- Title: Meta-analysis in Human Brain Mapping
Principal Investigator: Peter T. Fox, M.D.
Dates: September 15, 2006 - August 31, 2010
The overall objective of the present proposal is to develop, evaluate, distribute, and apply tools for quantitative meta-analysis of the human functional brain mapping (HFBM) literature. The BrainMap database may be used as an internet-based resource for retrieval, coding, and filtering papers that is required for an HFBM meta-analysis. BrainMap has been fully implemented in a multi-platform software environment (Java) and populated with >750 papers and > 3,000 experiments (>20% of the literature meeting our inclusion criteria). It is now proposed: to extend the functionality of coordinate-based, voxel- wise meta-analysis (CVM) (Aim 1); to extend network analysis of CVM datasets (Aim 2); to create optimal high-resolution brain templates for spatial normalization that are representative of large groups of subjects (Aim 3); and to develop methods for returning functional labels and metrics of label likelihood for any given anatomical coordinate and serve these labels through a function-label extension of the Talairach Daemon (Aim 4). In addition, we propose a structured data-sharing plan that will provide a formal means for sharing software tools, meta-analyses, a functional ontology, and coordinate data of the published HFBM literature. Addressing these aims will greatly advance the current status of meta-analysis in functional neuroimaging. The evaluations associated with each development will provide guidance for further development of tools and logistics.
- Title: Support for GENESIS
Principal Investigator: James Bower, Ph.D.
Dates: September 1, 2004 - June 31, 2013
The General Neural Simulation System (GENESIS) was first released for general use in 1988 as part of the first Methods in Computational Neuroscience Meeting at the Marine Biological Laboratory in Woods Hole, MA. Since its original release 19 years ago, GENESIS has provided one of the foundations for the growth of computational neuroscience both continuing to support education as well as research. With respect to summer courses, GENESIS continues to be part of the course in Woods Hole, as well as courses offered in the European Union, Mexico, India, Japan, and recently a new course in Brazil for Latin America. At last count GENESIS has also provided support for courses in at least 61 colleges and universities around the world where it has been used both as an instruction tool in realistic modeling of the nervous system, and as a simulation based tool for neurobiological education in general. The Book of GENESIS (Bower and Beeman, 1994, 1998), which was designed to support both computational and neurobiological instruction has sold more than 6,000 copies worldwide with more than double that number of copies having been distributed with the text now freely available on the Internet (Bower and Beeman, 2003). This substantial support for the use of GENESIS in instruction has also provided the base for extensive and growing use of this software system in biological research. Although certainly an underestimate, we are aware of 297 published GENESIS-dependent peer reviewed journal articles and book chapters not directly related to research in the P.I.'s laboratory. Further, more than a third of those reports (103) have been published during the period January 2004 to June 2007 (approximately the duration of the current NIH grant). As measured by the subjects of these publications, use of GENESIS has a growing emphasis on two types of simulations, those of large scale networks (using the parallel version of the platform), and those involving molecular biological modeling. GENESIS remains the only simulation system specifically designed from the outset to link multi-scale modeling efforts. With this grant, we seek continuing funding to support the expanding use of GENESIS, but also and importantly, to complete the implementation of a new version of the GENESIS platform. While maintaining backwards compatibility, GENESIS 3.0 is a complete rewrite and redesign of the system, replacing a 19-year-old structure. The rewrite will update and upgrade core GENESIS functionality while adding important new features, including model history control and tracking, a new web browser interface, and new features to support education as well as scholarly publication of models. Project Narrative Biological simulation technology is becoming an increasingly important part of both basic and translational research in medicine. The GENESIS system supported by this grant is one of the most used software systems supporting this type of research in the US, and will provide continuing support for the use and further development of this modeling platform. Newly proposed extensions include applications to medical education and scientific publishing as well as the continuing efforts to understand brain function and dysfunction.
- Title: Models of the Cerebellar Purkinje Cell and Cortex
Principal Investigator: James Bower, Ph.D.
Funding: National Science Foundation
Dates: 8/01/05 – 07/31/09
The purpose of this grant is to support a continuing series of combined modeling and experimental studies exploring the influence of the granule cell/parallel fiber afferent system on cerebellar Purkinje cells. Fundamental assumptions concerning the physiological effects of this pathway, and especially its parallel fiber component, are central to most theories of cerebellar cortical function. Most assume that synapses made by parallel fibers on Purkinje cells provide the primary excitatory drive on this cell’s output. Our previous NSF supported work have instead suggested that parallel fiber effects are modulatory, rather than “driving” due to counterbalanced influence of molecular layer inhibition. In fact, one of the major overarching results of our work to date is a new appreciation for the importance of molecular layer inhibition and in particular its relationship to parallel fiber excitation. What has emerged is a very different view of cortical circuitry. In this grant, we propose to continue our studies of the functional organization of cerebellar cortical circuitry by specifically experimentally testing modeling predictions regarding the role of molecular layer inhibition. This effort is expected to have a direct influence on our evolving understanding of the function of this important brain region.