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Biomedical subjects

E Courchesne

Publications and source records attributed to E Courchesne.

At least 19 recordsLinked to original sources
PubMed2006

Reduced minicolumns in the frontal cortex of patients with autism.

Cell minicolumns were shown to be narrower in frontal regions in brains of autistic patients compared with controls. This was not found in primary visual cortex. Within the frontal cortex, dorsal and orbital regions displayed the greatest differences while the mesial region showed the least change. We also found that minicolumns in the brain of a 3-year-old autistic child were indistinguishable from those of the autistic adult in two of three frontal regions, in contrast to the control brains. This may have been due to the small size of the columns in the adult autistic brain rather than to an accelerated development. The presence of narrower minicolumns supports the theory that there is an abnormal increase in the number of ontogenetic column units produced in some regions of the autistic brain during corticoneurogenesis.

Adult↗
PubMed2004

Autism as a disorder of neural information processing: directions for research and targets for therapy.

The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which they feed, is hampered by the large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging, and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself.

Animals↗
PubMed2002

Dynamic brain sources of visual evoked responses.

It has been long debated whether averaged electrical responses recorded from the scalp result from stimulus-evoked brain events or stimulus-induced changes in ongoing brain dynamics. In a human visual selective attention task, we show that nontarget event-related potentials were mainly generated by partial stimulus-induced phase resetting of multiple electroencephalographic processes. Independent component analysis applied to the single-trial data identified at least eight classes of contributing components, including those producing central and lateral posterior alpha, left and right mu, and frontal midline theta rhythms. Scalp topographies of these components were consistent with their generation in compact cortical domains.

Adult↗
PubMed2002

Transmission disequilibrium mapping at the serotonin transporter gene (SLC6A4) region in autistic disorder.

The serotonin transporter gene (SLC6A4, MIM 182138) is a candidate gene in autistic disorder based on neurochemical, neuroendocrine studies and the efficacy of potent serotonin transporter inhibitors in reducing ritualistic behaviors and related aggression. An insertion/deletion polymorphism (5-HTTLPR) in the promoter region and a variable number of tandem repeat polymorphism (VNTR) in the second intron, were previously identified and suggested to modulate transcription. Six previous family-based association studies of SLC6A4 in autistic disorder have been conducted, with four studies showing nominally significant transmission disequilibrium and two studies with no evidence of nominally significant transmission disequilibrium. In the present study, TDT was conducted in 81 new trios. A previous finding of transmission disequilibrium between a haplotype consisting of the 5-HTTLPR and intron 2 VNTR was replicated in this study, but not preferential transmission of 5-HTTLPR as an independent marker. Because of inconsistent transmission of 5-HTTLPR across studies, SLC6A4 and its flanking regions were sequenced in 10 probands, followed by typing of 20 single nucleotide polymorphisms (SNPs) and seven simple sequence repeat (SSR) polymorphisms in 115 autism trios. When individual markers were analyzed by TDT, seven SNP markers and four SSR markers (six SNPs, 5-HTTLPR and the second intron VNTR from promoter 1A through intron 2 of SLC6A4, one SSR from intron 7 of SLC6A4, one SNP from the bleomycin hydrolase gene (BLMH, MIM 602403) and one SSR telomeric to BLMH) showed nominally significant evidence of transmission disequilibrium. Four markers showed stronger evidence of transmission disequilibrium (TDT(max) P = 0.0005) than 5-HTTLPR.

Autistic Disorder↗
PubMed2002

Transmission disequilibrium testing of arginine vasopressin receptor 1A (AVPR1A) polymorphisms in autism.

Impairment in social reciprocity is a central component of autism. In preclinical studies, arginine vasopressin (AVP) has been shown to increase a range of social behaviors, including affiliation and attachment, via the V(1a) receptor (AVPR1A) in the brain. Both the behavioral effects of AVP and the neural distribution of the V1a receptor vary greatly across mammalian species. This difference in regional receptor expression as well as differences in social behavior may result from a highly variable repetitive sequence in the 5' flanking region of the V1a gene (AVPR1A). Given this comparative evidence for a role in inter-species variation in social behavior, we explored whether within our own species, variation in the human AVPR1A may contribute to individual variations in social behavior, with autism representing an extreme form of social impairment. We genotyped two microsatellite polymorphisms from the 5' flanking region of AVPR1A for 115 autism trios and found nominally significant transmission disequilibrium between autism and one of the microsatellite markers by Multiallelic Transmission/Disequilibrium test (MTDT) that was not significant after Bonferroni correction. We also screened approximately 2 kb of the 5' flanking region and the coding region and identified 10 single nucleotide polymorphisms.

