Studies examining implicit memory performance in Alzheimer's disease (AD) have yielded inconsistent findings, with these patients demonstrating impaired performance within some priming studies and intact performance within others. The present study examined the role of task sensitivity in detecting impaired priming in memory-impaired patients. Twelve healthy older adults and 12 AD patients were administered a picture fragment identification test. Task sensitivity was increased by employing stimulus cues expected to produce larger and more variable priming effects than obtained in previous studies. A simple comparison of priming scores revealed that the AD patients demonstrated significantly impaired priming relative to normal control participants. However, further analysis of priming in relation to certain stimulus characteristics revealed that AD patients often demonstrated impaired priming when overall priming effects were large but relatively intact priming when priming effects were small. These findings suggest that the prevention of ceiling effects in control participants may aid in the detection of impaired priming in patient populations. (JINS, 2001, 7, 294–301.)

Subtraction of serial scores, Least Squares Estimators, and Best Linear Unbiased Predictors (BLUPs) were compared for estimating rates of cognitive change for Mini-Mental State Exam (MMSE) and Dementia Rating Scale (DRS) scores for 299 probable Alzheimer's disease patients. The BLUPs provided cleaner group estimates of subjects' intercepts and slopes and are preferred. Regression analysis of the BLUP estimates of rate of change indicated that steeper declines were associated with higher levels of education and older age at onset. These effects were much smaller than those due to estimated initial cognitive test score. Differences in longitudinal metric characteristics of the MMSE and DRS were found, with the DRS yielding more precise change estimates. We discuss modeling these longitudinal data, and discuss use of the estimates of rate of change and intercept as data in their own right. (JINS, 2001, 7, 813–824.)

The study investigated longitudinal change in cognitive function in 87 patients with Huntington's disease (HD), using a range of neuropsychological tests, which tap mental manipulative abilities, memory, and frontal executive skills. Over a 1-year period the largest changes were noted in letter fluency, object recall, and Stroop Test performance, whereas no changes were noted over more than 3 years on the modified Wisconsin Card Sorting Test. Contrary to expectation, greater change was evident over 1 year for tasks with low compared to high cognitive demands. The differential sensitivity of tasks was attributed in part to inherent characteristics of the tests themselves: their capacity to detect minor gradations of change and their vulnerability to practice effects. However, the greater change for relatively automatic, speed-based tasks with low cognitive demands was interpreted as reflecting the evolution of HD, with a greater magnitude of change occurring in basal ganglia than cortical function. One purpose of the study was to identify tasks sensitive to the progression of HD and hence most suitable for the evaluation of therapies. Despite reaching statistical significance by virtue of the large group size, numerical differences in test scores over 1 year were very small, suggesting that the use of such tests to evaluate change in individuals or small groups of subjects would be problematic. The data highlight the slow progression of HD, the limitations of standard cognitive tests in detecting change over short periods, and the need for therapeutic studies that encompass a relatively prolonged time frame. (JINS, 2001, 7, 33–44.)

Differential performance on measures of episodic and semantic memory were examined in AD, cortical vascular dementia (CVaD), subcortical vascular dementia (SVaD), and controls. Groups were matched on age, education, and gender; dementia groups also were matched on severity. Recognition/retrieval differences were found only between SVaD and AD groups, not between CVaD and AD. Thus, recognition/retrieval differences are likely secondary to subcortical pathology rather than to vascular etiology per se. Similarly, significant numbers of memory errors were associated with cortical pathology, regardless of etiology. Error rate differences were found only between SVaD and AD groups, not between CVaD and AD. Finally, rapid forgetting was unique to AD; however, since no difference was found between SVaD and AD, rapid forgetting may occur only as AD progresses. No semantic memory measure differentiated AD from either CVaD or SVaD subjects. Results suggest that some previously reported episodic differences may be due to cortical versus white matter subcortical pathology, rather than to AD versus vascular etiology. (JINS, 2001, 7, 563–573.)

