Arterial spin labeling (ASL) is a magnetic resonance imaging (MRI) method that provides a highly repeatable quantitative measure of cerebral blood flow (CBF). As compared to the more commonly used blood oxygenation level dependent (BOLD) contrast-based methods, ASL techniques measure a more biologically specific correlate of neural activity, with the potential for more accurate estimation of the location and magnitude of neural function. Recent advances in acquisition and analysis methods have improved the somewhat limited sensitivity of ASL to perfusion changes associated with neural activity. In addition, ASL perfusion measures are insensitive to the low-frequency fluctuations commonly observed in BOLD experiments and can make use of imaging sequences that are less sensitive than BOLD contrast to signal loss caused by magnetic susceptibility effects. ASL measures of perfusion can aid in the interpretation of the BOLD signal change and, when combined with BOLD, can measure the change in oxygen utilization accompanying changes in behavioral state. Whether used alone to probe neural activity or in combination with BOLD techniques, ASL methods are contributing to the field's understanding of healthy and disordered brain function. (JINS, 2007, 13, 517–525.)

Blast-related head injuries are one of the most prevalent injuries among military personnel deployed in service of Operation Iraqi Freedom. Although several studies have evaluated symptoms after blast injury in military personnel, few studies compared them to nonblast injuries or measured symptoms within the acute stage after traumatic brain injury (TBI). Knowledge of acute symptoms will help deployed clinicians make important decisions regarding recommendations for treatment and return to duty. Furthermore, differences more apparent during the acute stage might suggest important predictors of the long-term trajectory of recovery. This study evaluated concussive, psychological, and cognitive symptoms in military personnel and civilian contractors (N = 82) diagnosed with mild TBI (mTBI) at a combat support hospital in Iraq. Participants completed a clinical interview, the Automated Neuropsychological Assessment Metric (ANAM), PTSD Checklist-Military Version (PCL-M), Behavioral Health Measure (BHM), and Insomnia Severity Index (ISI) within 72 hr of injury. Results suggest that there are few differences in concussive symptoms, psychological symptoms, and neurocognitive performance between blast and nonblast mTBIs, although clinically significant impairment in cognitive reaction time for both blast and nonblast groups is observed. Reductions in ANAM accuracy were related to duration of loss of consciousness, not injury mechanism. (JINS, 2011, 17, 000–000)

This study tested the hypothesis that affective arousal in response to eye contact is negatively associated with face identification skills in children with autism spectrum disorder (ASD). Participants were 20 children and adolescents with ASD and 20 age- and IQ-matched typically developing (TD) children. Skin conductance response (SCR), a psychophysiological measure of autonomic arousal, was collected while participants viewed faces with gaze directed toward them and faces with gaze averted away from them. Participants also completed an independent match-to-sample face recognition test. Children with ASD exhibited significantly larger SCRs than TD children to faces with direct and averted gaze. There were no differences between SCRs to direct gaze and averted gaze in either group. Children with ASD exhibited a marginally significant decrease in face recognition accuracy relative to TD children, particularly when face recognition depended on the eye region of the face. Face recognition accuracy among children with ASD was negatively correlated with the amplitude of SCRs to direct gaze but not to averted gaze. There was no association between face recognition accuracy and SCRs to gaze in the TD group. These findings suggest that autonomic reactivity to eye contact may interfere with face identity processing in some children with ASD. (JINS, 2008, 14, 947–955.)

