Executive functions are goal-directed control mechanisms that modulate the operation of other cognitive processes. Preterm born very-low-birth-weight (VLBW: birth weight<1500 grams) children have more problems with attention/executive function than their term born peers. The objective of this study is to examine if VLBW young adults had more self-reported attention/ executive problems and lower neuropsychological test results than controls. Furthermore, to investigate the relationship between self-reported attention/executive problems, general cognitive ability (IQ) and test results. Forty-two VLBW [mean birth weight 1237 (219) grams, and gestational age 29.3 (2.4) weeks] and 63 term born controls at age 19 years completed The BRIEF-A self-report of attention/executive functions in everyday life. The Wechsler Adult Intelligence Scale III was used to obtain IQ scores; subtests from Delis-Kaplan were used to assess attention/executive function. There were no differences between the VLBW young adults and controls on any of the BRIEF-A measures, but the VLBW subjects had lower scores on 8 of the 18 neuropsychological subtests (p<.01). Some correlations between BRIEF-A and the Stroop and TMT tests were found in the VLBW group. VLBW young adults do not report more problems regarding attention/executive function in daily life than controls despite lower results on several neuropsychological tests. (JINS, 2014, 20, 1–10)

Evidence suggests that standard learning and recall indexes are sensitive markers of verbal declarative memory ability in bipolar disorder (BD), but no study has examined performance across the full range of component process measures on the Hopkins Verbal Learning Test (HVLT-R) in a BD cohort. As the HVLT-R is part of a widely used battery of cognitive functioning backed by the U.S. Federal Drug Administration as the accepted battery for use in pro-cognitive trials assessing cognitive-enhancing drugs in the related disorder schizophrenia, estimating the utility of its measures in BD is important. Forty-nine BD patients and 51 healthy controls completed the HVLT-R, which was scored for 13 variables of interest, across 4 indices: recall and learning, recognition, strategic organization, and errors. BD patients had greater difficulty in learning the HVLT-R word list compared to controls. They also demonstrated impairment in delayed recall/recognition. There were no differences between the groups in terms of their slope of learning, retrieval index, retention percentage, semantic or serial clustering, errors, or level of retrieval. This pattern was consistent across symptomatic and euthymic patients. The HVLT-R has some utility in characterizing the component processes involved in memory function in BD, such that memory impairments appear to be attributable to deficient encoding processes during the acquisition phase of learning. In the case of planning pro-cognitive clinical trials, the encoding deficits in BD observed here may be sensitive enough to potentially respond to medications designed to enhance the verbal memory performance. (JINS, 2014, 20, 1–9)

Sickle cell disease (SCD) is blood disorder with a high risk for cerebral vascular morbidities that impact neurocognitive functioning. Specific cognitive abilities are known to be more sensitive to neurologic effects of SCD than IQ scores, yet there is little consensus about which measures to use to assess neurocognitive functioning. We evaluated the ability of the Executive Abilities: Methods and Instruments for Neurobehavioral Evaluation and Research (EXAMINER) Battery to detect neurologic effects in SCD. Thirty-two youth with SCD and sixty demographically-matched comparison youth completed the EXAMINER Battery and selected tests from the Woodcock-Johnson Tests of Cognitive Ability, 3rd edition (WJ-III). Neurologic severity was examined via clinical history for morbidities and midsagittal corpus callosum (CC) area. Results indicated cognitive performance decreased with increasing neurologic morbidity across all cognitive measures; two of four EXAMINER factors were related to CC area. The association with clinical history and midsagittal CC area appeared at least as large for the Examiner Battery scores as for the WJ-III measures. The Examiner Battery showed sensitivity to neurologic history and white matter effects in SCD; this new measure compares favorably to established measures of disease-related neurocognitive effects, but would benefit from further development. (JINS, 2014, 1, 1–12)

