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Introduction
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Publications
Publications (129)
Background
The neurometabolic profile of associated with autism spectrum disorder (ASD) has been reported to be abnormal by some studies showing region specific metabolite levels in ASD, while others report no group differences. The neurometabolic profile of the left dorsolateral prefrontal cortex (DLPFC) is of particular interest due to the DLPFC...
Clinical research aiming at objectively identifying and characterizing diseases via clinical observations and biological and radiological findings is a critical initial research step when establishing objective diagnostic criteria and treatments. Failure to first define such diagnostic criteria may lead research on pathogenesis and etiology to seri...
In some instances, when chemicals bind to proteins, they have the potential to induce a conformational change in the macromolecule that may misfold in such a way that makes it similar to the various target sites or act as a neoantigen without conformational change. Cross-reactivity then can occur if epitopes of the protein share surface topology to...
Individuals with intestinal barrier dysfunction are more prone to autoimmunity. Lipopolysaccharides (LPS) from gut bacteria have been shown to play a role in systemic inflammation, leading to the opening of the gut and blood-brain barrier (BBB). This study aims to measure antibodies against LPS and barrier proteins in samples positive for anti-Sacc...
Patients with Parkinson’s disease (PD) have increased susceptibility to bisphenol A (BPA) exposure since they have an impaired biotransformation capacity to metabolize BPA. PD subjects have reduced levels of conjugated BPA compared to controls. Reduced ability to conjugate BPA provides increased opportunity for unconjugated BPA to bind to albumin i...
Background:
The non-prescription medication paracetamol (acetaminophen, APAP) is currently recommended as a safe pain and fever treatment during pregnancy. However, recent studies suggest a possible association between APAP use in pregnancy and offspring neurodevelopment.
Objectives:
To conduct a review of publications reporting associations bet...
Many hypothyroid and autoimmune thyroid patients experience reactions with specific foods. Additionally, food interactions may play a role in a subset of individuals who have difficulty finding a suitable thyroid hormone dosage. Our study was designed to investigate the potential role of dietary protein immune reactivity with thyroid hormones and t...
Dietary management of autoimmune diabetes includes low glycemic foods classified from the glycemic index, but it does not consider the role that immunoreactive foods may play with the immunological etiology of the disease. We measured the reactivity of either monoclonal or polyclonal affinity-purified antibodies to insulin, insulin receptor alpha,...
Common features between autism spectrum disorders (ASDs) and cancer have been discerned using methodologies from a number of disciplines, including genetics, bioinformatics and epidemiological studies. To understand such apparent overlaps between these two conditions and the mechanisms that may underlie these linkages, it is important to look at th...
The wide range of factors associated with the induction of autism is invariably linked with either inflammation or oxidative stress, and sometimes both. The use of acetaminophen in babies and young children may be much more strongly associated with autism than its use during pregnancy, perhaps because of well-known deficiencies in the metabolic bre...
Autism spectrum disorder (ASD) is associated with difficulty in processing speech in a noisy background, but the neural mechanisms that underlie this deficit have not been mapped. To address this question, we used magnetoencephalography to compare the cortical responses between ASD and typically developing (TD) individuals to a passive mismatch par...
Autism spectrum disorder (ASD) is associated with difficulty in processing speech in a noisy background, but the neural mechanisms that underlie this deficit have not been mapped. To address this question, we used magnetoencephalography to compare the cortical responses between ASD and typically developing (TD) individuals to a passive mismatch par...
https://imfar.confex.com/imfar/2016/webprogram/Paper22096.html
Objective:
To investigate the relationship between fractional anisotropy (FA), a suggested biomarker for tissue integrity, and motor recovery in stroke patients following post-acute rehabilitation.
Design:
Retrospective study.
Setting:
Acute rehabilitation hospital.
Participants:
43 subjects, 28 diagnosed with ischemic stroke, and 15 diagnos...
and ranking the relative strengths of representation of pathway network components, we 1) identified 10 disease-associated and 30 function-associated pathways 2) revealed calcium signaling pathway and neuroactive ligand-receptor interaction as themost enriched, statistically significant pathways from the enrichment analysis, 3) showed calcium signa...
Tables and overlap matrix for ASD genes that associated with the enriched KEGG pathways and GO groups.
