Unraveling the gut-brain connection: The association of microbiota-linked structural brain biomarkers with behavior and mental health.

AIM: The gut microbiota can influence human behavior. However, due to the massive multiple-testing problem, research into the relationship between microbiome ecosystems and the human brain faces drawbacks. This problem arises when attempting to correlate thousands of gut bacteria with thousands of brain voxels. METHODS: We performed brain magnetic resonance imaging (MRI) scans on 133 participants and applied machine-learning algorithms (Ridge regressions) combined with permutation tests. Using this approach, we were able to correlate specific gut bacterial families with brain MRI signals, circumventing the difficulties of massive multiple testing while considering sex, age, and body mass index as confounding factors. RESULTS: The relative abundance (RA) of the Selenomonadaceae, Clostridiaceae, and Veillonellaceae families in the gut was associated with altered cerebellar, visual, and frontal T2-mapping and diffusion tensor imaging measures. Conversely, decreased relative abundance of the Eubacteriaceae family was also linked to T2-mapping values in the cerebellum. Significantly, the brain regions associated with the gut microbiome were also correlated with depressive symptoms and attentional deficits. CONCLUSIONS: Our analytical strategy offers a promising approach for identifying potential brain biomarkers influenced by gut microbiota. By gathering a deeper understanding of the microbiota-brain connection, we can gain insights into the underlying mechanisms and potentially develop targeted interventions to mitigate the detrimental effects of dysbiosis on brain function and mental health.

Increased brain fractional perfusion in obesity using intravoxel incoherent motion (IVIM) MRI metrics.

OBJECTIVE: This research seeks to shed light on the associations between brain perfusion, cognitive function, and mental health in individuals with and without obesity. METHODS: In this study, we employed the noninvasive intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) technique to examine brain fractional perfusion (FP) in two groups: individuals with obesity (N = 72) and healthy controls (N = 66). Additionally, we investigated potential associations between FP, cognitive function, and depressive symptoms in the participants with and without obesity. Finally, artificial intelligence algorithms (Boruta analysis) were also used. RESULTS: Participants with obesity exhibited increased FP within dopaminergic brain circuits, particularly involving prefrontal cortex areas, anterior and posterior sections of the cingulate cortex, the right striatum, and the midbrain. Additionally, these individuals demonstrated lower working memory and higher depressive symptoms compared to the control group. Notably, higher FP in the inferior temporal and occipital cortices correlated with greater depressive symptoms, whereas increased FP in the right ventral caudate and the midbrain was associated with better working memory performance. A link between inflammatory and metabolic variables, with a particular emphasis on monocytes, and FP in obesity was also evidenced by Boruta analysis. CONCLUSIONS: Increased brain perfusion in individuals with obesity is associated with cognitive function and mental health through interaction with metabolic and inflammatory factors.

Binge-Eating Precursors in Children and Adolescents: Neurodevelopment, and the Potential Contribution of Ultra-Processed Foods.

Binge-eating disorder (BED) is a highly prevalent disorder. Subthreshold BED conditions (sBED) are even more frequent in youth, but their significance regarding BED etiology and long-term prognosis is unclear. A better understanding of brain findings associated with BED and sBED, in the context of critical periods for neurodevelopment, is relevant to answer such questions. The present narrative review starts from the knowledge of the development of emotional self-regulation in youth, and the brain circuits supporting emotion-regulation and eating behaviour. Next, neuroimaging studies with sBED and BED samples will be reviewed, and their brain-circuitry overlap will be examined. Deficits in inhibition control systems are observed to precede, and hyperactivity of reward regions to characterize, sBED, with overlapping findings in BED. The imbalance between reward/inhibition systems, and the implication of interoception/homeostatic processing brain systems should be further examined. Recent knowledge of the potential impact that the high consumption of ultra-processed foods in paediatric samples may have on these sBED/BED-associated brain systems is then discussed. There is a need to identify, early on, those sBED individuals at risk of developing BED at neurodevelopmental stages when there is a great possibility of prevention. However, more neuroimaging studies with sBED/BED pediatric samples are needed.