This study describes psychometric properties of the NIH Toolbox Cognition Battery (NIHTB-CB) executive function measures in an adult sample. The NIHTB-CB was designed for use in epidemiologic studies and clinical trials for ages 3 to 85. A total of 268 self-described healthy adults were recruited at four university-based sites, using stratified sampling guidelines to target demographic variability for age (20–85 years), gender, education and ethnicity. The NIHTB-CB contains two computer-based instruments assessing executive function: the Dimensional Change Card Sort (a measure of cognitive flexibility) and a flanker task (a measure of inhibitory control and selective attention). Participants completed the NIHTB-CB, corresponding gold standard convergent and discriminant measures, and sociodemographic questionnaires. A subset of participants (N=89) was retested 7 to 21 days later. Results reveal excellent sensitivity to age-related changes during adulthood, excellent test–retest reliability, and adequate to good convergent and discriminant validity. The NIH Toolbox EF measures can be used effectively in epidemiologic and clinical studies. (JINS, 2014, 20, 1–10)

Theories of attention deficit/hyperactivity disorder (ADHD) increasingly highlight the role of neuropsychological impairment in ADHD; however, a consistent and identifiable pattern of performance on tests is not well established. The National Institutes of Health (NIH) Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (EXAMINER) battery provides measures of common variance across multiple executive function tests within specific domains and was used to characterize which executive functions are most affected in children with ADHD. Thirty-two children (24 male), ages 8–15 years (M = 12.02; SD = 2.29), diagnosed with ADHD and no comorbid disorder completed the NIH EXAMINER battery. Sixty age and gender matched healthy controls were chosen from a database of participants enrolled in the NIH EXAMINER multi-site study. Children with ADHD performed worse on the working memory score compared with the controls. No differences were found on the cognitive control or fluency scores. For children with ADHD, poorer working memory performance predicted parent report of child learning problems. Cognitive control and fluency scores did not predict learning problems. In summary, working memory emerges as a primary impairment in children with ADHD who have no comorbid disorders. Furthermore, working memory weaknesses may underlie the academic problems often seen in children with ADHD. (JINS, 2013, 19, 1–11)

Converging evidence indicates that a considerable amount of variance in self-estimated emotional competency can be directly attributed to genetic factors. The current study examined the associations between the polymorphisms of the Catechol-O-methyltransferase (COMT Met158Val) and the serotonin transporter (5-HTTLPR) and specific measures of the self-estimated effectiveness of an individual’s emotion perception and regulation. Emotional competence was measured in a large sample of 289 healthy women by using the Self-report Emotional Ability Scale (SEAS), which includes two subscales for the assessment of emotion perception and regulation in the intra-personal domain and two subscales for the assessment of emotion perception and regulation in the inter-personal domain. Participants’ reports of effective emotion regulation in everyday life were associated with the COMT Met-allele, with women homozygous for the Val-allele scoring lowest on this scale. Self-estimated effectiveness of emotion perception of the individual’s own emotions was related to the 5-HTTLPR. Both homozygous groups (s/s and l/l) rated their intra-personal emotion perception less effective than participants in the heterozygous s/l group. Taken together, the results indicate that genetic variants of the COMT and 5HTTLPR genes are differentially associated with specific measures of the self-estimated effectiveness of an individual’s emotion perception and regulation in the intra-personal domain. (JINS, 2014, 20, 1–9)

Although prospective memory (PM) is compromised in mild cognitive impairment (MCI), it is unclear which specific cognitive processes underlie these PM difficulties. We investigated older adults’ performance on a computerized event-based focal versus nonfocal PM task that made varying demands on the amount of attentional control required to support intention retrieval. Participants were nondemented individuals (mean age=81.8 years; female=66.1%) enrolled in a community-based longitudinal study, including those with amnestic MCI (aMCI), nonamnestic MCI (naMCI), subjective cognitive decline (SCD), and healthy controls (HC). Participants included in the primary analysis (n=189) completed the PM task and recalled and/or recognized both focal and nonfocal PM cues presented in the task. Participants and their informants also completed a questionnaire assessing everyday PM failures. Relative to HC, those with aMCI and naMCI were significantly impaired in focal PM accuracy (p<.05). In a follow-up analysis that included 13 additional participants who successfully recalled and/or recognized at least one of the two PM cues, the naMCI group showed deficits in nonfocal PM accuracy (p<.05). There was a significant negative correlation between informant reports of PM difficulties and nonfocal PM accuracy (p<.01). PM failures in aMCI may be primarily related to impairment of spontaneous retrieval processes associated with the medial temporal lobe system, while PM failures in naMCI potentially indicate additional deficits in executive control functions and prefrontal systems. The observed focal versus nonfocal PM performance profiles in aMCI and naMCI may constitute specific behavioral markers of PM decline that result from compromise of separate neurocognitive systems. (JINS, 2014, 20, 1–13)

