Search

Background: Sleep restriction (SR) has been shown to upregulate neuronal reward networks in response to food stimuli, but prior studies were short-term and employed severe SR paradigms., Objective: Our goal was to determine whether mild SR, achieved by delaying bedtimes by 1.5 h, influences neuronal networks responsive to food stimuli compared with maintained adequate sleep (AS) >7 h/night., Methods: A randomized controlled crossover study with 2 6-wk phases, AS (≥7 h sleep/night) and SR (-1.5 h/night relative to screening), was conducted. Adults with AS duration, measured using wrist actigraphy over a 2-wk screening period, and self-reported good sleep quality were enrolled. Resting-state and food-stimulated functional neuroimaging (fMRI) was performed at the endpoint of each phase. Resting-state fMRI data analyses included a priori region-of-interest seed-based functional connectivity, whole-brain voxel-wise analyses, and network analyses. Food task-fMRI analyses compared brain activity patterns in response to food cues between conditions. Paired-sample t tests tested differences between conditions., Results: Twenty-six participants (16 males; age 29.6 ± 5.3 y, body mass index 26.9 ± 4.0 kg/m 2 ) contributed complete data. Total sleep time was 7 h 30 ± 28 min/night during AS compared with 6 h 12 ± 26 min/night during SR. We employed different statistical approaches to replicate prior studies in the field and to apply more robust approaches that are currently advocated in the field. Using uncorrected P value of <0.01, cluster ≥10-voxel thresholds, we replicated prior findings of increased activation in response to foods in reward networks after SR compared with AS (right insula, right inferior frontal gyrus, and right supramarginal gyrus). These findings did not survive more rigorous analytical approaches (Gaussian Random Field theory correction at 2-tailed voxel P < 0.001, cluster P < 0.05)., Conclusions: The results suggest that mild SR leads to increased reward responsivity to foods but with low confidence given the failure to meet significance from rigorous statistical analyses. Further research is necessary to inform the mechanisms underlying the role of sleep on food intake regulation. This trial was registered at clinicaltrials.gov as NCT02960776., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: The striatal-pallidal pathway plays an important role in cognitive control and modulation of behaviors. Globus pallidus interna (GPi), as a primary output structure, is crucial in modulating excitation and inhibition. Studies of GPi in psychiatric illnesses are lacking given the technical challenges of examining this small and functionally diverse subcortical structure., Methods: 71 medication-naïve first episode schizophrenia (FES) participants and 73 healthy controls (HC) were recruited at the Shanghai Mental Health Center. Clinical symptoms and imaging data were collected at baseline and, in a subset of patients, 8 weeks after initiating treatment. Resting-state functional connectivity of sub-regions of the GP were assessed using a novel mask that combines two atlases to create 8 ROIs in the GP., Results: Baseline imaging data from 63 FES patients and 55 HC met quality standards and were analyzed. FES patients exhibited less negative connectivity and increased positive connectivity between the right anterior GPi and several cortical and subcortical areas at baseline compared to HC (P FWE  < 0.05). Positive functional connectivity between the right anterior GPi and several brain areas, including the right dorsal anterior cingulate gyrus, was associated with severity of positive symptoms (P FWE  < 0.05) and predicted treatment response after 8 weeks (n = 28, adjusted R 2  = 0.486, p < 0.001)., Conclusions: Our results implicate striatal-pallidal-thalamic pathways in antipsychotic efficacy. If replicated, these findings may reflect failure of neurodevelopmental processes in adolescence and early adulthood that decrease functional connectivity as an index of failure of the limbic/associative GPi to appropriately inhibit irrelevant signals in psychosis., Competing Interests: Declaration of competing interest Dr. Zhe Chen reports grants from the National Institutes of Health (NIH) and National Science Foundation (NSF) during the conduct of the study. Dr. Chen is also a founder and CEO of NeuroThX, LLC. Dr. Chen also received cloud computing resources supported by the Oracle for Research Award. These funders had no role in the design and conduct of the study, collection and analysis of data and decision to publish the manuscript. Unrelated to this work, Dr. Castellanos is on the Scientific Advisory Board of BOL Pharma, Israel. He is conducting a study of cannabidiol with medication provided by Greenwich Biosciences at no cost through an investigator-initiated study. He also serves as co-chief field editor of Frontiers in Neuroimaging. Dr. Goff has received no research funding or honoraria from commercial entities over the past three years. No other disclosures were reported., (Copyright © 2023. Published by Elsevier B.V.)

