Neuropsychological Measures Of Executive Function Research Articles

History of traumatic brain injury is associated with increased grey-matter loss in patients with mild cognitive impairment.

To investigate whether a history of traumatic brain injury (TBI) is associated with greater long-term grey-matter loss in patients with mild cognitive impairment(MCI). 85 patients with MCI were identified, including 26 with a previous history of traumatic brain injury (MCI[TBI-]) and 59 without (MCI[TBI+]). Cortical thickness was evaluated by segmenting T1-weighted MRI scans acquired longitudinally over a 2-year period. Bayesian multilevel modelling was used to evaluate group differences inbaseline cortical thickness and longitudinalchange, as well as group differences in neuropsychological measures of executive function. At baseline, theMCI[TBI+] group had less grey matter within right entorhinal, left medial orbitofrontal and inferior temporal cortexareas bilaterally. Longitudinally, theMCI[TBI+] group also exhibited greater longitudinal declines in left rostral middle frontal, the left caudal middle frontal and left lateral orbitofrontalareas sover the span of 2years (median = 1-2%, 90%HDI [-0.01%: -0.001%], probability of direction(PD) = 90-99%). The MCI[TBI+] group also displayedgreater longitudinal declines in Trail-Making-Test (TMT)-derived ratio (median: 0.737%, 90%HDI: [0.229%: 1.31%], PD = 98.8%) and differences scores (median: 20.6%, 90%HDI: [-5.17%: 43.2%], PD = 91.7%). Our findings support the notion that patients with MCI and a history of TBI are at risk of accelerated neurodegeneration, displayinggreatest evidence for cortical atrophy within the left middle frontal and lateral orbitofrontal frontal cortex. Importantly, these results suggest that long-term TBI-mediated atrophy is more pronounced in areas vulnerable to TBI-related mechanical injury, highlighting their potential relevance for diagnostic forms of intervention in TBI.

42 Associations Between Mild Traumatic Brain Injury, Executive Function, and Criminal Justice Involvement among Veterans and Service Members: a LIMBIC-CENC study

Objective:To examine relationships between history of mild traumatic brain injury (mTBI), neuropsychological measures of executive function, and lifetime history of criminal justice (CJ) involvement among combat-exposed Veterans and Service Members (V/SM).Participants and Methods:Participants were combat-exposed V/SM who completed a baseline assessment for the multicenter Long-term Impact of Military-Relevant Brain Injury Consortium - Chronic Effects of Neurotrauma Consortium study (N=1,341) and had adequate engagement/symptom reporting on measures of performance and symptom validity (i.e., Medical Symptom Validity Test and Mild Brain Injury Atypical Symptoms Scale). Neuropsychological battery included the Trail Making Test (A and B), Wechsler Adult Intelligence Scale-IV (WAIS-IV) Digit Span subtest, and the National Institute of Health (NIH) Toolbox Flanker subtest. Lifetime history of brain injury, criminal justice involvement, and demographics were collected. Participants were 87% male, 72% white, with a mean age of 40 years (SD=9.67). Eighty-one percent had at least some college education. Nineteen percent were active duty. Eighty percent of Veterans and 86% of Service Members reported a history of >1 mTBI, and of these 31% and 47% respectively experienced 3+ mTBIs.Results:Three groups were composed based on level of involvement with the CJ system: 1.) No history of arrests or incarcerations (3+ mTBIs: 64%), 2.) A lifetime history of arrest but no felony incarceration (3+ mTBIs: 34%), and 3.) A lifetime history of felony incarceration (3+ mTBIs: 2%). Ordinal regression analyses revealed that performance on a working memory task (Digit Span; b= 0.024, p= .041; OR= 1.024) was significantly associated with increased CJ involvement after adjusting for age, education, service status, and mTBIs. Performance on measures of processing speed (Trails A), set-shifting (Trails B), and inhibition (Flanker) were not significantly associated with CJ involvement. Number of mTBIs was significantly and positively associated with level of CJ involvement in all four models; Digit Span (p= .016), Trails A (p= .016), Trails B (p= .020), and Flanker (p= .008).Conclusions:Performance on most measures of executive functioning was not significantly associated with CJ involvement in this large, representative sample of V/SM who served in combat. Although performance on a working memory task was significantly associated with CJ involvement, the size of the effect was small and the association was in the opposite direction as expected. Number of mTBIs was significantly associated with level of CJ involvement, indicating that sustaining multiple mTBI may be linked to greater risk of CJ involvement. These findings suggest that social and psychological factors beyond executive dysfunction may better explain the relationship between history mTBIs and CJ involvement. Some aspects of military service and veteran status, such as interdisciplinary treatment for brain injury and physical, mental, and psychosocial health needs, may be protective against previously identified risk factors for arrest (e.g., deficits in executive functioning). Contextualizing mTBI within the larger behavioral health profile of V/SM, with emphasis placed on intervention for related co-morbidities, may reduce the impact of previous arrest on wellbeing and/or reduce the risk of future CJ involvement.

