Interest In Autism Spectrum Disorder Research Articles

Barking Up the Wrong Tree-Motor-Sensory Elements as Prodrome in Autism.

Autism spectrum disorder (ASD) has been intensely investigated since the term was first used over 80 years ago. The prevalence of ASD is constantly rising, and, currently, 1:36 children are diagnosed with this disorder. Despite the intense interest in ASD, the origins of this disorder remain obscure. This article explores motor issues and proprioceptive interoception difficulties as the prodrome of ASD. The importance of early intervention in the prognosis of ASD is common knowledge. Yet, since the communicational and social behaviors typical of ASD are observable only after the age of 18 months, diagnosis and early intervention are delayed. Therefore, the quest into the involvement of sensory-motor difficulties as a source of ASD traits, or at least as a potential early indicator, is warranted, with the intention of enabling early diagnosis and early intervention. This article examines the justification for this new avenue of early diagnosis and intervention and may open up a completely different way of viewing ASD. This new point of view may suggest an original path of assessment and intervention in infancy with this group of clients, possibly leading to improved prognosis for children and their families.

Reduced grey matter volume of amygdala and hippocampus is associated with the severity of autistic symptoms and language abilities in school-aged children with Autism Spectrum Disorder: an exploratory study.

The core symptoms of Autism Spectrum Disorder (ASD) are impairments in social interaction/communication and the presence of stereotyped and repetitive behaviour. The amygdala and hippocampus are involved in core functions in the "social brain" and, thus, may be of particular interest in ASD. Previous studies demonstrated inconsistent results, revealing both increased and reduced volume of these brain structures in individuals with ASD. In this study, we investigated the grey and white matter volumes of amygdala and hippocampus in primary-school-aged children with and without ASD. Also, we assessed the relationships between the volume of brain structures and behavioural measures in children with ASD. A total of 36 children participated in the study: 18 children with ASD (13 boys, age range 8.01-14.01years, mean age (Mage) = 10.02, standard deviation (SD) = 1.76) and 18 age- and sex-matched typically developing controls (13 boys, age range 7.06-12.03years, Mage = 10.00, SD = 1.38). The whole-brain structural magnetic resonance imaging (MRI) was applied to acquire T1 images for each child. The results showed a bilateral reduction in grey matter volume of amygdala and hippocampus in children with ASD, but no difference was found in white matter volume. Importantly, pathological reduction in grey matter volume of amygdala was associated with lower language skills and more severe autistic traits; also, a reduced grey matter volume of the left hippocampus was related to lower language skills in the ASD group.

Repetitive and restricted behaviors and interests in autism spectrum disorder: relation to individual characteristics and mental health problems

BackgroundAlthough repetitive and restricted behaviors and interests (RRBIs) may interfere with well-being and functioning in autistic individuals, research on their relation to sex, age, cognitive level, and mental health problems remains unclear. Much of the research to date has used broad categorizations rather than specific categorizations of RRBIs to examine the difference in RRBIs between individuals. The purpose of this study was to explore, in different groups of individuals, the presence of specific RRBI subtypes, and to examine the association of specific RRBI subtypes with symptoms of internalizing and externalizing behaviors.MethodsSecondary data analyses were conducted using the Simons Simplex Collection dataset, which included 2,758 participants (aged 4 to 18). Families of autistic children completed the Repetitive Behavior Scale–Revised (RBS-R) and the Child Behavior Checklist.ResultsAcross all RBS-R subtypes, results revealed no sex differences. Older children showed higher rates of Ritualistic/Sameness behaviors than younger children and adolescents, whereas younger and older children showed more Stereotypy than adolescents. Additionally, lower cognitive level groups showed higher rates of RBS-R subtypes except for Ritualistic/Sameness. After controlling for age and cognitive level, RBS-R subtypes accounted for a substantial amount of variance in internalizing and externalizing behaviors (23% and 25%, respectively). Specifically, Ritualistic/Sameness and Self-Injurious Behavior both predicted internalizing and externalizing behaviors, whereas Stereotypy only predicted internalizing behavior.ConclusionsThese findings have key clinical implications that emphasize not only the consideration of sex, age, and cognitive level, but also specific RRBIs and co-occurring mental health problems, when assessing for ASD and designing individualized interventions.

