Traumatic brain injury (TBI) is often associated with enduring impairments in high-level cognitive functioning, including working memory (WM). We examined WM function in predominantly chronic patients with mild, moderate and severe TBI and healthy comparison subjects behaviorally and, in a small subset of moderate-to-severe TBI patients, with event-related functional magnetic resonance imaging (fMRI), using a visual n-back task that parametrically varied WM load. TBI patients showed severity-dependent and load-related WM deficits in performance accuracy, but not reaction time. Performance of mild TBI patients did not differ from controls; patients with moderate and severe TBI were impaired, relative to controls and mild TBI patients, but only at higher WM-load levels. fMRI results show that TBI patients exhibit altered patterns of activation in a number of WM-related brain regions, including the dorsolateral prefrontal cortex and Broca's area. Examination of the pattern of behavioral responding and the temporal course of activations suggests that WM deficits in moderate-to-severe TBI are due to associative or strategic aspects of WM, and not impairments in active maintenance of stimulus representations. Overall, results demonstrate that individuals with moderate-to-severe TBI exhibit WM deficits that are associated with dysfunction within a distributed network of brain regions that support verbally mediated WM. (JINS, 2004, 10, 724–741.)

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)

In the past 25 years, scientific understanding of dyslexia and other learning disabilities has seen rapid progress in domains involving definition and classification, neuropsychological correlates, neurobiological factors, and intervention. I discuss this progress, emphasizing the central organizing influence of research and theory on basic academic skills on identification and sampling issues. I also emphasize how neuropsychological approaches to dyslexia have evolved and the importance of an interdisciplinary perspective for understanding dyslexia. (JINS, 2009, 15, 501–508.)

Impairment in semantic processing occurs early in Alzheimer's disease (AD) and differential impact on subtypes of semantic relations have been reported, yet there is little data on the neuroanatomic basis of these deficits. Patients with mild AD and healthy controls underwent 3 functional MRI auditory stimulation tasks requiring semantic or phonological decisions (match–mismatch) about word pairs (category–exemplar, category–function, pseudoword). Patients showed a significant performance deficit only on the exemplar task. On voxel-based fMRI activation analyses, controls showed a clear activation focus in the left superior temporal gyrus for the phonological task; patients showed additional foci in the left dorsolateral prefrontal and bilateral cingulate areas. On the semantic tasks, predominant activation foci were seen in the inferior and middle frontal gyrus (left greater than right) in both groups but patients showed additional activation suggesting compensatory recruitment of locally expanded foci and remote regions, for example, right frontal activation during the exemplar task. Covariance analyses indicated that exemplar task performance was strongly related to signal increase in bilateral medial prefrontal cortex. The authors conclude that fMRI can reveal similarities and differences in functional neuroanatomical processing of semantic and phonological information in mild AD compared to healthy elderly, and can help to bridge cognitive and neural investigations of the integrity of semantic networks in AD. (JINS, 1999, 5, 377–392.)

This review summarizes the clinical, imaging, and pathological features of frontotemporal dementia (FTD). Clinicians have become increasingly sensitive to FTD in the differential diagnosis of Alzheimer's disease. Clinical subgroups of FTD patients have been recognized, including patients with progressive non-fluent aphasia, semantic dementia, and behavioral disorder with executive difficulty. The clinical, neuroimaging and neuropathological profiles associated with these clinically defined subgroups are examined. (JINS, 2002, 8, 566–583.)

We explored the effect of education and occupational complexity on the rate of cognitive decline (as measured by the Mini-Mental State Examination) in 171 patients with a confirmed Alzheimer's disease (AD) diagnosis. Complexity was measured as substantive complexity of work and complexity of work with data, people, and things. Average lifetime occupational complexity was calculated based on years at each occupation. Participants were followed for an average of 2.5 years and 3.7 visits. In multivariate mixed-effects models, high education, high substantive complexity, and high complexity of work with data and people predicted faster rates of cognitive decline, controlling for age, gender, native language, dementia severity, and entry into the analyses at initial versus follow-up testing. These results provide support for the concept of cognitive reserve according to which greater reserve may postpone clinical onset of AD but also accelerate cognitive decline after the onset. (JINS, 2006, 12, 147–152.)

