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)

Inhibition of return is a bias in attention that reduces the likelihood of returning attention to previously viewed locations. This attention bias develops during the first 6 months of life and is putatively mediated by midbrain structures. The present study evaluated the effects of perinatal lesions on the development of inhibition of return. Thirty-three children with perinatal injury resulting in spastic diplegic cerebral palsy were grouped based on magnetic resonance exams. Children with anterior (n = 5), posterior (n = 12), diffuse (n = 8), or no apparent (n = 8) lesions were compared with a group of age-matched children without neurologic injury (n = 39) on an orienting task designed to elicit inhibition of return. Short-delay trials demonstrated grossly intact facilitation of attention for all groups. Long-delay trials that produced inhibition of return in the control and posterior injury groups indicated a disruption of inhibition of return in the groups with anterior and diffuse lesions. The findings are consistent with previous reports that anterior regions are important for the developing attention system, and that bilateral injury can result in unilateral disruption of visual attention. (JINS, 2001, 7, 275–284.)

Metabolic syndrome (MetS) is a clustering of vascular risk factors and is associated with increased risk of cardiovascular disease. Less is known about the relationship between MetS and cognition. We examined component vascular risk factors of MetS as correlates of different cognitive domains. The Northern Manhattan Study (NOMAS) includes 1290 stroke-free participants from a largely Hispanic multi-ethnic urban community. We used structural equation modeling (SEM) to model latent variables of MetS, assessed at baseline and an average of 10 years later, at which time participants also underwent a full cognitive battery. The two four-factor models, of the metabolic syndrome (blood pressure, lipid levels, obesity, and fasting glucose) and of cognition (language, executive function, psychomotor, and memory), were each well supported (CFI=0.97 and CFI=0.95, respectively). When the two models were combined, the correlation between metabolic syndrome and cognition was −.31. Among the metabolic syndrome components, only blood pressure uniquely predicted all four cognitive domains. After adjusting for age, gender, race/ethnicity, education, smoking, alcohol, and risk factor treatment variables, blood pressure remained a significant correlate of all domains except memory. In this stroke-free race/ethnically diverse community-based cohort, MetS was associated with cognitive function suggesting that MetS and its components may be important predictors of cognitive outcomes. After adjusting for sociodemographic and vascular risk factors, blood pressure was the strongest correlate of cognitive performance. Findings suggest MetS, and in particular blood pressure, may represent markers of vascular or neurodegenerative damage in aging populations. (JINS, 2014, 20, 1–10)

Previous research suggests that reduced self-awareness is common following traumatic brain injury (TBI). However, few studies have examined the magnitude of this problem in a sample representative of hospitalized individuals. In this longitudinal study, individuals with complicated mild to severe TBIs and their significant others (SO) were evaluated at 1 and 12 months postinjury on the Sickness Impact Profile. Awareness was measured by comparing the level of injury-related problems reported by a person with TBI and their SO. Overall, individuals with TBI did not report fewer difficulties than their SO. In contrast, they frequently reported more injury-related difficulties than their SO. As there is no commonly or universally accepted definition for differential awareness, the magnitude of underreporting and overreporting problems is presented using four different cutoff scores. A minimum discrepancy is proposed for defining awareness difficulties that is based on the standard error of measurement of the test–retest difference of the measure. Reduced self-awareness was inconsistent across both time and functional domains. These results suggest that reduced self-awareness is not the norm at 1 or 12 months postinjury and highlight the need for a more standardized approach to the measurement and classification of self-awareness. (JINS, 2007, 13, 561–570.)

Objectives: The aim of this study was to demonstrate the utility of an evidence-based assessment (EBA) model to establish a multimodal set of tools for identifying students at risk for perceived post-injury academic problems. Methods: Participants included 142 students diagnosed with concussion (age: M=14.95; SD=1.80; 59% male), evaluated within 4 weeks of injury (median=16 days). Demographics, pre-injury history, self- and parent-report measures assessing symptom severity and executive functions, and cognitive test performance were examined as predictors of self-reported post-injury academic problems. Results: Latent class analysis categorized participants into “high” (44%) and “low” (56%) levels of self-reported academic problems. Receiver operating characteristic analyses revealed significant discriminative validity for self- and parent-reported symptom severity and executive dysfunction and self-reported exertional response for identifying students reporting low versus high academic problems. Parent-reported symptom ratings [area under the receiver operating characteristic curve (AUC)=.79] and executive dysfunction (AUC=.74), and self-reported ratings of executive dysfunction (AUC=.84), symptoms (AUC=.80), and exertional response (AUC=.70) each classified students significantly better than chance (ps<.001). Hierarchical logistic regression indicated that, of the above, self-reported symptoms and executive dysfunction accounted for the most variance in the prediction of self-reported academic problems. Conclusions: Post-concussion symptom severity and executive dysfunction significantly predict perceived post-injury academic problems. EBA modeling identified the strongest set of predictors of academic challenges, offering an important perspective in the management of concussion by applying traditional strengths of neuropsychological assessment to clinical decision making. (JINS, 2016, 22, 1038–1049)

