The stress-buffering role of friendships in young people with childhood threat experiences: a preliminary report.

Background: High-quality friendships have a positive impact on the mental health of young people with childhood adversity (CA). Social stress buffering, the phenomenon of a social partner attenuating acute stress responses, is a potential yet unexplored mechanism that may underlie this relationship.Objective: This study examined whether perceived friendship quality was related to better mental health and lower neural stress response in young people with CA.Method: A total of N = 102 young people (aged 16-26) with low to moderate CA were included in the study. We first investigated associations between friendship quality, mental health, and CA. In a representative subset (n = 62), we assessed neural stress responses using the Montreal Imaging Stress Task. In our sample, CA was best described along two dimensions resembling threat or deprivation like experiences. Hence, we investigated both cumulative and dimensional effects of CA.Results: We found no support for social thinning after CA, meaning that the severity of CA (cumulative or dimensional) did not differentially impact friendship quality. High-quality friendships, on the other hand, were strongly associated with better mental health. Furthermore, acute stress increased state anxiety and enhanced neural activity in five frontolimbic brain regions, including the left hippocampus. We found weak support that threat experiences interacted with friendship quality to predict left hippocampal reactivity to stress. However, this effect did not survive multiple comparison correction.Conclusion: The absence of social thinning in our sample may suggest that the risk of developing impoverished social networks is low for rather well-functioning young people with low to moderate CA. Regardless, our findings align with prior research, consistently showing a strong association between high-quality friendships and better mental health in young people with CA. Future research is needed to examine whether friendships aid neural stress responses in young people with childhood threat experiences.

Young people with childhood adversity underwent acute stress induction, eliciting frontolimbic reactivity.High-quality friendships were strongly associated with better mental health.Weak support for friendship stress buffering did not survive multiple comparison correction.

Resilient functioning is associated with altered structural brain network topology in adolescents exposed to childhood adversity.

Childhood adversity is one of the strongest predictors of adolescent mental illness. Therefore, it is critical that the mechanisms that aid resilient functioning in individuals exposed to childhood adversity are better understood. Here, we examined whether resilient functioning was related to structural brain network topology. We quantified resilient functioning at the individual level as psychosocial functioning adjusted for the severity of childhood adversity in a large sample of adolescents (N = 2406, aged 14-24). Next, we examined nodal degree (the number of connections that brain regions have in a network) using brain-wide cortical thickness measures in a representative subset (N = 275) using a sliding window approach. We found that higher resilient functioning was associated with lower nodal degree of multiple regions including the dorsolateral prefrontal cortex, the medial prefrontal cortex, and the posterior superior temporal sulcus (z > 1.645). During adolescence, decreases in nodal degree are thought to reflect a normative developmental process that is part of the extensive remodeling of structural brain network topology. Prior findings in this sample showed that decreased nodal degree was associated with age, as such our findings of negative associations between nodal degree and resilient functioning may therefore potentially resemble a more mature structural network configuration in individuals with higher resilient functioning.

Depressive symptoms following traumatic brain injury are associated with resting-state functional connectivity.

BACKGROUND: To determine whether depressive symptoms in traumatic brain injury (TBI) patients were associated with altered resting-state functional connectivity (rs-fc) or voxel-based morphology in brain regions involved in emotional regulation and associated with depression. METHODS: In the present study, we examined 79 patients (57 males; age range = 17-70 years, M ± s.d. = 38 ± 16.13; BDI-II, M ± s.d. = 9.84 ± 8.67) with TBI. We used structural MRI and resting-state fMRI to examine whether there was a relationship between depression, as measured with the Beck Depression Inventory (BDI-II), and the voxel-based morphology or functional connectivity in regions previously identified as involved in emotional regulation in patients following TBI. Patients were at least 4 months post-TBI (M ± s.d. = 15.13 ± 11.67 months) and the severity of the injury included mild to severe cases [Glasgow Coma Scale (GCS), M ± s.d. = 6.87 ± 3.31]. RESULTS: Our results showed that BDI-II scores were unrelated to voxel-based morphology in the examined regions. We found a positive association between depression scores and rs-fc between limbic regions and cognitive control regions. Conversely, there was a negative association between depression scores and rs-fc between limbic and frontal regions involved in emotion regulation. CONCLUSION: These findings lead to a better understanding of the exact mechanisms that contribute to depression following TBI and better inform treatment decisions.

