Neural correlates of increased alcohol demand following alcohol cue exposure in adult heavy drinkers.

Alcohol use disorder is associated with overvaluation of alcohol relative to other rewards, in part due to dynamic increases in value in response to alcohol-related cues. In a neuroeconomic framework, alcohol cues increase behavioral economic demand for alcohol, but the neural correlates these cue effects are unknown. This functional magnetic resonance imaging study combined a neuroeconomic alcohol purchase task with an alcohol cue exposure in 72 heavy drinkers with established sensitivity to alcohol cues (51 % female; mean age=33.74). Participants reported how many drinks they would consume from $0-$80/drink following exposure to neutral and alcohol images in a fixed order. Participants purchased significantly more drinks in the alcohol compared to the neutral condition, which was also evident for demand indices (i.e., intensity, breakpoint, Omax, elasticity; ps<0.001; ds=0.46-0.92). Alcohol purchase decisions were associated with activation in rostral middle and medial frontal gyri, anterior insula, posterior parietal cortex, and dorsal striatum, among other regions. Activation was lower across regions in the alcohol relative to neutral cue condition, potentially due to greater automaticity of choices in the presence of alcohol cues or attenuation of responses due to fixed cue order. These results contribute to growing literature using neuroeconomics to understand alcohol misuse and provide a foundation for future research investigating decision-making effects of environmental alcohol triggers.

Vaping and smoking cue reactivity in young adult electronic cigarette users who have never smoked combustible cigarettes: A functional neuroimaging study.

Introduction: The rapid growth in the use of electronic cigarettes (e-cigarettes) among young adults who have never smoked combustible cigarettes is concerning, as it raises the potential for chronic vaping and nicotine addiction. A key characteristic of drug addiction is the elevated neural response to conditioned drug-related cues (i.e., cue reactivity). Generalized reactivity to both vaping and smoking cues may signify an increased risk for smoking initiation in non- smoking vapers. In this study, we used functional magnetic resonance imaging (fMRI) to evaluate brain responses to vaping and smoking cues in young adult never-smoking vapers. Methods: Sixty-six young adult never-smoking vapers underwent functional MRI while viewing visual cues pertaining to vaping, smoking, and nicotine-unrelated unconditioned reward (i.e., food). A priori region-of-interest analysis combined with exploratory whole-brain analysis was performed to characterize neural reactivity to vaping and smoking cues in comparison to food cues. Results: The medial prefrontal cortex and the posterior cingulate cortex, regions that play a key role in drug cue reactivity, showed significantly increased neural response to vaping cues compared to food cues. The posterior cingulate cortex additionally showed increased neural responses to smoking cues compared to food cues. Conclusions: Despite never having smoked combustible cigarettes, young adult vapers exhibited heightened neural susceptibility to both vaping and smoking cues within brain systems associated with cue reactivity. The findings shed light on the mechanisms underlying nicotine addiction and smoking initiation risk in this critical population and may contribute to the development of science-based interventions and regulatory measures in the future. IMPLICATIONS: The escalating vaping prevalence among US never-smoking young adults is alarming, due to its potential ramifications for nicotine addiction development. Nicotine addiction is characterized by elevated neural response to conditioned nicotine-related cues. Using functional neuroimaging, we showed that young adult non-smoking vapers exhibited heightened neural susceptibility to both vaping and smoking cues within brain systems previously associated with cue reactivity. Such cross-reactivity to both types of nicotine cues may serve as the mechanism underlying nicotine addiction and smoking initiation risk in this population. Our findings may contribute to the development of science-based interventions and regulatory measures addressing the vaping epidemic.

Anger, agency, risk and action: a neurobehavioral model with proof-of-concept in healthy young adults.

