Children surviving treatment for malignant brain tumors commonly have problems maintaining their premorbid levels of intellectual development and academic achievement. Our group has been especially interested in the effects of treatment on normal appearing white matter (NAWM) on MRI and the influence of NAWM volumes on neurocognitive functioning. The present study assessed NAWM and attentional abilities among 37 long-term survivors of malignant brain tumors, ranging in age from 1.7 to 14.8 (Mdn = 6.5) years at diagnosis, who had been treated with cranial radiation therapy with or without chemotherapy 2.6 to 15.3 (Mdn = 5.7) years earlier. On the Conners' Continuous Performance Test, the Overall Index and 7 of the other 10 indices were significantly deficient compared to age- and gender-corrected normative values. After statistically controlling for the effects of age at diagnosis and time elapsed from treatment, 5 of the 8 indices were significantly associated with cerebral white matter volumes and/or specific regional white matter volumes of the prefrontal/frontal lobe and cingulate gyrus. No gender effects were observed. The results of the present study further support the contention that NAWM is an important substrate for treatment-induced neurocognitive problems among survivors of malignant brain tumors of childhood. (JINS, 2004, 10, 180–189.)

In this paper, we present a review of semantic priming experiments in schizophrenia. Semantic priming paradigms show utility in assessing the role of deficits in semantic memory network access in the pathology of schizophrenia. The studies are placed in the context of current models of information processing. In this review we include all English-language reports (from peer-reviewed journals) of single-word semantic priming studies involving participants with schizophrenia. The studies to date show schizophrenic patients to exhibit variable semantic priming effects under automatic processing conditions, and consistent impairments under controlled0attentional conditions. We also describe associations with other neurocognitive dysfunction, neurochemical and electrophysiological disturbances, and clinical manifestations (such as thought disorder).

The aim of this study was to determine whether naming difficulties arise in individuals as young as their 50s. Participants of 25–35, 50–59, 60–69, and above 70 years of age were given a picture naming task. To uncover subtle naming difficulties, latencies were analyzed in addition to accuracy. To control whether the expected slower naming latencies could be due to a general slowing affecting all cognitive tasks, participants were also given an odd/even judgment task to assess cognitive processing speed. The results confirmed that participants in their 50s presented decline in naming performance, reflected by an increase in naming latencies, whereas adults in their 60s and their 70s showed both a decrease in accuracy and an increase in latency. Moreover, the increase in naming latencies remained significant even after controlling for odd/even judgment latencies, suggesting a degradation specific to the picture naming task. We assumed that these slower latencies may result from a language-specific impairment. As a further test for language-specific degradation, participants’ semantic capacities were also assessed with a synonym judgment task and the Pyramids and Palm Trees test. The above-70 group showed semantic degradation. The contributions of multiple factors to naming difficulties in aging are discussed. (JINS, 2013, 19, 1–8)

The effects of acute aerobic exercise on cognitive functions in humans have been the subject of much investigation; however, these studies are limited by several factors, including a lack of randomized controlled designs, focus on only a single cognitive function, and testing during or shortly after exercise. Using a randomized controlled design, the present study asked how a single bout of aerobic exercise affects a range of frontal- and medial temporal lobe-dependent cognitive functions and how long these effects last. We randomly assigned 85 subjects to either a vigorous intensity acute aerobic exercise group or a video watching control group. All subjects completed a battery of cognitive tasks both before and 30, 60, 90, or 120 min after the intervention. This battery included the Hopkins Verbal Learning Test-Revised, the Modified Benton Visual Retention Test, the Stroop Color and Word Test, the Symbol Digit Modalities Test, the Digit Span Test, the Trail Making Test, and the Controlled Oral Word Association Test. Based on these measures, composite scores were formed to independently assess prefrontal cortex- and hippocampal-dependent cognition. A three-way mixed Analysis of Variance was used to determine whether differences existed between groups in the change in cognitive function from pre- to post-intervention testing. Acute exercise improved prefrontal cortex- but not hippocampal-dependent functioning, with no differences found between delay groups. Vigorous acute aerobic exercise has beneficial effects on prefrontal cortex-dependent cognition and these effects can last for up to 2 hr after exercise. (JINS, 2015, 21, 791–801)

