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.)

In comparison to the basal ganglia, prefrontal cortex, and medial temporal lobes, the cerebellum has been absent from recent research on the neural substrates of categorization and identification, two prominent tasks in the learning and memory literature. To investigate the contribution of the cerebellum to these tasks, we tested patients with cerebellar pathology (seven with bilateral degeneration, six with unilateral lesions, and two with midline damage) on rule-based and information-integration categorization tasks and an identification task. In rule-based tasks, it is assumed that participants learn the categories through an explicit reasoning process. In information-integration tasks, optimal performance requires the integration of information from multiple stimulus dimensions, and participants are typically unaware of the decision strategy. The identification task, in contrast, required participants to learn arbitrary, color-word associations. The cerebellar patients performed similar to matched controls on all three tasks and performance did not vary with the extent of cerebellar pathology. Although the interpretation of these null results requires caution, these data contribute to the current debate on cerebellar contributions to cognition by providing boundary conditions on understanding the neural substrates of categorization and identification, and help define the functional domain of the cerebellum in learning and memory. (JINS, 2008, 14, 760–770.)

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by language and communication impairments, social impairments, and repetitive behaviors or restricted interests. Previous studies of semantic functions have found differences in semantic processing and differences in the activation of the language network in adults with ASD compared to controls. The goal of this study is to examine semantic functions in adolescents with ASD compared to typically developing adolescents. We utilized fMRI with a reading version of a response-naming task to investigate activation in 12 right-handed adolescent boys with ASD and 12 typically developing boys. Both groups performed the task at ceiling levels. Boys with ASD had significantly stronger activation than controls in Broca's area, which was less left lateralized in ASD individuals. Controls had a significant correlation between frontal and temporal language area activation in the left hemisphere, whereas ASD adolescents did not. Direct group comparisons revealed additional regions activated in the ASD group relative to the control group. These results suggest differences in semantic organization, approaches to the semantic task, or efficiency in semantic processing in ASD adolescents relative to typically developing adolescents. (JINS, 2008, 14, 967–979.)

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.)

Adenotonsillectomy (AT) is among the most common pediatric surgical procedures and is performed as often for obstructive sleep apnea (OSA) as for recurrent tonsillitis. This study compared behavioral, cognitive, and sleep measures in 27 healthy control children recruited from a university hospital-based pediatric general surgery clinic with 40 children who had OSA (AT/OSA+) and 27 children who did not have OSA (AT/OSA−) scheduled for AT. Parental ratings of behavior, sleep problems, and snoring, along with specific cognitive measures (i.e., short-term attention, visuospatial problem solving, memory, arithmetic) reflected greater difficulties for AT children compared with controls. Differences between the AT/OSA− and control groups were larger and more consistent across test measures than were those between the AT/OSA+ and control groups. The fact that worse outcomes were not clearly demonstrated for the AT/OSA+ group compared with the other groups was not expected based on existing literature. This counterintuitive finding may reflect a combination of factors, including age, daytime sleepiness, features of sleep-disordered breathing too subtle to show on standard polysomnography, and academic or environmental factors not collected in this study. These results underscore the importance of applying more sophisticated methodologies to better understand the salient pathophysiology of childhood sleep-disordered breathing. (JINS, 2008, 14, 571–581.)

Visual motion perception and pursuit eye movement deficits have been reported in autism. However, it is unclear whether these impairments are related to each other or to clinical symptoms of the disorder. High-functioning individuals with autism (41 with and 36 without delayed language acquisition) and 46 control subjects participated in the present study. All three subject groups were matched on chronological age and Full-Scale IQ. The autism group with delayed language acquisition had bilateral impairments on visual motion discrimination tasks, whereas the autism group without delay showed marginal impairments only in the left hemifield. Both autism groups showed difficulty tracking visual targets, but only the autism group without delayed language acquisition showed increased pursuit latencies and a failure to show the typical rightward directional advantage in pursuit. We observed correlations between performance on the visual perception and pursuit tasks in both autism groups. However, pursuit performance was correlated with manual motor skills only in the autism group with delayed language, suggesting that general sensorimotor or motor disturbances are a significant additional factor related to pursuit deficits in this subgroup. These findings suggest that there may be distinct neurocognitive phenotypes in autism associated with patterns of early language development. (JINS, 2008, 14, 980–989.)

