In his text, Behavioral Neurology of White Matter, Filley focuses our attention on the role of white matter in neurobehavioral functioning. He makes the point that much of clinical neuroscience, including neuropsychology and behavioral neurology, has focused on cognitive correlates of cortical lesions and disorders. Historically in neuropsychology, we have acknowledged the role of white matter more typically in vague terms of connecting pathways, but there has been a decided emphasis on cortical and subcortical gray matter regions as “where the action is.” Filley's insightful writing clearly supports his proposal that “the mind depends as much on the white matter as on its gray counterpart.

The present study sought to delineate empirically derived memory subtypes using the California Verbal Learning Test (CVLT; Delis et al., 1987) in a sample of adults with HIV-1 infection (N 5 154). Confirmatory factor analysis was used to evaluate eight models of the CVLT structure suggested by Wiegner and Donders (1999). A four-factor model, consisting of Attention Span, Learning Efficiency, Delayed Recall, and Inaccurate Recall appeared to be the best fitting model. Variables with the highest factor loadings from the model were entered in a two-stage cluster analysis. Four reliable CVLT clusters or subtypes were identified: Normal, Atypical, Subsyndromal, and Frontal-striatal. Internal and external validation of subtypes demonstrated that clusters were stable and clinically interpretable. Subtypes were meaningfully related to neuropsychological functioning, and to some extent, depressive symptomatology. Subtypes did not differ significantly with respect to subjective neurocognitive complaints and markers of HIV-1 disease. The present findings highlight the heterogeneity of memory profiles in HIV-1 infection and support a frontal-striatal conceptualization of verbal memory performance. The identification of robust HIV-1 memory subtypes may have important implications for the clinical management of adults infected with HIV-1 infection. (JINS, 2003, 9, 1–16.)

The current study presents both longitudinal behavioral data and functional activation data documenting the effects of early focal brain injury on the development of spatial analytic processing in two children, one with prenatal left hemisphere (LH) injury and one with right hemisphere (RH) injury. A substantial body of evidence has shown that adults and children with early, lateralized brain injury show evidence of spatial analytic deficits. LH injury compromises the ability to encode the parts of a spatial pattern, while RH injury impairs pattern integration. The two children described in this report show patterns of deficit consistent with the site of their injury. In the current study, their longitudinal behavioral data spanning the age range from preschool to adolescence are presented in conjunction with data from a functional magnetic resonance imaging (fMRI) study of spatial processing. The activation results provide evidence that alternative profiles of neural organization can arise following early focal brain injury, and document where in the brain spatial functions are carried out when regions that normally mediate them are damaged. In addition, the coupling of the activation with the behavioral data allows us to go beyond the simple mapping of functional sites, to ask questions about how those sites may have come to mediate the spatial functions. (JINS, 2003, 9, 604–622.)

The possible medicinal use of cannabinoids for chronic diseases emphasizes the need to understand the long-term effects of these compounds on the central nervous system. We provide a quantitative synthesis of empirical research pertaining to the non-acute (residual) effects of cannabis on the neurocognitive performance of adult human subjects. Out of 1,014 studies retrieved using a thorough search strategy, only 11 studies met essential a priori inclusion criteria, providing data for a total of 623 cannabis users and 409 non- or minimal users. Neuropsychological results were grouped into 8 ability domains, and effect sizes were calculated by domain for each study individually, and combined for the full set of studies. Using slightly liberalized criteria, an additional four studies were included in a second analysis, bringing the total number of subjects to 1,188 (i.e., 704 cannabis users and 484 non-users). With the exception of both the learning and forgetting domains, effect size confidence intervals for the remaining 6 domains included zero, suggesting a lack of effect. Few studies on the non-acute neurocognitive effects of cannabis meet current research standards; nevertheless, our results indicate that there might be decrements in the ability to learn and remember new information in chronic users, whereas other cognitive abilities are unaffected. However, from a neurocognitive standpoint, the small magnitude of these effect sizes suggests that if cannabis compounds are found to have therapeutic value, they may have an acceptable margin of safety under the more limited conditions of exposure that would likely obtain in a medical setting. (JINS, 2003, 9, 679–689.)