Attentional–inhibitory control and social–behavioral regulation are two outcome domains commonly impaired after childhood closed head injury (CHI). We compared neuropsychological tests of attentional–inhibitory control (vigilance, selective attention, response modulation) and social discourse and intentionality (inferencing, figurative language, and speech acts) with parent ratings of attention and behavioral regulation in relation to four injury- related variables: age at CHI, time since CHI, CHI injury severity, and frontal lobe injury moderated by CHI severity. Participants were 105 school-aged children in the chronic stage of CHI, divided into mild, moderate, and severe injury severity groups, and further subdivided according to frontal lobe injury. Outcome indices were imperfectly correlated in the group as a whole, although several relations between neurocognitive tests and parent ratings were observed within CHI subgroups. Different domains of cognitive function had different predictors. For attentional–inhibitory control, age at injury and time since injury were most predictive of outcome; for social discourse, predictors were injury severity and frontal lobe injury moderated by injury severity. Variability in cognitive outcome after childhood CHI is not random, but appears related to age, time, and biological features of the injury. (JINS, 2001, 7, 683–692.)

Previous research had demonstrated diminished interhemispheric Stroop effects in individuals with agenesis of the corpus callosum (ACC), suggesting an important role for the callosum in interhemispheric color-word and color-patch interactions. However, this outcome rested on the results of only 1 ACC participant, who had normal intelligence and a minimum of other neuropathology. In the research reported herein, the role of the corpus callosum in interhemispheric Stroop interference and facilitation was investigated in 9 individuals with complete or partial ACC and normal intelligence, and in non-ACC controls. Congruent, incongruent, or neutral stimulus pairs were presented either unilaterally (color-patch and color-word in the same visual field) or bilaterally (color-patch and color-word in different visual fields). Both unilateral and bilateral (interhemispheric) Stroop interference were found for both ACC and non-ACC groups, with no significant difference in magnitude, indicating that extracallosal pathways are sufficient for mediating this phenomenon. It is suggested that the anterior commissure is a more likely candidate for the interhemispheric transmission of the semantic information resulting in Stroop interference. (JINS, 2001, 7, 302–311.)

Previous studies conducted by our group have provided evidence for age-related reductions in cortical thickness in dorsal frontal and parietal regions between childhood and adulthood, and gray matter volume increases of mesial temporal and anterior diencephalic structures. The purpose of this study was to describe neurobehavioral correlates of these brain maturational changes using morphometric analyses of brain magnetic resonance images (MRI) and two tests of cognitive abilities. Participants were 35 normal children roughly stratified by age (7 to 16 years) and sex (20 boys and 15 girls) and frontal and mesial temporal regions were anatomically defined in each subjects' MRI data. The California Verbal Learning Test–Children's Version and the Rey-Osterrieth Complex Figure test were used as measures of verbal and visuospatial memory and organizational abilities. Analyses designed to show regionally specific relationships between the brain and behavioral measures revealed interesting results. Specifically, frontal lobe gray matter thinning was more strongly predictive of delayed verbal memory functioning than was the mesial temporal lobe gray matter volume, and this relationship did not appear to be mediated by factors indexed in chronological age. Similar, but less regionally specific relationships were observed for measures of visuospatial memory abilities and frontal lobe maturation. Functional imaging studies in the literature consistently report activation in frontal regions in adults during retrieval tasks. The relationship between frontal lobe maturation and delayed recall observed here may be reflective of the children's development towards the more adult-like frontal lobe function revealed in the functional imaging studies. (JINS, 2001, 7, 312–322.)