Individuals diagnosed with alcohol-related neurodevelopmental disorder (ARND) exhibit difficulty on hippocampally mediated memory tasks and show reduced hippocampal size. However inconsistencies exist regarding the affected memory functions and where within the hippocampi effects occur. Given recent studies showing anterior and posterior segments support distinct memory functions and sex dimorphisms in hippocampal function, we asked whether these factors influence memory performance in youth with ARND (n = 18) and typically developing controls (n = 17). Participants received a battery of memory tests and a structural MRI scan. Right and left hippocampi were manually traced; anterior and posterior segments were delineated at the uncus. Measured were intracranial volumes (ICV) and right and left hippocampi and hippocampal segments. Volumes were adjusted for ICV. Relative to controls, the ARND group had lower IQs and memory performance on most tasks and marginally smaller ICVs. Left and right hippocampal volumes and posterior segments were smaller in the ARND group. Although no sex differences were observed between groups, females overall had larger anterior hippocampi than males. Positive and negative associations between hippocampal and selective memory indices were found in the ARND group only. These findings are the first to suggest that posterior hippocampal development may be compromised in youth with ARND. (JINS, 2014, 20, 181–191)

Memory impairment affects 50% of multiple sclerosis (MS) patients. Altered resting-state functional connectivity (FC) has been observed in the default network (DN) of MS patients. No study to date has examined the association of DN FC to its behavioral concomitant, memory. The approach of the present study represents a methodological shift allowing straightforward interpretation of FC alterations in MS, as it presupposes specificity of a network to its paired cognitive function. We examined FC from fMRI collected during rest in the DN of 43 MS patients with and without memory-impairment. Memory-intact patients showed increased DN FC relative to memory-impaired patients. There were no regions of higher FC in memory-impaired patients. DN FC was positively correlated with memory function, such that higher FC was associated with better memory performance. Results were unchanged after controlling for cognitive efficiency, supporting specificity of the DN to memory and not cognitive status more generally. These findings support DN FC as a marker of memory function in MS patients that can be targeted by future treatment interventions. Pairing a functional network with its behavioral concomitant represents a straightforward method for interpreting FC alterations in patients with MS. (JINS, 2014, 20, 1–8)

The NIH Toolbox (NIHTB) Pattern Comparison Processing Speed Test was developed to assess processing speed within the NIHTB for the Assessment of Neurological Behavior and Function Cognition Battery (NIHTB-CB). This study highlights validation data collected in adults ages 18–85 on this measure and reports descriptive data, test–retest reliability, construct validity, and preliminary work creating a composite index of processing speed. Results indicated good test–retest reliability. There was also evidence for both convergent and discriminant validity; the Pattern Comparison Processing Speed Test demonstrated moderate significant correlations with other processing speed tests (i.e., WAIS-IV Coding, Symbol Search and Processing Speed Index), small significant correlations with measures of working memory (i.e., WAIS-IV Letter-Number Sequencing and PASAT), and non-significant correlations with a test of vocabulary comprehension (i.e., PPVT-IV). Finally, analyses comparing and combining scores on the NIHTB Pattern Comparison Processing Speed Test with other measures of simple reaction time from the NIHTB-CB indicated that a Processing Speed Composite score performed better than any test examined in isolation. The NIHTB Pattern Comparison Processing Speed Test exhibits several strengths: it is appropriate for use across the lifespan (ages, 3–85 years), it is short and easy to administer, and it has high construct validity. (JINS, 2014, 20, 1–12)