Introduction: Anger can engender action by individuals and groups. It is thus important to understand anger's behavioral phenotypes and their underlying neural substrates. Here, we introduce a construct we term agentic anger, a negatively valenced internal state that motivates action to achieve risky goals. We evaluate our neurobehavioral model via testable hypotheses in two proof-of-concept studies. Study 1 Methods: Study 1 used the Incentive Balloon Analogue Risk Task in a within-subjects, repeated measures design in 39 healthy volunteers to evaluate: (a) impact of blockade of reward on agentic anger, assessed by self-reports of negative activation (NA), (b) impact of achievement of reward on exuberance, assessed by self-reports of positive activation (PA), (c) the interrelationship of these valenced states, and (d) their relationship with personality. Study 1 Results: Task-induced NA was positively correlated with task-induced PA, risk-taking on the task and trait Social Potency (SP), a measure of trait agency and reward sensitivity on the Multidimensional Personality Questionnaire Brief-Form. Study 2 Methods: Study 2 assessed functional MRI response to stakes for risk-taking in healthy volunteers receiving 20 mg d-amphetamine in a double-blinded, placebo-controlled crossover design (N = 10 males), providing preliminary information on ventral striatal response to risky rewards during catecholamine activation. Study 2 Results: Trait SP and task-induced PA were strongly positively related to catecholamine-facilitated BOLD response in the right nucleus accumbens, a brain region where DA prediction error signal shapes action value and selection. Participants' task-induced NA was strongly positively related with trait SP and task-induced PA, replicating the findings of Study 1. Discussion: Together these results inform the phenomenology and neurobiology of agentic anger, which recruits incentive motivational circuitry and motivates personal action in response to goals that entail risk (defined as exposure to uncertainty, obstacles, potential harm, loss and/or financial, emotional, bodily, or moral peril). Neural mechanisms of agency, anger, exuberance, and risk-taking are discussed, with implications for personal and group action, decision-making, social justice, and behavior change.

Neuroeconomic predictors of smoking cessation outcomes: A preliminary study of delay discounting in treatment-seeking adult smokers.

Large proportions of smokers are unsuccessful in evidence-based smoking cessation treatment and identifying prognostic predictors may inform improvements in treatment. Steep discounting of delayed rewards (delay discounting) is a robust predictor of poor smoking cessation outcome, but the underlying neural predictors have not been investigated. Forty-one treatment-seeking adult smokers completed a functional magnetic resonance imaging (fMRI) delay discounting paradigm prior to initiating a 9-week smoking cessation treatment protocol. Behavioral performance significantly predicted treatment outcomes (verified 7-day abstinence, n = 18; relapse, n = 23). Participants in the relapse group exhibited smaller area under the curve (d = 1.10) and smaller AUC was correlated with fewer days to smoking relapse (r = 0.56, p < 0.001) Neural correlates of discounting included medial and dorsolateral prefrontal cortex, posterior cingulate, precuneus and anterior insula, and interactions between choice type and relapse status were present for the dorsolateral prefrontal cortex, precuneus and the striatum. This initial investigation implicates differential neural activity in regions associated with frontal executive and default mode activity, as well as motivational circuits. Larger samples are needed to improve the resolution in identifying the neural underpinnings linking steep delay discounting to smoking cessation.

Neuroanatomical foundations of delayed reward discounting decision making II: Evaluation of sulcal morphology and fractal dimensionality.

Delayed reward discounting (DRD) is a form of decision-making reflecting valuation of smaller immediate rewards versus larger delayed rewards, and high DRD has been linked to several health behaviors, including substance use disorders, attention-deficit/hyperactivity disorder, and obesity. Elucidating the underlying neuroanatomical factors may offer important insights into the etiology of these conditions. We used structural MRI scans of 1038 Human Connectome Project participants (Mage = 28.86, 54.7% female) to explore two novel measures of neuroanatomy related to DRD: 1) sulcal morphology (SM; depth and width) and 2) fractal dimensionality (FD), or cortical morphometric complexity, of parcellated cortical and subcortical regions. To ascertain unique contributions to DRD preferences, indicators that displayed significant partial correlations with DRD after family-wise error correction were entered into iterative mixed-effect models guided by the association magnitude. When considering only SM indicators, the depth of the right inferior and width of the left central sulci were uniquely associated with DRD preferences. When considering only FD indicators, the FD of the left middle temporal gyrus, right lateral orbitofrontal cortex, and left lateral occipital and entorhinal cortices uniquely contributed DRD. When considering SM and FD indicators simultaneously, the right inferior frontal sulcus depth and left central sulcus width; and the FD of the left middle temporal gyrus, lateral occipital cortex and entorhinal cortex were uniquely associated with DRD. These results implicate SM and FD as features of the brain that underlie variation in the DRD decision-making phenotype and as promising candidates for understanding DRD as a biobehavioral disease process.

