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.

Final Program, Thirty-Sixth Annual Meeting International Neuropsychological Society, February 6-9, 2008, Waikoloa, Hawaii, USA.

We investigated verb generation in children with spina bifida meningomyelocele (SBM; n = 55) and in typically developing controls (n = 32). Participants completed 6 blocks (40 trials each) of a task requiring them to produce a semantically related verb in response to a target noun and an additional 40 trials on which they were simply required to read target nouns aloud. After controlling for reading response time, groups did not differ significantly in verb generation response time or learning. Children with SBM produced more non-verb errors than controls and tended to repeat their mistakes over blocks. Verb generation performance was associated with brain volume measures in participants with SBM. Congenital cerebellar dysmorphology is associated with impaired performance in verb generation accuracy, although not with increased response times to produce verbs.(JINS, 2008, 14, 181–191.)

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.)

This review proposes a new taxonomy of automatic and controlled attention. The taxonomy distinguishes among the role of the attendee (puppet and robot, critic and actor), the attention process (stimulus orienting vs. response control), and the attention operation (activation vs. inhibition vs. adjustment), and identifies cognitive phenotypes by which attention is overtly expressed. We apply the taxonomy to four childhood attention disorders: attention deficit hyperactivity disorder, spina bifida meningomyelocele, traumatic brain injury, and acute lymphoblastic leukemia. Variations in attention are related to specific brain regions that support normal attention processes when intact, and produce disordered attention when impaired. The taxonomy explains group differences in behavioral inattention, hyperactivity, and impulsiveness, as well as medication response. We also discuss issues relevant to theories of the cognitive and neural architecture of attention: functional dissociations within and between automatic and controlled attention; the relative importance of type of brain damage and developmental timing to attention profile; cognitive-energetic models of attention and white matter damage; temporal processing deficits, attention deficits and cerebellar damage; and the issue of cognitive phenotypes as candidate endophenotypes. (JINS, 2008, 14, 673–690.)

On the mild end of the acquired brain injury spectrum, the terms concussion and mild traumatic brain injury (mTBI) have been used interchangeably, where persistent post-concussive syndrome (PPCS) has been a label given when symptoms persist for more than three months post-concussion. Whereas a brief history of concussion research is overviewed, the focus of this review is on the current status of PPCS as a clinical entity from the perspective of recent advances in the biomechanical modeling of concussion in human and animal studies, particularly directed at a better understanding of the neuropathology associated with concussion. These studies implicate common regions of injury, including the upper brainstem, base of the frontal lobe, hypothalamic-pituitary axis, medial temporal lobe, fornix, and corpus callosum. Limitations of current neuropsychological techniques for the clinical assessment of memory and executive function are explored and recommendations for improved research designs offered, that may enhance the study of long-term neuropsychological sequelae of concussion. (JINS, 2008, 14, 1–22.)

While the cognitive disturbances that frequently follow severe traumatic brain injury (TBI) are relatively well understood, the ways in which these affect the psychosocial functioning of people with TBI are yet to be determined and have thus received little attention in treatment research. Growing evidence indicates that a significant proportion of individuals with TBI demonstrate an inability to recognize affective information from the face, voice, bodily movement, and posture. Because accurate interpretation of emotion in others is critical for the successful negotiation of social interactions, effective treatments are necessary. Until recently, however, there have been no rehabilitation efforts in this area. The present review examines the literature on emotion perception deficits in TBI and presents a theoretical rationale for targeted intervention. Several lines of research relevant to the remediation of emotion perception in people with TBI are considered. These include work on emotion perception remediation with other cognitively impaired populations, current neuropsychological models of emotion perception and underlying neural systems, and recent conceptualizations of remediation processes. The article concludes with a discussion of the importance of carrying out efforts to improve emotion perception within a contextualized framework in which the day-to-day relevance of training is clear to all recipients. (JINS, 2008, 14, 511–525.)

Hemispatial neglect has been conceptualized as having dissociable and potentially clinically relevant subtypes. However, the question of whether patient performance on neglect subtype measures is consistent over time remains largely unanswered. We examined changes in performance over time on measures of motor, perceptual, and personal neglect in 21 patients with neglect from acute right hemisphere stroke. Patients were assessed on three occasions, separated by at least one week, using a lateralized target test, lateralized response test, and modified fluff test. Across three testing timepoints, 18 (85.7%) patients changed subtype performance patterns at least once. In 13 (61.9%) of these patients, inconsistency between timepoints was not adequately accounted for by recovery. On initial testing, seven, patients (33.3%) demonstrated more than one neglect subtype symptom; by the third testing timepoint none of the patients demonstrated multiple symptoms. In the setting of acute stroke, performance on three measures of neglect symptoms is inconsistent across time. However, the distribution of neglect subtype symptoms appears to become more discrete over time. These findings complicate our understanding of the pathophysiology and potential prognostic value of neglect subtypes, and suggest that treatment decisions based on subtype performance assessed at a single timepoint, may be of limited utility. (JINS, 2008, 14, 23–32.)

