, Nicotiana section Suaveolentes (Solanaceae).

BACKGROUND AND AIMS: The extent to which genome size and chromosome numbers evolve in concert is little understood, particularly after polyploidy (whole-genome duplication), when a genome returns to a diploid-like condition (diploidization). We study this phenomenon in 46 species of allotetraploid Nicotiana section Suaveolentes (Solanaceae), which formed <6 million years ago and radiated in the arid centre of Australia. METHODS: We analysed newly assessed genome sizes and chromosome numbers within the context of a restriction site-associated nuclear DNA (RADseq) phylogenetic framework. KEY RESULTS: RADseq generated a well-supported phylogenetic tree, in which multiple accessions from each species formed unique genetic clusters. Chromosome numbers and genome sizes vary from n = 2x = 15 to 24 and 2.7 to 5.8 pg/1C nucleus, respectively. Decreases in both genome size and chromosome number occur, although neither consistently nor in parallel. Species with the lowest chromosome numbers (n = 15-18) do not possess the smallest genome sizes and, although N. heterantha has retained the ancestral chromosome complement, n = 2x = 24, it nonetheless has the smallest genome size, even smaller than that of the modern representatives of ancestral diploids. CONCLUSIONS: The results indicate that decreases in genome size and chromosome number occur in parallel down to a chromosome number threshold, n = 20, below which genome size increases, a phenomenon potentially explained by decreasing rates of recombination over fewer chromosomes. We hypothesize that, more generally in plants, major decreases in genome size post-polyploidization take place while chromosome numbers are still high because in these stages elimination of retrotransposons and other repetitive elements is more efficient. Once such major genome size change has been accomplished, then dysploid chromosome reductions take place to reorganize these smaller genomes, producing species with small genomes and low chromosome numbers such as those observed in many annual angiosperms, including Arabidopsis.

How reliable is assessment of children's sentence comprehension using a self-directed app? A comparison of supported versus independent use.

This study reports on the feasibility of using the Test of Complex Syntax- Electronic (TECS-E), as a self-directed app, to measure sentence comprehension in children aged 4 to 5 ½ years old; how testing apps might be adapted for effective independent use; and agreement levels between face-to-face supported computerized and independent computerized testing with this cohort. A pilot phase was completed with 4 to 4;06-year-old children, to determine the appropriate functional app features required to facilitate independent test completion. Following the integration of identified features, children completed the app independently or with adult support (4-4;05 (n = 22) 4;06-4;11 months (n = 55) and 5 to 5;05 (n = 113)) and test re-test reliability was examined. Independent test completion posed problems for children under 5 years but for those over 5, TECS-E is a reliable method to assess children's understanding of complex sentences, when used independently.

Prefrontal Responses during Proactive and Reactive Inhibition Are Differentially Impacted by Stress in Anorexia and Bulimia Nervosa.

Binge eating is a distressing, transdiagnostic eating disorder symptom associated with impulsivity, particularly in negative mood states. Neuroimaging studies of bulimia nervosa (BN) report reduced activity in frontostriatal regions implicated in self-regulatory control, and an influential theory posits that binge eating results from self-regulation failures under stress. However, there is no direct evidence that psychological stress impairs self-regulation in binge-eating disorders, or that any such self-regulatory deficits generalize to binge eating in underweight individuals (i.e., anorexia nervosa bingeing/purging subtype; AN-BP). We therefore determined the effect of acute stress on inhibitory control in 85 women (BN, 33 women; AN-BP, 22 women; 30 control participants). Participants underwent repeated functional MRI scanning during performance of the Stop-signal anticipation task, a validated measure of proactive (i.e., anticipation of stopping) and reactive (outright stopping) inhibition. Neural and behavioral responses to induced stress and a control task were evaluated on 2 consecutive days. Women with BN had reduced proactive inhibition, while prefrontal responses were increased in both AN-BP and BN. Reactive inhibition was neurally and behaviorally intact in both diagnostic groups. Both AN-BP and BN groups showed distinct stress-induced changes in inferior and superior frontal activity during both proactive and reactive inhibition. However, task performance was unaffected by stress. These results offer novel evidence of reduced proactive inhibition in BN, yet inhibitory control deficits did not generalize to AN-BP. Our findings identify intriguing alterations of stress responses and inhibitory function associated with binge eating, but they counsel against stress-induced failures of inhibitory control as a comprehensive explanation for loss-of-control eating.SIGNIFICANCE STATEMENT Binge eating is a common psychiatric syndrome that feels uncontrollable to the sufferer. Theoretically, it has been related to reduced self-regulation under stress, but there remains no direct evidence for this link in binge-eating disorders. Here, we examined how experimentally induced stress affected response inhibition in control participants and women with anorexia nervosa and bulimia nervosa. Participants underwent repeated brain scanning under stressful and neutral conditions. Although patient groups had intact action cancellation, the slowing of motor responses was impaired in bulimia nervosa, even when the likelihood of having to stop increased. Stress altered brain responses for both forms of inhibition in both groups, yet performance remained unimpaired. These findings counsel against a simple model of stress-induced disinhibition as an adequate explanation for binge eating.

