The Children's Hospital of Philadelphia, Philadelphia, PA
2011-2013
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
The
Children's Hospital of Philadelphia, Philadelphia, PA
2008-2011
Principal
Investigator: Timothy Roberts, Ph.D.
Neonatal
Biomagnetometer (Co-Funded with the Lurie Family Foundation)
In
partnership with the Lurie Family Foundation, the NLM Family
Foundation has provided funding to the Children's Hospital
of Philadelphia for the purchase of a Neonatal Biomagnetometer,
a magnetoencephalography (MEG) system that provides non-invasive,
4-dimensional imaging of human brain function necessary
to detect developmental disorders. When installed, this
system will serve as the world's first dedicated infant-MEG
system serving children 18 months to two years, thereby
providing better opportunities for successful, appropriate
interventions to occur at an earlier age. This technology
conducts passive recordings of "brain waves" during
rest or stimulation through finger-tapping, sounds, and
pictures. A typical scan of the brain may take less than
one hour. MEG measures small electrical currents inside
the neurons of the brain and generates an accurate representation
of the magnetic fields produced by the neurons. Developmental
disorders, including autism spectrum disorders, attention
deficit hyperactivity disorders and learning disabilities,
exploit the ability of MEG to track deficits in rapid temporal
processing. This helps identify when and where in the brain
and at what stage of linguistic complexity deviations from
typical development occur, providing physicians with better
opportunities to treat children with the most appropriate
form of care. In addition to providing physicians with the
best insight into the exact location of abnormalities that
cause epilepsy and seizure disorders, the MEG also provides
state-of-the-art, pre-surgical mapping for brain tumors
and vascular malformations so that surgery can be planned
in an effort to minimize postoperative weakness or loss
of brain function.
Click
here to read the NLMFF Interview with Dr. Roberts
Children's
Hospital of Philadelphia
The Children's Hospital
of Philadelphia, Philadelphia, PA
2007-2010
Principal Investigator: Timothy Roberts, Ph.D.
MEG of Language Impairment in
Autism (Co-funded with the Lurie Family Foundation)
Language impairment is a devastating
feature of Autism Spectrum Disorders (ASD); however, presence
and severity of language impairment varies across the spectrum.
The purpose of this project is to use advanced brain imaging
(magnetoencephalography) to identify the temporal stage
of language processing, and the neural substrates thereof,
that depart from typical development in children with autism.
Using a battery of auditory processing and linguistic stimuli,
the investigator seeks to identify neural signatures or
endophenotypes, with which to more specifically characterize
language impairment in autism. Additionally, the use of
characteristic brain-level endophenotypes will be explored
as a mechanism for tightening the connection between experimental
and clinical laboratories. Experimental models of autism
might now be evaluated in terms of such electrophysiological
(as well as behavioral) traits associated with ASD and thus
provide a more specific approach for understanding the underlying
neurobiology. Furthermore, such specific brain-level phenotyping
may offer more specific measures for ongoing genomic efforts
at the Children's Hospital of Philadelphia and elsewhere.
Click
here to read the NLMFF Interview with Dr. Roberts
Children's
Hospital of Philadelphia
Massachusetts General Hospital, Boston, MA
2007-2010
Principal Investigator: Tal Kenet, Ph.D.
Sensory Perception Deficits and Cortical Coherence in Children with
Autism: A Study of the 'Noisy Cortex' Hypothesis
Autism is a behaviorally diagnosed disorder with defining impairments
in socialization, interests, and communication abilities.
