Research into the processing of lexical ambiguities has provided a valuable paradigm for investigating the functional architecture of the language processing system in normal and neurologically impaired populations and specifically, how basal ganglia circuits and the neurotransmitter dopamine may act to enhance and/or suppress various meanings relative to the context in which the lexical ambiguity appears. In this review, we develop the hypothesis that an integrated basal ganglia thalamocortical circuit linking the striatum and inferior frontal cortex is involved in the enhancement and suppression of ambiguous word meanings when a lexical ambiguity is presented within a linguistic context. Reference to behavioral, neurophysiological, and neurochemical studies of subcortical function in both healthy populations and people with Parkinson's disease will be used to provide further support for the proposal that the subcortex is integrally involved in ambiguous word processing. (JINS, 2008, 14, 351–364.)

While it is well known that repetition can enhance memory in amnesia, little is known about which forms of repetition are most beneficial. This study compared the effect on recognition memory of repetition of words in the same semantic context and in varied semantic contexts. To gain insight into the mechanisms by which these forms of repetition affect performance, participants were asked to make Remember/Know judgments during recognition. These judgments were used to make inferences about the contribution of recollection and familiarity to performance. For individuals with intact memory, the two forms of repetition were equally beneficial to overall recognition, and were associated with both enhanced Remember and Know responses. However, varied repetition was associated with a higher likelihood of Remember responses than was fixed repetition. The two forms of repetition also conferred equivalent benefits on overall recognition in amnesia, but in both cases, this enhancement was manifest exclusively in enhanced Know responses. We conclude that the repetition of information, and especially repetition in varied contexts, enhances recollection in individuals with intact memory, but exclusively affects familiarity in patients with severe amnesia. (JINS, 2008, 14, 365–372.)

Neuropsychological studies have shown that patients with Frontotemporal dementia (FTD) perform worse than patients with Alzheimer's disease (AD) on tests of conceptualization and verbal fluency, but better on tests of memory and visuospatial functions. However, it is not known if these distinct cognitive profiles are robust enough to be detected using a relatively brief dementia screening instrument such as the Mattis Dementia Rating Scale (MDRS). To address this issue, the MDRS subscale profiles of patients with autopsy-confirmed FTD (n = 17) or AD (n = 34) were compared. Results showed distinct cognitive profiles in which FTD patients performed worse than AD patients on the Initiation/Perseveration and Conceptualization subscales while performing better on the Memory and Construction subscales. The distinct subscale profiles correctly classified 85% of AD patients and 76% of FTD patients. Profiles were maintained in a subset of mildly-to-moderately demented patients (MDRS ≥ 105) and correctly classified 89% of these patients. In addition, FTD patients (mean = 30.0 points/year) declined faster than AD patients (mean = 14.8 points/year) on MDRS total and specific subscale scores. These results suggest that the MDRS may be a useful adjunct to other clinical measures for distinguishing FTD from AD and tracking the progression of the disorder. (JINS, 2008, 14, 373–383.)

This study examined quantitative magnetic resonance volumes of the thalamus and hippocampus and determined their relationship with cognitive function and clinical seizure characteristics in a sample of 46 unilateral temporal lobe epilepsy (TLE) subjects (20 left and 26 right) and 29 controls. The hippocampus and thalamus exhibited different patterns of volume abnormality, different associations with clinical seizure characteristics, and different patterns of relationship with cognitive measures. Hippocampal volume reduction was primarily ipsilateral to the seizure focus, and thalamic volume reduction was bilateral. Ipsilateral hippocampal volume was significantly correlated with both early neurodevelopmental features (age of seizure onset) and disease characteristics (duration of epilepsy), whereas thalamus integrity was related only to disease variables. Hippocampal volume showed a selective association with verbal memory performance. In contrast, both left and right thalamic volumes were significantly correlated with performance on both memory and nonmemory cognitive domains. These findings underscore the importance of thalamic atrophy in chronic TLE and its potential implications for cognition. (JINS, 2008, 14, 384–393.)

