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November 7, 2001        News Morgue Search  www.feat.org/search/news.asp

3 - New Papers From The International Meeting for Autism Research

[Abstract listing continues after following article.]

Innovative Technology Aids Children with Autism

First-Ever Autism Research Conference to Demonstrate Talking-Head “Baldi”

http://www.newswise.com/articles/2001/11/IMFAR2.UCM.html

As part of the International Meeting for Autism Research (IMFAR), being held on Nov. 9 and 10, research presentations will highlight innovative technology uses and educational methods in the treatment of autism, as well as current scientific findings into its cause. IMFAR is the first ever autism research conference to promote communication and facilitate interdisciplinary collaboration among scientists researching the disorder.

In addition to more than 200 research presentations, a state-of-the-science symposium will be held, featuring four scientists with expertise in the fields of genetics, neuroscience, the incidences (or epidemiological trends) and the diagnosis of autism.

Some of the research presentation highlights at the conference include:

·        Computer Animated Learning—A demonstration of “Baldi,” a computer-animated talking head, that mimics the speech of a real person to teach children with autism how to process language and emotion in face-to-face situations. (See Saturday Afternoon Slide Session Abstracts)

·        Video Modeling—Video-modeling as a way of teaching social behaviors to children with autism disorders. Parents review the video capsule and then mimic the situations with their children. (See Saturday Afternoon Slide Session Abstracts)

·        Teaching Emotion—How to go beyond a drill and practice format to teach emotion recognition so that children with autism develop a way to effectively read emotions from the facial expressions of others. (See Saturday Morning Slide Session Abstracts)

·        Environmental Toxins and the Effect on Autism—The growing concern over environmental toxins and vaccine antigens has created an uproar in the general public. This presentation will explore the implications of the vaccines and their effects on the causes of autism. (See Friday Afternoon Slide Session Abstracts)

·        Importance of Fathers as Treatment Providers—Past studies have shown that training parents how to use behavioral treatments is useful in increasing the skills of children with autism. Research has shown that overall, fathers have a lower level of involvement in parent training programs than mothers.

Research abstracts of these presentations and others can be viewed on IMFAR’s virtual newsroom at www.newswise.com/vpr/mtg2001.ucm.html. In addition, a media briefing on the state of the science will be held at noon Saturday, Nov. 10.

The International Meeting for Autism Research (IMFAR) is the

first-ever scientific research conference specifically devoted to the topic

of autism. The conference is underwritten collaboratively by the Cure Autism

Now Foundation, the UC Davis M.I.N.D. Institute and the National Alliance

for Autism Research (NAAR). Its mission is to provide a unique opportunity

for researchers, advocates, health care professionals, service providers and

others affected by autism to discuss and promote new research into the

condition. www.imfar.org In order to reach the IMFAR virtual newsroom,

please log onto http://www.newswise.com/vpr/mtg2001.ucm.html

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3 - New Papers From The International Meeting for Autism Research

The abstracts below are some of the scientific papers being presented

Friday afternoon by the researchers.  Additional Friday and Saturday’s

reports will be reproduced here in subsequent postings of the FEAT

Newsletter.  All of the information is from the IMFAR website

NEUROIMAGING

Brain Structural Abnormalities In Childhood Autism. S. R. Dager, B. Sparks, S. D. Friedman, D. W. W. Shaw, A. A. Artru, E. Aylward, G. Dawson.  University of Washington Departments of Psychiatry & Radiology, Seattle WA.

Objective: Autism spectrum disorder (ASD) is widely viewed as a disorder of brain development. To explore the specific gross neuroanatomical substrates of this developmental disorder, we examined brain morphometry in a large sample of carefully diagnosed 3-to 4-year-old children with ASD compared to age-matched normally developing (ND) and developmentally delayed (DD) control groups.

Methods: Volumes of the cerebrum, cerebellum, amygdala and hippocampus were measured from 3-D coronal MRI scans acquired from 45 children with ASD, 23 ND children and 12 DD children. The volumes were analyzed with respect to age, gender, clinical status and, for subregion analyses, volume of the cerebrum.

Results: Children with ASD were found to have significantly increased cerebral volumes compared to ND and DD children. No difference in cerebellar volume was observed between ASD and ND groups; the DD group had smaller cerebellar volumes compared to both other groups. In contrast to a recent report in older individuals with autism, volumetric measurements of amygdalae and hippocampi in this group of young children with ASD revealed enlargement that appeared proportional to increases in total cerebral volume. These findings appeared to be independent of non-verbal IQ. In a subgroup of ASD children with more strictly-defined autism, amygdalar enlargement appeared to be in excess of increased cerebral volume.

Conclusions: These structural findings suggest abnormal brain developmental processes early in the clinical course of autism. Research is currently underway to better elucidate mechanisms underlying these structural abnormalities and their longitudinal progression.

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Enlarged Head Circumference And Brain Volume In Autistic Infants And Toddlers.

