Gary D. Paige - US grants

The control of equilibrium in the elderly is an important public health concern because aging is accompanied by an increasing incidence of both dizziness and falls. The vestibular system is crucial in maintaining equilibrium through a variety of postural and orienting reflexes. One of its major functions is the vestibulo-ocular reflex (VOR), which generates compensatory rotations of the eyes during head movements in order to maintain ocular fixation on visual targets, and therefore a stable retinal image. The VOR is activated by two kinds of head motion; angular (the AVOR), driven by the semicircular canals, and linear (the LVOR), driven by the otoliths. An important feature of the VOR is its ability to adaptively modify performance in response to prolonged visual-vestibular mismatch during head movements. In addition, recent evidence has demonstrated that the VOR is also modulated by instantaneous viewing conditions (e.g. target distance and gaze), more so in the LVOR than the AVOR. This project focuses on the VOR because it is the most direct and accessible behavior from which mechanistic inferences about vestibular function can be derived. The LVOR has generally received less attention than the AVOR. Adaptive plasticity has only been demonstrated in the AVOR, and remains unexplored in the LVOR. Studies on aging have also been limited to the AVOR. In the past support period, progressive age-dependent deterioration was uncovered in the AVOR and its adaptive capabilities, especially when stressed by high head velocities and frequencies. We now turn our attention to the human LVOR, its relationship with the AVOR and with visual following, and novel adaptive mechanisms in different age groups. New techniques will be employed to study these functions in order to define their basic performance and plastic characteristics. We will also stress the LVOR and visually-driven adaptive mechanisms to uncover limitations and deteriorations with aging. We hypothesize that the LVOR will be more sensitive to aging than the AVOR, and that a comprehensive study of both VORs will allow us to infer mechanisms of fundamental interest as well as those relevant to age-dependent disequilibrium underlying dizziness and falls.

The vestibular system is crucial in maintaining equilibrium and orientation in space. One of its major functions is the vestibulo-ocular reflex (VOR). The VOR generates compensatory rotations of the eyes during head movements in order to maintain binocular fixation on visual targets, and therefore a stable retinal image. We focus on the VOR because it is the most direct and accessible behavior from which mechanistic inferences about vestibular function can be derived. The VOR is activated by two kinds of head acceleration; angular (the AVOR), driven by the semicircular canals, and linear (the LVOR), driven by the otoliths. Linear stimuli include two forms, translational motion and tilt relative to gravity. Each drives the LVOR in specific ways. An important feature of the VOR is its ability to adaptively modify performance in response to prolonged visual-vestibular mismatch during head movements. However, this phenomenon has only been demonstrated in the AVOR. In addition, the VOR is modulated by instantaneous viewing conditions (e.g. target distance and gaze), more so in the LVOR than the AVOR. The proposed experiments will determine how canal and otolith inputs interact to generate, and adaptively maintain, behaviorally useful ocular responses during angular, linear, and complex head movements. New techniques will be employed to study the LVOR and its relationships with the AVOR and vision over a broad range of motion profiles and fixation contexts. Relationships between translational and tilt LVORs will be elucidated. Novel adaptive mechanisms will be explored and characterized. We will determine whether plasticity in the AVOR and LVOR share neural elements. Specific endorgan lesions will be employed to directly assess the origin of VOR behaviors, and to elucidate unique adaptive processes that restore function.

