Early morning physical activity is associated with healthier white matter microstructure and happier children: the ActiveBrains project.

The background of this study is to examine the associations of individual and combined early morning patterns (i.e., active commuting to school, physical activity before school, having breakfast and good sleep) with white matter microstructure (WMM) and, whether the associated white mater microstructure outcomes were related to mental health outcomes in children with overweight or obesity. 103 children with overweight or obesity (10.0 ± 1.1 years old, 42 girls) from the ActiveBrains project participated in this cross-sectional study. Early morning patterns and mental health indicators (i.e., self-esteem, optimism, positive and negative affect, stress, depression and anxiety) were self-reported by the children using validated questionnaires. WMM was assessed by magnetic resonance imaging using diffusion tensor imaging. When examined independently, early morning patterns were not related with WMM (all P > 0.05). However, the combination of early morning patterns was related with WMM (P < 0.05). Specifically, physically active early morning patterns (i.e., active commuting to school and physical activity before school) were associated with global fractional anisotropy (FA) (ß = 0.298, P = 0.013) and global radial diffusivity (RD) (ß = - 0.272, P = 0.021), as well as with tract-specific FA (ß = 0.314, P = 0.004) and RD (ß = - 0.234, P = 0.032) in the superior longitudinal fasciculus (SLF). Furthermore, combined physically active early morning pattern-associated global (i.e., FA and RD) and tract-specific (i.e., FA and RD in the SLF) WMM indicators were positively associated with happiness (ß absolute value range from 0.252 to 0.298, all P < 0.05). A combination of physically active early morning patterns may positively relate to white matter microstructure in children with overweight or obesity, and, in turn, happiness.

Early life factors and structural brain network in children with overweight/obesity: The ActiveBrains project.

BACKGROUND: The aims of this study were to investigate the association of early life factors, including birth weight, birth length, and breastfeeding practices, with structural brain networks; and to test whether structural brain networks associated with early life factors were also associated with academic performance in children with overweight/obesity (OW/OB). METHOD: 96 children with OW/OB aged 8-11 years (10.03 ± 1.16) from the ActiveBrains project were included. Early life factors were collected from birth records and reported by parents as weight, height, and months of breastfeeding. T1-weighted images were used to identify structural networks using a non-negative matrix factorization (NNMF) approach. Academic performance was evaluated by the Woodcock-Muñoz standardized test battery. RESULTS: Birth weight and birth length were associated with seven networks involving the cerebellum, cingulate gyrus, occipital pole, and subcortical structures including hippocampus, caudate nucleus, putamen, pallidum, nucleus accumbens, and amygdala. No associations were found for breastfeeding practices. None of the networks linked to birth weight and birth length were linked to academic performance. CONCLUSIONS: Birth weight and birth length, but not breastfeeding, were associated with brain structural networks in children with OW/OB. Thus, early life factors are related to brain networks, yet a link with academic performance was not observed. IMPACT: Birth weight and birth length, but not breastfeeding, were associated with several structural brain networks involving the cerebellum, cingulate gyrus, occipital pole, and subcortical structures including hippocampus, caudate, putamen, pallidum, accumbens and amygdala in children with overweight/obesity, playing a role for a normal brain development. Despite no academic consequences, other behavioral consequences should be investigated. Interventions aimed at improving optimal intrauterine growth and development may be of importance to achieve a healthy brain later in life.

Physical activity, sedentary time, and fitness in relation to brain shapes in children with overweight/obesity: Links to intelligence.

OBJECTIVES: To examine the association between physical activity, sedentary time, and physical fitness with the shapes of subcortical brain structures in children with overweight/obesity. Further, we analyzed whether differences in the shapes of subcortical brain structures were related to intelligence. We hypothesized that those children with higher physical activity levels, lower sedentary time, and better fitness, would show greater expansion of the brain regions analyzed, and these expansions would be associated with higher intelligence. STUDY DESIGN: 100 children (10.0 ± 1.1 years, 40 girls) were included in the analyses. Physical activity and sedentary time were measured by accelerometry, and physical fitness was evaluated by a fitness battery. Shapes of subcortical brain structures were assessed by magnetic resonance imaging. Intelligence was measured by the Kaufmann Brief Intelligence test. RESULTS: Physical activity was related to expansion of the right/left pallidum, right/left putamen, and right thalamus (p < 0.05). Higher sedentary time was related to contraction of the left thalamus and right nucleus accumbens (p < 0.05). Higher levels of cardiorespiratory fitness were associated with expansion of the right amygdala (p = 0.022). Greater strength in the upper-limb was related to expansion of the right/left pallidum and the left nucleus accumbens (p < 0.038), and contraction of the left amygdala (p = 0.030). Better speed-agility was associated with expansion of the left nucleus accumbens (p = 0.036). Physical activity- and fitness-related expansion of the right pallidum was associated with higher intelligence (all p < 0.05). CONCLUSION: Physical activity, sedentary time, and physical fitness were significantly related to the shapes of subcortical brain structures, which in turn were related to intelligence in children with overweight/obesity.

