Archived | Autism Speaks: 2008 Basic and Clinical Awards (Summer) | Circa 2008 #NotAnAutisticAlly

2008 Environmental Factors Awards
2008 Basic and Clinical Awards (Winter)
2008 Basic and Clinical Awards (Summer)
2008 Epidemiology Awards
2008 Fellowships
2008 High Risk, High Impact Projects
2008 Pilot Awards (Winter)
2008 Pilot Awards (Summer)
2008 Treatment Awards

2008 Basic and Clinical Awards (Summer)

Glenys Dixon, B Psych
Telethon Institute for Child Health Research
$128,045 for 2 years

International trends in diagnoses and incidence of autism spectrum disorders

Although there have been numerous studies investigating the increased prevalence or “epidemic” or autism spectrum disorders (ASDs), it is still not clear whether this relates to a true increase in ASDs. Factors such as increased awareness by parents and clinicians, methods of reporting, and changing diagnostic criteria may account for this apparent increase. Examining the impact of these factors on the rate of ASD diagnoses will help to untangle whether ASDs are truly on the rise, or whether only the rate of diagnosis has increased. 

To attempt to provide the most accurate estimate of trends in the incidence of ASD, this study will analyze population-based records of ASD diagnoses which used diagnostic criteria that remained constant over time. Two datasets of ASD diagnoses will be analyzed: one from Denmark, and one from Western Australia. These datasets used different diagnostic criteria consistently (DSM for Western Australia, and ICD for Denmark). This study will determine whether the criteria used affected the age at which ASD is first diagnosed, and thus affected the perceived incidence. 

These results will help to answer the question of whether the perceived autism “epidemic” is real, and will provide valuable information for intervention services for children with ASD.

C.J. Malanga, M.D., Ph.D.
University of North Carolina School of Medicine
$450,000 for 3 years

Neuropharmacology of motivation and reinforcement in mouse models of autistic spectrum disorders

Behavioral and drug therapies are commonly used in combination to treat children with autism spectrum disorders. Behavioral therapies involve positive and negative reinforcement of motivated behaviors, the effectiveness of which rely on neural pathways involved in the perception of “reward.” However, the degree to which drug therapies can influence behavioral therapies by either enhancing or interfering with “reward” pathways is not well understood.

In this study, mouse models of autism spectrum disorders will be used to investigate the effects of drug treatment on motivated behaviors. To model behavioral therapy in mice, intracranial electrical stimulation, or ICSS will be used. ICSS measures motivated behaviors: an electrode implanted in a specific region of a mouse’s brain provides a “reward” sensation when a lever is pressed. Animals will self-stimulate by pressing the lever, and the administration of drugs known to affect the reward pathway can modulate this response. In this study, researchers will use ICSS to study motivated behaviors in three commonly used mouse models of autism (Fragile-X syndrome, Rett syndrome, and Angelman syndrome). These mice will be treated with drugs which are known to affect reward pathways, and drugs which are commonly used to treat autism, such as dopamine-blocking neuroleptics. These experiments will determine whether these drugs enhance or impair motivated behaviors in animals with autistic behaviors.

Understanding how drug treatment affects behavioral therapy and may allow for the better design of combined therapies in autistic children.

Christopher Monk, Ph.D.
University of Michigan
$450,000 for 3 years

Neural correlates of serotonin transporter gene polymorphisms and social impairment in ASD

A core symptom of autism spectrum disorders (ASD) is social impairment. A genetic variation has been identified which is associated with the symptom of social impairment, called the S allele of the serotonin transporter-linked promoter region. People who have one or two copies of the S allele in their genome tend to have increased social impairment, compared to those who have other genotypes. Neurologically, social deficits are thought to be related to overactivity of neurons in a specific brain regions, the amygdala and the ventral prefrontal cortex (vPFC). In this study, Dr. Monk and colleagues will examine the connection between the S allele and neural activity in the amygdala and vPFC, and how these factors contribute to social impairment. 

Using functional magnetic resonance imaging (fMRI), a method of visualizing neural activity in specific brain regions, they will examine the amygdala and pVFC in subjects while they perform a social task, such as recognizing emotions in facial expressions. The subjects will be chosen from four groups: autistics with two copies of the S allele or no copies of the S allele, and typical, non-autistic individuals with two copies of the S allele or no copies of the S allele. This experiment will allow the researchers to determine whether this genetic variant is associated with overactivity in the amygdala and pVFC, and how this relates to the severity of social impairment in both autistics and non-autistics.

Linking genotype to the abnormal activity of neural pathways responsible for social impairments will be important in understanding the causes of this debilitating symptom of autism.