Objectives: Cognitive dysfunction is a key feature of major depressive (MDD) and bipolar (BD) disorders. However, rather than a single cognitive profile corresponding to each diagnostic categories, recent studies have identified significant intra- and cross-diagnostic variability in patterns of cognitive impairment. The goal of this study was to contribute to the literature on cognitive heterogeneity in mood disorders by identifying cognitive subprofiles in a population of patients with MDD, BD type I, BD type II, and healthy adults. Methods: Participants completed a neuropsychological battery; scores were converted into Z-scores using normative data and submitted to hierarchical cluster analysis. Results: Three distinct neuropsychological clusters were identified: (1) a large cluster containing mostly control participants, as well as some patients with BD and MDD, who performed at above-average levels on all neuropsychological domains; (2) a cluster containing some patients from all diagnostic groups, as well as healthy controls, who performed worse than cluster 1 on most tasks, and showed impairments in motor inhibition and verbal fluency; (3) a cluster containing mostly patients with mood disorders with severe impairments in verbal inhibition and cognitive flexibility. Conclusions: These findings revealed multiple cognitive profiles within diagnostic categories, as well as significant cross-diagnostic overlap, highlighting the importance of developing more specific treatment approaches which consider patients’ demographic and cognitive profiles in addition to their diagnosis. (JINS, 2017, 23, 584–593)

Objectives: Intraindividual cognitive variability (IICV) has been shown to differentiate between groups with normal cognition, mild cognitive impairment (MCI), and dementia. This study examined whether baseline IICV predicted subsequent mild to moderate cognitive impairment in a cognitively normal baseline sample. Methods: Participants with 4 waves of cognitive assessment were drawn from the Wisconsin Registry for Alzheimer’s Prevention (WRAP; n=684; 53.6(6.6) baseline age; 9.1(1.0) years follow-up; 70% female; 74.6% parental history of Alzheimer’s disease). The primary outcome was Wave 4 cognitive status (“cognitively normal” vs. “impaired”) determined by consensus conference; “impaired” included early MCI (n=109), clinical MCI (n=11), or dementia (n=1). Primary predictors included two IICV variables, each based on the standard deviation of a set of scores: “6 Factor IICV” and “4 Test IICV”. Each IICV variable was tested in a series of logistic regression models to determine whether IICV predicted cognitive status. In exploratory analyses, distribution-based cutoffs incorporating memory, executive function, and IICV patterns were used to create and test an MCI risk variable. Results: Results were similar for the IICV variables: higher IICV was associated with greater risk of subsequent impairment after covariate adjustment. After adjusting for memory and executive functioning scores contributing to IICV, IICV was not significant. The MCI risk variable also predicted risk of impairment. Conclusions: While IICV in middle-age predicts subsequent impairment, it is a weaker risk indicator than the memory and executive function scores contributing to its calculation. Exploratory analyses suggest potential to incorporate IICV patterns into risk assessment in clinical settings. (JINS, 2016, 22, 1016–1025)

Objectives: Cognitive dysfunction from high altitude exposure is a major cause of civilian and military air disasters. Pilot training improves recognition of the early symptoms of altitude exposure so that countermeasures may be taken before loss of consciousness. Little is known regarding the nature of cognitive impairments manifesting within this critical window when life-saving measures may still be taken. Prior studies evaluating cognition during high altitude simulation have predominantly focused on measures of reaction time and other basic attention or motor processes. Memory encoding, retention, and retrieval represent critical cognitive functions that may be vulnerable to acute hypoxic/ischemic events and could play a major role in survival of air emergencies, yet these processes have not been studied in the context of high altitude simulation training. Methods: In a series of experiments, military aircrew underwent neuropsychological testing before, during, and after brief (15 min) exposure to high altitude simulation (20,000 ft) in a pressure-controlled chamber. Results: Acute exposure to high altitude simulation caused rapid impairment in learning and memory with relative preservation of basic visual and auditory attention. Memory dysfunction was predominantly characterized by deficiencies in memory encoding, as memory for information learned during high altitude exposure did not improve after washout at sea level. Retrieval and retention of memories learned shortly before altitude exposure were also impaired, suggesting further impairment in memory retention. Conclusions: Deficits in memory encoding and retention are rapidly induced upon exposure to high altitude, an effect that could impact life-saving situational awareness and response. (JINS, 2017, 23, 1–10)