Stressing diets? Amygdala networks, cumulative cortisol, and weight loss in adolescents with excess weight.

OBJECTIVE: The amygdala is importantly involved in stress and obesity, but its role on weight change and diet-related stress remains unexplored among adolescents with excess weight. We aimed to examine the functional connectivity of the Central and Basolateral amygdala nuclei (CeA and BLA) among adolescents, and to explore the longitudinal association between brain connectivity measures and diet-related cortisol and weight loss in adolescents with excess weight. METHODS: We compared resting-state functional connectivity between adolescents with excess (EW, N = 34; Age = 16.44 ± 1.66) and normal weight (NW, N = 36; Age = 16.50 ± 1.40) using a seed-based (CeA and BLA) whole-brain approach. Then, in a subset of 30 adolescents with EW, followed-up after 3-months of dietary/lifestyle intervention, we explored for interactions between connectivity in the CeA/BLA networks and weight loss. Regression analyses were performed to explore the relationship between accumulated cortisol and weight loss, and to test the potential effect of the amygdala networks on such association. RESULTS: In EW compared with NW, the CeA regions showed higher functional connectivity with anterior portions, and lower connectivity with posterior portions of the cingulate cortex, while the left BLA regions showed lower connectivity with the dorsal caudate and angular gyrus. In addition, higher connectivity between the left CeA-midbrain network was negatively associated with weight loss. Hair cortisol significantly predicted weight change (p = 0.012). However, this association was no longer significant (p = 0.164) when considering the CeA-midbrain network in the model as an additional predictor. CONCLUSIONS: Adolescents with EW showed functional connectivity alterations within the BLA/CeA networks. The CeA-midbrain network might constitute an important brain pathway regulating weight change.

Early life factors, gray matter brain volume and academic performance in overweight/obese children: The ActiveBrains project.

Early life factors may influence brain and academic outcomes later in life, especially during childhood. Here we investigate the associations of early life factors (i.e., birth weight, birth length, and breastfeeding) with gray matter volume, adjusted for body mass index and cardiorespiratory fitness, and ii) we test whether early-life factor-related differences in gray matter volume are associated with academic performance in overweight/obese children. 96 children with overweight/obesity aged 8-11 years participated. Birth weight, birth length and gestational age were collected from birth records, and breastfeeding practices were asked to parents. T1-weighted images were acquired with a 3.0 T Magnetom Tim Trio system. Academic performance was assessed with the Bateria III Woodcock-Muñoz Tests of Achievement. Whole-brain voxel-wise multiple regressions were used to test the associations of each early life factor with gray matter volume. Higher birth weight and birth length were associated with greater gray matter volume in 9 brain regions including the middle frontal gyrus, rectal gyrus, thalamus, putamen, middle temporal gyrus, lingual gyrus, middle occipital gyrus, calcarine cortex and cerebellum bilaterally (ß ranging from 0.361 to 0.539, t ranging from 3.46 to 5.62 and cluster size from 82 to 4478 voxels; p < 0.001); and greater duration of any breastfeeding was associated with greater gray matter volume in 3 regions including the bilateral inferior frontal gyrus and rolandic operculum (ß ranging from 0.359 to 0.408, t ranging from 4.01 to 4.32 and cluster size from 64 to 171 voxels; p < 0.001). No associations were found for duration of exclusive breastfeeding. Additionally, none of the gray matter regions that were associated with the early life factors were associated with academic performance (all p > 0.05). Our results demonstrate that birth weight, birth length, and breastfeeding are predictive of gray matter volume of numerous brain structures that are involved in higher order cognition and emotion regulation, but how these results relate to measures of academic achievement remain a matter of speculation.