REACT study protocol: resilience after the COVID-19 threat (REACT) in adolescents.

INTRODUCTION: COVID-19-related social isolation and stress may have significant mental health effects, including post-traumatic stress, anxiety and depression. These factors are thought to disproportionately affect populations at risk of psychopathology, such as adolescents with a history of childhood adversity (CA). Therefore, examining which factors may buffer the impact of COVID-19-related stress and isolation in vulnerable adolescents is critical. The Resilience After the COVID-19 Threat (REACT) study assesses whether emotion regulation capacity, inflammation and neuroimmune responses to stress induced in the laboratory prior to the pandemic predict responses to COVID-19-related social isolation and stress in adolescents with CA. We aim to elucidate the mechanisms that enable vulnerable adolescents to maintain or regain good mental health when confronted with COVID-19. METHODS AND ANALYSIS: We recruited 79 adolescents aged 16-26 with CA experiences from the Resilience After Individual Stress Exposure study in which we assessed emotion regulation, neural and immune stress responses to an acute stress task. Our sample completed questionnaires at the start of the UK lockdown ('baseline'; April 2020) and three (July 2020) and 6 months later (October 2020) providing crucial longitudinal information across phases of the pandemic progression and government response. The questionnaires assess (1) mental health, (2) number and severity of life events, (3) physical health, (4) stress perception and (5) loneliness and friendship support. We will use multilevel modelling to examine whether individual differences at baseline are associated with responses to COVID-19-related social isolation and stress. ETHICS AND DISSEMINATION: This study has been approved by the Cambridge Psychology Research Ethics Committee (PRE.2020.037). Results of the REACT study will be disseminated in publications in scientific peer-reviewed journals, presentations at scientific conferences and meetings, publications and presentations for the general public, and through social media.

RAISE study protocol: a cross-sectional, multilevel, neurobiological study of resilience after individual stress exposure.

INTRODUCTION: This paper describes the protocol for an ongoing project funded by the Royal Society, the Resilience After Individual Stress Exposure (RAISE) study; which aims to examine the factors and mechanisms that facilitate resilient functioning after childhood adversity (CA). METHODS AND ANALYSIS: We aim to recruit up to 200 participants. We will use dimension reduction techniques (principal component analysis) on standard-normally transformed individual parameters of mental health, social functioning and CA to calculate a composite measure of adaptive (ie, 'resilient') psychosocial functioning. To examine the neuroimmune responses to stress and their relationship with the brain and social environment, we will use a well validated functional MRI task; the Montreal imaging stress task and venepuncture. We will run group or dimensional comparisons in multiple levels of biological and psychological outcomes, as well as mediation and moderation analyses to study how key biological systems (ie, the hypothalamic-pituitary-adrenal axis and the immune system) interrelate and interact with brain function and social influences in order to facilitate resilient functioning after CA. We hypothesise that resilient functioning will be facilitated by reduced morning cortisol and cytokine levels before and after the stressor and improved neural responses to such stress, as well as increased gray matter volume in the hippocampus and prefrontal cortex, enhanced inhibitory control and emotion regulation, and more friendship and family support. ETHICS AND DISSEMINATION: This study has been reviewed and given favourable opinion by the National Research Ethics Service, NRES Committee East of England-Cambridge Central and external reviewers from the Royal Society (RGF\R1\180064 and RGF\EA\180029). The results of the RAISE study will be disseminated through (1) publications in scientific peer reviewed journals, (2) presentations on relevant scientific conferences and meetings, (3) publications and presentations for the general public and (4) through social media.

Psycho-social factors associated with mental resilience in the Corona lockdown.

