Estradiol effects on an emotional interference task in adolescents with current and remitted depression.

Attentional biases to emotional stimuli are thought to reflect vulnerability for mood disorder onset and maintenance. This study examined the association between the endogenous sex hormone estradiol and emotional attentional biases in adolescent females with either current or remitted depression. Three groups of participants (mean age ± SD) completed the Emotional Interrupt Task: 1) 20 adolescent females (15.1 ± 1.83 years) currently diagnosed with Major Depressive Disorder (MDD), 2) 16 adolescent females (16.4 ± 1.31 years) who had experienced at least one episode of MDD in their lifetime but currently met criteria for MDD in remission, and 3) 30 adolescent female (15.4 ± 1.83 years) healthy controls. Attentional interference (AI) scores were calculated as differences in target response reaction time between trials with emotional facial expressions versus neutral facial expressions. Estradiol levels were assayed by Salimetrics LLC using saliva samples collected within 30 min of waking on assessment days. Robust multiple regression with product terms evaluated estradiol's main effect on AI scores, as well as hypothesized estradiol × diagnostic group interactions. Although neither mean estradiol levels nor mean AI scores in the current-MDD and remitted-MDD groups differed from controls, the relationship between estradiol and overall AI score differed between control adolescents and the remitted-MDD group. Specifically, the remitted-MDD adolescents performed worse (i.e., showed greater attentional interference) when they had higher estradiol; no significant relationship existed in the current-MDD group. Because this finding was driven by angry and not happy stimuli, it appears higher estradiol levels were associated with greater susceptibility to the attention-capturing effects of negatively-valenced emotional content in girls at risk for MDD from prior history.

Brain Networks and Adolescent Alcohol Use.

Importance: Alcohol misuse in adolescence is a leading cause of disability and mortality in youth and is associated with higher risk for alcohol use disorder. Brain mechanisms underlying risk of alcohol misuse may inform prevention and intervention efforts. Objective: To identify neuromarkers of alcohol misuse using a data-driven approach, with specific consideration of neurodevelopmental sex differences. Design, Setting, and Participants: Longitudinal multisite functional magnetic resonance imaging (fMRI) data collected at ages 14 and 19 years were used to assess whole-brain patterns of functional organization associated with current and future alcohol use risk as measured by the Alcohol Use Disorder Identification Test (AUDIT). Primary data were collected by the IMAGEN consortium, a European multisite study of adolescent neurodevelopment. Model generalizability was further tested using data acquired in a single-site study of college alcohol consumption conducted in the US. The primary sample was a developmental cohort of 1359 adolescents with neuroimaging, phenotyping, and alcohol use data. Model generalizability was further assessed in a separate cohort of 114 individuals. Main Outcomes and Measures: Brain-behavior model accuracy, as defined by the correspondence between model-predicted and actual AUDIT scores in held-out testing data, Bonferroni corrected across the number of models run at each time point, 2-tailed α < .008, as determined via permutation testing. Results: Among 1359 individuals in the study, the mean (SD) age was 14.42 (0.40) years, and 729 individuals (54%) were female. The data-driven, whole-brain connectivity approach identified networks associated with vulnerability for future and current AUDIT-defined alcohol use risk (primary outcome, as specified above, future: ρ, 0.22; P < .001 and present: ρ, 0.27; P < .001). Results further indicated sex divergence in the accuracies of brain-behavior models, such that female-only models consistently outperformed male-only models. Specifically, female-only models identified networks conferring vulnerability for future and current severity using data acquired during both reward and inhibitory fMRI tasks. In contrast, male-only models were successful in accurately identifying networks using data acquired during the inhibitory control-but not reward-task, indicating domain specificity of alcohol use risk networks in male adolescents only. Conclusions and Relevance: These data suggest that interventions focusing on inhibitory control processes may be effective in combating alcohol use risk in male adolescents but that both inhibitory and reward-related processes are likely of relevance to alcohol use behaviors in female adolescents. They further identify novel networks of alcohol use risk in youth, which may be used to identify adolescents who are at risk and inform intervention efforts.

Food cue reactivity in successful laparoscopic gastric banding: A sham-deflation-controlled pilot study.

