Jeffrey Schall - US grants

DESCRIPTION (Adapted from the applicant's abstract): Normal vision begins and ends with a rapid, saccadic eye movement. While much is known about the final stages of saccade generation in the brainstem as well as about the first steps of visual processing, there is no information about how the target for a saccade is selected. Thus, the long-term objective of the proposed work is to understand how pattern recognition by the visual system and cognitive processing direct gaze. The purpose of these experiments is to investigate the respective roles in saccade target selection of two specific areas of cerebral cortex in rhesus monkey (Macaca mulatta): the frontal and supplementary eye fields, which are at the interface of visual processing and motor output. While in previous neurophysiological studies of these areas, saccades were directed by a single target, the proposed experiments are designed to study the neural activation associated with saccades generated in response to more complex stimulus arrays. Single neurons will be recorded while monkeys generate saccades to perform a variety of visual detection, search and matching tasks. The analysis of the data will aim to distinguish neurons with activity not solely dictated by the arrangement of the stimuli or the execution of the saccade but instead reflecting the processing required to discriminate the target from the distractors. Neuronal activity will also be recorded while monkeys generate saccades to stimuli presented during binocular rivalry in an effort to understand the factors involved in bringing the target to conscious awareness. The strength of this proposal lies in the simultaneous assessment of visuomotor behavior and the activity of neurons which are candidates for generating key elements of the observed behavior. Successful completion of these experiments will provide new knowledge about the neural mechanisms in frontal cortex responsible for selecting the target for a saccade and generating visually-guided eye movements. This information is necessary for understanding the nature of the gaze control problems associated with frontal lobe dysfunction consequent to a number of diseases.

DESCRIPTION (Adapted from applicant's abstract): The long-term goal of our research is to understand how the visual system decides where to look. The activity of many neurons will be monitored simultaneously in monkeys performing visual search tasks. Experiments will manipulate the properties of targets and distractors across or within trials. The frontal eye field will be studied because it is positioned anatomically to convert the outcome of visual processing into a command to orient gaze. The visuomotor thalamic nuclei that are connected with frontal eye field will be studied because very little is known about thalamocortical transformations in this pathway. Patterns of ensemble neural activity will be analyzed to evaluate specific hypotheses abut how visual information is encoded and flows between visual selection and saccade programming stages of processing (Aim 1) and to determine how cognitive representations influence the visual selection process (Aim 2). Reconstructions of recording sites will be correlated with connectivity and architecture to describe the functional architecture of the frontal eye field (Aim 3) and the visuomotor thalamic nuclei (Aim 4). Understanding how the brain normally selects visual stimuli for action is necessary to understand the causes of impaired visual behavior.

DESCRIPTION (provided by applicant): The long-term goal of this research is to understand how the brain controls and monitors the actions it produces to gain insight into the causes of dyscontrol underlying various psychopathologies. The activity of ensembles of neurons and local field potentials will be monitored in targeted layers of the frontal lobe of monkeys performing a saccade countermanding task that probes the ability to inhibit a movement at different degrees of preparation by presenting an infrequent but imperative stop signal. The frontal eye field will be studied to further elucidate the neural activity that determines whether and when a movement will occur. The supplementary eye field and anterior cingulate cortex will be studied to characterize the neural concomitants of supervisory control signals and to determine how executive control is exerted. Patterns of ensemble neural activity and laminar local field potentials will be analyzed through procedures specified by the race model of stop signal task performance to evaluate specific hypothesis about how the brain initiates and inhibits movements (Aim 1), monitors the consequences of movements (Aim 2) and exerts executive control to improve performance (Aim 3). These data will contribute to distinguishing between error, feedback and conflict monitoring theories of executive control.

animal care; vision; biomedical facility;