Recovery of cognitive function after mild head injury (MHI) is thought to be relatively swift and complete. The present study replicates and extends previous work in which university students with self-reported concussion demonstrated reduced P300 amplitude on a set of easy and difficult attention tasks, in addition to performing more poorly than controls on demanding cognitive tasks many years after injury. In the present study, 13 students with self-reported concussion (MHI group: M time since injury 5 8 years) and 10 controls were matched for age, sex, education, and a variety of cognitive, physical and emotional complaints. Controls outperformed the MHI group on the Digit Symbol substitution task and on a difficult dual task involving tone discrimination and visual working memory. Additionally, controls exhibited larger P300 amplitudes on both an easy and a difficult auditory discrimination task. A combination of electrophysiological, neuropsychological and self-report indices predicted group membership (MHI vs. control) with 88% accuracy. The present results, coupled with previous work, offer preliminary evidence that the combination of event-related potentials and demanding behavioral measures might reveal long-lasting, subtle cognitive problems associated with MHI. These findings may challenge existing notions of complete recovery after MHI.

Objectives: A substantial body of research has documented age-related declines in cognitive abilities among adults over 60, yet there is much less known about changes in cognitive abilities during midlife. The goal was to examine longitudinal changes in multiple cognitive domains from early midlife through old age in a large national sample, the Midlife in the United States (MIDUS) study. Methods: The Brief Test of Adult Cognition by Telephone (BTACT) was administered on two occasions (MIDUS 2, MIDUS 3), an average of 9 years apart. At MIDUS 3, those with the cognitive assessment (N=2518) ranged in age from 42 to 92 years (M=64.30; SD=11.20) and had a mean education of 14.68 years (SD=2.63). The BTACT includes assessment of key aging-sensitive cognitive domains: immediate and delayed free recall, number series, category fluency, backward digit span, processing speed, and reaction time for attention switching and inhibitory control, which comprise two factors: episodic memory and executive functioning. Results: As predicted, all cognitive subtests and factors showed very small but significant declines over 9 years, with differences in the timing and extent of change. Processing speed showed the earliest and steepest decrements. Those with higher educational attainment scored better on all tests except reaction time. Men had better executive functioning and women performed better on episodic memory. Conclusions: Examining cognitive changes in midlife provides opportunities for early detection of cognitive impairments and possibilities for preventative interventions. (JINS, 2018, 24, 805–820)

Neuropsychology is poised for transformations of its concepts and methods, leveraging advances in neuroimaging, the human genome project, psychometric theory, and information technologies. It is argued that a paradigm shift toward evidence-based science and practice can be enabled by innovations, including (1) formal definition of neuropsychological concepts and tasks in cognitive ontologies; (2) creation of collaborative neuropsychological knowledgebases; and (3) design of Web-based assessment methods that permit free development, large-sample implementation, and dynamic refinement of neuropsychological tests and the constructs these aim to assess. This article considers these opportunities, highlights selected obstacles, and offers suggestions for stepwise progress toward these goals. (JINS, 2011, 17, 000–000)

We administered the Multiscale Depression Inventory (MDI) and the Beck Depression Inventory (BDI) to 84 multiple sclerosis (MS) patients, 101 patients diagnosed with major depression and 87 nonmedical, nonpsychiatric controls. The MDI consists of three separate depression scales measuring mood, vegetative, and evaluative symptoms. We found that: (a) MS patients did not significantly differ from the controls in mood symptoms, (b) the depression prevalence rate in MS patients was significantly lower when measured by the mood scale (17·7%) than by the BDI (30·5%) or MDI total score (26·6%), and (c) MS patients showed significantly less mood disturbance than a non-MS comparison group matched on BDI measured depression severity. We suggest that the inclusion of nonmood symptoms in self-report depression scales may artificially raise both prevalence rates and severity ratings of MS related depression and that the most valid measure of depression in MS is mood disturbance. (JINS, 1995, I, 291–296.)