Serial neuropsychological assessment is often conducted to monitor changes in the cognitive abilities of individuals over time. Because practice effects occur and the reliability of test scores is less than perfect, it is difficult to judge whether varying test results should be attributed to chance trends or to real changes in underlying cognitive abilities. In a large sample of adults (age range, 49–81 years), we evaluated the influence of age, gender, and education on test–retest changes in performance after 3 years on Rey's Verbal Learning Test (VLT), the Stroop Color-Word Test (SCWT), and the Letter Digit Substitution Test (LDST). A new statistical method was applied to assess the significance of changes in test performance (i.e., the regression-based change method). The results showed that test–retest changes differed as a function of age for the VLT Total recall 1–3, VLT Total recall 1–5, VLT Delayed recall, and LDST measures. An age × gender interaction was found for the SCWT Interference change score, suggesting that the age-related decline in executive functioning after 3 years was more pronounced for males than for females. A normative change table with appropriate corrections for the relevant independent variables was established. (JINS, 2008, 14, 71–80.)

Spina bifida meningomyelocele with hydrocephalus (SBM) is commonly associated with anomalies of the corpus callosum (CC). We describe MRI patterns of regional CC agenesis and relate CC anomalies to functional laterality based on a dichotic listening test in 90 children with SBM and 27 typically developing controls. Many children with SBM (n = 40) showed regional CC anomalies in the form of agenesis of the rostrum and/or splenium, and a smaller number (n = 20) showed hypoplasia (thinning) of all CC regions (rostrum, genu, body, and splenium). The expected right ear advantage (REA) was exhibited by normal controls and children with SBM having a normal or hypoplastic splenium. It was not shown by children with SBM who were left handed, missing a splenium, or had a higher level spinal cord lesion. Perhaps the right hemisphere of these children is more involved in processing some aspects of linguistic stimuli. (JINS, 2008, 14, 771–781.)

Increased computer use in clinical settings offers an opportunity to develop new neuropsychological tests that exploit the control computers have over stimulus dimensions and timing. However, before adopting new tools, empirical validation is necessary. In the current study, our aims were twofold: to describe a computerized adaptive procedure with broad potential for neuropsychological investigations, and to demonstrate its implementation in testing for visual hemispatial neglect. Visual search results from adaptive psychophysical procedures are reported from 12 healthy individuals and 23 individuals with unilateral brain injury. Healthy individuals reveal spatially symmetric performance on adaptive search measures. In patients, psychophysical outcomes (as well as those from standard paper-and-pencil search tasks) reveal visual hemispatial neglect. Consistent with previous empirical studies of hemispatial neglect, lateralized impairments in adaptive conjunction search are greater than in adaptive feature search tasks. Furthermore, those with right hemisphere damage show greater lateralized deficits in conjunction search than do those with left hemisphere damage. We argue that adaptive tests, which automatically adjust to each individual's performance level, are efficient methods for both clinical evaluations and neuropsychological investigations and have the potential to detect subtle deficits even in chronic stages, when flagrant clinical signs have frequently resolved. (JINS, 2008, 14, 243–256.)

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.)

We compared motor imagery performance of normally limbed individuals with that of individuals with one or both hands missing since birth (i.e., hand amelia). To this aim, 14 unilaterally and 2 bilaterally amelic participants performed a task requiring the classification of hands depicted in different degrees of rotation as either a left or a right hand. On the same task, 24 normally limbed participants recapitulated previously reported effects; that is, that the hand motor dominance and, more generally, a lifelong use of hands are important determinants of left–right decisions. Unilaterally amelic participants responded slower to hands corresponding to their absent, compared with their existing, hand. Moreover, left and right hand amelic participants showed prolonged reaction times to hands (whether left or right) depicted in unnatural orientations compared with natural orientations. Among the bilateral amelics, the individual with phantom sensations, but not the one without, showed similar differentiation. These findings demonstrate that the visual recognition of a hand never physically developed is prolonged, but still modulated by different rotation angles. They are further compatible with the view that phantom limbs in hand amelia may constrain motor imagery as much as do amputation phantoms. (JINS, 2008, 14, 81–89.)