DESCRIPTION (provided by applicant): Sixteen members of the Vanderbilt Vision Research Center (VVRC) request continued support for predoctoral and postdoctoral training. Vision researchers at Vanderbilt have maintained an exceptionally strong training record with excellent research progress. Aggressive faculty recruiting during the last grant period has doubled the number of qualified preceptors and the number of NEI-funded research grants extending the program of research and training from traditional psychophysics and visual neuroscience to molecular eye research. Individuals trained during the last grant period have obtained competitive postdoctoral or faculty positions and developed independent careers in vision research. Training will continue in visual neuroscience and psychophysics and will be extended to molecular mechanisms in the eye such as transduction, retinal processing and retinal disease. Specific program requirements for predoctoral trainees include (1) The Visual System, a course team-taught by program faculty, (2) additional courses specified by the trainee's graduate program selected from an extensive curriculum covering molecular biology, neuroscience, perception and engineering, (3) participation in the Vanderbilt Vision Research Seminar series and related seminars on campus, (4) participation in international scientific meetings such as Association for Research in Vision & Ophthalmology, Vision Science Society and Society for Neuroscience, (5) participation in a Responsible Conduct of Research program, and (6) most importantly, research supervised by one or more preceptors. Postdoctoral trainees are required to fulfill the same requirements except (2) while they prepare an independent NRSA proposal. Trainees will be recruited nationally with emphasis on minority sources. Alliances with traditionally African-American institutions in Nashville such as Meharry Medical College, Fisk University and Tennessee State University facilitate minority recruiting. This training program develops independent, academic vision researchers through interdisciplinary training in vision and eye research fostered by the number and cohesiveness of vision and eye researchers at Vanderbilt.

The Vanderbilt Vision Research Center (VVRC) spanning the College of Arts and Science, Peabody College, School of Engineering and School of Medicine requests uninterrupted Core grant support for five modules. Animal Care provides specialized housing, breeding and enrichment, surgical preparation and assistance and other services not provided by the Division of Animal Care. Computer Programming and Support provides software and hardware support as well as custom programming of visual displays, real-time data acquisition and data analysis. Computer Graphics and Illustration provides digital and photographic facilities and services to produce color or monochrome illustrations for journals, slides and posters. Electronic and Machine Shops repair or design and fabricate specialized optical, mechanical and electronic instruments. New support is requested for an Image Processing module to provide aid in acquisition and analysis of fMRI and other image data. Administrative support is requested to insure continued smooth and stable operation of the VVRC research and training missions. Each module is directed by an investigator who has or is competing for NEI funding, has talented and experienced staff and provides services that are either otherwise not available or would be prohibitively expensive or slow. Over the last grant period, each module was used moderately by at least four investigators. During the last grant period VVRC investigators produced several hundred publications that made fundamental contributions to basic and clinical visual science. The Core grant has noticeably increased collaborations between vision researchers across the Vanderbilt campus and with other institutions; as a result, the strong basic research mission of the VVRC has been enhanced by participation of clinical researchers. The Core grant has improved our ability to recruit world-class vision researchers to Vanderbilt and, in conjunction with an NEI training grant, has improved our development of new vision scientists through the VVRC Training Program. The high level of performance of VVRC investigators, which depends on renewed Core grant support, will synergize with new campus- wide initiatives in neuroscience research and training at Vanderbilt.

The Vanderbilt Vision Research Center (VVRC) spanning the College of Arts and Science, Peabody College, School of Engineering and School of Medicine requests uninterrupted Core grant support for five modules. Animal Care provides specialized housing, breeding and enrichment, surgical preparation and assistance and other services not provided by the Division of Animal Care. Computer Programming and Support provides software and hardware support as well as custom programming of visual displays, real-time data acquisition and data analysis. Computer Graphics and Illustration provides digital and photographic facilities and services to produce color or monochrome illustrations for journals, slides and posters. Electronic and Machine Shops repair or design and fabricate specialized optical, mechanical and electronic instruments. New support is requested for an Image Processing module to provide aid in acquisition and analysis of fMRI and other image data. Administrative support is requested to insure continued smooth and stable operation of the VVRC research and training missions. Each module is directed by an investigator who has or is competing for NEI funding, has talented and experienced staff and provides services that are either otherwise not available or would be prohibitively expensive or slow. Over the last grant period, each module was used moderately by at least four investigators. During the last grant period VVRC investigators produced several hundred publications that made fundamental contributions to basic and clinical visual science. The Core grant has noticeably increased collaborations between vision researchers across the Vanderbilt campus and with other institutions; as a result, the strong basic research mission of the VVRC has been enhanced by participation of clinical researchers. The Core grant has improved our ability to recruit world-class vision researchers to Vanderbilt and, in conjunction with an NEI training grant, has improved our development of new vision scientists through the VVRC Training Program. The high level of performance of VVRC investigators, which depends on renewed Core grant support, will synergize with new campus- wide initiatives in neuroscience research and training at Vanderbilt.