Fitness, cortical thickness and surface area in overweight/obese children: The mediating role of body composition and relationship with intelligence.

Cortical thickness and surface area are thought to be genetically unrelated and shaped by independent neurobiological events suggesting that they should be considered separately in morphometric analyses. Although the developmental trajectories of cortical thickness and surface area may differ across brain regions and ages, there is no consensus regarding the relationships of physical fitness with cortical thickness and surface area as well as for its subsequent influence on intelligence. Thus, this study examines: (i) the associations of physical fitness components (i.e., cardiorespiratory fitness, speed-agility and muscular fitness) with overall and regional cortical thickness and surface area; (ii) whether body composition indicators (i.e., body mass index, fat-free mass index and fat mass index) mediate these associations; and (iii) the association of physical fitness and cortical thickness with intelligence in overweight/obese children. A total of 101 overweight/obese children aged 8-11 years were recruited in Granada, Spain. The physical fitness components were assessed following the ALPHA health-related fitness test battery. T1-weighted images were acquired with a 3.0 Tesla Siemens Magnetom Tim Trio system. We used FreeSurfer software version 5.3.0 to assess cortical thickness (mm) and surface area (mm2). The main results showed that cardiorespiratory fitness and speed-agility were related to overall cortical thickness (ß = 0.321 and ß = 0.302, respectively; both P < 0.05), and in turn, cortical thickness was associated with higher intelligence (ß = 0.198, P < 0.05). Muscular fitness was not related to overall cortical thickness. None of the three physical fitness components were related to surface area (p > 0.05). The associations of cardiorespiratory fitness and speed-agility with overall cortical thickness were mediated by fat mass index (56.86% & 62.28%, respectively). In conclusion, cardiorespiratory fitness and speed-agility, but not muscular fitness, are associated with overall cortical thickness, and in turn, thicker brain cortex is associated with higher intelligence in overweight/obese children. Yet, none of the three physical fitness components were related to surface area. Importantly, adiposity may hinder the benefits of cardiorespiratory fitness and speed-agility on cortical thickness. Understanding individual differences in brain morphology may have important implications for educators and policy makers who aim to determine policies and interventions to maximize academic learning and occupational success later in life.

Visceral adiposity and insular networks: associations with food craving.

BACKGROUND/OBJECTIVES: Accumulation of visceral adiposity can disrupt the brain's sensitivity to interoceptive feedback, which is coded in the insula. This study aimed to test the link between visceral fat and the functional connectivity of two insulae regions relevant for eating behavior: the middle-dorsal insula (mIns), which codes homeostatic changes, and the rostral insula (rIns), which codes stable representations of food properties. We also assessed the impact of visceral adiposity-associated insulae networks on food craving. SUBJECTS/METHODS: Seventy-five adults ranging in weight status (normal and excess weight) underwent resting-state functional magnetic resonance imaging (fMRI) and subjective food craving measures. We examined the association between visceral fat and seed-based functional connectivity of the mIns and the rIns, controlling for BMI, age, and sex, using multiple regressions in SPM8. We also tested if visceral fat mediated the association between insulae connectivity and food craving. RESULTS: Higher visceral adiposity was associated with decreased connectivity between the mIns and a cluster involving the hypothalamus and the bed nucleus of the stria terminalis. Decreased connectivity in this network was associated with greater food craving, a relation mediated by visceral adiposity. Visceral adiposity was also associated with increased connectivity between the mIns and the middle frontal gyri and the right intraparietal cortex, and between the rIns and the right amygdala. CONCLUSIONS: Accumulation of visceral adiposity is linked to disrupted functional connectivity within the mIns and rIns networks. Furthermore, the link between the mIns network and food craving is mediated by visceral fat. Findings suggest that visceral fat disrupts insula coding of bodily homeostatic signals, which may boost externally driven food cravings.

Maternal prepregnancy body mass index and offspring white matter microstructure: results from three birth cohorts.

