Hierarchical Principal Components for Data-Driven Multiresolution fMRI Analyses.

Understanding the organization of neural processing is a fundamental goal of neuroscience. Recent work suggests that these systems are organized as a multiscale hierarchy, with increasingly specialized subsystems nested inside general processing systems. Current neuroimaging methods, such as independent component analysis (ICA), cannot fully capture this hierarchy since they are limited to a single spatial scale. In this manuscript, we introduce multiresolution hierarchical principal components analysis (hPCA) and compare it to ICA using simulated fMRI datasets. Furthermore, we describe a parametric statistical filtering method developed to focus analyses on biologically relevant features. Lastly, we apply hPCA to the Human Connectome Project (HCP) to demonstrate its ability to estimate a hierarchy from real fMRI data. hPCA accurately estimated spatial maps and time series from networks with diverse hierarchical structures. Simulated hierarchies varied in the degree of branching, such as two-way or three-way subdivisions, and the total number of levels, with varying equal or unequal subdivision sizes at each branch. In each case, as well as in the HCP, hPCA was able to reconstruct a known hierarchy of networks. Our results suggest that hPCA can facilitate more detailed and comprehensive analyses of the brain's network of networks and the multiscale regional specializations underlying neural processing and cognition.

Relationship between functional connectivity and weight-gain risk of antipsychotics in schizophrenia.

BACKGROUND: The mechanisms by which antipsychotic medications (APs) contribute to obesity in schizophrenia are not well understood. Because AP effects on functional brain connectivity may contribute to weight effects, the current study investigated how AP-associated weight-gain risk relates to functional connectivity in schizophrenia. METHODS: Fifty-five individuals with schizophrenia (final N = 54) were divided into groups based on previously reported AP weight-gain risk (no APs/low risk [N = 19]; moderate risk [N = 17]; high risk [N = 18]). Resting-state functional magnetic resonance imaging (fMRI) was completed after an overnight fast ("fasted") and post-meal ("fed"). Correlations between AP weight-gain risk and functional connectivity were assessed at the whole-brain level and in reward- and eating-related brain regions (anterior insula, caudate, nucleus accumbens). RESULTS: When fasted, greater AP weight-gain risk was associated with increased connectivity between thalamus and sensorimotor cortex (pFDR = 0.021). When fed, greater AP weight-gain risk was associated with increased connectivity between left caudate and left precentral/postcentral gyri (pFDR = 0.048) and between right caudate and multiple regions, including the left precentral/postcentral gyri (pFDR = 0.001), intracalcarine/precuneal/cuneal cortices (pFDR < 0.001), and fusiform gyrus (pFDR = 0.008). When fed, greater AP weight-gain risk was also associated with decreased connectivity between right anterior insula and ventromedial prefrontal cortex (pFDR = 0.002). CONCLUSIONS: APs with higher weight-gain risk were associated with greater connectivity between reward-related regions and sensorimotor regions when fasted, perhaps relating to motor anticipation for consumption. Higher weight-gain risk APs were also associated with increased connectivity between reward, salience, and visual regions when fed, potentially reflecting greater desire for consumption following satiety.

Functional magnetic resonance imaging of headache: Issues, best-practices, and new directions, a narrative review.

OBJECTIVE: To ensure readers are informed consumers of functional magnetic resonance imaging (fMRI) research in headache, to outline ongoing challenges in this area of research, and to describe potential considerations when asked to collaborate on fMRI research in headache, as well as to suggest future directions for improvement in the field. BACKGROUND: Functional MRI has played a key role in understanding headache pathophysiology, and mapping networks involved with headache-related brain activity have the potential to identify intervention targets. Some investigators have also begun to explore its use for diagnosis. METHODS/RESULTS: The manuscript is a narrative review of the current best practices in fMRI in headache research, including guidelines on transparency and reproducibility. It also contains an outline of the fundamentals of MRI theory, task-related study design, resting-state functional connectivity, relevant statistics and power analysis, image preprocessing, and other considerations essential to the field. CONCLUSION: Best practices to increase reproducibility include methods transparency, eliminating error, using a priori hypotheses and power calculations, using standardized instruments and diagnostic criteria, and developing large-scale, publicly available datasets.