Objectives: Careful characterization of how functional decline co-evolves with cognitive decline in older adults has yet to be well described. Most models of neurodegenerative disease postulate that cognitive decline predates and potentially leads to declines in everyday functional abilities; however, there is mounting evidence that subtle decline in instrumental activities of daily living (IADLs) may be detectable in older individuals who are still cognitively normal. Methods: The present study examines how the relationship between change in cognition and change in IADLs are best characterized among older adults who participated in the ACTIVE trial. Neuropsychological and IADL data were analyzed for 2802 older adults who were cognitively normal at study baseline and followed for up to 10 years. Results: Findings demonstrate that subtle, self-perceived difficulties in performing IADLs preceded and predicted subsequent declines on cognitive tests of memory, reasoning, and speed of processing. Conclusions: Findings are consistent with a growing body of literature suggesting that subjective changes in everyday abilities can be associated with more precipitous decline on objective cognitive measures and the development of mild cognitive impairment and dementia. (JINS, 2018, 24, 104–112)

In addition to having difficulties with social communications, individuals with an autism spectrum disorder (ASD) often also experience impairment in higher-order, executive skills. The present study examined the effects of pharmacological modulation of the norepinephrine system on the severity of such impairments. A sample of 14 high-functioning adults with ASD and a demographically-matched comparison group of 13 typically developing individuals participated. An AX continuous performance test (AX-CPT) was used to evaluate working memory and inhibitory control. AX-CPT performance was assessed following administration of a single dose of propranolol (a beta adrenergic antagonist) and following placebo (sugar pill) administration. Individuals with ASD performed more poorly than non-ASD individuals in the working memory condition (BX trials). Importantly, administration of propranolol attenuated this impairment, with the ASD group performing significantly better in the propranolol condition than the placebo condition. Working memory performance of the non-ASD group was unaffected by propranolol/placebo administration. No group or medication effects were observed for the inhibition condition (AY trials). The present findings suggest that norepinephrine may play a role in some, but not necessarily all, cognitive impairments associated with ASD. Additional research is needed to fully understand whether this role is primarily causal or compensatory in nature. (JINS, 2012, 18, 556–564)

Objectives: Excessive adipose tissue, especially in the abdominal area, is associated with increased risk of dementia in older adults. However, the mechanisms underlying this relationship are poorly understood. As increased adiposity is also associated with lower circulating levels of brain-derived neurotrophic factor (BDNF), a key molecule modulating brain plasticity and neuronal regeneration, we hypothesized that the changes in cognition that occur as a result of excessive abdominal adiposity would be driven by lower levels of circulating BDNF. Methods: Fasting blood samples were obtained from 60 participants aged 40–60 years (mean±SD=52.3±5.6) and BDNF levels were assessed with an enzyme linked immunosorbent assay. Abdominal adiposity was measured using a ratio of waist circumference to hip circumference (WHR). Participants also completed a neuropsychological assessment battery to assess executive function. Statistical mediation was assessed using traditional causal steps and nonparametric bootstrapping. Results: Higher WHR was significantly associated with poorer performance on the Controlled Oral Word Association (COWA) letter fluency test (β=−0.489; p=.003) and lower levels of circulating BDNF (β=−0.345; p=.006). Linear regression and bootstrapping methods indicated that BDNF fully mediated the relationship between WHR and performance on the COWA (β=0.60; 95% confidence interval [−3.79, −0.26]). Conclusions: The relationship between higher WHR and verbal fluency was fully statistically mediated by circulating BDNF levels. The BDNF pathway is thus a useful probable mechanism through which executive function decline occurs in individuals with high abdominal adiposity. BDNF enhancing interventions (physical exercise and dietary restriction) could thus be used to improve executive function in these individuals. (JINS, 2016, 22, 1–8)

Two patients (G01, J02) with chronic nonfluent aphasia and sentence production deficits received syntactic mapping treatment to improve sentence production. The patients had dramatically different outcomes in that improved syntax production generalized to nontreatment tasks for G01, but not for JO2. To learn how treatment influenced the neural substrates for syntax production, both patients underwent pre- and posttreatment functional magnetic resonance imaging (fMRI) of sentence generation. G01 showed more robust activity posttreatment than pretreatment in Broca's area; ventral temporal activity decreased slightly from pre- to posttreatment. Comparison of J02's pretreatment and posttreatment images revealed little change, although activity was more diffuse pre- than posttreatment. Findings suggest that for G01, rehabilitation led to engagement of an area (Broca's area) used minimally during the pretreatment scan, whereas for J02, rehabilitation may have led to more efficient use of areas already involved in sentence generation during the pretreatment scan. fMRI findings are discussed in the context of sentence-production outcome and generalization. (JINS, 2006, 12, 132–146.)

