The objective of this study is to investigate the relationships among frontotemporal fiber tract compromise and task-switching performance in healthy controls and patients with temporal lobe epilepsy (TLE). We performed diffusion tensor imaging (DTI) on 30 controls and 32 patients with TLE (15 left TLE). Fractional anisotropy (FA) was calculated for four fiber tracts [uncinate fasciculus (UncF), arcuate fasciculus (ArcF), dorsal cingulum (CING), and inferior fronto-occipital fasciculus (IFOF)]. Participants completed the Trail Making Test-B (TMT-B) and Verbal Fluency Category Switching (VFCS) test. Multivariate analyses of variances (MANOVAs) were performed to investigate group differences in fiber FA and set-shifting performances. Canonical correlations were used to examine the overall patterns of structural-cognitive relationships and were followed by within-group bivariate correlations. We found a significant canonical correlation between fiber FA and task-switching performance. In controls, TMT-B correlated with left IFOF, whereas VFCS correlated with FA of left ArcF and left UncF. These correlations were not significant in patients with TLE. We report significant correlations between frontotemporal fiber tract integrity and set-shifting performance in healthy controls that appear to be absent or attenuated in patients with TLE. These findings suggest a breakdown of typical structure-function relationships in TLE that may reflect aberrant developmental or degenerative processes. (JINS, 2012, 18, 57–67)

Both HIV infection and high levels of early life stress (ELS) have been related to abnormalities in frontal-subcortical structures, yet the combined effects of HIV and ELS on brain structure and function have not been previously investigated. In this study we assessed 49 non-demented HIV-seropositive (HIV+) and 47 age-matched HIV-seronegative healthy control (HC) adults. Levels of ELS exposure were quantified and used to define four HIV-ELS groups: HC Low-ELS (N = 20); HC High-ELS (N = 27); HIV+ Low-ELS (N = 24); HIV+ High-ELS (N = 25). An automated segmentation tool measured volumes of brain structures known to show HIV-related or ELS-related effects; a brief neurocognitive battery was administered. A significant HIV-ELS interaction was observed for amygdala volumes, which was driven by enlargements in HIV+ High-ELS participants. The HIV+ High-ELS group also demonstrated significant reductions in psychomotor/processing speed compared with HC Low-ELS. Regression analyses in the HIV+ group revealed that amygdala enlargements were associated with higher ELS, lower nadir CD4 counts, and reduced psychomotor/processing speed. Our results suggest that HIV infection and high ELS interact to increase amygdala volume, which is associated with neurocognitive dysfunction in HIV+ patients. These findings highlight the lasting neuropathological influence of ELS and suggest that high ELS may be a significant risk factor for neurocognitive impairment in HIV-infected individuals. (JINS, 2012, 19, 1–12)

Identification of preclinical Alzheimer's disease (AD) is an essential first step in developing interventions to prevent or delay disease onset. In this study, we examine the hypothesis that deeper analyses of traditional cognitive tests may be useful in identifying subtle but potentially important learning and memory differences in asymptomatic populations that differ in risk for developing Alzheimer's disease. Subjects included 879 asymptomatic higher-risk persons (middle-aged children of parents with AD) and 355 asymptotic lower-risk persons (middle-aged children of parents without AD). All were administered the Rey Auditory Verbal Learning Test at baseline. Using machine learning approaches, we constructed a new measure that exploited finer differences in memory strategy than previous work focused on serial position and subjective organization. The new measure, based on stochastic gradient descent, provides a greater degree of statistical separation (p = 1.44 × 10−5) than previously observed for asymptomatic family history and non-family history groups, while controlling for apolipoprotein epsilon 4, age, gender, and education level. The results of our machine learning approach support analyzing memory strategy in detail to probe potential disease onset. Such distinct differences may be exploited in asymptomatic middle-aged persons as a potential risk factor for AD. (JINS, 2012, 18, 428–439)

Previous dual task studies have demonstrated that patients with sporadic Alzheimer's disease (AD) are impaired in their ability to perform two tasks simultaneously compared with healthy controls, despite being able to successfully perform the tasks alone relatively well. Yet, it remains unclear what the earliest clinical manifestation of this dual task coordination deficit is. This study examined dual task abilities in individuals who are at risk of early-onset familial AD due to an E280A presenilin-1 mutation. Thirty-nine carriers of the gene mutation who did not meet the criteria for AD and 29 non-carrier healthy controls were asked to perform digit recall accompanied by a secondary tracking task. Individuals who were carriers of the genetic mutation demonstrated significantly higher dual task costs than healthy non-carriers. Dual task performance was found to be more sensitive to this very early stage of FAD than episodic memory measures. The findings support the notion that a deficit in the coordination mechanism of the central executive may be a pre-clinical marker for the early detection of AD due to the E280A presenilin-1 gene mutation. (JINS, 2012, 18, 234–241)