Associations between anxiety, centromedial amygdala volume, and complex verbal fluency in middle-aged to older adults.

Symptoms of anxiety are related to decreases in cognitive performance in middle-aged to older adults (i.e., ages 50 and older; MOA). Verbal fluency (VF), assessed with the Delis-Kaplan Executive Function System (D-KEFS) Category Switching (VF-CS) task, captures elements of executive function such as semantic memory, response initiation and inhibition, and cognitive flexibility. The present study examined the link between anxiety symptoms and VF-CS to better understand how this association affects such executive functions in MOA. We hypothesized that higher subclinical Beck Anxiety Inventory (BAI) scores would be associated with lower VF-CS. To further investigate the underlying neurobiological basis of an expected inverse relationship, total amygdala volume, centromedial amygdala (CMA) volume, and basolateral amygdala (BLA) volume were examined as they related to VF-CS scores on the D-KEFS. Based on extant research on connectivity and functioning between the CMA and BLA, we hypothesized that larger BLA volumes would be associated with lower anxiety scores and exhibit positive relationships with VF-CS. A sample of 63 MOA were recruited from the Providence, Rhode Island area as a part of a parent study on cardiovascular diseases. Participants completed self-report measures about physical and emotional health, a neuropsychological assessment, and a magnetic resonance imaging scan (MRI). Multiple hierarchical regressions were performed to examine relationships between variables of interest. Contrary to hypotheses, no significant relationship emerged between VF-CS and BAI scores, and BLA volume was not associated with either BAI scores or VF-CS. However, a significant positive relationship was observed between CMA volume and VF-CS. The significant relationship found between CMA and VF-CS may reflect the upward slope of the quadratic relationship between arousal and cognitive performance on the Yerkes-Dodson curve. These findings newly implicate CMA volume specifically as a possible neuromarker linking emotional arousal and cognitive performance in MOA.

Investigating the neural substrates of Antagonistic Externalizing and social-cognitive Theory of Mind: an fMRI examination of functional activity and synchrony.

Recently developed quantitative models of psychopathology (i.e., Hierarchical Taxonomy of Psychopathology) identify an Antagonistic Externalizing spectrum that captures the psychological disposition toward criminal and antisocial behavior. The purpose of the present study was to examine relations between Antagonistic psychopathology (and associated Five-Factor model Antagonism/Agreeableness) and neural functioning related to social-cognitive Theory of Mind using a large sample (N = 973) collected as part of the Human Connectome Project (Van Essen et al., 2013a). No meaningful relations between Antagonism/Antagonistic Externalizing and Theory of Mind-related neural activity or synchrony were observed (p < .005). We conclude by outlining methodological considerations (e.g., validity of social cognition task and low test-retest reliability of functional biomarkers) that may account for these null results, and present recommendations for future research.

Delayed Reward Discounting as a Prognostic Factor for Smoking Cessation Treatment Outcome: A Systematic Review.

INTRODUCTION: While large proportions of smokers attempt to quit, rates of relapse remain high and identification of valid prognostic markers is of high priority. Delayed reward discounting (DRD) is a behavioral economic index of impulsivity that has been associated with smoking cessation, albeit inconsistently. This systematic review sought to synthesize the empirical findings on DRD as a predictor of smoking cessation treatment outcome, to critically appraise the quality of the literature, and to propose directions for future research. AIMS AND METHODS: A total of 734 articles were identified, yielding k = 14 studies that met the eligibility criteria. The Quality in Prognosis Studies (QUIPS) tool was used to assess methodological quality of the included studies. RESULTS: Individual study methods were highly heterogeneous, including substantial variation in research design, DRD task, clinical subpopulation, and treatment format. The predominant finding was that steeper DRD (higher impulsivity) was associated with significantly worse smoking cessation outcomes (10/14 studies). Negative results tended to be in pregnant and adolescent subpopulations. The QUIPS results suggested low risk of bias across studies; 11/14 studies were rated as low risk of bias for 5/6 QUIPS domains. CONCLUSIONS: This review revealed consistent low-bias evidence for impulsive DRD as a negative prognostic predictor of smoking cessation treatment outcome in adults. However, methodological heterogeneity was high, precluding meta-analysis and formal tests of small study bias. The prospects of targeting impulsive DRD as a potentially modifiable risk factor or providing targeted treatment for smokers exhibiting high levels of discounting are discussed. IMPLICATIONS: These findings indicate consistent evidence for DRD as a negative prognostic factor for smoking cessation outcome in adults. As such, DRD may be a useful as a novel treatment target or for identifying high-risk populations requiring more intensive treatment.