The primary purpose of this study was to test the hypothesis that multiple sclerosis (MS) patients have impaired acquisition rather than a retrieval deficit. Verbal memory impairment in MS was examined in 53 relapsing-remitting MS patients and 31 healthy controls (HC), and in a meta-analysis of studies that examined memory functioning in MS with list-learning tasks. The MS group demonstrated significantly lower acquisition and delayed recall performance than the HC group, and the meta-analysis revealed that the largest effect sizes were obtained for acquisition measures relative to delayed recall and recognition. Our data argue against a retrieval deficit as the sole explanation for verbal memory impairment in MS, and make a consistent case for the position that deficient acquisition contributes to the memory dysfunction of MS patients. Deficient acquisition may result from demyelination in relevant white matter tracts that reduces encoding efficiency as a result of impaired speed of information processing. (JINS, 2013, 19, 995–1008)

Neuropsychologists frequently are asked to comment on everyday functioning, but the research relies mostly on questionnaire-based assessment of daily functioning. While performance-based assessment of everyday functioning has many advantages over commonly used questionnaires, there are few empirically validated comprehensive performance-based measures. We present data here on a performance-based battery of daily living skills, the Functional Impact Assessment (FIA) in 47 unilateral stroke patients and 37 matched healthy controls. The FIA was validated by comparing it to performance on the self- and informant-report version of the Functional Activities Questionnaire (FAQ). We also examined the relationship between the FIA and cognitive functioning using the Neuropsychological Assessment Battery (NAB). The stroke group's performance on the FIA, FAQ (self and informant), and NAB (total and domain scores) was significantly (d′s ≥ .80) lower than the control group. The NAB total score and all domain scores were highly correlated with the FIA in the stroke group (r's > .7), and only one NAB domain score (visuospatial) was a unique predictor. This may be due to the fact that most of the NAB domains have a statistical problem of multicollinearity, which may explain why only the spatial domain was a unique predictor. While the informant FAQ was significantly correlated with FIA total score (r = .48, p < .01), the NAB total score was a significantly better predictor (r = .83, p < .001) than the informant FAQ. NAB total scaled score of less than 86 predicted impairment on the FIA with 92% sensitivity and 84% specificity. Our findings argue that the FIA is sensitive to deficits associated with stroke and is highly associated with all neuropsychological domains (attention, executive functions, language and spatial skills, and memory). (JINS, 2011, 17, 832–840)

Spatiotemporal brain activation profiles were obtained from 27 middle school students experiencing difficulties in reading comprehension as well as word-level skills (RD) and 23 age- and IQ-matched non-reading impaired students during performance of an oral pseudoword reading task using Magnetoencephalography (MEG). Based on their scores on standardized reading fluency tests 1 year later, students with RD who showed significant improvement were classified as Adequate Responders (AR) whereas those not demonstrating such gains were classified as Inadequate Responders (IR). At baseline, activation profiles of the AR group featured increased activity in the left supramarginal and angular gyri, as well as in the superior and middle temporal gyri, bilaterally compared to IR. The degree of activity in these regions was a significant predictor of the amount of subsequent gains in reading fluency. These results extend previous functional brain imaging findings of beginning readers, suggesting that recruitment of brain areas that typically serve as key components of the brain circuit for reading is an important factor in determining response to intervention in older struggling readers. (JINS, 2011, 17, 875–885)

Heterogeneity is observed in the patterns of cognition in Alzheimer’s disease (AD). Such heterogeneity might suggest the involvement of different etiological pathways or different host responses to pathology. A total of 627 subjects with mild/moderate AD underwent cognitive assessment with the Mini-Mental State Examination (MMSE) and the Dementia Rating Scale-2 (DRS-2). Latent class analysis (LCA) was performed on cognition subscale data to identify and characterize cognitive subgroups. Clinical, demographic, and genetic factors were explored for association with class membership. LCA suggested the existence of four subgroups; one group with mild and another with severe global impairment across the cognitive domains, one group with primary impairments in attention and construction, and another group with primary deficits in memory and orientation. Education, disease duration, age, Apolipoprotein E-ε4 (APOE ε4) status, gender, presence of grasp reflex, white matter changes, and early or prominent visuospatial impairment were all associated with class membership. Our results support the existence of heterogeneity in patterns of cognitive impairment in AD. Our observation of classes characterized by predominant deficits in attention/construction and memory respectively deserves further exploration as does the association between membership in the attention/construction class and APOE ε4 negative status. (JINS, 2010, 16, 233–243.)

