Kristen A. Lindgren

Language laterality in autism spectrum disorder and typical controls: A functional, volumetric, and diffusion tensor MRI study

Language and communication deficits are among the core features of autism spectrum disorder (ASD). Reduced or reversed asymmetry of language has been found in a number of disorders, including ASD. Studies of healthy adults have found an association between language laterality and anatomical measures but this has not been systematically investigated in ASD. The goal of this study was to examine differences in gray matter volume of perisylvian language regions, connections between language regions, and language abilities in individuals with typical left lateralized language compared to those with atypical (bilateral or right) asymmetry of language functions. Fourteen adolescent boys with ASD and 20 typically developing adolescent boys participated, including equal numbers of left- and right-handed individuals in each group. Participants with typical left lateralized language activation had smaller frontal language region volume and higher fractional anisotropy of the arcuate fasciculus compared to the group with atypical language laterality, across both ASD and control participants. The group with typical language asymmetry included the most right-handed controls and fewest left-handers with ASD. Atypical language laterality was more prevalent in the ASD than control group. These findings support an association between laterality of language function and language region anatomy. They also suggest anatomical differences may be more associated with variation in language laterality than specifically with ASD. Language laterality therefore may provide a novel way of subdividing samples, resulting in more homogenous groups for research into genetic and neurocognitive foundations of developmental disorders.

Identifying regional activity associated with temporally separated components of working memory using event-related functional MRI.

This study describes the neural circuitry underlying temporally separated components of working memory (WM) performance-stimulus encoding, maintenance of information during a delay, and the response to a probe. While other studies have applied event-related fMRI to separate epochs of WM tasks, this study differs in that it employs a methodology that does not make any a priori assumptions about the shape of the hemodynamic response (HDR). This is important because no one model of the HDR is valid across the range of activated brain regions and stimulus types. Systematic modeling inaccuracies may lead to the misattribution of activity to adjacent events. Twelve healthy subjects performed a numerical version of the Sternberg Item Recognition Paradigm adapted for rapid presentation event-related fMRI. This paradigm emphasized maintenance rather than manipulative WM processes and used a subcapacity WM load. WM trials with different delay lengths were compared to fixation. The HDR of the entire WM trial for each trial type was estimated using a finite impulse response (FIR). Regional activity associated with the Encode, Delay, and Probe epochs was identified using contrasts that were based on the FIR estimates and by examining the HDRs. Each epoch was associated with a distinct but overlapping pattern of regional activity. Activation of the dorsolateral prefrontal cortex, thalamus, and basal ganglia was exclusively associated with the probe. This suggests that frontostriatal neural circuitry participates in selecting an appropriate response based on the contents of WM.

Schizophrenic subjects show deficient inhibition but intact task switching on saccadic tasks

BACKGROUND Schizophrenic patients have executive function deficits, presumably on the basis of prefrontal cortex dysfunction. Although they consistently show impaired inhibition, the evidence of a task switching deficit is less consistent and is often based on performance of neuropsychological tests that require several cognitive processes (e.g., the Wisconsin Card Sort Test [WCST]). We investigated inhibition and task switching using saccadic tasks to determine whether schizophrenic patients have selective impairments of these executive functions. METHODS Sixteen normal and 21 schizophrenic subjects performed blocks of randomly mixed prosaccade and antisaccade trials. This gave rise to four trial types: prosaccades and antisaccades that were either repeated or switched. Response accuracy and latency were measured. Schizophrenic subjects also performed the WCST. RESULTS Schizophrenic subjects showed abnormal antisaccade and WCST performance. In contrast, task switching was normal and unrelated to either antisaccade or WCST performance. CONCLUSIONS The finding of intact task switching performance that is unrelated to other measures of executive function demonstrates selective rather than general impairments of executive functions in schizophrenia. The findings also suggest that abnormal WCST performance is unlikely to be a consequence of deficient task switching. We hypothesize that inhibition and task switching are mediated by distinct neural networks, only one of which is dysfunctional in schizophrenia.

fMRI activation during a language task in adolescents with ASD

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 Brocas 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.