Consumption of ultra-processed foods is associated with depression, mesocorticolimbic volume, and inflammation.

BACKGROUND: The consumption of ultra-processed foods and drinks (UPF) has been associated with depression and inflammation and preclinical studies showed that some UPF components disrupt the amygdala-hippocampal complex. We combine diet, clinical and brain imaging data to investigate the relationship between the UPF consumption, depressive symptoms, and brain volumes in humans, considering interactions with obesity, and the mediation effect of inflammation biomarkers. METHODS: One-hundred fifty-two adults underwent diet, depressive symptoms, anatomic magnetic resonance imaging assessments and laboratory tests. Relationships between the % of UPF consumption (in grams) of the total diet, depressive symptoms, and gray matter brain volumes were explored using several adjusted regression models, and in interaction with the presence of obesity. Whether inflammatory biomarkers (i.e., white blood cell count, lipopolysaccharide-binding protein, c-reactive protein) mediate the previous associations was investigated using R mediation package. RESULTS: High UPF consumption was associated with higher depressive symptoms in all participants (ß = 0.178, CI = 0.008-0.261) and in those with obesity (ß = 0.214, CI = -0.004-0.333). Higher consumption was also associated with lower volumes in the posterior cingulate cortex and the left amygdala, which in the participants with obesity also encompassed the left ventral putamen and the dorsal frontal cortex. White blood count levels mediated the association between UPF consumption and depressive symptoms (p = 0.022). LIMITATIONS: The present study precludes any causal conclusions. CONCLUSIONS: UPF consumption is associated with depressive symptoms and lower volumes within the mesocorticolimbic brain network implicated in reward processes and conflict monitoring. Associations were partially dependent on obesity and white blood cell count.

Early life factors and hippocampal functional connectivity in children with overweight/obesity.

OBJECTIVE: We investigated the association of anthropometric neonatal data (birth length and birth weight) and breastfeeding practices (exclusive and any breastfeeding) with hippocampal functional connectivity and its academic implication in children with overweight/obesity. METHODS: Ninety six children with overweight/obesity aged 8-11 years (10.01 ± 1.14), from the ActiveBrains project were included in this cross-sectional study. Anthropometric neonatal data were collected from birth records, whereas breastfeeding practices were reported by parents. A 3.0 Tesla Siemens Magnetom Tim Trio system was used to acquire T1-weighted and resting-state functional magnetic resonance images. Academic performance was assessed by the Woodcock-Muñoz standardized test. Hippocampal seed-based methods with post-hoc regression analyses were performed. Analyses were considered significant when surpassing Family-Wise Error corrections. RESULTS: Birth weight showed a positive association with the connectivity between the hippocampus and the pre- and postcentral gyri, and the cerebellum. In addition, breastfeeding was negatively associated with the connectivity between the hippocampus and the primary motor cortex and the angular gyrus. Any breastfeeding, in turn, showed a positive association with the connectivity between the hippocampus and the middle temporal gyrus. None of the connectivity outcomes related to early life factors was coupled with better academic abilities (all p > 0.05). CONCLUSIONS: Our findings suggest that birth weight at birth and breastfeeding are associated with hippocampal connectivity in children with overweight/obesity. Despite this, how the results relate to academic performance remains a matter of speculation. Our findings suggest that clinicians should recognize the importance early life factors for potentially avoiding consequences on offspring's brain development.

The nature of memory impairment in multiple sclerosis: understanding different patterns over the course of the disease.

