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BACKGROUND: Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk. METHODS: Data came from the Collaborative Study on the Genetics of Alcoholism (n = 3681; ages 11-36). Alcohol transitions (first: drink, intoxication, alcohol use disorder [AUD] symptom, AUD diagnosis), internalizing, and externalizing phenotypes came from the Semi-Structured Assessment for the Genetics of Alcoholism. EF was measured with the Tower of London and Visual Span Tasks. Polygenic scores (PGS) were computed for alcohol-related and behavioral phenotypes. Cox models estimated associations among PGS, behavior, and alcohol milestones. RESULTS: Externalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe AUD (HR⩾1.55). Initiation and AUD were associated with increased hazards for later depressive symptoms and suicidal ideation (HR⩾1.38), and initiation was associated with increased hazards for future conduct symptoms (HR = 1.60). EF was not associated with alcohol transitions. Drinks per week PGS was linked with increased hazards for alcohol transitions (HR⩾1.06). Problematic alcohol use PGS increased hazards for suicidal ideation (HR = 1.20). CONCLUSIONS: Behavioral markers of addiction vulnerability precede and follow alcohol transitions, highlighting dynamic, bidirectional relationships between behavior and emerging addiction.

BACKGROUND: Pathologic perivascular spaces (PVS), the fluid-filled compartments surrounding brain vasculature, may underlie cognitive decline in Parkinsons disease (PD). However, whether this impacts specific cognitive domains has not been investigated. OBJECTIVES: This study examined the relationship of PVS volume at baseline with domain-specific and global cognitive change over 2 years in PD individuals. METHODS: A total of 39 individuals with PD underwent 3T T1w magnetic resonance imaging to determine PVS volume fraction (PVS volume normalized to total regional volume) within (i) centrum semiovale, (ii) prefrontal white matter (medial orbitofrontal, rostral middle frontal, and superior frontal), and (iii) basal ganglia. A neuropsychological battery included assessment of cognitive domains and global cognitive function at baseline and after 2 years. RESULTS: Higher basal ganglia PVS at baseline was associated with greater decline in attention, executive function, and global cognition scores. CONCLUSIONS: While previous reports have associated elevated PVS volume in the basal ganglia with decline in global cognition in PD, our findings show such decline may affect the attention and executive function domains.

This study examined whether a 3-month mild-exercise intervention could improve executive function in healthy middle-aged and older adults in a randomized control trial. Ultimately, a total of 81 middle-aged and older adults were randomly assigned to either an exercise group or a control group. The exercise group received 3 months of mild cycle exercise intervention (3 sessions/week, 30-50 min/session). The control group was asked to behave as usual for the intervention period. Before and after the intervention, participants did color-word matching Stroop tasks (CWST), and Stroop interference (SI)-related reaction time (RT) was assessed as an indicator of executive function. During the CWST, prefrontal activation was monitored using functional near-infrared spectroscopy (fNIRS). SI-related oxy-Hb changes and SI-related neural efficiency (NE) scores were assessed to examine the underlying neural mechanism of the exercise intervention. Although the mild-exercise intervention significantly decreased SI-related RT, there were no significant effects of exercise intervention on SI-related oxy-Hb changes or SI-related NE scores in prefrontal subregions. Lastly, changes in the effects of mild exercise on NE with advancing age were examined. The 81 participants were divided into two subgroups (younger-aged subgroup [YA], older-aged subgroup [OA], based on median age [68 years.]). Interestingly, SI-related RT significantly decreased, and SI-related NE scores in all ROIs of the prefrontal cortex significantly increased only in the OA subgroup. These results reveal that a long-term intervention of very light-intensity exercise has a positive effect on executive function especially in older adults, possibly by increasing neural efficiency in the prefrontal cortex.

Evidence-based treatments for binge eating disorder (BED), such as cognitive behavioral therapy (CBT) lead to successful outcomes only about half the time. Individuals with BED often have measurable deficits in executive function (EF) that may challenge adherence to or impact of cognitive behavioral intervention components. The aim of this study was to evaluate the impact of adding EF training to CBT by combining CBT with a compensatory cognitive training approach (EF-CBT). Participants were 32 adults with BED, overweight/obesity, and comorbid anxiety or depression who were randomly assigned to four months of group treatment in either standard CBT or EF-CBT. Outcomes were assessed at baseline, post-treatment, and at 2-month follow-up. Results showed that EF-CBT was feasible and acceptable, comparable to CBT. Both groups significantly decreased loss of control (LOC) days, clinical impairment, and depression at post-treatment and 2-month follow-up; though there were no differences between groups. Neither group significantly reduced anxiety or weight. Exploratory analyses found that participants with lower EF treated with EF-CBT were less likely to have LOC at post-treatment than those with lower EF treated with CBT. Higher self-monitoring rates during treatment were associated with lower LOC at post-treatment and participants with lower EF were more likely to self-monitor in the EF-CBT arm relative to the CBT arm. These findings suggest that EF-CBT is feasible, acceptable and efficacious, although larger scale research is needed. EF-CBT may be particularly suited for individuals with BED who have lower EF.

ObjectiveThe study aim was to determine whether (A) differences in executive function (EF) and cognition precede weight gain or (B) weight gain causes changes to EF and cognition.MethodsData were gathered from the Adolescent Brain Cognitive Development (ABCD) Study (release 4.0; ages 9-12 years old [N = 2794]; 100% had healthy weight at baseline [i.e., 9/10 years old], 12.4% had unhealthy weight by ages 11/12 years). EF and cognition were assessed across several domains (e.g., impulsivity, inhibitory control, processing speed, memory); BMI was calculated from height and weight. Nested random-effects mixed models examined (A) BMI ~ EF × Time (i.e., variation in EF/cognition precedes weight gain) and (B) EF ~ BMI × Time (weight gain causes changes to EF/cognition) and controlled for sex, puberty, and caregiver education; random effects were site and subject.ResultsVariation in impulsivity, memory, learning, and processing speed was associated with greater increases in BMI trajectories from 9 to 12 years old. Weight gain was associated with a decrease in inhibitory control, but no other associations were observed.ConclusionsUnderlying variation in EF and cognition may be important for weight gain, but 2 years of weight gain may not be enough to have clinical implications for EF and cognition beyond inhibitory control. These findings suggest that more attention should be paid to the inclusion of EF programs in obesity prevention efforts.

This study examined the extent to which early cumulative risk predicts a range of behavioral and psychological outcomes (i.e., depression, future orientation, risky behavior, educational attainment, and socioeconomic outcomes) measured at ages 15 and 26 and whether executive function (EF) and/or behavioral regulation mediated and/or moderated these associations. Data for this study came from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development and included a sample of 1,364 participants (52% male) born in 1991 and followed through age 26. Results indicated that early cumulative risk was related to depression and risky behavior at age 15 as well as depression, income, future orientation, and educational attainment at age 26. Furthermore, both EF and behavioral regulation mediated relations among cumulative risk and academic achievement at age 15 and between cumulative risk and income and educational attainment at age 26. Finally, three significant interactions emerged for age 15 outcomes, indicating that EF and behavioral regulation may change relations between cumulative risk and depression, reading, and future orientation. Implications for future research are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Executive function encompasses effortful cognitive processes that are particularly susceptible to aging. Functional brain networks supporting executive function-such as the frontoparietal control network and the multiple demand system-have been extensively investigated. However, it remains unclear how structural networks facilitate and constrain the dynamics of functional networks to contribute to aging-related executive function declines. We examined whether changes in structural network modal controllability-a network's ability to facilitate effortful brain state transitions that support cognitive functions-are associated with changes in executive function cross-sectionally and longitudinally. Diffusion-weighted imaging and neuropsychological testing were conducted at two time points (Time 1: ages 56 to 66, N = 172; Time 2: ages 61 to 70, N = 267) in community-dwelling men from the Vietnam Era Twin Study of Aging. An executive function factor score was computed from six neuropsychological tasks. Structural networks constructed from white matter connectivity were used to estimate modal controllability in control network and multiple demand system. We showed that higher modal controllability in control network and multiple demand system was associated with better executive function at Time 2, after controlling for age, young adult general cognitive ability, and physical health status. Moreover, changes in executive function over a period of 5 to 6 years (Time 1-Time 2, N = 105) were associated with changes in modal controllability of the multiple demand system and weakly in the control network over the same time period. These findings suggest that changes in the ability of structural brain networks in facilitating effortful brain state transitions may be a key neural mechanism underlying aging-related executive function declines and cognitive aging.