Effective and Structural Connectivity in the Human Auditory Cortex

Language processing involves multiple neuronal structures in the human auditory cortex. Although a variety of neuroimaging and mapping techniques have been implemented to better understand language processing at the level of the auditory cortex, much is unknown regarding how and by what pathways these structures interact during essential tasks such as sentence comprehension. In this study, the effective and structural connectivity at the level of the auditory cortex were investigated. First, blood oxygenation level-dependent (BOLD) responses were measured with time-resolved functional magnetic resonance imaging (fMRI) during audition of short sentences. Once BOLD activation maps were obtained, the effective connectivity between primary auditory cortex and the surrounding auditory regions on the supratemporal plane and superior temporal gyrus (STG) were investigated using Granger causality mapping (GCM). Effective connectivity was observed between the primary auditory cortex and (1) the lateral planum polare and anterior STG, and (2) the lateral planum temporale and posterior STG. By using diffusion tensor probabilistic mapping (DTPM), rostral and caudal fiber pathways were detected between regions depicting effective connectivity. The effective and structural connectivity results of the present study provide further insight as to how auditory stimuli (i.e., human language) is processed at the level of the auditory cortex. Furthermore, combining BOLD fMRI-based GCM and DTPM analysis could provide a novel means to study effective and structural connectivity not only in the auditory cortex, but also in other cortical regions.

Prevalence of overweight and obesity in a large clinical sample of children with autism.

BACKGROUND Overweight and obesity are major pediatric public health problems in the United States; however, limited data exist on the prevalence and correlates of overnutrition in children with autism. METHODS Through a large integrated health care systems patient database, we identified 6672 children ages 2 to 20 years with an assigned ICD-9 code of autism (299.0), Asperger syndrome (299.8), and control subjects from 2008 to 2011 who had at least 1 weight and height recorded in the same visit. We calculated age-adjusted, sex-adjusted body mass index and classified children as overweight (body mass index 85th to 95th percentile) or obese (≥ 95th percentile). We used multinomial logistic regression to compare the odds of overweight and obesity between groups. We then used logistic regression to evaluate factors associated with overweight and obesity in children with autism, including demographic and clinical characteristics. RESULTS Compared to control subjects, children with autism and Asperger syndrome had significantly higher odds of overweight (odds ratio, 95% confidence interval: autism 2.24, 1.74-2.88; Asperger syndrome 1.49, 1.12-1.97) and obesity (autism 4.83, 3.85-6.06; Asperger syndrome 5.69, 4.50-7.21). Among children with autism, we found a higher odds of obesity in older children (aged 12-15 years 1.87, 1.33-2.63; aged 16-20 years 1.94, 1.39-2.71) compared to children aged 6 to 11 years. We also found higher odds of overweight and obesity in those with public insurance (overweight 1.54, 1.25-1.89; obese 1.16, 1.02-1.40) and with co-occurring sleep disorder (obese 1.23, 1.00-1.53). CONCLUSIONS Children with autism and Asperger syndrome had significantly higher odds of overweight and obesity than control subjects. Older age, public insurance, and co-occurring sleep disorder were associated with overweight or obesity in this population.

Hemispheric specialization of the lateral prefrontal cortex for strategic processing during spatial and shape working memory

OBJECTIVE We investigated whether spatial working memory (WM) is associated with functional specialization of the right prefrontal cortex (PFC) relative to WM for shapes. We designed spatial and shape WM tasks that are relatively easy to perform and that minimize both task-switching and manipulation demands. The tasks use identical stimuli and require the same motor response. METHODS We presented 12 subjects with target shapes that appeared in particular locations. Subjects maintained either the location or the shape of the targets in WM and responded to each probe by indicating whether it was a target. During a non-WM control task, subjects indicated whether the probe appeared on the right or left side of the screen. Subjects were scanned with a 3.0 T Siemens scanner and data were analyzed using SPM99. The WM tasks were compared to identify PFC activation that was different for spatial versus shape WM. Each WM task was also compared to the control task. RESULTS compared with shape WM, spatial WM performance was faster and more accurate and was associated with increased right ventrolateral and frontopolar PFC activation. In contrast, compared to spatial WM, shape WM was associated with increased left ventrolateral PFC activity. CONCLUSIONS These findings demonstrate hemispheric specialization for spatial versus shape WM in the ventrolateral PFC. The increased activity in the right PFC for spatial WM cannot be attributed to increased task difficulty, the stimuli used, or the response requirements. Rather, we propose that differences in performance and activation reflect the use of configural processing strategies for spatial WM.

