Laura Moreno-López

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 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.

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.

Brain Structural Correlates of Reward Sensitivity and Impulsivity in Adolescents with Normal and Excess Weight

Introduction Neuroscience evidence suggests that adolescent obesity is linked to brain dysfunctions associated with enhanced reward and somatosensory processing and reduced impulse control during food processing. Comparatively less is known about the role of more stable brain structural measures and their link to personality traits and neuropsychological factors on the presentation of adolescent obesity. Here we aimed to investigate regional brain anatomy in adolescents with excess weight vs. lean controls. We also aimed to contrast the associations between brain structure and personality and cognitive measures in both groups. Methods Fifty-two adolescents (16 with normal weight and 36 with excess weight) were scanned using magnetic resonance imaging and completed the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ), the UPPS-P scale, and the Stroop task. Voxel-based morphometry (VBM) was used to assess possible between-group differences in regional gray matter (GM) and to measure the putative differences in the way reward and punishment sensitivity, impulsivity and inhibitory control relate to regional GM volumes, which were analyzed using both region of interest (ROI) and whole brain analyses. The ROIs included areas involved in reward/somatosensory processing (striatum, somatosensory cortices) and motivation/impulse control (hippocampus, prefrontal cortex). Results Excess weight adolescents showed increased GM volume in the right hippocampus. Voxel-wise volumes of the second somatosensory cortex (SII) were correlated with reward sensitivity and positive urgency in lean controls, but this association was missed in excess weight adolescents. Moreover, Stroop performance correlated with dorsolateral prefrontal cortex volumes in controls but not in excess weight adolescents. Conclusion Adolescents with excess weight have structural abnormalities in brain regions associated with somatosensory processing and motivation.

Negative urgency, disinhibition and reduced temporal pole gray matter characterize the comorbidity of cocaine dependence and personality disorders ☆

BACKGROUND Individuals with cocaine dependence and co-occurring personality disorders are more likely to have increased impulsivity, dysfunctional beliefs, executive dysfunction and brain structural abnormalities by virtue of the conjoint impact of both pathologies. METHODS We recruited 32 cocaine dependent patients with comorbid Cluster B personality disorders, 44 cocaine dependent patients without comorbidities and 34 non-drug-using controls. They completed the UPPS-P impulsivity scale, the Personality Belief Questionnaire, and executive function tests of working memory, attention/response inhibition and shifting. A subsample (n=61) was also scanned using Magnetic Resonance Imaging. We used univariate ANOVAs for group comparisons, and tested the association between impulsivity, executive control and personality dysfunction and diagnoses using correlation and multivariate logistic regression analyses. RESULTS Cocaine dependent patients with personality disorders had elevated negative urgency and borderline beliefs, decreased inhibition and attention regulation, and reduced temporal pole gray matter with respect to the rest of the sample. Trait and cognitive measures correctly classified 73% of comorbid patients (60% sensitivity and 82% specificity). CONCLUSION The co-occurrence of cocaine dependence and personality disorders is associated with negative-mood impulsivity and beliefs, executive dysfunction and temporal pole attrition.

Cocaine use severity and cerebellar gray matter are associated with reversal learning deficits in cocaine-dependent individuals.

Cocaine addiction involves persistent deficits to unlearn previously rewarded response options, potentially due to neuroadaptations in learning‐sensitive regions. Cocaine‐targeted prefrontal systems have been consistently associated with reinforcement learning and reversal deficits, but more recent interspecies research has raised awareness about the contribution of the cerebellum to cocaine addiction and reversal. We aimed at investigating the link between cocaine use, reversal learning and prefrontal, insula and cerebellar gray matter in cocaine‐dependent individuals (CDIs) varying on levels of cocaine exposure in comparison with healthy controls (HCs). Twenty CDIs and 21 HCs performed a probabilistic reversal learning task (PRLT) and were subsequently scanned in a 3‐Tesla magnetic resonance imaging scanner. In the PRLT, subjects progressively learn to respond to one predominantly reinforced stimulus, and then must learn to respond according to the opposite, previously irrelevant, stimulus‐reward pairing. Performance measures were errors after reversal (reversal cost), and probability of maintaining response after errors. Voxel‐based morphometry was conducted to investigate the association between gray matter volume in the regions of interest and cocaine use and PRLT performance. Severity of cocaine use correlated with gray matter volume reduction in the left cerebellum (lobule VIII), while greater reversal cost was correlated with gray matter volume reduction in a partially overlapping cluster (lobules VIIb and VIII). Right insula/inferior frontal gyrus correlated with probability of maintaining response after errors. Severity of cocaine use detrimentally impacted reversal learning and cerebellar gray matter.