Patients with Alzheimer's Disease (AD) who have reached a stage of moderate to severe dementia are capable of completing a restricted range of cognitive tests and performing a limited range of activities of daily living (ADL). As part of an initiative to develop instruments to evaluate AD, we analyzed data describing the performance of a large number of ADL and scores on cognitive and global assessment measures in a cohort of patients with AD with moderate to severe cognitive impairment, defined as a Mini-Mental State Examination score ranging from 0–15 (out of 30). From the large pool of ADL, 19 met criteria of applicability, reliability, good scaling, concordant validity, and sensitivity to detect change in performance over 6–12 months. A total score derived from these 19 ADL ratings, comprising a scale termed the Alzheimer Disease Cooperative Study ADL-sev, correlated strongly with measures of cognition and of global dementia severity. Patients with moderate to severe AD showed a decline on the ADL-sev and cognitive measures over 6 and 12 months, consistent with the progression of AD. Detailed evaluation of ADL may provide a useful index to evaluate patients with moderate to severe AD and may complement cognitive assessment, especially for characterizing change in interventional or therapeutic studies. (JINS, 2005, 11, 446–453.)

Anorexia nervosa (AN) is a severe mental illness characterized in part by rigid thinking and ritualized behaviors involving eating and weight. Cognitive rigidity may play a role in the perpetuation of symptoms, and may provide information as to important brain-based abnormalities. Neuropsychological studies of patients with AN have shown cognitive dysfunction, but few have focused on cognitive flexibility. This study assessed set shifting in patients with AN, as a measure of cognitive flexibility. In this study, 15 patients with AN were compared with 11 healthy controls using a neuropsychological battery including the Wisconsin Card Sort Test (WCST). While patients with AN did not differ from controls on 5 measures of neuropsychological function, they made significantly more perseverative errors on the WCST, indicating a problem in set shifting. This finding suggests that patients with AN have a specific neurocognitive abnormality that may play a role in the development and persistence of this disorder. (JINS, 2006, 12, 431–435.)

This controlled prospective study examined the evolution and predictors of cognitive decline in Parkinson’s disease (PD). Consecutive patients diagnosed at baseline with PD (n = 89), established PD (EPD) patients (n = 52) with a mean disease duration of 6.5 years, and healthy control subjects (n = 64) underwent extensive neuropsychological assessment twice, approximately 3 years apart. A standardized regression-based method, normative data, and multivariate normative comparisons were used to assess the cognitive course of PD. Cognitive performance of newly diagnosed patients decreased significantly over time, particularly on measures of psychomotor speed and attention and to a lesser extent on tests of memory, visuospatial skills, and executive functions. About 50% of the patients showed cognitive decline and 9% developed dementia. Similar results were observed in EPD patients. None of the baseline features predicted cognitive change in newly diagnosed patients, whereas age at disease onset and axial impairment (postural and gait disorders) contributed to decline in established patients. We conclude that within few years after diagnosis, PD patients show faster rate of cognitive decline than matched healthy subjects, particularly in domains of attention and psychomotor speed. Selection bias probably led to underestimation of the true extent of cognitive decline in established patients. (JINS, 2009, 15, 426–437.)

Neuropsychologists are often asked to answer questions about the effects of cognitive deficits on everyday functioning. This study examined the relationship between and the cognitive correlates of self-report, performance-based, and direct observation measures commonly used as proxy measures for everyday functioning. Participants were 88 community-dwelling, cognitively healthy older adults (age 50–86 years). Participants completed standardized neuropsychological tests and questionnaires, and performed eight activities of daily living (e.g., water plants, fill a medication dispenser) while under direct observation in a campus apartment. All proxy measures of everyday function were sensitive to the effects of healthy cognitive aging. After controlling for age, cognitive predictors explained a unique amount of the variance for only the performance-based behavioral simulation measure (i.e., Revised Observed Tasks of Daily Living). The self-report instrumental activities of daily living (IADL) and the performance-based everyday problem-solving test (i.e., EPT) did not correlate with each other; however, both were unique predictors of the direct observation measure. These findings suggest that neuropsychologists must be cautious in making predictions about the quality of everyday activity completion in cognitively healthy older adults from specific cognitive functions. The findings further suggest that a self-report of IADLs and the performance-based EPT may be useful measures for assessing everyday functional status in cognitively healthy older adults. (JINS, 2011, 17, 853–864)

Motor impairments and cognitive dysfunction are common in multiple sclerosis (MS). We aimed to delineate the relationship between cognitive capacity and upper and lower motor function in 211 MS patients, and 120 healthy volunteers. Lower and upper motor function were assessed with the Timed 25 Foot Walk (T25FW) and the Nine Hole Peg Test (NHPT) as implemented in the Multiple Sclerosis Functional Composite (MSFC). Subjects also underwent neuropsychological evaluation. Hierarchical linear regression analysis was conducted separately for the MS and healthy groups with the T25FW and NHPT serving as the outcome measures. Cognitive performance indices served as predictors. As expected, healthy subjects performed better than the MS group on all measures. Processing speed and executive function tests were significant predictors of lower and upper motor function in both groups. Correlations were more robust in the MS group, where cognitive tests predicted variability in motor function after controlling for disease duration and physical disability. In conclusion, we find evidence of higher order cognitive control of motor function that appears to be particularly salient in this large and representative MS sample. The findings may have implications for risk assessment and treatment of mobility dysfunction in MS. (JINS, 2011, 17, 643–653)