Recent cannabis use is associated with smaller hippocampus volume: High-resolution segmentation of structural subfields in a large non-clinical sample.

There is mixed evidence that individuals who use cannabis have reduced hippocampal and amygdalar gray matter volume, potentially because of small sample sizes and imprecise morphological characterization. New automated segmentation procedures have improved the measurement of these structures and allow better examination of their subfields, which have been linked to distinct aspects of memory and emotion. The current study applies this new segmentation procedure to the Human Connectome Project Young Adult dataset (N = 1080) to investigate associations of cannabis use with gray matter volume in the hippocampus and amygdala. Results revealed significant bilateral inverse associations of hippocampal volume with recent cannabis use (THC+ urine drug screen; P < .005). Hippocampal subfield analyses indicated these associations were primarily driven by the head of the hippocampus, the first section of the cornu amonis (CA1), the subicular complex, and the molecular layer of the hippocampus. No associations were detected for age of cannabis initiation, the frequency of cannabis use across the lifespan, or the lifetime presence of cannabis use disorder. In one of the largest studies to date, these results support the hypothesis that recent cannabis use is linked to reduced hippocampal volume, but that this effect may dissipate following prolonged abstinence. Furthermore, these results clarify the specific subfields which may be most associated with recent cannabis use.

An fMRI investigation of the relations between Extraversion, internalizing psychopathology, and neural activation following reward receipt in the Human Connectome Project sample.

Quantitative models of psychopathology (i.e., HiTOP) propose that personality and psychopathology are intertwined, such that the various processes that characterize personality traits may be useful in describing and predicting manifestations of psychopathology. In the current study, we used data from the Human Connectome Project (N = 1050) to investigate neural activation following receipt of a reward during an fMRI task as one shared mechanism that may be related to the personality trait Extraversion (specifically its sub-component Agentic Extraversion) and internalizing psychopathology. We also conducted exploratory analyses on the links between neural activation following reward receipt and the other Five-Factor Model personality traits, as well as separate analyses by gender. No significant relations (p < .005) were observed between any personality trait or index of psychopathology and neural activation following reward receipt, and most effect sizes were null to very small in nature (i.e., r < |.05|). We conclude by discussing the appropriate interpretation of these null findings, and provide suggestions for future research that spans psychological and neurobiological levels of analysis.

Cerebrovascular Perfusion among Older Adults with and Without Cardiovascular Disease.

BACKGROUND AND PURPOSE: Cardiovascular disease (CVD) encompasses a range of disorders that affect health and functioning in older adults. While cognitive declines have been linked to both cardiovascular and cerebral blood perfusion, protective neurovascular mechanisms raise the question whether cerebrovascular perfusion differs as a function of cardiovascular health status. The present study examined whether cerebrovascular perfusion significantly differs between healthy older adults with and without diagnosed CVD. The study also examined whether previously documented sex differences in cerebral perfusion would be replicated. METHODS: Twenty CVD patients without significant heart failure and 39 healthy controls were recruited to undergo a comprehensive assessment, including an interview, echocardiogram, and magnetic resonance imaging). Arterial spin labeling was used to quantify cerebral blood perfusion. RESULTS: Both groups exhibited mean left ventricular ejection fractions that fell within normal limits. In line with previous research, women exhibited significantly higher cerebral perfusion than men. There were no significant group differences in whole brain cerebrovascular perfusion, regional perfusion, or white matter perfusion by patient status after accounting for sex and age. CONCLUSIONS: These findings suggest that the effects of mild CVD on cerebrovascular perfusion are minimal. Future studies are needed to investigate the mechanisms involved in maintaining cerebrovascular perfusion in the context of altered peripheral perfusion and to determine whether this finding extends to more acute or severe CVD.