Autistic Disorder↗
PubMed2002

Relationship between head circumference and brain volume in healthy normal toddlers, children, and adults.

OBJECTIVE: To quantify the relationship between brain volume and head circumference from early childhood to adulthood, and quantify how this relationship changes with age. METHODS: Whole-brain volume and head circumference measures were obtained from MR images of 76 healthy normal males aged 1.7 to 42 years. RESULTS: Across early childhood, brain volume and head circumference both increase, but from adolescence onward brain volume decreases while head circumference does not. Because of such changing relationships between brain volume and head circumference with age, a given head circumference was associated with a wide range of brain volumes. However, when grouped appropriately by age, head circumference was shown to accurately predict brain volume. Head circumference was an excellent prediction of brain volume in 1.7 to 6 years old children (r = 0.93), but only an adequate predictor in 7 to 42 year olds. CONCLUSIONS: To use head circumference as an accurate indication of abnormal brain volume in the clinic or research setting, the patient's age must be taken into account. With knowledge of age-dependent head circumference-to-brain volume relationship, head circumference (particularly in young children) can be an accurate, rapid, and inexpensive indication of normalcy of brain size and growth in a clinical setting.

Adolescent↗
PubMed2001

Unusual brain growth patterns in early life in patients with autistic disorder: an MRI study.

OBJECTIVE: To quantify developmental abnormalities in cerebral and cerebellar volume in autism. METHODS: The authors studied 60 autistic and 52 normal boys (age, 2 to 16 years) using MRI. Thirty autistic boys were diagnosed and scanned when 5 years or older. The other 30 were scanned when 2 through 4 years of age and then diagnosed with autism at least 2.5 years later, at an age when the diagnosis of autism is more reliable. RESULTS: Neonatal head circumferences from clinical records were available for 14 of 15 autistic 2- to 5-year-olds and, on average, were normal (35.1 +/- 1.3 cm versus clinical norms: 34.6 +/- 1.6 cm), indicative of normal overall brain volume at birth; one measure was above the 95th percentile. By ages 2 to 4 years, 90% of autistic boys had a brain volume larger than normal average, and 37% met criteria for developmental macrencephaly. Autistic 2- to 3-year-olds had more cerebral (18%) and cerebellar (39%) white matter, and more cerebral cortical gray matter (12%) than normal, whereas older autistic children and adolescents did not have such enlarged gray and white matter volumes. In the cerebellum, autistic boys had less gray matter, smaller ratio of gray to white matter, and smaller vermis lobules VI-VII than normal controls. CONCLUSIONS: Abnormal regulation of brain growth in autism results in early overgrowth followed by abnormally slowed growth. Hyperplasia was present in cerebral gray matter and cerebral and cerebellar white matter in early life in patients with autism.

Adolescent↗
PubMed2001

Atypical patterns of cerebral motor activation in autism: a functional magnetic resonance study.

BACKGROUND: Early neurodevelopmental pathogenesis in autism potentially affects emerging functional maps, but little imaging evidence is available. METHODS: We studied eight male autistic and eight matched normal subjects, using functional magnetic resonance imaging during visually paced finger movement, compared to a control condition (visual stimulation in the absence of motor response). RESULTS: Groupwise analyses showed activation in contralateral perirolandic cortex, basal ganglia, and thalamus, bilateral supplementary motor area, and ipsilateral cerebellum for both groups. However, activations were less pronounced in the autism group. Direct group comparisons demonstrated greater activation in perirolandic and supplementary motor areas in the control group and greater activation (or reduced deactivation) in posterior and prefrontal cortices in the autism group. Intraindividual analyses further showed that strongest activations were consistently located along the contralateral central sulcus in control subjects but occurred in locations differing from individual to individual in the autism group. CONCLUSIONS: Our findings, though based on a rather small sample, suggest abnormal individual variability of functional maps and less distinct regional activation/deactivation patterns in autism. The observations may relate to known motor impairments in autism and are compatible with the general hypothesis of disturbances of functional differentiation in the autistic cerebrum.