Reducing the viral load of SARS-CoV-2 in the saliva of patients with COVID-19.

OBJECTIVE: To evaluate the reduction in the salivary viral load using oral antiseptic mouthwashes in patients testing positive for COVID-19. METHODS: Sixty-three individuals were recruited after testing positive for COVID-19 by real-time RT-PCR assay and divided into 5 groups. Group 1 received sterile water, group 2 received 1.5% hydrogen peroxide solution (HP), group 3 received 0.12% chlorhexidine (CHX), group 4 received 0.1% sodium hypochlorite solution (NaClO), and group 5 received sequential rinses using CHX and HP. After collecting the initial saliva sample, individuals were asked to use the designated mouthwash for 1 min. Additional saliva samples were collected immediately after rinsing, 15, and 30 min after rinsing. Real-time RT-PCR assays for RNA detection of SARS-CoV-2 were performed on the saliva samples. RESULTS: There were no significant differences among the experimental groups and the control group in any period. Compared to the baseline values, there was a significant reduction in the number of copies of SARS-CoV-2 after 30 min in group 2 and immediately after the initial mouthwash in group 4. CONCLUSIONS: No experimental group demonstrated a significant reduction in the viral load compared to the control group.

Effect of health warning labels on motivation towards energy-dense snack foods: Two experimental studies.

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 similar effects on implicit motivation, although HWLs reduced explicit motivation more than IALs. Thus, aversive HWLs appear to act both through low level associative mechanisms affecting implicit motivation, and by additionally emphasizing explicit causal links to health outcomes thereby affecting explicitly motivated choice behaviours.

Dissociable hormonal profiles for psychopathology and stress in anorexia and bulimia nervosa.

BACKGROUND: Anorexia nervosa (AN) and bulimia nervosa (BN) are complex psychiatric conditions, in which both psychological and metabolic factors have been implicated. Critically, the experience of stress can precipitate loss-of-control eating in both conditions, suggesting an interplay between mental state and metabolic signaling. However, associations between psychological states, symptoms and metabolic processes in AN and BN have not been examined. METHODS: Eighty-five women (n = 22 AN binge/purge subtype, n = 33 BN, n = 30 controls) underwent remote salivary cortisol sampling and a 2-day, inpatient study session to examine the effect of stress on cortisol, gut hormones [acyl-ghrelin, peptide tyrosine tyrosine (PYY) and glucagon-like peptide-1] and food consumption. Participants were randomized to either an acute stress induction or control task on each day, and plasma hormones were serially measured before a naturalistic, ad libitum meal. RESULTS: Cortisol-awakening response was augmented in AN but not in BN relative to controls, with body mass index explaining the most variance in post-awakening cortisol (36%). Acute stress increased acyl-ghrelin and PYY in AN compared to controls; however, stress did not alter gut hormone profiles in BN. Instead, a group-by-stress interaction showed nominally reduced cortisol reactivity in BN, but not in AN, compared to controls. Ad libitum consumption was lower in both patient groups and unaffected by stress. CONCLUSIONS: Findings extend previous reports of metabolic dysfunction in binge-eating disorders, identifying unique associations across disorders and under stress. Moreover, we observed disrupted homeostatic signaling in AN following psychological stress, which may explain, in part, the maintenance of dysregulated eating in this serious illness.

Stone size on endoscopic view as a predictor of successful stone retrieval during flexible ureteroscopy: an in vitro analysis.

PURPOSE: Basketing plays an important role during flexible ureteroscopy, but it can be time-consuming, especially when fragments are too large to pass through the ureteral access sheath. We aim to present the optimal on-screen, endoscopic stone size that predicts successful basketing through various access sheaths. METHODS: A tipless basket, individually extended to 5 mm from multiple ureteroscopes: (Flex-Xc, Karl Storz; Flex-X2s, Karl Storz; LithoVue, Boston Scientific; or URF-P6R, Olympus) and via differently sized access sheaths (10-12 Fr through 13-15 Fr), was used in retrieval attempts of various artificial stone sizes (2 mm through 5 mm). A relative endoscopic stone size was recorded as the stone's maximum diameter on endoscopic view compared to the total image diameter. RESULTS: Basketing of stones up to 2.5 mm, yielding relative endoscopic stone sizes of 0.38 (Flex-Xc), 0.30 (Flex-X2s), 0.32 (LithoVue), and 0.34 (URF-P6R), was successful using all access sheaths. Only the 12-14 Fr and greater sheaths allowed for successful basketing of 3 mm stones. Larger stones did not successfully pass through any of the access sheaths. CONCLUSION: Successful stone retrieval can be predicted by estimating the stone's size on screen, which is influenced by the type of flexible ureteroscope and access sheath. In our testing, stones of approximately one-third of the screen size passed successfully in all cases.