Laparoscopic adjustable gastric banding (LAGB) offers a unique opportunity to examine the underlying neuronal mechanisms of surgically assisted weight loss due to its instant, non-invasive, adjustable nature. Six participants with stable excess weight loss (%EWL ≥ 45) completed 2 days of fMRI scanning 1.5-5 years after LAGB surgery. In a within-subject randomized sham-controlled design, participants underwent (sham) removal of ∼ 50% of the band's fluid. Compared to sham-deflation (i.e., normal band constriction) of the band, in the deflation condition (i.e., decreasing restriction) participants showed significantly lower activation in the anterior (para)cingulate, angular gyrus, lateral occipital cortex, and frontal cortex in response to food images (p < 0.05, whole brain TFCE-based FWE corrected). Higher activation in the deflation condition was seen in the fusiform gyrus, inferior temporal gyrus, lingual gyrus, lateral occipital cortex. The findings of this within-subject randomized controlled pilot study suggest that constriction of the stomach through LAGB may indirectly alter brain activation in response to food cues. These neuronal changes may underlie changes in food craving and food preference that support sustained post-surgical weight-loss. Despite the small sample size, this is in agreement with and adds to the growing literature of post-bariatric surgery changes in behavior and control regions.

Neuromodulation to Treat Substance Use Disorders in People With Schizophrenia and Other Psychoses: A Systematic Review.

BACKGROUND: Substance use disorders (SUDs) are a common yet poorly studied comorbidity in individuals with psychotic disorders. The co-occurrence of the two complicates recovery and interferes with pharmacological and behavioral treatment response and adherence. Recently, researchers have been exploring both invasive and non-invasive neuromodulation techniques as potential treatment methods for SUDs. We review the evidence that neuromodulation may reduce substance craving and consumption in individuals with schizophrenia. METHODS: A comprehensive literature search of PubMed, MEDLINE, and PsycINFO databases was conducted (N = 1,432). Of these, we identified seven studies examining the effects of repetitive transcranial magnetic stimulation (rTMS) and two studies using transcranial direct current stimulation (tDCS) on drug consumption and craving in schizophrenia or schizoaffective disorders. RESULTS: Despite the limited number of studies in this area, the evidence suggests that rTMS to the dorsolateral prefrontal cortex (DLPFC) may reduce cannabis and tobacco use in patients with schizophrenia and schizoaffective disorder. Findings with tDCS, however, were inconclusive. DISCUSSION: Our systematic review suggests that rTMS applied to DLPFC is a safe and promising therapeutic technique for the management of comorbid schizophrenia and SUDs, with the majority of the evidence in tobacco use disorder. However, there was substantial heterogeneity in study methods, underscoring the need to optimize stimulation parameters (e.g., frequency, duration, and target regions). Larger clinical trials are needed to establish the efficacy of rTMS in reducing drug consumption and craving in psychotic patients, ideally in comparison to existing pharmacological and behavioral interventions.

Real-time facial emotion recognition deficits across the psychosis spectrum: A B-SNIP Study.

Affective and non-affective psychotic disorders are associated with variable levels of impairment in affective processing, but this domain typically has been examined via presentation of static facial images. We compared performance on a dynamic facial expression identification task across six emotions (sad, fear, surprise, disgust, anger, happy) in individuals with psychotic disorders (bipolar with psychotic features [PBD] = 113, schizoaffective [SAD] = 163, schizophrenia [SZ] = 181) and healthy controls (HC; n = 236) derived from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP). These same individuals with psychotic disorders were also grouped by B-SNIP-derived Biotype (Biotype 1 [B1] = 115, Biotype 2 [B2] = 132, Biotype 3 [B3] = 158), derived from a cluster analysis applied to a large biomarker panel that did not include the current data. Irrespective of the depicted emotion, groups differed in accuracy of emotion identification (P < 0.0001). The SZ group demonstrated lower accuracy versus HC and PBD groups; the SAD group was less accurate than the HC group (Ps < 0.02). Similar overall group differences were evident in speed of identifying emotional expressions. Controlling for general cognitive ability did not eliminate most group differences on accuracy but eliminated almost all group differences on reaction time for emotion identification. Results from the Biotype groups indicated that B1 and B2 had more severe deficits in emotion recognition than HC and B3, meanwhile B3 did not show significant deficits. In sum, this characterization of facial emotion recognition deficits adds to our emerging understanding of social/emotional deficits across the psychosis spectrum.

Brain responses to anticipatory cues and milkshake taste in obesity, and their relationship to bariatric surgery outcome.

