María José Fernández-Serrano

Selective Alterations Within Executive Functions in Adolescents With Excess Weight

Increasing evidence underscores overlapping neurobiological pathways to addiction and obesity. In both conditions, reward processing of preferred stimuli is enhanced, whereas the executive control system that would normally regulate reward‐driven responses is altered. This abnormal interaction can be greater in adolescence, a period characterized by relative immaturity of executive control systems coupled with the relative maturity of reward processing systems. The aim of this study is to explore neuropsychological performance of adolescents with excess weight (n = 27, BMI range 24–51 kg/m2) vs. normal‐weight adolescents (n = 34, BMI range 17–24 kg/m2) on a comprehensive battery of executive functioning tests, including measures of working memory (letter‐number sequencing), reasoning (similarities), planning (zoo map), response inhibition (five‐digit test (FDT)–interference and Stroop), flexibility (FDT–switching and trail‐making test (TMT)), self‐regulation (revised‐strategy application test (R‐SAT)), and decision‐making (Iowa gambling task (IGT)). We also aimed to explore personality traits of impulsivity and sensitivity to reward. Independent sample t‐ and Z Kolmogorov–Smirnov tests showed significant differences between groups on indexes of inhibition, flexibility, and decision‐making (excess‐weight participants performed poorer than controls), but not on tests of working memory, planning, and reasoning, nor on personality measures. Moreover, regression models showed a significant association between BMI and flexibility performance. These results are indicative of selective alterations of particular components of executive functions in overweight adolescents.

Trait impulsivity and prefrontal gray matter reductions in cocaine dependent individuals.

BACKGROUND Impulsivity is thought to play a key role in cocaine addiction onset and progression; therefore, we hypothesized that different facets of impulsive personality may be significantly associated with brain structural abnormalities in cocaine-dependent individuals. METHODS Thirty-eight cocaine-dependent individuals and 38 non-drug using controls completed the UPPS-P scale (measuring five different facets of impulsivity: sensation seeking, lack of premeditation, lack of perseverance, and positive and negative urgency) and were scanned on a 3T MRI scanner. We used whole-brain voxel-based morphometry analyses (VBM) to detect differences in gray matter (GM) and white matter (WM) volumes between cocaine users and controls, and to measure differences in the way that impulsivity relates to GM and WM volumes in cocaine users vs. controls. RESULTS Cocaine-dependent individuals had lower GM volumes in a number of sections of the orbitofrontal cortex, right inferior frontal gyrus, right insula, left amygdala and parahippocampal gyrus, temporal gyrus, and bilateral caudate. They also had lower WM volumes in the left inferior and medial frontal gyrus, superior temporal gyrus, right anterior cingulate cortex, insula and caudate. There was a positive correlation between trait impulsivity and GM volume in the left inferior/middle frontal gyrus of cocaine-dependent individuals, a pattern directly opposed to the association in controls. Conversely, in cocaine users lack of premeditation was negatively correlated with GM volume in the insula and the putamen. CONCLUSIONS Trait impulsivity may influence cocaine dependence by impacting its neurobiological underpinnings in frontostriatal systems.

Neuropsychological consequences of alcohol and drug abuse on different components of executive functions

Several studies have shown alterations in different components of executive functioning in users of different drugs, including cannabis, cocaine and heroin. However, it is difficult to establish a specific association between the use of each of these drugs and executive alterations, since most drug abusers are polysubstance abusers, and alcohol is a ubiquitous confounding factor. Moreover, in order to study the association between consumption of different drugs and executive functioning, the patterns of quantity and duration of drugs used must be considered, given the association between these parameters and the executive functioning alteration degree. Based on the multicomponent approach to executive functions, the aims of the present study were: (i) to analyse the differential contribution of alcohol versus cocaine, heroin and cannabis use on executive functions performance; and (ii) to analyse the contribution made by the severity of the different drugs used (quantity and duration patterns) on these functions in a sample of polysubstance abusers that requested treatment for cannabis-, cocaine- or heroin-related problems. We administered measures of fluency, working memory, analogical reasoning, interference, cognitive flexibility, decision-making and self-regulation to two groups: 60 substance-dependent individuals (SDIs) and 30 healthy control individuals (HCIs). SDIs had significantly poorer performance than HCIs across all of the executive domains assessed. Results from hierarchical regression models showed the existence of common correlates of the use of alcohol, cannabis and cocaine on verbal fluency and decision-making; common correlates of quantity of cannabis and cocaine use on verbal working memory and analogical reasoning; common correlates of duration of cocaine and heroin use on shifting; and specific effects of duration of cocaine use on inhibition measures. These findings indicate that alcohol abuse is negatively associated with fluency and decision-making deficits, whereas the different drugs motivating treatment have both generalized and specific deleterious effects on different executive components.