Stochastic Models of Executive Control in Monkeys and Humans

Abstract

With National Science Foundation support, Drs. Logan, Palmeri, and Schall will conduct a three-year investigation of the executive control processes that underlie flexible responding in monkeys and humans. It is the hallmark of primate intelligence to be able to respond flexibly, focusing on different aspects of the same situation to produce arbitrary responses that are appropriate to current goals. The goal of this project is to specify executive processes computationally and neurally, focusing on the control of attention, categorization, and response preparation. To accomplish this goal, monkeys and humans will perform tasks that require them to make saccadic eye movements toward or away from targets that appear in displays of distractors. Experimental variables will be manipulated to selectively influence attention to the targets, categorization of targets and distractors, and preparation of eye movement responses. The timing and accuracy of eye movements will be recorded in both humans and monkeys performing the task, and the activity of ensembles of neurons in the frontal lobes of monkeys will be recorded while they are performing the task. The overt eye movement behavior of humans and monkeys and the neural activity of monkeys will be described in terms of a mathematically precise computational theory with three distinct components, as follows. (1) An attention component that selects behaviorally-relevant targets from a field of distractors; (2) a categorization component that selects goal-relevant interpretations of target stimuli; and (3) a response preparation component that selects responses necessary to accomplish the goals. The theory provides a common language that makes it possible to relate the overt behavior of humans to the overt behavior of monkeys and to relate the overt behavior of monkeys to the neural activity that underlies it.

The research is significant in three respects. First, it will advance understanding of executive control processes by specifying them concretely in terms of computational and neural processes. Executive control processes are critical in a variety of contexts in the workplace, educational settings, and mental health settings that require people to deal with competing goals and switch between various activities, including the workplace, education, and mental health. The research will have implications for human factors, ergonomics, design of training programs in education and industry, and diagnosis and treatment of mental disorders. Second, the research will advance understanding of neural processes by providing linking propositions that relate single-cell behavior to psychological states of the cognitive processes that the single cells implement. Single-cell behavior makes sense only in the context of the behavior it underlies, and the research will provide that relation. Third, the research will advance understanding of the computations that underlie cognitive processes of attention, categorization, and response preparation. Computational models of these processes are limited by an inability to "open the black box" and observe the inner brain processes that underlie them. Computational models with very different internal processes often predict the same overt behavior. The research will identify cognitive processes with neural behavior, allowing distinctions between these computational models of human and monkey cognition.

DESCRIPTION (provided by applicant): The Vanderbilt Vision Research Center (VVRC) spanning the College of Arts & Science, Peabody College of Education, School of Engineering and School of Medicine requests uninterrupted support for four modules plus support for one new module. (1) The Animal Care Module provides specialized breeding, enrichment, surgical support and veterinary care of nonhuman primates and other large animals as well as genotyping and phenotyping of transgenic mice. These services not provided by the Vanderbilt Division of Animal Care. (2) The Computer Module provides hardware installation and maintenance, software development for visual displays and real-time data acquisition and analysis, webpage maintenance and production of illustrations for journals, slides and posters. (3) The Image Processing Module aids acquisition and analysis of optical imaging, fMRI and other imaging data. This module will also provide access to and support of confocal microscopy. (4) The Shop Module repairs, designs and fabricates specialized optical, mechanical and electronic instruments. Support is also requested for a new Gene & Protein Analysis Module that will provide economical access to gene microarray and protein mass spectrometry services. Administrative support is requested to ensure continued smooth and stable operation of the VVRC research and training missions. Modules are directed by investigators with NEI funding, have talented and experienced staff and provide services that are otherwise not available or would be prohibitively expensive or slow. During the last grant period, each module was used moderately or extensively by no less than five investigators. VVRC investigators produced several hundred publications that made fundamental contributions to basic and clinical visual science. The Core grant has increased collaborations between basic and clinical vision researchers across the Vanderbilt campus and with other institutions. The Core grant has improved our ability to recruit world-class vision researchers to Vanderbilt resulting in a more-thandoubling of NEI-sponsored research at Vanderbilt. The high level of performance of VVRC investigators, which depends on renewed Core grant support, synergizes with campus-wide initiatives in biomedical research and training at Vanderbilt.

[unreadable] DESCRIPTION (provided by applicant): The long-term goal of our research is to understand how the visual system decides where to look. The activity of multiple neurons will be monitored simultaneously in monkeys performing visual search tasks designed to dissociate visual processing from saccade preparation. The frontal eye field will be studied because it is situated anatomically to sample the outcome of visual processing to orient attention and produce motor commands to orient gaze. Patterns of neural activity will be analyzed to evaluate specific hypotheses about how visual information is encoded for target selection among pools of neurons (Aim 1), to describe how sensory-motor mapping occurs between visual and saccade neurons (Aim 2) and to determine how short-term and long-term experience influences saccade target selection (Aim 3). Understanding how the brain selects visual stimuli for action is necessary to understand the causes of impaired visual behavior. [unreadable] [unreadable]