Childhood Obesity, Cortical Structure, and Executive Function in Healthy Children.

The development of executive function is linked to maturation of prefrontal cortex (PFC) in childhood. Childhood obesity has been associated with changes in brain structure, particularly in PFC, as well as deficits in executive functions. We aimed to determine whether differences in cortical structure mediate the relationship between executive function and childhood obesity. We analyzed MR-derived measures of cortical thickness for 2700 children between the ages of 9 and 11 years, recruited as part of the NIH Adolescent Brain and Cognitive Development (ABCD) study. We related our findings to measures of executive function and body mass index (BMI). In our analysis, increased BMI was associated with significantly reduced mean cortical thickness, as well as specific bilateral reduced cortical thickness in prefrontal cortical regions. This relationship remained after accounting for age, sex, race, parental education, household income, birth-weight, and in-scanner motion. Increased BMI was also associated with lower executive function. Reduced thickness in the rostral medial and superior frontal cortex, the inferior frontal gyrus, and the lateral orbitofrontal cortex partially accounted for reductions in executive function. These results suggest that childhood obesity is associated with compromised executive function. This relationship may be partly explained by BMI-associated reduced cortical thickness in the PFC.

The serotonin 2C receptor agonist lorcaserin, alone and in combination with the opioid receptor antagonist naltrexone, attenuates binge-like ethanol drinking.

The serotonin (5-HT) system has been implicated in the pathophysiology of alcohol (ethanol; EtOH) use disorders. Lorcaserin, a 5-HT2C receptor agonist, attenuates drug self-administration in animal models. We investigated the effects of lorcaserin on EtOH intake using the drinking-in-the-dark (DID) procedure, an animal model of binge-like drinking. We compared the effects of lorcaserin to those of the Food and Drug Administration (FDA)-approved drug naltrexone and examined the effects of combining lorcaserin and naltrexone. To examine whether effects were specific for EtOH, we examined the effects of lorcaserin and naltrexone, administered alone and in combination, on saccharin intake. Adult male C57BL/6J mice received EtOH access (20% v/v) for 2 h in the home-cage during the first 3 days of the DID procedure, beginning 3 h into the dark cycle. On day 4, mice were injected with lorcaserin, naltrexone, or a combination of lorcaserin and naltrexone prior to a 4-h EtOH access. Intake was measured at 2 and 4 h. Lorcaserin reduced EtOH intake in a dose-dependent fashion over the 2- and 4-h measurement periods. Naltrexone also reduced EtOH intake when administered alone, with dose-dependent effects being more pronounced over 2 h rather than the full 4-h session. Combining lorcaserin and naltrexone reduced binge-like EtOH drinking to a greater extent than either drug alone. A similar pattern of results was obtained for saccharin intake. These results suggest that lorcaserin and naltrexone can have additive effects on binge-like EtOH drinking. They also support continued research into the therapeutic potential of lorcaserin for alcohol use disorders.

Beyond choice architecture: advancing the science of changing behaviour at scale.

Addressing the global threats to population and planetary health requires changing many behaviours at scale. This demands consideration not only of the effect size of an intervention but also its reach - the proportion of the population exposed to the intervention.We propose that a relatively under-researched and generally poorly specified set of interventions involving changes to physical micro-environments - often referred to as Choice Architecture - has the potential to make a significant contribution to meeting this urgent challenge.Realising the potential of Choice Architecture interventions requires integration of basic - i.e. laboratory-based - and applied - i.e. field-based - research, generating interventions that can be delivered at scale alongside advancing theory. We illustrate this with examples to highlight the complementarity of laboratory and field studies informed by and in turn updating the results of evidence synthesis. The examples comprise two sets of interventions - changing the relative availability of products and changing their size - to reduce consumption of meat, energy from food and alcohol across populations.

Modelling delusions as temporally-evolving beliefs.

