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E Courchesne

Publications and source records attributed to E Courchesne.

At least 37 records · Page 2Linked to original sources
PubMed2000

Removal of eye activity artifacts from visual event-related potentials in normal and clinical subjects.

OBJECTIVES: Electrical potentials produced by blinks and eye movements present serious problems for electroencephalographic (EEG) and event-related potential (ERP) data interpretation and analysis, particularly for analysis of data from some clinical populations. Often, all epochs contaminated by large eye artifacts are rejected as unusable, though this may prove unacceptable when blinks and eye movements occur frequently. METHODS: Frontal channels are often used as reference signals to regress out eye artifacts, but inevitably portions of relevant EEG signals also appearing in EOG channels are thereby eliminated or mixed into other scalp channels. A generally applicable adaptive method for removing artifacts from EEG records based on blind source separation by independent component analysis (ICA) (Neural Computation 7 (1995) 1129; Neural Computation 10(8) (1998) 2103; Neural Computation 11(2) (1999) 606) overcomes these limitations. RESULTS: Results on EEG data collected from 28 normal controls and 22 clinical subjects performing a visual selective attention task show that ICA can be used to effectively detect, separate and remove ocular artifacts from even strongly contaminated EEG recordings. The results compare favorably to those obtained using rejection or regression methods. CONCLUSIONS: The ICA method can preserve ERP contributions from all of the recorded trials and all the recorded data channels, even when none of the single trials are artifact-free.

Adult↗
PubMed2000

Inverse correlation between frontal lobe and cerebellum sizes in children with autism.

Certain cognitive and behavioural deficits suggest that the frontal lobe functions abnormally in patients with autism, but little anatomical research is available to either verify or refute this. In contrast, several neuropathological and neuroimaging studies have demonstrated anatomical abnormalities in the cerebellum in autistic patients. The current study shows that frontal lobe cortex volume is increased in a subset of patients with autism and that this increase correlates with the degree of cerebellar abnormality. This evidence of concurrent structural abnormalities in both the frontal lobe and the cerebellum has important implications for understanding the development and persistence of the autistic disorder.

Autistic Disorder↗
PubMed2000

Regional size reduction in the human corpus callosum following pre- and perinatal brain injury.

This morphometric study examined two aspects of corpus callosum development: pediatric cortico-callosal topography and developmental neuroplasticity subsequent to perinatal brain injury. In vivo magnetic resonance imaging was used to quantify the total midsagittal cross-sectional area and five anterioposterior subregions of the callosum in 10 children with focal lesions and 86 healthy volunteer control subjects. Nine of the ten children with early injury showed a reduction in the total area of the callosum relative to matched controls. The area of the total callosum cross-section was inversely proportional to the size of lesion. All patients displayed region-specific size reduction. This regional thinning bore a topographical relationship to the lesion sites. Reduction in anterior subregions 1, 2 and 3 was respectively associated with lesions in the anterior inferior frontal area, the middle and superior frontal region, and the precentral area. Attenuation of subregion 4 corresponded to anterior parietal lesions, and thinning of subregion 5 occurred with posterior parietal injury. This cortical-callosal pattern coincides with adult and nonhuman primate mappings. Callosal thinning despite the early onset of the lesions suggests limits to developmental neuroplasticity.

Adolescent↗
PubMed2000

Normal brain development and aging: quantitative analysis at in vivo MR imaging in healthy volunteers.

PURPOSE: To quantitate neuroanatomic parameters in healthy volunteers and to compare the values with normative values from postmortem studies. MATERIALS AND METHODS: Magnetic resonance (MR) images of 116 volunteers aged 19 months to 80 years were analyzed with semiautomated procedures validated by means of comparison with manual tracings. Volumes measured included intracranial space, whole brain, gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF). Results were compared with values from previous postmortem studies. RESULTS: Whole brain and intracranial space grew by 25%-27% between early childhood (mean age, 26 months; age range, 19-33 months) and adolescence (mean age, 14 years; age range, 12-15 years); thereafter, whole-brain volume decreased such that volunteers (age range, 71-80 years) had volumes similar to those of young children. GM increased 13% from early to later (6-9 years) childhood. Thereafter, GM increased more slowly and reached a plateau in the 4th decade; it decreased by 13% in the oldest volunteers. The GM-WM ratio decreased exponentially from early childhood through the 4th decade; thereafter, it gradually declined. In vivo patterns of change in the intracranial space, whole brain, and GM-WM ratio agreed with published postmortem data. CONCLUSION: MR images accurately depict normal patterns of age-related change in intracranial space, whole brain, GM, WM, and CSF. These quantitative MR imaging data can be used in research studies and clinical settings for the detection of abnormalities in fundamental neuroanatomic parameters.

