Email this articleDate: 2009-04-02
Contact: Phyllis Brown
Phone: (916) 734-9023
Email: phyllis.brown@ucdmc.ucdavis.edu
SACRAMENTO -- The National Institutes of Health (NIH) has awarded Tony J. Simon, pediatric cognitive neuroscientist with the UC Davis M.I.N.D. Institute, a five-year, $2.6 million grant to study the syndrome associated with single most common genetic deletion in humans -- chromosome 22q11.2 deletion syndrome (22q11.2DS).
The deletion can lead to cognitive impairments and result in a broad range of disorders, including autism, attention-deficit hyperactivity disorder (ADHD) and schizophrenia.
"This grant will enable us to, through careful measurement, test both neurological and cognitive targets for 22q11.2 DS that will potentially lead us to the development of interventions and treatments," said Simon, associate professor-in-residence in the Department of Psychiatry and Behavioral Sciences and the director of the M.I.N.D. Institute's Cognitive Analysis and Brain Imaging Laboratory.
Simon's research focuses primarily on the learning difficulties associated with 22q11.2DS. By analyzing results from cognitive-processing experiments, Simon has advanced the hypothesis that children with learning disabilities with 22q11.2 DS have problems understanding space, time and approximate quantities and numbers -- what he calls 'spatiotemporal hypergranularity.'
"When the brain of one of these kids processes information about space and time, the result is poorer resolution -- just as a picture taken with a two megapixel digital camera cannot represent information with the same degree of detail as a 10 megapixel camera," Simon said. "That makes it impossible for them to process small distinctions in time, distance, length or related measurements. This affects the child's ability to construct more high-level conceptual knowledge about quantities and numbers."
Chromosome 22q11.2 deletion syndrome is also commonly referred to as Velocardiofacial syndrome or DiGeorge syndrome. The label also covers several other disorders with the same genetic cause. The deletion occurs near the middle of the 22nd chromosome at a location designated q11.2. The condition affects approximately one in 4,000 people worldwide and is linked to more than 180 physical, psychological and behavioral anomalies, including congenital heart defects, cleft palate and other medical conditions. Children with 22q11.2DS are at increased risk of ADHD, autism spectrum disorders, obsessive-compulsive disorder, and, later in life, schizophrenia.
A key part of Simon's research involves brain imaging that measures the brain's structure and connective patterns while they watch movies or work on tasks. Simon initially expected these studies would show signs of the disorder on more lateral, or exterior, cortical areas of the brain. These tend to be associated with goal-directed spatial task processing. Instead, most structural changes were located in the central or middle part of the brain, especially in such subcortical areas as the posterior thalamus and basal ganglia.
Simon said he thinks that anomalous development and dysfunction there probably sets off a cascade of problems in the circuitry of the later-developing, task-oriented parts of the brain. This might be the reason why children with the deletion aren't able to build brain circuits to optimally represent either spatial and temporal information or the numerical and mathematical information that relies on these more basic capabilities for its construction during development.
The NIH grant will allow Simon to measure spatial and temporal capabilities in a far more targeted way than before. That would allow Simon to lay the groundwork for research that would examine brain and cognitive differences during development of very small children with the deletion, to determine how, when and why the changes in mind and brain develop.
Simon also is preparing to develop highly specialized tools based on video games to expand those spatial and temporal capabilities and, potentially, a drug counterpart, derived in part from work being conducted at the M.I.N.D. Institute and elsewhere on fragile X syndrome, another main focus of Simon's laboratory.
"What's exciting about the grant is that we now have a target and are poised to test a clearly defined theoretical statement concerning the processing of space and time," Simon said. "My fondest hope is to help develop successful interventions so that one day those with this disorder can develop with few impairments in behavior and cognition, enabling them to lead full and productive lives."
The UC Davis M.I.N.D. Institute in Sacramento was founded in 1998 as a unique interdisciplinary research center where parents, community leaders, researchers, clinicians and volunteers collaborate to study and treat autism and other neurodevelopmental disorders. More information about the institute is available on the Web at
www.ucdmc.ucdavis.edu/mindinstitute.