The control of equilibrium in the elderly is an important public health concern because aging is accompanied by an increasing incidence of both dizziness and falls. The vestibular system is crucial in maintaining equilibrium through a variety of postural and orienting reflexes. One of its major functions is the vestibulo-ocular reflex (VOR), which generates compensatory rotations of the eyes during head movements in order to maintain ocular fixation on visual targets, and therefore a stable retinal image. The VOR is activated by two kinds of head motion; angular (the AVOR), driven by the semicircular canals, and linear (the LVOR), driven by the otoliths. An important feature of the VOR is its ability to adaptively modify performance in response to prolonged visual-vestibular mismatch during head movements. In addition, recent evidence has demonstrated that the VOR is also modulated by instantaneous viewing conditions (e.g. target distance and gaze), more so in the LVOR than the AVOR. This project focuses on the VOR because it is the most direct and accessible behavior from which mechanistic inferences about vestibular function can be derived. The LVOR has generally received less attention than the AVOR. Adaptive plasticity has only been demonstrated in the AVOR, and remains unexplored in the LVOR. Studies on aging have also been limited to the AVOR. In the past support period, progressive age-dependent deterioration was uncovered in the AVOR and its adaptive capabilities, especially when stressed by high head velocities and frequencies. We now turn our attention to the human LVOR, its relationship with the AVOR and with visual following, and novel adaptive mechanisms in different age groups. New techniques will be employed to study these functions in order to define their basic performance and plastic characteristics. We will also stress the LVOR and visually-driven adaptive mechanisms to uncover limitations and deteriorations with aging. We hypothesize that the LVOR will be more sensitive to aging than the AVOR, and that a comprehensive study of both VORs will allow us to infer mechanisms of fundamental interest as well as those relevant to age-dependent disequilibrium underlying dizziness and falls.

An essential goal of the nervous system is to maintain orientation and equilibrium relative to the outside world. Attaining this goal requires that we accurately localize ourselves within our surroundings, distinguish self-movement from that of environmental elements, and control movement through a complex world. These tasks are accomplished by neural systems that coordinate multiple motor behaviors with the aid of feedback from several sensory modalities. Vision and audition (the exteroceptive senses) provide information about the position and motion of external elements, proprioception conveys the position of the body and its parts, and vestibular inputs track head motion and orientation. These sensory inputs are processed by the brain, which generates the motor behaviors required to perform natural activities. Examples include coordinated eye and head movements that acquire and hold fixation on targets of interest, and guided hand movements that allow us to accurately interact with objects in the environment. This project will elucidate how these crucial and ubiquitous functions work and maintain coordination, and how they degenerate with natural aging. The endeavor is motivated by two important and related public health concerns: aging is accompanied by a progressive increase in the prevalence of disequilibrium, and in the risk and consequences of falls. Disequilibrium and falls both constitute failures of spatial orientation and equilibrium control. We hypothesize that the key to understanding these failures lies in how the aging nervous system utilizes multiple sensory inputs, central integrative processes, and adaptive mechanisms to produce and maintain cross- sensory concordance in the brain's representation of space. We will study physiological and psychophysical parameters that underlie how the brain utilizes vestibular, visual, and auditory inputs to localize external objects, and to control eye, head, and hand movements in order to acquire them. We will also elucidate how these sensory modalities interact to register motion of the body and external elements. Further, we will quantify adaptive capabilities that maintain accurate calibration between sensory modalities and their respective depictions of space. State-of-the-art and innovative techniques will be employed to isolate and combine specific sensory cues relevant to spatial localization and orientation, and over a broad range of ages. We hypothesize that aging entails quantifiable deterioration in spatial tasks, especially those that require integrative processes across sensory modalities. Further, we hypothesize that aging will result in quantifiable limitations in adaptive capabilities that are required to restore normal function in the presence of disease or age-dependent deterioration. A thorough understanding of these functions is required to facilitate the development of specific and effective interventions that might correct, or rehabilitate, potential age or disease induced deficits.