The purpose of this study was to investigate the effects of pediatric traumatic brain injury (TBI) on verbal and visual-spatial working memory (WM). WM tasks examined memory span through recall of the last item of a series of stimuli. Additionally, both verbal and visual-spatial tests had a dual-task condition assessing the effect of increasing demands on the central executive (CE). Inhibitory control processes in verbal WM were examined through intrusion errors. The TBI group (n = 73) performed more poorly on verbal and visual-spatial WM tasks than orthopedic-injured children (n = 30) and non-injured children (n = 40). All groups performed more poorly on the dual-task conditions, reflecting an effect of increasing CE load. This effect was not greater for the TBI group. There were no group differences in intrusion errors on the verbal WM task, suggesting that problems in WM experienced by children with TBI were not primarily due to difficulties in inhibitory control. Finally, injury-related characteristics, namely days to follow commands, accounted for significant variance in WM performance, after controlling for relevant demographic variables. Findings suggest that WM impairments in TBI are general rather than modality-specific and that severity indices measured over time are better predictors of WM performance than those taken at a single time point. (JINS, 2012, 18, 29–38)

Explicit and implicit attitudes toward people who have sustained traumatic brain injury (TBI) were investigated to determine if negative attitudes exist and if the terminology used (brain vs. head injury) exacerbated predicted negativity. Participants (n = 103) rated Tony (brain/head injury) and Peter (limb-injury) on 10 characteristics using a 7-point scale. Familiarity with brain injury was also measured. Implicit Association Tests (IAT) assessed potential negative bias. Tony (M = 36.84) was judged more negatively than Peter (M = 31.69). The term “brain” versus “head” injury resulted in more negative evaluations (Ms = 38.72 vs. 34.78). Participants familiar with TBI were more positive toward Tony than those unfamiliar (Ms = 34.98 vs. 39.80). Only those unfamiliar with TBI demonstrated implicit negative bias. Negative attitudes toward TBI are expressed explicitly with individuals openly endorsing less desirable characteristics. When people have more knowledge about or experience with brain injury, they are less likely to endorse negative stereotypes. (JINS, 2010, 16, 705–710.)

There are recent reports that alexithymia may be associated with brain dysfunction involving frontal lobes or right hemisphere regions. However, little is known about the relationship between alexithymia and cognitive deficits in Parkinson's disease (PD). The authors investigated the neuropsychological correlates of alexithymia in a population of 70 nondemented PD patients and 70 controls. Alexithymia was screened using the 20-item version of the Toronto Alexithymia Scale (TAS-20). Standardized scales that measure verbal episodic memory, executive functions, abstract reasoning, and visual–spatial and language abilities were adopted. PD patients with alexithymia performed worse than both PD patients without alexithymia and controls with or without alexithymia on tasks requiring visual–spatial processing. Moreover, regression analyses showed that, in PD patients, but not in controls, poor performance on a constructional praxis task predicted high scores on the TAS-20 subscale, which assesses difficulty in identifying emotions. These data evidence an association between alexithymia and visual–spatial processing alterations in PD patients, supporting the view that the right hemisphere could be specifically involved in the modulation of some facets of alexithymia. (JINS, 2007, 13, 980–992.)

Myelomeningocele is a common developmental malformation of the central nervous system that usually results in motor deficits. Previous studies of myelomeningocele have not examined motor adaptation, which involves changes in the control of movements that occur as a result of repeated task exposure but do not depend on conscious recall of the exposure. We studied motor adaptation in 17 children with myelomeningocele and shunted hydrocephalus, 19 children with attention deficit/hyperactivity disorder (ADHD), and 20 healthy siblings. All children were 8 to 15 years of age. They were administered 2 measures of motor adaptation known to be sensitive to subcortical abnormalities in adult neurological disorders. One task assessed the biasing in weight judgments that occurs after exposure to heavy versus light weights, and the other assessed the adaptation in reaching movements that occurs when vision is laterally displaced by prisms. Contrary to expectations, the groups did not differ in motor adaptation. Children in all 3 groups displayed significant biasing in their weight judgments and improvement in the accuracy of pointing during prism adaptation trials. Performance on the 2 motor adaptation tasks was not related to age or IQ. Weight biasing was positively related to a measure of response disinhibition. The findings suggest that myelomeningocele does not result in global impairment of motor skills, but instead in a profile of intact and impaired motor functions that potentially may be decomposed in accordance with the neuroscience of motor skills. (JINS, 2003, 9, 642–652.)