Adolescent↗
PubMed2000

Autism associated with the mitochondrial DNA G8363A transfer RNA(Lys) mutation.

We report a family with a heterogeneous group of neurologic disorders associated with the mitochondrial DNA G8363A transfer ribonucleic acid (RNA)Lys mutation. The phenotype of one child in the family was consistent with autism. During his second year of life, he lost previously acquired language skills and developed marked hyperactivity with toe-walking, abnormal reciprocal social interaction, stereotyped mannerisms, restricted interests, self-injurious behavior, and seizures. Brain magnetic resonance imaging (MRI) and repeated serum lactate studies were normal. His older sister developed signs of Leigh syndrome with progressive ataxia, myoclonus, seizures, and cognitive regression. Her laboratory studies revealed increased MRI T2-weighted signal in the putamen and posterior medulla, elevated lactate in serum and cerebrospinal fluid, and absence of cytochrome c oxidase staining in muscle histochemistry. Molecular analysis in her revealed the G8363A mutation of the mitochondrial transfer RNA(Lys) gene in blood (82% mutant mitochondrial DNA) and muscle (86%). The proportions of mutant mitochondrial DNA from her brother with autism were lower (blood 60%, muscle 61%). It is likely that the origin of his autism phenotype is the pathogenic G8363A mitochondrial DNA mutation. This observation suggests that certain mitochondrial point mutations could be the basis for autism in some individuals.

Adult↗
PubMed1999

Physical mapping of the serotonin 5-HT(7) receptor gene (HTR7) to chromosome 10 and pseudogene (HTR7P) to chromosome 12, and testing of linkage disequilibrium between HTR7 and autistic disorder.

The gene encoding the serotonin 5-HT(7) receptor (HTR7) has been considered as a candidate locus in several neuropsychiatric disorders, based on pharmacological evidence and ligand-binding studies. After determining over 3 kb of previously unpublished sequence from introns 1 and 2 of HTR7, a single base (C/T) polymorphism in the second intron of HTR7 was found. Allele-specific PCR was used to genotype the HTR7 marker in 53 trios consisting of subjects with autistic disorder and both parents. Using the transmission disequilibrium test (TDT), no evidence of preferential transmission of either allele was found (TDT chi(2) = 0.252, p = 0.602). Sequence data obtained from both intron 1 and intron 2 of HTR7, and from the 5-HT(7) pseudogene (HTR7P), was used to confirm localization of HTR7 to 10q23 and HTR7P to 12p13 using radiation hybrid analyses.

Autistic Disorder↗
PubMed1999

Functionally independent components of early event-related potentials in a visual spatial attention task.

Spatial visual attention modulates the first negative-going deflection in the human averaged event-related potential (ERP) in response to visual target and non-target stimuli (the N1 complex). Here we demonstrate a decomposition of N1 into functionally independent subcomponents with functionally distinct relations to task and stimulus conditions. ERPs were collected from 20 subjects in response to visual target and non-target stimuli presented at five attended and non-attended screen locations. Independent component analysis, a new method for blind source separation, was trained simultaneously on 500 ms grand average responses from all 25 stimulus-attention conditions and decomposed the non-target N1 complexes into five spatially fixed, temporally independent and physiologically plausible components. Activity of an early, laterally symmetrical component pair (N1aR and N1aL) was evoked by the left and right visual field stimuli, respectively. Component N1aR peaked ca. 9 ms earlier than N1aL. Central stimuli evoked both components with the same peak latency difference, producing a bilateral scalp distribution. The amplitudes of these components were no reliably augmented by spatial attention. Stimuli in the right visual field evoked activity in a spatio-temporally overlapping bilateral component (N1b) that peaked at ca. 180 ms and was strongly enhanced by attention. Stimuli presented at unattended locations evoked a fourth component (P2a) peaking near 240 ms. A fifth component (P3f) was evoked only by targets presented in either visual field. The distinct response patterns of these components across the array of stimulus and attention conditions suggest that they reflect activity in functionally independent brain systems involved in processing attended and unattended visuospatial events.