Functional brain changes associated with cognitive training in healthy older adults: A preliminary ALE meta-analysis.

Accumulating evidence suggests that cognitive training (CT) programs may provide healthy older adults (OAs) with cognitive benefits that are accompanied by alterations in neural activity. The current review offers the first quantitative synthesis of the available literature on the neural effects of CT in healthy aging. It was hypothesized that OAs would evidence increased and decreased neural activations across various challenging CTs, and that these effects would be observed as significantly altered clusters within regions of the frontoparietal network (FPN). Online databases and reference lists were searched to identify peer-reviewed publications that reported assessment of neural changes associated with CT programs in healthy OAs. Among the 2097 candidate studies identified, 14 studies with a total of 238 participants met inclusionary criteria. GingerALE software was used to quantify neural effects in a whole-brain analysis. The activation likelihood estimation technique revealed significant increases in activation following CT in the left hemisphere middle frontal gyrus, precentral gyrus, and posterior parietal cortex, extending to the superior occipital gyrus. Two clusters of diminished neural activity following CT were identified within the right hemisphere middle frontal gyrus and supramarginal gyrus, extending to the superior temporal gyrus. These results provide preliminary evidence of common neural effects of different CT interventions within regions of the FPN. Findings may inform future investigations of neuroplasticity across the lifespan, including clinical applications of CT, such as assessing treatment outcomes.

CHA2DS2-VASc Stroke Risk Index and Executive Functioning in Older Adults.

OBJECTIVE: CHA2DS2-VASc is a stroke risk classification system developed to improve the precision of stroke risk classification. The current study examined the validity of CHA2DS2-VASc in a sample of healthy older adults using executive function measures of processing speed, working memory, and cognitive flexibility that are sensitive to cerebrovascular risk factors. METHODS: Participants included 51 community-dwelling, healthy older adults (ages 53-86) recruited from both the community and cardiology clinics. CHA2DS2-VASc was utilized as a measure of stroke risk. Measures of executive functioning and processing speed included the Paced Auditory Serial Addition Test (PASAT), Delis-Kaplan Executive Function System (DKEFS) Number-Letter Switching, and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Coding. RESULTS: CHA2DS2-VASc scores significantly predicted scores on the PASAT, DKEFS Number-Letter Switching, and RBANS Coding, such that greater stroke risk was associated with poorer performances on tests of executive functioning and processing speed. These relationships were observed over and above the potential influence of educational attainment and symptoms of depression. CONCLUSION: Significant relations between stroke risk classification and performance on several measures of executive functioning provide support for a wider and more generalized use of CHA2DS2-VASc with healthy older adults. These findings further highlight the importance of early identification and treatment of stroke risk factors associated with cognitive decline. Findings suggest that CHA2DS2-VASc is a practical and useful tool for patients and their providers in the early detection of stroke risk and development of individualized treatment plans.

Peer influence, Frontostriatal connectivity, and delay discounting in African American emerging adults.

Prior research has demonstrated the importance of delay discounting in adverse health behaviors, such as addiction, attention deficit hyperactivity disorder, risk taking, and obesity. Nevertheless, the functional connectivity of neural circuitry associated with delay discounting and the ways in which the social environment may influence frontostriatal connectivity remain largely unknown, particularly in African Americans. Building on recent literature implicating frontostriatal connectivity during active delay discounting decision making and at rest, we used functional magnetic resonance imaging to assess the association between delay discounting and frontostriatal resting state connectivity (rsFC). We also examined the capacity of social relationships with parents and peers to longitudinally predict frontostriatal rsFC. The study cohort was composed of 91 rural African American emerging adults followed over a 6-year period. Greater (i.e., more positive) frontostriatal rsFC was associated with decreased delay discounting (i.e., less impulsive decision making). In addition, peer relationships at ages 20 and 21 significantly predicted frontostriatal rsFC at age 25 above and beyond parental influence. A significant indirect effect of peer affiliation on delay discounting through frontostriatal rsFC also emerged. These results indicate a role of frontostriatal connectivity in delay discounting decision making and highlight peers' unique influence on decision making behaviors through frontostriatal rsFC during emerging adulthood.