DESCRIPTION (provided by applicant): The long-term goal of our research is to understand how the visual system decides where to look. The activity of multiple neurons as well as local field potentials will be monitored simultaneously in monkeys performing visual search tasks designed to dissociate visual processing from saccade preparation. The frontal eye field will be studied because it is situated anatomically to sample the outcome of visual processing to orient attention and produce motor commands to orient gaze. Neural signals in frontal eye field will be analyzed to evaluate specific hypotheses about how visual information is processed for target selection and how saccade preparation relates to target selection (Aim 1) that will guide and constrain stochastic network models of the visual-to-motor transformation necessary to perform visual search (Aim 2). Neural signals in supplementary eye field will be analyzed to determine its contribution to target selection and error monitoring during visual search (Aim 3). The results of these experiments will be interpreted in the framework of a new Stage Theory of Attention and Decision which postulates that visually guided eye movements in complex environments are produced by a sequence of stages -- one stage that encodes and selects visual stimuli for attention followed by another stage that prepares to initiate saccades. This framework offers the opportunity to distinguish the respective contributions of these two, distinct stages to disorders of visual attention, orientation and mobility. PUBLIC HEALTH RELEVANCE: Clinical science has progressed by carving nature at its joints. The Stage Theory of Attention and Decision postulates that visually guided action in complex environments arises from the operation of one stage that encodes and selects visual stimuli for attention followed by another stage that prepares and initiates saccades. This framework offers the opportunity to distinguish the respective contributions of these two, distinct states to disorders of visual attention, orientation and mobility.

DESCRIPTION (provided by applicant): The long-term goal of our research is to understand how computational models of performance of visual tasks like locating and shifting gaze to a target a visual array map onto specific neural processes producing that performance. Elucidating this mapping provides converging constraints for discriminating between competing model architectures and provides functional explanations of neural circuit function. The aims of this proposal test, extend, refine, and integrate two major new computational models of target selection during visual search that we have recently developed. Data will consist of performance of monkeys and human participants searching for a target in a visual array in which target location can change unpredictably supplemented by neurophysiological data from FEF that was collected previously. The models provide quantitative accounts of detailed patterns of correct and error saccade behavior during visual search and also provide explanations for the temporal modulation of neurons in frontal eye field (FEF). Unlike previous models of visual search, ours account for the entire range of correct and error response probabilities and response time distributions during efficient and inefficient search, even when the target changes location unexpectedly. Aim 1 will develop, refine, and extend an INTERACTIVE RACE model of saccade target selection. We will test competing model architectures consisting of multiple stochastic accumulators (GO units) that govern when and where a saccade is made, where the nature of the interactions between GO units and the potential inclusion of a STOP unit for exerting cognitive control is manipulated across model variants. Successful models predict response probabilities and response time distributions in monkeys and humans and neural activity observed previously in monkeys. Aim 2 will test, refine, and extend a GATED ACCUMULATOR model of how visual salience is translated into a saccade command. The visual salience representation provided by FEF neurons will be the input to a neural network of stochastic GO units with alternative architectures that implement competing hypotheses about the role of feed forward, lateral and gating inhibition. Aim 3 will integrate these two models. This integration will be guided by new data from human participants performing visual search tasks in which key variables are manipulated to obtain new measures to test competing architectures.

Computer services are normally provided on a first-come, first-served basis, with provision for special projects or urgent deadlines. Faculty or laboratory personnel contact the staff through an email system that tracks job identity and duration. A Graphics Drop Box folder provides for transfer of large graphics files, and an automated poster printing system has been developed by the system administrator. As with other modules, investigators are charged for materials but not for labor. Realizing that demands for service occasionally produce conflict, we have insulated the staff from controversy concerning job priority. When conflicts arise, the module director resolves them. The staff are responsible for providing users with updates on job progress and modifications of projected completion dates. These individuals are also responsible for maintaining job logs which the module director consults when resolving usage conflicts. To manage the growing demands on the systems administrator and on the computer graphics services, we implemented two specific time management practices. First, the system administrator implemented the widely used Request Tracker work tracking system from Best Practical. The Request Tracker system is freely available Open Source software that runs on our Linux-based servers. An email for help from a user sent to the system generates an email to the systems administrator and opens a new ticket. The systems administrator can then use the Request Tracker web interface to monitor how much time is spent on a ticket and also: ensure that no jobs are overlooked. Email correspondence is routed through the tracking system which in turn provides a record of progress. The flexibility of this system provides an easy way for the programmer and systems administrator to keep track of their work. Second, to deal with the very heavy demand for poster printing before the Society for Neuroscience meeting and the ARVO and VSS spring meetings, a strict schedule for assisting, printing and delivering conference posters has been implemented to ensure that all posters are printed by the time of the conferences. With these procedures in place during the past grant cycle, very few conflict incidents required resolution, and those were resolved amicably.

