- Title: Neuroscience Training Program
Principal Investigator: Peter T. Fox, M.D.
Funding: NIH 5T35NS051166-04
Dates: July 1, 2005 - June 30, 2010
This is a new proposal to establish a training program for medical students in neurological research. The overall goal of the program is to train medical students for independent careers in basic and translational research. Research in the field of human brain mapping (HBM), an experimental discipline that establishes structure-function correspondences in the brain through the combined application of experimental psychology, human neurological science, and non-invasive neuroimaging will be emphasized. In HBM, meta-analysis is a tool for modeling neural systems wherein statistically significant effects from multiple studies are combined to assess convergence and guide interpretation. The primary goal is to quantitatively determine locations of consistent activity within the literature for certain paradigm classes and/or behavioral domains. This research training program is focused on the meta-analysis method known as activation likelihood estimation (ALE), a new technique developed at Georgetown Univ. In ALE, input data are location coordinates placed on a 3D image matrix and blurred using a Gaussian spread function that approximates intersubject anatomical variability. Students will be guided towards performing their own meta analysis on a wide range of topics, including, but not limited to, working memory, emotion provocation, and word generation. The faculty members comprise an interactive cadre of MD and PhD scientists who possess extensive research and mentoring experience. We have specific plans for recruitment and for identifying candidates from underrepresented racial/ethnic groups that capitalizes on our regional and institutional demographics. The laboratory training in this program will be complemented by enrichment activities and didactic instruction concerning ethical issues in medical research and the responsible conduct of research. Program administration will be overseen with periodic evaluation and strategic planning input from an External Advisory Committee comprised of six scientists with expertise relevant to research training.
- Title: International Conference on Functional Mapping of the Human Brain
Principal Investigator: Peter T. Fox, M.D.
Funding: NIH 5R13MH062008-09
Dates: September 15, 2000 - May 31, 2010
The mission of the OHBM is to promote the field of structural and functional brain mapping. In particular, OHBM emphasizes non-invasive, image-based investigation of the functional organization of the human brain. Trainees travel awards have been in place for the past 5 years. They support travel trainees who are first author on the most highly ranked abstracts. In past years, awardees have given more than 1/3 of all oral presentations at the annual meeting. Trainees include medical students, graduate students, residents in clinical neuroscience (neurology, psychiatry, neurosurgery) and post-doctoral fellows in fields related to human brain mapping. This program has been in effect for 5 years, with remarkable success. Past meetings of OHBM were in: Paris, France, 1995; Boston, MA, 1996; Copenhagen, Denmark, 1997; Montreal, Canada, 1998; Dusseldorf, Germany, 1999; San Antonio, Texas, 2000; Brighton, England, 2001; Sendai, Japan, 2002; and New York, NY, 2003. Upcoming meetings are planned for: Budapest, Hungary, 2004; Toronto Canada, 2005; Florence Italy, 2006; Melbourne Australia 2007; and Chicago, III 2008. This meeting has relevance for the NIMH in the following ways. First, virtually every presentation relates to the function and structure of the human brain, in both health and disease. Second, 1/6 of the scientific program (2 to12 themes) is devoted to the latest methods for image acquisition,analysis and metanalysis, i.e. neuroinformatics. Third, the entire educational program is devoted exclusively to the methods used to study the brain, with a strong emphasis on image anlaysis and other aspects of neuroinformatics.
- Title: Combining Neuroimaging and Genetics for Heritability Measurements
Principal Investigator: Peter Kochunov, Ph.D.
Funding: NIH 5K01EB006395-02
Dates: June 1, 2007 - May 31, 2012
Neuroimaging and genomics are two primary evolving arenas of modern neuroscience. However, despite the attractiveness of combining these two approaches they have rarely been merged to fully capitalize on their power. These fields, while disparate, have common features such as an ability to obtain very precise, non-invasive quantitative information using complex computational modeling. Bridging quantitative neuroimaging based phenotyping and statistical genomics creates a new field - genomic imaging. The purpose of this application for a mentored career development award, is to transition Peter Kochunov from a neuroimaging specialist to an independent investigator in genomic imaging. This will combine neuroimaging and analytical genomics methodologies to execute studies that will contribute to a better understating of the genetic underpinnings of brain structures. This could provide the basis for discovering new molecular targets and other approaches for the characterization, treatment and potential prevention of brain disorders and will constitute a significant advance for basic neuroscience. Genetically complex brain diseases cost the United States as much as $1.2 trillion annually. Insight into the biological underpinnings that predispose individuals to these types of illnesses hold the promise of yielding new therapeutic strategies and a significant reduction of this considerable health and financial burden. The outcome of this training will result in genomic image processing methods by which one can perform statistical genomics measurements on multi-dimensional phenotypes describing inter-subject cerebral variability in a pedigree-type scenario. This project will use state-of-the-art 3D MR brain images obtained from baboon and human pedigrees and genetic maps to calculate genetic control of gyral gray matter thickness, cortical shapes and regional white-matter anisotropy. We will perform interspecies comparisons and study the genomics of age-related atrophy trends in humans. The data sample consists of 200 pedigreed baboons (Papio hamadryas) and ~1000 human subjects from a previously studied Mexican- American pedigree that are genotyped for a 10 cM genetic linkage map and imaged with a state-of-the-art MR structural imaging protocol. Novel variance components methods will be developed to allow genetic analysis of the MR-derived multi-dimensional phenotypes. In addition to generating valuable, new data, this project will allow Peter Kochunov to undertake rigorous training in analytical genomics and accumulate first hand experience in executing genomic studies.