IntroductionEffects of chronic arterial stiffness on brain aging remain unclear. We, therefore, examined whether long-term trajectories of pulse pressure (PP) predicted brain microstructure, microstructure mediated PP-executive function associations, and APOE genotype modified PP-microstructure associations.MethodsWe examined associations of PP trajectories with brain microstructure measured using restriction spectrum imaging in 146 community-dwelling older adults, whether microstructure mediated PP trajectory-executive function associations, and whether PP-restriction spectrum imaging correlations were modified by APOE-ε4 status.ResultsParticipants with trajectories of high PP had lower restricted isotropic diffusion (RI) compared to those with low PP trajectories and PP-executive function associations were mediated by subcortical and white matter RI. High PP more strongly correlated with lower RI and higher hindered diffusion among APOE-ε4 carriers than non-carriers.DiscussionProlonged elevated PP predicts microstructural abnormalities which may contribute to impaired executive function. APOE-ε4 carriers may be most vulnerable to the adverse effects of PP on brain microstructure.

ObjectiveAlzheimer's disease (AD) is highly heritable, and AD polygenic risk scores (AD-PRSs) have been derived from genome-wide association studies. However, the nature of genetic influences very early in the disease process is still not well known. Here we tested the hypothesis that an AD-PRSs would be associated with changes in episodic memory and executive function across late midlife in men who were cognitively unimpaired at their baseline midlife assessment..MethodWe examined 1168 men in the Vietnam Era Twin Study of Aging (VETSA) who were cognitively normal (CN) at their first of up to three assessments across 12 years (mean ages 56, 62, and 68). Latent growth models of episodic memory and executive function were based on 6-7 tests/subtests. AD-PRSs were based on Kunkle et al. (Nature Genetics, 51, 414-430, 2019), p

BackgroundStudies have investigated white matter microstructure in relation to late-life cognitive impairments, with fractional anisotropy (FA) and mean diffusivity (MD) measures thought to capture demyelination and axonal degradation. However, new post-processing methods allow isolation of free water (FW), which captures extracellular fluid contributions such as atrophy and neuroinflammation, from tissue components. FW also appears to be highly relevant to late-life cognitive impairment. Here, we evaluated whether executive functions are associated with FW, and FA and MD corrected for FW (FAFWcorr and MDFWcorr).MethodWe examined 489 non-demented men in the Vietnam Era Twin Study of Aging (VETSA) at mean age 68. Two latent factors capturing 'common executive function' and 'working-memory specific' processes were estimated based on 6 tasks. Analyses focused on 11 cortical white matter tracts across three metrics: FW, FAFWcorr, and MDFWcorr.ResultsBetter 'common executive function' was associated with lower FW across 9 of the 11 tracts. There were no significant associations with intracellular metrics after false discovery rate correction. Effects also appeared driven by individuals with MCI (13.7% of the sample). Working memory-specific tasks showed some associations with FAFWcorr, including the triangularis portion of the inferior frontal gyrus. There was no evidence that cognitive reserve (i.e., general cognitive ability assessed in early adulthood) moderated these associations between executive function and FW or FA.DiscussionExecutive function abilities in early old age are associated primarily with extracellular fluid (FW) as opposed to white matter (FAFWcorr or MDFWcorr). Moderation analyses suggested cognitive reserve does not play a strong role in these associations, at least in this sample of non-demented men.

BackgroundAlthough it is known that plant-based foods are important for physical health, little is known about the relationship between plant-based foods and cognitive health. Emerging evidence suggests that some macronutrients may influence cognition, but it is unclear which domains of cognition are involved; more importantly, it is unknown how a plant-based diet relates to cognition.ObjectiveTo examine associations between a plant-based dietary pattern and cognitive functioning.MethodsParticipants were 3,039 older adults who participated in the 2011-2014 waves of the National Health and Nutrition Examination Survey (NHANES). The present cross-sectional study used data on macronutrient intake from 24-hour dietary interviews, as well as performance on tests of long-term memory and executive function (i.e., delayed word recall, digit symbol substitution test, and animal fluency). Principal component analysis was used to extract a dietary pattern consistent with a plant-based diet.ResultsGreater adherence to a dietary pattern consistent with a plant-based diet was related to better performance on all cognitive tasks. Secondary analyses indicated that the associations between a plant-based dietary pattern and executive function accounted for the association between a plant-based dietary pattern and memory. Furthermore, this same plant-based dietary pattern was associated with reduced baseline inflammation in a separate dataset.ConclusionsExperimental manipulations are needed to determine the potential causal relations of these associations, but these results suggest that a plant-based diet relates to better cognition, especially through improved executive control. Future work should also attempt to extend these results by examining potential mechanisms underlying these associations, such as reduced inflammation.

Increasingly, studies suggest benefits of natural environments or greenness on childrens health. However, little is known about cumulative exposure or windows of susceptibility to greenness exposure. Using inverse probability weighting of marginal structural models (IPW/MSM), we estimated effects of greenness exposure from birth through adolescence on executive function and behavior. We analyzed data of 908 children from Project Viva enrolled at birth in 1999-2002 and followed up until early adolescence. In mid-childhood (median 7.7 years) and early adolescence (13.1 years), executive function and behavior were assessed using the Behavior Rating Inventory of Executive Function and the Strengths and Difficulties Questionnaire (SDQ). Greenness was measured at birth, early childhood, mid-childhood, and early adolescence, using the Normalized Difference Vegetation Index. We used inverse probability weighting of marginal structural models to estimate effects of interventions that ensure maximum greenness exposure versus minimum through all intervals; and that ensure maximum greenness only in early childhood (vs. minimum through all intervals). Results of the effects of maximum (vs. minimum) greenness at all timepoints did not suggest associations with mid-childhood outcomes. Estimates of maximum greenness only in early childhood (vs. minimum) suggested a beneficial association with mid-childhood SDQ (-3.21, 99 %CI: -6.71,0.29 mother-rated; -4.02, 99 %CI: -7.87,-0.17 teacher-rated). No associations were observed with early adolescent outcomes. Our results for persistent maximum greenness exposure on behavior, were not conclusive with confidence intervals containing the null. The results for maximum greenness only in early childhood may shed light on sensitive periods of greenness exposure for behavior regulation.

The brain's prefrontal cortex directs higher-order cognitive and behavioral processes that are important for attention, working memory, and inhibitory control. We investigated whether gestational exposure to organophosphate (OP) pesticides was associated with these abilities in childhood and early adolescence. Between 1999 and 2000, we enrolled pregnant women in a birth cohort drawn from an agricultural region of California. We measured dialkyl phosphate (DAP) metabolites of OP pesticides in maternal pregnancy urine samples (13 and 26 weeks) and estimated associations with behaviors related to attention-deficit/hyperactivity disorder and executive function, assessed longitudinally; 351 families provided neurodevelopmental outcome data at any point when the child was aged 7-12 years. We assessed function across multiple dimensions (e.g., working memory, attention), methods (e.g., behavior reports, child assessment), and reporters (e.g., mothers, teachers, child self-reports). Higher gestational DAP concentrations were consistently associated with behaviors related to attention-deficit/hyperactivity disorder and executive function. For example, a 10-fold increase in gestational DAP concentration was associated with poorer longitudinally assessed Behavior Rating Inventory of Executive Function scores, as reported by mothers (β = 4.0 (95% confidence interval: 2.1, 5.8); a higher score indicates more problems), and Weschler Intelligence Scale for Children-Fourth Edition Working Memory scores (a 3.8-point reduction; β = -3.8 (95% confidence interval: -6.2, -1.3)). Reducing gestational exposure to OP pesticides through public health policy is an important goal.