The SARS-CoV-2 pandemic is not only a threat to physical health but is also having severe impacts on mental health. Although increases in stress-related symptomatology and other adverse psycho-social outcomes, as well as their most important risk factors have been described, hardly anything is known about potential protective factors. Resilience refers to the maintenance of mental health despite adversity. To gain mechanistic insights about the relationship between described psycho-social resilience factors and resilience specifically in the current crisis, we assessed resilience factors, exposure to Corona crisis-specific and general stressors, as well as internalizing symptoms in a cross-sectional online survey conducted in 24 languages during the most intense phase of the lockdown in Europe (22 March to 19 April) in a convenience sample of N = 15,970 adults. Resilience, as an outcome, was conceptualized as good mental health despite stressor exposure and measured as the inverse residual between actual and predicted symptom total score. Preregistered hypotheses (osf.io/r6btn) were tested with multiple regression models and mediation analyses. Results confirmed our primary hypothesis that positive appraisal style (PAS) is positively associated with resilience (p < 0.0001). The resilience factor PAS also partly mediated the positive association between perceived social support and resilience, and its association with resilience was in turn partly mediated by the ability to easily recover from stress (both p < 0.0001). In comparison with other resilience factors, good stress response recovery and positive appraisal specifically of the consequences of the Corona crisis were the strongest factors. Preregistered exploratory subgroup analyses (osf.io/thka9) showed that all tested resilience factors generalize across major socio-demographic categories. This research identifies modifiable protective factors that can be targeted by public mental health efforts in this and in future pandemics.

The Resilient Emotional Brain: A Scoping Review of the Medial Prefrontal Cortex and Limbic Structure and Function in Resilient Adults With a History of Childhood Maltreatment.

Childhood maltreatment (CM) is one of the strongest predictors of adult mental illness, although not all adults with CM develop psychopathology. Here, we describe the structure and function of the emotional brain regions that may contribute to resilient functioning after CM. We review studies that report medial prefrontal cortex, amygdala, and hippocampus (limbic regions) structure, function, and/or connections in resilient adults (i.e., those reporting CM without psychopathology) versus vulnerable adults (i.e., those reporting CM with psychopathology) or healthy adults (those without CM and with no psychopathology). We find that resilient adults have larger hippocampal gray and white matter volume and greater connectivity between the central executive network and the limbic regions. In addition, resilient adults have improved ability to regulate emotions through medial prefrontal cortex-limbic downregulation, lower hippocampal activation to emotional faces, and increased amygdala habituation to stress. We highlight the need for longitudinal designs that examine resilient functioning across domains and consider gender, type, timing, and nature of CM assessments and further stressors to further improve our understanding of the role of the emotional brain in resilient functioning after CM.

Neural correlates of visual memory in patients with diffuse axonal injury.

PRIMARY OBJECTIVE: To investigate the neural substrates of visual memory in a sample of patients with traumatic brain injury (TBI). We hypothesized that patients with decreased grey and white matter volume in frontal and parietal cortices as well as medial temporal and occipital lobes would perform poorly on the tests of visual memory analysed. METHODS AND PROCEDURES: 39 patients and 53 controls were assessed on tests of visual memory and learning from the Cambridge Neuropsychological Test Automated Battery (CANTAB). Patients with TBI were scanned with magnetic resonance imaging (MRI). Partial correlations and multiple regression analyses were used to examine relationships between cognitive variables and MRI volumetric findings. This study complements and extends previous studies by performing volumetric comparisons on a variety of resolution levels, from whole brain to voxel-based level analysis. MAIN OUTCOMES AND RESULTS: Patients with TBI performed significantly worse than controls in all the tasks assessed. Performance was associated with wide-spread reductions in grey and white matter volume of several cortical and subcortical structures as well as with cerebrospinal fluid space enlargement in accordance with previous studies of memory in patients with TBI and cognitive models suggesting that memory problems involve the alteration of multiple systems. CONCLUSIONS: Our results propose that compromised visual memory in patients with TBI is related to a distributed pattern of volume loss in regions mediating memory and attentional processing.

Anything goes? Regulation of the neural processes underlying response inhibition in TBI patients.

Despite evidence for beneficial use of methylphenidate in response inhibition, no studies so far have investigated the effects of this drug in the neurobiology of inhibitory control in traumatic brain injury (TBI), even though impulsive behaviours are frequently reported in this patient group. We investigated the neural basis of response inhibition in a group of TBI patients using functional magnetic resonance imaging and a stop-signal paradigm. In a randomised double-blinded crossover study, the patients received either a single 30mg dose of methylphenidate or placebo and performed the stop-signal task. Activation in the right inferior frontal gyrus (RIFG), an area associated with response inhibition, was significantly lower in patients compared to healthy controls. Poor response inhibition in this group was associated with greater connectivity between the RIFG and a set of regions considered to be part of the default mode network (DMN), a finding that suggests the interplay between DMN and frontal executive networks maybe compromised. A single dose of methylphenidate rendered activity and connectivity profiles of the patients RIFG near normal. The results of this study indicate that the neural circuitry involved in response inhibition in TBI patients may be partially restored with methylphenidate. Given the known mechanisms of action of methylphenidate, the effect we observed may be due to increased dopamine and noradrenaline levels.