Reduced IQ, learning difficulties and poor school performance have been reported in small-for-gestational-age (SGA) subjects. However, few studies include a comprehensive neuropsychological assessment. Our aim was to study neuropsychological functioning in young adults born SGA at term. A comprehensive neuropsychological test battery was administered to 58 SGA subjects (birth weight <10th centile) born at term, and 81 term non-SGA controls (birth weight ≥10th centile). The SGA group obtained significantly (p < .01) lower scores on the attention, executive and memory domains compared to non-SGA controls and showed higher risk of obtaining scores below −1.5 SD on the memory domain (odds ratio = 13.3, 95% confidence interval: 1.57, 112.47). At a subtest level, the SGA group obtained lower scores on most neuropsychological tests, with significant differences on 6 of 46 measures: the Trail Making Test 3 (letter sequencing), the Wechsler Memory Scale mental control and the auditory immediate memory scale, the Design Fluency, the Stroop 3 (inhibition) and the Visual Motor Integration (VMI) motor coordination subtest. Young adults born SGA score more poorly on neuropsychological tests compared with non-SGA controls. Differences were modest, with more significant differences in the memory domain. (JINS, 2014, 20, 1–11)

The n-back task is a widely used neuroimaging paradigm for studying the neural basis of working memory (WM); however, its neuropsychometric properties have received little empirical investigation. The present study merged clinical neuropsychology and functional magnetic resonance imaging (fMRI) to explore the construct validity of the letter variant of the n-back task (LNB) and to further identify the task-evoked networks involved in WM. Construct validity of the LNB task was investigated using a bootstrapping approach to correlate LNB task performance across clinically validated neuropsychological measures of WM to establish convergent validity, as well as measures of related but distinct cognitive constructs (i.e., attention and short-term memory) to establish discriminant validity. Independent component analysis (ICA) identified brain networks active during the LNB task in 34 healthy control participants, and general linear modeling determined task-relatedness of these networks. Bootstrap correlation analyses revealed moderate to high correlations among measures expected to converge with LNB (|ρ|≥0.37) and weak correlations among measures expected to discriminate (|ρ|≤0.29), controlling for age and education. ICA identified 35 independent networks, 17 of which demonstrated engagement significantly related to task condition, controlling for reaction time variability. Of these, the bilateral frontoparietal networks, bilateral dorsolateral prefrontal cortices, bilateral superior parietal lobules including precuneus, and frontoinsular network were preferentially recruited by the 2-back condition compared to 0-back control condition, indicating WM involvement. These results support the use of the LNB as a measure of WM and confirm its use in probing the network-level neural correlates of WM processing. (JINS, 2014, 20, 1–15)

Patterns of verbal fluency deficits have been explored across different neurodegenerative disorders. This study sought to investigate the specific pattern of verbal fluency performance in cerebral small vessel disease (SVD), which is the most common cause of vascular cognitive impairment, and compare this with Alzheimer's disease (AD). Participants with SVD (n = 45), AD (n = 24) and healthy controls (n = 80) completed assessments of semantic and phonemic fluency. Mixed-model analyses of covariance were used to compare performance on the different fluency tasks between the groups, and a discriminant function analysis was conducted to examine group differentiation. The SVD group was impaired in both fluency tasks when compared to the controls. In contrast, the AD group displayed impairment in semantic fluency only. Discriminant function analysis revealed that fluency scores correctly classified 80% of SVD patients and 92% of AD patients. The pattern of performance observed in the SVD group may reflect deficits in executive function and processing speed impacting equivalently on semantic and phonemic fluency. The differences between the SVD and AD groups highlighted in this study may be useful for distinguishing between these conditions. (JINS, 2014, 20, 1–9)