Neuropsychological profiling of impulsivity and compulsivity in cocaine dependent individuals

RationaleResearch on the relative impact of trait impulsivity vs. drug exposure on neuropsychological probes of response inhibition vs. response perseveration has been posited as a valid pathway to explore the transition between impulsivity and compulsivity on psychostimulant dependence.ObjectivesThe objectives of this study are to examine performance differences between cocaine-dependent individuals (CDI) and healthy comparison individuals (HCI) on neuropsychological probes of inhibition and perseveration and to examine the predictive impact of trait impulsivity—a proxy of premorbid vulnerability, and severity of cocaine use—a proxy of drug exposure, on CDI’s performance.MethodsForty-two CDI and 65 HCI were assessed using the UPPS-P Scale (trait impulsivity), the Stroop and go/no-go (inhibition) and revised-strategy application and probabilistic reversal tests (perseveration).ResultsCDI, compared to HCI, have elevated scores on trait impulsivity and perform significantly poorer on inhibition and perseveration, with specific detrimental effects of duration of cocaine use on perseveration.ConclusionsCDI have both inhibition and perseveration deficits; both patterns were broadly indicative of orbitofrontal dysfunction in the context of reinforcement learning. Impulsive personality and cocaine exposure jointly contribute to deficits in response perseveration or compulsivity.

Impact of severity of drug use on discrete emotions recognition in polysubstance abusers

Neuropsychological studies support the association between severity of drug intake and alterations in specific cognitive domains and neural systems, but there is disproportionately less research on the neuropsychology of emotional alterations associated with addiction. One of the key aspects of adaptive emotional functioning potentially relevant to addiction progression and treatment is the ability to recognize basic emotions in the faces of others. Therefore, the aims of this study were: (i) to examine facial emotion recognition in abstinent polysubstance abusers, and (ii) to explore the association between patterns of quantity and duration of use of several drugs co-abused (including alcohol, cannabis, cocaine, heroin and MDMA) and the ability to identify discrete facial emotional expressions portraying basic emotions. We compared accuracy of emotion recognition of facial expressions portraying six basic emotions (measured with the Ekman Faces Test) between polysubstance abusers (PSA, n=65) and non-drug using comparison individuals (NDCI, n=30), and used regression models to explore the association between quantity and duration of use of the different drugs co-abused and indices of recognition of each of the six emotions, while controlling for relevant socio-demographic and affect-related confounders. Results showed: (i) that PSA had significantly poorer recognition than NDCI for facial expressions of anger, disgust, fear and sadness; (ii) that measures of quantity and duration of drugs used significantly predicted poorer discrete emotions recognition: quantity of cocaine use predicted poorer anger recognition, and duration of cocaine use predicted both poorer anger and fear recognition. Severity of cocaine use also significantly predicted overall recognition accuracy.

Neural Correlates of the Severity of Cocaine, Heroin, Alcohol, MDMA and Cannabis Use in Polysubstance Abusers: A Resting-PET Brain Metabolism Study

Introduction Functional imaging studies of addiction following protracted abstinence have not been systematically conducted to look at the associations between severity of use of different drugs and brain dysfunction. Findings from such studies may be relevant to implement specific interventions for treatment. The aim of this study was to examine the association between resting-state regional brain metabolism (measured with 18F-fluorodeoxyglucose Positron Emission Tomography (FDG-PET) and the severity of use of cocaine, heroin, alcohol, MDMA and cannabis in a sample of polysubstance users with prolonged abstinence from all drugs used. Methods Our sample consisted of 49 polysubstance users enrolled in residential treatment. We conducted correlation analyses between estimates of use of cocaine, heroin, alcohol, MDMA and cannabis and brain metabolism (BM) (using Statistical Parametric Mapping voxel-based (VB) whole-brain analyses). In all correlation analyses conducted for each of the drugs we controlled for the co-abuse of the other drugs used. Results The analysis showed significant negative correlations between severity of heroin, alcohol, MDMA and cannabis use and BM in the dorsolateral prefrontal cortex (DLPFC) and temporal cortex. Alcohol use was further associated with lower metabolism in frontal premotor cortex and putamen, and stimulants use with parietal cortex. Conclusions Duration of use of different drugs negatively correlated with overlapping regions in the DLPFC, whereas severity of cocaine, heroin and alcohol use selectively impact parietal, temporal, and frontal-premotor/basal ganglia regions respectively. The knowledge of these associations could be useful in the clinical practice since different brain alterations have been associated with different patterns of execution that may affect the rehabilitation of these patients.