Dynamic multi-site graph convolutional network for autism spectrum disorder identification

Multi-site learning has attracted increasing interests in autism spectrum disorder (ASD) identification tasks by its efficacy on capturing data heterogeneity of neuroimaging taken from different medical sites. However, existing multi-site graph convolutional network (MSGCN) often ignores the correlations between different sites, and may obtain suboptimal identification results. Moreover, current feature extraction methods characterizing temporal variations of functional magnetic resonance imaging (fMRI) signals require the time series to be of the same length and cannot be directly applied to multi-site fMRI datasets. To address these problems, we propose a dual graph based dynamic multi-site graph convolutional network (DG-DMSGCN) for multi-site ASD identification. First, a sliding-window dual-graph convolutional network (SW-DGCN) is introduced for feature extraction, simultaneously capturing temporal and spatial features of fMRI data with different series lengths. Then we aggregate the features extracted from multiple medical sites through a novel dynamic multi-site graph convolutional network (DMSGCN), which effectively considers the correlations between different sites and is beneficial to improve identification performance. We evaluate the proposed DG-DMSGCN on public ABIDE I dataset containing data from 17 medical sites. The promising results obtained by our framework outperforms the state-of-the-art methods with increase in identification accuracy, indicating that it has a potential clinical prospect for practical ASD diagnosis. Our codes are available on https://github.com/Junling-Du/DG-DMSGCN.

Randomized Double-Blind Crossover Study for Evaluating a Probiotic Mixture on Gastrointestinal and Behavioral Symptoms of Autistic Children.

Autism spectrum disorders (ASDs) represent a diagnostic challenge with a still partially uncertain etiology, in which genetic and environmental factors have now been assessed. Among the hypotheses underlying the involvement of biological and environmental factors, the gut–brain axis is of particular interest in autism spectrum disorders. Several studies have highlighted the related incidence of particular gastrointestinal symptoms (GISs) in children suffering from ASDs. Probiotics have shown success in treating several gastrointestinal dysbiotic disorders; therefore, it is plausible to investigate whether they can alleviate behavioral symptoms as well. On these bases, a randomized double-blind crossover study with a placebo was conducted, evaluating the effects of a mixture of probiotics in a group of 61 subjects aged between 24 months and 16 years old with a diagnosis of ASD. Behavioral evaluation was performed through the administration of a questionnaire including a Parenting Stress Index (PSI) test and the Vineland Adaptive Behavior Scale (VABS). The Psycho-Educational Profile and the Autism Spectrum Rating Scale (ASRS) were also evaluated. Microbial composition analyses of fecal samples of the two groups was also performed. The study showed significant improvements in GISs, communication skills, maladaptive behaviors, and perceived parental stress level after the administration of probiotics. Microbiome alpha diversity was comparable between treatment arms and no significant differences were found, although beta diversity results were significantly different in the treatment group between T0 and T1 time points. Streptococcus thermophilus, Bifidobacterium longum, Limosilactobacillus fermentum, and Ligilactobacillus salivarius species were identified as some of the most discriminant taxa positively associated with T1 samples. This preliminary study corroborates the relationship between intestinal microbiota and ASD recently described in the literature.

A-294 Mind-Wandering in Autism Spectrum Disorder: An Exploratory Multi-Case Study

Abstract Objective: Executive dysfunction has become a recent topic of interest in autism spectrum disorder (ASD) due to proposed contributions to functional impairments and decreased quality of life. Executive function in ASD is not conclusive; thus, a novel performance measure to explore a constellation of executive function subsets is mind-wandering. This multi-case study aimed to explore mind-wandering through the executive failure hypothesis and the meta-awareness hypothesis with autistic teens and young adults. Methods: Six autistic individuals with intact intellectual functioning were extensively investigated using a sustained attention task, thought probes, open-ended interviews, and retrospective trait questionnaires. Inclusion criteria included an FSIQ > 80 on either the WISC-V or WAIS-IV. Executive function was measured using the DKEFS Verbal Fluency subtest. Retrospective trait questionnaires included: Metacognitions Questionnaire-30, Spontaneous and Deliberate Mind-Wandering Scales, and Mind Excessively Wandering Scale. Results: Responses revealed that the sampled autistic individuals engaged in a variety of task-related, task-unrelated, intentional, unintentional, directed, and undirected mind-wandering events, both with and without awareness. Notably, autistic individuals in this sample reported engaging in intentional mind-wandering without awareness as well as unintentional mind-wandering despite exceptional executive functioning, raising questions about the validity of the executive failure and meta-awareness hypotheses in ASD. Conclusion: Overall, despite underlying difficulties in executive control and meta-awareness, autistic individuals in this multi-case study successfully reported on their own experience of thought and were able to exert control over their own thinking. As such, future research should further explore how extent of mind-wandering ability may relate to cognitive-based interventions as well as diagnostic differentials within ASD.