A meta-analysis was conducted to evaluate possible neuropsychological effects of treatments for cancer in adults. A search revealed 30 studies, encompassing 29 eligible samples, and leading to inclusion of a total of 838 patients and control participants. A total of 173 effect sizes (Cohen's d) were extracted across 7 cognitive domains and as assessed in the literature via 3 methods of comparison (post-treatment compared with normative data, controls, or baseline performance). Statistically significant negative effect sizes were found consistently across both normative and control methods of comparison for executive function, verbal memory, and motor function. The largest effects were for executive function and verbal memory normative comparisons (−.93 and −.91, respectively). When limiting the sample of studies in the analyses to only those with relatively “less severe” diagnoses and treatments, the effects remained. While these results point toward some specific cognitive effects of systemic cancer therapies in general, no clear clinical implications can yet be drawn from these results. More research is needed to clarify which treatments may produce cognitive decrements, the size of those effects, and their duration, while ruling out a wide variety of possible mediating or moderating variables. (JINS, 2003, 9, 967–982.)

We investigated the frequency and neurocognitive correlates of attention deficit hyperactivity disorder and traits of this disorder (ADHD/Traits) after childhood stroke and orthopedic diagnosis in medical controls. Twenty-nine children with focal stroke lesions and individually matched children with clubfoot or scoliosis were studied with standardized psychiatric, intellectual, academic, adaptive, executive, and motivation function assessments. Lifetime ADHD/Traits were significantly more common in stroke participants with no prestroke ADHD than in orthopedic controls (16/28 vs. 7/29; Fisher's Exact p < .02). Lifetime ADHD/Traits in the orthopedic controls occurred exclusively in males with clubfoot (7/13; 54%). Participants with current ADHD/Traits functioned significantly worse (p < .005) than participants without current ADHD/Traits on all outcome measures. Within the stroke group, current ADHD/Traits was associated with significantly lower verbal IQ and arithmetic achievement (p < .04), more nonperseverative errors (p < .005), and lower motivation (p < .004). A principal components analysis of selected outcome variables significantly associated with current ADHD/Traits revealed “impaired neurocognition” and “inattention-apathy” factors. The latter factor was a more consistent predictor of current ADHD/Traits in regression analyses. These findings suggest that inattention and apathy are core features of ADHD/Traits after childhood stroke. This association may provide clues towards the understanding of mechanisms underlying the syndrome. (JINS, 2003, 9, 815–829.)

In this study we examined the independent and interactive effects of lifetime patterns of drinking and smoking on cognitive performance in elderly African Americans. A sample of 230 individuals with varying histories of alcohol and cigarette use was drawn from the Hillsborough Elder African American Life Study, a community-based, cross-sectional study of older adults aged 60 to 84. Dependent variables were the results of a neuropsychological battery that provided measures of general cognitive ability, executive function, and memory. Specifically, our study addressed (1) whether individuals with a lifetime history of sustained smoking and/or drinking show lower levels of cognitive performance in comparison to lifetime abstainers, (2) whether cumulative lifetime doses of alcohol or cigarettes, or of the two substances in interaction, have an effect on cognition, and (3) whether individuals who have histories of periodic, intense use of either alcohol or cigarettes show lower levels of cognitive performance in comparison to lifetime abstainers. When significant results were obtained, effect sizes were small, not exceeding 5% of the variance. A single exception occurred for the intensity analyses, in which drinking explained approximately 16% of the variance in global cognitive ability after adjusting for the contributions of control variables. In these analyses, drinking was found to have a U-shaped effect on global cognitive ability and total acquisition in the memory trials. Specifically, moderate users performed at a lower level than abstainers or heavy users, who did not differ from each other. (JINS, 2003, 9, 690–697.)

Contralesional neglect may be induced by either unawareness of contralesional stimuli (attentional neglect, AN) or failure to act in contralesional space (intentional neglect, IN). We examined whether contralesional cold caloric stimulation differentially affects AN versus IN. Patients with left-sided neglect (n = 16) from right-hemisphere lesions performed target cancellation and line bisection tasks. Using a video-based apparatus that reverses the right and left side of stimuli, patients with abnormal cancellation performance were divided into those with AN and those with IN. The 5 subjects with normal cancellation performance but rightward bisection bias were also separated into 2 neglect groups. Subjects performed cancellation or bisection tasks before and immediately after irrigation of the left auditory canal with ice water. Caloric stimulation induced brisk rightward nystagmus in all subjects. Subjects with AN cancelled more left-sided targets after stimulation than those with IN (p = .02). Whereas caloric stimulation significantly shifted bisection error leftward for both IN and AN groups (p < .0001), AN patients exhibited a greater magnitude of shift than the IN patients. While the basis for differential performance remains undefined, the data indicate that caloric stimulation influences AN more than IN. (JINS, 2003, 9, 983–988.)