22 Cognitive Reserve's Relationship to Brain Burden in Parkinson's Disease Without Dementia

Objective:Individuals with Parkinson's disease (PD) have varying trajectories of cognitive decline. One reason for this heterogeneity may be "cognitive reserve": where higher education/IQ/current mental engagement compensates for increasing brain burden (Stern et al., 2020). With few exceptions, most studies examining cognitive reserve in PD fail to include brain metrics. This study's goal was to examine whether cognitive reserve moderated the relationship between neuroimaging indices of brain burden (diffusion free water fraction and T2-weighted white matter changes) and two commonly impaired domains in PD: executive function and memory. We hypothesized cognitive reserve would mitigate the relationship between higher brain burden and worse cognitive performance.Participants and Methods:Participants included 108 individuals with PD without dementia (age mean=67.9±6.3, education mean=16.6±2.5) who were prospectively recruited for two NIH-funded projects at the University of Florida. All received neuropsychological measures of executive function (Trails B, Stroop, Letter Fluency) and memory (delayed recall: Hopkin's Verbal Learning Test-Revised, WMS-III Logical Memory). Domain specific z-score composites were created using data from age/education matched non-PD peer controls (N=62). For the Cognitive Reserve (CR) proxy, a z-score composite included years of education, WASI-II Vocabulary, and Wechsler Test of Adult Reading. At the time of testing, participants completed multiple MRI scans (T1-weighted, diffusion, Fluid Attenuated Inversion Recovery) from which the following were extracted: 1) whole-brain free water within the white matter (a measure of microstructural integrity and neuroinflammation), 2) white matter hyperintensities/white matter total volume (WMH/WMV), and bilaterally-averaged edge weights of white matter connectivity between 3) dorsolateral prefrontal cortex and caudate and 4) entorhinal cortex and hippocampi. Separate linear regressions for each brain metric used executive function and memory composites as dependent variables; predictors were age, CR proxy, respective brain metric, and a residual centered interaction term (brain metric*CR proxy). Identical models were run in dichotomized short and long disease duration groups (median split=6 years).Results:In all models, a lower CR proxy significantly predicted worse executive function (WMH/WMV: beta=0.49, free water: beta=0.54, frontal edge weight: beta=0.49, p's<0.001) and memory (WMH/WMV: beta=0.42, free water: beta=0.35, temporal edge weight: beta=0.39, p's <0.01). For neuroimaging metrics, higher free water significantly predicted worse executive function (beta=-0.39, p=0.002) but not memory. No other brain metrics were significant predictors of either domain. Accounting for PD duration, higher free water predicted worse executive function for those with both short (beta=-0.49, p=0.04) and long disease duration (beta=-0.48, p=0.02). Specifically in those with long disease duration, higher free water (beta=-0.57 p=0.02) and lower edge weights between entorhinal cortex and hippocampi (beta=0.30, p=0.03) predicted worse memory. Overall, no models contained significant interactions between the CR proxy and any brain metric.Conclusions:Results replicate previous work showing that a cognitive reserve proxy relates to cognition. However, cognitive reserve did not moderate brain burden's relationship to cognition. Across the sample, greater neuroinflammation was associated with worse executive function. For those with longer disease duration, higher neuroinflammation and lower medial temporal white matter connectivity related to worse memory. Future work should examine other brain burden metrics to determine whether/how cognitive reserve influences the cognitive trajectory of PD.

