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Biomedical subjects

E Courchesne

Publications and source records attributed to E Courchesne.

At least 55 records · Page 3Linked to original sources
PubMed1997

Brainstem, cerebellar and limbic neuroanatomical abnormalities in autism.

Recent autopsy and/or quantitative magnetic resonance imaging studies of autistic patients have identified agenesis of the superior olive, dysgenesis of the facial nucleus, reduced numbers of Purkinje neurons, hypoplasia of the brainstem and posterior cerebellum, and increased neuron-packing density of the medial, cortical and central nuclei of the amygdala and the medial septum. As neurogenesis occurs for these different neuron types during approximately the fifth week of gestation, the possibility is raised that this may be a 'window of vulnerability' for autism; the likely etiologic heterogeneity of autism suggests that other windows of vulnerability are also possible.

Autistic Disorder↗
PubMed1997

From impasse to insight in autism research: from behavioral symptoms to biological explanations.

The incomplete interface between remediation-oriented research and basic science research has hampered progress toward gaining insight into the etiologies of autism, despite the availability of abundant research data. Investigators of these two research domains differ in their background training and primary goals, which necessarily affect their missions, perspectives, research questions posed, methodologies selected, and interpretation of data from the research. Miscommunication between the two types of researchers has brought about disagreement on nearly every aspect of the research process. We discuss both sides of the impasse: a traditional clinical practice perspective based on the requirement for finding immediate answers to the remediation question and the basic science perspective with the goal of delineating the sequence of biological changes from the initial cause(s) of abnormal development to behavioral outcome. Although remediation-oriented research aims at alleviation of symptoms for today's patients, we propose that a basic science perspective seeks insight into the triggering causes and pathogenesis of the disorder from which better diagnosis and remediation may be devised for patients in the future. We suggest that research in autism can progress beyond the impasse of disagreement and competition toward information integration and insight by means of dialogue, data exchange, discussion, collaboration, and cooperation.

Adolescent↗
PubMed1997

Evidence of linkage between the serotonin transporter and autistic disorder.

The serotonin transporter gene (HTT) is a primary candidate in autistic disorder based on efficacy of potent serotonin transporter inhibitors in reducing rituals and routines. We initiated a candidate gene study of HTT in trios consisting of probands with autistic disorder and both parents. Preliminary transmission/disequilibrium test (TDT) analysis with 86 families revealed no evidence for linkage or linkage disequilibrium between autistic disorder and a polymorphism in the second intron of HTT. However, preferential transmission of a short variant of the HTT promoter was found in the same 86 trios (TDT chi 2 = 4.69, 1 d.f., P = 0.030). In further analyses, we considered haplotypes of the HTT promoter variant and second intron locus as alleles in a multiallelic TDT. Results confirmed the significance of the effect of this region (TDT chi 2 = 11.85, 4 d.f., P = 0.018). This provides preliminary evidence of linkage and association between HTT and autistic disorder.

Adolescent↗
PubMed1997

Autism or atypical autism in maternally but not paternally derived proximal 15q duplication.

Duplications of proximal 15q have been found in individuals with autistic disorder (AD) and varying degrees of mental retardation. Often these abnormalities take the form of a supernumerary inverted duplicated chromosome 15, more properly described as an isodicentric chromosome 15, or idic(15). However, intrachromosomal duplications also have been reported. In a few cases, unaffected mothers, as well as their affected children, carry the same duplications. During the course of the genotyping of trios of affected probands with AD and their parents, at the positional candidate locus D15S122, an intrachromosomal duplication of proximal 15q was detected by microsatellite analysis in a phenotypically normal mother. Microsatellite and methylation analyses of the pedigree in the following report show that, among three children, the two with autism or atypical autism have maternal inheritance of a 15q11-q13 duplication whereas the third child, who is unaffected, did not inherit this duplication. Their mother's 15q11-q13 duplication arose de novo from her father's chromosomes 15. This finding documents, for the first time, the significance of parental origin for duplications of 15q11-q13. In this family, paternal inheritance leads to a normal phenotype, and maternal inheritance leads to autism or atypical autism.

Aneuploidy↗
PubMed1996

Visual attention abnormalities in autism: delayed orienting to location.

These studies provide evidence for slowed spatial orienting of attention in autism. A group of well-defined adult autistic subjects and age-matched normal controls performed a traditional spatial cueing task in which attention-related response facilitation is indexed by speed of target detection. To address the concern that motor impairment may interfere with interpretation of response time measures in those with neurologic abnormality, we also used a new adaptation of the traditional task that depended on accuracy of response (target discrimination) rather than speed of response. This design allowed separation of time to process and respond to target information from the time to move and engage (orient) attention. Results from both tasks were strikingly similar. Normal subjects oriented attention very quickly, and showed maximal performance facilitation at a cued location within 100 ms. Autistic subjects oriented attention much more slowly and showed increasing benefits of a spatial cue with increasing cue-to-target delays. These results are consistent with previous reports that patients with autism, the majority of whom have developmental abnormalities of the cerebellum, as well as those with acquired damage to the cerebellum, are slow to shift attention between and within modalities. This paper also addresses the variability in behavioral findings in autism, and suggests that many of the apparently contradictory findings may actually reflect sampling differences in patterns of brain pathology.