BACKGROUND AND AIMS: Prepregnancy maternal obesity is a global health problem and has been associated with offspring metabolic and mental ill-health. However, there is a knowledge gap in understanding potential neurobiological factors related to these associations. This study explored the relation between maternal prepregnancy body mass index (BMI) and offspring brain white matter microstructure at the age of 6, 10, and 26 years in three independent cohorts. SUBJECTS AND METHODS: The study used data from three European birth cohorts (n = 116 children aged 6 years, n = 2466 children aged 10 years, and n = 437 young adults aged 26 years). Information on maternal prepregnancy BMI was obtained before or during pregnancy and offspring brain white matter microstructure was measured at age 6, 10, or 26 years. We used magnetic resonance imaging-derived fractional anisotropy (FA) and mean diffusivity (MD) as measures of white matter microstructure in the brainstem, callosal, limbic, association, and projection tracts. Linear regressions were fitted to examine the association of maternal BMI and offspring white matter microstructure, adjusting for several socioeconomic and lifestyle-related confounders, including education, smoking, and alcohol use. RESULTS: Maternal BMI was associated with higher FA and lower MD in multiple brain tracts, for example, association and projection fibers, in offspring aged 10 and 26 years, but not at 6 years. In each cohort maternal BMI was related to different white matter tract and thus no common associations across the cohorts were found. CONCLUSIONS: Maternal BMI was associated with higher FA and lower MD in multiple brain tracts in offspring aged 10 and 26 years, but not at 6 years of age. Future studies should examine whether our observations can be replicated and explore the potential causal nature of the findings.

Inflammatory biomarkers and brain health indicators in children with overweight and obesity: The ActiveBrains project.

INTRODUCTION: Chronic inflammation plays an important role on the pathogenesis of several cardiovascular and metabolic diseases, as well as on brain function and behaviour. The aim of the present study was to examine the associations between inflammatory biomarkers and a wide range of brain health indicators (i.e., academic performance, executive function, behavioural and emotional functioning, and brain volume) in children with overweight/obesity. METHODS: A total of 107 children (10.0 ±â€¯1.1 years, 41% girls) from the ActiveBrains project were included in the analysis. Five inflammatory biomarkers were analysed in plasma: white blood cell (WBC) count, interleukin-6 (IL-6), interleukin-1ß, tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP). Academic performance was assessed by Woodcock-Muñoz Tests of Achievement. Executive function was assessed through the Design Fluency Test for cognitive flexibility, the Stroop test for cognitive inhibition, and the Delayed Non-Match-to-Sample task for working memory. Behavioural and emotional functioning was evaluated through the Behavior Assessment System for Children (BASC) questionnaire. Total and regional brain volume was assessed by magnetic resonance imaging. RESULTS: IL-6 was inversely associated with adaptive skills (ß = -0.228; p = 0.030), while TNF-α was related to mathematics (ß = -0.198; p = 0.034). In addition, CRP was positively associated with externalizing (ß = 0.246; p = 0.046) and internalizing problems (ß = 0.234; p = 0.039), as well as the behavioural symptoms index (ß = 0.236; p = 0.047). However, these significant associations disappeared after multiple comparisons correction. Inflammatory biomarkers were not associated with executive function and total brain volumes. Regarding regional brain analyses, WBC was positively associated with gray matter volume in the left middle temporal gyrus (ß = 0.387; p < 0.001, k = 44), and CRP was positively associated with gray matter volume in the right superior temporal gyrus (ß = 0.439; p < 0.001, k = 29). Additionally, when adjusting by total brain volume, CRP was positively associated with gray matter volume in the right supplementary motor cortex (ß = 0.453; p < 0.001, k = 51). Moreover, both, IL-6 (ß = 0.366; p < 0.001, k = 81) and TNF-α (ß = 0.368; p < 0.001, k = 62) were positively associated with white matter volume around the right inferior frontal gyrus pars opercularis, while CRP was inversely associated with white matter volume around the left superior frontal gyrus (ß = -0.482; p < 0.001, k = 82). After adjusting by total brain volume, CRP was also inversely associated with white matter volume in 3 additional clusters (ß ranging from -0.473 to -0.404; p < 0.001, k = 87). CONCLUSIONS: Inflammation was slightly associated with brain health (i.e., academic performance, behavioural and emotional functioning and regional brain volume) in children with overweight or obesity. Further larger longitudinal and interventional studies are warranted to elucidate the short-term and long-term effect of systemic low-grade inflammation on children's brain health.

Increased food choice-evoked brain activation in adolescents with excess weight: Relationship with subjective craving and behavior.

