Juan Verdejo-Román

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.

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.

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.

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. Hum Brain Mapp, 36:–237, 2015.

Decreased insular and increased midbrain activations during decision-making under risk in adolescents with excess weight

Functional magnetic resonance imaging (fMRI) was used to explore the brain substrates of decisions under risk in excess weight adolescents. Decreased activations of the brain regions signaling risk (orbitofrontal cortex [OFC], insula) were expected during anticipation of higher rewards and increased activations of the brain regions involved in reward processing (OFC, striatum) were expected after reward receipt in excess weight adolescents compared to normal weight controls.

Cocaine users with comorbid Cluster B personality disorders show dysfunctional brain activation and connectivity in the emotional regulation networks during negative emotion maintenance and reappraisal

Cocaine dependence often co-occurs with Cluster B personality disorders. Since both disorders are characterized by emotion regulation deficits, we predicted that cocaine comorbid patients would exhibit dysfunctional patterns of brain activation and connectivity during reappraisal of negative emotions. We recruited 18 cocaine users with comorbid Cluster B personality disorders, 17 cocaine users without comorbidities and 21 controls to be scanned using functional magnetic resonance imaging (fMRI) during performance on a reappraisal task in which they had to maintain or suppress the emotions induced by negative affective stimuli. We followed region of interest (ROI) and whole-brain approaches to investigate brain activations and connectivity associated with negative emotion experience and reappraisal. Results showed that cocaine users with comorbid personality disorders had reduced activation of the subgenual anterior cingulate cortex during negative emotion maintenance and increased activation of the lateral orbitofrontal cortex and the amygdala during reappraisal. Amygdala activation correlated with impulsivity and antisocial beliefs in the comorbid group. Connectivity analyses showed that in the cocaine comorbid group the subgenual cingulate was less efficiently connected with the amygdala and the fusiform gyri and more efficiently connected with the anterior insula during maintenance, whereas during reappraisal the left orbitofrontal cortex was more efficiently connected with the amygdala and the right orbitofrontal cortex was less efficiently connected with the dorsal striatum. We conclude that cocaine users with comorbid Cluster B personality disorders have distinctive patterns of brain activation and connectivity during maintenance and reappraisal of negative emotions, which correlate with impulsivity and dysfunctional beliefs.

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

The brains 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. Brains 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 systems 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 brains reward system to food versus monetary rewards in obesity and overweight. Hum Brain Mapp 38:666–677, 2017.

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

Abstract 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. HighlightsGraph analyses unraveled connectivity alterations associated to excess weight.Excess weight is associated with reduced functional connectivity during food processing.Excess weight is associated with increased functional connectivity to monetary rewards.Altered networks linked to food and monetary reward processing were significantly different.

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

Abstract 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 &bgr; 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 (&bgr; 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 &bgr; ranging from 0.564 to 0.611. Both clusters were related to better academic performance (&bgr; 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. HighlightsPhysical fitness components are positively associated with gray matter volumes in overweight/obese children.Cardiorespiratory fitness and speed‐agility affect development of distinctive brain regions.Cardiorespiratory fitness and speed‐agility related‐changes in brain volumes are associated with better academic performance.Muscular fitness is not associated with cortical and subcortical brain volumes.Physical activity that involves aerobic exercise and motor‐agility tasks is important for the brain and academic performance.

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.