6 A review of neuropsychological measures of executive functioning in the Japanese and Japanese-American population

Objective:There are approximately 1.5 million Japanese and Japanese Americans in the United States, with the Japanese population increasing steadily over the past two decades. Given the growing number of the Japanese population, it is likely that a clinical neuropsychologist may encounter a Japanese patient, particularly for neurocognitive disorder evaluations given the aging population. Literature has reported that cross-cultural bias in neuropsychological testing and cultural factors affect individuals’ test performance. In order to conduct and interpret neuropsychological assessments for this population, it is important to use normative data and consider the impact of various factors such as acculturation, language, and generation in the U.S. Availability of normative cognitive test data for Japanese-Americans is limited. Tests with most extensive use, adaptation, validation, and norming were identified. Many clinically used measures of executive functioning (EF) have been translated into Japanese and studied in multiple clinical populations. We present information on tests in this domain given their appropriateness for use in cross-linguistic and cross-cultural evaluations.Participants and Methods:Available studies of neuropsychological tests measuring EF that have been translated and normed in the Japanese and/or Japanese-American patient population are reported. Review of the literature was conducted by authors of Japanese descent familiar with neuropsychological assessment and Japanese and Japanese-American culture. We prioritized studies published in both English and Japanese and those that included commonly utilized tests in the U.S, allowing for maximum accessibility and utility for Western-based neuropsychologists. Additionally, inclusion priority was given to studies published in English which report the clinical diagnoses, age range, and gender characteristics of the sample population. The Wisconsin card sorting test (WCST) and Trail Making Test (TMT) were reviewed.Results:The WCST and the TMT, with its variant, was the most normed EF cognitive test currently available. The Keio version Japanese-Trail Making Test (J-TMT) and a simplified version of the Trail Making Test (S-TMT) has been utilized in Japan, however norms are still lacking. Of the available studies, the S-TMT and J-TMT were found to be moderately correlated with the TMT. The Keio version WCST (KWCST) (Kao et al., 2012) was correlated to education level (Abe et al., 2004), appropriately differentiating severity of social anxiety disorder (Fujii et al., 2013), patients with schizophrenia (Banno et al., 2012), and cognitive impairment in Parkinson’s disease (Yoshii et al., 2019).Conclusions:Information regarding translated and normed tests are presented to assist clinical neuropsychologists provide competent services to Japanese-Americans. The J-TMT and the S-TMT may be clinically useful as an evaluation of attention for the Japanese population. The KWCST has also been found to be an appropriate tool for this population. However, publicly available norms for these assessments are still sparse, and there is very limited information about administration of these tests by English-speaking neuropsychologists with the use of interpreters. Further work is needed to increase access to and awareness of linguistically and culturally appropriate versions of clinical measures to better serve the Japanese and Japanese-American population.

Executive functioning and the pursuit of happiness

Executive functioning and happiness are each associated with successful learning and other desirable individual and societal outcomes; however, it is unclear whether a relation exists between them. Executive regulation of happiness pursuits in daily life, operationalized as hedonic (e.g., pursuing pleasure) and eudaimonic (e.g., pursuing personal growth) motives for action, may be a way the constructs relate to each other. In this initial investigation, we aimed to explore whether objectively measured executive functioning skills relate to happiness motives. A sample of 119 college students completed six objective neuropsychological measures of executive functioning and self-reported levels of hedonic and eudaimonic motives for action in daily life. Correlation and regression analyses examined the relations among temporal discounting and two latent executive functioning factors (inhibitory control and working memory) with hedonic and eudaimonic motives, as well as their interaction. Results suggested a possible association between higher levels of eudaimonic motives and preference for higher delayed rewards, as well as poorer working memory. Further analyses suggested that endorsing high levels of eudaimonic and hedonic motives simultaneously (i.e., the “full life”) was associated with poorer inhibitory control and working memory performance, whereas endorsing low levels of both simultaneously (i.e., the “empty life”) was associated with a preference for more immediate monetary rewards. Findings are discussed in the context of goal conflict and risk assessment among individuals who endorse the “full life”. Overall, these findings suggest that complex relations may exist between executive functioning and trait-level happiness pursuits, and have implications for possible interventions aimed at enhancing happiness-related motives and cognitive processes to facilitate learning. Given the exploratory nature of the present study, further investigations are necessary.

Is executive dysfunction a potential contributor to the comorbidity between basic reading disability and attention-deficit/hyperactivity disorder?

ABSTRACT Our study is one of the few to analyze executive functioning (EF) in a comprehensive, multi-modal fashion as a potential contributor to the comorbidity between attention-deficit/hyperactivity disorder (ADHD) and basic reading disability (RD). We included multiple, traditional, neuropsychological measures of EF, along with the Behavior Rating Inventory of Executive Function (BRIEF) questionnaire, to assess inhibit, shift, working memory (WM), planning, generation fluency, and problem-solving. Participants included 263 children, ages 8–12 years, with RD, ADHD, RD/ADHD, and typically developing controls. When using the traditional measures in a 2 × 2 MANCOVA, we found both RD and ADHD had poor cognitive EF in most areas at the group level, with phonological loop deficits being more specific to RD and behavioral regulation deficits being more specific to ADHD. Children with RD/ADHD performed comparably to those with RD and ADHD alone. Results were similar on the BRIEF. In contrast, only WM predicted both basic reading and inattention when the data were assessed in a continuous fashion. It also explained the correlations between basic reading and inattention, being worthy of longitudinal research to determine if it is a shared contributor to RD/ADHD. When comparing hypotheses as to the nature of RD/ADHD, we found the multiple deficit hypothesis was better supported by our EF data than the phenocopy hypothesis or the cognitive subtype hypothesis.