There is substantial variability in percent total weight loss (%TWL) following bariatric surgery. Functional brain imaging may explain more variance in post-surgical weight loss than psychological or metabolic information. Here we examined the neuronal responses during anticipatory cues and receipt of drops of milkshake in 52 pre-bariatric surgery men and women with severe obesity (OW, BMI = 35-60 kg/m2) (23 sleeve gastrectomy (SG), 24 Roux-en-Y gastric bypass (RYGB), 3 laparoscopic adjustable gastric banding (LAGB), 2 did not undergo surgery) and 21 healthy-weight (HW) controls (BMI = 19-27 kg/m2). One-year post-surgery weight loss ranged from 3.1 to 44.0 TWL%. Compared to HW, OW had a stronger response to milkshake cues (compared to water) in frontal and motor, somatosensory, occipital, and cerebellar regions. Responses to milkshake taste receipt (compared to water) differed from HW in frontal, motor, and supramarginal regions where OW showed more similar response to water. One year post-surgery, responses to high-fat milkshake cues normalized in frontal, motor, and somatosensory regions. This change in brain response was related to scores on a composite health index. We found no correlation between baseline response to milkshake cues or tastes and%TWL at 1-yr post-surgery. In RYGB participants only, a stronger response to low-fat milkshake and water cues (compared to high-fat) in supramarginal and cuneal regions respectively was associated with more weight loss. A stronger cerebellar response to high-fat vs low-fat milkshake receipt was also associated with more weight loss. We confirm differential responses to anticipatory milkshake cues in participants with severe obesity and HW in the largest adult cohort to date. Our brain wide results emphasizes the need to look beyond reward and cognitive control regions. Despite the lack of a correlation with post-surgical weight loss in the entire surgical group, participants who underwent RYGB showed predictive power in several regions and contrasts. Our findings may help in understanding the neuronal mechanisms associated with obesity.

Subcortical surface morphometry in substance dependence: An ENIGMA addiction working group study.

While imaging studies have demonstrated volumetric differences in subcortical structures associated with dependence on various abused substances, findings to date have not been wholly consistent. Moreover, most studies have not compared brain morphology across those dependent on different substances of abuse to identify substance-specific and substance-general dependence effects. By pooling large multinational datasets from 33 imaging sites, this study examined subcortical surface morphology in 1628 nondependent controls and 2277 individuals with dependence on alcohol, nicotine, cocaine, methamphetamine, and/or cannabis. Subcortical structures were defined by FreeSurfer segmentation and converted to a mesh surface to extract two vertex-level metrics-the radial distance (RD) of the structure surface from a medial curve and the log of the Jacobian determinant (JD)-that, respectively, describe local thickness and surface area dilation/contraction. Mega-analyses were performed on measures of RD and JD to test for the main effect of substance dependence, controlling for age, sex, intracranial volume, and imaging site. Widespread differences between dependent users and nondependent controls were found across subcortical structures, driven primarily by users dependent on alcohol. Alcohol dependence was associated with localized lower RD and JD across most structures, with the strongest effects in the hippocampus, thalamus, putamen, and amygdala. Meanwhile, nicotine use was associated with greater RD and JD relative to nonsmokers in multiple regions, with the strongest effects in the bilateral hippocampus and right nucleus accumbens. By demonstrating subcortical morphological differences unique to alcohol and nicotine use, rather than dependence across all substances, results suggest substance-specific relationships with subcortical brain structures.

The Association of Impulsivity and Family History of Alcohol Use Disorder on Alcohol Use and Consequences.