OBJECTIVE: We used functional magnetic resonance imaging (fMRI) to assess brain regions associated with food choices between appetizing (i.e., high sugar, high fat) and plain food in adolescents with excess weight and those with normal weight. The associations between choice-evoked brain activation and subjective food craving and behavioral food choices were also evaluated. METHODS: Seventy-three adolescents (aged 14-19 years), classified into excess weight (n = 38) or normal weight (n = 39) groups, participated in the study. We used a food-choice fMRI task, between appetizing and plain food, to analyse brain activation differences between groups. Afterwards, participants assessed their "craving" for each food presented in the scanner. RESULTS: Adolescents with excess weight showed higher brain activation in frontal, striatal, insular and mid-temporal regions during choices between appetizing and standard food cues. This pattern of activations correlated with behavioral food choices and subjective measures of craving. CONCLUSIONS: Our findings suggest that adolescents with excess weight have greater food choice-related brain reactivity in reward-related regions involved in motivational and emotional responses to food. Increased activation in these regions is generally associated with craving, and increased dorsolateral prefrontal cortex is specifically associated with appetizing food choices among adolescents with excess weight, which may suggest greater conflict in these decisions. These overweight- and craving-associated patterns of brain activation may be relevant to decision-making about food consumption.

Independent functional connectivity networks underpin food and monetary reward sensitivity in excess weight.

Overvaluation of palatable food is a primary driver of obesity, and is associated with brain regions of the reward system. However, it remains unclear if this network is specialized in food reward, or generally involved in reward processing. We used functional magnetic resonance imaging (fMRI) to characterize functional connectivity during processing of food and monetary rewards. Thirty-nine adults with excess weight and 37 adults with normal weight performed the Willingness to Pay for Food task and the Monetary Incentive Delay task in the fMRI scanner. A data-driven graph approach was applied to compare whole-brain, task-related functional connectivity between groups. Excess weight was associated with decreased functional connectivity during the processing of food rewards in a network involving primarily frontal and striatal areas, and increased functional connectivity during the processing of monetary rewards in a network involving principally frontal and parietal areas. These two networks were topologically and anatomically distinct, and were independently associated with BMI. The processing of food and monetary rewards involve segregated neural networks, and both are altered in individuals with excess weight.

A whole brain volumetric approach in overweight/obese children: Examining the association with different physical fitness components and academic performance. The ActiveBrains project.

Obesity, as compared to normal weight, is associated with detectable structural differences in the brain. To the best of our knowledge, no previous study has examined the association of physical fitness with gray matter volume in overweight/obese children using whole brain analyses. Thus, the aim of this study was to examine the association between the key components of physical fitness (i.e. cardiorespiratory fitness, speed-agility and muscular fitness) and brain structural volume, and to assess whether fitness-related changes in brain volumes are related to academic performance in overweight/obese children. A total of 101 overweight/obese children aged 8-11 years were recruited from Granada, Spain. The physical fitness components were assessed following the ALPHA health-related fitness test battery. T1-weighted images were acquired with a 3.0 T S Magnetom Tim Trio system. Gray matter tissue was calculated using Diffeomorphic Anatomical Registration Through Exponentiated Lie algebra (DARTEL). Academic performance was assessed by the Batería III Woodcock-Muñoz Tests of Achievement. All analyses were controlled for sex, peak high velocity offset, parent education, body mass index and total brain volume. The statistical threshold was calculated with AlphaSim and further Hayasaka adjusted to account for the non-isotropic smoothness of structural images. The main results showed that higher cardiorespiratory fitness was related to greater gray matter volumes (P < 0.001, k = 64) in 7 clusters with ß ranging from 0.493 to 0.575; specifically in frontal regions (i.e. premotor cortex and supplementary motor cortex), subcortical regions (i.e. hippocampus and caudate), temporal regions (i.e. inferior temporal gyrus and parahippocampal gyrus) and calcarine cortex. Three of these regions (i.e. premotor cortex, supplementary motor cortex and hippocampus) were related to better academic performance (ß ranging from 0.211 to 0.352; all P < 0.05). Higher speed-agility was associated with greater gray matter volumes (P < 0.001, k = 57) in 2 clusters (i.e. the inferior frontal gyrus and the superior temporal gyrus) with ß ranging from 0.564 to 0.611. Both clusters were related to better academic performance (ß ranging from 0.217 to 0.296; both P < 0.05). Muscular fitness was not independently associated with greater gray matter volume in any brain region. Furthermore, there were no statistically significant negative association between any component of physical fitness and gray matter volume in any region of the brain. In conclusion, cardiorespiratory fitness and speed-agility, but not muscular fitness, may independently be associated with greater volume of numerous cortical and subcortical brain structures; besides, some of these brain structures may be related to better academic performance. Importantly, the identified associations of fitness and gray matter volume were different for each fitness component. These findings suggest that increases in cardiorespiratory fitness and speed-agility may positively influence the development of distinctive brain regions and academic indicators, and thus counteract the harmful effect of overweight and obesity on brain structure during childhood.

