The past decade has witnessed an exponential growth in research on autism, a neurodevelopmental disorder affecting social, language, communication, and behavioral development. This growth is fuelled by many factors, including rising prevalence rates; increased media attention and public awareness; the creation of new parent-based research foundations; and targeted federal funding opportunities. Researchers have taken advantage of new theoretical frameworks and exciting scientific technologies that are now being employed to address key questions about the underlying causes and pathophysiology of autism. Advances in developmental neuropsychology and cognitive neuroscience, including the application of magnetic resonance imaging (MRI) methods, have had a particularly significant impact in providing insights into the neurobiology of autism. Several of these key advances, which are closely tied to changes in the way the developmental phenotype of autism has been conceptualized, are highlighted in the papers comprising this Symposium issue.

Functional neuroimaging studies of face processing deficits in autism have typically focused on visual processing regions, such as the fusiform face area (FFA), which have shown reduced activity in autism spectrum disorders (ASD), though inconsistently. We recently reported reduced activity in the inferior frontal region in ASD, implicating impaired mirror-neuron systems during face processing. In the present study, we used fMRI during a face processing task in which subjects had to match faces presented in the upright versus inverted position. Typically developing (TD) children showed a classic behavioral inversion effect, increased reaction time for inverted faces, while this effect was significantly reduced in ASD subjects. The fMRI data showed similar responses in the fusiform face area for ASD and TD children, with both groups demonstrating increased activation for inverted faces. However, the groups did differ in several brain regions implicated in social cognition, particularly prefrontal cortex and amygdala. These data suggest that the behavioral differences in processing upright versus inverted faces for TD children are related not to visual information processing but to the social significance of the stimuli. Our results are consistent with other recent studies implicating frontal and limbic dysfunction during face processing in autism. (JINS, 2008, 14, 922–932.)

MRI diffusion-tensor tracking (DTT) was performed in 17 high-functioning adolescents/adults with autism and 17 pairwise-matched controls. White matter pathways involved in face processing were examined due to the relevance of face perception to the social symptoms of autism, and due to known behavioral and functional imaging findings in autism. The hippocampo-fusiform (HF) and amygdalo-fusiform (AF) pathways had normal size and shape but abnormal microstructure in the autism group. The right HF had reduced across-fiber diffusivity (D-min) compared with controls, opposite to the whole-brain effect of increased D-min. In contrast, left HF, right AF, and left AF had increased D-min and increased along-fiber diffusivity (D-max), more consistent with the whole-brain effect. There was a general loss of lateralization compared with controls. The right HF D-min was markedly low in the autism subgroup with lower Benton face recognition scores, compared with the lower-Benton control subgroup, and compared with the higher-Benton autism subgroup. Similar behavioral relationships were found for performance IQ. Such results suggest an early functionally-significant pathological process in right HF consistent with small-diameter axons (with correspondingly slower neural transmission) and/or higher packing density. In left AF and HF, changes were interpreted as secondary, possibly reflecting axonal loss and/or decreased myelination. (JINS, 2008, 14, 933–946.)

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

Currently, the heterogeneity in the developmental trajectories of autism spectrum disorders (ASD) is poorly understood. Preschool children with ASD participating in a longitudinal study received a battery of neurocognitive tasks that measured the learning of reward associations (Lrn-Rew), spatial working memory (SpatWM), and imitation from memory and novelty preference (Mem/Nov), as well as a measure of nonverbal problem-solving ability (NVDQ). Growth curve analyses via HLM were used to predict the variability in growth rates between age 4 to age 6.5 in Vineland Socialization and Communication scores. Individual differences in both Lrn-Rew and Mem/Nov were significantly related to Socialization and Communication growth rates above and beyond NVDQ, whereas SpatWM was not. Thus, specific aspects of neurocognitive functioning appear to be important predictors of developmental variability during the preschool years in children with ASD. We speculate that these findings support the combined role of ventromedial prefrontal and medial temporal lobe systems in the early pathogenesis of ASD and may be useful in predicting developmental trajectory. The benefits and challenges of assessing specific neurocognitive functions in children with autism is discussed with regard to general cognitive/developmental ability and the behavioral requirements of most assessment settings. (JINS, 2008, 14, 956–966.)

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.)

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.)

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.)

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.)

Deficits in inhibitory abilities are frequently observed in normal aging. However, few studies have explored the generality of these deficits in a single group of participants. Here, we used an adaptation of the Simon task to differentially assess perceptual and motor inhibition using the same stimuli and task design and to determine whether these processes use separate or shared cognitive resources. We were interested in determining whether (1) normal aging is associated with the use of separate (as previously evidenced in young participants) or similar cognitive resources to perform perceptual and motor inhibition tasks; (2) older participants present a specific impairment in one of these two processes. Analyses of reaction times indicated that motor and perceptual inhibitory processes share some cognitive resources and both are impaired in normal aging. These results can be interpreted by considering that a dedifferentiation process is responsible for the inhibitory deficits presented by older participants. (JINS, 2008, 14, 1014–1021.)