Early life exposure to per- and polyfluoroalkyl substances (PFAS) may adversely impact neurodevelopment, but epidemiological findings are inconsistent. In the Project Viva pre-birth cohort, we examined associations of prenatal and childhood PFAS plasma concentrations with parent and teacher assessments of childrens behavior problems [Strengths and Difficulties Questionnaire (SDQ)] and executive function abilities [Behavior Rating Inventory of Executive Function (BRIEF)] at age 6-10 years (sample sizes 485-933). PFAS concentrations in pregnant Project Viva mothers (in 1999-2002) and children at ages 6-10 (in 2007-10) were similar to concentrations at similar time points in women and children in the nationally representative U.S. National Health and Nutrition Examination Survey. We observed no consistent associations of prenatal PFAS concentrations with behavior or executive function. Childhood concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), perfluorononanoate (PFNA) and perfluorodecanoate (PFDA) were associated with higher parent-rated SDQ Total Difficulties scores (mean = 6.7, standard deviation (SD) = 4.9), suggesting greater behavioral problems (top (Q4) versus bottom (Q1) quartile PFOA: 1.5, 95% confidence interval (CI): 0.3, 2.7; PFOS: 1.4, 95% CI: 0.3, 2.5; PFHxS: 1.2, 95% CI: 0.1, 2.3; PFNA: 1.2, 95% CI: 0.1, 2.2; PFDA: 1.1, 95% CI: 0.0, 1.1); teacher-rated SDQ scores did not show associations. Higher childhood PFOS was associated with higher (indicating more problems) parent-rated BRIEF General Executive Composite (GEC) scores (standardized to mean = 50, SD = 10) (Q4 vs. Q1: 2.4, 95% CI: 0.2, 4.6), while teacher BRIEF GEC scores indicated more problems among children with higher PFHxS (Q4 vs. Q1: 3.5, 95% CI: -0.8, 6.3). There were no consistent patterns of sexual dimorphism in associations. In a cohort of U.S. children, we observed cross-sectional associations of childhood PFAS concentrations with greater behavioral and executive function problems, but no consistent associations with prenatal PFAS.

Obesity is associated with a multitude of negative health sequalae. Behavioral weight loss (BWL) is currently the recommended behavioral treatment for obesity; however, it is not effective for approximately half of the individuals who participate. BWL requires individuals to carry out many tasks requiring executive function (EF; i.e., higher order cognitive functions such as planning and problem solving) in order to be successful. Growing research supports that lower EF may be associated with attenuated weight loss following BWL, and targeting EF in treatment could improve outcomes. This paper aims to describe the rationale for the development of Novel Executive Function Training for Obesity (NEXT), which adapts Compensatory Cognitive Training to be delivered in conjunction with BWL. We summarize evidence relating EF to obesity and reduced weight loss following BWL, as well as the past success of cognitive training on EF. Then we describe the treatment model for NEXT followed by initial data suggesting that NEXT is feasible and acceptable and may impact EF and weight. Obesity treatments incorporating cognitive training, especially those that train compensatory strategies, may improve weight-loss outcomes and provide a more durable treatment than traditional interventions, but larger randomized control trials are necessary.

Midlife blood pressure is associated with structural brain changes, cognitive decline, and dementia in late life. However, the relationship between early adulthood blood pressure exposure, brain structure and function, and cognitive performance in midlife is not known. A better understanding of these relationships in the preclinical stage may advance our mechanistic understanding of vascular contributions to late-life cognitive decline and dementia and may provide early therapeutic targets. To identify resting-state functional connectivity of executive control networks (ECNs), a group independent components analysis was performed of functional MRI scans of 600 individuals from the Coronary Artery Risk Development in Young Adults longitudinal cohort study, with cumulative systolic blood pressure (cSBP) measured at nine visits over the preceding 30 y. Dual regression analysis investigated performance-related connectivity of ECNs in 578 individuals (mean age 55.5 ± 3.6 y, 323 female, 243 Black) with data from the Stroop color-word task of executive function. Greater connectivity of a left ECN to the bilateral anterior gyrus rectus, right posterior orbitofrontal cortex, and nucleus accumbens was associated with better executive control performance on the Stroop. Mediation analyses showed that while the relationship between cSBP and Stroop performance was mediated by white matter hyperintensities (WMH), resting-state connectivity of the ECN mediated the relationship between WMH and executive function. Increased connectivity of the left ECN to regions involved in reward processing appears to compensate for the deleterious effects of WMH on executive function in individuals across the burden of cumulative systolic blood pressure exposure in midlife.

ObjectiveThe goal was to conduct exploratory analysis to determine if executive functions (EFs) and food responsiveness/satiety responsiveness (appetitive behaviours that describe one's tendency to eat in the presence of food or food cues) interact to influence weight status among preschool children participating in a trial promoting self-regulation around energy-dense foods.MethodsAt baseline, parents completed the Behaviour Rating Inventory of Executive Function-Preschool and the Child Eating Behaviour Questionnaire. Children completed anthropometric measurements at the preschool. Spearman's correlation, linear regression, and tests of interaction were conducted. The relationship between weight status and EFs among those who were high vs low in food responsiveness and satiety responsiveness was examined.ResultsChildren (n = 92) had a mean age of 5.1 years and body mass index (BMI) percentile of 57.6; half (54%) were male. There were significant correlations between food responsiveness and several EFs (emotional control, inhibitory control, working memory, and plan/organize). In the stratified analysis, children with high food responsiveness or low satiety responsiveness had higher BMI percentiles as emotional control skills worsened. BMI percentiles were not elevated among children with low food responsiveness and poor emotional control.ConclusionThese results suggest that EFs may be more relevant to weight status if preschool children had high levels of food responsiveness or low levels of satiety responsiveness (ie, increased tendency to be influenced by environmental food cues). This analysis should be replicated with direct measures of executive function and appetitive behaviours in larger samples of young children to examine longitudinal impact on weight status.

People often learn from the outcomes of their actions, even when these outcomes do not involve material rewards or punishments. How does our brain provide this flexibility? We combined behavior, computational modeling, and functional neuroimaging to probe whether learning from abstract novel outcomes harnesses the same circuitry that supports learning from familiar secondary reinforcers. Behavior and neuroimaging revealed that novel images can act as a substitute for rewards during instrumental learning, producing reliable reward-like signals in dopaminergic circuits. Moreover, we found evidence that prefrontal correlates of executive control may play a role in shaping flexible responses in reward circuits. These results suggest that learning from novel outcomes is supported by an interplay between high-level representations in prefrontal cortex and low-level responses in subcortical reward circuits. This interaction may allow for human reinforcement learning over arbitrarily abstract reward functions.

