The Children's Hospital of Philadelphia, Philadelphia, PA
Principal Investigator: Timothy Roberts, Ph.D.
Longitudinal MEG of Auditory Processing in ASD
The project will be supported by the resources of the Children's Hospital of Philadelphia (CHOP). This will allow for the utilization of the extensive expertise of the scientific staff (physicists, neuropsychologists, neuroscientists, bioengineers, radiologists) as well as the support staff (research assistants, MR technologists, etc.). CHOP has extensive non-invasive imaging resources including whole-cortex magnetoencephalography (MEG), 3T MRI with 32-channel head coil and very large autism and control populations. The project builds upon extensive structural and functional studies of the auditory system in autism that Dr. Roberts’ group has conducted over the last five years, funded in part by the NLMFF. Given the strong evidence for an abnormal trajectory of brain development in autism spectrum disorders (ASD), set in the context of inter-subject heterogeneity, this study adopts an intra-subject longitudinal design in a well-characterized cohort, with advanced functional, structural imaging (including imaging of white matter, recording of brain waves, and measurement of brain chemistry) and neuropsychological assessment follow-up of this cohort at 2+ years of their original exam.
Click here to read the NLMFF Interview with Dr. Roberts
Children's Hospital of Philadelphia
Massachusetts General Hospital, Boston, MA
Principal Investigator: Martha Herbert, MD, PhD
Magnetic Resonance Pilot Study of Brain Tissue Pathophysiology and Perfusion in Autism
This project addresses how we can learn about ways that several different aspects of the brain interact with each other, and how these interactions may be different in people with Autism Spectrum Conditions (ASCs) as compared with people who have had typical development (TDs). Specifically, the brain is both a physical organ with cells, blood flow, fluids and metabolic processes – and also an information-processing system that generates, relays and coordinates signals.
This study is designed to test whether there is a relationship between problems with the physical functions of the brain and problems with the signaling functions of the brain in ASCs. The reason Dr. Herbert’s team thinks that such a relationship exists is that the physical brain is responsible for generating the brain’s electrical signals, and if there are problems with the health of the brain tissue, this is likely to compromise the quality of the signals the brain is able to generate. There are ways of measuring each aspect of brain function in living individuals using non-invasive scanning methods, which do not require any injections and are not known to carry health risks. Dr. Herbert’s group can use the magnetic resonance (MR) scanner to measure the density of various chemicals in the brain, the quality and density of the fibers connecting the neurons, and the rate and intensity of blood flow. They can use electroencephalography or magnetoencephalography to measure the intensity and patterns of signals in the brain. They will use several MR scanning techniques to measure physical properties of the brain including 31Phosphorus Spectroscopy, Proton (1H) Spectroscopy, Glutathione Spectroscopy, GABA Spectroscopy, and Arterial Spin Labeling.
All of the children in this study will be part of a study where their brain signaling is measured by MEG. Therefore Dr. Herbert’s group will be able to compare the brain tissue and brain chemistry measures from Magnetic Resonance scanning with the brain signaling measures from MEG. This study is the first time these various measures have been combined. If correct in their predictions, Dr. Herbert’s group will proceed with using this collection of measures to evaluate the impact upon the brain of treatments, particularly those that target either metabolism or electrical brain signaling. They may find stronger effects in some measures than others, and this will help them to sharpen the studies that follow this pilot study.
TRANSCEND Research Laboratory- Martha Herbert
Massachusetts General Hospital, Boston, MA
Principal Investigator: Tal Kenet, Ph.D.
Local Functional Connectivity in ASD (Co-funded with the Simons Foundation)
Functional connectivity in the brain refers to the synchronization of neuronal assemblies for the purpose of transferring information within and between these assemblies. Long-range cortical functional connectivity refers to connectivity between distant cortical areas, and is often reduced in autism spectrum disorders (ASD). The nature of local cortical functional connectivity (connectivity within a neuronal assembly) has remained elusive in studies of ASD, but it has been generally believed that local functional connectivity is increased in ASD. Dr. Kenet and colleagues used magnetoencephalography (MEG), a technique that reveals cortical activity with high spatial and temporal resolution, to measure functional connectivity both locally and between distant cortical regions while ASD and typical individuals viewed houses and faces. Contrary to the prevailing hypothesis, they showed that local functional connectivity was reduced, not increased, in ASD. Furthermore, the strength of local functional connectivity correlated with ASD severity, and statistical classification using local and long-range functional connectivity data identified ASD diagnosis with 90% accuracy. Finally, they found that the strengths of local and long-range functional connectivity were correlated in both ASD and typical individuals. These results suggest that failure to adequately synchronize neuronal assemblies both within and across cortical regions is characteristic of ASD. For this grant, Dr. Kenet’s group will study local functional connectivity in ASD in multiple cortical areas during performance of both visual and auditory paradigms by younger subjects. Second, they will examine the links between local and long-range functional connectivity, to determine how the two patterns interact. Lastly, they intend to identify a set of measures of local and/or long-range functional connectivity that correlate highly with diagnosis and severity of ASD, for future development into early biomarkers of ASD.
Massachusetts General Hospital, Martinos Center for Biomedical Imaging