The present study further explored the phenomenon of “diagnosis threat” (Suhr & Gunstad, 2002), by examining the potential explanatory roles of anxiety, effort, and depression. Individuals with mild head injury history were randomly assigned to receive either neutral instructions (controls, N = 25) or to have attention called to their head injury history as a reason for invitation into the study (diagnosis threat, N = 28). Depression was measured at baseline. Following the neuropsychological battery, ratings of effort, test pressure, and state anxiety were completed. The diagnosis threat group performed worse than controls on attention/working memory, psychomotor speed, and memory tasks, but not on measures of executive functioning, post-test anxiety, or effort. Effort, anxiety and depression were not related to cognitive performance, nor did depression interact with expectations in explaining group differences in performance. Results provide further support for the “diagnosis threat” effect, but offer no support for effort, anxiety, or depression explanations for diminished performance. (JINS, 2005, 11, 23–29.)

Alcohol and other drug use are common in youth, but neurocognitive sequelae are unclear. This study examines the relationship between neuropsychological functioning and protracted substance use in adolescence. One hundred fifteen adolescents, ages 13 to 19 years, were recruited from inpatient substance abuse treatment programs and followed for 4 years. Adolescents were administered a comprehensive battery of neuropsychological tests and evaluated on substance use involvement during treatment, and at 6-month, 1-year, 2-year, and 4-year follow-up time points. Protracted substance abuse over the 4 years of follow-up was associated with significantly poorer subsequent functioning on tests of attention. In addition, alcohol and drug withdrawal accounted for significant variance in visuospatial functioning, above and beyond demographic, educational, and health variables in detoxified late adolescents and young adults. Results suggest that alcohol and drug withdrawal may be a more powerful marker of protracted neuropsychological impairments than other indices of youthful alcohol and drug involvement. (JINS, 1999, 5, 481–493.)

The List Sorting Working Memory Test was designed to assess working memory (WM) as part of the NIH Toolbox Cognition Battery. List Sorting is a sequencing task requiring children and adults to sort and sequence stimuli that are presented visually and auditorily. Validation data are presented for 268 participants ages 20 to 85 years. A subset of participants (N=89) was retested 7 to 21 days later. As expected, the List Sorting Test had moderately high correlations with other measures of working memory and executive functioning (convergent validity) but a low correlation with a test of receptive vocabulary (discriminant validity). Furthermore, List Sorting demonstrates expected changes over the age span and has excellent test–retest reliability. Collectively, these results provide initial support for the construct validity of the List Sorting Working Memory Measure as a measure of working memory. However, the relationship between the List Sorting Test and general executive function has yet to be determined. (JINS, 2014, 20, 1–12)

For nearly a century, the primary method employed by psychologists to define and test the validity of constructs evaluated by assessment instruments has been shared-variance techniques such as intervariable correlations or factor analysis with large normative or mixed clinical samples. To illustrate the shortcomings of this approach, we conducted (1) correlational analyses of immediate- and delayed-memory measures separately in normal participants and in homogeneous samples of patients with either Alzheimer's disease or Huntington's disease; and (2) factor analysis of immediate and delayed-recall and recognition measures in a large, homogeneous sample of patients with Alzheimer's disease. The findings revealed that cognitive measures that share variance in the intact brain—thereby giving the facade of assessing a unitary construct—can dissociate and contribute to unique variance in the damaged brain, but only if the pathology occurs in brain regions known to disrupt vital cognitive processes tapped by those measures. The results illustrate that shared-variance procedures applied to normal or mixed clinical populations can mask some of the most vital cognitive constructs, such as the classic distinction between short- and long-term memory. Implications of these findings for research and clinical practice are discussed. (JINS, 2003, 9, 936–946.)

Numerous studies have suggested that frontal cortex plays a strategic, rather than an absolute, role in memory performance. Typically, frontal patients are reported to have impaired recall but normal recognition memory. A recent meta-analysis, however, has questioned this conclusion. To further investigate the role of frontal cortex in long-term memory, patients with focal frontal lesions and age- and education-matched controls were tested on a new version of the California Verbal Learning Test (CVLT–II). Frontal patients exhibited a number of deficits on this test, including overall poorer recall, an increased tendency to make intrusions, reduced semantic clustering, and impaired yes/no recognition performance. Further analysis of the error rates in the yes/no recognition task revealed that frontal patients were most likely to mistakenly endorse 2 types of distractors: semantically related words and words from an interference list. These findings are discussed with respect to the role of frontal dysfunction in false recollections and poor source memory, as well as the distinction between the roles of frontal and temporal cortex in long-term memory. (JINS, 2002, 8, 539–546.)