Adolescent↗
PubMed2001

Evidence for a cerebellar role in reduced exploration and stereotyped behavior in autism.

BACKGROUND: Although limited environmental exploration in autism is an obvious behavioral feature and may be a manifestation of "restricted interests" as described in DSM-IV criteria, there have been no behavioral or neurobiological studies of this important aspect of the disorder. Given consistent reports of cerebellar abnormality in autism, combined with animal research showing a relationship between exploration and the cerebellum, this study aimed to test the possible link between cerebellar abnormality and exploration in autism. METHODS: The relationship between visuospatial exploration, stereotyped motor movements, and magnetic resonance imaging measures of the cerebellar vermis, whole brain volume, and frontal lobes in 14 autistic and 14 normal children was investigated. Children were exposed to a large room with several exploration containers and instructed to play. Exploration behavior was videotaped and scored for percentage of time engaged in exploration, number of containers explored, as well as stereotyped movements. RESULTS: Children with autism spent significantly less time in active exploration and explored fewer containers overall than normal children. Measures of decreased exploration were significantly correlated with the magnitude of cerebellar hypoplasia of vermal lobules VI-VII in the autistic children, but no relationship to vermis size was found with normal control children. Further, measures of rates of stereotyped behavior were significantly negatively correlated with area measures of cerebellar vermis lobules VI-VII and positively correlated with frontal lobe volume in the autism sample. CONCLUSIONS: Reduced environmental exploration and repetitive behavior may have particularly important developmental consequences for children with autism because it may lead them to miss learning opportunities that fall outside their scope of interest. Our findings represent the first documented link between the restricted range of interests and stereotyped behaviors pathognomonic of autism and particular neuroanatomic sites.

Autistic Disorder↗
PubMed2001

Attention function and dysfunction in autism.

Impairments of attention are among the most consistently reported cognitive deficits in autism, and they continue to be a key focus of research. This is in no doubt due to the importance of normal attention function to the development of many so-called "higher level" cognitive operations, and to the likely involvement of attention dysfunction in certain clinical features of autism. Autistic individuals display a wide range of attentional abilities and deficits across the many domains of attention function, including selective, sustained, spatial, and shifting attention operations. This unique pattern of attention function and dysfunction has profound implications for the development and treatment of autistic children. The present review will explore this pattern of attentional strengths and weaknesses and the neural defects that underlie them.

Attention↗
PubMed2001

Analysis and visualization of single-trial event-related potentials.

In this study, a linear decomposition technique, independent component analysis (ICA), is applied to single-trial multichannel EEG data from event-related potential (ERP) experiments. Spatial filters derived by ICA blindly separate the input data into a sum of temporally independent and spatially fixed components arising from distinct or overlapping brain or extra-brain sources. Both the data and their decomposition are displayed using a new visualization tool, the "ERP image," that can clearly characterize single-trial variations in the amplitudes and latencies of evoked responses, particularly when sorted by a relevant behavioral or physiological variable. These tools were used to analyze data from a visual selective attention experiment on 28 control subjects plus 22 neurological patients whose EEG records were heavily contaminated with blink and other eye-movement artifacts. Results show that ICA can separate artifactual, stimulus-locked, response-locked, and non-event-related background EEG activities into separate components, a taxonomy not obtained from conventional signal averaging approaches. This method allows: (1) removal of pervasive artifacts of all types from single-trial EEG records, (2) identification and segregation of stimulus- and response-locked EEG components, (3) examination of differences in single-trial responses, and (4) separation of temporally distinct but spatially overlapping EEG oscillatory activities with distinct relationships to task events. The proposed methods also allow the interaction between ERPs and the ongoing EEG to be investigated directly. We studied the between-subject component stability of ICA decomposition of single-trial EEG epochs by clustering components with similar scalp maps and activation power spectra. Components accounting for blinks, eye movements, temporal muscle activity, event-related potentials, and event-modulated alpha activities were largely replicated across subjects. Applying ICA and ERP image visualization to the analysis of sets of single trials from event-related EEG (or MEG) experiments can increase the information available from ERP (or ERF) data.