Sex Differences in Effects of Mood, Eating-Related Behaviors, and BMI on Food Appeal and Desire to Eat: A Cross-Sectional Survey Study.

Although sex differences in food intake have been observed consistently, contributing factors are not well understood. Using a cross-sectional online survey (n = 306; 151 men, 155 women), this study aimed to assess how sex impacts relationships between food ratings (appeal/desire to eat for high-calorie (HC) and low-calorie (LC) food images) and eating-related attitudes/behaviors, body mass index (BMI), and mood. Across participants, increased state- and trait-based hunger, disinhibition, and cravings were associated with both increased HC appeal and desire (p < 0.001). Increased state-based hunger and cravings were associated with greater LC desire (p < 0.001). Greater satiety was associated with decreased desire for both HC and LC (p < 0.001), while greater anxiety was associated with increased desire for both HC and LC (p < 0.001). Significant associations between BMI and food ratings were not observed. Women reported greater dietary restraint, trait-based hunger, disinhibition, eating disorder-related behaviors, depression, and stress compared to men, in addition to greater appeal and familiarity with LC foods (all p < 0.05). Significant effects of sex on the associations between food ratings and eating-related attitudes/behaviors, BMI, and mood were not observed, however. Findings support the importance of considering mood and eating-related attitudes/behaviors in investigations of food cue responsivity.

Appetitive and Metabolic Responses to an Exercise versus Dietary Intervention in Adults with Obesity.

Introduction/Purpose: Dietary restriction (DIET) and aerobic exercise (AEX) interventions may impact energy balance differently. Our aim was to describe the effects of weight loss interventions via DIET or AEX on measures of energy balance. Methods: Adults with overweight or obesity were randomized to 12 weeks of DIET or AEX with similar calorie deficit goals. A study day was conducted before and after the intervention to assess subjective and hormonal (ghrelin, peptide-YY, glucagon-like peptide-1) appetite responses to a control meal, ad libitum energy intake (EI) at a single meal, and over three days of free-living conditions and eating behavior traits. Resting metabolic rate (RMR) was measured with indirect calorimetry and adjusted for body composition measured by dual X-ray absorptiometry. Non-exercise activity was measured using accelerometers. Results: Forty-four individuals were included (age: 37 ± 9 years, body mass index: 30.6 ± 3.1 kg/m2). Both interventions resulted in weight and fat mass loss. The DIET group lost fat-free mass, although differences between groups were not significant (DIET: -1.2 ± 1.7 kg, p<0.001; AEX: 0.4 ± 1.5 kg, p=0.186; p=0.095 interaction). There were no differences in RMR after body composition adjustment. Both interventions were associated with an increase in dietary restraint (DIET: 4.9 ± 1.2, AEX: 2.8 ± 0.7; p<0.001 in both groups). Hunger decreased with DIET (-1.4 ± 0.5, p=0.003), and disinhibition decreased with AEX (-1.5 ± 0.5, p<0.001), although these changes were not different between groups (i.e., no group × time interaction). No other differences in appetite, EI, or non-exercise physical activity were observed within or between groups. Conclusions: AEX did not result in compensatory alterations in appetite, ad libitum EI, or physical activity, despite assumed increased energy expenditure. Modest evidence also suggested that disinhibition and hunger may be differentially impacted by weight loss modality.

An implicit priming intervention alters brain and behavioral responses to high-calorie foods: a randomized controlled study.

