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.

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.

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.

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.

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.

The contribution of brain imaging to the understanding of psychopathy.

Psychopathy is a personality type characterized by both callous emotional dysfunction and deviant behavior that affects society in the form of actions that harm others. Historically, researchers have been concerned with seeking data and arguments to support a neurobiological foundation of psychopathy. In the past few years, increasing research has begun to reveal brain alterations putatively underlying the enigmatic psychopathic personality. In this review, we describe the brain anatomical and functional features that characterize psychopathy from a synthesis of available neuroimaging research and discuss how such brain anomalies may account for psychopathic behavior. The results are consistent in showing anatomical alterations involving primarily a ventral system connecting the anterior temporal lobe to anterior and ventral frontal areas, and a dorsal system connecting the medial frontal lobe to the posterior cingulate cortex/precuneus complex and, in turn, to medial structures of the temporal lobe. Functional imaging data indicate that relevant emotional flow breakdown may occur in both these brain systems and suggest specific mechanisms via which emotion is anomalously integrated into cognition in psychopathic individuals during moral challenge. Directions for future research are delineated emphasizing, for instance, the relevance of further establishing the contribution of early life stress to a learned blockage of emotional self-exposure, and the potential role of androgenic hormones in the development of cortical anomalies.

Brain Volumetric Correlates of Right Unilateral Versus Bitemporal Electroconvulsive Therapy for Treatment-Resistant Depression.

OBJECTIVE: The selection of a bitemporal (BT) or right unilateral (RUL) electrode placement affects the efficacy and side effects of ECT. Previous studies have not entirely described the neurobiological underpinnings of such differential effects. Recent neuroimaging research on gray matter volumes is contributing to our understanding of the mechanism of action of ECT and could clarify the differential mechanisms of BT and RUL ECT. METHODS: To assess the whole-brain gray matter volumetric changes observed after treating patients with treatment-resistant depression with BT or RUL ECT, the authors used MRI to assess 24 study subjects with treatment-resistant depression (bifrontotemporal ECT, N=12; RUL ECT, N=12) at two time points (before the first ECT session and after ECT completion). RESULTS: Study subjects receiving BT ECT showed gray matter volume increases in the bilateral limbic system, but subjects treated with RUL ECT showed gray matter volume increases limited to the right hemisphere. The authors observed significant differences between the two groups in midtemporal and subcortical limbic structures in the left hemisphere. CONCLUSIONS: These findings highlight that ECT-induced gray matter volume increases may be specifically observed in the stimulated hemispheres. The authors suggest that electrode placement may relevantly contribute to the development of personalized ECT protocols.

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.

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.

Increased corticolimbic connectivity in cocaine dependence versus pathological gambling is associated with drug severity and emotion-related impulsivity.

Neural biomarkers for the active detrimental effects of cocaine dependence (CD) are lacking. Direct comparisons of brain connectivity in cocaine-targeted networks between CD and behavioural addictions (i.e. pathological gambling, PG) may be informative. This study therefore contrasted the resting-state functional connectivity networks of 20 individuals with CD, 19 individuals with PG and 21 healthy individuals (controls). Study groups were assessed to rule out psychiatric co-morbidities (except alcohol abuse and nicotine dependence) and current substance use or gambling (except PG). We first examined global connectivity differences in the corticolimbic reward network and then utilized seed-based analyses to characterize the connectivity of regions displaying between-group differences. We examined the relationships between seed-based connectivity and trait impulsivity and cocaine severity. CD compared with PG displayed increased global functional connectivity in a large-scale ventral corticostriatal network involving the orbitofrontal cortex, caudate, thalamus and amygdala. Seed-based analyses showed that CD compared with PG exhibited enhanced connectivity between the orbitofrontal and subgenual cingulate cortices and between caudate and lateral prefrontal cortex, which are involved in representing the value of decision-making feedback. CD and PG compared with controls showed overlapping connectivity changes between the orbitofrontal and dorsomedial prefrontal cortices and between amygdala and insula, which are involved in stimulus-outcome learning. Orbitofrontal-subgenual cingulate cortical connectivity correlated with impulsivity and caudate/amygdala connectivity correlated with cocaine severity. We conclude that CD is linked to enhanced connectivity in a large-scale ventral corticostriatal-amygdala network that is relevant to decision making and likely to reflect an active cocaine detrimental effect.

Amygdala activation and symptom dimensions in obsessive-compulsive disorder.

BACKGROUND: Despite knowledge of amygdala involvement in fear and anxiety, its contribution to the pathophysiology of obsessive-compulsive disorder (OCD) remains controversial. In the context of neuroimaging studies, it seems likely that the heterogeneity of the disorder might have contributed to a lack of consistent findings. AIMS: To assess the influence of OCD symptom dimensions on amygdala responses to a well-validated emotional face-matching paradigm. METHOD: Cross-sectional functional magnetic resonance imaging (fMRI) study of 67 patients with OCD and 67 age-, gender- and education-level matched healthy controls. RESULTS: The severity of aggression/checking and sexual/religious symptom dimensions were significantly associated with heightened amygdala activation in those with OCD when responding to fearful faces, whereas no such correlations were seen for other symptom dimensions. CONCLUSIONS: Amygdala functional alterations in OCD appear to be specifically modulated by symptom dimensions whose origins may be more closely linked to putative amygdala-centric processes, such as abnormal fear processing.

Functional alteration in frontolimbic systems relevant to moral judgment in cocaine-dependent subjects.

Cocaine addiction is characterized by persistent decision-making deficits, which are linked to structural and functional abnormalities in frontolimbic systems. Moral judgment is as a special instance of decision making, in which both cognitive and emotional signals must be adequately integrated to decide how to resolve moral dilemmas. Here, we employed a moral dilemmas functional magnetic resonance imaging (fMRI) task to explore possible alterations of frontolimbic systems in cocaine-dependent subjects. We also explored if these alterations relate to more basic deficits in functional connectivity within these systems during spontaneous resting-state activation. Ten cocaine-dependent subjects and 14 non-drug-using controls participated in the study. Cocaine-dependent subjects were carefully selected to discard potentially confounding co-morbidities, and they underwent a uniform supervised abstinence period of 10 days. Both groups were scanned, and fMRI maps were generated to identify (1) brain response to moral dilemmas; and (2) the strength of functional connectivity within frontolimbic systems during resting-state. During the moral dilemmas task, cocaine-dependent subjects showed reduced activation involving frontolimbic structures as the anterior cingulate cortex (ACC), left insula and brain stem. Connectivity analyses showed that cocaine users had less resting-state functional connectivity between ACC, thalamus, insula and brain stem. These results demonstrate that cocaine-dependent subjects have functional alterations in the frontolimbic systems that support moral judgment and social decision making.

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.

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.

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.

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.

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.