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.

Cocaine‐specific neuroplasticity in the ventral striatum network is linked to delay discounting and drug relapse

AIMS To contrast functional connectivity on ventral and dorsal striatum networks in cocaine dependence relative to pathological gambling, via a resting-state functional connectivity approach; and to determine the association between cocaine dependence-related neuroadaptations indexed by functional connectivity and impulsivity, compulsivity and drug relapse. DESIGN Cross-sectional study of 20 individuals with cocaine dependence (CD), 19 individuals with pathological gambling (PG) and 21 healthy controls (HC), and a prospective cohort study of 20 CD followed-up for 12 weeks to measure drug relapse. SETTING AND PARTICIPANTS CD and PG were recruited through consecutive admissions to a public clinic specialized in substance addiction treatment (Centro Provincial de Drogodependencias) and a public clinic specialized in gambling treatment (AGRAJER), respectively; HC were recruited through community advertisement in the same area in Granada (Spain). MEASUREMENTS Seed-based functional connectivity in the ventral striatum (ventral caudate and ventral putamen) and dorsal striatum (dorsal caudate and dorsal putamen), the Kirby delay-discounting questionnaire, the reversal-learning task and a dichotomous measure of cocaine relapse indicated with self-report and urine tests. FINDINGS CD relative to PG exhibit enhanced connectivity between the ventral caudate seed and subgenual anterior cingulate cortex, the ventral putamen seed and dorsomedial pre-frontal cortex and the dorsal putamen seed and insula (P≤0.001, kE=108). Connectivity between the ventral caudate seed and subgenual anterior cingulate cortex is associated with steeper delay discounting (P≤0.001, kE=108) and cocaine relapse (P≤0.005, kE=34). CONCLUSIONS Cocaine dependence-related neuroadaptations in the ventral striatum of the brain network are associated with increased impulsivity and higher rate of cocaine relapse.

Social stress increases cortisol and hampers attention in adolescents with excess weight.

Objective To experimentally examine if adolescents with excess weight are more sensitive to social stress and hence more sensitive to harmful effects of stress in cognition. Design and Methods We conducted an experimental study in 84 adolescents aged 12 to 18 years old classified in two groups based on age adjusted Body Mass Index percentile: Normal weight (n=42) and Excess weight (n=42). Both groups were exposed to social stress as induced by the virtual reality version of the Trier Social Stress Task --participants were requested to give a public speech about positive and negative aspects of their personalities in front of a virtual audience. The outcome measures were salivary cortisol levels and performance in cognitive tests before and after the social stressor. Cognitive tests included the CANTAB Rapid Visual Processing Test (measuring attention response latency and discriminability) and the Iowa Gambling Task (measuring decision-making). Results Adolescents with excess weight compared to healthy weight controls displayed increased cortisol response and less improvement of attentional performance after the social stressor. Decision-making performance decreased after the social stressor in both groups. Conclusion Adolescents who are overweight or obese have increased sensitivity to social stress, which detrimentally impacts attentional skills.

Preliminary validation of the Spanish version of the Frontal Systems Behavior Scale (FrSBe) using Rasch analysis

Primary objective: To explore the construct validity of the Spanish version of the Frontal Systems Behavioral Scale (FrSBe) using Rasch modelling. Methods: Item responses of 245 Spanish subjects were analysed using Rasch analysis: self-rating of 65 participants with TBI or stroke (sample A), family-rating of the same 65 participants (sample B) and self-rating of 115 healthy individuals (sample C). Results: After removing or grouping several problematic items, the Apathy and the Executive Dysfunction sub-scales were found to be valid measures for samples A and B and the Disinhibition sub-scale was valid for samples B and C. Person Separation Index of reliability of sub-scales was greater than 0.83 for sample B and ∼0.72 for A and C. All items showed disordered threshold categories in samples A and B and five items were ordered in sample C. Conclusions: With a few modifications, the sub-scales of the FrSBe-Spanish version are adequate measures for the assessment of the behavioural syndromes derived from frontal systems dysfunction in persons with brain injury. The family-rating form is preferable to the self-rating form. Only the Disinhibition scale is a valid measure for the behavioural assessment of the normal population. A reduction of response categories is suggested.