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Eric Courchesne

Publications and source records attributed to Eric Courchesne.

At least 19 recordsLinked to original sources
PubMed2007

Abnormalities on the neurological examination and EEG in young children with pervasive developmental disorders.

This study examined the nature and frequency of neurological and EEG abnormalities in 60 young children (ages 2-6 years) with pervasive developmental disorders. A number of standard neurological functions could not be adequately assessed due to the young age of the children and/or limited comprehension and cooperation. The most common neurological deficits were hyporeflexia, stereotypies, and hypotonia. EEG abnormalities were identified in 32% of the children while only two children were known to have clinical seizures. The frequency of cases with hypotonia or hyporeflexia was more common than in older children with this diagnosis. Results also indicate that EEG abnormalities are common in this young population but clinical seizures are rare, confirming other studies.

Autistic Disorder↗
PubMed2006

Failing to deactivate: resting functional abnormalities in autism.

Several regions of the brain (including medial prefrontal cortex, rostral anterior cingulate, posterior cingulate, and precuneus) are known to have high metabolic activity during rest, which is suppressed during cognitively demanding tasks. With functional magnetic resonance imaging (fMRI), this suppression of activity is observed as "deactivations," which are thought to be indicative of an interruption of the mental activity that persists during rest. Thus, measuring deactivation provides a means by which rest-associated functional activity can be quantitatively examined. Applying this approach to autism, we found that the autism group failed to demonstrate this deactivation effect. Furthermore, there was a strong correlation between a clinical measure of social impairment and functional activity within the ventral medial prefrontal cortex. We speculate that the lack of deactivation in the autism group is indicative of abnormal internally directed processes at rest, which may be an important contribution to the social and emotional deficits of autism.

Adult↗
PubMed2005

When is the brain enlarged in autism? A meta-analysis of all brain size reports.

BACKGROUND: Multiple studies have reported increased brain size in autism, while others have found no difference from normal. These conflicting results may be due to a lack of accounting for age-related changes in brain enlargement, use of small sample sizes, or differences in data acquisition methods. METHODS: Reports of autism head circumference (HC), magnetic resonance imaging (MRI), and post-mortem brain weight (BW) that met specific criteria were identified and analyzed. Percent difference from normal values (%Diff) and standardized mean differences (SMD) were calculated to compare brain size across studies and measurement methods. Curve fitting, analysis of variance, and heterogeneity analyses were applied to assay the effects of age and measurement type on reported brain size in autism. RESULTS: A fitted curve of HC and MRI %Diff values from 15 studies revealed a largely consistent pattern of brain size changes. Specifically, brain size in autism was slightly reduced at birth, dramatically increased within the first year of life, but then plateaued so that by adulthood the majority of cases were within normal range. Analysis of variance of MRI and post-mortem %Diff values by age group (young child, older child, adult) and measurement type (MRI, BW) revealed a significant main effect of both age and measurement type, with the youngest ages (2-5) showing the greatest deviation from normal. Random effects heterogeneity analysis revealed a significant effect of age on HC and MRI SMD. CONCLUSIONS: These findings reveal a period of pathological brain growth and arrest in autism that is largely restricted to the first years of life, before the typical age of clinical identification. Study of the older autistic brain, thus, reflects the outcome, rather than the process, of pathology. Future research focusing on this early process of brain pathology will likely be critical to elucidate the etiology of autism.

Adolescent↗
PubMed2005

Activity and functional connectivity of inferior frontal cortex associated with response conflict.

The traditional Stroop test of cognitive interference requires overt speech responses. One alternative, the counting Stroop, generates cognitive interference similar to the traditional Stroop test but allows button press responses. Previous counting Stroop studies have used concrete words in the control condition, which may have masked inferior frontal activation. We studied 7 healthy young adults using fMRI on a counting Stroop condition, with a nonlinguistic control condition (geometric shapes). As expected, we found activation in bilateral inferior frontal gyri, as well as in lateral and medial prefrontal, inferior parietal, and extrastriate cortices. Additional functional connectivity analyses using inferior frontal activation clusters (right area 44, left area 47) as seed volumes showed connectivity with superior frontal area 8 and anterior cingulate gyrus, suggesting that the role of inferior frontal cortex was related to response conflict and inhibition. Connectivity with left perisylvian language areas was not observed, which further underscores the nonlinguistic nature of inferior frontal activity. We conclude that bilateral inferior frontal cortex is involved in response suppression associated with interference in the counting Stroop task.

Adult↗
PubMed2005

Localized enlargement of the frontal cortex in early autism.