Neuropsychological studies of temporal lobe epilepsy have focused heavily on the nature and extent of memory dysfunction and its relationship to the neuropathological status of the hippocampus and related mesial temporal lobe structures. In this study, we examined whole brain and lobar quantitative MRI volumes and comprehensive neuropsychological performance in 58 patients with temporal lobe epilepsy and 62 healthy controls in order to determine (1) the nature and degree of extratemporal structural abnormalities in localization-related temporal lobe epilepsy; (2) the nature and degree of cognitive abnormalities outside of anterograde memory function; and (3) the relationship of volumetric abnormalities to neuropsychological status. Temporal lobe epilepsy patients exhibited significant reduction in the volume of adjusted (age, gender, height) total cerebral tissue (−5.8%), more evident in white (−9.8%) compared to gray matter (−3.0%) tissue volumes. Significant volumetric reductions were evident across frontal, temporal and parietal but not occipital lobe regions. Subarachnoid but not total ventricular CSF was significantly increased in epilepsy patients. Neuropsychological abnormality was generalized in nature, consistent with the generalized nature of the morphometric abnormalities, and reductions in cerebral tissue volumes were directly associated with poorer cognitive performance. In summary, patients with temporal lobe epilepsy exhibited clinically significant structural and functional abnormalities that extended outside the epileptogenic temporal lobe. The degree to which these structural and cognitive abnormalities are due to factors that cause the epilepsy, as opposed to reflecting the consequences of chronic epilepsy (e.g., duration and severity of epilepsy), remain to be determined. (JINS, 2003, 9, 353–362.)

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.)

Patients diagnosed with bipolar disorder (BPD), by definition, have problems with emotional regulation. However, it remains uncertain whether these patients are also deficient at processing other people's emotions, particularly while manic. The present study examined the ability of 25 manic bipolar patients and 25 healthy participants on tasks of facial recognition and facial affect recognition at three different presentation durations: 500 ms, 750 ms, and 1000 ms. The groups did not differ in terms of age, education, sex, ethnicity, or estimated IQ. The groups did not differ significantly on either a novel computerized facial recognition task or the Benton Facial Recognition Test. In contrast, the bipolar group performed significantly more poorly than did the comparison group on a novel facial affect labeling task. Although the patient group had slower reaction times on all 3 computerized tasks, the presentation duration did not have an effect on performance in the patients. This study suggests that patients with bipolar disorder are able to recognize faces, but have difficulty processing facial affective cues. (JINS, 2003, 9, 623–632.)

There is debate regarding the integrity of semantic memory in dementia of the Alzheimer type (DAT). One view argues that DAT is associated with a breakdown in semantic memory; the other argues that DAT is associated with predominantly preserved semantic memory and a breakdown in retrieval. The classic release from proactive interference (RPI) paradigm was used to shed light on this debate. Individuals with early-stage DAT (n = 36) and healthy older adult controls (n = 45) participated in an RPI paradigm. Each trial was a Brown–Peterson task in which participants read three-word lists, counted (for 0, 3, 6, or 9 s), and recalled the words. Both groups showed significant proactive interference (PI), but the size of the PI was significantly smaller in the DAT group. The group difference in PI may be due to the faster forgetting rate in the DAT group. Both groups showed significant RPI and there was no group difference in size when RPI was considered in terms of PI levels. Both groups showed PI and RPI in prior list intrusions. The DAT group's significant buildup and release of PI based on semantic categories suggest predominantly preserved semantic memory activity, at least, in early-stage DAT individuals. (JINS, 2003, 9, 830–838.)

Many recent findings in Western countries suggest that episodic recall is the most sensitive discriminator between patients with mild Alzheimer disease (AD) and the normal elderly, while semantic memory tends best to differentiate between moderate and severe AD patients. The present study is the first to examine in detail the episodic memory of Chinese AD patients in Hong Kong with a locally developed list learning test, comparing procedures that do or do not encourage the use of semantic organization. The performance of 28 AD patients was compared to that of 30 normal controls. AD patients did significantly worse in terms of acquisition and retention and also benefited significantly less from external organization cues. In the discriminant function analysis, the rate of forgetting in the random condition and the total retention score in the blocked condition were found to be the best predictors for differentiating between AD patients and controls. On the other hand, in the differentiation between mild and moderate AD, semantic clustering in the blocked condition was found to be the best predictor. Results of the present study were discussed in the light of the previous findings reported in the Western countries and the neuropathological changes of AD patients. (JINS, 2003, 9, 363–375.)