Introduction: Memory deficit is one of the most common and severe cognitive impairments in patients with multiple sclerosis and can greatly affect their quality of life. However, there is currently no agreement as to the nature of memory deficit in multiple sclerosis. Methods: This cross-sectional study, carried out at the Dr. Josep Trueta and Santa Caterina hospitals in Girona (Spain), was designed to determine the semiology of verbal memory deficit in the different stages of the disease. To this end, a modification of Rey's verbal auditory test was created by introducing two recognition trials between the five learning trials, thus monitoring what happens in terms of acquisition versus the retrieval of information during the learning phase. Linear regression models were used to evaluate verbal episodic memory performance between-groups adjusting results by age, sex, educational level, and the presence of anxiety and/or depressive symptoms. Results: 133 patients with multiple sclerosis, clinically isolated syndrome, and radiologically isolated syndrome and 55 healthy controls aged 18-65 years were assessed. It was observed that the memory processes of multiple sclerosis patients worsen with the progression of the disease. In this respect, patients in pre-diagnostic phases (radiologically isolated syndrome and clinically isolated syndrome) show no differences in verbal episodic memory compared to the healthy controls. Patients in the inflammatory stage (relapsing-remitting multiple sclerosis) show a previously learned information retrieval deficit, while patients in progressive stages (secondary progressive multiple sclerosis and primary progressive multiple sclerosis) do not even correctly acquire information. Discussion: These results provide significant information to assist in understanding the nature of memory deficits in multiple sclerosis over the course of the disease. These results are discussed in terms of possible cognitive rehabilitation strategies depending on the evolutive stage and are related to neuropathological mechanisms involved in the progression of the disease.

Ultra-Processed Foods and Drinks Consumption Is Associated with Psychosocial Functioning in Adolescents.

Adolescents show one of the highest rates of ultra-processed foods and drinks (UPF) consumption, and studies indicate an association between their consumption and internalizing problems. We aim to investigate whether UPF consumption associates with dysfunctions in other psychosocial domains, as well as sex effects. In 560 Spanish adolescents (14-17 years old), we assessed the UPF products consumed in the previous day, fruits and vegetables consumption (servings/day), and physical activity (days/week). Psychosocial functioning (total and subscales) was assessed through the Pediatric Symptom Checklist-Youth self-report. Associations between UPF and psychosocial functioning were assessed using linear regression models, adjusting for sex, age, fruits and vegetables consumption, and physical activity. Sex-specific associations were also explored. Participants reported a daily consumption of 7.72 UPF servings per day, with male adolescents showing higher consumption than female adolescents. Consumption of fruits and vegetables and physical activity levels were lower than recommended. Psychosocial impairment was present in 26.2% of the participants. Higher UPF consumption was associated with higher presence of depressive symptoms and internalizing and externalizing problems in the whole sample and in male adolescents. The present study supports previous studies suggesting that UPF consumption may interact with mental health problems and indicates that these effects may go beyond internalizing problems.

Neurogenetics of Dynamic Connectivity Patterns Associated With Obsessive-Compulsive Symptoms in Healthy Children.

Background: Obsessive-compulsive symptoms (OCSs) during childhood predispose to obsessive-compulsive disorder and have been associated with changes in brain circuits altered in obsessive-compulsive disorder samples. OCSs may arise from disturbed glutamatergic neurotransmission, impairing cognitive oscillations and promoting overstable functional states. Methods: A total of 227 healthy children completed the Obsessive Compulsive Inventory-Child Version and underwent a resting-state functional magnetic resonance imaging examination. Genome-wide data were obtained from 149 of them. We used a graph theory-based approach and characterized associations between OCSs and dynamic functional connectivity (dFC). dFC evaluates fluctuations over time in FC between brain regions, which allows characterizing regions with stable connectivity patterns (attractors). We then compared the spatial similarity between OCS-dFC correlation maps and mappings of genetic expression across brain regions to identify genes potentially associated with connectivity changes. In post hoc analyses, we investigated which specific single nucleotide polymorphisms of these genes moderated the association between OCSs and patterns of dFC. Results: OCSs correlated with decreased attractor properties in the left ventral putamen and increased attractor properties in (pre)motor areas and the left hippocampus. At the specific symptom level, increased attractor properties in the right superior parietal cortex correlated with ordering symptoms. In the hippocampus, we identified two single nucleotide polymorphisms in glutamatergic neurotransmission genes (GRM7, GNAQ) that moderated the association between OCSs and attractor features. Conclusions: We provide evidence that in healthy children, the association between dFC changes and OCSs may be mapped onto brain circuits predicted by prevailing neurobiological models of obsessive-compulsive disorder. Moreover, our findings support the involvement of glutamatergic neurotransmission in such brain network changes.

Dissecting ultra-processed foods and drinks: Do they have a potential to impact the brain?