ObjectivesGeriatric depression often presents with memory and cognitive complaints that are associated with increased risk for Alzheimer's disease (AD). In a parent clinical trial of escitalopram combined with memantine or placebo for geriatric depression and subjective memory complaints, we found that memantine improved executive function and delayed recall performance at 12 months (NCT01902004). In this report, we used positron emission tomography (PET) to assess the relationship between in-vivo amyloid and tau brain biomarkers and clinical and cognitive treatment response.DesignIn a randomized double-blind placebo-controlled trial, we measured 2-(1-{6-[(2-[F18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene) malononitrile ([18F]FDDNP) binding at baseline and assessed mood and cognitive performance at baseline, posttreatment (6 months), and naturalistic follow-up (12 months).ParticipantsTwenty-two older adults with major depressive disorder and subjective memory complaints completed PET scans and were included in this report.ResultsAcross both treatment groups, higher frontal lobe [18F]FDDNP binding at baseline was associated with improvement in executive function at 6 months (corrected p = .045). This effect was no longer significant at 12 months (corrected p = .12). There was no association of regional [18F]FDDNP binding with change in mood symptoms (corrected p = .2).Conclusions[18F]FDDNP binding may predict cognitive response to antidepressant treatment. Larger trials are required to further test the value of [18F]FDDNP binding as a biomarker for cognitive improvement with antidepressant treatment in geriatric depression.

IntroductionCognitive composite scores offer a means of precisely measuring executive functioning (EF).MethodsWe developed the Uniform Data Set v3.0 EF composite score (UDS3-EF) in 3507 controls from the National Alzheimer's Coordinating Center dataset using item-response theory and applied nonlinear and linear demographic adjustments. The UDS3-EF was validated with other neuropsychological tests and brain magnetic resonance imaging from independent research cohorts using linear models.ResultsFinal model fit was good-to-excellent: comparative fit index = 0.99; root mean squared error of approximation = 0.057. UDS3-EF scores differed across validation cohorts (controls > mild cognitive impairment > Alzheimer's disease-dementia ≈ behavioral variant frontotemporal dementia; P

Background: Emerging evidence suggests that opioid receptor antagonists, such as naltrexone, are effective pharmacotherapies for alcohol, opioid, and possibly stimulant use disorders. It is posited that naltrexone exerts its effects, in part, by increasing functional connectivity between neural reward circuitry and frontal systems implicated in executive function. Yet no studies had examined whether executive function moderates these effects. Objectives: This study examined whether a composite measure of executive function (EF) moderates the effect of naltrexone on craving for methamphetamine and subjective responses following infusion of the drug. Methods: Individuals with methamphetamine use disorder (N = 30; 27% female) completed baseline neurocognitive assessments of premorbid and executive function, and an executive function factor was computed. Participants then underwent a randomized, double-blind, cross-over study of titration with naltrexone and placebo. Participants then received a 30-mg intravenous methamphetamine infusion and completed subjective response questionnaires at 8 times in the 120 minutes post-infusion. Results: Multilevel mixed models indicated a significant EF × medication interaction, reflecting greater effects of naltrexone to decrease "desire to access the drug", "want more of the drug", "crave the drug", "feel drug effects" and "feel high" in participants with low EF compared to those with high EF (Bs = .36-1.29, SEs = .14-.17, ps

"Executive functions" (EFs) is an umbrella term for higher cognitive control functions such as working memory, inhibition, and cognitive flexibility. One of the most challenging problems in this field of research has been to explain how the wide range of cognitive processes subsumed as EFs are controlled without an all-powerful but ill-defined central executive in the brain. Efforts to localize control mechanisms in circumscribed brain regions have not led to a breakthrough in understanding how the brain controls and regulates itself. We propose to re-conceptualize EFs as emergent consequences of highly distributed brain processes that communicate with a pool of highly connected hub regions, thus precluding the need for a central executive. We further discuss how graph-theory driven analysis of brain networks offers a unique lens on this problem by providing a reference frame to study brain connectivity in EFs in a holistic way and helps to refine our understanding of the mechanisms underlying EFs by providing new, testable hypotheses and resolves empirical and theoretical inconsistencies in the EF literature.

BACKGROUND:Executive function (EF) is vital to human beings. It has been linked to many genes and family environmental factors in separate studies, but few studies have examined the potential interactions between gene(s) and environmental factor(s). The current study explored the whole genome to identify SNPs, genes, and pathways that interacted with parental warmth (PW) on EF. RESULTS:Nine EF tasks were used to measure its three components (common EF, updating, shifting) based on the model proposed by Miyake et al. (2000). We found that rs111605473, LAMP5, SLC4A7, and LRRK1 interacted significantly with PW to affect the updating component of EF, and the GSE43955 pathway interacted significantly with PW to affect the common EF component. CONCLUSIONS:The current study is the first to identify genes that interacted with PW to affect EF. Further studies are needed to reveal the underlying mechanism.

The Met-allele of the COMT Val158Met polymorphism slows metabolism and increases bioavailability of dopamine (DA) in the prefrontal cortex compared to the Val-allele. Healthy Met-carriers outperform Val-carriers on executive function (EF) tests, yet this 'advantage' disappears in methamphetamine (METH) dependence. Met-carriers may be disproportionately vulnerable to METH-related perturbations of DA, yet it is unknown whether COMT modulates METH effects on CSF DA biomarkers. Participants were 75 METH+ and 47 METH- men who underwent neurocognitive testing, COMT genotyping, and lumbar puncture. CSF was assayed for DA and its metabolite, homovanillic acid (HVA). Separate linear models regressed DA, HVA, and HVA/DA ratios on COMT, METH and their interaction. Pearson correlations examined associations between DA and EF. Significant interactions indicated that METH+ had lower DA and higher HVA/DA ratios among Met/Met, but not Val/Met-or Val/Val. Met/Met-exhibited the highest DA levels among METH-, whereas DA levels were comparable between Met/Met-and Val-carriers among METH+. Higher DA correlated with better EF in METH- Met/Met, but did not predict EF in the entire sample. DA was expectedly higher in METH- Met/Met, yet a discordant genotype-phenotype profile emerged in METH+ Met/Met, consistent with the notion that slow DA clearance exacerbates METH-associated DA dysregulation.

ObjectiveTo examine feasibility, convergent validity and biases associated with a mobile color-word interference test (mCWIT) among older persons living with HIV (PLHIV).MethodOver a 14-day period, 58 PLHIV and 32 HIV-uninfected individuals (aged 50-74) completed the mCWIT on smartphones once per day in real-world settings. Participants also completed a comprehensive laboratory-based neuropsychological evaluation.ResultsA high rate of compliance was observed (86%) in the repeated administration of the mCWIT. A practice effect was observed in the overall sample concerning mCWIT subscores, and these learning effects were greater for PLHIV. Stabilization of performance was observed after 6 (HIV+) and 7 days (HIV-) for completion time and after 2 (HIV-) and 3 days (HIV+) for mCWIT errors. A minor fatigue effect was observed in the overall sample which was unassociated with group status. Moderate to strong correlations were found between mCWIT completion time and mCWIT errors with global neurocognition and with all of the individual neurocognitive domains. The strongest associations were with mCWIT completion time and laboratory-based global neurocognition, executive function, and working memory scores.ConclusionsCognitive testing administered within the context of a person's daily life provides qualitatively different data than neuropsychological testing completed in clinical settings, and it may constitute a more ecologically valid indicator of cognitive performance than traditional methods. Mobile cognitive testing has potential to help characterize real-time cognitive performance and serve as a complementary assessment tool to traditional methods.

BackgroundChildhood trauma is known to impart risk for several adverse life outcomes. Yet, its impact during adolescent development is not well understood. We aimed to investigate the relationships among childhood trauma, functional brain connectivity, executive dysfunction (ED), and the development of high-risk drinking in adolescence.MethodsData from the National Consortium on Alcohol and Neurodevelopment in Adolescence (sample size = 392, 55% female) cohort were used. This included resting-state functional magnetic resonance imaging at baseline, childhood trauma and ED self-reports, and detailed interviews on alcohol and substance use collected at baseline and at 4 annual follow-ups. We used longitudinal regression analyses to confirm the relationship between childhood trauma and ED, identified the mediating functional brain network hubs, and used these linkages to predict future high-risk drinking in adolescence.ResultsChildhood trauma severity was significantly related to ED in all years. At baseline, distributed functional connectivity from hub regions in the bilateral dorsal anterior cingulate cortex, right anterior insula, right intraparietal sulcus, and bilateral pre- and postcentral gyri mediated the relationship between childhood trauma and ED. Furthermore, high-risk drinking in follow-up years 1-4 could be predicted with high accuracy from the trauma-affected functional brain networks that mediated ED at baseline, together with age, childhood trauma severity, and extent of ED.DiscussionFunctional brain networks, particularly from hub regions important for cognitive and sensorimotor control, explain the relationship between childhood trauma and ED and are important for predicting future high-risk drinking. These findings are relevant for the prognosis of alcohol use disorders.