BACKGROUND: Conditioned food cues (e.g., smell, sight) can affect intake of foods associated with those cues, regardless of homeostatic need. As such, altering automatic associations with food cues could support weight loss or maintenance efforts by affecting the salience of those cues and the effort required to resist consumption. OBJECTIVES: This study investigated neuronal and behavioral effects of an implicit priming (IP) intervention, in which negatively valenced images were paired with high-calorie foods and positively valenced images with low-calorie foods. Priming images were presented immediately before food images, but below conscious perception (20 ms). We hypothesized that this evaluative conditioning approach could alter food cue responses by modifying affective associations. METHODS: The final sample included 41 adults with BMI ≥25 kg/m2 (n = 22, active IP; n = 19, control IP). In control IP, food images were primed with neutral, scrambled images. Participants completed a visual food cue task during fMRI, both before and after IP. To determine the replicability of prior behavioral findings, food image ratings were completed before and after IP as a secondary outcome. RESULTS: In a whole-brain analysis, reduced dorsolateral prefrontal cortex (dlPFC) response to high-calorie foods was observed after active compared with control IP (t = 4.93, P = 0.033). With a region of interest analysis, reduced response to high-calorie foods in active compared with control IP was also observed in the striatum (t = 2.40, P = 0.009) and insula (t = 2.38, P = 0.010). Active compared with control IP was associated with reduced high-calorie food ratings (F = 4.70, P = 0.038). CONCLUSIONS: Reduced insula and striatum response to high-calorie foods after active compared with control IP suggests effectiveness of IP in altering food cue salience. Reduced dlPFC response to high-calorie foods after active compared with control IP may reflect fewer attentional resources being directed to those images and reduced engagement of inhibitory processes.This trial was registered at clinicaltrials.gov as NCT02347527.

Mindfulness-based intervention in adolescents at risk for excess weight gain: 1.5-year follow-up of pilot randomized controlled trial.

BACKGROUND: Mindfulness-based intervention (MBI) may offer a novel means of preventing excess weight gain in adolescents, theoretically by decreasing stress-eating through altering executive functioning (EF) and food-reward sensitivity. METHODS: N = 54 12-17y girls and boys at-risk for excess weight gain (i.e., BMI ≥70th percentile or two biological parents with reported obesity [BMI ≥30 kg/m2]) participated in a 1.5-year follow-up of a pilot randomized controlled trial comparing 6-week/6-session MBI (n = 29) and a health education (HE) control (n = 25). Laboratory stress-eating, food-reward sensitivity, EF, perceived stress, and BMI/adiposity were re-assessed at 1.5-years with validated measures. Changes from baseline to 1.5-year follow-up were explored with ANCOVA, accounting for the respective baseline outcome, age, and sex. RESULTS: Compared to MBI (M = -21, SE = 59), HE had greater increases in stress-eating from baseline to 1.5-years (M = 194, SE = 63, Cohen's d = 0.59, p = .01). There were no other between-condition differences. DISCUSSION: MBI may prevent worsening stress-eating for adolescents at-risk for excess weight gain. The potential for MBI as an intervention for stress-eating and ultimately, weight stabilization warrants testing in an adequately-powered trial.

Stable Meta-Networks, Noise, and Artifacts in the Human Connectome: Low- to High-Dimensional Independent Components Analysis as a Hierarchy of Intrinsic Connectivity Networks.

Connectivity within the human connectome occurs between multiple neuronal systems-at small to very large spatial scales. Independent component analysis (ICA) is potentially a powerful tool to facilitate multi-scale analyses. However, ICA has yet to be fully evaluated at very low (10 or fewer) and ultra-high dimensionalities (200 or greater). The current investigation used data from the Human Connectome Project (HCP) to determine the following: (1) if larger networks, or meta-networks, are present at low dimensionality, (2) if nuisance sources increase with dimensionality, and (3) if ICA is prone to overfitting. Using bootstrap ICA, results suggested that, at very low dimensionality, ICA spatial maps consisted of Visual/Attention and Default/Control meta-networks. At fewer than 10 components, well-known networks such as the Somatomotor Network were absent from results. At high dimensionality, nuisance sources were present even in denoised high-quality data but were identifiable by correlation with tissue probability maps. Artifactual overfitting occurred to a minor degree at high dimensionalities. Basic summary statistics on spatial maps (maximum cluster size, maximum component weight, and average weight outside of maximum cluster) quickly and easily separated artifacts from gray matter sources. Lastly, by using weighted averages of bootstrap stability, even ultra-high dimensional ICA resulted in highly reproducible spatial maps. These results demonstrate how ICA can be applied in multi-scale analyses, reliably and accurately reproducing the hierarchy of meta-networks, large-scale networks, and subnetworks, thereby characterizing cortical connectivity across multiple spatial scales.

Altered between-network connectivity in individuals prone to obesity.