Adolescent↗
PubMed1999

Spatial attention deficits in patients with acquired or developmental cerebellar abnormality.

Recent imaging and clinical studies have challenged the concept that the functional role of the cerebellum is exclusively in the motor domain. We present evidence of slowed covert orienting of visuospatial attention in patients with developmental cerebellar abnormality (patients with autism, a disorder in which at least 90% of all postmortem cases reported to date have Purkinje neuron loss), and in patients with cerebellar damage acquired from tumor or stroke. In spatial cuing tasks, normal control subjects across a wide age range were able to orient attention within 100 msec of an attention-directing cue. Patients with cerebellar damage showed little evidence of having oriented attention after 100 msec but did show the effects of attention orienting after 800-1200 msec. These effects were demonstrated in a task in which results were independent of the motor response. In this task, smaller cerebellar vermal lobules VI-VII (from magnetic resonance imaging) were associated with greater attention-orienting deficits. Although eye movements may also be disrupted in patients with cerebellar damage, abnormal gaze shifting cannot explain the timing and nature of the attention-orienting deficits reported here. These data may be consistent with evidence from animal models that suggest damage to the cerebellum disrupts both the spatial encoding of a location for an attentional shift and the subsequent gaze shift. These data are also consistent with a model of cerebellar function in which the cerebellum supports a broad spectrum of brain systems involved in both nonmotor and motor function.

Adolescent↗
PubMed1999

Functionally independent components of the late positive event-related potential during visual spatial attention.

Human event-related potentials (ERPs) were recorded from 10 subjects presented with visual target and nontarget stimuli at five screen locations and responding to targets presented at one of the locations. The late positive response complexes of 25-75 ERP average waveforms from the two task conditions were simultaneously analyzed with Independent Component Analysis, a new computational method for blindly separating linearly mixed signals. Three spatially fixed, temporally independent, behaviorally relevant, and physiologically plausible components were identified without reference to peaks in single-channel waveforms. A novel frontoparietal component (P3f) began at approximately 140 msec and peaked, in faster responders, at the onset of the motor command. The scalp distribution of P3f appeared consistent with brain regions activated during spatial orienting in functional imaging experiments. A longer-latency large component (P3b), positive over parietal cortex, was followed by a postmotor potential (Pmp) component that peaked 200 msec after the button press and reversed polarity near the central sulcus. A fourth component associated with a left frontocentral nontarget positivity (Pnt) was evoked primarily by target-like distractors presented in the attended location. When no distractors were presented, responses of five faster-responding subjects contained largest P3f and smallest Pmp components; when distractors were included, a Pmp component appeared only in responses of the five slower-responding subjects. Direct relationships between component amplitudes, latencies, and behavioral responses, plus similarities between component scalp distributions and regional activations reported in functional brain imaging experiments suggest that P3f, Pmp, and Pnt measure the time course and strength of functionally distinct brain processes.

Adult↗
PubMed1999

Brain weight in autism: normal in the majority of cases, megalencephalic in rare cases.

The brain weights of 21 postmortem autism cases (5 new and 16 previously published) were compared with normal brain weights from six autopsy studies. Of the 21 cases, 17 had normal brain weights and 1 was micrencephalic. Compared with the normal median (1,460 g), three autism cases were megalencephalic: two (1,810 g and 1,820 g) had been previously reported and one (1,880 g) was a new case. Brain weight is thus normal in most postmortem cases of autism. There are, however, rare cases of megalencephaly and possibly micrencephaly.

Adolescent↗
PubMed1999

Neuroanatomic contributions to slowed orienting of attention in children with autism.