The enrichment analyses data for KEGG and GO (BP, CC and MF) groups were shown in four separate sheets labeled as "KEGG", "BP", "CC", and "MF". Each data sheet contains two parts: the one above is a table of the enriched gene sets, and the one bel...
SFARI genes from Human Gene Module (updated December, 2014).
(XLS)
Bioregulatory systems medicine (BrSM) is a paradigm that aims to advance current medical practices. The basic scientific and clinical tenets of this approach embrace an interconnected picture of human health, supported largely by recent advances in systems biology and genomics, and focus on the implications of multi-scale interconnectivity for impr...
Functional connectivity is abnormal in autism, but the nature of these abnormalities remains elusive. Different studies, mostly using fMRI, have found increased, decreased, or even mixed pattern functional connectivity abnormalities in autism, but no unifying framework has emerged to date. We measured functional connectivity in individuals with aut...
Functional connectivity is abnormal in autism, but the nature of these abnormalities remains elusive. Different studies, mostly using functional magnetic resonance imaging, have found increased, decreased, or even mixed pattern functional connectivity abnormalities in autism, but no unifying framework has emerged to date. We measured functional con...
Autism has been viewed as a highly heritable neurobiological condition of mysterious but presumably genetic origin, which involves lifelong neurocognitive, perceptual and emotional deficits. This conceptual framing has led to a focus on searching for underlying genetic causes of differences in the autistic brain, particularly in anatomical structur...
Background
Extensive evidence indicates that cortical connectivity patterns are abnormal in autism spectrum disorders (ASD), showing both over- and under-connectivity. Since, however, studies to date focused on either spatial or spectral dimensions, but not both simultaneously, much remains unknown about the nature of these abnormalities. In partic...
Although autism spectrum conditions (ASCs) are defined behaviorally, they also involve multileveled disturbances of underlying biology that find striking parallels in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMF/RFR). Part I of this paper will review the critical contributions pathophysiology may make to...
We report the history of a child with autism and epilepsy who, after limited response to other interventions following her regression into autism, was placed on a gluten-free, casein-free diet, after which she showed marked improvement in autistic and medical symptoms. Subsequently, following pubertal onset of seizures and after failing to achieve...
Motor stereotypies are defined as patterned, repetitive, purposeless movements. These stigmatizing motor behaviors represent one manifestation of the third core criterion for an Autistic Disorder (AD) diagnosis, and are becoming viewed as potential early markers of autism. Moreover, motor stereotypies might be a tangible expression of the underlyin...
Long-range cortical functional connectivity is often reduced in autism spectrum disorders (ASD), but the nature of local cortical functional connectivity in ASD has remained elusive. We used magnetoencephalography to measure task-related local functional connectivity, as manifested by coupling between the phase of alpha oscillations and the amplitu...
Background: The autism spectrum disorders (ASDs) are a heterogeneous group of neurodevelopmental disorders that share a behavioral phenotype classically described as impairment of social communication accompanied by repetitive or stereotyped behaviors. Biological models supported by neuroimaging studies are converging on a biological phenotype shar...
Background: The hypothesis that long-range functional connectivity (FC) is reduced in ASD while local FC is increased is widely accepted. While a large body of evidence supports the hypothesis of reduced long-range FC in ASD, there is no neurophysiological evidence in support of increased local FC in ASD. The nature of local neurophysiological inte...
Variants of SHANK3, a gene encoding a structural component of the postsynaptic density, have been associated with autism. Mice engineered to carry mutant genes showed autism-like behavioral features that included repetitive grooming and disinclination to socialize.
Volumetric magnetic resonance imaging (MRI) brain data provide a valuable tool for detecting structural differences associated with various neurological and psychiatric disorders. Analysis of such data, however, is not always straightforward, and complications can arise when trying to determine which brain structures are "smaller" or "larger" in li...
Background: The autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders that share specific a behavioral phenotype classically described as impairment of social reciprocity and communication, accompanied by repetitive behaviors. Biological models supported by neuroimaging studies are converging on a biological phen...
This chapter outlines how genetic and environmental factors may converge on common mechanisms pertinent to neurodevelopmental disorders, and the ways that high heritability can involve not only high genetic but also high environmental contributions. The chapter is organized as follows. Part One discusses the mechanisms by which genome and environme...