Antisaccades and Task Switching

Abstract: Executive functions allow us to respond flexibly rather than stereotypically to the environment. We examined two such functions, task switching and inhibition in the antisaccade paradigm, in two studies. One study involved 18 normal subjects; the other, 21 schizophrenic patients and 16 age‐matched controls. Subjects performed blocks of randomly mixed prosaccades and antisaccades. Repeated trials were preceded by the same type of trial (i.e., an antisaccade following an antisaccade), and switched trials were preceded by a trial of the opposite type. We measured accuracy rate and latency as indices of processing costs. Whereas schizophrenic patients had a threefold increase in error rate for antisaccades compared to normals, the effect of task switching on their accuracy did not differ from that in normal subjects. Moreover, the accuracy rate of trials combining antisaccade and task switching was equivalent to a multiplication of the accuracy rates from trials in which each was done alone. Schizophrenic latencies were disproportionately increased for antisaccades, but again they were no different from normal subjects in the effect of task switching. In both groups the effect of task switching on antisaccades was a paradoxical latency reduction. We conclude that the executive dysfunction in schizophrenia is not generalized but selective, sparing task switching from exogenous cues, in which the switch is limited to a stimulus‐response remapping. The accuracy data in both groups support independence of antisaccade and task‐switching functions. The paradoxical task‐switching benefit in antisaccadic latency effects challenges current models of task switching. It suggests either carryover inhibition by antisaccadic performance in the prior trial or facilitation of antisaccades by simultaneous performance of other cognitive operations.

What Is Perseverated in Schizophrenia? Evidence of Abnormal Response Plasticity in the Saccadic System

Although perseveration is sometimes attributed to defective set switching, the authors have recently shown that set-switching is normal in schizophrenia. In this article, the authors tested for persistent states of the saccadic response system, rather than set perseveration. Schizophrenic and healthy subjects performed antisaccades and prosaccades. The authors analyzed for 3 carry-over effects. First, whereas the latency of the current saccade correlated with that of the prior saccade in both groups, the correlations under mixed-task conditions declined in healthy but not in schizophrenic subjects. Second, antisaccades in penultimate trials delayed upcoming saccades in schizophrenic but not in healthy subjects. Third, schizophrenic subjects were more likely to erroneously perseverate the direction of a prior antisaccade but not a prior prosaccade. The authors concluded that, in schizophrenia, the effects of correct antisaccades are persistent not weak. Saccades in schizophrenia are characterized by perseveration of antisaccade-induced changes in the saccadic response system rather than failures to switch task set.

Deficient saccadic inhibition in Asperger’s disorder and the social-emotional processing disorder

Background: Both Asperger’s disorder and the social-emotional processing disorder (SEPD), a form of non-verbal learning disability, are associated with executive function deficits. SEPD has been shown to be associated with deficient saccadic inhibition. Objective: To study two executive functions in Asperger’s disorder and SEPD, inhibition and task switching, using a single saccadic paradigm. Methods: 22 control subjects and 27 subjects with developmental social processing disorders—SEPD, Asperger’s disorder, or both syndromes—performed random sequences of prosaccades and antisaccades. This design resulted in four trial types, prosaccades and antisaccades, that were either repeated or switched. The design allowed the performance costs of inhibition and task switching to be isolated. Results: Subjects with both Asperger’s disorder and SEPD showed deficient inhibition, as indicated by increased antisaccade errors and a disproportionate increase in latency for antisaccades relative to prosaccades. In contrast, task switching error and latency costs were normal and unrelated to the costs of inhibition. Conclusions: This study replicates the finding of deficient saccadic inhibition in SEPD, extends it to Asperger’s disorder, and implicates prefrontal cortex dysfunction in these syndromes. The finding of intact task switching shows that executive function deficits in Asperger’s disorder and SEPD are selective and suggests that inhibition and task switching are mediated by distinct neural networks.