Children and adolescents with Klinefelter syndrome (XXY) have been reported to show deficits in language processing including VIQ < PIQ and a learning disability in reading and spelling. However, whether this is characteristic of adults with Klinefelter syndrome has not been established. Thirty-five men with Klinefelter syndrome, aged 16 to 61, and 22 controls were evaluated with a comprehensive neuropsychological battery. The Klinefelter patients scored significantly below controls in language skills, verbal processing speed, verbal and nonverbal executive abilities, and motor dexterity. Within the Klinefelter sample, three cognitive subgroups were identified: VIQ 7 or more points below PIQ (n = 10), VIQ within 6 points of PIQ (n = 12), and PIQ 7 or more points below VIQ (n = 12). The deficits detected in language, verbal processing speed, and verbal executive skills were found to be isolated to the VIQ < PIQ subgroup, while the abnormalities in motor dexterity and nonverbal executive skills were confined to the PIQ < VIQ subgroup. Older age was significantly correlated with increases in VIQ relative to PIQ in the patient group, which suggests the intriguing possibility that the PIQ < VIQ subgroup primarily emerges in young adulthood, perhaps in response to the reported hormonal abnormalities detected in Klinefelter syndrome patients during puberty. (JINS, 2001, 7, 446–456)

CVLT and WMS–R Digit Span variables were used to calculate indexes of seven specific short- and long-term memory processes: working memory span and central executive functions, and long-term memory encoding, consolidation, retention, retrieval, control abilities. Scores on these indexes were then cluster-analyzed to determine whether subtypes of memory performance exist that correspond to deficits in these theoretical memory constructs. Parallel analyses were conducted with two large samples (N = 150 and N = 151) of individuals who had sustained a traumatic brain injury (TBI). Findings showed that TBI results in subgroups of memory disorders with specific deficits in consolidation, retention, and retrieval processes. Control problems (keeping track of list versus non-list items) only appeared in conjunction with retrieval deficits. Working memory span and central executive functioning (i.e., the ability to manipulate information in working memory) do not appear to be deficits characteristic of TBI as no such clusters emerged in the analyses. By using specific indexes of memory processes, and in contrast to previous studies, patterns of memory dysfunction were found that correspond to deficits in theoretically meaningful memory constructs. (JINS, 2001, 7, 574–585.)

Forty-one boys diagnosed with Duchenne muscular dystrophy (DMD) were each compared to an unaffected sibling on a battery of neuropsychological tests. Verbal, visuospatial, attention/memory, abstract thinking, and academic achievement skills were tested. Results indicated the boys with DMD performed similarly to their siblings on the majority of measures, indicating intact verbal, visuospatial, long-term memory, and abstract skills. However, the DMD group did significantly more poorly than their siblings on specific measures of story recall, digit span, and auditory comprehension, as well as in all areas of academic achievement (reading, writing, and math). This profile indicates that verbal working memory skills are selectively impaired in DMD, and that that likely contributes to limited academic achievement. The association between the known impact of the genetic mutation on the development of the central nervous system and boys' cognitive profile is discussed. (JINS, 2001, 7, 45–54.)

We describe the standardization of three new tests of knowledge of quantity facts, number operations and multiplication facts. We also report a validation study in which a group of 50 patients with cortical degenerative disorders were tested on these three new tests of number processing. Our results show that the quantity facts and number operations tests are sensitive measures of number processing abilities. Performance on the three new tests and the Graded Difficulty Arithmetic (GDA) test were found to be significantly impaired in the Alzheimer's Disease (AD) group. The frontotemporal dementia (FTD) group was subdivided into those with a semantic dementia (SD) and those with prominent frontal features (Non-SD). The semantic dementia subgroup was more impaired than both the AD patient group and the nonsemantic FTD subgroup on the quantity facts test. A more fine grained analysis reveals several interesting patterns of performance, including a dissociation between impaired performance on the quantity facts and number operations tests and preserved performance on the GDA. The findings attest the value of comparing performance on the GDA and our new tests in delineating the nature of an individual's number processing deficits. Implications for the relation between simple arithmetic fact knowledge and higher level number processing are discussed. (JINS, 2001, 7, 825–834.)