Microstructural degeneration and cerebrovascular risk burden underlying executive dysfunction after stroke

Executive dysfunction affects 40% of stroke patients, but is poorly predicted by characteristics of the stroke itself. Stroke typically occurs on a background of cerebrovascular burden, which impacts cognition and brain network structural integrity. We used structural equation modelling to investigate whether measures of white matter microstructural integrity (fractional anisotropy and mean diffusivity) and cerebrovascular risk factors better explain executive dysfunction than markers of stroke severity.126 stroke patients (mean age 68.4 years) were scanned three months post-stroke and compared to 40 age- and sex-matched control participants on neuropsychological measures of executive function. Executive function was below what would be expected for age and education level in stroke patients as measured by the organizational components of the Rey Complex Figure Test, F(3,155) = 17, R2 = 0.25, p < 0.001 (group significant predictor at p < 0.001) and the Trail-Making Test (B), F(3,157) = 3.70, R2 = 0.07, p < 0.01 (group significant predictor at p < 0.001). A multivariate structural equation model illustrated the complex relationship between executive function, white matter integrity, stroke characteristics and cerebrovascular risk (root mean square error of approximation = 0.02).Pearson’s correlations confirmed a stronger relationship between executive dysfunction and white matter integrity (r = − 0.74, p < 0.001), than executive dysfunction and stroke severity (r = 0.22, p < 0.01). The relationship between executive function and white matter integrity is mediated by cerebrovascular burden. White matter microstructural degeneration of the superior longitudinal fasciculus in the executive control network better explains executive dysfunction than markers of stroke severity. Executive dysfunction and incident stroke can be both considered manifestations of cerebrovascular risk factors.

Dementia Worry and Neuropsychological Performance in Healthy Older Adults.

Dementia is one of the most feared diseases in American society. However, limited research exists regarding how worrying about dementia may influence peoples' cognitive abilities. The current study examines how dementia worry affects performance on neuropsychological domains of executive function, memory, attention, and processing speed in a healthy older adult population. Participants (n=40) were screened for depression using the Patient Health Questionnaire-8 (PHQ-8, scores > 10 were excluded) and for mild cognitive impairment using the Telephone Interview for Cognitive Status (TICS, scores < 32 were excluded). All participants were administered common neuropsychological tests of executive function, memory, attention, and processing speed. Participants were also asked to complete the Dementia Worry Scale (DWS), a measure assessing the level of dementia worry individuals experience in daily life. A multivariate effect of dementia worry on neuropsychological measures of executive function was supported. Specifically, higher levels of dementia worry were significantly related to poorer performance on combined measures of executive function (Wilk's Lambda=0.821, F (2, 36)=3.934, p=.028). Dementia worry significantly affects scores on specific neuropsychological measures. Inasmuch, dementia worry may have both functional implications for older adults, as well as assessment implications for practicing neuropsychologists. Further research is necessary to parse apart whether dementia worry represents a psychological variable affecting cognitive performance and/or serves as an early marker of cognitive decline.

Integrating Three Characteristics of Executive Function in Non-Demented Aging: Trajectories, Classification, and Biomarker Predictors.

With longitudinal executive function (EF) data from the Victoria Longitudinal Study, we investigated three research goals pertaining to key characteristics of EF in non-demented aging: (a) examining variability in EF longitudinal trajectories, (b) establishing trajectory classes, and (c) identifying biomarker predictors discriminating these classes. We used a trajectory analyses sample (n = 781; M age = 71.42) for the first and second goals and a prediction analyses sample (n = 570; M age = 70.10) for the third goal. Eight neuropsychological EF measures were used as indicators of three EF dimensions: inhibition, updating, and shifting. Data-driven classification analyses were applied to the full trajectory distribution. Machine learning prediction analyses tested 15 predictors from genetic, functional, lifestyle, mobility, and demographic risk domains. First, we observed: (a) significant variability in EF trajectories over a 40-year band of aging and (b) significantly variable patterns of EF decline. Second, a four-class EF trajectory model was observed, characterized with classes differentiated by an algorithm of level and slope information. Third, the highest group class was discriminated from lowest by several prediction factors: more education, more novel cognitive activity, lower pulse pressure, younger age, faster gait, lower body mass index, and better balance. First, with longitudinal variability in EF aging, the data-driven approach showed that long-term trajectories can be differentiated into separable classes. Second, prediction analyses discriminated class membership by a combination of multiple biomarkers from demographic, lifestyle, functional, and mobility domains of risk for brain and cognitive aging decline.