OBJECTIVE: Investigating intrinsic brain functional connectivity may help identify the neurobiology underlying cognitive patterns and biases contributing to obesity propensity. To address this, the current study used a novel whole-brain, data-driven approach to examine functional connectivity differences in large-scale network interactions between obesity-prone (OP) and obesity-resistant (OR) individuals. METHODS: OR (N = 24) and OP (N = 25) adults completed functional magnetic resonance imaging (fMRI) during rest. Large-scale brain networks were identified using independent component analysis (ICA). Voxel-specific between-network connectivity analysis assessed correlations between ICA component time series' and individual voxel time series, identifying regions strongly connected to many networks, i.e., "hubs". RESULTS: Significant group differences in between-network connectivity (OP vs. OR; FDR-corrected) were observed in bilateral basal ganglia (left: q = 0.009; right: q = 0.010) and right dorsolateral prefrontal cortex (dlPFC; q = 0.026), with OP>OR. Basal ganglia differences were largely driven by a more strongly negative correlation with a lateral sensorimotor network in OP, with dlPFC differences driven by a more strongly negative correlation with an inferior visual network in OP. CONCLUSIONS: Greater between-network connectivity was observed in the basal ganglia and dlPFC in OP, driven by stronger associations with lateral sensorimotor and inferior visual networks, respectively. This may reflect a disrupted balance between goal-directed and habitual control systems and between internal/external monitoring processes.

Autism Spectrum Disorder Symptoms are Associated with Connectivity Between Large-Scale Neural Networks and Brain Regions Involved in Social Processing.

The neurobiology of autism spectrum disorder remains poorly understood. The present study addresses this knowledge gap by examining the relationship between functional brain connectivity and Autism Diagnostic Observation Schedule (ADOS) scores using publicly available data from the Autism Brain Imaging Data Exchange (ABIDE) database (N = 107). This relationship was tested across all brain voxels, without a priori assumptions, using a novel statistical approach. ADOS scores were primarily associated with decreased connectivity to right temporoparietal junction, right anterior insula, and left fusiform gyrus (p < 0.05, corrected). Seven large-scale brain networks influenced these associations. Findings largely encompassed brain regions involved in processing socially relevant information, highlighting the importance of these processes in autism spectrum disorder.

Effects of Exercise during Weight Loss Maintenance on Appetite Regulation in Women.

Exercise is accepted as a method to improve weight loss maintenance; however, the mechanisms by which this occurs have yet to be elucidated. In this pilot study, 13 women with obesity underwent a structured weight loss program (goal 8%-10% weight loss) and were then randomized to either a 12-wk diet (n = 7) or an aerobic exercise training (n = 6) intervention aimed at maintaining weight loss. At baseline, post-weight loss, and following the weight loss maintenance interventions, measurements of appetite (hunger and satiety) and appetite-regulating hormones (leptin, ghrelin, peptide tyrosine tyrosine, and glucagon-like peptide 1) were obtained after an overnight fast and for 3 h after a standardized test meal. Ad libitum energy intake was measured at a lunch meal. During the weight loss phase, participants lost 9.1% ± 1.1% of baseline body weight. Participants in both groups maintained weight loss during the 12-wk weight loss maintenance intervention. No differences in fasting leptin (P = 0.68) or in ghrelin (P = 0.30), peptide tyrosine tyrosine (P = 0.93), and glucagon-like peptide 1 (P = 0.98) area under the curve were detected between groups. Similarly, ratings of hunger (P = 0.99) and satiety (P = 0.65) area under the curve after the standardized test meal also did not differ between the groups nor did ad libitum energy intake at lunch. In summary, the 12-wk diet and exercise interventions were equally effective at maintaining weight loss in women, and no differences in measures of appetite regulation and food intake were found.

Hemodynamic responses are abnormal in isolated cervical dystonia.