E. Courchesne, C. M. Karns, H. H. Bartholomeusz, K. Pierce. Lab for Res. on the Neuroscience of Autism, Children’s Hospital Res. Ctr., La Jolla, CA 92037.

We have recently reported abnormally enlarged brain volume (BV) in autistic toddlers. More than 37% of the 2-4 year olds with autism in that study met clinical criteria for macrencephaly (Courchesne et al. 2001). To examine whether this abnormal overgrowth was present at birth, we obtained birth head circumference (HC) measures from hospital records for a subset (N = 16) of these 2-6 year-old boys with autism. We also measured HC and BV from MR images obtained at 2-6 years of age. Previous studies have shown that HC and BV are highly correlated at birth and in young children.

In the present study, HC and BV were strongly correlated (R= 0.87) in autistic boys ages 2-6 years. We found that, at birth, 81% of these children (13 of 16) had HC measures below the 50^th percentile of CDC growth charts.  HC measures at birth were used to estimate BV using the relationship between HC and brain weight from Cooke et al. (1977); these estimates of BV were not different from published MRI brain volumes of normal neonates (Huppi et al.  1998).

Although these children with autism had normal HC at birth, by ages 2-6 all had HC measures above the 50^th percentile and 69% (11 of 16) were above the 90^th percentile (compared to norms from Roche et al 1987). The present MRI study suggests that in autism, there is abnormally accelerated growth of the head and brain during the first years of postnatal life.

Funded by NINDS grant #2-R01-NS-19855

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MRI Results From Preschoolers With Pervasive Developmental Disorders.

N. Akshoomoff, C. Lord, H. R. Davis, R. Ziccardi, C. Karns, S. Pizzo, A. J.

Lincoln, R. A. Carper, Z. D. Tigue, R. Y. Courchesne, and E. Courchesne.  Laboratory for Research on the Neurscience of Autism, Children’s Hospital Research Center, La Jolla, CA 92037.

In a recently completed studied, we found early age-related MRI abnormalities in the cerebrum and cerbellum in autism (Courchesne et al., in press). Between the ages of 2 and 5, children later diagnosed with autism had larger than normal whole brain volume cerebral and cerebellar white matter volume, and cerebral cortical gray matter.

Here we compare the MRI results from a group of 11 boys who were also scanned between the ages of 2 and 5 but received a final diagnosis of PDD-NOS at age 5 with the young autistic and normal participants from that study. Whole brain volume and cerebellar white matter volume were significantly larger than normal in the boys with a diagnosis of PDD-NOS.

The size of the posterior cerebellar vermis was not significantly different from normal in the PDD-NOS group. The posterior cerebellar vermis was significantly smaller than normal in the lower functioning autistic boys (i. e., those with a nonverbal IQ and expressive language scores less than 70).

Brain measurements for the PDD-NOS group and autistic boys matched for nonverbal IQ and expressive language levels (standard scores greater than 70) were quite similar. Differences in early behavioral profiles between these two groups will be discussed. Overall, these results suggest that during the preschool period, brain volume measurements are abnormally large across pervasive developmental disorder subtypes and specific differences in cerebral and cerebellar measurements are related to functional outcome.

Funded by NINDS grant# 2-RO1-NS-19855.

* * *

Gray And White Matter Volume On MRI In Autism.  A. H. Cody, L. Keyes-Elstein, and J. Piven. Department of Psychiatry, University of North Carolina, Chapel Hill, NC 27599.

A number of studies have suggested that both head circumference and brain volume may be enlarged in autism. We examined gray and white matter volumes in a sample of adolescents and adults with autism who were previously reported to have enlarged total brain volumes in comparison to age, gender and PIQ comparable controls (Piven, et al., 1996).

Clarification of the nature of this enlargement (i. e., structures and underlying tissues involved and growth patterns) will inform about underlying developmental brain mechanisms in autism as well as contribute to further refinements of our notions about the phenotype in this condition.

We employed an automated tissue classification technique to measure gray and white brain tissue volumes in 23 autistic and 15 control males (a subset of the subjects examined in a previous report from our group; scan quality was not sufficient on all subjects to perform this level of more advanced tissue segmentation). After adjusting for age and nonverbal intelligence, results showed that in the subjects with autism, both gray and white matter volumes were significantly increased in the temporal and parietal lobes.

We are currently examining the timing of these developmental changes in a longitudinal sample of 18-35 month old children with autism.

Funding: NIH grant #5 RO1 MH61696 “Longitudinal MRI Study of Brain

Development in Autism”

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Macrocephaly And Brachycephaly In Autism: Correspondence Of Brain And Cranial Size/ Shape .

C. Deutsch, S. Hodge, H. Tager-Flusberg, S. Folstein, S. Steele, E. Lauer, G. Harris, M. Herbert, S. Reading, and J. Sherman. Shriver Center, 200 Trapelo Road, Waltham, MA 02254, Boston University School of Medicine, Center for Morphometric Analysis, Massachusetts General Hospital, Harvard Medical School.