We examined the sensitivity of the Rey Auditory Verbal Learning Test (AVLT), California Verbal Learning Test (CVLT), Boston Naming Test (BNT), and Multilingual Aphasia Examination Visual Naming subtest (MAE VN) to lateralized temporal lobe epilepsy (TLE) in patients who subsequently underwent anterior temporal lobectomy. For the AVLT (n = 189), left TLE patients performed more poorly than their right TLE counterparts [left TLE = 42.9 (10.6), right TLE = 47.7 (9.9); p < .002 (Cohen's d = .47)]. Although statistically significant, the CVLT group difference (n = 212) was of a smaller magnitude [left LTE = 40.7 (11.1), right TLE = 43.8 (9.9); (p < .03, Cohen's d = .29)] than the AVLT. Group differences were also present for both measures of confrontation naming ability [BNT: left LTE = 43.1 (8.9), right TLE = 48.1 (8.9); p < .001 (Cohen's d = .56); MAE VN: left TLE = 42.2, right TLE = 45.6, p = .02 (Cohen's d = .36)]. When these data were modeled in independent logistic regression analyses, the AVLT and BNT both significantly predicted side of seizure focus, although the positive likelihood ratios were modest. In the subset of 108 patients receiving both BNT and AVLT, the AVLT was the only significant predictor of seizure laterality, suggesting individual patient variability regarding whether naming or memory testing may be more sensitive to lateralized TLE. (JINS, 2008, 14, 394–400.)

A detailed morphometric analysis of the cerebellum in autism with and without macrocephaly. Four subject groups (N = 65; male; IQs ≥ 65; age 7 to 26 years) were studied with quantitative MRI; normocephalic and macrocephalic individuals with autism without mental retardation were compared to normocephalic and benign macrocephalic typically developing individuals. Total cerebellum volumes and surface areas of four lobular midsagittal groups were measured. Independent t-tests between autism and control subjects matched for head size revealed no significant differences. Multivariate analyses of variance were also performed, using the diagnostic group as the fixed factor, cerebellar measures as the dependent variables and total intracranial volume, total brain volume, age, verbal IQ, and performance IQ as covariates. No significant differences were found; however, a trend was noted in which macrocephalic individuals with autism consistently exhibited slightly smaller cerebellar volume or surface area when compared to individuals with benign macrocephaly. In autism, with and without macrocephaly, cerebellar structures were found to be proportional to head size and did not differ from typically developing subjects. (JINS, 2008, 14, 401–413.)

The regional distribution of degeneration of the corpus callosum (CC) in dementia is not yet clear. This study compared regional CC size in participants (n = 179) from the Cache County Memory and Aging Study. Participants represented a range of cognitive function: Alzheimer's disease (AD), vascular dementia (VaD), mild ambiguous (MA–cognitive problems, but not severe enough for diagnosis of dementia), and healthy older adults. CC outlines obtained from midsagittal magnetic resonance images were divided into 99 equally spaced widths. Factor analysis of these callosal widths identified 10 callosal regions. Multivariate analysis of variance revealed significant group differences for anterior and posterior callosal regions. Post-hoc pairwise comparisons of CC regions in patient groups as compared to the control group (controlling for age) revealed trends toward smaller anterior and posterior regions, but not all were statistically significant. As compared to controls, significantly smaller anterior and posterior CC regions were found in the AD group; significantly smaller anterior CC regions in the VaD group; but no significant CC regional differences in the MA group. Findings suggest that dementia-related CC atrophy occurs primarily in the anterior and posterior portions. (JINS, 2008, 14, 414–423.)

Attentional deficits are common and significant sequelae of pediatric traumatic brain injury (TBI). However, little is known about how the underlying neural processes that support different components of attention are affected. The present study examined brain activation patterns using fMRI in a group of young children who sustained a TBI in early childhood (n = 5; mean age = 9.4), and a group of age-matched control children with orthopedic injuries (OI) (n = 8) during a continuous performance task (CPT). Four children in the TBI group had moderate injuries, and one had a severe injury. Performance on the CPT task did not differ between groups. Both TBI and OI children activated similar networks of brain regions relevant to sustained attention processing, but the TBI group demonstrated several areas of significantly greater activation relative to controls, including frontal and parietal regions. These findings of over-activation of the relevant attention network in the TBI group contrast with those obtained in imaging studies of Attention-Deficit/Hyperactivity Disorder where under-activation of the attention network has been documented. This study provides evidence that young children's brains function differently following a traumatic brain injury, and that these differences persist for years after the injury. (JINS, 2008, 14, 424–435.)