Stewart Mostofsky, M.D.
Kennedy Krieger Institute
$450,000 for 3 years

Novel approaches for investigating the neurology of autism: detailed morphometric analysis and correlation with motor impairment

Identifying changes in brain anatomy can be a critical tool in diagnosing and evaluating neurological disorders. In studies of the brain structure of children with autism, it has been shown that the sizes of certain brain regions are increased in volume. However, more detailed information on brain anatomy than simply size will be necessary to understand the differences between autistic and non-autistic brains. In this study, the authors will use new computational tools and imaging techniques to study the structure of the autistic brain in greater detail. They will also examine whether the differences observed correlate with impaired motor skills, a common symptom of autism. 

To examine the brain structure of autistic children, these researchers will use a computational technique known as large deformation diffeomorphic metric mapping, or LDDMM, to measure not just the size but the shape of particular brain regions. They will also use diffusion tensor imaging to examine the structure of white matter tracts, which carry neural information between brain regions. These structural analyses will provide much more detail than simple measurements of the area or volume brain regions. Next, they will collect behavioral data on motor coordination from their subjects, and determine whether changes in the shape, size, or white matter tracts of any particular brain regions are associated with particular motor difficulties.

More accurate identification of changes to brain anatomy in autism may provide new and powerful tools for the early diagnosis and evaluation of autism. 

Laurent Mottron, M.D., Ph.D.
Université de Montréal
$448,827 for 3 years

Behavioral and functional neuroimaging investigations of visual perception and cognition in autistics

It has been consistently found that autism is associated with superior sensory perception, independent of social function. Autistics score very highly on tests of perceptual detection and higher-level visual reasoning. Autistics may tend to perceive the world as it is, whereas non-autistics may tend to perceive the world according to their expectations. 

In this research, Dr. Mottron and his colleagues will examine the neural basis of this enhanced visual perception and reasoning in autistics. They will use functional MRI and EEGs to image and measure the activity of specific brain regions in autistic subjects during visual problem solving and reasoning tests. Using various tests of visual perception, they will characterize the versatility, scope, and limitations of autistics’ enhanced performance on these tests, and determine which brain regions and neural pathways are involved. 

A more complete understanding of autistic individuals’ strength in perception and visual reasoning may have important implications with respect to selecting and creating parenting, teaching, and workplace strategies that leverage these abilities. 

Nicholas Ponzio, Ph.D.
University of Medicine and Dentistry of New Jersey
$449,997 for 3 years

Influence of the maternal immune response on the development of autism

Clinical and experimental evidence points to a role for the immune system during pregnancy in the development of autism spectrum disorders (ASD). Both T cells and cytokines (proteins which are produced by and regulate the behavior of immune cells) are implicated in various neurological disorders. Cytokines present in the maternal immune system can cross the placenta and enter fetal tissues, and this may affect fetal development. Preliminary results from the Ponzio laboratory have shown that the one such cytokine, interleukin-2 (IL-2) may affect fetal brain development, as the offspring of pregnant mice injected with IL-2 display abnormal behaviors. In the present study, these researchers will examine the role of maternal cytokines and immune cells as an environmental trigger for ASD.

Cytokines will be administered to pregnant mice by injection, and the effects on fetal brain development will be examined by behavioral testing of offspring for features selectively found in autism. IL-2 may act directly on the developing brain, or it may stimulate other components of the mother’s immune system which in turn affects brain development. To determine which subsets of maternal immune cells and cytokines are stimulated by Il-2 treatment, the maternal immune system will be characterized by molecular and cell immunological techniques.

Correlating the activations of the immune system during pregnancy and the development of autistic-like characteristics in offspring will have clinical relevance for understanding the underlying causes of autism.

Helen Tager-Flusberg, Ph.D.
Boston University
$450,000 for 3 years

Novel methods for testing language comprehension in children with ASD

Delays and deficits in language development are among the cardinal features of autism, and a substantial minority of individuals with autism never aquire functional speech. It is not known how much spoken language these non-verbal individuals actually understand. A key problem is that it is difficult to assess a nonverbal child’s receptive language skills using standardized testing measures. The primary goal of the present study is to develop novel methods for testing language comprehension of children with autism, and to use these methods to test developmental changes in language in preschool-aged children. 

This project will investigate the use of eye movements as a sensitive measure of language processing in young children with autism. Tracking eye movements is routinely used to measure comprehension in normally developing preverbal infants. The feasibility of using this method with preschool-aged autistic children will be evaluated using a series of experimental tasks to test the children’s comprehension of various language structures (nouns, verbs, relational language, noun phrases, verb phrases, and word order). Performance on eye-tracking measures will be compared to standardized test scores to test the hypothesis that children with autism will show significantly greater comprehension of spoken language when tested using eye-movement measures than when evaluated on standard tests. Children will be invited to return six months after their initial testing to repeat the experiments and test the sensitivity of eye-tracking measures to developmental changes in language knowledge.

This research will pave the way for developing new approaches to evaluating the comprehension skills of children with autism that can be used in research and applied clinical settings.

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