IntroductionIdentifying clinical measures that track disease in the earliest stages of frontotemporal lobar degeneration (FTLD) is important for clinical trials. Familial FTLD provides a unique paradigm to study early FTLD. Executive dysfunction is a clinically relevant hallmark of FTLD and may be a marker of disease progression.MethodsNinety-three mutation carriers with no symptoms or minimal/questionable symptoms (MAPT, n = 31; GRN, n = 28; C9orf72, n = 34; Clinical Dementia Rating scale plus NACC FTLD Module < 1) and 78 noncarriers enrolled through Advancing Research and Treatment in Frontotemporal Lobar Degeneration/Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects studies completed the Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (NIH-EXAMINER) and the UDS neuropsychological battery. Linear mixed-effects models were used to identify group differences in cognition at baseline and longitudinally. We examined associations between cognition, clinical functioning, and magnetic resonance imaging volumes.ResultsNIH-EXAMINER scores detected baseline and differences in slopes between carriers and noncarriers, even in carriers with a baseline Clinical Dementia Rating scale plus NACC FTLD Module = 0. NIH-EXAMINER declines were associated with worsening clinical symptoms and brain volume loss.DiscussionThe NIH-EXAMINER is sensitive to cognitive changes in presymptomatic familial FTLD and is a promising surrogate endpoint.

OBJECTIVE:HIV-associated neurocognitive impairment continues to be prevalent and clinically relevant. We examined the relationship between neurocognition and full plasma HIV RNA suppression among study participants over a 15 year period at a large research program. DESIGN/METHODS:We analyzed the combined prospective studies of the HIV Neurobehavioral Research Program (HNRP) at the University of California at San Diego. Participants were eligible for analysis if on three drug cART with comprehensive neuropsychological testing results. Participants who reported recent non-adherence were excluded. The primary outcome was plasma HIV RNA of ≤50 copies/ml. Generalized estimating equation was used to assess for associations with full virologic suppression taking into account longitudinal visits. RESULTS:There were 1943 participants at baseline, of whom 69.4% had plasma HIV RNA ≤50 copies/ml. Participants with full suppression were slightly older, less likely to abuse cocaine, and had significantly better executive function. Multivariate analysis with incorporation of longitudinal visits (total = 5555) confirmed current cocaine abuse to be strongly associated with lack of virologic suppression (odds ratio = 0.45, 95% confidence interval = 0.31-0.63). In contrast, increasing age, increasing years of HIV infection, and increasing executive function (odds ratio = 1.18 for T score change of 10, 95% confidence interval = 1.07-1.30) were associated with full virologic suppression. Lack of virologic suppression at baseline was associated with a significant subsequent decline in executive function. CONCLUSIONS:In a 15 year research cohort of almost 2000 HIV-infected individuals on cART, better executive function was associated with full virologic suppression, possibly as a result rather than a cause.

ObjectivesChildren with temporal lobe epilepsy (TLE) exhibit executive dysfunction on traditional neuropsychological tests. There is limited evidence of different functional network alterations associated with this clinical executive dysfunction. This study investigates working memory deficits in children with TLE by assessing deactivation of the default mode network (DMN) on functional Magnetic Resonance Imaging (fMRI) and the relationship of DMN deactivation with fMRI behavioral findings and neuropsychological test performance.Experimental designfMRI was conducted on 15 children with TLE and 15 healthy controls (age: 8-16 years) while performing the N-back task in order to assess deactivation of the DMN. N-back accuracy, N-back reaction time, and neuropsychological tests of executive function (Delis-Kaplan Executive Function System [D-KEFS] Color-Word Interference and Card Sort tests) were also assessed.Principal observationsDuring the N-back task, children with TLE exhibited significantly less deactivation of the DMN, primarily in the precuneus/posterior cingulate cortex compared with controls. These alterations significantly correlated with N-back behavioral findings and D-KEFS results.ConclusionsChildren with TLE exhibit executive dysfunction which correlates with DMN alterations. These findings suggest that the level of deactivation of specific functional networks may contribute to cognitive impairment in children with TLE. The findings also indicate that children with TLE have network alterations in extratemporal lobe brain regions.

ObjectiveTo examine (a) changes in parental involvement across early emerging adulthood, (b) whether yearly fluctuations in parental involvement were associated with adherence and glycated hemoglobin (HbA1c) over time, and (c) whether higher involvement was more beneficial for those with poorer executive function (EF).MethodsA total of 228 high school seniors (M age = 17.76) with type 1 diabetes reported on mothers' and fathers' acceptance, knowledge of diabetes activities, disclosure to mothers and fathers regarding diabetes, and adherence at four yearly time points. At baseline, participants completed performance-based measures of EF. HbA1c was collected from assay kits.ResultsGrowth curve models revealed significant declines in disclosure to fathers and mothers' and fathers' knowledge of diabetes activities; no changes were found in mothers' or fathers' acceptance nor disclosure to mothers. Multilevel models indicated significant between-person effects for nearly all aspects of parental involvement with more acceptance, knowledge, and disclosure associated with better HbA1c and adherence. Within-person effects for disclosure to fathers, and mothers' and fathers' knowledge indicated that in years when emerging adults perceived higher amounts of these types of involvement (compared with their own average), HbA1c was lower. Within-person effects were found for acceptance to mothers, disclosure to mothers and fathers, and mothers' diabetes knowledge for adherence. Disclosure to fathers and mothers' knowledge of diabetes activities were especially beneficial for HbA1c for those with poorer EF performance.ConclusionsParental involvement in diabetes management remains important during the high-risk time of emerging adulthood, especially for those with poorer EF.

Background and purposeExecutive function (EF) decline is common after brain radiation therapy (RT), yet the etiology is unclear. We analyzed the association between longitudinal changes in frontal lobe white matter microstructure and decline in EF following RT in brain tumor patients on a prospective clinical trial.Materials and methodsDiffusion tensor imaging was obtained on 22 patients with brain tumors prior to RT, as well as 3- and 6-months post-RT, in a prospective, observational trial. Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were calculated within the superficial white matter (SWM) of the anterior cingulate (AC) and dorsolateral prefrontal cortex. Measures of cognitive flexibility, verbal fluency, and verbal set-shifting were obtained pre- and post-RT. Reliable change indices were calculated to determine significant baseline to 6-month EF changes.ResultsDecreases in FA and increases in MD were observed in the caudal AC (CAC) at 3-months post-RT. CAC changes were characterized by increased RD bilaterally. From baseline to 6-months post-RT, decreased FA and increased MD and RD of the CAC was associated with decline in verbal set-shifting ability, whereas increased MD in the CAC was associated with a decline in cognitive flexibility.ConclusionWhite matter underlying the AC may be particularly vulnerable to radiation effects. Early microstructural loss within AC SWM represents an important biomarker for EF decline, and dose reduction in this region may represent a possibility for cognitive preservation for patients receiving radiotherapy.