Neural correlates of impaired self-awareness of apathy, disinhibition and dysexecutive deficits in cocaine-dependent individuals.

Cocaine addiction is characterized by impaired self-awareness about cognitive and motivational deficits, leading to poor treatment outcomes. However, there is still limited understanding of the neurophysiological underpinnings of this impairment. We aimed to establish if impaired self-awareness is underpinned by brain structural phenotypes among cocaine-dependent individuals (CDI). Sixty-five CDI and 65 designated informants completed the Frontal Systems Behavior Scale, and a subsample of 40 CDI were scanned via magnetic resonance imaging. We applied multiple regression models to establish the association between levels of self-awareness indexed by Frontal Systems Behavior Scale's discrepancy scores (i.e. informant ratings minus self-reports of apathy, disinhibition and dysexecutive deficits) and gray matter volumes indexed by magnetic resonance imaging voxel-based measures within five brain regions of interest: anterior cingulate cortex, orbitofrontal cortex (OFC), striatum, insula and dorsolateral prefrontal cortex (DLPFC). We also examined the neural underpinnings of underestimation versus overestimation of deficits, by splitting the CDI group according to the positive or negative value of their discrepancy scores. We found that poorer self-awareness of apathy deficits was associated with greater gray matter volume in the dorsal striatum, and poorer self-awareness of disinhibition deficits was associated with greater gray matter volume in the OFC in the whole sample. More underestimation and more overestimation of executive deficits were linked to lower DLPFC volume. We show that impaired self-awareness of cognitive and motivational deficits in cocaine addiction has a neural underpinning, implicating striatum, OFC and DLPFC structural phenotypes.

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.

Depression following traumatic brain injury: A functional connectivity perspective.

INTRODUCTION: Despite the mounting evidence that depression is one of the most common psychiatric sequelae in survivors of traumatic brain injury (TBI), no studies so far have attempted to provide an explanation in terms of functional network integrity. This proof of concept study investigated the association between the severity of depressive symptoms and resting network integrity in a sample of patients with TBI and a group of healthy controls. METHODS: We first examined the association between depression symptomatology and global functional connectivity and then attempted to characterize the extent of differences in functional network integrity. RESULTS: The severity of depressive symptoms in patients with TBI was associated with neuroadaptations within the insula, the thalamus and the subgenual anterior cingulate cortex (ACC). Specifically, patients with TBI displayed increased connectivity between the insula and a region encompassing the rolandic operculum and the superior temporal cortex and reduced connectivity between the thalamus and the dorsolateral prefrontal cortex. CONCLUSIONS: These findings show the network level involvement of the insula, the thalamus and the subgenual ACC in the depressive symptomatology of patients with TBI and tentatively propose that TBI-induced depression may result from altered functional connectivity of a set of networks associated with emotional regulation. However, other factors including a number of adjustment issues and challenges may also lead to depression in this population.

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.

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.

Asociación diferencial entre el metabolismo regional de la corteza prefrontal y las estructuras límbicas y el tiempo de abstinencia en individuos dependientes de sustancias / Differential association between the regional metabolism of the prefrontal cortex and limbic structures, and the time of abstinence in substance dependent individuals

A pesar de la existencia de numerosos estudios de neuroimagen cerebral demostrado la presencia de alteraciones del metabolismo cerebral en consumidores de drogas, pocos estudios han tratado de evaluar la asociación entre la duración de la abstinencia y el metabolismo cerebral de los consumidores. El objetivo de este estudio fue investigar la asociación entre el metabolismo cerebral de la glucosa (medido con 18-F fluor-desoxi-glucosa y tomografía por emisión de positrones) y la duración de la abstinencia en un grupo de 49 policonsumidores de drogas con abstinencia prolongada. Las imágenes fueron preprocesadas y analizadas usando SPM5 y SPSS 15. Tras el pre-procesamiento de las imágenes se extrajo el nivel del consumo de glucosa en un conjunto pre-establecido de regiones de interés y se llevaron a cabo correlaciones bivariadas entre el metabolismo de estas regiones y la duración de la abstinencia de los participantes. Se encontró una correlación negativa entre la duración de la abstinencia y el metabolismo regional de la amígdala y el hipocampo bilateralmente y una correlación positiva entre la duración de la abstinencia y la porción opercular del giro frontal inferior izquierdo. Las asociaciones encontradas sugieren la implicación diferencial de estas estructuras en el mantenimiento de la abstinencia y subrayan la necesidad de trabajar la regulación del estrés, el craving y el control de la conducta incluso tras importantes periodos de abstinencia (AU)