Brain reward system's alterations in response to food and monetary stimuli in overweight and obese individuals.

The brain's reward system is crucial to understand obesity in modern society, as increased neural responsivity to reward can fuel the unhealthy food choices that are driving the growing obesity epidemic. Brain's reward system responsivity to food and monetary rewards in individuals with excessive weight (overweight and obese) versus normal weight controls, along with the relationship between this responsivity and body mass index (BMI) were tested. The sample comprised 21 adults with obesity (BMI > 30), 21 with overweight (BMI between 25 and 30), and 39 with normal weight (BMI < 25). Participants underwent a functional magnetic resonance imaging (fMRI) session while performing two tasks that involve the processing of food (Willing to Pay) and monetary rewards (Monetary Incentive Delay). Neural activations within the brain reward system were compared across the three groups. Curve fit analyses were conducted to establish the association between BMI and brain reward system's response. Individuals with obesity had greater food-evoked responsivity in the dorsal and ventral striatum compared with overweight and normal weight groups. There was an inverted U-shape association between BMI and monetary-evoked responsivity in the ventral striatum, medial frontal cortex, and amygdala; that is, individuals with BMIs between 27 and 32 had greater responsivity to monetary stimuli. Obesity is associated with greater food-evoked responsivity in the ventral and dorsal striatum, and overweight is associated with greater monetary-evoked responsivity in the ventral striatum, the amygdala, and the medial frontal cortex. Findings suggest differential reactivity of the brain's reward system to food versus monetary rewards in obesity and overweight. Hum Brain Mapp 38:666-677, 2017. © 2016 Wiley Periodicals, Inc.

Brain substrates of social decision-making in dual diagnosis: cocaine dependence and personality disorders.

Cocaine dependence frequently co-occurs with personality disorders, leading to increased interpersonal problems and greater burden of disease. Personality disorders are characterised by patterns of thinking and feeling that divert from social expectations. However, the comorbidity between cocaine dependence and personality disorders has not been substantiated by measures of brain activation during social decision-making. We applied functional magnetic resonance imaging to compare brain activations evoked by a social decision-making task-the Ultimatum Game-in 24 cocaine dependents with personality disorders (CDPD), 19 cocaine dependents without comorbidities and 19 healthy controls. In the Ultimatum Game participants had to accept or reject bids made by another player to split monetary stakes. Offers varied in fairness (in fair offers the proposer shares ~50 percent of the money; in unfair offers the proposer shares <30 percent of the money), and participants were told that if they accept both players get the money, and if they reject both players lose it. We contrasted brain activations during unfair versus fair offers and accept versus reject choices. During evaluation of unfair offers CDPD displayed lower activation in the insula and the anterior cingulate cortex and higher activation in the lateral orbitofrontal cortex and superior frontal and temporal gyri. Frontal activations negatively correlated with emotion recognition. During rejection of offers CDPD displayed lower activation in the anterior cingulate cortex, striatum and midbrain. Dual diagnosis is linked to hypo-activation of the insula and anterior cingulate cortex and hyper-activation of frontal-temporal regions during social decision-making, which associates with poorer emotion recognition.

Changes in choice evoked brain activations after a weight loss intervention in adolescents.

This study was aimed to investigate if treatment-related success in weight loss (i.e., reductions of BMI and fat percentage) is linked to significant changes in choice evoked brain activity in adolescents with excess weight. Sixteen adolescents with excess weight (age range: 12-18; BMI range: 22-36) performed the Risky-Gains Task during functional Magnetic Resonance Imaging (fMRI) both before and after a 12-week weight loss intervention. Success in weight loss was selectively associated with increased activation in the anterior insula. We concluded that adolescents with the greatest increases in activation of the insula-related interoceptive neural circuitry also show greater reductions in BMI and fat mass.