The objective was to identify the trajectories of onset of memory and other cognitive loss in persons destined to develop mild cognitive impairment (MCI) or dementia. Healthy, community dwelling, cognitively intact elders (n = 156, mean age at entry = 83 years) were examined annually for an average of greater than 7 years. Those who developed at least two consecutive Clinical Dementia Ratings ≥ 0.5 were classified as having MCI. Longitudinal mixed effects models with a change point were used to model the aging process in those with and without an MCI diagnosis during follow-up and to model the rate of change relative to the age of onset of MCI. MCI had a preclinical stage of accelerated cognitive loss that was observed 3 to 4 years before the diagnosis of MCI on tests of verbal memory, animal fluency, and visuospatial constructions. Evidence from memory performance before the change point suggests that a slow decline in memory precedes the period of accelerated decline in the development of MCI. Aging transitions leading to MCI and dementia are characterized by unique linear and nonlinear cognitive changes in several domains that precede the diagnosis of MCI and dementia by at least several years. (JINS, 2008, 14, 192–198.)

There is a growing literature examining working memory deficits using functional imaging and there has been great convergence in the findings, to date, but interpretations have varied. Investigators consistently observed recruitment of neural resources in clinical samples, with some examiners attributing these findings to neural inefficiency and others attributing differences to neural compensation and/or brain reorganization. It is the goal of this paper to address the current interpretation of altered brain activation in clinical imaging studies of working memory dysfunction with specific emphasis on findings in prefrontal cortex (PFC). Throughout this review, the methods used to examine brain reorganization associated with working memory dysfunction are critiqued with the goal of understanding how study design has influenced data interpretation. It is proposed that much of what has been considered “aberrant” neural activity is not indicative of neural compensation, as it has been typically defined, and does not represent brain reorganization. Instead, recruitment of neural resources in PFC can be explained by a natural, and largely overlooked, role of cognitive control in accommodating neural dysfunction secondary to brain injury and disease. This paper provides predictions based on this proposition and a critique of the current methods available for testing these predictions. (JINS, 2008, 14, 526–534.)

Because of its high prevalence and implications for quality of life and possibly even disease progression, depression has been intensively studied in multiple sclerosis (MS) over the past 25 years. Despite the publication of numerous excellent empirical research papers on this topic during that time, the publication of theoretical work that attempts to explain depression in a comprehensive way is scarce. In this study, we present a theoretical model that attempts to integrate existing work on depression in MS and provide testable hypotheses for future work. The model suggests that risk for depression begins with the onset of MS. MS results in disease-related changes such as increased lesion burden/brain atrophy and immunological anomalies that are associated with depression in MS, but explain only a relatively limited proportion of the variance. Common sequelae of MS including fatigue, physical disability, cognitive dysfunction, and pain, have all been shown to have an inconsistent or relatively weak relationship to depression in the literature. In the model, we propose that four variables—social support, coping, conceptions of the self and illness, and stress—may moderate the relationship between the above common MS sequelae with depression and help to explain inconsistencies in the literature. (JINS, 2008, 14, 691–724.)

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.)

Author Index Thirty-Sixth Annual Meeting International Neuropsychological Society, February 6-9, 2008, Waikoloa, Hawaii, USA.

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.)

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.)

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.)

Unilateral neglect, a lack of awareness for one side of space, is a common and debilitating consequence of stroke. Previous work has identified a relationship between enduring left neglect and diminished general alertness and shown that increasing alertness can temporarily reduce the severity of the spatial bias. In that research, alertness was modulated by loud tones or with pharmacological stimulants. Here we examine whether cognitive, endogenously driven changes can produce similar short-term improvements. Time-pressure is associated with increased subjective arousal and increased activation in cortical regions associated with alertness. Here five patients completed a spatial cancellation task with and without instructions regarding a time limit. Significant reductions in neglect severity were observed when patients believed that they were acting under time-pressure, despite the conditions being equivalent in the actual (unlimited) time available. Functional imaging work has highlighted the secondary effects that damage to networks mediating alertness can have on structurally intact spatial systems. The results here suggest that activation of presumably spared function in these damaged networks can induce moment-by-moment changes in spatial function and, crucially, that this can be achieved using entirely endogenous means. (JINS, 2008, 14, 33–41.)