Objectives: The objective was to review the literature on diffusion tensor imaging as well as resting-state functional magnetic resonance imaging and electroencephalography (EEG) to unveil neuroanatomical and neurophysiological substrates of Alzheimer’s disease (AD) as a brain neural network pathology affecting structural and functional cortical connectivity underlying human cognition. Methods: We reviewed papers registered in PubMed and other scientific repositories on the use of these techniques in amnesic mild cognitive impairment (MCI) and clinically mild AD dementia patients compared to cognitively intact elderly individuals (Controls). Results: Hundreds of peer-reviewed (cross-sectional and longitudinal) papers have shown in patients with MCI and mild AD compared to Controls (1) impairment of callosal (splenium), thalamic, and anterior–posterior white matter bundles; (2) reduced correlation of resting state blood oxygen level-dependent activity across several intrinsic brain circuits including default mode and attention-related networks; and (3) abnormal power and functional coupling of resting state cortical EEG rhythms. Clinical applications of these measures are still limited. Conclusions: Structural and functional (in vivo) cortical connectivity measures represent a reliable marker of cerebral reserve capacity and should be used to predict and monitor the evolution of AD and its relative impact on cognitive domains in pre-clinical, prodromal, and dementia stages of AD. (JINS, 2016, 22, 138–163)

MRI diffusion-tensor tracking (DTT) was performed in 17 high-functioning adolescents/adults with autism and 17 pairwise-matched controls. White matter pathways involved in face processing were examined due to the relevance of face perception to the social symptoms of autism, and due to known behavioral and functional imaging findings in autism. The hippocampo-fusiform (HF) and amygdalo-fusiform (AF) pathways had normal size and shape but abnormal microstructure in the autism group. The right HF had reduced across-fiber diffusivity (D-min) compared with controls, opposite to the whole-brain effect of increased D-min. In contrast, left HF, right AF, and left AF had increased D-min and increased along-fiber diffusivity (D-max), more consistent with the whole-brain effect. There was a general loss of lateralization compared with controls. The right HF D-min was markedly low in the autism subgroup with lower Benton face recognition scores, compared with the lower-Benton control subgroup, and compared with the higher-Benton autism subgroup. Similar behavioral relationships were found for performance IQ. Such results suggest an early functionally-significant pathological process in right HF consistent with small-diameter axons (with correspondingly slower neural transmission) and/or higher packing density. In left AF and HF, changes were interpreted as secondary, possibly reflecting axonal loss and/or decreased myelination. (JINS, 2008, 14, 933–946.)

Neuropsychological and neuroimaging changes have been observed in individuals with the Huntington's disease (HD) gene expansion prior to the onset of manifest HD. This cross-sectional fMRI study of preclinical HD (pre-HD) individuals was conducted to determine if functional brain changes precede deficits in behavioral performance and striatal atrophy. Twenty-six pre-HD and 13 demographically matched healthy participants performed a time reproduction task while undergoing fMRI scanning. Pre-HD participants were divided into two groups (n = 13 each): FAR (>12 years to estimated onset [YEO] of manifest HD) and CLOSE (<12 YEO). The CLOSE group demonstrated behavioral deficits, striatal atrophy, and reduced neural activation in the left putamen, SMA, left anterior insula and right inferior frontal gyrus. The FAR group showed reduced neural activation in the right anterior cingulate and right anterior insula. The FAR group also demonstrated increased neural activation in the left sensorimotor, left medial frontal gyrus, left precentral gyrus, bilateral superior temporal gyri and right cerebellum. The fMRI changes in the FAR group occurred in the relative absence of striatal atrophy and behavioral performance deficits. These results suggest that fMRI is sensitive to neural dysfunction occurring more than 12 years prior to the estimated onset of manifest HD. (JINS, 2007, 13, 758–769.)