Dysfunctional involvement of emotion and reward brain regions on social decision making in excess weight adolescents.

Obese adolescents suffer negative social experiences, but no studies have examined whether obesity is associated with dysfunction of the social brain or whether social brain abnormalities relate to disadvantageous traits and social decisions. We aimed at mapping functional activation differences in the brain circuitry of social decision making in adolescents with excess versus normal weight, and at examining whether these separate patterns correlate with reward/punishment sensitivity, disordered eating features, and behavioral decisions. In this fMRI study, 80 adolescents aged 12 to 18 years old were classified in two groups based on age adjusted body mass index (BMI) percentiles: normal weight (n = 44, BMI percentiles 5th-84th) and excess weight (n = 36, BMI percentile ≥ 85th). Participants were scanned while performing a social decision-making task (ultimatum game) in which they chose to "accept" or "reject" offers to split monetary stakes made by another peer. Offers varied in fairness (Fair vs. Unfair) but in all cases "accepting" meant both players win the money, whereas "rejecting" meant both lose it. We showed that adolescents with excess weight compared to controls display significantly decreased activation of anterior insula, anterior cingulate, and midbrain during decisions about Unfair versus Fair offers. Moreover, excess weight subjects show lower sensitivity to reward and more maturity fears, which correlate with insula activation. Indeed, blunted insula activation accounted for the relationship between maturity fears and acceptance of unfair offers. Excess weight adolescents have diminished activation of brain regions essential for affective tracking of social decision making, which accounts for the association between maturity fears and social decisions.

Neural substrates of cognitive flexibility in cocaine and gambling addictions.

BACKGROUND: Individuals with cocaine and gambling addictions exhibit cognitive flexibility deficits that may underlie persistence of harmful behaviours. AIMS: We investigated the neural substrates of cognitive inflexibility in cocaine users v. pathological gamblers, aiming to disambiguate common mechanisms v. cocaine effects. METHOD: Eighteen cocaine users, 18 pathological gamblers and 18 controls performed a probabilistic reversal learning task during functional magnetic resonance imaging, and were genotyped for the DRD2/ANKK Taq1A polymorphism. RESULTS: Cocaine users and pathological gamblers exhibited reduced ventrolateral prefrontal cortex (PFC) signal during reversal shifting. Cocaine users further showed increased dorsomedial PFC (dmPFC) activation relative to pathological gamblers during perseveration, and decreased dorsolateral PFC activation relative to pathological gamblers and controls during shifting. Preliminary genetic findings indicated that cocaine users carrying the DRD2/ANKK Taq1A1+ genotype may derive unique stimulatory effects on shifting-related ventrolateral PFC signal. CONCLUSIONS: Reduced ventrolateral PFC activation during shifting may constitute a common neural marker across gambling and cocaine addictions. Additional cocaine-related effects relate to a wider pattern of task-related dysregulation, reflected in signal abnormalities in dorsolateral and dmPFC.

Insula tuning towards external eating versus interoceptive input in adolescents with overweight and obesity.

This study was aimed to examine if adolescent obesity is associated with alterations of insula function as indexed by differential correlations between insula activation and perception of interoceptive feedback versus external food cues. We hypothesized that, in healthy weight adolescents, insula activation will positively correlate with interoceptive sensitivity, whereas in excess weight adolescents, insula activation will positively correlate with sensitivity towards external cues. Fifty-four adolescents (age range 12-18), classified in two groups as a function of BMI, excess weight (n = 22) and healthy weight (n = 32), performed the Risky-Gains task (sensitive to insula function) inside an fMRI scanner, and completed the heartbeat perception task (measuring interoceptive sensitivity) and the Dutch Eating Behaviour Questionnaire (measuring external eating as well as emotional eating and restraint) outside the scanner. We found that insula activation during the Risky-Gains task positively correlated with interoceptive sensitivity and negatively correlated with external eating in healthy weight adolescents. Conversely, in excess weight adolescents, insula activation positively correlated with external eating and negatively correlated with interoceptive sensitivity, arguably reflecting obesity related neurocognitive adaptations. In excess weight adolescents, external eating was also positively associated with caudate nucleus activation, and restrained eating was negatively associated with insula activation. Our findings suggest that adolescent obesity is associated with disrupted tuning of the insula system towards interoceptive input.