Children with prenatal alcohol exposure (PAE) show deficits in verbal learning and spatial memory, as well as abnormal hippocampal development. The relationship between their memory and neuroanatomic impairments, however, has not been directly explored. Given that the hippocampus is integral for the synthesis and retrieval of learned information and is particularly vulnerable to the teratogenic effects of alcohol, we assessed whether reduced learning and recall abilities in children with fetal alcohol spectrum disorders (FASDs) are associated with abnormal hippocampal volumes. Nineteen children with FASDs and 18 typically developing controls aged 9 to 15 years were assessed for verbal learning and verbal and spatial recall and underwent structural magnetic resonance imaging. Images were analyzed for total intracranial volume and for right and left hippocampal volumes. Results revealed smaller left hippocampi and poorer verbal learning and verbal and spatial recall performance in children with FASDs than controls, as well as positive correlations between selective memory indices and hippocampal volumes only in the FASD group. Additionally, hippocampal volumes increased significantly with age in controls only, suggesting that PAE may be associated with long-term abnormalities in hippocampal development that may contribute to impaired verbal learning and verbal and spatial recall. (JINS, 2008, 14, 1022–1033.)

This study investigated the role of visuospatial tasks in identifying cognitive decline in patients with Alzheimer's disease (AD), by correlating neuropsychological performance with cerebral perfusion measures. There were 157 participants: 29 neurologically healthy controls (age: 70.3 ± 6.6, MMSE ≥ 27), 86 patients with mild AD (age: 69.18 ± 8.28, MMSE ≥ 21) and 42 patients moderate/severe AD (age: 68.86 ± 10.69, MMSE 8–20). Single Photon Emission Computerized Tomography (SPECT) was used to derive regional perfusion ratios, and correlated using partial least squares (PLS) with neuropsychological test scores from the Benton Line Orientation (BLO) and the Rey-Osterrieth Complex Figure (RO). Cross-sectional analysis demonstrated that mean scores differed in accordance with disease status: control group (BLO 25.5, RO 33.3); mild AD (BLO 20.1, RO 25.5); moderate/severe AD (BLO 10.7, RO 16). Correlations were observed between BLO/RO and right parietal SPECT regions in the AD groups. Visuospatial performance, often undersampled in cognitive batteries for AD, is clearly impaired even in mild AD and correlates with functional deficits as indexed by cerebral perfusion ratios on SPECT implicating right hemisphere circuits. Furthermore, PLS reveals that usual spatial tasks probe a distributed brain network in both hemispheres including many areas targeted by early AD pathology. (JINS, 2008, 14, 1034–1045.)

We report the adaptation of the Aachen Aphasia Test (AAT) to the Portuguese language (PAAT) and the results of its standardization in 125 persons with aphasia and 153 healthy controls. Patients with aphasia had a previous syndromic diagnosis, obtained through a Portuguese aphasia battery, which served as a reference. The control group was stratified by age and educational level. Hierarchical cluster analyses showed good construct validity. The increasing degree of difficulty and complexity throughout the item sets comprising subtests was confirmed. The discriminatory power of the PAAT for the selection of aphasic from non-aphasic persons proved to be as high as for the AAT versions in other languages. Classification of standard aphasic syndromes by means of discriminant analyses was good. Internal consistency, measured by means of Cronbach's alpha coefficient, was high to very high for the different PAAT subtests. Performance differences caused by age or educational level among the healthy control persons emphasized the need for correction factors. In conclusion, the PAAT showed robust psychometrical properties, comparable to the original German and to adaptations to other languages. It constitutes a useful tool for cross-linguistic and multicenter studies. (JINS, 2008, 14, 1046–1056.)

Some researchers have suggested that general self-report depression scales may be inadequate for assessing depression among individuals with Multiple Sclerosis (MS), because many of such items represent MS disease symptoms. However, research has been mixed on this issue: whereas some studies provide support for symptom overlap, others have found opposing evidence. We investigated this issue in two different MS samples with three different strategies. We (1) examined reliable change in depression symptom categories at two time points over three years, (2) assessed the relationship between variables associated with depression and different depression symptom subscales, and (3) assessed the relationship between symptom subscales and physical disability. In each instance we found significant evidence that items meant to assess vegetative symptoms of depression may be influenced by presence of MS disease symptoms or were not associated with other core elements or central correlates of depression. (JINS, 2008, 14, 1057–1062.)