Although previous studies have shown that individuals with autism spectrum disorder (ASD) excel at visual search, underlying neural mechanisms remain unknown. This study investigated the neurofunctional correlates of visual search in children with ASD and matched typically developing (TD) children, using an event-related functional magnetic resonance imaging design. We used a visual search paradigm, manipulating search difficulty by varying set size (6, 12, or 24 items), distractor composition (heterogeneous or homogeneous) and target presence to identify brain regions associated with efficient and inefficient search. While the ASD group did not evidence accelerated response time (RT) compared with the TD group, they did demonstrate increased search efficiency, as measured by RT by set size slopes. Activation patterns also showed differences between ASD group, which recruited a network including frontal, parietal, and occipital cortices, and the TD group, which showed less extensive activation mostly limited to occipito-temporal regions. Direct comparisons (for both homogeneous and heterogeneous search conditions) revealed greater activation in occipital and frontoparietal regions in ASD than in TD participants. These results suggest that search efficiency in ASD may be related to enhanced discrimination (reflected in occipital activation) and increased top-down modulation of visual attention (associated with frontoparietal activation). (JINS, 2008, 14, 990–1003.)

This study reports the executive function profile in people with schizophrenia, with a simultaneous comparison of chronicity and of those with predominately disorganization versus psychomotor poverty symptoms. The patients were split into one set defined according to symptoms (29 with disorganization, 29 with negative symptoms) and the other representing chronicity (22 first-episode, 35 chronic) and compared with 28 healthy controls on a broad range of executive process measures. Differences were investigated in both the severity and profile of impairments. Impairment patterns interacted with symptom groups, with disorganization and psychomotor poverty symptom groups showing different profiles of executive impairment. In contrast, across these same executive processes, impairment profiles were similar between first episode and chronic schizophrenia and became more similar, particularly for working memory, when controlling for disorganization symptoms. The executive profile, therefore, is related to symptom type rather than chronicity. (JINS, 2008, 14, 782–792.)

Seventeen patients diagnosed with Parkinson's disease completed a complex computer-based task that involved planning and management while also performing an attention-demanding secondary task. The tasks were performed concurrently, but it was necessary to switch from one to the other. Performance was compared to a group of healthy age-matched control participants and a group of young participants. Parkinson's patients performed better than the age-matched controls on almost all measures and as well as the young controls in many cases. However, the Parkinson's patients achieved this by paying relatively less attention to the secondary task and focusing attention more on the primary task. Thus, Parkinson's patients can apparently improve their performance on some aspects of a multidimensional task by simplifying task demands. This benefit may occur as a consequence of their inflexible exaggerated attention to some aspects of a complex task to the relative neglect of other aspects. (JINS, 2008, 14, 257–265.)

Mild cognitive impairment (MCI) is regarded as the prodromal stage of dementia disorders, such as Alzheimer's disease (AD).

Objective: To compare the neuropsychological profiles of MCI subjects with normal concentrations of total tau (T-τ) and Aβ42 in CSF (MCI-norm) to MCI subjects with deviating concentrations of the biomarkers (MCI-dev). MCI-norm (N = 73) and MCI-dev (N = 73) subjects were compared to normal controls (N = 50) on tests of speed/attention, memory, visuospatial function, language and executive function.

Results: MCI-norm performed overall better than MCI-dev, specifically on tests of speed and attention and episodic memory. When MCI-dev subjects were subclassified into those with only high T-tau (MCI-tau), only low Aβ42 (MCI-Aβ) and both high T-tau and low Aβ42 (MCI-tauAβ), MCI-tauAβ tended to perform slightly worse. MCI-tau and MCI-Aβ performed quite similarly.

Conclusions: Considering the neuropsychological differences, many MCI-norm probably had more benign forms of MCI, or early non-AD forms of neurodegenerative disorders. Although most MCI-dev performed clearly worse than MCI-norm on the neuropsychological battery, some did not show any deficits when compared to age norms. A combination of CSF analyses and neuropsychology could be a step toward a more exact diagnosis of MCI as prodromal AD. (JINS, 2008, 14, 582–590.)