Re-appraisal of negative emotions in cocaine dependence: dysfunctional corticolimbic activation and connectivity.

Cocaine dependence is associated with pronounced elevations of negative affect and deficient regulation of negative emotions. We aimed to investigate the neural substrates of negative emotion regulation in cocaine-dependent individuals (CDI), as compared to non-drug-using controls, using functional magnetic resonance imaging (fMRI) during a re-appraisal task. Seventeen CDI abstinent for at least 15 days and without other psychiatric co-morbidities and 18 intelligence quotient-matched non-drug-using controls participated in the study. Participants performed the re-appraisal task during fMRI scanning: they were exposed to 24 blocks of negative affective or neutral pictures that they should Observe (neutral pictures), Maintain (sustain the emotion elicited by negative pictures) or Suppress (regulate the emotion elicited by negative pictures through previously trained re-appraisal techniques). Task-related activations during two conditions of interest (Maintain>Observe and Suppress>Maintain) were analyzed using the general linear model in SPM8 software. We also performed psychophysiological interaction (PPI) seed-based analyses based on one region from each condition: the dorsolateral prefrontal cortex (dlPFC-Maintain>Observe) and the inferior frontal gyrus (IFG-Suppress>Maintain). Results showed that cocaine users had increased right dlPFC and bilateral temporoparietal junction activations during Maintain>Observe, whereas they showed decreased right IFG, posterior cingulate cortex, insula and fusiform gyrus activations during Suppress>Maintain. PPI analyses showed that cocaine users had increased functional coupling between the dlPFC and emotion-related regions during Maintain>Observe, whereas they showed decreased functional coupling between the right IFG and the amygdala during Suppress>Maintain. These findings indicate that CDI have dysfunctional corticolimbic activation and connectivity during negative emotion experience and re-appraisal.

The effects of physical activity on white matter microstructure in children with overweight or obesity: The ActiveBrains randomized clinical trial.

Background: Emerging research supports the idea that physical activity benefits brain development. However, the body of evidence focused on understanding the effects of physical activity on white matter microstructure during childhood is still in its infancy, and further well-designed randomized clinical trials are needed. Aim: This study aimed: (i) to investigate the effects of a 20-week physical activity intervention on global white matter microstructure in children with overweight or obesity, and (ii) to explore whether the effect of physical activity on white matter microstructure is global or restricted to a particular set of white matter bundles. Methods: In total, 109 children aged 8 to 11 years with overweight or obesity were randomized and allocated to either the physical activity program or the control group. Data were collected from November 2014 to June 2016, with diffusion tensor imaging (DTI) data processing and analyses conducted between June 2017 and November 2021. Images were pre-processed using the Functional Magnetic Resonance Imaging (MRI) of the Brain´s Software Library (FSL) and white matter properties were explored by probabilistic fiber tractography and tract-based spatial statistics (TBSS). Results: Intention-to-treat analyses were performed for all children who completed the pre-test and post-test DTI assessment, with good quality DTI data (N = 89). Of them, 83 children (10.06±1.11 years, 39 % girls, intervention group=44) met the per-protocol criteria (attended at least 70 % of the recommended sessions). Our probabilistic fiber tractography analysis did not show any effects in terms of global and tract-specific fractional anisotropy (FA) and mean diffusivity (MD) in the per-protocol or intention-to-treat analyses. Additionally, we did not observe any effects on the voxel-wise DTI parameters (i.e., FA and MD) using the most restricted TBSS approach (i.e., per protocol analyses and p-corrected image with a statistical threshold of p < 0.05). In the intention-to-treat analysis, we found that our physical activity program had a borderline effect (p-corrected image with a statistical threshold of p < 0.1) on 7 different clusters, including a cluster in the corpus callosum. Conclusion: We conclude that a 20-week physical activity intervention was not enough to induce changes in global and tract-specific white matter during childhood. The effects of physical activity on white matter microstructure could be restricted to local changes in several white matter tracts (e.g., the body of the corpus callosum). However, our results were not significant, and more interventions are needed to determine whether and how physical activity affects white matter microstructure during childhood.