Ultra-processed foods and drinks (UPF) are formulation of ingredients, mostly of exclusive industrial use, that result from a series of industrial processes. They usually have a low nutrient but high energy density, with a high content of saturated and trans fats, and added sugars. In addition, they have characteristic organoleptic properties, and usually contain sophisticated additives, including artificial sweeteners, to intensify their sensory qualities and imitate the appearance of minimally processed foods. In addition, recent research has warned about the presence of chemicals (e.g., bisphenol) and neo-formed contaminants in these products. UPF production and consumption growth have been spectacular in the last decades, being specially consumed in children and adolescents. UPF features have been associated with a range of adverse health effects such as overeating, the promotion of inflammatory and oxidative stress processes, gut dysbiosis, and metabolic dysfunction including problems in glucose regulation. The evidence that these UPF-related adverse health effects may have on the neural network implicated in eating behavior are discussed, including the potential impact on serotonergic and dopaminergic neurotransmission, brain integrity and function. We end this review by placing UPF in the context of current food environments, by suggesting that an increased exposure to these products through different channels, such as marketing, may contribute to the automatic recruitment of the brain regions associated with food consumption and choice, with a detrimental effect on inhibitory-related prefrontal cortices. While further research is essential, preliminary evidence point to UPF consumption as a potential detrimental factor for brain health and eating behavior.

Endocannabinoid signaling of homeostatic status modulates functional connectivity in reward and salience networks.

RATIONALE: Endocannabinoids are well poised to regulate crosstalk between energy sensing of hunger and satiety and reward-driven motivation. OBJECTIVES: Here, we aimed to unravel associations between plasma endocannabinoids and brain connectivity in homeostatic and reward circuits across hunger and satiety states. METHODS: Fifteen participants (7 females) underwent two counter-balanced resting-state functional magnetic resonance imaging scans, one after overnight fasting and one after consumption of a standardized filling meal (satiety). Before each scan, we drew blood to measure plasma endocannabinoid concentrations (anandamide [AEA], anandamide-derived POEA, and 2-arachidonoylglycerol [2-AG]), analyzed with liquid chromatography tandem mass spectrometry. RESULTS: We found that AEA levels were associated with increased connectivity between the lateral hypothalamus and the ventral striatum during satiety. Furthermore, fasting AEA levels correlated with connectivity between the ventral striatum and the anterior cingulate cortex and the insula. CONCLUSIONS: Altogether, results suggest that peripheral AEA concentrations are sensitive to homeostatic changes and linked to neural communication in reward and salience networks. Findings may have significant implications for understanding normal and abnormal interactions between homeostatic input and reward valuation.

Obesity-associated deficits in inhibitory control are phenocopied to mice through gut microbiota changes in one-carbon and aromatic amino acids metabolic pathways.

BACKGROUND: Inhibitory control (IC) is critical to keep long-term goals in everyday life. Bidirectional relationships between IC deficits and obesity are behind unhealthy eating and physical exercise habits. METHODS: We studied gut microbiome composition and functionality, and plasma and faecal metabolomics in association with cognitive tests evaluating inhibitory control (Stroop test) and brain structure in a discovery (n=156), both cross-sectionally and longitudinally, and in an independent replication cohort (n=970). Faecal microbiota transplantation (FMT) in mice evaluated the impact on reversal learning and medial prefrontal cortex (mPFC) transcriptomics. RESULTS: An interplay among IC, brain structure (in humans) and mPFC transcriptomics (in mice), plasma/faecal metabolomics and the gut metagenome was found. Obesity-dependent alterations in one-carbon metabolism, tryptophan and histidine pathways were associated with IC in the two independent cohorts. Bacterial functions linked to one-carbon metabolism (thyX,dut, exodeoxyribonuclease V), and the anterior cingulate cortex volume were associated with IC, cross-sectionally and longitudinally. FMT from individuals with obesity led to alterations in mice reversal learning. In an independent FMT experiment, human donor's bacterial functions related to IC deficits were associated with mPFC expression of one-carbon metabolism-related genes of recipient's mice. CONCLUSION: These results highlight the importance of targeting obesity-related impulsive behaviour through the induction of gut microbiota shifts.