Alpha Rhythm↗
PubMed2001

Broca's area and the discrimination of frequency transitions: a functional MRI study.

The left inferior frontal lobe has been traditionally viewed as a "language area," although its involvement in the discrimination of rapid nonverbal frequency changes has been also shown. Using functional MRI, we studied seven healthy adults during discrimination of relatively slow (200 ms) tonal frequency glides. Compared to a control task, in which subjects indiscriminately responded to white noise bursts, tonal discrimination was associated with bilateral superior and middle temporal and medial frontal activations. Inferior frontal activations were bilateral, but stronger on the left. Contrary to previous studies comparing discrimination of slow frequency changes to rest, our results suggest that such discriminations-when compared to an auditory control task-activate the left inferior frontal gyrus. Our findings are consistent with a participation of Broca's area in nonlinguistic processes besides its known roles in semantic, syntactic, and phonological functions.

Adult↗
PubMed2001

Event-related brain response abnormalities in autism: evidence for impaired cerebello-frontal spatial attention networks.

Although under some conditions the attention-related late positive event-related potential (ERP) response (LPC) is apparently normal in autism during visual processing, the LPC elicited by visuospatial processing may be compromised. Results from this study provide evidence for abnormalities in autism in two components of the LPC generated during spatial processing. The early frontal distribution of the LPC which may reflect attention orienting was delayed or missing in autistic subjects during conditions in which attention was to peripheral visual fields. The later parietal distribution of the LPC which may be associated with context updating was smaller in amplitude in autistic subjects regardless of attention location. Both abnormalities suggest disruption of function in spatial attention networks in autism. Evidence that the cerebellar abnormalities in autism may underlie these deficits comes from: (1) similar results in ERP responses and spatial attention deficits in patients with cerebellar lesions; (2) brain-behavior correlations in normally functioning individuals associating the size of the posterior cerebellar vermis and the latency of the frontal LPC; and (3) a previously reported complementary correlation between the size of the posterior vermal lobules and spatial orienting speed. Although the scalp-recorded LPC is thought to be cortically generated, it may be modulated by subcortical neural activity. The cerebellum may serve as a modulating influence by affecting the task-related antecedent attentional process. The electrophysiological abnormalities reported here index spatial attention deficits in autism that may reflect cerebellar influence on both frontal and parietal spatial attention function.

Adolescent↗
PubMed2001

Face processing occurs outside the fusiform 'face area' in autism: evidence from functional MRI.

Processing the human face is at the focal point of most social interactions, yet this simple perceptual task is difficult for individuals with autism, a population that spends limited amounts of time engaged in face-to-face eye contact or social interactions in general. Thus, the study of face processing in autism is not only important because it may be integral to understanding the social deficits of this disorder, but also, because it provides a unique opportunity to study experiential factors related to the functional specialization of normal face processing. In short, autism may be one of the only disorders where affected individuals spend reduced amounts of time engaged in face processing from birth. Using functional MRI, haemodynamic responses during a face perception task were compared between adults with autism and normal control subjects. Four regions of interest (ROIs), the fusiform gyrus (FG), inferior temporal gyrus, middle temporal gyrus and amygdala were manually traced on non-spatially normalized images and the percentage ROI active was calculated for each subject. Analyses in Talairach space were also performed. Overall results revealed either abnormally weak or no activation in FG in autistic patients, as well as significantly reduced activation in the inferior occipital gyrus, superior temporal sulcus and amygdala. Anatomical abnormalities, in contrast, were present only in the amygdala in autistic patients, whose mean volume was significantly reduced as compared with normals. Reaction time and accuracy measures were not different between groups. Thus, while autistic subjects could perform the face perception task, none of the regions supporting face processing in normals were found to be significantly active in the autistic subjects. Instead, in every autistic patient, faces maximally activated aberrant and individual-specific neural sites (e.g. frontal cortex, primary visual cortex, etc.), which was in contrast to the 100% consistency of maximal activation within the traditional fusiform face area (FFA) for every normal subject. It appears that, as compared with normal individuals, autistic individuals 'see' faces utilizing different neural systems, with each patient doing so via a unique neural circuitry. Such a pattern of individual-specific, scattered activation seen in autistic patients in contrast to the highly consistent FG activation seen in normals, suggests that experiential factors do indeed play a role in the normal development of the FFA.