Virtual reality (VR) assessment paradigms have the potential to address the limited ecological validity of pen and paper measures of executive function (EF) and the pragmatic and reliability issues associated with functional measures. To investigate the ecological validity and construct validity of a newly developed VR measure of EF, the Virtual Library Task (VLT); a real life analogous task—the Real Library Task (RLT); and five neuropsychological measures of EF were administered to 30 patients with traumatic brain injury (TBI) and 30 healthy Controls. Significant others for each participant also completed the Dysexecutive Questionnaire (DEX), which is a behavioral rating scale of everyday EF. Performances on the VLT and the RLT were significantly positively correlated indicating that VR performance is similar to real world performance. The TBI group performed significantly worse than the Control group on the VLT and the Modified Six Elements Test (MSET) but the other four neuropsychological measures of EF failed to differentiate the groups. Both the MSET and the VLT significantly predicted everyday EF suggesting that they are both ecologically valid tools for the assessment of EF. The VLT has the advantage over the MSET of providing objective measurement of individual components of EF. (JINS, 2012, 18, 440–450)

HIV-associated neurocognitive dysfunction persists in the highly active antiretroviral therapy (HAART) era and may be exacerbated by comorbidities, including substance use and hepatitis C virus (HCV) infection. However, the neurocognitive impact of HIV, HCV, and substance use in the HAART era is still not well understood. In the current study, 115 HIV-infected and 72 HIV-seronegative individuals with significant rates of lifetime substance dependence and HCV infection received comprehensive neuropsychological assessment. We examined the effects of HIV serostatus, HCV infection, and substance use history on neurocognitive functioning. We also examined relationships between HIV disease measures (current and nadir CD4, HIV RNA, duration of infection) and cognitive functioning. Approximately half of HIV-infected participants exhibited neurocognitive impairment. Detectable HIV RNA but not HIV serostatus was significantly associated with cognitive functioning. HCV was among the factors most consistently associated with poorer neurocognitive performance across domains, while substance use was less strongly associated with cognitive performance. The results suggest that neurocognitive impairment continues to occur in HIV-infected individuals in association with poor virologic control and comorbid conditions, particularly HCV coinfection. (JINS, 2012, 18, 68–78)

The Montreal Cognitive Assessment (MoCA) is a brief instrument developed for the screening of milder forms of cognitive impairment. The present study aims to assess the construct related validity of the MoCA through the establishment of the factorial, convergent, and discriminant related validities, and the reliability of data. In a Portuguese sample of 830 participants, several models were tested using Confirmatory Factor Analysis. Although all tested models showed a good fit, the six-factor model based on the conceptual model proposed by the MoCA's authors showed a significantly better fit. The results allowed us to establish the factorial, convergent, and discriminant validity of this six-dimensional structure. An overall psychometric adequacy of the items, and a good reliability were also found. This study contributes to overcome an important gap in the construct related validity of this instrument. The present findings corroborate the six-dimensional structure of the MoCA and provide good evidence of the construct related validity. The MoCA has proved to be an appropriate measure for cognitive screening taking into account different cognitive domains, which will enable clinicians and researchers to use this test and its six latent dimensions to achieve a better understanding of the individuals’ cognitive profile. (JINS, 2012, 18, 242–250)

This study explored whether remote blast-related MTBI and/or current Axis I psychopathology contribute to neuropsychological outcomes among OEF/OIF veterans with varied combat histories. OEF/OIF veterans underwent structured interviews to evaluate history of blast-related MTBI and psychopathology and were assigned to MTBI (n = 18), Axis I (n = 24), Co-morbid MTBI/Axis I (n = 34), or post-deployment control (n = 28) groups. A main effect for Axis I diagnosis on overall neuropsychological performance was identified (F(3,100) = 4.81; p = .004), with large effect sizes noted for the Axis I only (d = .98) and Co-morbid MTBI/Axis I (d = .95) groups relative to the control group. The latter groups demonstrated primary limitations on measures of learning/memory and processing speed. The MTBI only group demonstrated performances that were not significantly different from the remaining three groups. These findings suggest that a remote history of blast-related MTBI does not contribute to objective cognitive impairment in the late stage of injury. Impairments, when present, are subtle and most likely attributable to PTSD and other psychological conditions. Implications for clinical neuropsychologists and future research are discussed. (JINS, 2012, 18, 1–11)