BACKGROUND: Evidence from behavioral, imaging, and postmortem studies indicates that the frontal lobe, as well as other brain regions such as the cerebellum and limbic system, develops abnormally in children with autism. It is not yet clear to what extent the frontal lobe is affected; that is, whether all regions of frontal cortex show the same signs of structural maldevelopment. METHODS: In the present study, we measured cortical volume in four subregions of the frontal cortex in 2-year-old to 9-year-old boys with autism and normal control boys. RESULTS: The dorsolateral region showed a reduced age effect in patients when compared with control subjects, with a predicted 10% increase in volume from 2 years of age to 9 years of age compared with a predicted 48% increase for control subjects. In a separate analysis, dorsolateral and medial frontal regions were significantly enlarged in patients aged 2 to 5 years compared with control subjects of the same age, but the precentral gyrus and orbital cortex were not. CONCLUSIONS: These data indicate regional variation in the degree of frontocortical overgrowth with a possible bias toward later developing or association areas. Possible mechanisms for these regional differences are discussed.

Age Factors↗
PubMed2005

Auditory spatial localization and attention deficits in autistic adults.

The objective of this study was to compare autistic adults and matched control subjects in their ability to focus attention selectively on a sound source in a noisy environment. Event-related brain potentials (ERPs) were recorded while subjects attended to a fast paced sequence of brief noise bursts presented in free-field at a central or peripheral location. Competing sequences of noise bursts at adjacent locations were to be ignored. Both behavioral measures of target detection and auditory ERP amplitudes indicated that control subjects were able to focus their attention more sharply on the relevant sound source than autistic subjects. These findings point to a fundamental deficit in the spatial focusing of auditory attention in autism, which may be a factor that impedes social interactions and sensory-guided behavior, particularly in noisy environments.

Adult↗
PubMed2005

Why the frontal cortex in autism might be talking only to itself: local over-connectivity but long-distance disconnection.

Although it has long been thought that frontal lobe abnormality must play an important part in generating the severe impairment in higher-order social, emotional and cognitive functions in autism, only recently have studies identified developmentally early frontal lobe defects. At the microscopic level, neuroinflammatory reactions involving glial activation, migration defects and excess cerebral neurogenesis and/or defective apoptosis might generate frontal neural pathology early in development. It is hypothesized that these abnormal processes cause malformation and thus malfunction of frontal minicolumn microcircuitry. It is suggested that connectivity within frontal lobe is excessive, disorganized and inadequately selective, whereas connectivity between frontal cortex and other systems is poorly synchronized, weakly responsive and information impoverished. Increased local but reduced long-distance cortical-cortical reciprocal activity and coupling would impair the fundamental frontal function of integrating information from widespread and diverse systems and providing complex context-rich feedback, guidance and control to lower-level systems.

Autistic Disorder↗
PubMed2005

Autism at the beginning: microstructural and growth abnormalities underlying the cognitive and behavioral phenotype of autism.

Autistic symptoms begin in the first years of life, and recent magnetic resonance imaging studies have discovered brain growth abnormalities that precede and overlap with the onset of these symptoms. Recent postmortem studies of the autistic brain provide evidence of cellular abnormalities and processes that may underlie the recently discovered early brain overgrowth and arrest of growth that marks the first years of life in autism. Alternative origins and time tables for these cellular defects and processes are discussed. These cellular and growth abnormalities are most pronounced in frontal, cerebellar, and temporal structures that normally mediate the development of those same higher order social, emotional, speech, language, speech, attention, and cognitive functions that characterize autism. Cellular and growth pathologies are milder and perhaps nonexistent in other structures (e.g., occipital cortex), which are known to mediate functions that are often either mildly affected or entirely unaffected in autistic patients. It is argued that in autism, higher order functions largely fail to develop normally in the first place because frontal, cerebellar, and temporal cellular and growth pathologies occur prior to and during the critical period when these higher order neural systems first begin to form their circuitry. It is hypothesized that microstructural maldevelopment results in local and short distance overconnectivity in frontal cortex that is largely ineffective and in a failure of long-distance cortical-cortical coupling, and thus a reduction in frontal-posterior reciprocal connectivity. This altered circuitry impairs the essential role of frontal cortex in integrating information from diverse functional systems (emotional, sensory, autonomic, memory, etc.) and providing context-based and goal-directed feedback to lower level systems.

Autistic Disorder↗
PubMed2005

The functional neuroanatomy of spatial attention in autism spectrum disorder.