A multicenter randomized control trial (RCT) was conducted to evaluate the effects of a treatment for dysexecutive problems after acquired brain injury (ABI) on daily life functioning. Seventy-five ABI patients were randomly allocated to either the experimental treatment, multifaceted strategy training for executive dysfunction, or a control treatment, computerized cognitive function training. Assessment took place before, directly after, and 6 months post-treatment. The primary outcome measure, the Role Resumption List (RRL), and two other follow-up measures, the Treatment Goal Attainment (TGA) and the Executive Secretarial Task (EST), were indications of daily life executive functioning. The experimental group improved significantly more over time than the controls on the RRL and attained significantly higher scores on the TGA and EST. We conclude that our treatment has resulted in significant improvements of executive functioning in daily life, lasting at least 6 months post-treatment. Although control patients’ satisfaction and subjective well-being were at the same level, the experimental group had better abilities to set and accomplish realistic goals, to plan, initiate, and regulate a series of real-life tasks, and to resume previous roles with respect to work, social relations, leisure activities, and mobility. (JINS, 2010, 16, 118–129.)

Spina bifida myelomeningocele (SBM), a neural tube defect that is the product of a complex pattern of gene-environment interactions, is associated with naturally occurring, systematic variability in the neural phenotype and in environmental factors that lead to systematic variability in the cognitive phenotype. We characterize the basis for variability in the cognitive phenotype of children with SBM with reference to a model of key biological, cognitive, and environmental events unfolding over the course of development from infancy to middle age. The cognitive phenotype is not domain-specific, but represents manifestations of unobservable constructs involving associative and assembled processing, the latter directly reflecting the impact of the neural phenotype on core deficits involving movement, timing, and attention orienting. The expression of the cognitive phenotype is variable, being moderated by features of the neural phenotype involving secondary CNS insults (such as hydrocephalus) that impair assembled processing, as well as by environmental factors (such as poverty, parenting, and education) that impair associative processing. The preservation of strengths in associative processing depends in part on the severity of the CNS deficits in SBM and the impact of the environment. (JINS, 2006, 12, 285–296.)

Given the importance of identifying dementia prodromes for future treatment efforts, we examined two methods of diagnosing mild cognitive impairment (MCI) and determined whether empirically-derived MCI subtypes of these diagnostic methods were consistent with one another as well as with conventional MCI subtypes (i.e., amnestic, non-amnestic, single-domain, multi-domain). Participants were diagnosed with MCI using either conventional Petersen/Winblad criteria (n = 134; >1.5 SDs below normal on one test within a cognitive domain) or comprehensive neuropsychological criteria developed by Jak et al. (2009) (n = 80; >1 SD below normal on two tests within a domain), and the resulting samples were examined via hierarchical cluster and discriminant function analyses. Results showed that neuropsychological profiles varied depending on the criteria used to define MCI. Both criteria revealed an Amnestic subtype, consistent with prodromal Alzheimer's disease (AD), and a Mixed subtype that may capture individuals in advanced stages of MCI. The comprehensive criteria uniquely yielded Dysexecutive and Visuospatial subtypes, whereas the conventional criteria produced a subtype that performed within normal limits, suggesting its susceptibility to false positive diagnostic errors. Whether these empirically-derived MCI subtypes correspond to dissociable neuropathologic substrates and represent reliable prodromes of dementia will require additional follow-up. (JINS, 2013, 19, 1–11)

Recently, there has been renewed interest in the study of cognitive fatigue. It is known that fatigue is one of the most disabling symptoms in numerous neurological populations, including stroke, multiple sclerosis, Parkinson's disease, and traumatic brain injury. Behavioral studies of cognitive fatigue are hampered by lack of correlation of self-report measures with objective performance. Neuroimaging studies provide new insight about cognitive fatigue and its neural correlates. Impairment within the cortico-striatal network, involved in effort–reward calculation, has been suggested to be critically related to fatigue. The current review surveys the recent neuroimaging literature, and suggests promising avenues for future research. (JINS, 2013, 19, 1–5)

We examined change in neuropsychological test performance related to type 2 diabetes mellitus across a 6-year interval. A population-based sample of 274 elderly participants (36 with diabetes and 238 without diabetes) was examined at four occasions at a 2-year interval. The participants were 80–93 years of age (M = 82.8 years) and without dementia at baseline. The test battery included tests of speed, visuospatial ability, short-term memory, semantic memory, episodic memory, and the Mini Mental Status Examination. Several models, taking into account diabetes and demographic data, were analyzed using SAS Proc Mixed multilevel modeling. At baseline, there were no significant differences in the neuropsychological tests related to diabetes. The longitudinal analyses, however, showed that diabetes was a significant predictor of decline for many of the tests. These findings points to the conclusion that type 2 diabetes is associated with accelerated cognitive decline in old age that may result in dementia. (JINS, 2004, 10, 599–607.)