GENE & PROTEIN ANALYSIS MODULE Space & equipment The GENE ANALYSIS SERVICE will use the newly organized Vanderbilt Technologies for Advanced Genomics (VANTAGE)). VANTAGE is a genomics core laboratory consolidation initiated by an $8.6 million ARRA funded NIH award to Vanderbilt University Medical Center. It is a new collaborative shared resource that accelerates discovery in genome sciences and personalized medicine, providing state-of-the art research shared resource facilities and technology. VANTAGE occupies 12,505 square feet of newly renovated laboratory space for new cutting edge scientific equipment. Renovation was completed in May 2012, and all the core labs are now fully operational. The consolidation includes the operational merger of the Vanderbilt DNA Resources and Genome Sciences Resource cores and offers lllumina genotyping (lllumina HiSeq2500 and lllumina MiSeqV2), DNA extraction and banking, Affymetrix-based genotyping and expression microarrays, Sanger sequencing and Next Generation Sequencing among many other specialized services. The lllumina HiSeq system includes the lllumina cBOT Cluster Generation System, an automated system that creates clonal clusters from DNA library templates, preparing them for sequencing on the lllumina HiSeq. These resources are now part of an overall structure that takes full advantage of physical co-location together. VANTAGE works closely with VANGARD (VANderbilt Technologies for Advanced Genomics Analysis and Research Design) to assist researchers in experimental design and results evaluation. VANTAGE/VANGARD holds weekly Genomic Design Studios, which offer a panel of experts to review research proposals set forth by those in the Vanderbilt research community. These occur each Tuesday at and host up to 7 researchers who register in advance online. Computing resources include ACCRE High Performance Computing with over 4000 processors, 17 TFLOPS, 300 TB GPFS storage via a BluArc Titan SAN storage system, and 70TB of fast-access and reliable storage space, scalable as-needed. Numerous workstations are available, ranging from six core to single core Xeon processors, with 6 to 24 gigabyte of RAM per workstation (Windows, Mac and Linux OS), and over 50 terabytes of file space. Complete backup of critical data performed nightly. Two Windows 2008 and five Ubuntu 64-bit dedicated servers, with 24 to 256 gigabyte of RAM per server. 50 terabytes of storage space are dedicated directly for research, backed up and verified daily. The Center for Quantitative Sciences utilizes an Ethernet network with Windows Server 2008 64 bit, Windows 7 (32 and 64 bit), Windows XP (32 and 64 bit), OS X, and GNU/Linux (32 and 64 bit) servers and workstations. The network includes fourteen Intel Xeon Quad core workstations, seventeen Intel Xeon workstations, eight Intel Pentium 4 workstations, two Intel Quad core workstations, two dual processor AMD Opteron 275 workstations, Three Intel Xeon eight core servers with 192, 64 and 24 gigabytes of memory, two Dual Intel Xeon 6 core with 48 and 128 gigabytes of memory, and Dual 12 core AMD server with 256 gigabytes of memory. These 46 computers contain more than 100 terabytes of storage capacity, which are backed up nightly by a Hewlett Packard Ultrium LT03 40 tape backup system. All campus-wide servers are accessible from these computers via the network. Software includes MATLAB, S-PLUS, SAS, SPSS, STATA, StatXact, Resampling Stats, EGRET, EPICURE, CART, MARS, TREE-NET, NCSS, nQuery, EaSt, PASS and other statistical applications, MS Visual Studio.Net, Digital Fortran, Visual Basic, MS Access 2010 and MySQL for Relational Database Projects, Ruby on Rails, BWA, GATK, Tophat, Cufflinks, Cuffdiff, DESeq, baySeq, GenomeStudio, zCall, optiCall, GALAXY instance, and others. Conversion of statistical data is accomplished using DBMS/Copy or Open Database Connectivity Drivers and the accompanying software packages. In addition to a fully equipped molecular biology laboratory with all standard benchtop equipment needed to routinely perform biomedical research, VANTAGE is equipped with the following state-of-the-art instrumentation: Geospiza and Clarity/GenoLogics LIMS ABI 3730XL and 3730 capillary array sequencers