The frequency and determinants of abnormal test performance by normal individuals are critically important to clinical inference. Here we compare two approaches to predicting rates of abnormal test performance among healthy individuals with the rates actually shown by 327 neurologically normal adults aged 18–92 years. We counted how many participants produced abnormal scores, defined by three different cutoffs with test batteries of varied length, and the number of abnormal scores they produced. Observed rates generally were closer to predictions based on a series of Monte Carlo simulations than on the binomial model. They increased with the number of tests administered, decreased as more stringent cutoffs were used to identify abnormality, varied with the degree of correlation among test scores, and depended on individual differences in age, education, race, sex, and estimated premorbid IQ. Adjusting scores for demographic variables and premorbid IQ did not reduce rates of abnormal performance. However, it eliminated the contribution of these variables to rates of abnormal test performance. These findings raise fundamental questions about the nature and interpretation of abnormal test performance by normal, healthy adults. (JINS, 2008, 14, 436–445.)

Disturbances of visual perception frequently accompany neurodegenerative disorders but have been little studied in Huntington's disease (HD) gene carriers. We used psychophysical tests to assess visual perception among individuals in the prediagnostic and early stages of HD. The sample comprised four groups, which included 201 nongene carriers (NG), 32 prediagnostic gene carriers with minimal neurological abnormalities (PD1); 20 prediagnostic gene carriers with moderate neurological abnormalities (PD2), and 36 gene carriers with diagnosed HD. Contrast sensitivity for stationary and moving sinusoidal gratings, and tests of form and motion discrimination, were used to probe different visual pathways. Patients with HD showed impaired contrast sensitivity for moving gratings. For one of the three contrast sensitivity tests, the prediagnostic gene carriers with greater neurological abnormality (PD2) also had impaired performance as compared with NG. These findings suggest that early stage HD disrupts visual functions associated with the magnocellular pathway. However, these changes are only observed in individuals diagnosed with HD or who are in the more symptomatic stages of prediagnostic HD. (JINS, 2008, 14, 446–453.)

Although most neuropsychological batteries used with multiple sclerosis (MS) patients now exclude tests that require significant motor writing or manual manipulation speed, many of the most sensitive commonly used cognitive tests nonetheless require some type of rapid oral motor response. The aim of this study is to examine the extent to which primary oral motor articulation speed problems of individuals with MS contribute to performance and group differences on neuropsychological tasks requiring a rapid spoken response. Fifty MS patients and 50 healthy controls were administered the PASAT, COWAT, Animal Naming, and SDMT tests, in addition to a measure of rudimentary oral motor speed known as the maximum repetition rate of syllables and multisyllabic combinations (MRR) task. Regression analyses revealed that the amount of variance accounted for by the group (MS-Control) variable was reduced the following amounts for the tasks when the MRR was entered before the group variable: SDMT, 10% to 6%; PASAT, 4% to 2%; COWAT, 5% to 2%; Animal Naming, 11% to 7%. Our data suggest that rudimentary oral motor speed is slowed in MS patients and makes an important contribution to group differences in performance on commonly used neuropsychological tasks requiring a rapid spoken response. (JINS, 2008, 14, 454–462.)

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.)

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.)