Despite the existence of numerous neuroimaging studies demonstrating significant brain functional alterations in substance users, only a few studies have tried to analyze the association between the duration of abstinence and brain metabolism within substance users. The aim of this study was to examine the association between resting-state regional brain metabolism (measured with 18F-fluordeoxyglucose Positron Emission Tomography (FDGPET) and duration of drug abstinence in a sample of 49 abstinent polysubstance users. PET images were pre-processed and analyzed using SPM5 and SPSS 15. After image pre-processing, the level of glucose uptake in a pre-established set of regions of interest was extracted and bivariate correlations between this and the duration of abstinence of the participants were conducted. Results showed a negative correlation between duration of abstinence and the amygdale and the hippocampus bilaterally and a positive correlation between duration of abstinence and the left inferior frontal operculum. The associations found suggest different involvement of these structures in maintaining abstinence and emphasize the need to work on stress regulation, craving and behaviour control even after significant periods of abstinence (AU)

[Differential association between the regional metabolism of the prefrontal cortex and limbic structures, and the time of abstinence in substance dependent individuals]. / Asociación diferencial entre el metabolismo regional de la corteza prefrontal y las estructuras límbicas y el tiempo de abstinencia en individuos dependientes de sustancias.

Despite the existence of numerous neuroimaging studies demonstrating significant brain functional alterations in substance users, only a few studies have tried to analyze the association between the duration of abstinence and brain metabolism within substance users. The aim of this study was to examine the association between resting-state regional brain metabolism (measured with 18F-fluordeoxyglucose Positron Emission Tomography (FDGPET) and duration of drug abstinence in a sample of 49 abstinent polysubstance users. PET images were pre-processed and analyzed using SPM5 and SPSS 15. After image pre-processing, the level of glucose uptake in a pre-established set of regions of interest was extracted and bivariate correlations between this and the duration of abstinence of the participants were conducted. Results showed a negative correlation between duration of abstinence and the amygdale and the hippocampus bilaterally and a positive correlation between duration of abstinence and the left inferior frontal operculum. The associations found suggest different involvement of these structures in maintaining abstinence and emphasize the need to work on stress regulation, craving and behaviour control even after significant periods of abstinence.

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.

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.

Neural correlates of hot and cold executive functions in polysubstance addiction: association between neuropsychological performance and resting brain metabolism as measured by positron emission tomography.

The study of substance-abuse-related neuropsychological deficits and brain alterations may provide a better understanding of the neuroadaptations associated with addiction. In this study we investigated the association between performance on neuropsychological tests of cold and hot executive functions and regional brain metabolism. Measured with positron emission tomography (PET), in a sample of 49 substance-dependent individuals (SDI). Neuropsychological performance in the SDI group was compared to that of a non-drug-using control group of 30 participants, and associated with two sets of PET-derived dependent measures: one based on regions of interest (examining mean uptake in selected regions), and a second based on voxel uptake measures (using Statistical Parametric Mapping voxel-based whole-brain analyses). Behavioral analyses showed that SDI had poorer performance than controls across executive function and emotion processing measures. Regression models showed that SDI's performance in "cold" executive tests (i.e., updating, inhibition and flexibility) was associated with regional metabolism in the dorsolateral prefrontal cortex (DLPFC), mid-superior frontal gyrus, superior and inferior temporal gyrus and inferior parietal cortex, whereas performance in "hot" executive functions (i.e., self-regulation, decision-making and emotion perception) was associated with DLPFC, mid-superior frontal gyrus, anterior and mid-posterior cingulate, and temporal and fusiform gyrus. These results are discussed in terms of their relevance for the understanding of cognitive dysfunction and neuroadaptations linked to addiction.

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.