BACKGROUND: Extensive research indicates that having a positive family history of alcohol use disorder (FHP) and impulsivity are 2 risk factors for problem drinking. To our knowledge, no study has investigated which facets of impulsivity interact with family history to increase risk for problem drinking. The goal of this study was to: (i) examine whether FHP individuals with higher levels of impulsivity are more likely to engage in problematic drinking, and (ii) identify which facets of impulsivity interact with FHP to increase risk for problems. METHODS: The data consisted of a combined sample of 757 participants (50% female, 73% White, mean age = 32.85, SD = 11.31) drawn from the Transdisciplinary Tobacco Use Research Center and the Center for the Translational Neuroscience of Alcohol. Analyses of covariance and cumulative logistic regression models investigated the association of family history and impulsivity-related traits with drinking quantity, frequency, and alcohol-related problems. Models were adjusted for age, sex, race, ethnic group, education level, and data source. RESULTS: Significant interactions between impulsivity and family history were found for measures of alcohol-related problems. Specifically, there was a stronger positive association of Barratt Impulsiveness Scale (BIS) poor self-regulation with interpersonal, F(1, 504) = 6.27, p = 0.01, and impulse control alcohol-related problems, F(1, 504) = 6.00, p = 0.01, among FHP compared to FHN individuals. Main effects of family history and impulsivity on alcohol quantity and frequency of use and problems were also found. CONCLUSIONS: These findings suggest that having both a family history of AUD and high BIS poor self-regulation is more strongly associated with alcohol-related consequences in the interpersonal and impulse control domains. Given the heterogeneity of impulsivity, these findings highlight the need for additional research to examine which facets of impulsivity are associated with which alcohol outcomes to narrow phenotypic risk for alcohol misuse.

A preliminary study of association between adolescent estradiol level and dorsolateral prefrontal cortex activity during emotion regulation.

Non-human primate models have been useful in clarifying estradiol's role in cognitive processing. These animal studies indicate estradiol impacts cognitive processes supported by regions within dorsolateral prefrontal cortex (DLPFC). Although human functional neuroimaging studies have begun to find similar relationships between estradiol in women for some forms of 'cold' cognitive control, to date no studies have examined the relationship between estradiol and DLPFC function in the context of active attempts to regulate one's emotions. Here, we asked whether peripheral 17-beta estradiol levels in adolescent girls in different pubertal developmental stages (age = 14.9 years ± 1.74) were related to engagement of DLPFC regions during the use of a cognitive strategy for regulating emotion known as reappraisal using functional Magnetic Resonance Imaging. Findings indicated that higher estradiol levels predicted greater DLPFC activity during the down-regulation of negative emotion using reappraisal. This is the first report of an association between estradiol level and DLPFC activity during cognitive reappraisal of negative emotion. The study suggests a possibility that estradiol might positively contribute to regulatory function of a cortical system important for emotional experiences.

Mega-Analysis of Gray Matter Volume in Substance Dependence: General and Substance-Specific Regional Effects.

OBJECTIVE: Although lower brain volume has been routinely observed in individuals with substance dependence compared with nondependent control subjects, the brain regions exhibiting lower volume have not been consistent across studies. In addition, it is not clear whether a common set of regions are involved in substance dependence regardless of the substance used or whether some brain volume effects are substance specific. Resolution of these issues may contribute to the identification of clinically relevant imaging biomarkers. Using pooled data from 14 countries, the authors sought to identify general and substance-specific associations between dependence and regional brain volumes. METHOD: Brain structure was examined in a mega-analysis of previously published data pooled from 23 laboratories, including 3,240 individuals, 2,140 of whom had substance dependence on one of five substances: alcohol, nicotine, cocaine, methamphetamine, or cannabis. Subcortical volume and cortical thickness in regions defined by FreeSurfer were compared with nondependent control subjects when all sampled substance categories were combined, as well as separately, while controlling for age, sex, imaging site, and total intracranial volume. Because of extensive associations with alcohol dependence, a secondary contrast was also performed for dependence on all substances except alcohol. An optimized split-half strategy was used to assess the reliability of the findings. RESULTS: Lower volume or thickness was observed in many brain regions in individuals with substance dependence. The greatest effects were associated with alcohol use disorder. A set of affected regions related to dependence in general, regardless of the substance, included the insula and the medial orbitofrontal cortex. Furthermore, a support vector machine multivariate classification of regional brain volumes successfully classified individuals with substance dependence on alcohol or nicotine relative to nondependent control subjects. CONCLUSIONS: The results indicate that dependence on a range of different substances shares a common neural substrate and that differential patterns of regional volume could serve as useful biomarkers of dependence on alcohol and nicotine.

VEGFA GENE variation influences hallucinations and frontotemporal morphology in psychotic disorders: a B-SNIP study.