Macrocephaly has come under increasing scrutiny as an indicator of cerebral hyperplasia in autism, begging the question of whether enlargement is uniform or disproportionate. Work in our laboratory suggests that there is a disproportionate enlargement, in which there is increased width but not length (i. e., a brachycephalic pattern). We have found both macrocephaly and cephalic disproportion to be overrepresented both among the probands and their unaffected first-degree relatives.

In this study, we have correlated cranial disproportion (using direct anthropometry) and brain disproportion (using MRI morphometry). Calvarial width was defined as the distance between the lateral eurions, and length as the distance between the glabella and the opisthocranion. Cerebral width was measured between the most lateral pixel columns abutting the right and left cerebral exterior outline, and length as the distance between the most anterior and posterior coronal images containing a cerebral exterior outline.

The correspondence between cranial and brain measurements was high.  For instance, the ratio of the principal axes of width to length correlated .92 between brain and calvarium (p < .01). These results are consistent with earlier reports of disproportionate brain growth, which we interpret using embryologically derived models.

This work was funded by a grant from NIDCD PO1 DC03610, which is part of the NICHD/ NIDCD Collaborative Programs for Excellence in Autism.

* * *

Large Brains With Increased White Matter Volume In Two Groups Of Autistic Boys.

M. R. Herbert, S. M. Hodge, S. Steele, K. Adrien, N. Makris, D. Kennedy, G.  Harris, N. Lange, H. Tager-Flusberg, V. S. Caviness. Ctr for Morphometric Anal, Mass Gen Hosp, Charlestown, MA 02129 and BU Medical Ctr, Boston, MA 02118.

Objective: To characterize regional distribution of increased brain volume in two independent samples of autistic boys. Methods: MRI-based gray-white matter segmentation was performed distinguishing major regions of the entire brain.

Subjects: Three groups of boys with PIQ > 80, 7-11y. A: 16 Autistic (Nosology Project ), B: 19 Autistic (Language in Autism Project), C: 15 Control (Nosology).

Results: Compared with controls, autistic total brain volume was significantly larger in B (p<. 048) and nearly so in A (p<. 054). Central white matter volume was significantly greater than in controls in both A (p<. 007) and B (p<. 008), while cerebral cortex volume was not different in A or B than C. Central white matter volume was about half of cerebral cortex volume (CTX/ CWM in cc: A-755/ 441 ,B-759/ 435, C-740/ 384 ), but it accounted for 58% of the increase over controls in total brain volume in A and 52% in B.

Conclusion: Increased central white matter volume accounts for a disproportionately large share of the greater brain volume often seen in autistic boys.

Implications: Seeking mechanisms for disregulation of white matter development in utero and in early life may yield insights regarding cause, treatment and prevention of autism.

Supported by: NINDS Multi-Institutional Program Project Grant NS 20489, the Cure Autism Now Foundation, NIH grants NS02126, NS27950, DA09467 and NS37483; NIDCD (P01 DC03610 and R01 DC01234), NIH grants NS34189 and MH57180 as part of the Human Brain Project; the Fairway Trust; and the Giovanni Armenise-Harvard Fdtn for Advanced Scientific Research.

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Left Temporal Lobe Lesions In Children With Autism: An Mri Study.  J. H. Miles and C. H. Wang. Departments of Psychiatry and Neurology, Biochemistry, and Child Health, University of Missouri, Columbia, MO. 65212.

Autism is a neurodevelopmental disorder with symptoms consistent with limbic system dysfunction. Previous neuropathological findings have identified microscopic abnormalities and in both hippocampus and amygdala.  Recent functional MRI studies also suggest that autism may be related to the disorder of information processing in these areas.

To study the roles of left temporal lobe lesions in autism, we report here three patients with autism in whom lesions in the left temporal lobe were identified through MRI examinations. All three patients were diagnosed with autism using DSM-IV criteria.

The first patient is a 15 year-old boy with severe autistic symptoms.  His MRI showed a 2x3 cm arachnoid cyst located in the left sylvian fissure compressing the operculum of the inferior frontal and the anterior temporal lobes. The left temporal pole is significantly smaller that the right. This patient also has a seizure disorder and an abnormal EEG.

The second patient is a 5 year-old boy with severe autistic features.  His MRI showed an enlarged temporal horn of the left lateral ventricle with a decreased volume of the left hippocampal gyrus.

The third patient is an 8 year-old boy with mild to moderate autistic symptoms. His MRI showed an 8 mm arachnoid cyst in the deep left mesial temporal lobe. This lesion resulted in partial obliteration of the hippocampus and the neighboring optic radiation. This patient also has a seizure disorder with EEG abnormalities.

These MRI findings suggest that the left temporal lobe lesions may be associated with the manifestation of autism.

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