Few follow-up studies of children with very low birth weight (VLBW, <1,500 g) have examined neuropsychological sequelae at later ages or neonatal risks as predictors of these outcomes. The present study assessed cognitive skills at mean age 16 years in 48 participants with <750 g birth weight, 47 with 750–1,499 g birth weight, and 52 term-born controls. Our major objectives were to delineate the long-term cognitive consequences of VLBW, and to determine if risks for periventricular brain insults accounted for variations in outcomes. Analysis revealed poorer outcomes for the <750 g group than for term-born controls on nearly all measures, with specific impairments in visual–motor skills, spatial memory, and executive function. Predictors of outcome for participants with VLBW included lower birth weight, lower weight for gestational age, and a longer period of oxygen requirement for chronic lung disease. The longer-term consequences of VLBW are consistent with expectations based on early brain pathology and suggest limitations to functional plasticity. (JINS, 2004, 10, 987–1004.)

Patterns of brain activation associated with covert performance of the Stroop Color–Word task were studied in young, healthy, adult volunteers using blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI). Comparisons of the incongruous Stroop condition were made with both color naming and word reading baselines. Areas of the left and right anterior cingulate, the right precuneus, and the left pars opercularis displayed larger BOLD signal responses during the incongruous Stroop condition than during baseline conditions. Activation of BOLD signals in these areas was highly repeatable. In a second experiment, pupil diameter was used to assess cognitive load in 7 individuals studied during overt and covert performance of both Stroop and color naming conditions. Cognitive load was similar in overt and covert response conditions. Results from the BOLD study indicate that brain regions participating in selective visual attention and in the selection of motor programs involved in speech were activated more by the Stroop task than by the baseline tasks. The neural substrate involved in the resolution of the perceptual and motor conflicts elicited by the Stroop Color–Word task does not appear to be a single brain region. Rather, a network of brain regions is implicated, with separate regions within this system supporting distinct functions. (JINS, 1999, 5, 308–319.)

Limited data exist comparing the performance of computerized neurocognitive tests (CNTs) for assessing sport-related concussion. We evaluated the reliability and validity of three CNTs—ANAM, Axon Sports/Cogstate Sport, and ImPACT—in a common sample. High school and collegiate athletes completed two CNTs each at baseline. Concussed (n=165) and matched non-injured control (n=166) subjects repeated testing within 24 hr and at 8, 15, and 45 days post-injury. Roughly a quarter of each CNT’s indices had stability coefficients (M=198 day interval) over .70. Group differences in performance were mostly moderate to large at 24 hr and small by day 8. The sensitivity of reliable change indices (RCIs) was best at 24 hr (67.8%, 60.3%, and 47.6% with one or more significant RCIs for ImPACT, Axon, and ANAM, respectively) but diminished to near the false positive rates thereafter. Across time, the CNTs’ sensitivities were highest in those athletes who became asymptomatic within 1 day before neurocognitive testing but was similar to the tests’ false positive rates when including athletes who became asymptomatic several days earlier. Test–retest reliability was similar among these three CNTs and below optimal standards for clinical use on many subtests. Analyses of group effect sizes, discrimination, and sensitivity and specificity suggested that the CNTs may add incrementally (beyond symptom scores) to the identification of clinical impairment within 24 hr of injury or within a short time period after symptom resolution but do not add significant value over symptom assessment later. The rapid clinical recovery course from concussion and modest stability probably jointly contribute to limited signal detection capabilities of neurocognitive tests outside a brief post-injury window. (JINS, 2016, 22, 24–37)

Morphometric analysis of magnetic resonance (MR) scans in 88 traumatic brain injury (TBI) patients demonstrated significantly larger ventricle-to-brain ratios (VBR) and temporal horn volumes, and significantly smaller fornix-to-brain ratios (FBR) and corpus callosum (CC) area measurements, compared to 73 controls. Additionally, TBI patients were grouped according to Glasgow Coma Scale (GCS) for a within-TBI sample comparison so that severity of injury on brain morphology could be examined. The severe TBI group (GCS = 3–6) differed from the mild and moderate injury groups on measures of the internal capsule, VBR, temporal horn volume, and CC. In a separate analysis wherein the TBI subjects were grouped by degree of fornix atrophy, the group with the smallest fornix size demonstrated the lowest memory performance. Furthermore, anatomic measures correlated with severity of injury, and tests of memory and motor function. Results demonstrate the diffuse nature of degeneration in TBI with more severe injury, and that quantified MR identified morphologic changes relate to neuropsychological outcome. (JINS, 1995, 1, 17–28.)