Adolescent↗
PubMed1996

Neurologic abnormalities in infantile autism.

Neuroanatomic, pathologic, and neurobehavioral studies point to a cerebellar and parietal abnormality in autism. We used a standardized protocol to examine neurologic function in 28 pediatric autistic subjects and 24 pediatric normal healthy volunteer controls. As a group, the autistic subjects had quantitative measures from magnetic resonance imaging suggesting hypoplasia or hyperplasia of the cerebellar vermis, as well as measurements of posterior corpus callosum suggesting abnormalities of posterior cortex. In groups of tests that reflect cerebellar and parietal function, the neurologic abnormalities detectable by clinical examination were significantly greater for autistic subjects than for normal controls. These studies confirm that the structural and behavioral deficit in autism does lead to abnormalities that can be detected on the clinical neurologic examination.

Adolescent↗
PubMed1995

NMR intensity of corpus callosum differs with age but not with diagnosis of autism.

NMR signal intensities in five regions of the midsagittal corpus callosum were measured in autism patients and normal controls. An age-related increase in signal was observed in the anterior regions in both groups. No significant differences in intensity were detected between the groups. The finding of normal myelination supports the attribution of callosal narrowing to absence of axons rather than absence of myelin.

Age Distribution↗
PubMed1995

Reduced size of corpus callosum in autism.

OBJECTIVE: To determine via magnetic resonance imaging if the posterior corpus callosum is reduced in the midline cross-sectional area in autistic patients, consistent with previous reports of parietal lobe abnormalities. DESIGN: Case-control study. SETTING: Tertiary care facility. PATIENTS AND OTHER PARTICIPANTS: Fifty-one autistic patients (45 males and six females; age range, 3 to 42 years), including both mentally retarded and nonretarded patients who met several diagnostic criteria for autism were prospectively selected. Fifty-one age-and sex-matched volunteer normal control subjects were also included. INTERVENTION: None. MAIN OUTCOME MEASURES: Computer-aided measurement of cross-sectional area, areas of five subregions, and thickness profile. RESULTS: Overall size reduction, concentrated in posterior subregions. CONCLUSIONS: Evidence is found of a reduced size of the corpus callosum in autistic patients. This reduction is localized to posterior regions, where parietal lobe fibers are known to project. This finding further supports the idea that parietal lobe involvement may be a consistent feature in autism.

Adolescent↗
PubMed1995

Sensory modulation of auditory stimuli in children with autism and receptive developmental language disorder: event-related brain potential evidence.

Three groups of age- and PIQ-matched children (Autism, Receptive Developmental Language Disorder, and normal controls) participated in two event-related brain potential (ERP) experiments. Each of these experiments was aimed at evaluating whether either of the two clinical groups of children demonstrated abnormalities in two auditory ERP components, N1 and P2, which are known to be dependent on stimulus characteristics (frequency, intensity, and probability), and believed to be generated within primary and secondary cortex. Results of Experiment 1 provide partial support for the idea that both clinical groups failed to fully process changes in stimulus intensity as indexed by the N1 component. Results are discussed in reference to potential abnormalities in serotonergic regulation of auditory cortex.

Adolescent↗
PubMed1995

Cross-sectional area of the posterior hippocampus in autistic patients with cerebellar and corpus callosum abnormalities.

Using MRI methods previously shown to optimize visualization of cytoarchitectonic details in the body of the hippocampal formation caudal to the pes hippocampi, we imaged and quantified the hippocampus proper including the subiculum and the dentate gyrus in 33 autistic patients between the ages of 6 and 42 years and in 23 age-matched normal healthy volunteers. Measures of these structures in autistic patients and normal healthy volunteers differed nonsignificantly, by less than 1.4%, regardless of whether or not the autistic patients were retarded or had a history of seizure episodes. By contrast, measures of vermian lobules VI and VII and the posterior portion of the corpus callosum in these same autistic and normal volunteers differed significantly, by more than 9.9%. The lack of a significant difference in the cross-sectional size of the posterior hippocampal formation between autistic and normal 6- to 42-year-olds is discrepant with predictions based on some, but not all, autopsy studies. This suggests that there is a need for additional quantitative autopsy study of the hippocampal formation and quantitative MRI study of rostral hippocampal regions that we did not explore in the present report. Also, quantitative autopsy and MRI studies have yet to examine hippocampal development in autistic patients younger than 6 years of age; whether early stages of growth are normal or not is unknown.

Adolescent↗
PubMed1994

Impairment in shifting attention in autistic and cerebellar patients.