Neuropsychology, with its emphasis on standardized and empirically based methods, has made a number of scientific contributions to address growing concerns about concussions resulting from sports injuries. This study employs a test–retest paradigm to determine the immediate effects of concussion in high-school and college athletes. The Standardized Assessment of Concussion (SAC) was administered to 1,313 male athletes prior to the beginning of the competitive season. Reliable change indices and multiple regression models were computed on retest scores obtained from 68 noninjured athletes who were readministered the SAC at either 60 or 120 days following baseline testing. Receiver operating characteristic (ROC) curve analyses were used to test these models with data obtained on 50 athletes tested immediately following concussion. The results indicate that a decline of 1 point on the SAC at retesting classified injured and noninjured participants with a level of 94% sensitivity and 76% specificity. The RCI and multiple regression models provided comparable levels of group classification, but provided cut-offs that are conservative for use with this population. The results support and extend previous research findings indicating that the SAC is a valid instrument for detecting the immediate effects of mild traumatic brain injury. (JINS, 2001, 7, 693–702.)

Rapid rate of recovery has been associated with better outcome following closed-head injuries, but few studies have compellingly demonstrated this. This study used growth curve analyses of Disability Rating Scale (DRS) scores at acute hospitalization discharge, 1, 3, and 6 months post injury in a sample of 55 patients with a closed-head injury. Six month post-injury outcome measures were taken from significant other (SO) responses on the NYU Head Injury Family Interview (NYU-HIFI) including severity and burden ratings of affective/neurobehavioral disturbance, cognitive deficits, and physical/dependency status. Rate of recovery (linear and curvilinear recovery curve components) was significantly related to the level of affective/neurobehavioral severity, and the severity and burden of SO-perceived cognitive deficits. Only the intercept of the DRS recovery curve was associated with the SO-perceived severity and burden of physical/dependency status. Growth curve modeling is a meaningful and powerful tool in predicting head injury outcome. (JINS, 2001, 7, 457–467.)

Gender specific discrepancies on psychometric examination are often interpreted to reflect static differences in cerebral hemisphere specialization, but dynamic alterations relating to circulating gonadal hormones may also be relevant after puberty. The often cited inference of a right hemisphere advantage in males and left hemisphere advantage in females derived from small but reliable differences on spatial tasks and verbal tasks, for example, may to some extent relate to gender-specific differences in circulating gonadal hormones. Performance fluctuations on other higher order cognitive tasks through the menstrual cycle tend to support a temporal association between alterations in cerebral laterality and hormone fluctuations. A potential left hemisphere advantage after menstruation when estrogen and progesterone levels are high in contrast to a right hemisphere advantage at menstruation when estrogen and progesterone levels are low has also received support from shifts in visual field perception. The present investigation continues this line of work by measurement of prospective changes in unirhinal olfactory acuity in the menstrual, ovulatory, and midluteal phases of the menstrual cycle in 11 healthy women who agreed to blood assays of estradiol and progesterone prior to completing a modified version of the Connecticut Chemosensory Perception Exam (CCPE). The CCPE detection of n-butanol showed a clear pattern of changes over the menstrual cycle marked by an asymmetry favoring the right nostril during menstruation when estradiol and progesterone levels were low, an asymmetry favoring the left nostril during ovulation when estradiol levels were high and progresterone levels were low, and an absence of asymmetry during the midluteal phase when estradiol levels decreased and progesterone levels increased. Preliminary correlation analyses revealed a potential competitive influence of estradiol and progesterone on this apparent shift in cerebral laterality. There is thus sufficient evidence to conclude that dynamic changes in relative cerebral hemisphere advantages have a temporal relation to fluctuations in circulating gonadal hormones and to suggest the value of additional investigation of more specific causal relations. (JINS, 2001, 7, 703–709.)