Autism is an emerging area of basic and clinical research, and has only recently been recognized as a major topic in biomedical research, and is now an intense growth area in behavioral and educational treatments. This resource provides a comprehensive summary of all current knowledge related to the behavioral, experiential, and biomedical features...
An analysis of EEG synchrony between homologous early visual areas tested the hypothesis that interhemispheric functional connectivity during visual stimulation is reduced in children with autism compared to controls.
EEG power and coherence within and between two homologous regions of the occipital cortex were measured during long latency flash vi...
Background: Children with autism have long been recognized to have atypical sensory perception with hypersensitivity to many external stimuli. They have also been shown to have decreased functional connectivity, which has been hypothesized to underlie the predominant perceptual-cognitive style termed weak central coherence. We previously showed tha...
Background: Brain morphometry in autism spectrum disorders (ASD) has yielded heterogeneous findings. Diverse clinical features of autism may theoretically be associated with a range of brain regions. Abnormalities in amygdala are thought to be correlated with emotion and particularly with fear, while abnormalities in caudate are thought to be assoc...
Background: The contribution of white matter to volumetric differences between brains of individuals with autism and with typical development has largely been based on data from high functioning individuals. We previously reported a disproportionate contribution of white matter, and in particular of superficial (radiate) white matter, to volume inc...
Background: A significant body of evidence has accumulated in support of the cortical hypo-connectivity hypothesis of autism; the hypothesis states that individuals with autism spectrum disorders (ASD) have weaker than normal long-range cortical functional connectivity that may contribute to their cognitive abnormalities. Our own studies show that...
This review presents a rationale and evidence for contributions of environmental influences and environmentally vulnerable physiology to autism spectrum disorders (ASDs).
Recent studies suggest a substantial increase in ASD prevalence above earlier Centers for Disease Control figures of one in 150, only partly explicable by data artifacts, undersco...
BACKGROUND: Twenty years of research on early intensive treatment using applied behavior analysis (ABA) for children with autism has consistently produced robust effects. There appears to be a subset of children whose response to intensive ABA treatments includes achieving a level of functioning personal use only that is indistinguishable from typi...
Twenty years of research on early intensive treatment using applied behavior analysis (ABA) for children with autism has consistently produced robust effects. There appears to be a subset of children whose response to intensive ABA treatments includes achieving a level of functioning that is indistinguishable from typically developing peers. The pu...
In this article we address analytic challenges inherent in brain volumetrics (i.e., the study of volumes of brains and brain regions). It has sometimes been assumed in the literature that deviations in regional brain size in clinical samples are directly related to maldevelopment or pathogenesis. However, this assumption may be incorrect; such volu...
Background: The tissue nature of brain enlargement in young autistic subjects has not yet been clearly established. Published findings do not support an increase in neuronal density in gray matter or the attribution of white matter enlargement to an increase in myelinated fibers. Given the growing documentation of metabolic findings in autism, thes...
Background: A significant body of evidence has accumulated in support of the cortical hypo-connectivity hypothesis of autism; the hypothesis states that individuals with autism spectrum disorders (ASD) have weaker than normal long-range cortical functional connectivity that may contribute to their cognitive abnormalities. Our own studies show that...
Background: Given the frequent replication in ASD research of the findings of large brains, increased white matter and of atypical connectivity, it is important to investigate the nature and distribution of the tissue changes that may be contributing to these observed abnormalities.
Objectives: Our goal is to investigate white matter structural int...
Background: Growing documentation of metabolic alterations in autism increases the need to characterize metabolism in brain tissue. Magnetic Resonance Spectroscopy (MRS) is constrained by the impossibility of performing whole brain acquisitions and the need to place localized voxels, as well as the impact of acquisition protocols on findings. Liter...
Background: Autistics show a diminished ability to integrate complex information but enhanced perceptual processing abilities for a variety of simple sensory stimuli. fcMRI scans have shown diminished long distance functional connectivity between visual and frontal cortices in autistics but increased functional connectivity in thalamocortical circu...
Although Autism Spectrum Disorders (ASD) are generally assumed to be lifelong, we review evidence that between 3% and 25% of children reportedly lose their ASD diagnosis and enter the normal range of cognitive, adaptive and social skills. Predictors of recovery include relatively high intelligence, receptive language, verbal and motor imitation, an...