Individuals with anorexia nervosa (AN) are often characterized as possessing excessive self-control and are unusual in their ability to reduce or avoid the consumption of palatable foods. This behavior promotes potentially life-threatening weight loss and suggests disturbances in reward processing. We studied whether individuals with AN showed evidence of increased self-control by examining the tendency to delay receipt of a monetary, non-food related, reward. Underweight AN (n = 36) and healthy controls (HC, n = 28) completed a monetary intertemporal choice task measuring delay discounting factor. Individuals with AN reduced the value of a monetary reward over time significantly less than HC (F[1,61] = 5.03; p = 0.029). Secondary analyses indicated that the restricting subtype of AN, in particular, showed significantly less discounting than HC (F[1,46] = 8.3; p = 0.006). These findings indicate that some individuals with AN show less temporal discounting than HC, suggestive of enhanced self-control that is not limited to food consumption. This is in contrast to other psychiatric disorders, for example, substance abuse, which are characterized by greater discounting. Though preliminary, these findings suggest that excessive self-control may contribute to pathological processes and individuals with AN may have neuropsychological characteristics that enhance their ability to delay reward and thereby may help to maintain persistent food restriction. (JINS, 2012, 18, 1–8)

To identify the cognitive characteristics predictive of incident dementia in Parkinson’s disease (PD), we examined the baseline neuropsychological profiles of 18 initially non-demented patients with PD who met diagnostic criteria for dementia (PDD) at one-year follow-up. PDD participants’ baseline neuropsychological test scores were compared to the baseline performance of 18 patients with PD who did not meet criteria for dementia at one-year follow-up (PDND) and 18 normal controls (NC). The three groups were matched on baseline demographic and disease variables. Relative to the PDND group, the incident PDD participants demonstrated significantly poorer performance on digits backward (Wechsler Memory Scale–Revised), word list learning and recognition (California Verbal Learning Test), and perseverative errors on the Wisconsin Card Sorting Test. Each of these baseline neuropsychological variables exhibited adequate diagnostic classification accuracy in predicting PDD and PDND group membership at follow-up. These results suggest that subtle frontal0executive dysfunction is evident during the immediate PDD prodrome and may be of prognostic value in identifying PD patients at risk for dementia. Accordingly, neuropsychological evaluation may facilitate early identification of PDD and thereby inform appropriate dispositional planning. (JINS, 2003, 9, 17–24.)

Hypoxia damages multiple organ systems especially those with high oxygen utilization such as the central nervous system. The purpose of this study was to compare the neuropathological and neuropsychological effects of hypoxia in patients with either carbon monoxide poisoning or obstructive sleep apnea. Neuroimaging revealed evidence of hippocampal atrophy in both groups although a linear relationship between hippocampal volume and memory performance was found only for selected tests and only in the sleep apnea group. There were significant correlations between hippocampal volume and performance on measures related to nonverbal/information processing. Generalized brain atrophy, as measured by the ventricle-to-brain ratio, was more common in the carbon monoxide poisoning group compared to the obstructive sleep apnea group. Performance on tests of executive function improved following treatment with nasal continuous positive airway pressure treatment in the obstructive sleep apnea group but there was no associated improvement in general intellectual function. We found that hypoxia due to obstructive sleep apnea and CO poisoning resulted in neuropathological changes and neuropsychological impairments. The observed group differences provide insight into the relationship between etiology of injury, neuropathological changes, and clinical presentation. (JINS, 2004, 10, 60–71.)