We have recently reported (Saykin et al., 1999b) selective activation of left medial temporal lobe structures during processing of novel compared to familiar words using functional magnetic resonance imaging (fMRI). The current study describes the relationship between a widely used clinical test of verbal learning, the California Verbal Learning Test (CVLT), and the previously reported fMRI activations. Thirteen right-handed healthy adult participants were studied with whole brain echo-planar fMRI while listening to novel and recently learned (familiar) words intermixed pseudorandomly in an event-related design. These participants were also tested with the CVLT. Scores for CVLT Trial 1 (immediate encoding of novel words) and recognition discriminability (recognition of familiar vs. novel words) were correlated with fMRI signal change during processing of novel versus familiar words using a covariance model implemented in SPM96. For the novel words analysis, voxels in the right anterior hippocampus correlated significantly with Trial 1 (r = .76 at the maxima). For the recognition analysis, a significant cluster of voxels was found in the right dorsolateral prefrontal cortex (r = .88 at the maxima). Our prior results of separable left medial temporal activation to novel and familiar words, together with results of the covariance analyses reported here, suggest that in addition to the left medial temporal lobe (MTL) regions that are engaged during novel and familiar word processing, the right hippocampus and right frontal lobe are also involved, particularly in those participants with better memory ability. This positive relationship between fMRI activation and CVLT performance suggests a role for these right hemisphere regions in successful memory processing of verbal material, perhaps reflecting more efficient encoding and retrieval strategies that facilitate memory. (JINS, 2001, 7, 55–62.)

Gulf War unexplained illnesses (GWUI) are a heterogeneous collection of symptoms of unknown origin known to be more common among veterans of the Gulf War than among nonveterans. In the present study we focused on one of these unexplained illnesses. We tested the hypothesis that in a sample of Persian Gulf War veterans chronic fatigue syndrome (CFS) was associated with cognitive deficits on computerized cognitive testing after controlling for the effects of premorbid cognitive differences. We obtained Armed Forces Qualification Test (AFQT) data acquired around the date of induction into the military on 94 veterans of the Gulf War, 32 with CFS and 62 healthy controls. Controls performed better than participants diagnosed with CFS on the AFQT. Cognitive deficits were associated with CFS on 3 of 8 variables after the effect of premorbid AFQT scores was removed with ANCOVA. (JINS, 2001, 7, 835–839.)

The ability to generate items belonging to categories in verbal fluency tasks has been attributed to frontal cortex. Nonverbal fluency (e.g., design fluency) has been assessed separately and found to rely on the right hemisphere or right frontal cortex. The current study assessed both verbal and nonverbal fluency in a single group of patients with focal, frontal lobe lesions and age- and education-matched control participants. In the verbal fluency task, participants generated items belonging to both letter cues (F, A, and S) and category cues (animals and boys' names). In the design fluency task, participants generated novel designs by connecting dot arrays with 4 straight lines. A switching condition was included in both verbal and design fluency tasks and required participants to switch back and forth between different sets (e.g., between naming fruits and furniture). As a group, patients with frontal lobe lesions were impaired, compared to control participants, on both verbal and design fluency tasks. Patients with left frontal lesions performed worse than patients with right frontal lesions on the verbal fluency task, but the 2 groups performed comparably on the design fluency task. Both patients and control participants were impacted similarly by the switching conditions. These results suggest that verbal fluency is more dependent on left frontal cortex, while nonverbal fluency tasks, such as design fluency, recruit both right and left frontal processes. (JINS, 2001, 7, 586–596.)

The present study explored the explanatory power of Mittenberg's “expectation as etiology” theory for the persistence of postconcussion syndrome (PCS) complaints. One hundred forty-one participants completed a PCS symptom checklist under 2 conditions. Normal controls, healthy athletes and depressed individuals reported current symptoms and symptoms expected following a hypothetical mild head injury. Head-injured athletes, chronic headache sufferers, and a 2nd sample of normal controls reported current symptoms and retrospective symptoms (prior to their injury/illness or from some point in the past). Depressed individuals reported more current symptoms than normal controls and healthy athletes, demonstrating that “PCS” symptoms are not specific to PCS. All groups expected more symptoms following mild head injury than currently experienced, supporting the idea that individuals expect negative consequences following head injury. However, healthy athletes expected fewer symptoms than normals or depressed individuals, possibly due to preexisting expectations for speedy recovery. Both head-injured athletes and headache sufferers reported more current symptoms than the past, but not at a rate lower than baseline of normal controls. Results suggest that the “expectation as etiology” hypothesis may be too specific, and that, following any negative event, people may attribute all symptoms to that negative event (the “good old days” hypothesis). (JINS, 2001, 7, 323–333.)