Visual Search for Circumscribed Interests in Autism Is Similar to That of Neurotypical Individuals.

Intense interests are a core symptom of autism spectrum disorders (ASD) and can be all-encompassing for affected individuals. This observation raises the hypothesis that intense interests in ASD are related to pervasive changes in visual processing for objects within that category, including visual search. We assayed visual processing with two novel tasks, targeting category search and exemplar search. For each task, three kinds of stimuli were used: faces, houses, and images personalized to each participant’s interest. 25 children and adults with ASD were compared to 25 neurotypical (NT) children and adults. We found no differences in either visual search task between ASD and NT controls for interests. Thus, pervasive alterations in perception are not likely to account for ASD behavioral symptoms.

Characterization of Special Interests in Autism Spectrum Disorder: A Brief Review and Pilot Study Using the Special Interests Survey.

Special interests (SIs) are part of the diagnostic criteria for autism spectrum disorder (ASD). Though they can have both positive and negative effects on functioning and long-term outcomes, research on SIs is limited. This pilot study used a newly developed parent-report measure, the Special Interest Survey, to characterize SIs in 1992 children with ASD. The mean number of current special interests reported was 9, with television, objects, and music being most commonly endorsed interests. The mean age of onset reported across all categories was 5.24years, with duration of past interests most often exceeding 2years. Age of onset, interference, and relative unusualness of the SI was varied across categories. Interference was significantly correlated with the unusualness of the SIs.

A Review of Default Mode Network Connectivity and Its Association With Social Cognition in Adolescents With Autism Spectrum Disorder and Early-Onset Psychosis.

Recent studies have demonstrated substantial phenotypic overlap, notably social impairment, between autism spectrum disorder (ASD) and schizophrenia. However, the neural mechanisms underlying the pathogenesis of social impairments across these distinct neuropsychiatric disorders has not yet been fully examined. Most neuroimaging studies to date have focused on adults with these disorders, with little known about the neural underpinnings of social impairments in younger populations. Here, we present a narrative review of the literature available through April 2020 on imaging studies of adolescents with either ASD or early-onset psychosis (EOP), to better understand the shared and unique neural mechanisms of social difficulties across diagnosis from a developmental framework. We specifically focus on functional connectivity studies of the default mode network (DMN), as the most extensively studied brain network relevant to social cognition across both groups. Our review included 29 studies of DMN connectivity in adolescents with ASD (Mean age range = 11.2–21.6 years), and 14 studies in adolescents with EOP (Mean age range = 14.2–24.3 years). Of these, 15 of 29 studies in ASD adolescents found predominant underconnectivity when examining DMN connectivity. In contrast, findings were mixed in adolescents with EOP, with five of 14 studies reporting DMN underconnectivity, and an additional six of 14 studies reporting both under- and over-connectivity of the DMN. Specifically, intra-DMN networks were more frequently underconnected in ASD, but overconnected in EOP. On the other hand, inter-DMN connectivity patterns were mixed (both under- and over-connected) for each group, especially DMN connectivity with frontal, sensorimotor, and temporoparietal regions in ASD, and with frontal, temporal, subcortical, and cerebellar regions in EOP. Finally, disrupted DMN connectivity appeared to be associated with social impairments in both groups, less so with other features distinct to each condition, such as repetitive behaviors/restricted interests in ASD and hallucinations/delusions in EOP. Further studies on demographically well-matched groups of adolescents with each of these conditions are needed to systematically explore additional contributing factors in DMN connectivity patterns such as clinical heterogeneity, pubertal development, and medication effects that would better inform treatment targets and facilitate prediction of outcomes in the context of these developmental neuropsychiatric conditions.

A Nexus Model of Restricted Interests in Autism Spectrum Disorder.