Previous research has demonstrated that adult autistic patients are abnormally slow to orient attention, with degree of slowed orienting associated with severity of cerebellar hypoplasia. This research was extended to children who, at ages two through six, met diagnostic criteria for autism and underwent magnetic resonance imaging (MRI). An average of 3 years later, when old enough to participate in behavioral experiments, the children returned to the laboratory and completed a spatial attention paradigm. Degree of slowed attentional orienting to visual cues was significantly correlated with degree of cerebellar hypoplasia, but not with size of other neuroanatomic regions. Additionally, there was a trend for orienting speed to differ between diagnostic outcome subgroups; children with confirmed diagnoses of autism at time of behavioral testing had larger orienting deficits than those who no longer met diagnostic criteria for autism. This research is among the first to establish a specific brain-behavior link in autistic children.

Atrophy↗
PubMed1998

Linkage-disequilibrium mapping of autistic disorder, with 15q11-13 markers.

Autistic disorder is a complex genetic disease. Because of previous reports of individuals with autistic disorder with duplications of the Prader-Willi/Angelman syndrome critical region, we screened several markers across the 15q11-13 region, for linkage disequilibrium. One hundred forty families, consisting predominantly of a child with autistic disorder and both parents, were studied. Genotyping was performed by use of multiplex PCR and capillary electrophoresis. Two children were identified who had interstitial chromosome 15 duplications and were excluded from further linkage-disequilibrium analysis. Use of the multiallelic transmission-disequilibrium test (MTDT), for nine loci on 15q11-13, revealed linkage disequilibrium between autistic disorder and a marker in the gamma-aminobutyric acidA receptor subunit gene, GABRB3 155CA-2 (MTDT 28.63, 10 df, P=.0014). No evidence was found for parent-of-origin effects on allelic transmission. The convergence of GABRB3 as a positional and functional candidate along with the linkage-disequilibrium data suggests the need for further investigation of the role of GABRB3 or adjacent genes in autistic disorder.

Autistic Disorder↗
PubMed1998

Magnetic resonance imaging study of the brain in autism.

Autism is a neuropsychiatric disorder of social, cognitive, and language development. Cerebellar abnormality in autism has been shown consistently from autopsy and magnetic resonance image (MRI) studies. A new MRI study with careful methodologic designs identified two subgroups of autistic patients: hypoplasia and hyperplasia of cerebellar vermian lobules VI-VII. The existence of these two subtypes was also supported via the meta-analysis of data from separate research groups. In addition to the cerebellar abnormality, recent MRI studies in autism demonstrated abnormalities in the parietal lobe and the posterior subregions of the corpus callosum where parietal cortical fibers are concentrated. Furthermore, neurobehavioral correlates of cerebellar and parietal abnormalities have also been investigated. In contrast, there is a lack of significant difference in the cross-sectional size of the posterior hippocampal formation between autistic and normal subjects, which is discrepant with predictions based on some autopsy studies.

Autistic Disorder↗
PubMed1997

Attentional activation of the cerebellum independent of motor involvement.

The cerebellum traditionally has been viewed as a neural device dedicated to motor control. Although recent evidence shows that it is involved in nonmotor operations as well, an important question is whether this involvement is independent of motor control and motor guidance. Functional magnetic resonance imaging was used to demonstrate that attention and motor performance independently activate distinct cerebellar regions. These findings support a broader concept of cerebellar function, in which the cerebellum is involved in diverse cognitive and noncognitive neurobehavioral systems, including the attention and motor systems, in order to anticipate imminent information acquisition, analysis, or action.

Adult↗
PubMed1997

Attention coordination and anticipatory control.

The coordination of the direction of selective attention is an adaptive function that may be one of the many anticipatory tools under cerebellar control. This chapter presents neurobehavioral, neurophysiological, and neuroimaging data to support our hypothesis that the cerebellum plays a role in attentional functions. We discuss the idea that the cerebellum is a master computational system that anticipates and adjusts responsiveness in a variety of brain systems (e.g., sensory, attention, memory, language, affect) to efficiently achieve goals determined by cerebral and other subcortical systems.

Adaptation, Physiological↗