The present study examined whether patients with obsessive-compulsive disorder (OCD) focus on details at the expense of global aspects. A recent study of our group using Navon letters (e.g., the letter “S” composed out of “A” letters) did not yield differences between OCD patients and controls on local processing. However, the task used may have lacked sensitivity, because it did not involve a response conflict condition (i.e., global and local level associated with different responses). In the current study, we gradually varied between-level conflict. Twenty-eight OCD patients and 30 healthy controls had to attend to the global and the local level of each item. OCD patients displayed comparable performance: Patients neither displayed a preference to respond to the local level nor enhanced interference from the local level. In conclusion, the present study does not support the idea that a generalized bias to “miss the forest for the trees” forms part of the vulnerability to OCD. (JINS, 2008, 14, 489–493.)

The potential influence of recruitment context in neuropsychological (NP) research is seldom addressed in the literature. Our experience with a previous large-scale study of MS cognitive impairment led us to speculate that referral questions and motivation bias significantly impact conclusions drawn from NP testing. We re-analyzed data from Benedict et al. (2006) and compared the results obtained across three groups of patients: paid research volunteers, clinical patients undergoing evaluation for routine monitoring of cognitive status, and clinical patients referred for diagnostic clarification, determination of disability benefits, and other more complex issues. Research volunteers were significantly younger and less frequently cognitively impaired compared to the clinical groups, greatly affecting prevalence estimates (45.6 to 65.6%). Significant correlations between depression and cognitive impairment were present only among the research volunteers. NP testing significantly predicted vocational outcomes in all groups. These results suggest that greater attention should be paid to the reasons patients agree to participate in NP testing. (JINS, 2008, 14, 494–498.)

Pediatric Neuropsychological Intervention. Scott J. Hunter and Jacobus Donders (Eds.). 2007. New York: Cambridge University Press, 493 pp., $115.00 (HB).

Pediatric neuropsychologists have a new resource to add to their growing collection of texts. Hunter and Donders have edited an invaluable resource with chapters on basic developmental and assessment issues, reviews of both common and less commonly known conditions that often result in disability, and suggestions for empirically based treatment. The editors' goal is to direct researchers toward intervention studies to demonstrate that practice is indeed based on evidence.

Progress in Neurotherapeutics and Neuropsychopharmacology. Volume 1. Jeffrey L. Cummings (Ed). 2006. Cambridge, England: Cambridge University Press, 169 pp., $122.00 (HB).

Progress in Neurotherapeutics and Neuropsychopharmacology provides an overview of what is for most neuropsychologists a new content area—clinical trials. Had I not spent five years in the pharmaceutical industry, I probably would have not given the topic of neurotherapeutics a second thought. This book can be useful on a number of counts. First, knowledge of neurotherapeutics is an indirect method for understanding the basic science of neurological diseases since drug development hinges upon appreciating the pathology of the disease. Second, three factors make neuropsychologists uniquely qualified to understand neurotherapeutics in the form of clinical trials—knowledge of most neurological disease states and research training. Finally, all clinical trials have a primary outcome measure. When the primary outcome measure is cognition, our contribution as neuropsychologists can be paramount. My introduction to neurotherapeutics was as outcome rater. An increasing number of neuropsychologists are being recruited by the pharmaceutical industry to work in medical affairs, mostly as medical science liaisons. For those interested in a career alternative, or the topic of neurotherapeutics, this text provides a starting point.

Recent and relevant.

Mild Traumatic Brian Injury and Postconcussion Syndrome: The New Evidence Base for Diagnosis and Treatment, by Michael A. McCrea. 2007. New York: Oxford University Press. 224 pp., $39.95 (PB).

Few topics in neuropsychology, or healthcare for that matter, have been as controversial for as long a time as mild traumatic brain injury (MTBI) and postconcussive syndrome (PCS). The controversy spills from healthcare into the medico-legal arena for obvious reasons, but is far from being only an issue of interest in forensic circles. Patients with MTBI who report symptoms of PCS are among the most common customers in clinics around the world. The controversy persists, in large part, because of the challenges associated with objectively capturing, describing and understanding the issue. Dr. McCrae's book speaks directly to these challenges by reviewing the dramatic increase in research on MTBI and PCS over the last ten or so years.

Minutes from the Board of Governors Mid-Year Meeting, July 3, 2007, and minutes from the Mid-Year Business Meeting, July 6, 2007.