This study investigated the functional neuroanatomical correlates of spatial attention impairments in autism spectrum disorders (ASD) using an event-related functional magnetic resonance imaging (FMRI) design. Eight ASD participants and 8 normal comparison (NC) participants were tested with a task that required stimulus discrimination following a spatial cue that preceded target presentation by 100 msec (short interstimulus interval [ISI]) or 800 msec (long ISI). The ASD group showed significant behavioral spatial attention impairment in the short ISI condition. The FMRI results showed a reduction in activity within frontal, parietal, and occipital regions in ASD relative to the NC group, most notably within the inferior parietal lobule. ASD behavioral performance improved in the long ISI condition but was still impaired relative to the NC group. ASD FMRI activity in the long ISI condition suggested that the rudimentary framework of normal attention networks were engaged in ASD including bilateral activation within the frontal, parietal, and occipital lobes. Notable activation increases were observed in the superior parietal lobule and extrastriate cortex. No reliable activation was observed in the posterior cerebellar vermis in ASD participants during either long or short ISI conditions. In addition, no frontal activation during short ISI and severely reduced frontal activation during long ISI was observed in the ASD group. Taken together, these findings suggest a dysfunctional cerebello-frontal spatial attention system in ASD. The pattern of findings suggests that ASD is associated with a profound deficit in automatic spatial attention abilities and abnormal voluntary spatial attention abilities. This article also describes a method for reducing the contribution of physical eye movements to the blood-oxygenation level dependent activity in studies of ASD.

Adolescent↗
PubMed2004

Abnormal activity patterns in premotor cortex during sequence learning in autistic patients.

BACKGROUND: Evidence for frontal abnormality in autism has accumulated in recent years. Our own studies have shown abnormal activation in prefrontal cortex during finger tapping and visuomotor coordination. Studies in healthy adults suggest reduced premotor and increased prefrontal activity during advanced learning stages. We examined hemodynamic changes during visuomotor learning in autistic patients. METHODS: We studied eight high-functioning autistic patients and eight control subjects during learning of an 8-digit sequence over a period of 8 min, using functional magnetic resonance imaging. RESULTS: Autistic patients showed overall less prefrontal activation during late visuomotor learning; however, the main finding was a complementary one of enhanced activation in right pericentral and premotor cortex. In the autism group, Brodmann areas 3, 4, and 6 of the right hemisphere became more involved during late learning stages (trials 25-48), compared with early stages (trials 1-24). This effect was not seen in the control group. CONCLUSIONS: Our findings suggests that in autistic patients 1) primary sensorimotor and premotor cortex, which is normally predominant in early stages of visuomotor learning, plays an atypical role in later stages, even when learning is evident; and 2) handedness and side of execution interact with asymmetry of visuomotor learning activations, contrary to what is seen in normal adults.

Adult↗
PubMed2004

The brain response to personally familiar faces in autism: findings of fusiform activity and beyond.

Past functional MRI (FMRI) studies of autism have reported reduced activation in response to the faces of strangers primarily in the 'fusiform face area' (FFA). An alternative and potentially stronger test of FFA function in autism is one that attempts to affect levels of FFA activity using factors believed to modulate function in this brain region, such as face familiarity and the perception of face identity. The current study presented personally meaningful faces, such as mother and co-worker, as well as stranger faces in a rapid event-related FMRI design. Seven autistic and nine normal control adults participated and pressed a button in response to all female faces. A deconvolution analysis revealed significant FFA activity in response to familiar and stranger faces in both autism and normal control groups. Individuals with autism also showed greater fusiform activity in response to familiar faces than stranger faces, as well as the prototypical right hemisphere dominance in response to both types of faces. Normal subjects showed additional activation to familiar faces in the posterior cingulate, amygdala and medial frontal lobes, including the anterior cingulate. Subjects with autism showed a similar, but more limited, network in response to familiar faces. This network included the amygdala and implies that this structure, involved in multiple socio-emotional functions, can be responsive in autism in the presence of stimuli that represent high reward value, such as mother's face. Furthermore, the presence of a distinct network to process familiar faces in autism, one that included limbic structures and was not found in response to the faces of strangers, suggests socio-emotional processing in autism. A potentially noteworthy trend, however, was evidence for a reduction in medial frontal lobe function in the autism group. The main finding of FFA activity in autism stands in contrast to most past FMRI studies of face processing in this disorder. This positive result may reflect the use of personally significant faces that enhanced attention and motivation in the autistic participants. Furthermore, given the proposed role of the FFA in establishing person identity, the use of almost a dozen different personally familiar faces for each participant (totalling 32 non-repeating faces) may have additionally maximized FFA involvement. Therefore, dysfunction in the FFA found in other studies of autism may reflect defects in systems that modulate the FFA, rather than the FFA itself.