Restricted interests (RIs) in autism spectrum disorder (ASD) are clinically impairing interests of unusual focus or intensity. They are a subtype of restricted and repetitive behaviors which are one of two diagnostic criteria for the disorder. Despite the near ubiquity of RIs in ASD, the neural basis for their development is not well understood. However, recent cognitive neuroscience findings from nonclinical samples and from individuals with ASD shed light on neural mechanisms that may explain the emergence of RIs. We propose the nexus model of RIs in ASD, a novel conceptualization of this symptom domain that suggests that RIs may reflect a co-opting of brain systems that typically serve to integrate complex attention, memory, semantic, and social communication functions during development. The nexus model of RIs hypothesizes that when social communicative development is compromised, brain functions typically located within the lateral surface of cortex may expand into social processing brain systems and alter cortical representations of various cognitive functions during development. These changes, in turn, promote the development of RIs as an alternative process mediated by these brain networks. The nexus model of RIs makes testable predictions about reciprocal relations between the impaired development of social communication and the emergence of RIs in ASD and suggests novel avenues for treatment development.

Nonclinical Factors in Autism Diagnosis: Results From a National Health Care Provider Survey.

The prevalence of autism spectrum disorder (ASD) has increased 10-fold in the past 40 years, and disparities have been noted by race/ethnicity and socioeconomic status, prompting concern about diagnostic accuracy. Provider perceptions of ASD diagnostic accuracy are not known. We conducted a survey of providers who diagnose ASD assessing how nonclinical factors might affect ASD diagnostic rates. The mixed-mode survey was sent to the members of the Society of Developmental and Behavioral Pediatrics with clinical interest in ASD (n = 400). Respondents used a Likert-type scale to address how often they and their colleagues overdiagnosed or underdiagnosed ASD. They were also asked how families grouped by race/ethnicity, education, socioeconomic status, and urbanicity perceived an ASD diagnosis. Sixty-three percent of providers completed the survey. Eight point seven percent of providers self-reported that they overdiagnose ASD at least sometimes. However, 58% of providers reported that local colleagues overdiagnose ASD at least sometimes. Seven point eight percent of providers self-reported underdiagnosing ASD at least sometimes and cited parents not wanting a diagnosis as one of the most common reasons they may underdiagnose. Providers reported that non-white and rural families were more likely to think that ASD diagnosis was "a bad thing" than "a good thing" than white and urban and suburban families, respectively. Providers report moderate rates of ASD misdiagnosis and perceive differences in diagnostic preferences according to family characteristics. The study results may help explain the trends and disparities in ASD diagnosis.

Obsessive-Compulsive Disorder in Autism Spectrum Disorder Across the Lifespan.

Obsessive-compulsive disorder is a relatively common disorder seen in autism spectrum disorder across the lifespan. Many obsessive-compulsive disorder symptoms can present similarly to the core features of autism spectrum disorder and it is often difficult to differentiate between obsessive-compulsive disorder and stereotypic behaviors or restricted interests in autism spectrum disorder. However, there are differences between the 2 disorders. This article is a review of the current literature with the goal of helping the clinician to diagnose and treat obsessive-compulsive disorder in a patient with autism spectrum disorder.

A case study of suicidality presenting as a restricted interest in autism Spectrum disorder

BackgroundSuicidality has been under-researched in autism spectrum disorders (ASD). Most studies have linked increased suicidality in ASD to psychiatric comorbidities such as depression. Here we investigated, from a neuropsychological and clinical standpoint, the relationship between core ASD symptoms, i.e., restricted behaviors and social and communication impairments, and the suicidal behaviors in an adult male individual with ASD, with no psychiatric comorbidities.Case presentationWe report the case of a 21-year-old male with ASD who attempted suicide twice, in the absence of other psychiatric diagnoses. His behavior and communication skills were rigid. His suicidality was characterized by a rigid, detailed, and pervasive thinking pattern, akin to restricted interests. Consistently, from a neuropsychological standpoint, we found below-average planning and attention skills, and mind-reading skills were rigid and lacked spontaneity.ConclusionsOur case-study suggests that specific clinical and neuropsychological dimensions might be related to suicidal behaviors in ASD. Clinically, the repetitive and rigid suicide-oriented thinking of our patient was not part of a depressive episode. Instead, it followed a purely logical, inflexible, and pervasive reasoning pattern focused on a topic that fascinated him – i.e., suicide --, akin to restricted behaviors. From a neuropsychological standpoint, restrictive suicide-oriented thinking in our patient seems to be related to attention and executive anomalies that have been linked to repetitive and restricted behaviors in ASD. New tools need to be developed to assess persistent suicidal thoughts in this population, as they might be related to intrinsic features of ASD.