Introduction: Delusions demand an explanation in terms of their neural, psychological, and sociological mechanisms. We must bridge these levels of explanation in order to understand and ultimately treat delusions. To this end, debates continue as to the number of contributing factors, how those factors interact, and their underlying computational mechanisms.Methods: One popular family of models suggests that two separate insults are necessary, a problem with perception and an independent problem with belief. In particular, new work proposes that the belief problem entails a bias against disconfirmatory evidence - yielding the characteristic fixity of delusions. Here, we evaluate that claim, as well as explanations of delusions more broadly.Results: We suggest that such a bias may not explain enough of the variance in belief updating in delusional participants, and, more fundamentally, it might rule out specific accounts of delusions, since, such a bias might prevent them from forming in the first place, under particular assumptions about cognitive architectures.Conclusion: We suggest conceptualising delusions as an evolving uncertainty driven negotiation between beliefs and evidence, in which initial formation is fuelled by unexpected uncertainty, but, once formed, the delusion engenders new expectations about uncertainty that tune down updating but also facilitate the elastic assimilation of contradictory evidence.

The impact on selection of non-alcoholic vs alcoholic drink availability: an online experiment.

BACKGROUND: Increasing the availability of healthier food increases its selection and consumption. However, there is an absence of evidence related to alcohol. This study aimed to estimate the impact of increasing the absolute and relative availability of non-alcoholic compared to alcoholic drinks on selection. We also assessed whether effects were modified by cognitive resource. METHODS: UK adult weekly alcohol consumers (n = 808) were recruited to an online experiment with a hypothetical drink selection task. Participants were randomly assigned to one of eight conditions, in a 4 (availability) × 2 (cognitive resource) factorial design. The four availability conditions were: i. Reference 1 (two non-alcoholic, two alcoholic drinks); ii. Reference 2 (four non-alcoholic, four alcoholic drinks); iii. Increased non-alcoholic drinks (six non-alcoholic, two alcoholic drinks); iv. Increased alcoholic drinks (two non-alcoholic, six alcoholic drinks). The two cognitive resource conditions were: a. Low (high time pressure); b. High (low time pressure). Logistic regression was used to assess selection of a non-alcoholic drink. RESULTS: 49% of participants selected a non-alcoholic drink in the Increased non-alcoholic drinks condition, compared to 36% in Reference 1, 39% in Reference 2, and 26% in the Increased alcoholic drinks condition. Non-alcoholic drink selection was similar between Reference 1 and 2 when the total number of drinks increased (absolute availability) but the proportion of non-alcoholic compared to alcoholic drinks (relative availability) was unchanged (OR = 1.15, 95% CI 0.77, 1.73). In contrast, the odds of selecting a non-alcoholic drink were 71% higher when both absolute and relative availability of non-alcoholic compared to alcoholic drinks was increased from Reference 1 to the Increased non-alcoholic drinks condition (OR: 1.71, 95% CI 1.15, 2.54), and 48% higher when increased from Reference 2 to the Increased non-alcoholic drinks condition (OR: 1.48, 95% CI 0.99, 2.19). There was no evidence of an effect of cognitive resource. CONCLUSIONS: Greater availability of non-alcoholic drinks, compared to alcoholic drinks, increased their online selection, an effect that may be larger when changing their relative availability, i.e., increasing the proportion of non-alcoholic drinks. Naturalistic studies are needed to determine the impact of availability interventions on reducing alcohol purchasing and consumption.

BMI-related cortical morphometry changes are associated with altered white matter structure.

BACKGROUND: While gross measures of brain structure have shown alterations with increasing body mass index (BMI), the extent and nature of such changes has varied substantially across studies. Here, we sought to determine whether small-scale morphometric measures might prove more sensitive and reliable than larger scale measures and whether they might offer a valuable opportunity to link cortical changes to underlying white matter changes. To examine this, we explored the association of BMI with millimetre-scale Gaussian curvature, in addition to standard measures of morphometry such as cortical thickness, surface area and mean curvature. We also assessed the volume and integrity of the white matter, using white matter signal intensity and fractional anisotropy (FA). We hypothesised that BMI would be linked to small-scale changes in Gaussian curvature and that this phenomenon would be mediated by changes in the integrity of the underlying white matter. METHODS: The association of global measures of T1-weighted cortical morphometry with BMI was examined using linear regression and mediation analyses in two independent groups of healthy young to middle aged human subjects (n1 = 52, n2 = 202). In a third dataset of (n3 = 897), which included diffusion tensor images, we sought to replicate the significant associations established in the first two datasets, and examine the potential mechanistic link between BMI-associated cortical changes and global FA. RESULTS: Gaussian curvature of the white matter surface showed a significant, positive association with BMI across all three independent datasets. This effect was mediated by a negative association between the integrity of the white matter and BMI. CONCLUSIONS: Increasing BMI is associated with changes in white matter microstructure in young to middle-aged healthy adults. Our results are consistent with a model whereby BMI-linked cortical changes are mediated by the effects of BMI on white matter microstructure.