While longitudinal studies of children treated for brain tumors have consistently revealed declines on measures of intellectual functioning, greater specification of cognitive changes following treatment is imperative for isolating vulnerable neural systems and developing targeted interventions. Accordingly, this cross-sectional study evaluated the performance of childhood brain tumor survivors (n = 50) treated with conformal radiation therapy, solid tumor survivors (n = 40) who had not received central nervous system (CNS) -directed therapy, and healthy sibling controls (n = 40) on measures of working memory [Digit Span and computerized self-ordered search (SOS) tasks]. Findings revealed childhood brain tumor survivors were impaired on both traditional [Digit Span Backward- F(2,127)= 5.98; p < .01] and experimental [SOS-Verbal- F(2,124)= 4.18; p < .05; SOS-Object- F(2,126)= 5.29; p < .01] measures of working memory, and performance on working memory measures correlated with intellectual functioning (Digit Span Backward- r = .45; p < .0001; SOS- r = −.32 to −.26; p < .01). Comparison of performance on working memory tasks to recognition memory tasks (computerized delayed match-to-sample) offered some support for greater working memory impairment. This pattern of findings is consistent with vulnerability in functional networks that include prefrontal brain regions and has implications for the clinical management of children with brain tumors. (JINS, 2012, 18, 1–10)

Systematic cognitive training produces long-term improvement in cognitive function and less difficulty in performing activities of daily living. We examined whether cognitive training was associated with reduced rate of incident dementia. Participants were from the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study (n = 2,802). Incident dementia was defined using a combination of interview- and performance-based methods. Survival analysis was used to determine if ACTIVE treatment affected the rate of incident dementia during 5 years of follow-up. A total of 189 participants met criteria for incident dementia. Baseline factors predictive of incident dementia were older age, male gender, African American race, fewer years of education, relationship other than married, no alcohol use, worse MMSE, worse SF-36 physical functioning, higher depressive symptomatology, diabetes, and stroke (all p < .05). A multivariable model with significant predictors of incident dementia and training group revealed that cognitive training was not associated with a lower rate of incident dementia. Cognitive training did not affect rates of incident dementia after 5 years of follow-up. Longer follow-up or enhanced training may be needed to fully explore the preventive capacity of cognitive training in forestalling onset of dementia. (JINS, 2012, 18, 1–9)

After traumatic injury, the brain undergoes a prolonged period of degenerative change that is paradoxically accompanied by cognitive recovery. The spatiotemporal pattern of atrophy and the specific relationships of atrophy to cognitive changes are ill understood. The present study used tensor-based morphometry and neuropsychological testing to examine brain volume loss in 17 traumatic brain injury (TBI) patients and 13 controls over a 4-year period. Patients were scanned at 2 months, 1 year, and 4 years post-injury. High-dimensional warping procedures were used to create change maps of each subject's brain for each of the two intervals. TBI patients experienced volume loss in both cortical areas and white matter regions during the first interval. We also observed continuing volume loss in extensive regions of white matter during the second interval. Neuropsychological correlations indicated that cognitive tasks were associated with subsequent volume loss in task-relevant regions. The extensive volume loss in brain white matter observed well beyond the first year post-injury suggests that the injured brain remains malleable for an extended period, and the neuropsychological relationships suggest that this volume loss may be associated with subtle cognitive improvements. (JINS, 2012, 18, 1–13)

This study sought to characterize neuropsychological functioning in MJ-using adolescents and emerging adults (ages 18–26) and to investigate whether gender moderated these effects. Data were collected from 59 teens and emerging adults including MJ users (n = 23, 56% female) and controls (n = 35, 50% female) aged 18–26 (M = 21 years). Exclusionary criteria included independent Axis I disorders (besides SUD), and medical and neurologic disorders. After controlling for reading ability, gender, subclinical depressive symptoms, body mass index, and alcohol and other drug use, increased MJ use was associated with slower psychomotor speed/sequencing ability (p < .01), less efficient sustained attention (p < .05), and increased cognitive inhibition errors (p < .03). Gender significantly moderated the effects of MJ on psychomotor speed/sequencing ability (p < .003) in that males had a more robust negative relationship. The current study demonstrated that MJ exposure was associated with poorer psychomotor speed, sustained attention and cognitive inhibition in a dose-dependent manner in young adults, findings that are consistent with other samples of adolescent MJ users. Male MJ users demonstrated greater cognitive slowing than females. Future studies need to examine the neural substrates underlying with these cognitive deficits and whether cognitive rehabilitation or exercise interventions may serve as a viable treatments of cognitive deficits in emerging adult MJ users. (JINS, 2012, 18, 1–11)