Subjective cognitive complaints are a criterion for the diagnosis of mild cognitive impairment (MCI), despite their uncertain relationship to objective memory performance in MCI. We aimed to examine self-reported cognitive complaints in subgroups of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) MCI cohort to determine whether they are a valuable inclusion in the diagnosis of MCI or, alternatively, if they contribute to misdiagnosis. Subgroups of MCI were derived using cluster analysis of baseline neuropsychological test data from 448 ADNI MCI participants. Cognitive complaints were assessed via the Everyday Cognition (ECog) questionnaire, and discrepancy scores were calculated between self- and informant-report. Cluster analysis revealed Amnestic and Mixed cognitive phenotypes as well as a third Cluster-Derived Normal subgroup (41.3%), whose neuropsychological and cerebrospinal fluid (CSF) Alzheimer’s disease (AD) biomarker profiles did not differ from a “robust” normal control group. This cognitively intact phenotype of MCI participants overestimated their cognitive problems relative to their informant, whereas Amnestic MCI participants with objective memory impairment underestimated their cognitive problems. Underestimation of cognitive problems was associated with positive CSF AD biomarkers and progression to dementia. Overall, there was no relationship between self-reported cognitive complaints and objective cognitive functioning, but significant correlations were observed with depressive symptoms. The inclusion of self-reported complaints in MCI diagnostic criteria may cloud rather than clarify diagnosis and result in high rates of misclassification of MCI. Discrepancies between self- and informant-report demonstrate that overestimation of cognitive problems is characteristic of normal aging while underestimation may reflect greater risk for cognitive decline. (JINS, 2014, 20, 1–12)

The use of videoconference technology to deliver health care diagnostics and treatment continues to grow at a rapid pace. Telepsychiatry and telepsychology applications are well-accepted by patients and providers, and both diagnostic and treatment outcomes have generally been similar to traditional face-to-face interactions. Preliminary applications of videoconference-based neuropsychological assessment (teleneuropsychology) have yielded promising results in the feasibility and reliability of several standard tests, although large-scale studies are lacking. This investigation was conducted to determine the reliability of video teleconference (VTC) - based neuropsychological assessment using a brief battery of standard neuropsychological tests commonly used in the evaluation of known or suspected dementia. Tests included the Mini-Mental State Examination (MMSE), Hopkins Verbal Learning Test-Revised, Digit Span forward and backward, short form Boston Naming Test, Letter and Category Fluency, and Clock Drawing. Tests were administered via VTC and in-person to subjects, counterbalanced using alternate test forms and standard instructions. Two hundred two adult subjects were tested in both rural and urban settings, including 83 with cognitive impairment and 119 healthy controls. We found highly similar results across VTC and in-person conditions, with significant intraclass correlations (mean=.74; range: 0.55–0.91) between test scores. Findings remained consistent in subjects with or without cognitive impairment and in persons with MMSE scores as low as 15. VTC-based neuropsychological testing is a valid and reliable alternative to traditional face-to-face assessment using selected measures. More VTC-based studies using additional tests in different populations are needed to fully explore the utility of this new testing medium. (JINS, 2014, 20, 1–6)

Prospective memory (PM) is dependent on executive processes known to be impaired in Huntington's disease (HD); however, no study to the authors’ knowledge has investigated PM in this group. We examined performance-based, semi-naturalistic, and self-reported PM in 20 individuals diagnosed with mild–moderate HD and 20 demographically similar controls. Relative to controls, HD participants demonstrated significantly lower scores in time-based PM, event-based PM (at a trend level), and the semi-naturalistic PM trial, all of which were marked by omission errors. HD participants demonstrated comparable recognition memory for the PM intentions relative to controls. HD and control participants also showed comparable scores in self-reported PM complaints. The results suggest that HD is associated with deficits in the strategic aspects of PM. HD-associated PM deficits also are evident in real-world situations, which may relate to an apparent meta-memory deficit for PM functioning as indicated by HD participants’ overestimation of their PM performance on self-report. (JINS, 2014, 20, 1–8)