Adult↗
PubMed2001

Development of the hippocampal formation from 2 to 42 years: MRI evidence of smaller area dentata in autism.

Autism, a neuropsychiatric disorder that severely impairs social, language and cognitive development, has a clinical onset in the first years of life. Because components of the limbic system mediate memory, social and affective functions that are typically disturbed in autism, a developmental defect in the limbic system has been hypothesized to underlie different autistic symptoms, but no developmental study has been performed. To obtain neuroanatomical evidence of limbic system abnormality in autism, we measured the cross-sectional area of the area dentata (AD; dentate gyrus + CA4) and combined area of the subiculum and CA1-CA3 (CAS) using in vivo MRI. Autistic patients aged 29 months to 42 years (n = 59) and healthy normal controls (n = 51) participated. The cross-sectional area of the AD was significantly smaller than normal in autism, the largest deviation from normal size (-13.5%) being found in autistic children aged 29 months to 4 years. Strong age-related increases were seen in the cross-sectional area of CAS, but autistic and normal subjects were not significantly different. This is the first direct evidence that anatomical abnormality within the limbic system exists from the earliest years of the disorder, and persists throughout development and to middle age.

Adolescent↗
PubMed2001

Prenatal, perinatal, and neonatal factors in autism, pervasive developmental disorder-not otherwise specified, and the general population.

OBJECTIVES: To examine various pre-, peri-, and neonatal factors in autistic participants and in pervasive developmental disorder-not otherwise specified (PDD-NOS) participants and to compare the incidence of each factor to that of the normal population. METHODS: Seventy-four participants (66 males, 8 females) were diagnosed with autism at 2.5 through 4 years of age using the most accurate and up-to-date methods, including the Diagnostic and Statistical Manual of Mental Disorders and the Autism Diagnostic Interview-Revised. At age 5, all participants were reevaluated using the Diagnostic and Statistical Manual of Mental Disorders, the Autism Diagnostic Interview-Revised, the Childhood Autism Rating Scale, and the Autism Diagnostic Observation Schedule-Revised, resulting in 61 autistic and 13 PDD-NOS participants. Twenty-eight pre-, peri-, and neonatal factors were examined in these 2 groups using both medical records and parental interviews. Incidences were compared with those of the US population as reported in the Report of Final Natality Statistics, 1995. This grand scale population group was used to closely approximate comparison to a normal, unbiased population. Results were analyzed using the binomial probability test, with a P value of <.05, constituting a significant difference in incidence. A Bonferroni correction was applied to the data to adjust for the number of factors investigated. RESULTS: Although most of the factors showed comparable incidences between the index and control groups, several factors showed statistically significant differences. Following the Bonferroni correction, the autism group was found to have a significantly higher incidence of uterine bleeding, a lower incidence of maternal vaginal infection, and less maternal use of contraceptives during conception when compared with the general population. Similarly, the PDD-NOS group showed a higher incidence of hyperbilirubinemia when compared with the general population. CONCLUSIONS: The results of this study support previous findings suggesting a consistent association of unfavorable events in pregnancy, delivery, and the neonatal phase and the pervasive developmental disorders. However, interpretation of the meaningfulness of these results is difficult, as the specific complications that carried the highest risk of autism and PDD-NOS represented various forms of pathologic processes with no presently apparent unifying feature. Additional studies are needed to corroborate and strengthen these associations, as well as to determine the possibility of an underlying unifying pathological process. This study's analysis of obstetric and neonatal complications in combination with the use of participants diagnosed at an early age provides some interesting concepts to consider. Perhaps future research will confirm certain pre-, peri-, and neonatal associations that could be used to generate a high-risk historical profile with which to use in conjunction with currently employed diagnostic tools. This may, in turn, help to determine the reliability of a diagnosis of autism in younger children, leading to earlier intervention and assistance for an improved outcome in long-term functionality and quality of life.

Apgar Score↗