Our objectives were to examine cognitive outcomes for extremely preterm/extremely low birth weight (EPT/ELBW, gestational age <28 weeks and/or birth weight <1000 g) children in kindergarten and the associations of these outcomes with neonatal factors, early childhood neurodevelopmental impairment, and socioeconomic status (SES). The sample comprised a hospital-based 2001–2003 birth cohort of 148 EPT/ELBW children (mean birth weight 818 g; mean gestational age 26 weeks) and a comparison group of 111 term-born normal birth weight (NBW) classmate controls. Controlling for background factors, the EPT/ELBW group had pervasive deficits relative to the NBW group on a comprehensive test battery, with rates of cognitive deficits that were 3 to 6 times higher in the EPT/ELBW group. Deficits on a measure of response inhibition were found in 48% versus 10%, odds ratio (95% confidence interval) = 7.32 (3.32, 16.16), p < .001. Deficits on measures of executive function and motor and perceptual-motor abilities were found even when controlling for acquired verbal knowledge. Neonatal risk factors, early neurodevelopmental impairment, and lower SES were associated with higher rates of deficits within the EPT/ELBW group. The findings document both global and selective cognitive deficits in EPT/ELBW children at school entry and justify efforts at early identification and intervention. (JINS, 2011, 17, 1067–1079)

Episodic memory is one of the most important cognitive domains that involves acquiring, storing and recalling new information. In this article, we describe a new measure developed for the NIH Toolbox, called the Picture Sequence Memory Test (PSMT) that is the first to examine episodic memory across the age range from 3 to 85. We describe the development of the measure and present validation data for ages 20 to 85. The PSMT involves presentation of sequences of pictured objects and activities in a fixed order on a computer screen and simultaneously verbally described, that the participant must remember and then reproduce over three learning trials. The results indicate good test–retest reliability and construct validity. Performance is strongly related to well-established “gold standard” measures of episodic memory and, as expected, much less well correlated with those of a measure of vocabulary. It shows clear decline with aging in parallel with a gold standard summary measure and relates to several other demographic factors and to self-reported general health status. The PSMT appears to be a reliable and valid test of episodic memory for adults, a finding similar to those found for the same measure with children. (JINS, 2014, 20, 1–9)

The original California Verbal Learning Test (CVLT) employed a semantic clustering index that used the words recalled during a given trial as the baseline for calculating expected values of chance clustering (recall-based expectancy). Although commonly used in cognitive psychology, clustering indices that use recall-based calculations of expectancy are implied by the assumption that organizational processes do not occur until after words are retrieved from memory. This assumption contradicts the generally held assumptions among neuropsychologists that (1) organization is an antecedent to recall, and (2) increases in the use of organizational strategies will result in better recall performance. After reviewing a brief history of clustering metrics, we used Monte Carlo simulations, informative examples, and patient data to examine clustering indices that use the word list as a baseline for calculating expectancy and propose these list-based expectancy measures as a refinement of the clustering indices used on the original CVLT. These indices are used on the recently published CVLT–II. (JINS, 2002, 8, 425–435.)

The aim of this study was to examine the associations of apolipoprotein E (APOE) genotype, metabolic changes in the posterior cingulate detected by 1H magnetic resonance spectroscopy (MRS), and neuropsychologic measures of memory and cognition both in normally aging elderly, and in patients with mild cognitive impairment (MCI) and AD. We studied 67 controls, 18 MCI and 33 AD patients. We used the Dementia Rating Scale total score (DRSTOT) as a measure of general cognitive function and the total learning from the Auditory Verbal Learning Test (AVTOT) as a measure of memory performance. No differences were noted on 1H-MRS metabolite ratios or cognitive measures across APOE genotype within control and patient groups. In controls, age was a significant predictor of both cognitive test scores, and NAA/Cr was a univariate associate of DRSTOT. All 3 1H-MRS metabolite ratios, N-acetylaspartate (NAA)/creatine (Cr), myoinositol (MI)/Cr, and NAA/MI, were univariate associates of AVTOT and DRSTOT scores in the combined MCI and AD group. In stepwise regression analyses in the combined patient group only NAA/MI entered the models. These data suggest NAA/Cr could be a modest predictor of general cognitive function in both healthy elderly and impaired patients, while MI/Cr is a more specific marker for neuropsychologic dysfunction associated with neurodegenerative disease. Among 1H-MRS measurements, the NAA/MI ratio maybe the most efficient predictor of memory and cognitive function in patients with MCI and AD. (JINS, 2002, 8, 934–942.)