Neuroimaging studies using functional magnetic resonance imaging (fMRI), which measures brain activity by detecting the changes in blood oxygenation levels, are advancing our understanding of the pathophysiology of dystonia. Neurobiological disturbances in dystonia, however, may affect neurovascular coupling and impact the interpretability of fMRI studies. We evaluated here whether the hemodynamic response patterns during a behaviorally matched motor task are altered in isolated cervical dystonia (CD). Twenty-five CD patients and 25 healthy controls (HCs) underwent fMRI scanning during a paced finger tapping task (nondystonic task in patients). Imaging data were analyzed using a constrained principal component analysis-a statistical method that combines regression analysis and principal component analysis and enables the extraction of task-related functional networks and determination of the spatial and temporal hemodynamic response patterns associated with the task performance. Data from three patients and two controls were removed due to excessive movement. No significant differences in demographics or motor performance were observed. Three task-associated functional brain networks were identified. During task performance, reduced hemodynamic responses were seen in a sensorimotor network and in a network that included key nodes of the default mode, executive control and visual networks. During rest, reductions in hemodynamic responses were seen in the cognitive/visual network. Lower hemodynamic responses within the primary sensorimotor network in patients were correlated with the increased dystonia severity. Pathophysiological disturbances in isolated CD, such as alterations in inhibitory signaling and dopaminergic neurotransmission, may impact neurovascular coupling. Not accounting for hemodynamic response differences in fMRI studies of dystonia could lead to inaccurate results and interpretations.

Mindfulness-based group intervention in adolescents at-risk for excess weight gain: A randomized controlled pilot study.

OBJECTIVES: To assess feasibility/acceptability of a mindfulness-based approach to excess weight prevention in adolescents at-risk for excess weight gain. To pilot test efficacy of a mindfulness-based intervention for improving food reward sensitivity, stress-eating, executive function (EF), and BMI/adiposity. METHODS: A pilot randomized controlled trial was conducted with 12-17y adolescents at-risk for excess weight gain based on above-average weight (body mass index [BMI]≥70%ile) or parental history of obesity (BMI≥30 kg/m2). Adolescents were randomized to a mindfulness-based (n = 29) or health education control group (n = 25) that met for six weekly one-hour sessions. Feasibility/acceptability were determined from attendance and acceptability survey ratings. At baseline, six-week and six-month follow-up, adolescents' perceived stress was measured with the Perceived Stress Scale, food reward sensitivity with a behavioral task, stress-eating during a laboratory test meal, and EF with the parent-reported Behavior Rating Inventory of Executive Function and NIH Toolbox. At the same intervals, BMI indices and body fat by air displacement plethysmography were assessed in a fasted state. RESULTS: Median session attendance was 6:6 sessions in both conditions; program acceptability ratings were above-average. Compared to health education, adolescents in mindfulness had lower food reward sensitivity at six-months (Cohen's d = 0.64, p = .01). There were no between-condition differences in BMI (mindfulness vs. health educationΔsix-months 95%CI 0.20, 1.52 kg/m2 vs. 0.21, 1.62 kg/m2) or adiposity (-3.64, -0.61% vs. -4.31, -1.04%) changes. CONCLUSIONS: A mindfulness-based group intervention is feasible/acceptable among adolescents at-risk for excess weight. In this pilot sample, mindfulness and health education were equivocal for BMI/adiposity outcomes. Future trials with a larger, adequately-powered sample and longer-term follow-up are necessary to test efficacy of a mindfulness-based intervention for food reward sensitivity, stress-eating, EF, and stabilizing growth trajectories in youth at-risk for adult obesity.

Comparison of surgical versus diet-induced weight loss on appetite regulation and metabolic health outcomes.

Bariatric surgery is associated with significant and sustained weight loss and improved metabolic outcomes. It is unclear if weight loss alone is the main mechanism of improved metabolic health. The purpose of this trial was to compare indices of appetite regulation, insulin sensitivity and energy intake (EI) between participants achieving 10 kg of weight loss via Roux-en-Y Gastric Bypass (RYGB) or dietary restriction (DIET); intake of a very low calorie liquid diet (800 kcal/d; 40% protein, 40% fat, 20% carbohydrate that matched the post-RYGB dietary protocol). Adults qualifying for bariatric surgery were studied before and after 10 kg of weight loss (RYGB [n = 6]) or DIET [n = 17]). Appetite (hunger, satiety, and prospective food consumption [PFC]), appetite-related hormones, and metabolites (ghrelin, PYY, GLP-1, insulin, glucose, free fatty acids [FFA], and triglycerides [TG]) were measured in the fasting state and every 30 min for 180 min following breakfast. Participants were provided lunch to evaluate acute ad libitum EI, which was similarly reduced in both groups from pre to post weight loss. Fasting ghrelin was reduced to a greater extent following RYGB compared to DIET (P = 0.04). Area under the curve (AUC) for ghrelin (P = 0.01), hunger (P < 0.01) and PFC (P < 0.01) increased after DIET compared to RYGB, following 10 kg weight loss. Satiety AUC increased after RYGB and decreased after DIET (P < 0.01). Glucose and insulin (fasting and AUC) decreased in both groups. FFA increased in both groups, with a greater increase in AUC seen after RYGB versus DIET (P = 0.02). In summary, appetite-related indices were altered in a manner that, if maintained, may promote a sustained reduction in energy intake with RYGB compared to DIET. Future work with a larger sample size and longer follow-up will be important to confirm and extend these findings.