Deficits in executive function and suppression of default mode network in obesity.

BACKGROUND: Although nutritional and metabolic factors are well established in obesity, neurocognitive determinants are less understood. Using data from the Human Connectome Project, this study concurrently investigated neurocognitive performance, neural activation during a working memory task, and cortical brain morphometry in relation to obesity in a group of young adults, 22-35 years old. METHODS: Using a case-control design, obese individuals (n = 243, body mass index [BMI] ≥ 30 kg/m2) were compared to a control group of lean BMI individuals (n = 469, BMI = 18-24.9 kg/m2). Performance tests comprised a battery of behavioral neurocognitive assessments. Neural activity was measured as blood-oxygenation-level-dependent (BOLD) activity during an N-Back task using functional magnetic resonance imaging (fMRI). Cortical morphometry included indices of volume, thickness, and surface area. RESULTS: Relative to the control group, the obese group exhibited significantly worse performance in terms of the National Institutes of Health Toolkit (NIH) 9-Hole Peg Board, Penn Working Memory Test, Delay Discounting, Penn Progressive Matrices, NIH Picture Vocabulary Test, Dimensional Change Card Sort Test and the in-scanner N-Back working memory test (FDR-corrected ps<0.05; ds = 0.231-0.405). The obese group also exhibited significantly greater BOLD activation in N-Back task-negative regions, including the ventromedial prefrontal cortex, posterior cingulate, and right precentral gyrus (FDR-corrected ps<0.05). Supplemental functional connectivity analyses provided evidence that the implicated regions were part of the default mode network. Significant differences in morphometry were present in the medial orbitofrontal cortex, rostral anterior cingulate cortex, inferior and superior parietal gyri, and temporal pole (FDR-corrected p<0.001). A data-driven integrative model classified 73.8% of participants correctly. CONCLUSIONS AND RELEVANCE: This multimodal investigation suggests diverse aspects of neurocognition are associated with obesity, particularly implicating deficits in executive function and ineffective suppression of the default mode network.

Associations Between Drinking and Cortical Thickness in Younger Adult Drinkers: Findings From the Human Connectome Project.

BACKGROUND: Previous neuroimaging studies examining relations between alcohol misuse and cortical thickness have revealed that increased drinking quantity and alcohol-related problems are associated with thinner cortex. Although conflicting regional effects are often observed, associations are generally localized to frontal regions (e.g., dorsolateral prefrontal cortex [DLPFC], inferior frontal gyrus [IFG], and anterior cingulate cortex). Inconsistent findings may be attributed to methodological differences, modest sample sizes, and limited consideration of sex differences. METHODS: This study examined neuroanatomical correlates of drinking quantity and heavy episodic drinking in a large sample of younger adults (N = 706; Mage  = 28.8; 51% female) using magnetic resonance imaging data from the Human Connectome Project. Exploratory analyses examined neuroanatomical correlates of executive function (flanker task) and working memory (list sorting). RESULTS: Hierarchical linear regression models (controlling for age, sex, education, income, smoking, drug use, twin status, and intracranial volume) revealed significant inverse associations between drinks in past week and frequency of heavy drinking and cortical thickness in a majority of regions examined. The largest effect sizes were found for frontal regions (DLPFC, IFG, and the precentral gyrus). Follow-up regression models revealed that the left DLPFC was uniquely associated with both drinking variables. Sex differences were also observed, with significant effects largely specific to men. CONCLUSIONS: This study adds to the understanding of brain correlates of alcohol use in a large, gender-balanced sample of younger adults. Although the cross-sectional methodology precludes causal inferences, these findings provide a foundation for rigorous hypothesis testing in future longitudinal investigations.

Neurocompensatory Effects of the Default Network in Older Adults.

