Driving Biological Projects
 As noted in Core 1, Computational Foundations, the overall goal of this inter-disciplinary, multi-institutional
center is to create, develop, deploy, and train others in the use of computational tools for
the quantitative analysis and visualization of medical imaging data. Our ultimate goal is to develop
tool elements that can be reused and linked into any flexible fabric for linking operations important to
refining, analyzing, collaborating on and presenting / depicting / sharing biomedical image data.
To focus the technical development of such tools, Driving Biological Projects from schizophrenia
will be used initially, and then replaced with subsequent DPBs from other diseases, e.g., multiple
sclerosis, Alzheimer’s disease, epilepsy, and prenatal alcohol syndrome. We view schizophrenia as a
particularly appropriate choice because it is a disorder that has been the focus of many neuroimaging
studies, including collaborations with computer scientists. All of these efforts have led to important
advances in the field. New developments in neuroimaging promise to take our understanding even
further, to a more complete understanding of the neural circuits that are disrupted in schizophrenia as
well as the relationship between brain abnormalities, cognitive functioning, and genetic influences.
The overall goal of Core 3 is to use computational tools for the quantitative analysis and
visualization of MRI, Diffusion Tensor Imaging (DTI) and fMRI, to further our understanding of brain
abnormalities in schizophrenia and other brain diseases. Core 3 has four Driving Biological Projects
(DBPs), which are grouped into two thrusts.
Core 3-1--Thrust 1 is directed by Drs. Shenton (DBP1) and Saykin (DBP2). The focus of this
thrust is to utilize neuroimaging tools to evaluate fronto-temporal connectivity abnormalities in
schizophrenia, as well as abnormalities in hemispheric connections (i.e., corpus callosum), and
abnormalities in the anterior limb of the internal capsule. Improved segmentation techniques, coregistration
of structural MRI, DTI-MR, and fMRI, as well as novel processing tools for evaluating
white matter fiber tracts and interregional functional connectivity are needed to accomplish these
goals, and they will be developed in conjunction with Cores 1 and 2. Findings from this project, which
involve both structural and functional information about brain abnormalities in schizophrenia, will be
correlated with neurocognitive, clinical, and behavioral data in order to understand further the
relationship between brain abnormalities and cognition/behavior in schizophrenia. Common imaging,
cognitive, and clinical measures will be used across both sites (DBP1 and DBP2). This shared
approach has led the PIs to combine the scientific aims into one proposal, rather than two (thus
combining the allowable number of pages).
Core 3-2—Thrust 2 is directed by Drs. Steven Potkin (DBP3) and James Kennedy (DBP4). The
main thrust of this core is to utilize improved segmentation, co-registration, statistics, and circuitry
analysis tools to evaluate abnormal brain networks in schizophrenia. The dorsal prefrontal cortex and
its associated local and distal connections are viewed as key to understanding schizophrenia.
Abnormalities in dorsal prefontal cortex structure and function, either primary or secondary to its
many connected regions, as revealed by MRI, are viewed as explaining various characteristics of the
illness. It is well documented that schizophrenia is heritable; therefore, the genetic contribution will
also be considered by developing innovative methods in conjunction with Cores 1 and 2, which will
combine imaging data, genetic data, neurocognitive data, and clinical profiles. Newly identified
patterns will form subgroups of characteristics, and perhaps endophenotypes, of the illness. Such
definition will move us closer to the underlying biology, aiding our further understanding of the
etiology of schizophrenia and leading to the development of newer and more effective treatments.
The collaboration between Irvine and Toronto will bring together capabilities in schizophrenia, brain
imaging, and genetics, as well as the essential expertise as DBPs for Cores 1 and 2. |