Rapid eye movement (REM) sleep behavior disorder (RBD) is a sleep disturbance that commonly occurs in Dementia with Lewy bodies (DLB). Retrospective examination of DLB course has shown that RBD and cognitive decline may precede the onset of parkinsonism and visual hallucinations. Therefore, some patients with DLB may initially present with dementia and RBD, but would not meet current formal criteria for probable DLB at that time. The purpose of this study is to determine whether patients with dementia and RBD, who do not have parkinsonism or visual hallucinations, have cognitive profiles that can be distinguished from autopsy-confirmed definite AD, but not from clinically probable DLB. If so, this would support the hypothesis that the presence of RBD and dementia, as the only presenting symptoms, reflects the early manifestation of DLB. Results show that early dementia in probable DLB and dementia with RBD are neuropsychologically indistinguishable. Both groups differ from definite AD of a similar early stage with significantly worse visual perceptual organization, sequencing and letter fluency but significantly better confrontation naming and verbal memory. In addition, follow-up data from a subset of patients with dementia and RBD reveal the subsequent development of parkinsonism or hallucinations 1 to 6 years later. Results indicate that the presentation of dementia and RBD is suggestive of underlying Lewy body disease and not Alzheimer's disease. This provides further evidence in support of including RBD as one of the core diagnostic features of DLB. (JINS, 2002, 8, 907–914.)

Recent studies have described neuromaturation and cognitive development across the lifespan, yet few neuroimaging studies have investigated task-related alterations in brain activity during adolescence. We used functional magnetic resonance imaging (fMRI) to examine brain response to a spatial working memory (SWM) task in 49 typically developing adolescents (25 females and 24 males; ages 12–17). No gender or age differences were found for task performance during SWM. However, age was positively associated with SWM brain response in left prefrontal and bilateral inferior posterior parietal regions. Age was negatively associated with SWM activation in bilateral superior parietal cortex. Gender was significantly associated with SWM response; females demonstrated diminished anterior cingulate activation and males demonstrated greater response in frontopolar cortex than females. Our findings indicate that the frontal and parietal neural networks involved in spatial working memory change over the adolescent age range and are further influenced by gender. These changes may represent evolving mnemonic strategies subserved by ongoing adolescent brain development. (JINS, 2005, 11, 631–644.)

The purpose of this study was to examine the relation between the subjective report of feeling foggy at one-week post concussion and acute neuropsychological outcome. The outcome variables were derived from a computerized neuropsychological screening battery, Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT). Participants were 110 high school students who sustained a sports-related concussion and were evaluated 5–10 days post injury (M = 6.8 days). Athletes were divided into two groups on the basis of self-reported fogginess. The first group reported no fogginess (n = 91), whereas the second group reported experiencing some degree of fogginess (n = 19) on a 6-point scale. The athletes with persistent fogginess experienced a large number of other post-concussion symptoms, compared to the athletes with no reported fogginess. In addition, the athletes with persistent fogginess had significantly slower reaction times, reduced memory performance, and slower processing speed. Thus, athletes with any degree of self-reported fogginess at one-week post injury are likely to have adverse effects from their concussions in multiple domains. (JINS, 2004, 10, 904–906.)

Cognitive impairments in schizophrenia are well documented and correlated with functional disability. Although some patients demonstrate normal neuropsychological (NP) functioning, little is known about their functional disability. We examined the cross-sectional functional implications of NP normality and symptomatic remission in older outpatients diagnosed with schizophrenia or schizoaffective disorder, who were administered a NP battery and performance-based measures of functional and social competence, with their real-world functioning rated by case managers. NP status was classified by the General Deficit Score (GDS) and remission status was based on the Positive and Negative Syndrome Scale (PANSS), yielding four subsamples of patients: NP normal-remitted (n = 21), NP normal-symptomatic (n = 22), NP impaired-remitted (n = 90), and NP impaired-symptomatic (n = 97). NP normal patients demonstrated better functional and social competence and better ratings of real world functioning, after controlling for premorbid abilities. However, compared to normative date, NP normal patients manifested disability in several real-world domains, including residential status. These results suggest that NP status is a better predictor of functional outcome then symptom status or the interaction of the two factors. The disability seen in NP normal cases indicates that factors other than cognitive impairments may determine aspects of everyday outcomes in schizophrenia. (JINS, 2008, 14, 479–488.)

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)