Eating in the absence of hunger in young children is related to brain reward network hyperactivity and reduced functional connectivity in executive control networks.

BACKGROUND: Recent work has implicated disinhibited eating behaviours (DEB) as a potential pathway toward obesity development in children. However, the underlying neurobiology of disinhibited eating behaviours in young, healthy weight children, prior to obesity development, remains unknown. OBJECTIVES: This study tested the relationship between DEB and intrinsic neuronal activity and connectivity in young children without obesity. METHODS: Brain networks implicated in overeating including reward, salience and executive control networks, and the default mode network were investigated. DEB was measured by the eating in the absence of hunger (EAH) paradigm with postlunch kilocalories consumed from highly palatable foods (EAH kcal) used as the predictor. Intrinsic neuronal activity within and connectivity between specified networks were measured via resting-state functional magnetic resonance imaging. Eighteen typically developing children (mean age = 5.8 years) were included. RESULTS: EAH kcal was positively associated with activity of the nucleus accumbens, a major reward network hub (P < 0.05, corrected). EAH kcal was negatively associated with intrinsic prefrontal cortex connectivity to the striatum (P < 0.01, corrected). CONCLUSIONS: These results suggest that neural aspects of DEB are detectable in young children without obesity, providing a potential tool to better understand the development of obesity in this population.

Predicting academic career outcomes by predoctoral publication record.

BACKGROUND: For students entering a science PhD program, a tenure-track faculty research position is often perceived as the ideal long-term goal. A relatively small percentage of individuals ultimately achieve this goal, however, with the vast majority of PhD recipients ultimately finding employment in industry or government positions. Given the disparity between academic career ambitions and outcomes, it is useful to understand factors that may predict those outcomes. Toward this goal, the current study examined employment status of PhD graduates from biomedical sciences programs at the University of Colorado Anschutz Medical Campus (CU AMC) and related this to metrics of predoctoral publication records, as well as to other potentially important factors, such as sex and time-since-degree, to determine if these measures could predict career outcomes. METHODS: Demographic information (name, PhD program, graduation date, sex) of CU AMC biomedical sciences PhD graduates between 2000 and 2015 was obtained from University records. Career outcomes (academic faculty vs. non-faculty) and predoctoral publication records (number and impact factors of first-author and non-first-author publications) were obtained via publicly available information. Relationships between predoctoral publication record and career outcomes were investigated by (a) comparing faculty vs. non-faculty publication metrics, using t-tests, and (b) investigating the ability of predoctoral publication record, sex, and time-since-degree to predict career outcomes, using logistic regression. RESULTS: Significant faculty vs. non-faculty differences were observed in months since graduation (p < 0.001), first-author publication number (p = 0.001), average first-author impact factor (p = 0.006), and highest first-author impact factor (p = 0.004). With sex and months since graduation as predictors of career outcome, the logistic regression model was significant (p < 0.001), with both being male and having more months since graduation predicting career status. First-author related publication metrics (number of publications, average impact factor, highest impact factor) all significantly improved model fit (χ2 < 0.05 for all) and were all significant predictors of faculty status (p < 0.05 for all). Non-first-author publication metrics did not significantly improve model fit or predict faculty status. DISCUSSION: Results suggest that while sex and months since graduation also predict career outcomes, a strong predoctoral first-author publication record may increase likelihood of obtaining an academic faculty research position. Compared to non-faculty, individuals employed in faculty positions produced more predoctoral first-author publications, with these being in journals with higher impact factors. Furthermore, first-author publication record, sex, and months since graduation were significant predictors of faculty status.

Greater Reward-Related Neuronal Response to Hedonic Foods in Women Compared with Men.