Executive function (EF), its importance for scholastic achievement and the question of whether or not EF is malleable, have become a topic of intense interest. Education or schooling is often seen as effective approaches to enhance EF due to the specific school-related requirements as compared to kindergarten or pre-school. However, no study to date has investigated whether targeted training focusing on those domains might be comparable with regular schooling in improving EF and fluid intelligence (Gf). The aim of the present study was to replicate and extend the previously demonstrated schooling effects on EF by using a school-cutoff design, and to further investigate whether a theoretically motivated intervention targeting specific EF, i.e., working memory (WM) or inhibitory control (IC), could achieve comparable effects with schooling in both, WM and IC, as well as Gf. 91 6-year-old kindergarteners and first-graders with similar chronological age participated the study. We compared the performance of a first-grade schooling group with that of two kindergarten training groups as well as a business-as-usual kindergarten control group. Participants were assessed in WM, IC and Gf at baseline, immediately after the intervention (posttest), as well as 3 months after training completion (follow-up). The results showed that the schooling group indeed outperformed the kindergarten groups at baseline in several cognitive tasks. Furthermore, both the WM and IC training showed pronounced gains in the trained tasks, as well as varying degrees of improvement in non-trained outcome measures. Most importantly, both training groups achieved comparable performance with the schooling group, which was especially apparent in Gf at follow-up. Our findings provide further evidence for the malleability of EF demonstrating that both, long-term and short-term interventions can facilitate the acquisition of those important skills, and as such, our work has important implications for educational practice.

People with schizophrenia demonstrate impairments in selective attention, working memory, and executive function. Given the overlap in these constructs, it is unclear if these represent distinct impairments or different manifestations of one higher-order impairment. To examine this question, we administered tasks from the basic cognitive neuroscience literature to measure visual selective attention, working memory capacity, and executive function in 126 people with schizophrenia and 122 healthy volunteers. Patients demonstrated deficits on all tasks with the exception of selective attention guided by strong bottom-up inputs. Although the measures of top-down control of selective attention, working memory, and executive function were all intercorrelated, several sources of evidence indicate that working memory and executive function are separate sources of variance. Specifically, both working memory and executive function independently contributed to the discrimination of group status and independently accounted for variance in overall general cognitive ability as assessed by the MATRICS battery. These two cognitive functions appear to be separable features of the cognitive impairments observed in schizophrenia.

Psychotic like experiences (PLE's) are common in the general population, particularly during adolescence, which has generated interest in how PLE's emerge, and the extent to which they reflect either risk for, or resilience to, psychosis. The "attachment-developmental-cognitive" (ADC) model is one effort to model the effect of risk factors on PLEs. The ADC model proposes attachment insecurity as an early environmental insult that can contribute to altered neurodevelopment, increasing the likelihood of PLE's and psychosis. In particular, early-life attachment disruptions may negatively impact numerous aspects of executive function (EF), including behavioral inhibition and emotion regulation. Yet despite the relationship of disrupted attachment to EF impairments, no studies have examined how these factors may combine to contribute to PLE's in adolescents. Here, we examined the relative contributions of daily-life EF and attachment difficulties (avoidance and anxiety) to PLEs in typically developing youth (N=52; ages 10-21). We found that EF deficits and high attachment insecurity both accounted for a significant proportion of the variance in PLE's, and interacted to predict PLE manifestation. Specifically, positive PLEs were predicted by greater trouble monitoring behavioral impact, less difficulty completing tasks, greater difficulty regulating emotional reactions, greater difficulty controlling impulses and higher attachment anxiety. Negative PLEs were predicted by greater difficulty in alternating attention, transitioning across situations, and regulating emotional reactions as well as higher attachment anxiety. These results are consistent with the ADC model, providing evidence that early-life attachment disruptions may impact behavioral regulation and emotional control, which together may contribute to PLEs.

HIV-associated neurocognitive disorders (HAND) are frequently associated with impaired executive function and verbal fluency. Given limited knowledge concerning HAND in Sub-Saharan-Africa and lack of Cameroonian adult neuropsychological (NP) test norms, we administered four executive function [Halstead Category Test (HCT), Wisconsin Card Sorting Test (WCST), Color Trails-II (CTT2), and Stroop Color-Word-Interference (SCWT)] and three verbal fluency (Category, Action, and Letter Fluency) tests to 742 adult Cameroonians (395 HIV-, 347 HIV+). We developed demographically-corrected NP test norms and examined the effects of HIV and related variables on subjects' executive function and verbal fluency. HIV+ subjects had significantly lower T-scores on CTT2 (P = 0.005), HCT (P = 0.032), WCST (P

OBJECTIVE:The objective of this study was to examine 1) whether teens' glycemic control and adherence to type 1 diabetes treatment regimen worsen during the transition from late adolescence to emerging adulthood, and 2) whether teens' executive function (EF), as measured by performance and self-reported problems with EF, is predictive of these changes (after controlling for general intelligence). RESEARCH DESIGN AND METHODS:High school seniors with type 1 diabetes (N = 236; mean age 17.74 years) were assessed at three yearly time points. At baseline, during the senior year of high school, participants completed a self-report measure of problems with EF and performance-based measures of EF and general intelligence (IQ). Glycemic control was determined on the basis of results collected from HbA1c assay kits, and teens reported their adherence at all three time points. RESULTS:HbA1c increased significantly across the three time points and adherence declined. EF performance was not associated with adherence or HbA1c at baseline, nor with changes in adherence over time. However, better EF performance predicted slower increases in HbA1c over time (i.e., slope) while controlling for IQ. Teens' self-reported problems with EF were associated with worse glycemic control and poorer adherence at baseline (i.e., intercept), but they did not predict changes in either HbA1c or adherence over time (i.e., slope). CONCLUSIONS:Abilities involved in performance on EF tests may be one resource for maintaining better glycemic control during the transition to emerging adulthood. Assessment of such EF abilities may allow for the identification of individuals who are most at risk for deterioration of glycemic control during this transition.

PurposeDeaf children are frequently reported to be at risk for difficulties in executive function (EF); however, the literature is divided over whether these difficulties are the result of deafness itself or of delays/deficits in language that often co-occur with deafness. The purpose of this study is to discriminate these hypotheses by assessing EF in populations where the 2 accounts make contrasting predictions.MethodWe use a between-groups design involving 116 children, ages 5-12 years, across 3 groups: (a) participants with normal hearing (n = 45), (b) deaf native signers who had access to American Sign Language from birth (n = 45), and (c) oral cochlear implant users who did not have full access to language prior to cochlear implantation (n = 26). Measures include both parent report and performance-based assessments of EF.ResultsParent report results suggest that early access to language has a stronger impact on EF than early access to sound. Performance-based results trended in a similar direction, but no between-group differences were significant.ConclusionsThese results indicate that healthy EF skills do not require audition and therefore that difficulties in this domain do not result primarily from a lack of auditory experience. Instead, results are consistent with the hypothesis that language proficiency, whether in sign or speech, is crucial for the development of healthy EF. Further research is needed to test whether sign language proficiency also confers benefits to deaf children from hearing families.

Older HIV-infected men are at higher risk for both depression and cognitive impairments, compared to HIV-uninfected men. We evaluated the association between longitudinal patterns of depressive symptoms and attention/executive function in HIV-infected and HIV-uninfected men aged 50+ years to understand whether HIV infection influenced the long-term effect of depression on attention/executive function. Responses to the Center for Epidemiologic Studies-Depression scale and attention/executive function tests (Trail Making Test Part B and Symbol Digit Modalities Test) were collected semiannually from May 1986 to April 2015 in 1611 men. Group-based trajectory models, stratified by HIV status, were used to identify latent patterns of depressive symptoms and attention/executive function across 12 years of follow-up. We identified three depression patterns for HIV-infected and HIV-uninfected men (rare/never 50.0 vs. 60.6%, periodically depressed 29.6 vs. 24.5%, chronic high 20.5 vs.15.0%, respectively) and three patterns of attention/executive function for HIV-infected and HIV-uninfected men (worst-performing 47.4 vs. 45.1%; average 41.9 vs. 47.0%; best-performing 10.7 vs. 8.0%, respectively). Multivariable logistic regression models were used to assess associations between depression patterns and worst-performing attention/executive function. Among HIV-uninfected men, those in the periodically depressed and chronic high depressed groups had higher odds of membership in the worst-performing attention/executive function group (adjusted odds ratio [AOR] = 1.45, 95% CI 1.04, 2.03; AOR = 2.25, 95% CI 1.49, 3.39, respectively). Among HIV-infected men, patterns of depression symptoms were not associated with patterns of attention/executive function. Results suggest that HIV-uninfected, but not HIV-infected, men with chronic high depression are more likely to experience a long-term pattern of attention/executive dysfunction.