IMAGING MODULE The Cell Imaging Shared Resource (CISR) provides expert microscopy services for over 275 Vanderbilt University laboratories (most are NIH-funded), including six NIH research centers. Trained users have access to the facilities 24 hours/day, seven days a week. The CISR has an 18-year history of outstanding service, reliability and self-sufficiency; total microscope usage is currently over 15,000 hours/year. The CISR is a core lab that is located in three separate facilities, but consists of a single staff that is highly trained in multiple microscopy methods. Dr. David Piston established the CISR in 1993 and in 2000 recruited Dr. Sam Wells to be the managing director of optical microscopy. In 2001, Dr. Jay Jerome was recruited to expand the CISR offerings to include electron microscopy. As of 2009, the CISR is directed by Dr. Sam Wells with Dr. Jerome as technical director of electron microscopy. Dr. Piston, who was the Resource Director from 1993 to 2008, continues to serve as the Scientific Director. In general, the resource staff members learn from each other and the power users so that they become aware of the strengths and limitations of different microscopic methods. This allows the staff to assist investigators in finding the correct tool to answer their particular scientific question. Funding for the CISR includes six NIH-funded research centers, institutional support, and hourly usage fees.

The Department of Psychology Wilson Hall Animal Facility is an AAALAC-approved animal care facility on the ground floor of Wilson Hall, located within a security access area. The facility houses the animals and research laboratories for WRC investigators affiliated with the Department of Psychology and the Department of Hearing & Speech Science. The component of this module in Wilson Hall consists of animal housing and quarantine rooms (3006 sq ft), a 3-room sterile surgery suite with preparation and recovery rooms (509 sq ft) and support areas (939 sq ft). The facility currently houses 35 macaques, 16 squirrel monkeys, 2 owl monkeys, 4 tree shrews, 62 galagos, and 2 rats. Over the years it has housed a variety of other species used for vision research such as squirrels, slow loris, talapoin and patas monkeys, and cats (including the rare albino). Networked PCs are supported by the Computer module to monitor facility security, animal use and health status, protocols and purchases through the Department of Psychology in coordination with the Division of Aninnal Care through the eSirius software system. high-pressure steam cage washer two CO2 monitors several stereotaxic instruments with multiple two pulse oximeters (one of which is attachments for large and small nonhuman MRI compatible) primate and rodent species a vital signs monitoring system one steam autoclave (SurgiVet Advisor Monitor) one AN74i Anprolene gas sterilizer with two Hewlett-Packard ECG monitors Etox-I Ethylene Oxide monitor two Isoflurane anesthesia machines The W R C and the College budget additional funds to assure that this equipment is maintained properly. Also, in the last grant period theWRC with additional support from the Center for Integrative & Cognitive Neuroscience and the College of Arts & Science has made the following investments to improve the operation and services of this module: ? Bair Hugger convective warming system ? i-Stat Portable Clinical Analyzer for tests of blood gases, electrolytes, metabolites and coagulation ? MR-compatible pulse oximeter ? NUVO VistOR LED surgical light with video camera and associated hardware to display and record events at the surgical sight for training and record-keeping ? SurgiVet Advisor vital signs monitor with ECG, Sp02, heartrate, non-invasive blood pressure, respiration including data logger. This system replaces and expands on an out-of-date Hewlett Packard system. The improved accuracy and increased monitoring channels improve the lACUC/USDA compliance of W R C primate researchers.

Electronics shop facilities occupy two rooms in Wilson Hall (WH529 100 sq ft and WH616 60 sq ft). These facilities are equipped with an assortment of testing equipment including oscilloscopes, signal generators, power supplies, data acquisition devices, microcontrollers, and signal tracers. They also have the necessary complement of assembly tools including soldering irons, crimpers, cutters, holding fixtures, heat guns, prototyping tools, circuit boards, and electronic enclosures. We also stock the typical assortment of electronic components ~ resistors, capacitors, integrated circuits, switches, connectors, wires and cables. Also installed is software for electronic circuit design, printed circuit boards, schematics, and mechanical drawings. In the last grant period the WRC with the Center for Integrative & Cognitive Neuroscience enhanced the capabilities of the instrumentation shop by purchasing a 20-ton hydraulic press.