Study of corpus callosum cellular microstructure using diffusion microscopy MRI in subjects with autism spectrum disorders

Neurons in the supragranular layers of the human cerebral cortex play an important role in long-range cortico-cortical connections. Alterations to these layers are of special interest in autism spectrum disorder (ASD) as they could play a significant role in altered connectivity between distal regions of cortex. The present study isolated sampling boxes through the use of an automated boundary identification technique. A two-dimensional analysis of the Nissl-stained tissue was then performed to examine whether differences in cell size and number are present in ASD tissue. The analysis focused on layers II and III of association cortex sampled from frontal (BA9), temporal (BA21), and parietal (BA7) regions. In previous studies, both BA9 and BA21 have been linked to alterations in cortical connectivity in ASD. Aside from the expected differences between cortical layers and regions, data analysis revealed that ASD tissue possessed a higher density of cells, the magnitude of which was layer dependent, and that the cell profiles were of a smaller size. The results of this study suggest that cellular abnormalities with respect to cell size and number are present in multiple areas of association cortex, specifically within layers that are involved in long-range connectivity. Additionally, the results comport with previous findings of altered cortical minicolumns in frontal and temporal areas and further suggest that similar irregularities may also be present in parietal areas.

Temperament and character in men with autism spectrum disorder: A reanalysis of scores on the Temperament and Character Inventory by individual case matching.

BackgroundInterest in autism spectrum disorders (ASD) in adulthood is increasing. Although a person may be diagnosed with ASD, the diagnosis reveals little about the individual's temperament, character, and personality. Also, relatively little is known about the personality of adults with ASD.MethodA reanalysis of scores on the Temperament and Character Inventory (TCI) administered to a group of 66 normally intelligent men aged 18–63 years, diagnosed with ASD, by individual case matching to a comparison group of 66 men from the general population drawn from the TCI manual.ResultsCompared to the comparison group, men with ASD scored significantly higher on the scale for Harm Avoidance, and lower on Novelty Seeking, Reward Dependence, Self-Directedness, and Cooperativeness.ConclusionsIn this study the score pattern for temperament and character found in men with ASD by individual case matching confirms and strengthens earlier general group matching findings emerging from our 2012 study and from studies from Sweden and the Netherlands.

Resting-state Gamma-band EEG Abnormalities in Autism.

Gamma-band rhythmic abnormalities have been of significant interests in autism spectrum disorders (ASD). Most studies used magnetoencephalography (MEG) due to its advantage in measuring weak gamma signals as compared to electroencephalography (EEG). However, EEG is more accessible, portable, and importantly, more sensitive to cortical sources located at the crowns of gyri, than MEG. Therefore, it is extremely valuable if EEG can be used to detect gamma-band abnormalities in ASD, which could provide complementary insights on pathology of ASD. One challenge in detecting gamma-band neural activities is to remove muscular artifacts, which share the same frequency band. In the present study, we used a previously developed time-frequency independent component analysis (ICA)approach to probe EEG gamma-band abnormalities in ASD. We examined functional connectivity (FC) patterns on intrinsic connectivity networks (ICNs), i.e., the ICs representing distributed neural activities obtained from ICA, using the metrics of spectral power of individual ICNs and coherence between different ICNs. Seven ICNs that reassembled ICNs obtained from EEG data in the band of 2-30 Hz, were successfully identified in the gamma-band (31-50 Hz) data by the approach. Local over-connectivity in the bilateral frontal and left parietal ICNs, as well as long-range under-connectivity between left and right motor ICNs, were observed in ASD. In addition, the age-related effect was identified in the left motor and left parietal ICNs in healthy control, but not in ASD. These findings demonstrated a mixed pattern of gamma-band FC changes in ASD. It further indicated that the developed approach is promising in reconstructing gamma-band patterns from resting-state EEG signals.