Background: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life., Methods: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed., Results: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth., Conclusions: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy., (Copyright © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Introduction: COVID-19 affects multiple organ systems causing substantial long-term morbidity. The implications of the Post-Acute Sequelae of SARS-CoV-2 infection, particularly for primary care, remain unknown. This cross-sectional study examines new symptoms reported at primary care encounters during three post-acute follow-up intervals after initial SARS-CoV-2 infection., Methods: Electronic health record data from the NYU Langone COVID Deidentified Dataset were queried for adults with a positive SARS-CoV-2 PCR test, and then restricted to those with a new ICD-10-CM code documented at a post-acute COVID-related primary care follow-up >14 days after testing positive. New diagnoses and the corresponding Clinical Classifications Software Refined categories were assessed at the following intervals: 0.5-3 months ("subacute"), 3-6 months ("prolonged"), and 6-9 months ("persistent")., Results: Out of 3,154 patients, a new ICD-10-CM code was documented among 499 patients (∼16%). Respiratory complaints, including cough, shortness of breath, dyspnea, and hypoxemia, were most common. Malaise and fatigue were reported consistently among 10-13% of patients at all three time-intervals. Musculoskeletal pain, circulatory symptoms, and sleep-wake disorders were also observed at primary care follow-up., Conclusion: This cross-sectional study provides support of a post-acute COVID syndrome, demonstrating that patients continue to experience symptoms after the acute infection period. Extensive follow-up data allowed for examining new symptoms up to 9 months after initial SARS-CoV-2 infection. Understanding of the course of multi-organ post-acute sequelae is restricted by cross-sectional study design limitations. Standardized, sequelae-related ICD-10-CM codes to specify the type and duration of post-acute COVID-related symptoms would enable better monitoring of the growing number of SARS-CoV-2 infection survivors., Competing Interests: Conflict of interest: None., (© Copyright 2021 by the American Board of Family Medicine.)

Importance: Large-scale neuroimaging studies have revealed group differences in cortical thickness across many psychiatric disorders. The underlying neurobiology behind these differences is not well understood., Objective: To determine neurobiologic correlates of group differences in cortical thickness between cases and controls in 6 disorders: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia., Design, Setting, and Participants: Profiles of group differences in cortical thickness between cases and controls were generated using T1-weighted magnetic resonance images. Similarity between interregional profiles of cell-specific gene expression and those in the group differences in cortical thickness were investigated in each disorder. Next, principal component analysis was used to reveal a shared profile of group difference in thickness across the disorders. Analysis for gene coexpression, clustering, and enrichment for genes associated with these disorders were conducted. Data analysis was conducted between June and December 2019. The analysis included 145 cohorts across 6 psychiatric disorders drawn from the ENIGMA consortium. The numbers of cases and controls in each of the 6 disorders were as follows: ADHD: 1814 and 1602; ASD: 1748 and 1770; BD: 1547 and 3405; MDD: 2658 and 3572; OCD: 2266 and 2007; and schizophrenia: 2688 and 3244., Main Outcomes and Measures: Interregional profiles of group difference in cortical thickness between cases and controls., Results: A total of 12 721 cases and 15 600 controls, ranging from ages 2 to 89 years, were included in this study. Interregional profiles of group differences in cortical thickness for each of the 6 psychiatric disorders were associated with profiles of gene expression specific to pyramidal (CA1) cells, astrocytes (except for BD), and microglia (except for OCD); collectively, gene-expression profiles of the 3 cell types explain between 25% and 54% of variance in interregional profiles of group differences in cortical thickness. Principal component analysis revealed a shared profile of difference in cortical thickness across the 6 disorders (48% variance explained); interregional profile of this principal component 1 was associated with that of the pyramidal-cell gene expression (explaining 56% of interregional variation). Coexpression analyses of these genes revealed 2 clusters: (1) a prenatal cluster enriched with genes involved in neurodevelopmental (axon guidance) processes and (2) a postnatal cluster enriched with genes involved in synaptic activity and plasticity-related processes. These clusters were enriched with genes associated with all 6 psychiatric disorders., Conclusions and Relevance: In this study, shared neurobiologic processes were associated with differences in cortical thickness across multiple psychiatric disorders. These processes implicate a common role of prenatal development and postnatal functioning of the cerebral cortex in these disorders.

Introduction: Over the course of the 20th century, there has been a sharp increase in the consumption of saturated fat and refined sugars. This so-called "western diet" (WD) has been extensively linked to biological alterations and associated functional deficits in the hippocampus of animals. However, the effects of a WD on the human hippocampus are less well-characterized. This preliminary study aimed to extend prior animal work by investigating the effects of a WD on hippocampal volume in children. Methods: Twenty-one healthy children (ages 5-9) completed a structural T1-weighted magnetic resonance imaging scan. Bilateral hippocampal volumes (as regions-of-interest) and bilateral amygdala volumes (as medial temporal lobe control regions-of-interest) were calculated. WD variables were derived from the parent-completed Youth/Adolescent Food Frequency Questionnaire. Specifically, variables were calculated as percent of daily calories consumed from sugars, fats, or a combination of these (WD). Results: While the relationships between overall WD consumption and bilateral hippocampal volumes were not significant, increased fat consumption was significantly related to decreased left hippocampal volume. Sugar consumption was not related to hippocampal size. Control region volumes were not related to any diet variables. Discussion: This study is the first to directly link diet-specifically fat consumption-to decreased left hippocampal volume in children. This extends previous work showing smaller left hippocampal volume related to obesity in pediatric samples. Though preliminary, findings represent an important step toward understanding the impact of diet on child brain development., (Copyright © 2020 Stadterman, Belthoff, Han, Kadesh, Yoncheva and Roy.)