The Iowa Gambling Task (IGT) is the major plank of behavioral support for the Somatic Marker Hypothesis—a prominent theory of emotionally-based decision making. Despite its widespread use, some have questioned the ecological and discriminative validity of the IGT because a substantial proportion of neurologically-normal adults display a response pattern indistinguishable from those with ventromedial prefrontal cortical brain lesions. In a large sample of healthy adults, we examined the statistical influence of several demographic variables on two versions of the IGT, with the specific prediction that educational attainment would moderate learning across trials. Results confirmed a highly significant effect of education. On the commonly used original version of the IGT, performance tended to improve more rapidly, and reach a higher eventual positive score, as the level of education increased. Age and gender were nonsignificant effects in the model, and Caucasians had slightly better IGT performance than their non-Caucasian counterparts. Conclusions are that education level, among neurologically-normal adults, should be treated as a stratification or matching variable in case-control research using this task. (JINS, 2008, 14, 1063–1068.)

A formula for the reliability of difference scores was used to estimate the reliability of Delis-Kaplan Executive Function System (D-KEFS; Delis et al., 2001) contrast measures from the reliabilities and correlations of their components. In turn these reliabilities were used to calculate standard errors of measurement. The majority of contrast measures had low reliabilities: of the 51 reliability coefficients calculated in the present study, none exceeded 0.7 and hence all failed to meet any of the criteria for acceptable reliability proposed by various experts in psychological measurement. The mean reliability of the contrast scores was 0.27, the median reliability was 0.30. The standard errors of measurement were large and, in many cases, equaled or were only marginally smaller than the contrast scores' standard deviations. The results suggest that, at present, D-KEFS contrast measures should not be used in neuropsychological decision making. (JINS, 2008, 14, 1069–1073.)

This research compares the performance of a sample of non-litigating participants with severe brain injury on both the WMT and TOMM under conditions of (1) full effort, (2) distraction, or (3) simulated malingering. The study included 60 participants with a severe brain injury and used restricted randomization to assign participants to the groups. Following Craik (1982) an auditory distraction task was used during the learning phase of each test in the distraction group, while a scenario adapted from Tombaugh (1997) was used to encourage simulation of memory impairment in the simulated malingering group. The results of this study clearly showed that while both tests demonstrated excellent sensitivity, the false positive rates for the WMT were significantly greater than those for the TOMM. It was concluded that the so-called “effort” components of the WMT required more cognitive capacity than was previously believed. (JINS, 2008, 14, 1074–1080.)

Controversy continues about which brain structures and circuitry underlie the retrieval of past (remote) memories—autobiographical, personal semantic, or general semantic—and also about which lesion sites are critical for retrograde amnesia (RA) to occur (Kopelman, 2008). This issue relates, of course, to the differential predictions of consolidation theory and of multiple trace theory regarding patterns of retrograde amnesia (and indeed the predictions of other theories). The controversy also relates to issues regarding the differential pattern of left hemisphere versus right hemisphere damage, particularly in the temporal lobes, an issue which has influenced the literature since important studies by De Renzi et al. (1987) and O'Connor et al. (1992). De Renzi et al. (1987) described a woman who, following an episode of herpes encephalitis that affected the left temporal lobe, showed a severe impairment of semantic memory with relatively preserved autobiographical memories, whereas O'Connor et al. (1992) reported a patient with right temporal lobe damage (also from herpes encephalitis), who showed disproportionately severe impairment in the recall of autobiographical incidents, relative to remote semantic memories. It is this latter contrast between left- and right-sided damage which the present authors address.

Patients with damage to the mesial and anterior portions of the temporal lobes suffer from a memory impairment involving both anterograde and retrograde amnesia. In the retrograde domain, it has been suggested that the relative severity of autobiographical and nonautobiographical memory impairment may depend on the prevalent side of the temporal damage. Here we present two patients suffering from damage to the mesial and anterior portions of the temporal lobes (hippocampal formation, parahippocampal gyrus and polar cortex) as a result of herpes encephalitis. In the first case, A.S., damage predominantly affected the right temporal lobe, whereas in the second patient, R.S., the damage was bilateral but more severe on the left side. A detailed investigation of the retrograde memory deficit demonstrated a partial double dissociation between the two patients, with A.S. almost exclusively impaired in the autobiographical domain (both episodic and semantic) and R.S. with poor performances in all domains, but much more severe in the nonautobiographical (both public events and general semantic knowledge) than in the autobiographical one. These findings reinforce the view of specialization of right and left temporal lobes in the retrieval of retrograde autobiographical and nonautobiographical memories, respectively. (JINS, 2008, 14, 1083–1094.)