Brain Functional Connectivity Correlates of Subclinical Obsessive-Compulsive Symptoms in Healthy Children.

OBJECTIVE: Commonly observed subclinical obsessive-compulsive symptoms in healthy children may predispose to obsessive-compulsive disorder (OCD). Therefore, investigating the underlying neurobiology may be relevant to identify alterations in specific brain circuits potentially accounting for clinical heterogeneity in OCD without the confounding effects of clinical samples. We analyzed the brain correlates of different obsessive-compulsive symptoms in a large group of healthy children using functional connectivity measures. METHOD: We evaluated 227 healthy children (52% girls; mean [SD] age 9.71 [0.86] years; range, 8-12.1 years). Participants underwent clinical assessment with the Obsessive-Compulsive Inventory-Child Version and a resting-state functional magnetic resonance imaging examination. Total and symptom-specific severity were correlated with voxelwise global functional connectivity degree values. Significant clusters were then used as seeds of interest in seed-to-voxel analyses. Modulating effects of age and sex were also assessed. RESULTS: Global functional connectivity of the left ventral putamen and medial dorsal thalamus correlated negatively with total obsessive-compulsive symptom severity. Seed-to-voxel analyses revealed specific negative correlations from these clusters with limbic, sensorimotor, and insular regions in association with obsessing, ordering, and doubt-checking symptoms, respectively. Hoarding symptoms were associated with negative correlations between the left medial dorsal thalamus and a widespread pattern of regions, with such associations modulated by sex and age. CONCLUSION: Our findings concur with prevailing neurobiological models of OCD on the importance of cortico-striato-thalamo-cortical dysfunction to account for symptom severity. Notably, we showed that changes in cortico-striato-thalamo-cortical connectivity are present at subclinical stages, which may result in an increased vulnerability for OCD. Moreover, we mapped different symptom dimensions onto specific cortico-striato-thalamo-cortical circuit attributes.

Obesity Impairs Short-Term and Working Memory through Gut Microbial Metabolism of Aromatic Amino Acids.

The gut microbiome has been linked to fear extinction learning in animal models. Here, we aimed to explore the gut microbiome and memory domains according to obesity status. A specific microbiome profile associated with short-term memory, working memory, and the volume of the hippocampus and frontal regions of the brain differentially in human subjects with and without obesity. Plasma and fecal levels of aromatic amino acids, their catabolites, and vegetable-derived compounds were longitudinally associated with short-term and working memory. Functionally, microbiota transplantation from human subjects with obesity led to decreased memory scores in mice, aligning this trait from humans with that of recipient mice. RNA sequencing of the medial prefrontal cortex of mice revealed that short-term memory associated with aromatic amino acid pathways, inflammatory genes, and clusters of bacterial species. These results highlight the potential therapeutic value of targeting the gut microbiota for memory impairment, specifically in subjects with 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.

Neural-based valuation of functional foods among lean and obese individuals.

Functional foods may contribute to establish healthy eating habits and reduce obesity and related comorbidities. Differences in the brain mechanisms underpinning the valuation of functional foods in individuals with excess weight may inform the development of attractive functional foods. We aimed to compare brain function during the Willingness to Pay task for functional vs standard foods between individuals with healthy weight (HW), overweight (OW), and obesity (OB). We hypothesized that, in participants with OB, willingness to pay for functional foods would evoke greater activation/connectivity in brain regions previously associated with subjective value. Thirty-six HW, 19 OW, and 20 OB adults performed a functional magnetic resonance imaging-Willingness to Pay task that requires them to decide how much they would pay for presented standard and functional food images tasted in a previous buffet. Whole-brain analyses compared task-related activation and connectivity between participants with OB, OW, and HW. Individuals with OB, relative to HW, showed more similar willingness to pay for functional and standard food. At the brain level, they also showed hyperactivation in the ventral posterior cingulate cortex and the right angular gyrus, as well as an increased functional connectivity between the ventral posterior cingulate cortex and the intraparietal cortices to the valuation of the functional vs the standard foods. Increased willingness to pay for functional foods in people with excessive weight may be driven by recruitment of brain regions that direct attention to internal goals.