Executive functions (EF) encompass a variety of higher-order capacities such as judgment, planning, decision-making, response monitoring, insight, and self-regulation. Measuring such abilities quantitatively and establishing their neural correlates has proven to be challenging. Here, using a lesion-deficit approach, we report the neural correlates of a variety of EF tests that were developed under the auspices of the NINDS-supported EXAMINER project (Kramer, 2011; www.examiner.ucsf.edu). We administered a diverse set of EF tasks that tap three general domains—cognitive, social/emotional, and insight—to 37 patients with focal lesions to the frontal lobes, and 25 patients with lesions outside the frontal lobes. Using voxel-based lesion-symptom mapping (VLSM), we found that damage to the ventromedial prefrontal cortex (vmPFC) was predominately associated with deficits in social/emotional aspects of EF, while damage to dorsolateral prefrontal cortex (dlPFC) and anterior cingulate was predominately associated with deficits in cognitive aspects of EF. Evidence for an important role of some non-frontal regions (e.g., the temporal poles) in some aspects of EF was also found. The results provide further evidence for the neural basis of EF, and extend previous findings of the dissociation between the roles of the ventromedial and dorsolateral prefrontal sectors in organizing, implementing, and monitoring goal-directed behavior. (JINS, 2013, 19, 1–12)

We aimed to identify brain functional correlates of working memory performance in aging, in hopes of facilitating understanding of mechanisms that promote better versus worse working memory in late-life. Among 64 healthy adults, aged 23 to 78, we examined the relationship between age, working memory performance, and brain functional response during task performance. We focused on the association between working memory load-modulated functional response and individual differences in performance and whether these function-performance relationships differed with age. As expected, older age was associated with poorer working memory performance. Older age was also associated with reduced load-modulated activation including in bilateral prefrontal and parietal regions and left caudate as well as reduced deactivation including in the medial prefrontal cortex. Contrary to findings of hyperactivation in aging, we found no evidence of increased activation with older age. Positive associations identified between brain response and performance did not differ with age. Our findings suggest that the neural mechanisms underlying better versus worse working memory performance are age-invariant across adulthood, and argue against a pattern of functional reorganization in aging. Results are discussed within the broader literature, in which significant heterogeneity in findings between studies has been common. (JINS, 2014, 20, 1–6)

Approximately 50% of persons with multiple sclerosis experience cognitive impairment, which adversely affects daily functioning. Although patients report that fatigue contributes to cognitive difficulties, previous empirical studies do not show a clear association. This study assessed coping style as a moderator of the relationship between fatigue and cognition in a 3-year longitudinal sample. Scores on the Fatigue Impact Scale and the Coping Orientation to Problems Experienced (COPE) at baseline were modeled to predict later performance on a composite of cognitive tests to investigate the hypothesis that coping would have a significant moderating effect on fatigue in predicting cognitive performance. Findings partially supported hypotheses by showing that avoidant coping moderated the relationship between fatigue and cognitive performance. Patients who experienced relatively high fatigue performed better on cognitive tests if they used less avoidant coping. Those who reported lower fatigue had relatively good cognitive performance regardless of their coping style. This study provides evidence that coping style is associated with the ability to deal with stress, like fatigue, and their interaction can impact functional outcomes of disease. These results could benefit understanding of prognosis and improve treatment for patients with MS. (JINS, 2014, 20, 1–5.)

Language facilitates communication and efficient encoding of thought and experience. Because of its essential role in early childhood development, in educational achievement and in subsequent life adaptation, language was included as one of the subdomains in the NIH Toolbox for the Assessment of Neurological and Behavioral Function Cognition Battery (NIHTB-CB). There are many different components of language functioning, including syntactic processing (i.e., morphology and grammar) and lexical semantics. For purposes of the NIHTB-CB, two tests of language—a picture vocabulary test and a reading recognition test—were selected by consensus based on literature reviews, iterative expert input, and a desire to assess in English and Spanish. NIHTB-CB’s picture vocabulary and reading recognition tests are administered using computer adaptive testing and scored using item response theory. Data are presented from the validation of the English versions in a sample of adults ages 20–85 years (Spanish results will be presented in a future publication). Both tests demonstrated high test–retest reliability and good construct validity compared to corresponding gold-standard measures. Scores on the NIH Toolbox measures were consistent with age-related expectations, namely, growth in language during early development, with relative stabilization into late adulthood. (JINS, 2014, 20, 1–10)