The purpose of this chapter is to reflect upon the implications of the identification of active pathophysiological processes in autism spectrum disorders (ASD), and to reflect back upon prior findings and formulations in the light of these recent discoveries. This chapter articulates challenges posed by these discoveries to deeply held assumptions...
Background: Recently, a significant body of evidence has accumulated in support of the cortical hypo-connectivity hypothesis of autism; the hypothesis states that individuals with autism have weaker than normal long range cortical functional connectivity, which may contribute to the cognitive abnormalities underlying autism. The majority of the stu...
Background: While autism spectrum disorders likely arise from gene-environment interactions, environmental risk factors are greatly underrepresented in ASD literature, with the possible exception of articles on thimerosal and vaccines.
Objectives: To quantify the share of autism research literature devoted to various types of chemical substances,...
Background: Autistics show a diminished ability to integrate complex information. This may relate to altered functional connectivity. EEG coherence measures electrocortical synchrony of oscillatory brain rhythms across neural networks, which is hypothesized as a mechanism for functional connectivity, binding of neural activity and integration of co...
Background: Although the autism research literature has grown dramatically in recent years, research on related disorders may suggest topics not yet pursued in pervasive developmental disorder (PDD) research.
Objectives: We sought an objective, quantitative, comprehensive method to compare the topics studied in PDD, related disorders, and biomedici...
We review evidence to support a model where the disease process underlying autism may begin when an in utero or early postnatal environmental, infectious, seizure, or autoimmune insult triggers an immune response that increases reactive oxygen species (ROS) production in the brain that leads to DNA damage (nuclear and mitochondrial) and metabolic e...
Data sharing in autism neuroimaging presents scientific, technical, and social obstacles. We outline the desiderata for a data-sharing scheme that combines imaging with other measures of phenotype and with genetics, defines requirements for comparability of derived data and recommendations for raw data, outlines a core protocol including multispect...
In this review, we contrast previous models of autism pathogenesis with newer models inspired by some recently appreciated
and previously minimally considered pathological and clinical features of the disease. Autism has conventionally been viewed
as an incurable behavioral disorder resulting solely from genetic defects impacting brain development....
Basal ganglia (BG) enlargement has been found in studies of adults with bipolar disorder (BPD), while the few studies of BPD youths have had mixed findings. The BG (caudate, putamen, globus pallidus, nucleus accumbens) is interconnected with limbic and prefrontal cortical structures and therefore may be implicated in BPD.
Sixty-eight youths (46 wit...
Although autism is a neurobehavioral syndrome defined exclusively by behavioral criteria, abnormalities are identified at many other levels in individuals and cohorts who meet these criteria, including genetics, neurochemistry and metabolism, immunology, neuroanatomy, and electrophysiology, and in multiple domains including sensory-motor and social...
It has been speculated that autism and specific language impairment share common underlying neural substrates because of the overlap in language impairment issues and evidence suggesting parallels in other domains and implying a possible shared genetic risk. Anatomically the two sets of disorders have generally been studied using different methodol...
Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,181 [corrected] families with at least two affected...
Autism is defined behaviorally, as a syndrome of abnormalities involving language, social reciprocity and hyperfocus or reduced behavioral flexibility. It is clearly heterogeneous, and it can be accompanied by unusual talents as well as by impairments, but its underlying biological and genetic basis is unknown. Autism has been modeled as a brain-ba...
Autism spectrum disorders (ASD) are defined by behavior and diagnosed by clinical history and observation but have no biomarkers and are presumably, etiologically and biologically heterogeneous. Given brain abnormalities and high monozygotic concordance, ASDs have been framed as neurobiologically based and highly genetic, which has shaped the resea...
Autism research priorities have been shaped by underlying models. The model of autism as a genetically determined hard-wired brain disorder, dominant in recent years, has led to a search for "brain genes" and brain alterations. But this model has produced limited results, has rested on an over-interpretation of evidence for heritability, and has al...
Few magnetic resonance imaging (MRI) studies of bipolar disorder (BPD) have investigated the entire cerebral cortex. Cortical gray matter (GM) volume deficits have been reported in some studies of adults with BPD; this study assessed the presence o