The neural interface between negative emotion regulation and motivation for change in cocaine dependent individuals under treatment.

BACKGROUND: Emotion regulation is important for cocaine addiction treatment success, particularly during early abstinence. In addition, the neural underpinnings of emotion processing overlap with those of motivation and goal-directed behavior. We examined if the neural underpinnings of emotion maintenance and its regulation correlate with cocaine treatment motivation. METHODS: Forty-five cocaine dependent individuals (CDIs) starting outpatient treatment in a public specialized addiction treatment clinic in Granada (Spain) underwent fMRI scans while performing a Reappraisal task, and completed the University of Rhode Island Change Assessment Scale (URICA), to measure treatment motivation. We conducted correlation analyses to examine the association between emotion maintenance and regulation related brain activation and URICA's Readiness to Change scores. We also explored links between Emotional reports during the fMRI reappraisal task, duration of abstinence, and anxiety and depression symptoms. RESULTS: Readiness to Change scores were positively correlated with activations in the right dorsolateral prefrontal and right parietal cortices, the midbrain (p ≤ 0.001, cluster extents ≥109 voxels), and basolateral amygdala (PFWE-SVC<0.05), while negatively with emotion maintenance related activation in the same cortical areas and activations in the dorsomedial frontal cortex, the nucleus accumbens and the left fusiform gyrus. Emotional reactivity negatively correlated with right dorsolateral prefrontal cortex reappraisal related activation (r= -0.40, p = 0.007), and the Regulate score positively correlated with the left fusiform gyrus emotion maintenance related activation (r = 0.31, p = 0.04). CONCLUSIONS: Emotional related activation in frontoparietal, accumbens, fusiform, amygdala and midbrain regions engaged during emotion regulation and its maintenance correlate with early treatment motivation in CDIs.

Food Addiction Symptoms and Amygdala Response in Fasted and Fed States.

Few studies have investigated the underlying neural substrates of food addiction (FA) in humans using a recognised assessment tool. In addition, no studies have investigated subregions of the amygdala (basolateral (BLA) and central amygdala), which have been linked to reward-seeking behaviours, susceptibility to weight gain, and promoting appetitive behaviours, in the context of FA. This pilot study aimed to explore the association between FA symptoms and activation in the BLA and central amygdala via functional magnetic resonance imaging (fMRI), in response to visual food cues in fasted and fed states. Females (n = 12) aged 18-35 years completed two fMRI scans (fasted and fed) while viewing high-calorie food images and low-calorie food images. Food addiction symptoms were assessed using the Yale Food Addiction Scale. Associations between FA symptoms and activation of the BLA and central amygdala were tested using bilateral masks and small-volume correction procedures in multiple regression models, controlling for BMI. Participants were 24.1 ± 2.6 years, with mean BMI of 27.4 ± 5.0 kg/m2 and FA symptom score of 4.1 ± 2.2. A significant positive association was identified between FA symptoms and higher activation of the left BLA to high-calorie versus low-calorie foods in the fasted session, but not the fed session. There were no significant associations with the central amygdala in either session. This exploratory study provides pilot data to inform future studies investigating the neural mechanisms underlying FA.

Glycated Hemoglobin, but not Insulin Sensitivity, is Associated with Memory in Subjects with Obesity.

OBJECTIVE: Obesity has been related to later-life dementia. Serum glucose levels and insulin resistance are known to influence cognition in individuals with diabetes. This study aimed to evaluate memory function in middle-aged individuals with obesity in association with glucose metabolism and brain iron content. METHODS: This was a cross-sectional case-control study including 121 participants aged 27.2 to 66.6 years (56 without obesity, 65 with obesity) stratified according to sex and menopausal status. Insulin sensitivity, body composition, brain iron content, and memory function were evaluated by euglycemic hyperinsulinemic clamp, dual-energy x-ray absorptiometry, magnetic resonance relaxometry (R2*), and California Verbal Learning Test, respectively. RESULTS: Women with obesity, but not men, had lower scores in some California Verbal Learning Tests in association with metabolic parameters and increased brain iron content compared with controls. Fasting plasma glucose, glycated hemoglobin (HbA1c; within normal range), and R2* were negatively associated with memory scores, whereas insulin sensitivity showed positive associations. Remarkably, only HbA1c levels and R2* in the right inferior fronto-orbital region remained significant after controlling for age, sex, education, and BMI. CONCLUSIONS: Impairments in memory function in middle-aged women with obesity are associated with HbA1c levels and brain iron content independently of insulin sensitivity. These results may have implications in the design of therapeutic strategies in women with obesity.