Mild traumatic brain injury (mild TBI) is often associated with postconcussive symptoms such as headache, memory problems, and irritability. However, high rates of similar symptoms in groups without a history of TBI raise questions about the clinical validity of the postconcussive syndrome. This study was conducted to address these issues through systematic examination of symptoms reported by those with and without a history of mild TBI or orthopedic injury. Responses to the Postconcussion Syndrome Checklist (PCSC), demographic information, and medical history were collected via online questionnaire from 3027 non-referred university students (2280 without a history of mild TBI or orthopedic injury, 491 with a history of orthopedic injury, and 256 with post-acute mild TBI). Although the mild TBI group reported higher mean levels of symptoms, confirmatory factor analyses demonstrated that symptoms clustered into parallel cognitive, somatic, affective, and sensory factors in all three groups. Despite modestly higher mean symptoms among those with a history of mild TBI, symptom clusters did not differ from non-TBI groups. These findings cast doubts about the clinical validity of the “postconcussive syndrome” and raise questions about pathways by which mild TBI and other factors may influence the expression of chronic symptoms. (JINS, 2012, 18, 451–460)

Three types of HIV-associated neurocognitive disorders (HAND) exist that are distinguished by presence and severity of impairment in cognitive and everyday functioning. Although well-validated neurocognitive measures exist, determining impairment in everyday functioning remains a challenge. We aim to determine whether Self-Report measures of everyday functioning are as effective in characterizing HAND as Performance-Based measures. We assessed 674 HIV-infected participants with a comprehensive neurocognitive battery; 233 met criteria for a HAND diagnosis by having at least mild neurocognitive impairment. Functional decline was measured via Self-Report and Performance-Based measures. HAND diagnoses were determined according to published criteria using three approaches to assess functional decline: (1) Self-Report measures only, (2) Performance-Based measures only, and (3) Dual-method combining Self-Report and Performance-Based measures. The Dual-method classified the most symptomatic HAND, compared to either singular method. Singular method classifications were 76% concordant with each other. Participants classified as Performance-Based functionally impaired were more likely to be unemployed and more immunosuppressed, whereas those classified as Self-Report functionally impaired had more depressive symptoms. Multimodal methods of assessing everyday functioning facilitate detection of symptomatic HAND. Singular Performance-Based classifications were associated with objective functional and disease-related factors; reliance on Self-Report classifications may be biased by depressive symptoms. (JINS, 2012, 18, 79–88)

Neurologically normal individuals show a bias toward the left side of space, referred to as pseudoneglect due to its similarity to clinical hemispatial neglect. The left bias appears to be stronger in the lower visual field during free-viewing, which could result from preferential dorsal stream processing. The current experiments used modified greyscales tasks, incorporating motion and isoluminant color, to explore whether targeting dorsal or ventral stream processing influenced the strength of the left bias. It was expected that the left bias would be stronger on the motion task than on a task incorporating isoluminant color. In Study 1, similar left biases were observed during prolonged viewing for luminance, motion and red, but not green color. The unexpected finding of a leftward bias for red under prolonged viewing was replicated in Study 2. A leftward bias for motion was also evident during 150 ms viewing in Study 2. In Study 3, the left bias was not apparent when using a blue/yellow condition, suggesting the left bias for red under prolonged viewing was likely unique to red. Furthermore, the leftward bias for red disappeared under brief viewing conditions. It is suggested that dorsal stream processing likely underlies visual field differences in pseudoneglect. (JINS, 2012, 18, 251–259)

Existing evidence suggests that psychosocial stress is associated with cognitive impairment in older adults. Perceived discrimination is a persistent stressor in African Americans that has been associated with several adverse mental and physical health outcomes. To our knowledge, the association of discrimination with cognition in older African Americans has not been examined. In a cohort of 407 older African Americans without dementia (mean age = 72.9; SD = 6.4), we found that a higher level of perceived discrimination was related to poorer cognitive test performance, particularly episodic memory (estimate = −0.03; SE = .013; p < .05) and perceptual speed tests (estimate = −0.04; SE = .015; p < .05). The associations were unchanged after adjusting for demographics and vascular risk factors, but were attenuated after adjustment for depressive symptoms (Episodic memory estimate = −0.02; SE = 0.01; Perceptual speed estimate = −0.03; SE = 0.02; both p's = .06). The association between discrimination and several cognitive domains was modified by level of neuroticism. The results suggest that perceived discrimination may be associated with poorer cognitive function, but does not appear to be independent of depressive symptoms. (JINS, 2012, 18, 1–10)