The present study examined the role of executive control functions (ECF) in adaptive risk-taking during adolescence. Healthy individuals aged 8-25 were administered ECF measures and the Balloon Analogue Risk Task (BART), a computerized measure of risk-taking propensity. Findings demonstrated that adolescents who executed a more consistent response strategy evidenced better performance on the BART. Greater working memory (WM) predicted lower response variability and WM capacity mediated the relationship between age and variability. Results suggest that intra-individual response variability may index adaptive risk-taking and that the development of ECF, specifically WM, may play an integral role in adaptive decision making during adolescence and young adulthood.

White matter abnormalities are prevalent in neuropsychiatric disorders such as schizophrenia, but it is unclear whether these abnormalities represent a cause or consequence of these disorders. Reduced levels of the myelin protein 2'-3'-cyclic nucleotide 3'-phosphodiesterase (CNP) are associated with the schizophrenic symptom catatonia in both humans and mouse models. In this issue of the JCI, Janova et al. show that reduced CNP levels correlate with catatonia and white matter inflammation in human subjects. Furthermore, they demonstrate that microglial ablation prevents and alleviates catatonic signs in Cnp-/- mice, indicating that microglial-mediated inflammation causes catatonia. Together, this study identifies a cellular mechanism by which subtle myelin abnormalities cause low-grade neuroinflammation and catatonic behavior.

The association of dialysis initiation with changes in cognitive function among patients with advanced chronic kidney disease is poorly described. To better define this, we enrolled participants with advanced chronic kidney disease from the Chronic Renal Insufficiency Cohort in a prospective study of cognitive function. Eligible participants had a glomerular filtration rate of 20 ml/min/1.73m2 or less, or dialysis initiation within the past two years. We evaluated cognitive function by a validated telephone battery at regular intervals over two years and analyzed test scores as z scores. Of 212 participants, 123 did not transition to dialysis during follow-up, 37 transitioned to dialysis after baseline, and 52 transitioned to dialysis prior to baseline. In adjusted analyses, the transition to dialysis was associated with a significant loss of executive function, but no significant changes in global cognition or memory. The estimated net difference in cognitive z scores at two years for participants who transitioned to dialysis during follow-up compared to participants who did not transition to dialysis was -0.01 (95% confidence interval -0.13, 0.11) for global cognition, -0.24 (-0.51, 0.03) for memory, and -0.33 (-0.60, -0.07) for executive function. Thus, among adults with advanced chronic kidney disease, dialysis initiation was associated with loss of executive function with no change in other aspects of cognition. Larger studies are needed to evaluate cognition during dialysis initiation.

Deaf children are often described as having difficulty with executive function (EF), often manifesting in behavioral problems. Some researchers view these problems as a consequence of auditory deprivation; however, the behavioral problems observed in previous studies may not be due to deafness but to some other factor, such as lack of early language exposure. Here, we distinguish these accounts by using the BRIEF EF parent report questionnaire to test for behavioral problems in a group of Deaf children from Deaf families, who have a history of auditory but not language deprivation. For these children, the auditory deprivation hypothesis predicts behavioral impairments; the language deprivation hypothesis predicts no group differences in behavioral control. Results indicated that scores among the Deaf native signers (n = 42) were age-appropriate and similar to scores among the typically developing hearing sample (n = 45). These findings are most consistent with the language deprivation hypothesis, and provide a foundation for continued research on outcomes of children with early exposure to sign language.

ObjectiveDisturbances in functional connectivity have been suggested to contribute to cognitive and emotion processing deficits observed in bipolar disorder (BD). Functional connectivity between medial prefrontal cortex (mPFC) and other brain regions may be particularly abnormal. The goal of the present study was to characterize the temporal dynamics of the default mode network (DMN) connectivity in BD and examine its association with cognition.MethodIn a preliminary study, euthymic BD (n = 15) and healthy comparison (HC, n = 19) participants underwent resting-state functional MRI, using high-resolution sequences adapted from the Human Connectome Project, and completed neuropsychological measures of processing speed and executive function. A seed-based approach was used to measure DMN correlations in each participant, with regions of interest in the mPFC, posterior cingulate cortex (PCC), and lateral parietal cortex. Subsequently, to characterize temporal dynamics, correlational analyses between the mPFC and other DMN nodes were repeated using a sliding-window correlational analysis with subsets of the time series.ResultsWhen averaged across the entire scan, there were no group differences in overall connectivity strength between the mPFC and other regions of the DMN. However, dynamic connectivity between the mPFC and PCC was altered in BD, such that connectivity was less variable (i.e., more rigid) over time. Decreased connectivity variability was associated with slower processing speed and reduced cognitive set-shifting in BD patients.ConclusionsVariability in resting-state functional connectivity may be an index of internetwork flexibility that is reduced in BD and a correlate of ongoing cognitive impairment during periods of euthymia. (PsycINFO Database Record

BackgroundTraffic-related air pollution exposure may influence brain development and function and thus be related to neurobehavioral problems in children, but little is known about windows of susceptibility.AimsExamine associations of gestational and childhood exposure to traffic-related pollution with executive function and behavior problems in children.MethodsWe studied associations of pre- and postnatal pollution exposures with neurobehavioral outcomes in 1212 children in the Project Viva pre-birth cohort followed to mid-childhood (median age 7.7years). Parents and classroom teachers completed the Behavior Rating Inventory of Executive Function (BRIEF) and the Strengths and Difficulties Questionnaire (SDQ). Using validated spatiotemporal models, we estimated exposure to black carbon (BC) and fine particulate matter (PM2.5) in the third trimester of pregnancy, from birth to 3years, from birth to 6years, and in the year before behavioral ratings. We also measured residential distance to major roadways and near-residence traffic density at birth and in mid-childhood. We estimated associations of BC, PM2.5, and other traffic exposure measures with BRIEF and SDQ scores, adjusted for potential confounders.ResultsHigher childhood BC exposure was associated with higher teacher-rated BRIEF Behavioral Regulation Index (BRI) scores, indicating greater problems: 1.0 points (95% confidence interval (CI): 0.0, 2.1) per interquartile range (IQR) increase in birth-age 6BC, and 1.7 points (95% CI: 0.6, 2.8) for BC in the year prior to behavioral ratings. Mid-childhood residential traffic density was also associated with BRI score (0.6, 95% CI: 0.1, 1.1). Birth-age 3BC was not associated with BRIEF or SDQ scores. Third trimester BC exposure was not associated with teacher-rated BRI scores (-0.2, 95% CI: -1.1, 0.8), and predicted lower scores (fewer problems) on the BRIEF Metacognition Index (-1.2, 95% CI: -2.2, -0.2) and SDQ total difficulties (-0.9, 95% CI: -1.4, -0.4). PM2.5 exposure was associated with teacher-rated BRIEF and SDQ scores in minimally adjusted models but associations attenuated with covariate adjustment. None of the parent-rated outcomes suggested adverse effects of greater pollution exposure at any time point.ConclusionsChildren with higher mid-childhood exposure to BC and greater near-residence traffic density in mid-childhood had greater problems with behavioral regulation as assessed by classroom teachers, but not as assessed by parents. Prenatal and early childhood exposure to traffic-related pollution did not predict greater executive function or behavior problems; third trimester BC was associated with lower scores (representing fewer problems) on measures of metacognition and behavioral problems.