- Title: Neuroanatomical endophenotypes in Persistent Developmental Stuttering
Principal Investigator: Matthew Cykowski, M.D.
Funding: NIH 5F32DC009116-02
Dates: August 1, 2007 - July 31, 2009
Persistent developmental stuttering (PDS) affects 1% of the adult population with a lifetime incidence of approximately 4%. The major aim of this application is to identify quantitative neuroanatomical endophenotypes associated with PDS. Endophenotypes are susceptibility-related phenotypes, even in individuals who do not overtly display symptoms of a disorder. Linkage analysis of stuttering can use endophenotypes to understand the genes implicated, an approach now taken in many complex genetic disorders. Knowing the genes predisposing susceptibility to PDS will aid in the understanding and treatment of the disorder. Understanding the nature and cause of PDS is one of the missions of the NIDCD, Voice, Speech, and Language Program. The proposed work also falls in line with other stated goals of the NIDCD, such as understanding the genetic bases of language disorders in childhood, a natural future extension of this work. There are two specific aims in the application which will complement the solid foundation of behavioral and neurophysiologic traits of adults who stutter (AWS) with quantitative neuroanatomical traits. This is based on the reasoning that: PDS is a complex genetic disorder, endophenotypes are now routinely used to study such disorders, brain morphology has several highly heritable features, and preliminary studies suggest PDS is associated with subtle cortical folding abnormalities. Specific Aim 1 of this project will characterize the cortical thickness (Aim 1A) and regional gyrification profiles (Aim 1B) of AWS. This will be done by rater-indendent means using automated image analysis tools. Additionally, diffusion-weighted imaging will be employed in Specific Aim 2 to assess the connectional architecture of the brain, through tract-based comparisons (Aim 2A) and a tract-tracing approach to the corpus callosum (Aim 2B). The studies of Aim 2A are appropriate because studies of AWS have described focused abnormalities in the left hemisphere speech system with diffusion tensor imaging. The proposed work will attempt to first replicate, and then extend, this potential endophenotype. Additionally, tractography methods will be used to evaluate hypothesized aberrant connections within the corpus callosum, a highly heritable structure. These studies will provide a rater-independent, cost-effective, minimally-invasive tool for dissecting the genes involved in susceptibility to the disorder. Relevance : Developmental stuttering is a speech disorder affecting both children and adults. It is known to have a genetic basis, but the genes involved are still largely unknown. Understanding the genetic basis of the disorder will help improve diagnostic approaches and treatment strategies.
- Title: US Psychiatric Genetics Research Training Program
Principal Investigator: Michael A. Escamilla, M.D.
Dates: July 1, 2006 - June 30, 2009
The goal of this training grant is to provide U.S. biomedical scientists (MD and PhD) with the skills needed to study the genetic basis of mental illness in the American Latino population. This training program will build on several NIH funded genetics research projects on mental illnesses in Latinos being conducted at the Psychiatric Genetics Center (PGC) at the University of Texas Health Sciences Center at San Antonio (UTHSCSA). We currently have a training program in psychiatric genetics for mental health professionals from Costa Rica (funded by the NIMH and the Fogarty International Center). This grant will enable us to educate U.S. based researchers with the same extensive training program currently available to Costa Rica scientists, training will cover five main areas: 1) Characterization of psychiatric phenotypes and endophenotypes, 2) Cultural competence as applied to research in Latino populations, 3) Molecular biology methods and techniques for the mapping and identification of genes which predispose to mental illness in the Latino population, 4) Statistical analysis of collected data and 5) Ethics of psychiatric genetics research with cross-ethnic populations. This program proposes to provide training along three tracks: Track 1 consisting of 9 months of training for PGY III and IV Psychiatry Residents. Track 2 consists of 2 to 3 year clinical research fellowships for Psychiatrists and/or Psychologists (expected to have recently completed their specialty training). Track 3 will consist of 2 to 3 years of training for basic science post-doctoral trainees. At the completion of their training, students will have acquired expertise in the field of Psychiatric Genetics, in conducting ethical, effective research with Hispanic populations and in developing collaborative endeavors with researchers from the U.S. and Latin America. The principal goal of our current training grant application is to develop a cadre of investigators with the ability to design and carry out psychiatric genetic research studies in the Latino population of the United States. Specific aims of the program follow.