Adolescent↗
PubMed2004

Cerebellar function in autism: functional magnetic resonance image activation during a simple motor task.

BACKGROUND: The cerebellum is one of the most consistent sites of neuroanatomic abnormality in autism, yet it is still unclear how such pathology impacts cerebellar function. In normal subjects, we previously demonstrated with functional magnetic resonance imaging (fMRI) a dissociation between cerebellar regions involved in attention and those involved in a simple motor task, with motor activation localized to the anterior cerebellum ipsilateral to the moving hand. The purpose of the present investigation was to examine activation in the cerebella of autistic patients and normal control subjects performing this motor task. METHODS: We studied eight autistic patients and eight matched normal subjects, using fMRI. An anatomic region-of-interest approach was used, allowing a detailed examination of cerebellar function. RESULTS: Autistic individuals showed significantly increased motor activation in the ipsilateral anterior cerebellar hemisphere relative to normal subjects, in addition to atypical activation in contralateral and posterior cerebellar regions. Moreover, increased activation was correlated with the degree of cerebellar structural abnormality. CONCLUSIONS: These findings strongly suggest dysfunction of the autistic cerebellum that is a reflection of cerebellar anatomic abnormality. This neurofunctional deficit might be a key contributor to the development of certain diagnostic features of autism (e.g., impaired communication and social interaction, restricted interests, and stereotyped behaviors).

Adolescent↗
PubMed2004

Electroencephalographic brain dynamics following manually responded visual targets.

Scalp-recorded electroencephalographic (EEG) signals produced by partial synchronization of cortical field activity mix locally synchronous electrical activities of many cortical areas. Analysis of event-related EEG signals typically assumes that poststimulus potentials emerge out of a flat baseline. Signals associated with a particular type of cognitive event are then assessed by averaging data from each scalp channel across trials, producing averaged event-related potentials (ERPs). ERP averaging, however, filters out much of the information about cortical dynamics available in the unaveraged data trials. Here, we studied the dynamics of cortical electrical activity while subjects detected and manually responded to visual targets, viewing signals retained in ERP averages not as responses of an otherwise silent system but as resulting from event-related alterations in ongoing EEG processes. We applied infomax independent component analysis to parse the dynamics of the unaveraged 31-channel EEG signals into maximally independent processes, then clustered the resulting processes across subjects by similarities in their scalp maps and activity power spectra, identifying nine classes of EEG processes with distinct spatial distributions and event-related dynamics. Coupled two-cycle postmotor theta bursts followed button presses in frontal midline and somatomotor clusters, while the broad postmotor "P300" positivity summed distinct contributions from several classes of frontal, parietal, and occipital processes. The observed event-related changes in local field activities, within and between cortical areas, may serve to modulate the strength of spike-based communication between cortical areas to update attention, expectancy, memory, and motor preparation during and after target recognition and speeded responding.

Adult↗
PubMed2004

Brain development in autism: early overgrowth followed by premature arrest of growth.

Due to the relatively late age of clinical diagnosis of autism, the early brain pathology of children with autism has remained largely unstudied. The increased use of retrospective measures such as head circumference, along with a surge of MRI studies of toddlers with autism, have opened a whole new area of research and discovery. Recent studies have now shown that abnormal brain overgrowth occurs during the first 2 years of life in children with autism. By 2-4 years of age, the most deviant overgrowth is in cerebral, cerebellar, and limbic structures that underlie higher-order cognitive, social, emotional, and language functions. Excessive growth is followed by abnormally slow or arrested growth. Deviant brain growth in autism occurs at the very time when the formation of cerebral circuitry is at its most exuberant and vulnerable stage, and it may signal disruption of this process of circuit formation. The resulting aberrant connectivity and dysfunction may lead to the development of autistic behaviors. To discover the causes, neural substrates, early-warning signs and effective treatments of autism, future research should focus on elucidating the neurobiological defects that underlie brain growth abnormalities in autism that appear during these critical first years of life.

Anthropometry↗
PubMed2004

Outcome classification of preschool children with autism spectrum disorders using MRI brain measures.