The psychometric criterion of mild cognitive impairment (MCI) generally involves having an unusually low score on memory testing (i.e., −1.5 SDs). However, healthy older adults can obtain low scores, particularly when multiple memory measures are administered. In turn, there is a substantial risk of psychometrically misclassifying MCI in healthy older adults. This study examined the base rates of low memory scores in older adults (55–87 years; n = 550) from the Wechsler Memory Scale–Third Edition (WMS-III; Wechsler, 1997b) standardization sample. The WMS-III consists of four co-normed episodic memory tests (i.e., Logical Memory, Faces, Verbal Paired Associates, and Family Pictures) that yield eight age- and demographically-adjusted standard scores (Auditory Recognition and Working Memory tests not included). When the eight age-adjusted scores were examined simultaneously, 26% of older adults had one or more scores at or below the 5th percentile (i.e., −1.5 SDs). On the eight demographically- adjusted scores, 39% had at least one score at or below the 5th percentile. There was an inverse relationship between intellectual abilities and prevalence of low memory scores, particularly with the age-adjusted WMS-III scores. Understanding the base rates of low scores can reduce the overinterpretation of low memory scores and minimize false-positive misclassification.Drs. Brooks, Iverson, and Feldman have no known, perceived, or actual conflict of interest with this research. Dr. Holdnack is the Senior Research Director with The Psychological Corporation. (JINS, 2008, 14, 463–478.)

One theory of normal cognitive aging asserts that decreases in simple processing speed mediate the age-related decline of fluid intelligence. Another possibility is that age-related atrophic changes in frontal brain structures undermine the functioning of executive abilities, thereby producing the same decline. In this study, we used principal components analysis to derive a measure of fluid–spatial intelligence in 197 normal adults between 20 and 92 years of age. Measures of perceptual comparison speed, working memory, and executive ability, as well as regional brain volumes based on high resolution magnetic resonance imaging were obtained from a subsample of 112 participants. We then conducted a series of hierarchical multiple regression analyses to test whether (1) the processing speed theory, (2) frontal–executive theory, or (3) some combination of these best accounted for age-related variation in fluid intelligence. The results showed that perceptual comparison speed, executive ability, and frontal lobe volume each made significant contributions to a regression equation that explained 57% of the variance in fluid intelligence. These findings suggest that both the processing speed and frontal–executive theory of cognitive aging are partially correct and complement one another. (JINS, 2000, 6, 52–61.)

In the present study, the correspondence between clinician-assessed and self-reported neurocognitive performance was contrasted with scores obtained from psychometric neuropsychological tests in 148 psychiatric in-patients. Results revealed that self-reported cognitive functioning was strongly associated with depressive symptomatology but was only poorly related to psychometric neurocognitive performance, particularly in schizophrenia. After illness denial was controlled for, the overall association between subjective and objective test performance was slightly increased but still failed to reach significance in six out of eight analyses. In approximately 20% to 40% of all cases, clinicians judged memory performance to be normal despite substantial impairment revealed by neuropsychological test results (attention parameters: 7–51%). Since (ecological) validity and reliability have been demonstrated for many neurocognitive paradigms, the present results question the validity of non-psychometric neurocognitive assessment and call for a complementation of clinical judgment with neurocognitive assessment. Reasons for decreased sensitivity of self-reported and clinician-assessed neurocognitive functioning are discussed. (JINS, 2004, 10, 623–633.)

Individual differences associated with age and various neurological conditions are often found in many different neuropsychological and cognitive variables. These variables are frequently treated as though they were independent of one another, with the results interpreted in terms of effects on task-specific processes. However, an alternative perspective evaluates the breadth of the individual difference influences, and takes relations with other variables into account when considering effects on specific neurocognitive variables. This analytical procedure is illustrated in analyses of the WAIS-IV and WMS-IV standardization data, and of data from the Virginia Cognitive Aging Project. (JINS, 2009, 15, 650–661.)