MRI and autopsy evidence of early maldevelopment of cerebellar vermis and hemispheres in autism raise the question of how cerebellar maldevelopment contributes to the cognitive and social deficits characteristic of autism. Compared with normal controls, autistic patients and patients with acquired cerebellar lesions were similarly impaired in a task requiring rapid and accurate shifts of attention between auditory and visual stimuli. Neurophysiologic and behavioral evidence rules out motor dysfunction as the cause of this deficit. These findings are consistent with the proposal that in autism cerebellar maldevelopment may contribute to an inability to execute rapid attention shifts, which in turn undermines social and cognitive development, and also with the proposal that the human cerebellum is involved in the coordination of rapid attention shifts in a fashion analogous to its role in the coordination of movement.

Adolescent↗
PubMed1994

The brain in infantile autism: posterior fossa structures are abnormal.

Infantile autism is a neurologic disorder of social, cognitive, and language development. Earlier MRI studies found hypoplasia of posterior vermal lobules VI and VII and cerebellar hemispheres in the majority of autistic patients, and recent autopsy analyses find severe Purkinje neuron loss in the posterior vermis (lobules VI and VII and VIII to X) and hemispheres. A second type of cerebellar pathology in infantile autism was recently found: hyperplasia (excessive enlargement) of posterior vermal lobules VI and VII. If the autistic samples in some MRI studies that did not detect cerebellar hypoplasia were actually composed of both the hypoplasia and hyperplasia subtypes, then the autistic mean size reported in such studies would have appeared to be near the normal mean size only because it would be the sum of the two opposite subtypes. To test this possibility, we statistically reanalyzed previously published vermal area measures of 78 autistic patients from four separate studies. The results revealed that the autistic patient samples from these four studies were indeed composed of both the hypoplasia subtype (87%, 92%, 89%, and 84% of patients) and the hyperplasia subtype (13%, 8%, 11%, and 16% of patients). Cerebellar abnormalities have been found in 15 autopsy and quantitative MRI reports from nine laboratories involving a total of 226 autistic cases. Autism may be one of the first developmental neuropsychiatric disorders for which substantial concordance exists among several independent microscopic and macroscopic studies as to the location and type of neuroanatomic maldevelopment. Onset might be as early as the second trimester. Discovery of the etiologies underlying cerebellar maldevelopment may be the key to uncovering some of the causes of infantile autism.

Adolescent↗
PubMed1994

Abnormality of cerebellar vermian lobules VI and VII in patients with infantile autism: identification of hypoplastic and hyperplastic subgroups with MR imaging.

OBJECTIVE: Infantile autism is a neurobehavioral disorder that is widely believed to have etiologically distinct subtypes, including subtypes with a genetic basis, but no neuroanatomic evidence firmly supports this belief. To date, only one type of cerebellar abnormality has been identified in patients with autism: hypoplasia of the vermis and hemispheres. By using a large sample of autistic patients and healthy volunteers along with precise MR imaging and quantitative procedures, we sought to replicate previous reports of cerebellar vermian hypoplasia in autism and to identify additional subtypes of cerebellar abnormality. MATERIALS AND METHODS: Using MR technology, we imaged and measured posterior and anterior vermian regions in 50 autistic patients (2-40 years old) and 53 healthy control subjects (3-37 years old). The autistic patients had social, language, cognitive, behavioral, and medical history characteristics that were typical of the general autistic population. By using precise procedures for positioning and aligning MR slices, we obtained comparable MR images within and across subject groups. RESULTS: Statistical analyses showed two subgroups of autistic patients, one (86% of the patients) with findings consistent with vermian hypoplasia and another (12% of the patients) with evidence of vermian hyperplasia. The hypoplasia subgroup included 43 patients whose mean midsagittal area for vermian lobules VI and VII was 237 +/- 38 mm2, and the hyperplasia subgroup included six patients whose mean area was 377 +/- 12 mm2. Thus, the area of lobules VI and VII in the hypoplasia subgroup was 16% smaller than the mean area in the control subjects (282 +/- 42 mm2) (p < .0001), whereas that in the hyperplasia subgroup was 34% larger (p < .0001). Analyses showed that these two subtypes of vermian abnormalities were present across all ages of autistic patients studied. CONCLUSION: Two different subtypes of autistic patients can be identified on the basis of the presence of vermian hypoplasia or hyperplasia as seen on MR images. Possible origins for vermian hypoplasia include environmental trauma and genetic factors.

Adolescent↗
PubMed1993

Contextual probability evaluation in autistic, receptive developmental language disorder, and control children: event-related brain potential evidence.

Compared 8- to 14-year-old children with either autism or receptive developmental language disorder (RDLD) to age- and IQ-matched normal controls in their ability to detect both frequent (p = .70) and infrequent (p = .30) randomly presented auditory stimuli under task and no-task conditions. Event-related brain potentials (ERPs), behavioral reaction times, and target detection accuracy rates were measured. Although the three groups of children performed in a similar manner on behavioral measures, only the children with autism demonstrated an abnormally small amplitude of the P3b, a component of the ERP. This result is interpreted in terms of (a) the consistency of this finding with other ERP studies involving older individuals with autism; and (b) its significance with respect to the difficulty children with autism have in modifying their expectancies to contextually relevant sequences of auditory information.

Acoustic Stimulation↗