OBJECTIVE: The current study aimed to identify how sex influences neurobiological responses to food cues, particularly those related to hedonic eating, and how this relates to obesity propensity, using functional magnetic resonance imaging (fMRI). METHODS: Adult men and women who were either obesity resistant (OR) or obesity prone (OP) underwent fMRI while viewing visual food cues (hedonic foods, neutral foods, and nonfood objects) in both fasted and fed states. RESULTS: When fasted, a significant sex effect on the response to hedonic vs. neutral foods was observed, with greater responses in women than men in the nucleus accumbens (P = 0.0002) and insula (P = 0.010). Sex-based differences were not observed in the fed state. No significant group effects (OP vs. OR) or group-by-sex interactions were observed in fasted or fed states. CONCLUSIONS: Greater fasted responses to hedonic food cues in reward-related brain regions were observed in women compared with men, suggesting that women may be more sensitive to the reward value of hedonic foods than men when fasted. This may indicate sex-dependent neurophysiology underlying eating behaviors.

Exposure to maternal diabetes in utero and offspring eating behavior: The EPOCH study.

The risk of becoming overweight among offspring exposed to gestational diabetes (GDM) in utero is two-fold higher than in the general population. The responsible mechanisms are likely multifactorial, with some evidence that GDM exposure alters brain satiety signaling, which may impact eating behavior. To better understand these effects, we investigated the relationship between GDM exposure, eating behavior, and total energy intake in 268 adolescents from the Exploring Perinatal Outcomes among Children cohort, who were exposed (n = 50) or not exposed (n = 217) to GDM in utero. Eating behavior was measured by the Eating in the Absence of Hunger in Children and Adolescents (EAH-C) questionnaire, which included subscale scores for Negative Affect, External Stimuli, and Fatigue/Boredom. Total energy intake (kcal/day) was derived from the Block Kid's Food Questionnaire. The associations between GDM exposure and the outcomes of total score and each EAH-C subscale were evaluated in separate multivariable models. In addition to the main predictor, GDM, the models included a GDM-by-sex interaction term and were adjusted for important covariates. The associations between EAH-C total and subscale scores and the outcome of total energy intake were also tested in separate multivariable models. Female offspring exposed to GDM in utero (vs unexposed males and females) were more likely to continue eating beyond satiation due to feelings of boredom and fatigue (ß = 0.47, 95% CI: 0.11, 0.83), and in general (EAH-C total score; ß = 4.20, 95% CI: 0.56, 7.86) compared to unexposed males. All EAH-C subscale and total scores were significantly, positively associated with higher energy intake (p < 0.05 for all, respectively). Our findings highlight the need for further investigation into the possible early life programming of eating behaviors by GDM exposure in utero.

Nicotinic modulation of salience network connectivity and centrality in schizophrenia.

Although functional abnormalities of the salience network are associated with schizophrenia, the acute effects of nicotine on its function and network dynamics during the resting state in patients are poorly understood. In this study, the effects of a 7 mg nicotine patch (vs. placebo) on salience network connectivity were examined in 17 patients with schizophrenia and 19 healthy subjects. We hypothesized abnormal connectivity between the salience network and other major networks (e.g. executive network) in patients under placebo administration and amelioration of this difference after nicotine. We also examined effects of nicotine on betweenness centrality (a measure of the influence of a region on information transfer throughout the brain) and local efficiency (a measure of local information transfer) of the network. A hybrid independent component analysis (ICA)/seed-based connectivity approach was implemented in which the salience network was extracted by ICA and cortical network peaks (anterior cingulate cortex (ACC), left and right insula) were used as seeds for whole-brain seed-to-voxel connectivity analysis. Significant drug X diagnosis interactions were observed between the ACC seed and superior parietal lobule and ventrolateral prefrontal cortex. A significant interaction effect was also observed between the left insula seed and middle cingulate cortex. During placebo conditions, abnormal connectivity predicted negative symptom severity and lower global functioning in patients. A significant drug X diagnosis interaction was also observed for betweenness centrality of the ACC. These results suggest that nicotine may target abnormalities in functional connectivity between salience and executive network areas in schizophrenia as well as affect the ability of the salience network to act as an integrator of global signaling in the disorder.