Adolescents are generally characterized as impulsive. However, impulsivity is a multi-dimensional construct that involves multiple component processes. Which of these components contribute to adolescent impulsivity is currently unclear. This study focused on the neural mechanisms underlying individual differences in distinct components of temporal discounting (TD), i.e., the preference for smaller immediate rewards over larger delayed rewards. Participants were 58 adolescents (12-16 years-old) who performed an fMRI TD task with both monetary and snack rewards. Using mixed-effects modeling, we determined participants' average impatience, and further decomposed TD choices into: 1) amount sensitivity (unique contribution of the magnitude of the immediate reward); and 2) delay sensitivity (unique contribution of delay duration). Adolescents' average impatience was positively correlated with frontoparietal and ventral striatal activity during delayed reward choices, and with ventromedial prefrontal cortex activity during immediate reward choices. Adolescents' amount sensitivity was positively associated with ventral striatal and dorsal anterior cingulate cortex activity during immediate reward choices. Delay sensitivity was positively correlated with inferior parietal cortex activity during delayed reward choices. As expected, snacks were discounted more steeply than money, and TD of both reward types was associated with overlapping activation in the inferior parietal cortex. Exploring whether testosterone or estradiol were associated with TD and its neural correlates revealed no significant associations. These findings indicate that distinct components contribute uniquely to TD choice and that individual differences in amount sensitivity are uniquely associated with activation of reward valuation areas, while individual differences in delay sensitivity are uniquely associated with activation of cognitive control areas., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Selective attention to phonology, i.e., the ability to attend to sub-syllabic units within spoken words, is a critical precursor to literacy acquisition. Recent functional magnetic resonance imaging evidence has demonstrated that a left-lateralized network of frontal, temporal, and posterior language regions, including the visual word form area, supports this skill. The current event-related potential (ERP) study investigated the temporal dynamics of selective attention to phonology during spoken word perception. We tested the hypothesis that selective attention to phonology dynamically modulates stimulus encoding by recruiting left-lateralized processes specifically while the information critical for performance is unfolding. Selective attention to phonology was captured by manipulating listening goals: skilled adult readers attended to either rhyme or melody within auditory stimulus pairs. Each pair superimposed rhyming and melodic information ensuring identical sensory stimulation. Selective attention to phonology produced distinct early and late topographic ERP effects during stimulus encoding. Data-driven source localization analyses revealed that selective attention to phonology led to significantly greater recruitment of left-lateralized posterior and extensive temporal regions, which was notably concurrent with the rhyme-relevant information within the word. Furthermore, selective attention effects were specific to auditory stimulus encoding and not observed in response to cues, arguing against the notion that they reflect sustained task setting. Collectively, these results demonstrate that selective attention to phonology dynamically engages a left-lateralized network during the critical time-period of perception for achieving phonological analysis goals. These findings suggest a key role for selective attention in on-line phonological computations. Furthermore, these findings motivate future research on the role that neural mechanisms of attention may play in phonological awareness impairments thought to underlie developmental reading disabilities., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Acetate and formate are major fermentation products of Escherichia coli. Below pH 7, the balance shifts to lactate; an oversupply of acetate or formate retards growth. E. coli W3110 was grown with aeration in potassium-modified Luria broth buffered at pH 6.7 in the presence or absence of added acetate or formate, and the protein profiles were compared by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Acetate increased the steady-state expression levels of 37 proteins, including periplasmic transporters for amino acids and peptides (ArtI, FliY, OppA, and ProX), metabolic enzymes (YfiD and GatY), the RpoS growth phase regulon, and the autoinducer synthesis protein LuxS. Acetate repressed 17 proteins, among them phosphotransferase (Pta). An ackA-pta deletion, which nearly eliminates interconversion between acetate and acetyl-coenzyme A (acetyl-CoA), led to elevated basal levels of 16 of the acetate-inducible proteins, including the RpoS regulon. Consistent with RpoS activation, the ackA-pta strain also showed constitutive extreme-acid resistance. Formate, however, repressed 10 of the acetate-inducible proteins, including the RpoS regulon. Ten of the proteins with elevated basal levels in the ackA-pta strain were repressed by growth of the mutant with formate; thus, the formate response took precedence over the loss of the ackA-pta pathway. The similar effects of exogenous acetate and the ackA-pta deletion, and the opposite effect of formate, could have several causes; one possibility is that the excess buildup of acetyl-CoA upregulates stress proteins but excess formate depletes acetyl-CoA and downregulates these proteins.