Vascular endothelial growth factor A (VEGFA) dysfunction may contribute to a number of pathological processes that characterize psychotic disorders. However, the influence of VEGFA gene variants on clinical and neuroimaging phenotypes in psychotic disorders has yet to be shown. In the present study, we examined whether different VEGFA gene variants influence psychosis risk, symptom severity, cognition, and brain volume. The study group included 480 probands (Bipolar I disorder with psychosis, n = 205; Schizoaffective disorder, n = 112; Schizophrenia, n = 163) and 126 healthy controls that were recruited across six sites in the B-SNIP consortium. VEGFA variants identified for analysis (rs699947, rs833070, and rs2146323) were quantified via SNP chip array. We assessed symptoms and cognition using standardized clinical and neuropsychological batteries. The dorsolateral prefrontal cortex (DLPFC), medial temporal lobe, and hippocampal volumes were quantified using FreeSurfer. In our sample, VEGFA rs2146323 A- carriers showed reduced odds of being a proband (p = 0.037, OR = 0.65, 95% CI = 0.43-0.98) compared to noncarriers, but not for rs699947 or rs833070. In probands, rs2146323 A- carriers demonstrated fewer hallucinations (p = 0.035, Cohen's d = 0.194), as well as significantly greater DLPFC (p < 0.05, Cohen's d = -0.21) and parahippocampal volumes (p < 0.01, Cohen's d = -0.27). No clinical or neuroimaging associations were identified for rs699947 or rs833070. In general, we found that the three SNPs exhibited several significant negative relationships between psychosis symptoms and brain structure. In the probands and control groups, positive relationships were identified between several cognitive and brain volume measures. The findings suggest VEGFA effects in the DLPFC and hippocampus found in animals may also extend to humans. VEGFA variations may have important implications in identifying dimensional moderators of function that could be targeted through VEGFA-mediated interventions.

The effect of age and smoking on the hippocampus and memory in late middle age.

From middle age the hippocampus atrophies at an accelerating rate. Factors that further this acceleration may hasten memory decline and the onset of memory disorder. We studied associations between smoking history, age, ApoE e4 genotype, vascular risk factors, hippocampal volume, and cognition in 67 middle-aged subjects (mean age = 56 years) who were offspring of parents with dementia. Subjects underwent isotropic T1-weighted 3 T MRI brain scanning with FreeSurfer volumetric data extraction for the hippocampus, a neuropsychological assessment battery, extensive medical data collection, and ApoE genotyping. ApoE e4, vascular risk variables, and alcohol history were unrelated to hippocampal volume. Hippocampal volume correlated negatively with age and positively with memory performance, but not with global cognition. Aging diminished hippocampal volume by 0.52% per year. Female subjects (only two males smoked) with a heavy smoking history (≥ 9.5 pack-years; n = 11) exhibited hippocampal volumes that were 7.4% smaller than the volumes of females (n = 37) with a light or no smoking history. In our sample by late middle age, a history of moderate to heavy smoking is associated with hippocampal atrophy equivalent to 12 years of aging. Since only a small number of subjects within the sample have a smoking history, validation of this finding in larger samples is desirable.

Relationship between fMRI response during a nonverbal memory task and marijuana use in college students.

Marijuana (MJ) is widely used among college students, with peak use between ages 18-22. Research suggests memory dysfunction in adolescent and young adult MJ users, but the neural correlates are unclear. We examined functional magnetic resonance imaging (fMRI) response during a memory task among college students with varying degrees of MJ involvement. Participants were 64 college students, ages 18-20, who performed a visual encoding and recognition task during fMRI. MJ use was ascertained for 3 months prior to scanning; 27 individuals reported past 3-month MJ use, and 33 individuals did not. fMRI response was modeled during encoding based on whether targets were subsequently recognized (correct encoding), and during recognition based on target identification (hits). fMRI response in left and right inferior frontal gyrus (IFG) and hippocampal regions of interest was examined between MJ users and controls. There were no group differences between MJ users and controls on fMRI response during encoding, although single sample t-tests revealed that MJ users failed to activate the hippocampus. During recognition, MJ users showed less fMRI response than controls in right hippocampus (Cohen's d = 0.55), left hippocampus (Cohen's d = 0.67) and left IFG (Cohen's d = 0.61). Heavier MJ involvement was associated with lower fMRI response in left hippocampus and left IFG. This study provides evidence of MJ-related prefrontal and hippocampal dysfunction during recognition memory in college students. These findings may contribute to our previously identified decrements in academic performance in college MJ users and could have substantial implications for academic and occupational functioning.

Relating neural processing of reward and loss prospect to risky decision-making in individuals with and without Gambling Disorder.