The hemispheric asymmetry reduction in older adults (HAROLD) is a neurocompensatory process that has been observed across several cognitive functions but has not yet been examined in relation to task-induced relative deactivations of the default mode network. The present study investigated the presence of HAROLD effects specific to neural activations and deactivations using a functional magnetic resonance imaging (fMRI) n-back paradigm. It was hypothesized that HAROLD effects would be identified in relative activations and deactivations during the paradigm, and that they would be associated with better 2-back performance. Forty-five older adults (M age = 63.8; range = 53-83) were administered a verbal n-back paradigm during fMRI. For each participant, the volume of brain response was summarized by left and right frontal regions of interest, and laterality indices (LI; i.e., left/right) were calculated to assess HAROLD effects. Group level results indicated that age was significantly and negatively correlated with LI (i.e., reduced left lateralization) for deactivations, but positively correlated with LI (i.e., increased left lateralization) for activations. The relationship between age and LI for deactivation was significantly moderated by performance level, revealing a stronger relationship between age and LI at higher levels of 2-back performance. Findings suggest that older adults may employ neurocompensatory processes specific to deactivations, and task-independent processes may be particularly sensitive to age-related neurocompensation.

Cannabis involvement and neuropsychological performance: findings from the Human Connectome Project

Background: There is evidence that heavy cannabis use is associated with decrements in cognitive performance, but findings are mixed and studies are often limited by small sample sizes and narrow adjustment for potential confounding variables. In a comparatively large sample, the current study examined associations between multiple indicators of cannabis use in relation to performance on a variety of neuropsychological tasks. Methods: Participants were 1121 adults (54% female) enrolled in the Human Connectome Project. Cannabis involvement comprised recent cannabis use (positive tetrahydrocannabinol screen), total number of lifetime uses, cannabis use disorder and age at first use. The neuropsychological battery comprised performance in episodic memory, fluid intelligence, attention, working memory, executive function, impulsive decision-making, processing speed and psychomotor dexterity. Covariates were age, sex, income, family structure and alcohol and tobacco use. Results: Positive urinary tetrahydrocannabinol status was associated with worse performance in episodic memory and processing speed, and positive cannabis use disorder status was associated with lower fluid intelligence (all p < 0.005). No other significant associations were present. Limitations: The sample was limited to young adults aged 22­36 years. The measures of cannabis involvement were relatively coarse. Conclusion: Beyond an array of potential confounders, recent cannabis use was associated with deficits in memory and psychomotor performance, and cannabis use disorder was associated with lower overall cognitive functioning in a large normative sample of adults. The findings pertaining to recent use have particular relevance for occupational settings.

Higher Peripheral Inflammatory Signaling Associated With Lower Resting-State Functional Brain Connectivity in Emotion Regulation and Central Executive Networks.

BACKGROUND: Researchers document bidirectional pathways linking peripheral inflammation and neural circuitries subserving emotion processing and regulation. To extend this work, we present results from two independent studies examining the relationship between inflammation and resting-state functional connectivity (rsFC), as measured by functional magnetic resonance imaging. METHODS: Study 1 involved 90 rural African American young adults, 25 years of age (52% female), and study 2 involved 82 urban African American youths, 13 to 14 years of age (66% female). Both studies measured circulating inflammatory biomarkers (C-reactive protein, interleukin 6, interleukin 10, tumor necrosis factor alpha), and the measures were averaged to form a composite. Study 2 also enumerated classical monocytes, a key leukocyte subpopulation involved in immune-to-brain signaling. All participants completed a resting-state functional magnetic resonance imaging scan. RESULTS: Consistent with our prediction, higher scores on the inflammatory composite were associated with lower rsFC within an emotion regulation network in study 1, controlling for sex. Study 2 replicated study 1, showing that higher scores on the inflammatory composite were associated with lower rsFC within the emotion regulation network, controlling for sex, age, and pubertal status, and found a similar pattern for rsFC within a central executive network. Study 2 also found that higher numbers of classical monocytes were associated with lower rsFC within both the emotion regulation and central executive networks. There was no relationship between rsFC in the anterior salience or default mode networks with inflammation in either study. CONCLUSIONS: With these findings, we document relationships between peripheral inflammation and rsFC within an emotion regulation and central executive network and replicate these associations with the emotion regulation network across two independent samples.