It is often assumed that negative affect impairs the executive functions that underlie our ability to control and focus our thoughts. However, support for this claim has been mixed. Recent work has suggested that different negative affective states like anxiety and anger may reflect physiologically separable states with distinct effects on cognition. However, the effects of these 2 affective states on executive function have never been assessed. As such, we induced anxiety or anger in participants and examined the effects on executive function. We found that anger did not impair executive function relative to a neutral mood, whereas anxiety did. In addition, self-reports of induced anxiety, but not anger, predicted impairments in executive function. These results support functional models of affect and cognition, and highlight the need to consider differences between anxiety and anger when investigating the influence of negative affect on fundamental cognitive processes such as memory and executive function. (PsycINFO Database Record

We examined differences in regional brain activation during tests of executive function in individuals with Hoarding Disorder (HD), Obsessive Compulsive Disorder (OCD), and healthy controls (HC) using functional magnetic resonance imaging (fMRI). Participants completed computerized versions of the Stroop and Go/No-Go task. We found that during the conflict monitoring and response inhibition condition in the Go/No-Go task, individuals with HD had significantly greater activity than controls in the anterior cingulate cortex (ACC) and right dorsolateral prefrontal cortex (DLPFC). HD also exhibited significantly greater right DLPFC activity than OCD. We also observed significant differences in activity between HD and HC and between HD and OCD in regions (ACC, anterior insula, orbitofrontal cortex, and striatum) involved in evaluating stimulus-response-reward associations, or the personal and task-relevant value of stimuli and behavioral responses to stimuli. These results support the hypothesis that individuals with HD have difficulty deciding on the value or task relevance of stimuli, and may perceive an abnormally high risk of negative feedback for difficult or erroneous cognitive behavior.

ObjectiveCalifornia children's exposures to polybrominated diphenyl ether flame retardants (PBDEs) are among the highest measured worldwide. We previously reported associations for prenatal and childhood PBDE exposures with decrements in attention, processing speed, fine motor coordination, and cognition in children at ages 5 and 7 years. Here, we investigate associations of PBDEs with attention and executive function at ages 9 to 12 years in the expanded CHAMACOS cohort.MethodsWe measured PBDEs in prenatal and child age 9 year serum samples for families enrolled in the study since pregnancy ("CHAM1", N=321). In a subsequent cohort for which families were enrolled at child age 9 ("CHAM2", N=301), we measured PBDEs in maternal and child samples collected at child age 9, and used predictive modeling to estimate prenatal exposure levels. We examined associations of measured and estimated PBDE concentrations on children's attention and executive functioning at ages 9, 10½, and 12 years.ResultsGeometric means for prenatal and childhood ΣPBDE levels (sum of PBDE-47, -99, -100, -153) for the expanded CHAMACOS cohort were 26.3 and 63.2 ng/g lipid, respectively, and did not differ significantly between CHAM1 and CHAM2 families. We found consistent associations of prenatal exposure to PBDEs with poorer attention and executive function, measured with parent report and direct neuropsychological testing of the child. For example, using GEE models of repeated outcome measures at ages 9 and 12, a 10-fold increase in prenatal ΣPBDE was associated with poorer response consistency on the Conners' Continuous Performance Test II (β=2.9; 95% CI: 0.9, 4.8) and poorer working memory on the Behavioral Rating Inventory of Executive Function (β=2.5; 95% CI: 0.5, 4.4). Child age 9 ΣPBDE levels were associated with poorer parent-reported attention and executive function for girls but not boys.ConclusionsOur results suggest that the prefrontal cortex may be a potential target for PBDE exposure and add to a growing literature showing that these ubiquitous toxicants may adversely affect neurodevelopment.

ObjectiveCalifornia children's exposures to polybrominated diphenyl ether flame retardants (PBDEs) are among the highest measured worldwide. We previously reported associations for prenatal and childhood PBDE exposures with decrements in attention, processing speed, fine motor coordination, and cognition in children at ages 5 and 7 years. Here, we investigate associations of PBDEs with attention and executive function at ages 9 to 12 years in the expanded CHAMACOS cohort.MethodsWe measured PBDEs in prenatal and child age 9 year serum samples for families enrolled in the study since pregnancy ("CHAM1", N=321). In a subsequent cohort for which families were enrolled at child age 9 ("CHAM2", N=301), we measured PBDEs in maternal and child samples collected at child age 9, and used predictive modeling to estimate prenatal exposure levels. We examined associations of measured and estimated PBDE concentrations on children's attention and executive functioning at ages 9, 10½, and 12 years.ResultsGeometric means for prenatal and childhood ΣPBDE levels (sum of PBDE-47, -99, -100, -153) for the expanded CHAMACOS cohort were 26.3 and 63.2 ng/g lipid, respectively, and did not differ significantly between CHAM1 and CHAM2 families. We found consistent associations of prenatal exposure to PBDEs with poorer attention and executive function, measured with parent report and direct neuropsychological testing of the child. For example, using GEE models of repeated outcome measures at ages 9 and 12, a 10-fold increase in prenatal ΣPBDE was associated with poorer response consistency on the Conners' Continuous Performance Test II (β=2.9; 95% CI: 0.9, 4.8) and poorer working memory on the Behavioral Rating Inventory of Executive Function (β=2.5; 95% CI: 0.5, 4.4). Child age 9 ΣPBDE levels were associated with poorer parent-reported attention and executive function for girls but not boys.ConclusionsOur results suggest that the prefrontal cortex may be a potential target for PBDE exposure and add to a growing literature showing that these ubiquitous toxicants may adversely affect neurodevelopment.

This study investigated the relationship between insulin-resistance and constituent components of executive function in a sample of neurologically intact older adult subjects using the homeostasis model assessment (HOMA-IR) and latent factors of working memory, cognitive control and processing speed derived from confirmatory factor analysis. Low-density lipoprotein (LDL), mean arterial pressure (MAP), along with body mass index (BMI) and white matter hypointensity (WMH) were used to control for vascular risk factors, adiposity and cerebrovascular injury. The study included 119 elderly subjects recruited from the University of California, San Francisco Memory and Aging Center. Subjects underwent neuropsychological assessment, fasting blood draw and brain magnetic resonance imaging (MRI). Partial correlations and linear regression models were used to examine the HOMA-IR-executive function relationship. Pearson correlation adjusting for age showed a significant relationship between HOMA-IR and working memory (rp = -.18; p = .047), a trend with cognitive control (rp = -.17; p = .068), and no relationship with processing speed (rp = .013; p = .892). Linear regression models adjusting for demographic factors (age, education, and gender), LDL, MAP, BMI, and WMH indicated that HOMA-IR was negatively associated with cognitive control (r = -.256; p = .026) and working memory (r = -.234; p = .054). These results suggest a greater level of peripheral insulin-resistance is associated with decreased cognitive control and working memory. After controlling for demographic factors, vascular risk, adiposity and cerebrovascular injury, HOMA-IR remained significantly associated with cognitive control, with working memory showing a trend. These findings substantiate the insulin-resistance-executive function hypothesis and suggest a complex interaction, demonstrated by the differential impact of insulin-resistance on processing speed and specific aspects of executive function.

BackgroundA specific form of small-vessel vasculopathy-cerebral microbleeds (CMBs)-has been linked to various types of dementia in adults. We assessed the incidence of CMBs and their association with neurocognitive function in pediatric brain tumor survivors.MethodsIn a multi-institutional cohort of 149 pediatric brain tumor patients who received cranial radiation therapy (CRT) between 1987 and 2014 at age