OBJECTIVE: To test the hypothesis that a combination of magnetic resonance imaging (MRI) brain measures obtained during early childhood distinguish children with autism spectrum disorders (ASD) from typically developing children and is associated with functional outcome. METHOD: Quantitative MRI technology was used to measure gray and white matter volumes (cerebrum and cerebellum), total brain volume, and the area of the cerebellar vermis in 52 boys with a provisional diagnosis of autism (aged 1.9-5.2 years) and 15 typically developing young children (aged 1.7-5.2 years). Diagnostic confirmation and cognitive outcome data were obtained after the children reached 5 years of age. RESULTS: A discriminant function analysis of the MRI brain measures correctly classified 95.8% of the ASD cases and 92.3% of the control cases. This set of variables also correctly classified 85% of the ASD cases as lower functioning and 68% of the ASD cases as higher functioning. CONCLUSIONS: These results indicate that variability in cerebellar and cerebral size is correlated with diagnostic and functional outcome in very young children with ASD.

Analysis of Variance↗
PubMed2004

The autistic brain: birth through adulthood.

PURPOSE OF REVIEW: We discuss evidence of brain maldevelopment in the first years of life in autism and new neuroanatomical and functional evidence from later ages of development. RECENT FINDINGS: Head circumference, an accurate indicator of brain size in children, was reported to jump from normal or below normal size in the first postnatal months in autistic infants to the 84 th percentile by about 1 year of age; this abnormally accelerated growth was concluded by 2 years of age. Infants with extreme head (and therefore brain) growth fell into the severe end of the clinical spectrum and had more extreme neuroanatomical abnormalities. In the frontal and temporal lobes in autism, there have been reports of abnormal increases in gray and white matter at 2 to 4 years; reduced metabolic measures; deviant diffusion tensor imaging results in white matter; underdeveloped cortical minicolumns; and reduced functional activation during socio-emotional, cognitive and attention tasks. Cerebellar abnormalities included abnormal volumes, reduced number and size of Purkinje neurons in the vermis and hemispheres, molecular defects, and reduced functional activation in posterior regions. SUMMARY: A new neurobiological phenomenon in autism has been described that precedes the onset of clinical behavioral symptoms, and is brief and age-delimited to the first two years of life. The neurobiological defects that precede, trigger, and underlie it may form part of the developmental precursors of some of the anatomical, functional, and behavioral manifestations of autism. Future studies of the first years of life may help elucidate the factors and processes that bring about the unfolding of autistic behavior.

Autistic Disorder↗
PubMed2003

Evidence of brain overgrowth in the first year of life in autism.

CONTEXT: Autism most commonly appears by 2 to 3 years of life, at which time the brain is already abnormally large. This raises the possibility that brain overgrowth begins much earlier, perhaps before the first clinically noticeable behavioral symptoms. OBJECTIVES: To determine whether pathological brain overgrowth precedes the first clinical signs of autism spectrum disorder (ASD) and whether the rate of overgrowth during the first year is related to neuroanatomical and clinical outcome in early childhood. DESIGN, SETTING, AND PARTICIPANTS: Head circumference (HC), body length, and body weight measurements during the first year were obtained from the medical records of 48 children with ASD aged 2 to 5 years who had participated in magnetic resonance imaging studies. Of these children, 15 (longitudinal group) had measurements at 4 periods during infancy: birth, 1 to 2 months, 3 to 5 months, and 6 to 14 months; and 33 (partial HC data group) had measurements at birth and 6 to 14 months (n = 7), and at birth only (n = 28). MAIN OUTCOME MEASURES: Age-related changes in infants with ASD who had multiple-age measurements, and the relationship of these changes to brain anatomy and clinical and diagnostic outcome at 2 to 5 years were evaluated by using 2 nationally recognized normative databases: cross-sectional normative data from a national survey and longitudinal data of individual growth. RESULTS: Compared with normative data of healthy infants, birth HC in infants with ASD was significantly smaller (z = -0.66, P<.001); after birth, HC increased 1.67 SDs and mean HC was at the 84th percentile by 6 to 14 months. Birth HC was related to cerebellar gray matter volume at 2 to 5 years, although the excessive increase in HC between birth and 6 to 14 months was related to greater cerebral cortex volume at 2 to 5 years. Within the ASD group, every child with autistic disorder had a greater increase in HC between birth and 6 to 14 months (mean [SD], 2.19 [0.98]) than infants with pervasive developmental disorder-not otherwise specified (0.58 [0.35]). Only 6% of the individual healthy infants in the longitudinal data showed accelerated HC growth trajectories (>2.0 SDs) from birth to 6 to 14 months; 59% of infants with autistic disorder showed these accelerated growth trajectories. CONCLUSIONS: The clinical onset of autism appears to be preceded by 2 phases of brain growth abnormality: a reduced head size at birth and a sudden and excessive increase in head size between 1 to 2 months and 6 to 14 months. Abnormally accelerated rate of growth may serve as an early warning signal of risk for autism.

Anthropometry↗