Patients with dementia, particularly those with frontotemporal dementia (FTD), are reported to display marked negative symptoms, including apathy, lack of initiative, and flattened affect, similar to those observed in schizophrenic patients. However, negative symptoms have yet to be formally quantified in an FTD population. Twenty-seven patients with FTD (11 primarily right-sided, 8 primarily left-sided, and 4 symmetric) and 7 patients with Alzheimer's disease were rated on the Scale for the Assessment of Negative Symptoms, the Positive and Negative Syndrome Scale, and the Emotional Blunting scale. The FTD patients registered significantly more negative symptoms than the Alzheimer's patients, averaging a threefold increase; groups did not significantly differ in positive symptoms. Negative symptom scale scores were negatively correlated with nonverbal executive skills (23–44% shared variance), verbal executive skills (up to 25% shared variance) and verbal memory (up to 20% shared variance), but were unrelated to measures of attention, verbal and nonverbal information processing, nonverbal memory, language, and constructional skill. In contrast, positive symptoms were positively correlated with constructional skill (19% shared variance) and attentional scores (15% shared variance). These findings add to the existing literature relating negative symptoms to anterior cerebral hypofunction, and suggest that positive symptoms, at least in this population, may be tied to increased posterior activation. (JINS, 2003, 9, 698–709.)

Efficient behavioral functioning requires early perceptual inhibition of irrelevant stimuli and later motor inhibition of inappropriate responses. The Perceptual and Motor Conflict Tasks were developed to differentially assess perceptual and motor inhibition, and to determine whether these processes utilize separate or shared cognitive resources. The computerized tasks include six subtests involving a box or an arrow appearing in various locations. Subjects respond by pressing a key on the left or right side of a keyboard. In different subtests, arrow direction or stimulus location determines correct responses. Perceptual inhibition assessment requires the subject to respond to a conflicting arrow direction while ignoring stimulus location. Motor inhibition assessment involves the subject responding in the direction opposite to that indicated by a centrally located arrow. In a neurologically normal sample (N = 44), reaction time analyses yielded significant Perceptual and Motor Conflict main effects, with slower performance under conflict conditions, but no significant Perceptual × Motor interaction. The lack of a significant Perceptual × Motor interaction, according to the additive factor model, indicates that these two processes utilize distinct cognitive resources. Nevertheless, performance on the two conflict tasks was significantly correlated with each other, and Perceptual Conflict performance was significantly correlated with Stroop interference. (JINS, 2003, 9, 25–30.)

Performance on some neuropsychological tests is best expressed as an intra-individual measure of association (such as a parametric or non-parametric correlation coefficient or the slope of a regression line). Examples of the use of intra-individual measures of association (IIMAs) include the quantification of performance on tests designed to assess temporal order memory or the accuracy of time estimation. The present paper presents methods for comparing a patient's performance with a control or normative sample when performance is expressed as an IIMA. The methods test if there is a significant difference between a patient's IIMA and those obtained from controls, yield an estimate of the abnormality of the patient's IIMA, and provide confidence limits on the level of abnormality. The methods can be used with normative or control samples of any size and will therefore be of particular relevance to single-case researchers. A method for comparing the difference between a patient's scores on two measures with the differences observed in controls is also described (one or both measures can be IIMAs). All the methods require only summary statistics (rather than the raw data from the normative or control sample); it is hoped that this feature will encourage the development of norms for tasks that use IIMAs to quantify performance. Worked examples of the statistical methods are provided using data from a clinical case and controls. A computer program (for PCs) that implements the methods is described and made available. (JINS, 2003, 9, 989–1000.)

Klinefelter syndrome (KS) is a sex chromosome abnormality associated with male infertility and mild cognitive deficits. Individuals with KS have been reported to have impaired verbal ability, as well as deficits in executive function. To further understand the nature of their deficits, we assessed specific elements of frontal lobe function such as working memory and relational reasoning. Men with KS exhibited a deficit in a transitive inference task in which participants ordered a set of names based on a list of propositions about the relative heights of the people named. This deficit was present even for items in which the propositions were given in order, so a chaining strategy could be used. Men with KS are also impaired on the n-back task, which uses letters as stimuli. In contrast, these men performed as well as controls in nonverbal reasoning (Raven's Progressive Matrices). These results suggest that men with KS have intact nonverbal reasoning abilities, but that a difficulty in encoding verbal information into working memory may underlie their executive and linguistic impairments. (JINS, 2003, 9, 839–846.)