Disrupted functional connectivity in adolescent obesity

Background/objective Obesity has been associated with brain alterations characterised by poorer interaction between a hypersensitive reward system and a comparatively weaker prefrontal-cognitive control system. These alterations may occur as early as in adolescence, but this notion remains unclear, as no studies so far have examined global functional connectivity in adolescents with excess weight. Subjects/methods We investigated functional connectivity in a sample of 60 adolescents with excess weight and 55 normal weight controls. We first identified parts of the brain displaying between-group global connectivity differences and then characterised the extent of the differences in functional network integrity and their association with reward sensitivity. Results Adolescent obesity was linked to neuroadaptations in functional connectivity within brain hubs linked to interoception (insula), emotional memory (middle temporal gyrus) and cognitive control (dorsolateral prefrontal cortex) (pFWE < 0.05). The connectivity between the insula and the anterior cingulate cortex was reduced in comparison to controls, as was the connectivity between the middle temporal gyrus and the posterior cingulate cortex and cuneus/precuneus (pFWE < 0.05). Conversely, the middle temporal gyrus displayed increased connectivity with the orbitofrontal cortex (pFWE < 0.05). Critically, these networks were correlated with sensitivity to reward (p < 0.05). Conclusions These findings suggest that adolescent obesity is linked to disrupted functional connectivity in brain networks relevant to maintaining balance between reward, emotional memories and cognitive control. Our findings may contribute to reconceptualization of obesity as a multi-layered brain disorder leading to compromised motivation and control, and provide a biological account to target prevention strategies for adolescent obesity.

Prefrontal Gray Matter and Motivation for Treatment in Cocaine-Dependent Individuals with and without Personality Disorders

Addiction treatment is a long-term goal and therefore prefrontal–striatal regions regulating goal-directed behavior are to be associated with individual differences on treatment motivation. We aimed at examining the association between gray matter volumes in prefrontal cortices and striatum and readiness to change at treatment onset in cocaine users with and without personality disorders. Participants included 17 cocaine users without psychiatric comorbidities, 17 cocaine users with Cluster B disorders, and 12 cocaine users with Cluster C disorders. They completed the University of Rhode Island Change Assessment Scale, which measures four stages of treatment change (precontemplation, contemplation, action, and maintenance) and overall readiness to change, and were scanned in a 3 T MRI scanner. We defined three regions of interest (ROIs): the ventromedial prefrontal cortex (including medial orbitofrontal cortex and subgenual and rostral anterior cingulate cortex), the dorsomedial prefrontal cortex (i.e., superior medial frontal cortex), and the neostriatum (caudate and putamen). We found that readiness to change correlated with different aspects of ventromedial prefrontal gray matter as a function of diagnosis. In cocaine users with Cluster C comorbidities, readiness to change positively correlated with gyrus rectus gray matter, whereas in cocaine users without comorbidities it negatively correlated with rostral anterior cingulate cortex gray matter. Moreover, maintenance scores positively correlated with dorsomedial prefrontal gray matter in cocaine users with Cluster C comorbidities, but negatively correlated with this region in cocaine users with Cluster B and cocaine users without comorbidities. Maintenance scores also negatively correlated with dorsal striatum gray matter in cocaine users with Cluster C comorbidities. We conclude that the link between prefrontal–striatal gray matter and treatment motivation is modulated by co-existence of personality disorders.

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.

Negative mood induction normalizes decision making in male cocaine dependent individuals

RationaleDecision making is thought to play a key role in psychostimulant relapse, but very few studies have addressed the issue of how to counteract decision-making deficits in addicted individuals. According to the somatic marker framework, pervasive decision-making problems in addicted individuals may relate to abnormalities in the processing of emotional signals that work to anticipate the prospective outcomes of potential decisions.ObjectiveThe present study was conducted to test whether the induction of different emotional states (positive, negative, or drug-related) could either normalize or further impair decision-making performance in male cocaine polysubstance-using individuals (CPSI), as indexed by the Iowa gambling task (IGT).MethodsForty-two CPSI and 65 healthy control individuals (all males) were randomly allocated in four affective conditions using a parallel-group design. Participants in the different conditions performed the IGT during exposure to neutral, positive, negative, or drug-related sets of affective images.ResultsThe results showed that the CPSI exposed to the negative affective context showed a preference for the risk-averse safe choices of the IGT and had a net performance indistinguishable from that of controls. On the other hand, CPSI exposed to positive, drug-related, and neutral contexts showed the typical pattern of disadvantageous performance in the IGT and performed significantly poorer than controls. The impact of the negative mood induction could not be explained in terms of baseline differences in decision-making skills, personality traits related to sensitivity to reward/punishment, or trait positive/negative affect.ConclusionsWe conclude that negative mood induction can normalize decision-making performance in male CPSI, which may have important implications for the treatment of cocaine use-related disorders.