Cognitive reserve is widely recognized as a moderator of cognitive decline in patients with senile dementias such as Alzheimer’s disease. The same effect may occur in multiple sclerosis (MS), an immunologic disorder affecting the central nervous system. While MS is traditionally considered an inflammatory, white matter disease, degeneration of gray matter is increasingly recognized as the primary contributor to progressive cognitive decline. Our aim was to determine if individual differences in estimated cognitive reserve protect against the progression of cognitive dysfunction in MS. Ninety-one patients assessed twice roughly 5 years apart were identified retrospectively. Cognitive testing emphasized mental processing speed. Cognitive reserve was estimated by years of education and by performance on the North American Adult Reading Test (NAART). After controlling for baseline characteristics, both years of education (p = .013) and NAART scores (p = .049) significantly improved regression models predicting cognitive decline. Symbol Digit Modalities Test (SDMT) performance showed no significant change in patients with > 14 years of education, whereas it declined significantly in patients with ≤ 14 years of education. We conclude that greater cognitive reserve as indexed by either higher premorbid intelligence or more years of education protects against the progression of cognitive dysfunction in MS. (JINS, 2010, 16, 829–835.)

Posttraumatic stress disorder (PTSD) has been associated with neuropsychological impairments across multiple domains, but consensus regarding the cognitive profile of PTSD has not been reached. In this study of women with PTSD related to intimate partner violence (n = 55) and healthy, demographically similar comparison participants (NCs; n = 20), we attempted to control for many potential confounds in PTSD samples. All participants were assessed with a comprehensive neuropsychological battery emphasizing executive functioning, including inhibition, switching, and abstraction. NCs outperformed PTSD participants on most neuropsychological measures, but the differences were significant only on speeded tasks (with and without executive functioning components). The PTSD group’s mean performance was within the average range on all neuropsychological tests. Within the PTSD group, more severe PTSD symptoms were associated with slower processing speed, and more severe dissociative symptoms were associated with poorer reasoning performance. These results suggest that women with PTSD related to intimate partner violence demonstrate slower than normal processing speed, which is associated with the severity of psychiatric symptoms. We speculate that the cognitive slowing seen in PTSD may be attributable to reduced attention due to a need to allocate resources to cope with psychological distress or unpleasant internal experiences. (JINS, 2009, 15, 879–887.)

The vast majority of traumatic brain injuries (TBI) in children are of mild severity. Even if only a small proportion of children with mild TBI suffer negative outcomes, then mild TBI is a serious public health problem. This review summarizes the literature regarding the neurobehavioral outcomes associated with mild TBI in children and adolescents, focusing on the longstanding debate regarding postconcussive symptoms and attendant conceptual and methodological issues. The review also discusses future research directions, the long-term goal of which is to develop a comprehensive and integrated biopsychosocial model of outcomes that helps guide clinical management. (JINS, 2010, 16, 953–960.)

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.)

These studies provide evidence for slowed spatial orienting of attention in autism. A group of well-defined adult autistic subjects and age-matched normal controls performed a traditional spatial cueing task in which attention-related response facilitation is indexed by speed of target detection. To address the concern that motor impairment may interfere with interpretation of response time measures in those with neurologic abnormality, we also used a new adaptation of the traditional task that depended on accuracy of response (target discrimination) rather than speed of response. This design allowed separation of time to process and respond to target information from the time to move and engage (orient) attention. Results from both tasks were strikingly similar. Normal subjects oriented attention very quickly, and showed maximal performance facilitation at a cued location within 100 ms. Autistic subjects oriented attention much more slowly and showed increasing benefits of a spatial cue with increasing cue-to-target delays. These results are consistent with previous reports that patients with autism, the majority of whom have developmental abnormalities of the cerebellum, as well as those with acquired damage to the cerebellum, are slow to shift attention between and within modalities. This paper also addresses the variability in behavioral findings in autism, and suggests that many of the apparently contradictory findings may actually reflect sampling differences in patterns of brain pathology. (JINS, 1996, 2, 541–550.)