Undiagnosed Dementia in Patients with Peripheral Arterial Disease: A Systematic Review of the Literature

Objective: It is purported that patients with peripheral arterial disease (PAD) may have impaired cognitive function due to concomitant cerebrovascular disease. Such disease may be clinically unrecognised but can impact on a patient’s recovery and prognosis. The purpose of this systematic review was to interrogate the body of published evidence on undiagnosed dementia in PAD patients. Methods: A search strategy encompassing MEDLINE, Scopus, and the Cochrane database was developed to identify peer reviewed articles examining rates of undiagnosed dementia in patients with PAD. The following search terms were used: “PAD”; “PVD”; “dementia”; “peripheral arterial disease”; “peripheral vascular disease”; “cognitive impairment”; “Alzheimer’s disease”, and “cogniti”. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2009 guidelines were followed throughout. The primary outcome was the incidence of previously undiagnosed dementia in patients with PAD. Results: The initial electronic literature search yielded 1 492 titles. After removal of duplicates, 994 abstracts were screened in order to ascertain if they were potentially eligible for inclusion. Abstract review yielded 62 full texts for further evaluation, and from this eight case–control studies consisting of 1 161 patients were included in the review. Analysis of these studies revealed that PAD patients performed significantly worse than controls on a variety of neuropsychological measures of executive function (six out of eight studies). Conclusion: The review indicated that PAD patients are more likely to have undiagnosed dementia than healthy controls. This condition may impact on their ability to comply with treatment strategies and should be borne in mind when managing this challenging patient cohort.

The Relationship between Intelligence and Executive Functions in Hispanic Patients with Mild Traumatic Brain Injury

Executive functions have been described as the “brain of the brain” and to include a variety of processes, including, but not limited to, abstraction, formulation of intentions, reasoning, formulation of strategies, monitoring their success, working memory, and the self-regulation of behavior. Executive functions have been determined to be associated with the integrity of the frontal lobes. On the other hand, intelligence has also been described in similar terms, and the concept of general intelligence, or the g factor has also been associated with the frontal lobes. As constructs, intelligence and executive functions have been also described as “overlapping” in many features, while maintaining a certain degree of conceptual independence. The purpose of this study was to compare the intellectual functioning of a sample of patients with mild traumatic brain injury, obtained by means of the Reynolds Intellectual Assessment Scales (RIAS), with their performance in a number of neuropsychological measures of executive functions, such as the Halstead Category Test (HCT), the Wisconsin Card Sorting Test (WCST), the Stroop Word and Color Test (SWCT), and the Trail Making Test (TMT). Pearson Product Moment Correlations were obtained between the various measures of the RIAS and the measures of executive functions (HCT, WCST, SWCT, TMT). Whereas the magnitudes of the correlations were within the moderate range, intelligence, particularly non-verbal intelligence and working memory were noted to be significantly correlated with the measures of executive functions. The conclusion was reached that intelligence and executive functions are related to each other as constructs, but yet maintain a certain degree of independence.

Proteomic Discovery: Elevated Neurogranin Levels in Children with Sickle Cell Disease