Despite evidence for executive dysfunction in school-aged preterm children, less is known about the early development of these difficulties or their underlying neuropathology. This study used prospective longitudinal data from a regional cohort of 88 very preterm and 98 full-term comparison children to examine the executive functioning (EF) of preschool children born very preterm. The relationship between the severity of neonatal cerebral white matter (WM) abnormalities on magnetic resonance imaging (MRI) at term equivalent and children's EF at ages two and four years (corrected age) was examined. At age four, very preterm children with WM abnormalities performed less well than full-term children on the Detour Reaching Box, a measure of behavioral inhibition and cognitive flexibility, even after controlling for child IQ, SES, and medical background. Examination of patterns of EF performance between the ages of 2 and 4 years showed that the performance of all groups improved with age. However, very preterm children with mild and moderate-severe WM abnormalities were characterized by higher rates of consistent performance impairments. These findings support the presence of early and persistent executive difficulties in preschool children born very preterm, and highlight the importance of white matter pathology in the development of executive impairments. (JINS, 2008, 14, 90–101.)

Adolescents with spina bifida (SB) vary in their ability to adapt to the disease, and it is likely that numerous risk and protective factors affect adaptation outcomes. The primary aim was to test neuropsychological impairment, exemplified herein by executive dysfunction, as a risk factor in the Ecological Model of Adaptation for Adolescents with SB. Specific hypotheses were that: (1) executive functioning predicts the adaptation outcome of functional independence in adolescents with SB; (2) executive functioning mediates the impact of neurological severity on functional independence; and (3) family and adolescent protective factors are related to functional independence and moderate the relationship between executive functioning and functional independence. Forty-three adolescents aged 12–21 years completed neuropsychological measures and an interview that assessed risk, adolescent and family protective factors, and functional independence. Age, level of lesion, executive functioning, and the protective factor adolescent activities were significantly correlated with the functional independence outcome. In hierarchical regression analysis, the model accounted for 61% of the variance in functional independence outcomes. Executive functioning mediated the impact of neurological severity on functional independence. (JINS, 2008, 14, 793–804.)

Subjective memory complaints (SMCs) are known to be inconsistently related to current memory impairment in older adults but this association has not been well investigated in primary care provider (PCP) settings. To characterize the complexity of the relationship between SMCs and objective memory in older outpatients of PCPs, we collected neuropsychological, subjective memory, depression and medical chart data from outpatients aged 65 and older, without documented dementia diagnoses, in eleven PCP offices in and around the Pittsburgh metropolitan area. Results indicated that self-estimates of current memory ability were most strongly associated with objective memory performance; in contrast, perception of worsening memory over the past year showed no association; and specific memory-related activities were only weakly associated. Women were more likely than men to show inconsistency between SMCs and objective memory performance. Only two of the 11 most significantly memory-impaired participants endorsed SMCs and only four had PCP chart documentation of memory problems. Eliciting SMCs in non-demented older adults can be of clinical value in a PCP setting, but significant limitations of patient self-report in more memory-impaired patients underscore the need to develop brief, objective indicators of memory impairment for PCP office use when there is suspicion of decline. (JINS, 2008, 14, 1004–1013.)

The primary impairment in early Alzheimer's disease (AD) is encoding/consolidation, resulting from medial temporal lobe (MTL) pathology. AD patients perform poorly on cued-recall paired associate learning (PAL) tasks, which assess the ability of the MTLs to encode relational memory. Since encoding and retrieval processes are confounded within performance indexes on cued-recall PAL, its specificity for AD is limited. Recognition paradigms tend to show good specificity for AD, and are well tolerated, but are typically less sensitive than recall tasks. Associate-recognition is a novel PAL task requiring a combination of recall and recognition processes. We administered a verbal associate-recognition test and cued-recall analogue to 22 early AD patients and 55 elderly controls to compare their ability to discriminate these groups. Both paradigms used eight arbitrarily related word pairs (e.g., pool-teeth) with varying degrees of imageability. Associate-recognition was equally effective as the cued-recall analogue in discriminating the groups, and logistic regression demonstrated classification rates by both tasks were equivalent. These preliminary findings provide support for the clinical value of this recognition tool. Conceptually it has potential for greater specificity in informing neuropsychological diagnosis of AD in clinical samples but this requires further empirical support. (JINS, 2008, 14, 591–600.)

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.)