Autism is also characterized by deficits in processing of
simple visual and auditory information such as loudness
discrimination or perception of moving dots, as well as
complex visual and auditory information such as faces and
language. Additionally, there is evidence of abnormal tactile
sensitivity in autism. These functional findings are complemented
by anatomical ones, the most robust of which is that the
brains are large. Other neuroanatomical findings include
neuroinflammation, and disrupted inhibitory circuitry. To
date, no robust models have been formulated for either the
neurobiological origin of the observed abnormalities, or
the relationship between the pervasive anatomic abnormalities
and the neural systems dysfunctions which are characteristic
of autism. Furthermore, while the observed anatomical pathologies
are distributed rather than localized, the vast majority
of functional studies focus on localized features. The main
objective of this project is to test the model that the
neural substrates underlying the functional deficits of
autism at the cortical level stem from a noisy cortex which
has a poor signal to noise ratio. To this end, Dr. Kenet
will employ magnetoencephalograpy (MEG) to record functional
activation in response to sensory stimuli in children with
autism and age matched controls. The central hypotheses
are: (1) that the cortex of individuals with autism is inherently
and internally a "noisy" cortex, i.e. a cortex with a low
signal to noise ratio; (2) that the "noisiness"
of the cortex is widely distributed rather than localized,
resulting in widespread functional abnormalities; and (3)
that from this distributed "noisy" cortex emanates
a network in which connectivity is disrupted, with ensuing
functional abnormalities that include widespread perceptual
deficits, and alterations in neural circuitry that may drive
higher order cognitive and social impairments emanating
at least in part from abnormal network properties.
Massachusetts General Hospital, Martinos Center for Biomedical Imaging
Massachusetts General Hospital , Boston , MA
2010
Principal Investigator: Martha R. Herbert, M.D., Ph.D.
NIRS Imaging and its Utility and Importance in Infants
The investigators are engaged in a DoD-funded comprehensive multisystem study of development beginning in early infancy to allow them to understand the mechanisms by which autism's brain-behavior-body relationships emerge. They propose that Near-Infrared Spectroscopy (NIRS) can make a unique contribution to studying autism's emergence by providing an infant- and toddler-friendly technology for examining the metabolic and vascular underpinnings of brain changes in early autism. They propose that NIRS measures of cerebral perfusion and of the redox state of the mitochondrial marker cytochrome c oxidase may provide objective early indicators of risk for autism. Reduced cerebral perfusion has been abundantly documented in autism, and mitochondrial abnormalities are of emerging interest as well. The investigators hypothesize that these cerebral and metabolic changes may temporally precede behavioral abnormalities. They propose that their detection may eventually allow the early institution of medical measures that could improve perfusion and mitochondrial function and that this could prevent autism or reduce its severity. They also propose that the investigation of neurovascular coupling, which can be done by simultaneous NIRS-EEG, may illuminate changes which may arguably be at ground zero of autism. If abnormalities in cerebral perfusion and metabolism develop dynamically in infancy in at least some cases, they may be central to mechanisms of autistic regression. Early detection of these abnormalities could lead to avenues of early medical intervention or even prevention of autism. The purpose of this equipment grant will be to purchase an OxiplexTS FD-NIRS system ISS Inc. device which would allow the investigators to perform the above measures. They will initially study those at-risk infants in the DoD funded study, "A Multisystem Evaluation of Infants At Risk for Autism" whose parents would consent to this additional evaluation, and will also seek funding for a larger cohort and for studying older children and adults.
Martha Herbert
Massachusetts General Hospital , Boston , MA
2006-2009
Principal Investigator: Martha R. Herbert, M.D., Ph.D.
Electrophysiological Studies of Gating, Timing and Connectivity in Autism
Although
autism is defined by three types of behavioral impairments,
recent findings in autism research are pointing toward widespread
network signal coordination or connectivity problems as
underlying what we see as autism - various parts of the
brain do not synchronize normally. Reduced connectivity
has been found using methods that are better at locating
things in space than in time; for example, functional MRI
can give us pictures of where the brain activates but is
not useful for revealing the sequence of activation, because
it cannot register changes that happen in intervals shorter
than a second. Electroencephalography (EEG) on the other
hand has a time resolution at the millisecond level-more
than a thousand times more fine-grained time resolution
than can be achieved with MRI. To get the most detailed
measurements of short range and long range coordination
(which the investigator expects will each have a different
kind of abnormality in autism) it is necessary to use a
high-density electrode array which covers as much of the
entire scalp as possible with electrodes that are closely
spaced. To do so, the NLM Family Foundation supported the
purchase of a 128-lead EEG machine to upgrade the investigator's
capacity from her 32 lead system which limits the measurements
she can make. The investigator believes that electrophysiological
measures are key to showing the ways that brain functional
changes are related to sensorimotor, perceptual, learning
and behavioral differences in autism.
Martha Herbert |