Sickle cell disease (SCD) is an inherited hemoglobinopathy that frequently causes neurological complications, such as stroke, silent cerebral infarct (SCI) and other forms of brain injury, including loss of cognition. SCI is defined as any ischemic lesion visible on T2-weighted magnetic resonance imaging (MRI) that is not associated with a focal neurologic deficit in the same vascular distribution, and is the most commonly recognized form of brain injury in SCD. SCI is associated with decreased neurocognitive function and increased risk for new or enlarging SCI/stroke. The purpose of this study was to use mass spectrometry (MS) based proteomics to discover and validate plasma brain proteins associated with brain injury in children with SCD. The plasma samples used for the proteomics discovery analyses were from two groups: screening samples of participants in the Silent Cerebral Infarct Multi-Center Clinical Trial (SIT Trial) (n=15), and 6 age-matched, healthy non-SCD controls, three of whom had sickle cell trait. Samples from children with SCD were divided into two groups: those with SCI (n=7) and those without SCI (n=8) matched for age, hemoglobin (Hb) and white blood cell counts. To identify circulating markers of SCI, plasma proteomes were analyzed using a sequential separation approach of Hb and top abundant plasma protein depletion, followed by reverse phase separation of intact proteins, trypsin digestion and tandem MS. Neurogranin (NRGN), a small calmodulin-binding synaptic protein (PMID 9886843), was the most abundant brain-enriched protein found in the plasma of children with SCD. We developed a NRGN sandwich immunoassay for verification of MS analysis results in an independent cohort from the SIT Trial longitudinal samples. For this verification study, plasma samples from the SIT Trial and 25 normal controls were tested for NRGN levels at study entry and exit by immunoassay. The majority of the SCD samples were obtained from an ancillary study to collect longitudinal samples that started after the SIT Trial had begun. There was no overlap between the discovery and the verification group samples. The normal control samples were from 25 healthy, age and gender comparable non-SCD pediatric controls unrelated to the SIT Trial, without evidence of acute/chronic illness. From the discovery SCD group, 1172 unambiguous proteins were identified; 639 proteins were identified from normal controls, as shown in Figure 1. Twenty-five percent (289/1172) of these proteins were found solely in the SCI group. Our MS protein identification data were filtered against this list of expressed brain proteins to produce a composite list of brain proteins found in plasma from children with SCD, but not found in plasma from age, gender and race-matched healthy control children. Twenty-five plasma proteins known to be expressed in one or more cell type enriched in the human brain based on bioinformatics searches were more abundant in the SCD vs control groups, as shown in Table 1. Median NRGN levels were higher at study entry in children with SCD (0.44 ng/mL, N=98), in comparison to a healthy, non-SCD control group (0.12 ng/mL, N=25, p &lt; 0.0001), as shown in Figure 2. Using the longitudinal samples from the SIT Trial, there were no differences in NRGN levels between the observation group and the treatment group (p=0.35) over time. There was no significant difference in median NRGN levels between the observation group and the treatment group at the initial visit (0.36 vs 0.19, p=0.069) or final visit (0.39 vs 0.52, p=0.52). Using the initial visit samples from the SIT Trial, there was no significant difference in median NRGN levels between the non-SCI (n=35) and SCI groups (n=61) (p=0.073). There was no significant correlation between NRGN levels and neuropsychological measures of executive function (rho=0.089, p=0.58) and IQ (rho=-0.081, p=0.62). Our non-biased proteomic discovery studies demonstrate that NRGN levels are increased in children with SCD, when compared to normal children. Additional studies will be necessary to determine whether NRGN levels correlate with specific forms of neurologic injury. Further validation studies of larger cohorts with a multi-analyte ELISA of these brain proteins identified in plasma (Table 1) are warranted, and could help establish possible links between brain-specific proteins and neurocognitive outcomes. Disclosures Lance: NIH: Research Funding; KKI: Research Funding. Faulcon:FDA: Employment, Other: Although the author is a FDA/CTP employee, this work was not done as part his/her official duties. This publication reflects the views of the author and should not be construed to reflect the FDA/CTP's views or policies.. Fu:GSK: Employment. Yang:ImmunArray: Patents &amp; Royalties: ImmunArray. Strouse:Global Blood Therapeutics: Consultancy. Barron-Casella:Mast Pharmaceudicals - spouse: Consultancy; ImmunArray - spouse: Patents &amp; Royalties. Van Eck:ImmunArray: Consultancy, Patents &amp; Royalties. Casella:NIH: Research Funding; Mast Pharmaceuticals: Consultancy; Immunoarray Ltd.: Patents &amp; Royalties. Everett:ImmunArray: Consultancy, Patents &amp; Royalties.

Procrastination as evidence of executive functioning impairment in college students

Research addressing procrastination behavior has historically focused upon personality and situational factors to explain the nature of this problematic behavior. Although researchers have identified personality traits that are closely associated with procrastination behavior, the literature is sparse in addressing other possible explanations, particularly those related to brain functioning. Considering that procrastination is described with terms such as “poor time management,” “lack of planning,” and “poor judgment,” amongst others, one might consider whether executive functioning systems are functioning adequately in these individuals. Individuals who demonstrate difficulties with executive functioning tend to share the same characteristics that are applied to those who procrastinate. Preliminary self-report research by Jurado and Rosselli found that undergraduates who reported higher levels of procrastination, also reported high levels of executive functioning difficulties. This research project replicated and extended these findings utilizing three common neuropsychological measures of executive functioning. The results from these measures demonstrated that individuals who showed impairment in executive functioning also reported difficulties with executive functioning and procrastination.