ADMINISTRATIVE COMPONENT Jeff Schall will remain the PI of this grant; his qualifications are detailed in the Personal Statement. The Core Steering Committee will remain comprised of the PI and the Module Directors (Animal - Anna Roe, Computer - Frank Tong, Gene & Protein Analysis with Histology - David Calkins & Kevin Schey, Image Processing - Vivien Casagrande & Rene Marois, Shop - Jon Kaas). Two modules have co-directors to provide appropriate expertise for the diversity of services offered. Now, what about the NEI ROI funding status of the proposed module directors? It is the case that Roe and Tong do not currently hold NEI ROI funding, but we have no doubt that these experienced, productive and well-regarded vision researchers will regain funding. Meanwhile, Marois has never held NEI funding because his work is regarded as too cognitive. Nevertheless, at Vanderbilt he interacts daily with the NEI funded researchers, and he is an expert in fMRI methods, so the WRC interests are best served with him as Imaging module director! Decisions about the distribution of core resources and staff support are made through consensus by the Core Steering Committee in consultant with concerned WRC faculty. The degree of collegiality at Vanderbilt consistently thwarts contention. To carry out the WRC research and training missions, the service of an able Administrative Assistant is essential: All WRC investigators agree that the current Administrative Assistant, Gale Newton, is very conversant, organized and self-motivated, and they express high satisfaction with Gale's performance. This position is needed to (1) maintain up-to-date Core grant module usage records and other information for progress reports and competing renewals, (2) monitor and update allocation of funds through the VUMC Scholarship system (necessary for the Imaging and the Gene & Protein Analysis modules), (3) oversee the secure and equitable distribution of shared equipment (e.g., Minolta luminance monitors, computer projector), (4) maintain and reconcile expense ledgers, (5) serve as a liaison to other units within Vanderbilt, to other vision research centers and to NEI, (6) maintain relevant IRB and lACUC records, (7) organize and distribute the agenda for AA/RC module director and staff meetings, and (8) order supplies and equipment used by 3 or more WRC laboratories. The administrative assistant also provides services not directly related to the management of Core Grant activities; therefore, 20% of her salary is provided by the College of Arts & Science and the Center for Integrative & Cognitive Neuroscience^. This allows her to (1) maintain records and process documents for our NEI-sponsored Vision Training Program, (2) maintain a calendar coordinated with other seminar series on campus and notify the vision research community of seminars and journal clubs, (3) arrange lodging, reimbursements, itinerary, etc. for visiting scientists and prospective trainees (during the last grant period the administrative office organized 70 seminars including 25 visiting speakers listed in the Appendix. (4) provide administrative support for The Visual System course, (5) maintain an updated electronic and campus mail list of administrators, faculty, staff and trainees with interests in vision research, (6) distribute information to WRC faculty and trainees concerning seminars and other business of the WRC and (7) price and order equipment for WRC or individual investigators. Core faculty depend on the administration service for coordinated flow of information about seminars and other vision research and training matters. The module directors use this service to an extensive degree to monitor the effective use of resources. Funds for the administrative assistant are needed because Office of Management and Budget Circular A-21 prohibits using direct costs of research grants for clerical/administrative salaries, and Vanderbilt has no other source that can provide the necessary amount of administrative support for the WRC. As noted above, a clear priority system for usage is codified in the titles of faculty affiliated with the WRC. First priority goes to Investigators, faculty with funding from NEI or another agency that supports bona fide vision or eye research. Second priority is granted to Associates, faculty who are engaged actively in vision or eye research as assessed by regular publications. Among this group, higher priority is given to faculty who are actively competing for NEI or other funding to support vision and eye research. Affiliates are faculty who are integral to the larger vision research community but who never use any of the modules. Only Investigators and Associates are included in this application. When vision and eye research is not compromised. Core services are also provided to non-vision researchers who are part of the local research community to foster cross-disciplinary collaboration and encourage new vision research. The goal of this priority system is to leverage Core resources maximally to facilitate funded research and promote unfunded research for investigators to (re)gain NEI funding. When competing requests for services arise, the Module Director and involved investigators meet to negotiate an effective task-swapping schedule. Any disagreements that cannot be resolved between a Module Director and participating investigators are brought before the Director or the Steering Committee as a whole for resolution. Through the last grant period no scheduling conflicts rose to this level. The culture of collegiality and communication we enjoy has ensured equitable access to all module services and efficient anticipation, recognition and solution of problems as they arise. On a daily basis, the Core modules operate relatively independently through the experience and dedication Of the staff. The in vitro imaging, gene analysis and protein analysis services are each accessed through a Scholarship System implemented by the VUMC Office of Research designed to comply with federal policy and ensure that support to a given core service appropriately and directly translates into benefits for WRC investigators. Instead of a discount or co-pay, participating faculty receive scholarship vouchers that are redeemed to access particular core services. These vouchers are issued to WRC investigators by the PI and module directors according to historical patterns of usage and proposals for new research endeavors. The sum total of scholarship vouchers cannot exceed the sum of actual direct salary support to staff in each service. The scholarship mechanism requires accurate tracking of the vouchers every month to ensure that the necessary pool of credit for each service is provided for WRC researchers but also that excessive investment is not underutilized This tracking is accomplished by the WRC Administrative Assistant using a web-based system {Core Facilities Usage and Invoicing System, CORES) managed by the VUMC Office of Research to verify that the total pool of credit represents actual direct support of each core service.