Neuroimaging studies demonstrate alterations in fronto-striatal neurocircuitry in gambling disorder (GD) during anticipatory processing, which may influence decision-making impairments. However, to date little is known about fronto-striatal anticipatory processing and emotion-based decision-making. While undergoing neuroimaging, 28 GD and 28 healthy control (HC) participants performed the Monetary Incentive Delay Task (MIDT). Pearson correlation coefficients assessed out-of-scanner Iowa Gambling Task (IGT) performance with the neural activity during prospect (A1) processing on the MIDT across combined GD and HC groups. The HC and GD groups showed no significant difference in out-of-scanner IGT performance, although there was a trend for higher IGT scores in the HC group on the last two IGT trial blocks. Whole-brain correlations across combined HC and GD groups showed that MIDT BOLD signal in the ventral striatum/caudate/ventromedial prefrontal cortex and anterior cingulate regions during the prospect of winning positively correlated with total IGT scores. The GD group also contained a higher proportion of tobacco smokers, and correlations between neural activations in prospect on the MIDT may relate in part to gambling and/or smoking pathology. In this study, fronto-striatal activity during the prospect of reward and loss on the MIDT was related to decision-making on the IGT, with blunted activation linked to disadvantageous decision-making. The findings from this work are novel in linking brain activity during a prospect-of-reward phase with performance on a decision-making task in individuals with and without GD.

Longitudinal influence of alcohol and marijuana use on academic performance in college students.

BACKGROUND: Alcohol and marijuana are the two most abused substances in US colleges. However, research on the combined influence (cross sectional or longitudinal) of these substances on academic performance is currently scant. METHODS: Data were derived from the longitudinal 2-year Brain and Alcohol Research in College Students (BARCS) study including 1142 freshman students who completed monthly marijuana use and alcohol consumption surveys. Subjects were classified into data-driven groups based on their alcohol and marijuana consumption. A linear mixed-model (LMM) was employed using this grouping factor to predict grade point average (GPA), adjusted for a variety of socio-demographic and clinical factors. RESULTS: Three data-driven clusters emerged: 1) No/low users of both, 2) medium-high alcohol/no-low marijuana, and 3) medium-high users of both substances. Individual cluster derivations between consecutive semesters remained stable. No significant interaction between clusters and semester (time) was noted. Post-hoc analysis suggest that at the outset, compared to sober peers, students using moderate to high levels of alcohol and low marijuana demonstrate lower GPAs, but this difference becomes non-significant over time. In contrast, students consuming both substances at moderate-to-high levels score significantly lower at both the outset and across the 2-year investigation period. Our follow-up analysis also indicate that when students curtailed their substance use over time they had significantly higher academic GPA compared to those who remained stable in their substance use patterns over the two year period. CONCLUSIONS: Overall, our study validates and extends the current literature by providing important implications of concurrent alcohol and marijuana use on academic achievement in college.

Psychometrically improved, abbreviated versions of three classic measures of impulsivity and self-control.

Self-reported impulsivity confers risk factor for substance abuse. However, the psychometric properties of many self-report impulsivity measures have been questioned, thereby undermining the interpretability of study findings using these measures. To better understand these measurement limitations and to suggest a path to assessing self-reported impulsivity with greater psychometric stability, we conducted a comprehensive psychometric evaluation of the Barratt Impulsiveness Scale-11 (BIS-11), the Behavioral Inhibition and Activation Scales (BIS/BAS), and the Brief Self-Control Scale (BSCS) using data from 1,449 individuals who participated in substance use research. For each measure, we evaluated (a) latent factor structure, (b) measurement invariance, (c) test-criterion relationships between the measures, and (d) test-criterion relations with drinking and smoking outcomes. Notably, we could not replicate the originally published latent structure for the BIS, BIS/BAS, or BSCS or any previously published alternative factor structure (English language). Using exploratory and confirmatory factor analysis, we identified psychometrically improved, abbreviated versions of each measure: 8-item, 2-factor BIS-11 (root-mean-square error of approximation [RMSEA] = .06, comparative fit index [CFI] = .95); 13-item, 4-factor BIS/BAS (RMSEA = .04, CFI = .96); and 7-item, 2-factor BSCS (RMSEA = .05, CFI = .96). These versions evidenced (a) stable, replicable factor structures, (b) scalar measurement invariance, ensuring our ability to make statistically interpretable comparisons across subgroups of interest (e.g., sex, race, drinking/smoking status), and (c) test-criterion relationships with each other and with drinking/smoking. This study provides strong support for using these psychometrically improved impulsivity measures, which improve data quality directly through better scale properties and indirectly through reducing response burden.