A Randomized Placebo-Controlled Cross-Over Pilot Study of Riluzole for Drug-Refractory Irritability in Autism Spectrum Disorder

Riluzole is a glutamatergic modulator of particular interest in autism spectrum disorder (ASD). In this 12-week randomized, double-blind, placebo-controlled, crossover pilot study we evaluated the safety and tolerability of 5-week of adjunctive riluzole treatment (vs. 5-week of placebo, with 2-week washout period) targeting ASD-associated drug-refractory irritability in eight individuals age 12-25years. All participants tolerated riluzole 200mg per day, however there were no statistically significant findings for the overall treatment effect, the treatment effect by week within period of the study, or a cross-over effect across the periods of the study on the Clinical Global Impression Improvement Scale or the Aberrant Behavior Checklist Irritability subscale. The results of this trial indicate that 5-week of riluzole treatment was well tolerated, but had no significant effect on the target symptoms. Trial Registration ClinicalTrials.gov Identifier NCT02081027, Registered 5 August 2013, First participant enrolled 19 September 2013.

The Survey of Favorite Interests and Activities: Assessing and understanding restricted interests in children with autism spectrum disorder.

Restricted interests are an established diagnostic symptom of autism spectrum disorder. While there is considerable evidence that these interests have maladaptive consequences, they also provide a range of benefits. This article introduces a new instrument, the Survey of Favorite Interests and Activities, and uses it to examine the nature of restricted interests in autism spectrum disorder. Respondents report substantial benefits of restricted interests as well as areas of difficulty. The Survey of Favorite Interests and Activities assesses Social Flexibility, Perseveration, Respondent Discomfort, Adaptive Coping, and Atypicality. All scales have Cronbach's α > 0.70. Age and socioeconomic status have little effect on Survey of Favorite Interests and Activities scales; nor does gender with the exception of interest Atypicality. The expected pattern of correlations with existing scales was found. Research and clinical implications are discussed.

Common functional variants of the glutamatergic system in Autism spectrum disorder with high and low intellectual abilities.

The genetic architecture underlying Autism spectrum disorder (ASD) has been suggested to differ between individuals with lower (IQ≤70; LIQ) and higher intellectual abilities (IQ>70; HIQ). Among the identified pathomechanisms, the glutamatergic signalling pathway is of specific interest in ASD. We investigated 187 common functional variants of this neurotransmitter system for association with ASD and with symptom severity in two independent samples, a German (German-ALL: N=583 families) and the Autism Genome Project cohort (AGP-ALL: N=2001 families), split into HIQ, and LIQ subgroups. We did not identify any association withstanding correction for multiple testing. However, we report a replicated nominal significant under-transmission (OR<0.79, p<0.04) of the AKAP13 rs745191-T allele in both LIQ cohorts, but not in the much larger HIQ cohorts. At the phenotypic level, we nominally replicated associations of CAMK2A-rs2241694 with non-verbal communication in both combined LIQ and HIQ ASD cohorts. Variants PLD1-rs2124147 and ADCY1-rs2461127 were nominally associated with impaired non-verbal abilities and AKAP2-rs3739456 with repetitive behaviour in both LIQ cohorts. All four LIQ-associated genes are involved in G-protein coupled signal transduction, a downstream pathway of metabotropic glutamate receptor activation. We conclude that functional common variants of glutamatergic genes do not have astrong impact on ASD, but seem to moderately affect ASD risk and phenotypic expression. Since most of our nominally replicated hits were identified in the LIQ cohort, further investigation of the glutamatergic system in this subpopulation might be warranted.

Two-dimensional analysis of the supragranular layers in autism spectrum disorder

Neurons in the supragranular layers of the human cerebral cortex play an important role in long-range cortico-cortical connections. Alterations to these layers are of special interest in autism spectrum disorder (ASD) as they could play a significant role in altered connectivity between distal regions of cortex. The present study isolated sampling boxes through the use of an automated boundary identification technique. A two-dimensional analysis of the Nissl-stained tissue was then performed to examine whether differences in cell size and number are present in ASD tissue. The analysis focused on layers II and III of association cortex sampled from frontal (BA9), temporal (BA21), and parietal (BA7) regions. In previous studies, both BA9 and BA21 have been linked to alterations in cortical connectivity in ASD. Aside from the expected differences between cortical layers and regions, data analysis revealed that ASD tissue possessed a higher density of cells, the magnitude of which was layer dependent, and that the cell profiles were of a smaller size. The results of this study suggest that cellular abnormalities with respect to cell size and number are present in multiple areas of association cortex, specifically within layers that are involved in long-range connectivity. Additionally, the results comport with previous findings of altered cortical minicolumns in frontal and temporal areas and further suggest that similar irregularities may also be present in parietal areas.