Multiple Levels of Control Processes for Wisconsin Card Sorts: An Observational Study.

We explored short-term behavioral plasticity on the Modified Wisconsin Card Sorting Test (M-WCST) by deriving novel error metrics by stratifying traditional set loss and perseverative errors. Separating the rule set and the response set allowed for the measurement of performance across four trial types, crossing rule set (i.e., maintain vs. switch) and response demand (i.e., repeat vs. alternate). Critically, these four trial types can be grouped based on trial-wise feedback on t − 1 trials. Rewarded (correct) maintain t − 1 trials should lead to error enhancement when the response demands shift from repeat to alternate. In contrast, punished (incorrect) t − 1 trials should lead to error suppression when the response demands shift from repeat to alternate. The results supported the error suppression prediction: An error suppression effect (ESE) was observed across numerous patient samples. Exploratory analyses show that the ESE did not share substantial portions of variance with traditional neuropsychological measures of executive functioning. They further point into the direction that striatal or limbic circuit neuropathology may be associated with enhanced ESE. These data suggest that punishment of the recently executed response induces behavioral avoidance, which is detectable as the ESE on the WCST. The assessment of the ESE might provide an index of response-related avoidance learning on the WCST.

Executive Functions in Insomnia Disorder: A Systematic Review and Exploratory Meta-Analysis.

Background: Executive functions (EFs) are involved in the control of basic psychological processes such as attention and memory and also contribute to emotion regulation. Research on the presence of EFs impairments in insomnia yielded inconsistent results. Therefore, we performed a systematic review of the literature on three EFs: inhibitory control, working memory, and cognitive flexibility in adults with insomnia in order to investigate the presence and magnitude of insomnia-related EFs impairments.Methods: PubMed, Scopus, Medline, and PsycINFO were searched. Risk of bias assessment of included studies was performed by two independent researchers. Findings were summarised using both a narrative approach and meta-analysis. Cohen's d was calculated at 95% confidence interval (CI) as effect size of between groups differences.Results: Twenty-eight studies comparing adult individuals with a diagnosis of insomnia and healthy controls on neuropsychological measures of EFs were included. Narrative synthesis revealed substantial variability across study findings. Factors that were primarily hypothesised to account for this variability are: objective sleep impairments and test sensitivity. Exploratory meta-analysis showed impaired performance of small to moderate magnitude in individuals with insomnia as compared to controls in reaction times, but not accuracy rates, of inhibitory control (d = −0.32, 95% CI: −0.52 to −0.13) and cognitive flexibility tasks (d = −0.30, 95% CI: −0.59 to −0.01). Performance in working memory tasks was also significantly impacted (d = −0.19, 95% CI: −0.38 to −0.00). Effects sizes were larger when insomnia was associated with objective sleep impairments, rather than normal sleep.Conclusions: We gathered evidence supporting small to moderate deficits in EFs in individuals with insomnia. Due to the small sample size results should be considered preliminary and interpreted carefully.

Alzheimer’s disease and the processing of uncertainty during choice task performance: Executive dysfunction within the Hick–Hyman law

ABSTRACTThe Hick–Hyman law states that choice response time (RT) increases linearly with increasing information uncertainty. Neuroimaging studies suggest that the representation of uncertainty in support of response generation is mediated by the cognitive control network (CCN), which is disrupted in Alzheimer’s disease (AD). Thus, we predicted that patients with AD would be sensitive to increased uncertainty particularly under conditions that place demands on the internal representation of uncertainty, and that choice RT performance under these conditions would be associated with performance on tests of executive function. Cognitively normal older adults (CN) and patients with AD completed card-sorting tasks that separately manipulated either externally cued uncertainty (i.e., number of sorting piles with a fixed probability of each stimulus type) or more internally driven uncertainty (i.e., the probability of each stimulus type with a fixed number of sorting piles). Consistent with our predictions, AD patients were impaired relative to CN particularly on the internally driven uncertainty task, and RT in this task was associated with performance on neuropsychological measures of executive functioning but not episodic memory. We suggest that this pattern of findings is consistent with presumed disruptions to the CCN in AD and provides neuropsychological evidence in support of the role of the CCN in the representation of uncertainty.