Default mode network activity and white matter integrity in healthy middle-aged ApoE4 carriers.

Alzheimer's disease (AD) is most commonly detected during old age, but the underlying neuropathologic changes likely appear decades earlier, especially among patients possessing genetic risk factors, such as the isoform E4 of the apolipoprotein E (ApoE4). In this study, we used magnetic resonance imaging (MRI) to assess default mode network (DMN) connectivity in 22 ApoE4 non-carriers and 14 matched ApoE4 carriers as well as white matter fractional anisotropy (FA) in 15 ApoE4 non-carriers and 11 demographically matched ApoE4 carriers. Cognitive tests were also administered. All of the participants were middle-aged adults. The analysis revealed no cognitive or white matter FA differences between carriers and non-carriers. However, in DMN regions previously implicated in AD, we did detect decreased functional connectivity. Our findings suggest that functional MRI abnormalities may be detectable well before cognitive decline or white matter changes among individuals at increased genetic risk for AD.

Structural angle and power images reveal interrelated gray and white matter abnormalities in schizophrenia.

We present a feature extraction method to emphasize the interrelationship between gray and white matter and identify tissue distribution abnormalities in schizophrenia. This approach utilizes novel features called structural phase and magnitude images. The phase image indicates the relative contribution of gray and white matter, and the magnitude image reflects the overall tissue concentration. Three different analyses are applied to the phase and magnitude images obtained from 120 healthy controls and 120 schizophrenia patients. First, a single-subject subtraction analysis is computed for an initial evaluation. Second, we analyze the extracted features using voxel based morphometry (VBM) to detect voxelwise group differences. Third, source based morphometry (SBM) analysis was used to determine abnormalities in structural networks that co-vary in a similar way. Six networks were identified showing significantly lower white-to-gray matter in schizophrenia, including thalamus, right precentral-postcentral, left pre/post-central, parietal, right cuneus-frontal, and left cuneus-frontal sources. Interestingly, some networks look similar to functional patterns, such as sensory-motor and vision. Our findings demonstrate that structural phase and magnitude images can naturally and efficiently summarize the associated relationship between gray and white matter. Our approach has wide applicability for studying tissue distribution differences in the healthy and diseased brain.

Sex differences in the effects of marijuana on simulated driving performance.

In the United States, one in six teenagers has driven under the influence of marijuana. Driving under the influence of marijuana and alcohol is equally prevalent, despite the fact that marijuana use is less common than alcohol use. Much of the research examining the effects of marijuana on driving performance was conducted in the 1970s and led to equivocal findings. During that time, few studies included women and driving simulators were rudimentary. Further, the potency of marijuana commonly used recreationally has increased. This study examined sex differences in the acute effects of marijuana on driving performance using a realistic, validated driving simulator. Eighty-five subjects (n = 50 males, 35 females) participated in this between-subjects, double-blind, placebo controlled study. In addition to an uneventful, baseline segment of driving, participants were challenged with collision avoidance and distracted driving scenarios. Under the influence of marijuana, participants decreased their speed and failed to show expected practice effects during a distracted drive. No differences were found during the baseline driving segment or collision avoidance scenarios. No differences attributable to sex were observed. This study enhances the current literature by identifying distracted driving and the integration of prior experience as particularly problematic under the influence of marijuana.

Sex, drugs, and cognition: effects of marijuana.

Despite the knowledge that many drugs affect men and women differently, few studies exploring the effects of marijuana use on cognition have included women. Findings from both animal and human studies suggest marijuana may have more marked effects in women. This study examined sex differences in the acute effects of marijuana on cognition in 70 (n=35 male, 35 female) occasional users of marijuana. Tasks were chosen to tap a wide variety of cognitive domains affected by sex and/or marijuana including attention, cognitive flexibility, time estimation, and visuospatial processing. As expected, acute marijuana use impaired performance on selective and divided attention, time estimation, and cognitive flexibility. While there did not appear to be sex differences in marijuana's effects on cognition, women requested to discontinue the smoking session more often than men, likely leading to an underestimation of differences. Further study of psychological differences in marijuana's effects on men and women following both acute and residual effects of marijuana is warranted.