DESCRIPTION (provided by applicant): Support is requested to continue a productive collaboration aimed to develop, test, and extend computational models of eye movement control in visual decision making and visual search. Our research program is guided by converging constraints from computational, behavioral, and neurophysiological perspectives that link detailed patterns of behavior in humans and monkeys performing visual saccade tasks with patterns of modulation in neurons recorded in monkeys through the use of computational models that predict behavioral and neural dynamics. We propose new computational modeling of existing monkey behavioral and neurophysiological experiments and new computational modeling of new human experiments that mirror and significantly extend experiments previously conducted with monkeys. Our theoretical foundation is a class of stochastic accumulation of evidence models that mathematical psychologists and systems neuroscientists have converged upon as a general theoretical framework to understand and explain the time course of visual decision making; these include an interactive race model and a gated accumulator model we proposed previously. Unlike most approaches, (1) we quantitatively test alternative model architectures (including race, diffusion, competitive, gated accumulators) on detailed behavioral data in both humans and monkeys, including response probabilities and distributions of correct and error response times for saccades, (2) we constrain model mechanisms and model parameters based on neurophysiological recordings, specifically neurons in frontal eye field (FEF) hypothesized to represent the evolving time-course of task-relevant visual evidence, (3) we quantitatively test model architectures on how well they predict the recorded dynamics of neurons involved in make a visual decision, specifically neurons in FEF that determine when and where the eyes move. Aim 1 will develop and test the gated accumulator model against alternative models of countermanding and control of saccadic eye movements. Aim 2 will develop and test the gated accumulator model against alternative models of speed-accuracy control of saccadic eye movements in visual search. Aim 3 will investigate how to scale the broad class of stochastic accumulator models, including gated accumulator, from a single accumulator associated with each response to ensembles of thousands of accumulator neurons associated with each response. To understand normal behavior as well as illness, disability, and disease, abstract computational models, like stochastic accumulation of evidence models, can be a just right theoretical level in that best-fitting parameters of these models can characterize well individual differences in behavior and provide theoretical markers for understanding brain measures - our models provide that just right theoretical level. Yet to the extent that certain neurological conditions have a biophysical basis at the level of individual neurons and neural circuits, we also need to understand how these abstract computational models map onto neural circuits - making this mapping is also core to our proposed work.

PROJECT SUMMARY: ANIMAL SERVICES MODULE The Vanderbilt Vision Research Center (VVRC) includes faculty investigators with strong interest in discerning relationships between visual circuits and behavior, between cortical structures and physiology, and between brain regions and perception/behavior in non-human primate and prosimian species. These cognitive- and systems-level investigations require access to expert veterinary husbandry and surgical skills, especially for longitudinal studies requiring use of the same animal cohort over many months. The purpose of the VVRC Instrumentation Module is to provide a comprehensive veterinary service for support of vision research using non-human primates that is not covered by staff members supported by individual grants. This module is a VVRC-intrinsic core, housed in Wilson Hall and administered through the Department of Psychology, and is not part of a VUMC institutional facility; therefore, the service is provided to VVRC members by request and not through the VUMC Office of Research scholarship platform. In the current funding period the animal module contributed resources in support of 11 investigators with 55 publications resulting from use of the service. These are indicated as such in our Progress Report Core Publications by Investigator document. Availability of this module during the current period saved VVRC investigators over $240,905 in veterinary technician and facility costs that otherwise would have to be obtained elsewhere. A survey of researcher plans indicates that the use of this service will increase, with moderate to extensive use by 14 of 36 VVRC investigators. The Animal Services Module, housed in Wilson Hall near primary users, is directed by VVRC Investigator Jeff Schall, PhD. Using this space and personnel supported by this Core mechanism, the VVRC Animal Services Module will: (1) provide expert assistance with nonhuman primate surgical procedures, (2) provide training on best, aseptic, nonhuman primate surgical practices, and (3) support breeding of prosimian species used for vision research. These services and resources will enhance the scope of experimentation NEI-funded VVRC investigators conduct, promote innovation through specialized veterinary procedures to those who otherwise would not have such capabilities, including early-career vision scientists competing for extramural funding for their laboratories and established investigators who rely upon the use of non-human primates for their research.