Participants diagnosed with mild cognitive impairment (MCI), dementia and controls completed measures that required decoding emotions from point-light displays of bodily motion, and static images of facial affect. Both of these measures tap social cognitive processes that are considered critical for social competency. Consistent with prior literature, both clinical groups were impaired on the static measure of facial affect recognition. The dementia (but not the MCI) group additionally showed difficulties interpreting biological motion cues. However, this did not reflect a specific deficit in decoding emotions, but instead a more generalized difficulty in processing visual motion (both to action and to emotion). These results align with earlier studies showing that visual motion processing is disrupted in dementia, but additionally show for the first time that this extends to the recognition of socially relevant biological motion. The absence of any MCI related impairment on the point-light biological emotion measure (coupled with deficits on the measure of facial affect recognition) also point to a potential disconnect between the processes implicated in the perception of emotion cues from static versus dynamic stimuli. For clinical (but not control) participants, performance on all recognition measures was inversely correlated with level of semantic memory impairment. (JINS, 2012, 18, 1–8)

Individuals with amnestic mild cognitive impairment (aMCI) show deficits on traditional episodic memory tasks and reductions in speed of performance on reaction time tasks. We present results on a novel task, the Cued-Recall Retrieval Speed Task (CRRST), designed to simultaneously measure level and speed of retrieval. A total of 390 older adults (mean age, 80.2 years), learned 16 words based on corresponding categorical cues. In the retrieval phase, we measured accuracy (% correct) and retrieval speed/reaction time (RT; time from cue presentation to voice onset of a correct response) across 6 trials. Compared to healthy elderly adults (HEA, n = 303), those with aMCI (n = 87) exhibited poorer performance in retrieval speed (difference = −0.13; p < .0001) and accuracy on the first trial (difference = −0.19; p < .0001), and their rate of improvement in retrieval speed was slower over subsequent trials. Those with aMCI also had greater within-person variability in processing speed (variance ratio = 1.22; p = .0098) and greater between-person variability in accuracy (variance ratio = 2.08; p = .0001) relative to HEA. Results are discussed in relation to the possibility that computer-based measures of cued-learning and processing speed variability may facilitate early detection of dementia in at-risk older adults. (JINS, 2012, 18, 260–268)

Explosive blast is a frequent cause of traumatic brain injury (TBI) among personnel deployed to Afghanistan and Iraq. Functional magnetic resonance imaging (fMRI) with an event-related stimulus-response compatibility task was used to compare 15 subjects with mild, chronic blast-related TBI with 15 subjects who had not experienced a TBI or blast exposure during deployment. Six TBI subjects reported multiple injuries. Relative to the control group, TBI subjects had slightly slower responses during fMRI and increased somatic complaints and symptoms of post-traumatic stress disorder (PTSD) and depression. A between-group analysis indicated greater activation during stimulus-response incompatibility in TBI subjects within the anterior cingulate gyrus, medial frontal cortex, and posterior cerebral areas involved in visual and visual-spatial functions. This activation pattern was more extensive after statistically controlling for reaction time and symptoms of PTSD and depression. There was also a negative relationship between symptoms of PTSD and activation within posterior brain regions. These results provide evidence for increased task-related activation following mild, blast-related TBI and additional changes associated with emotional symptoms. Limitations of this study include no matching for combat exposure and different recruitment strategies so that the control group was largely a community-based sample, while many TBI subjects were seeking services. (JINS, 2012, 18, 89–100)

We tested the hypothesis that maternal worm infections in pregnancy affect infant motor and neurocognitive development, and that anthelminthic treatment during pregnancy can reverse these effects. We used measures which examine infant motor, cognitive and executive function, including inhibition. We assessed 983 Ugandan infants aged 15 months, using locally appropriate measures within the Entebbe Mother and Baby Study, a trial of anthelminthic treatment during pregnancy. Key exposures were maternal worm infections and anthelminthic treatment during pregnancy. Effects of other health and social factors were controlled for statistically. Of the five major worm species found in the pregnant women, two had influences on the developmental measures: Maternal Mansonella perstans and Strongyloides stercoralis infections showed negative associations with the A-not B-task, and Language, respectively. Performance on other psychomotor and cognitive measures was associated with illnesses during infancy and infants’ behavior during assessment, but not with maternal worm infections. There were no positive effects of maternal anthelminthic treatment on infant abilities. Mansonella perstans and Strongyloides stercoralis infection during pregnancy seem associated with impaired early executive function and language, respectively, but single-dose anthelminthic treatment during pregnancy was not beneficial. The biological mechanisms that could underlie these neurocognitive effects are discussed. (JINS, 2012, 18, 1019–1030)