Automated Indices of Clustering and Switching of Semantic Verbal Fluency in Parkinson's Disease.

Deficits in semantic verbal fluency (SVF) can stem from dysfunction of an executive control system and/or of semantic knowledge. Previous analyses of SVF responses were devised to characterize these two components including switching and mean cluster size (MCS) indices, but these rely on subjective experimenter-based assessment of the words' relatedness. To address this limitation, computational data-driven SVF indices have been developed. Our aim is to assess the validity and usefulness of these automated indices in the context of cognitive decline in Parkinson's disease (PD). This is a retrospective study including 50 advanced PD patients with (n=28) or without (n=22) mild cognitive impairment (PD-MCI). We analyzed animal SVF outputs using an automated computational approach yielding switching, MCS, and cumulative relatedness (CuRel) indices. We compared these indices to the classic experimenter-based switching and MCS indices to assess concurrent validity, and against neuropsychological measures of executive functioning and semantic knowledge to assess construct validity. We also examined whether these indices were impaired and predicted PD-MCI. Automated switching indices, but not MCS or CuRel, showed evidence of concurrent and construct validity, and characterized individual difference in advanced PD. Automated switching indices also outperformed the experimenter-dependent index in predicting the presence of PD-MCI. Computational methods hold promise as fine-grained, unbiased indices reflecting the executive component of SVF, but none of the methods provided valid measures of semantic knowledge in PD. Our data also confirm that SVF are not adequate tests of semantic memory in patients with executive dysfunction such as PD. (JINS, 2018, 24, 1047-1056).

Stability of genetic and environmental influences on executive functions in midlife.

Research on executive functions (EFs) has revealed that individual differences in general EF abilities are highly correlated across the first few decades of life, especially at the level of genetic influences. Our work has also provided evidence for substantial heritability of this Common EF factor in midlife, but it remains unclear whether individual differences in Common EFs continue to show strong stability in middle age. We examined data from 1,464 middle-aged twins from the Vietnam Era Twin Study of Aging, most of whom completed 7 neuropsychological measures of EFs at 2 points in middle age (Mages = 56 and 62). Confirmatory factor analysis indicated that individual differences in Common EF, a latent factor explaining variation in seven neuropsychological EF tasks, were highly correlated across this 6-year period (r = .97), and that the same genetic and environmental influences were operating across this interval (genetic and shared environmental correlations = 1.0, nonshared environment correlation = .95). Similar phenotypic and genetic stability was observed for a Working Memory (WM)-Specific latent factor, which explained additional variance in working memory span tasks not captured by Common EF (r = .98, genetic correlation = 1.0, nonshared environmental correlation = .88). There was a large mean-level performance decline in Common EF (d = -.60) but not WM-Specific (d = -.03). These results suggest that there is substantial decline in Common EF abilities across middle age but that individual differences are almost perfectly stable. (PsycINFO Database Record

Genetic and environmental architecture of executive functions in midlife.

Research on executive functions (EFs) has revealed evidence for general abilities that underlie performance across multiple EF tasks and domains. This Common EF factor is highly stable in adolescence through young adulthood, correlates with other important cognitive abilities, and is explained largely by genetic influences. However, little is known about Common EF beyond young adulthood. This study examines 3 hypotheses regarding the latent structure, genetic/environmental etiology, and cognitive correlates of Common EF in middle age. We examined data from 1,284 middle-aged twins (51-60 years) in the Vietnam Era Twin Study of Aging who completed 7 neuropsychological measures of EFs, as well as measures of general cognitive ability and processing speed. Our confirmatory factor analysis indicated that Common EF explained variation across all 7 EF tasks. Inhibition and shifting were subsumed entirely under the Common EF factor, and there was an additional working memory span-specific factor. Common EF was heritable in midlife (a2 = .46), with additional evidence for both shared environmental influences (c2 = .41) and nonshared environmental influences (e2 = .13). Higher Common EF was moderately associated with higher general cognitive ability, measured both in early adulthood and midlife, and faster processing speed in midlife. These correlations were primarily driven by shared genetic influences. These results support the hypothesis that Common EF captures similar EF abilities in midlife as in adolescence and young adulthood. However, environmental influences may explain a larger portion of variance in this construct as individuals age. (PsycINFO Database Record

Assessment-2The Evolution of Ecological Validity within Neuropsychological Executive Function Measures

Assessment-2The Evolution of Ecological Validity within Neuropsychological Executive Function Measures