Hypothalamic Networks in Adolescents With Excess Weight: Stress-Related Connectivity and Associations With Emotional Eating.

OBJECTIVE: Adolescents with excess weight are particularly sensitive to stress, which may contribute to the presence of emotional eating behaviors. It is proposed that this may be due to alterations in the connectivity between hypothalamic networks and regions of the "emotional nervous system," involved in the regulation of energy balance and stress processing. However, this remains to be clarified in adolescents with excess weight. METHOD: We investigated whole-brain differences in the functional connectivity of the medial and lateral hypothalamus (MH and LH) between adolescents with excess weight (EW, n = 53; mean age = 14.64 years, SD = 1.78) and normal weight (NW, n = 51; mean age = 15.29 years, SD = 1.75) using seed-based resting-state analyses. Then, in a subset of 22 adolescents with EW (mean age = 15.75 years, SD = 1.70) and 32 with NW (mean age = 15.27, SD = 2.03), we explored for group interactions between the MH/LH networks and stress response in the Trier Social Stress Task (TSST) and emotional eating, assessed with the Dutch Eating Behavior Questionnaire (DEB-Q). RESULTS: Compared to NW, EW showed higher functional connectivity in the LH-orbitofrontal cortex, ventral striatum, anterior insula, and in the MH-middle temporal cortex networks. EW also showed lower connectivity in the LH-cerebellum, and in the MH-middle prefrontal, pre-, and postcentral gyri networks. In EW, higher connectivity of the LH-nucleus accumbens and LH-midbrain networks were associated with stress response. Higher connectivity in the LH-midbrain was also associated with a greater presence of emotional eating behaviors in EW. CONCLUSION: Adolescents with EW showed functional connectivity alterations within both MH/LH networks. Alterations in the LH network were linked with higher levels of stress response and emotional-driven eating patterns.

Food addiction linked to changes in ventral striatum functional connectivity between fasting and satiety.

INTRODUCTION: The concept of "food addiction" (FA) has gained popularity in view of clinical and neurobiological overlaps between excessive food intake and addictive disorders. However, no studies have examined the link between FA and striatocortical circuits involved in addictive disorders, or the influence of homeostatic status, which regulates the drive to eat, on these systems. This study aims to investigate changes in striatal functional connectivity between fasted and fed conditions among adults ranging in body mass index (BMI) and FA symptoms. METHODS: Thirty adults were recruited from the general community and completed self-reported surveys including demographics, FA symptoms using the Yale Food Addiction Scale, as well as height and weight measures, used to determine BMI. Participants completed two 3-T MRI scans, one in a fasted state and one in a fed state. We conducted seed-based analyses to examine between-session ("fasted > fed") change in resting-state functional connectivity of the ventral and dorsal striatum, and its association with FA scores (controlling for BMI). RESULTS: Higher symptoms of FA correlated with greater changes in ventral caudate-hippocampus connectivity between fasted and fed conditions. FA symptoms did not correlate with connectivity in the dorsal caudate circuit. Post-hoc analyses revealed that participants with higher symptoms of FA had ventral caudate-hippocampus hyperconnectivity in the fasted scan only, as well as a significant reduction of this connectivity between the fasted and fed scans. CONCLUSIONS: Heightened connectivity in the ventral striatum during a fasted state, which has been linked to reward prediction signals, underpins symptoms of FA. In contrast, connectivity in the dorsal striatum or "habit" system is unrelated to homeostatic status and FA symptoms, and is thus less relevant for subclinical manifestations of FA.