Description: The vestibulo-ocular reflex (VOR) is a set of reflexes activated by two forms of head acceleration; angular (the AVOR) driven by the semicircular canals, an linear (the LVOR) driven by the otoliths. Because linear accelerations arise during both translational motion and head tilt relative to gravity, but requir different compensatory responses, the LVOR is comprised of translational and tilt forms. During the previous period of support, the response dynamics of th LVOR, its modulation by fixation distance, and its interactions with vision an the AVOR were studied. The studies in this proposal are the logical sequel of the work done during the last period. Several new questions will be addressed. 1. Are the different LVORs driven by distinct sets of labyrinthine inputs and processed by independent central pathways? 2. How are linear accelerations properly parsed into tilt and translation, given that the otoliths respond ambiguously to them? 3. Are the various LVOR and AVOR components and parameter under independent adaptive control, or do they share elements? 4. Finally, since the VOR and motion perception share common sensory inputs as well as goals of spatial orientation, do these perceptual processes have similar properties and limitations? New experiments are described that will address these concerns in both humans and monkeys. Novel techniques will be explored, and specific endorgan lesions will be employed to directly assess the origin o VOR behaviors and elucidate processes that restore function.

This research is aimed at examining the properties and the neural substrate of the temporary storage mechanism necessary to ensure continuity of visual stimulation of an active observer. We use psychophysical measures and lesions of physiologically identified regions in selected extrastriate cortical areas in macaque monkeys to explore the role of these cortical areas in storing one of the fundamental features of the visual stimulus, its direction of motion. During the past year we performed a number of experiments that not only provide new insights into the mechanisms of short-term sensory storage but also suggest and point to new psychophysical tools for the study of short-term memory of active observers. (1) We found that the decline in retention of low- and high-level motion stimuli with time is similar for the two types of motion and is accelerated in the presence of motion noise. This result suggests that the process underlying temporary storage of direction information may be common to the two types of motion. It also points to the existence of inhibitory interactions within the networks encoding and storing sensory information. (2) The use of motion stimuli masked by noise also allowed us to uncover selective contribution of areas MT and MST to motion processing. Lesions of MT/MST produced a large, permanent deficit in the discrimination of direction only with motion stimuli masked by noise. (3) We recently found that lesions of areas MT/MST severely limit the retention of information about motion direction. If confirmed, this result for the first time demonstrates the involvement of intermediate visual cortical areas in temporary storage of visual information. These studies provide an important link between the experiments involving saccade-contingent display updating (Hayhoe, Pelz and Ballard) and psychophysical studies of patients with brain lesions (Merigan). In particular, we plan to use noise masking, which allowed us to uncover many of the properties of the temporary storage mechanism, in the study of short-term memory of active human observers performing visual memory tasks. Moreover, the finding of the deficit in motion erception in the presence of directional noise and in short-term memory after MT/MST lesions suggests a number of new tasks for the study of the effects of cortical lesions in humans.

The otolith organs ambiguously transduce linear forces due to both tilt and translation. The ambiguity is thought to be resolved by frequency-selective processing, with low-frequency stimuli conveying tilt, and high-frequency conveying translation. For low frequency or prolonged accelerations along the naso-occipital (NO) axis, this processing results in the sensation of pitch, and a corresponding illusory movement of the horizon (a form of "elevator illusion"). To investigate this illusion in humans, centripetal accelerations produced by a rotating sled were presented to human subjects. Subjects were rotated at 127 /s at zero eccentricity until angular vection and nystagmus ended, and then were slowly oscillated over B140 cm eccentricity (peak centripetal acceleration of 0.25 g) at frequencies between 0.005 and 0.025 Hz, resulting in an effective dynamic displacement of the gravity vector (effective 14 pitch tilt). A monocularly viewed laser spot was projected onto a head-fixed screen in a dark room, and subjects maintained this spot on the perceived horizon using a joystick to control the vertical position. Alternatively, subjects were instructed to keep their eyes on the horizon in complete darkness without the presence of the laser spot, while eye movements were recorded. During stimulation, subjects perceived a tilt and an associated illusory movement of the horizon, and responded by smoothly adjusting the laser spot or gaze vertically to compensate. The responses at lower frequencies were larger than at higher frequencies. Phase usually lagged the stimuli, and more so for the higher frequencies of stimulation. These findings demonstrate a low-pass characteristic of tilt perception and reflex eye movements in response to roll tilt, analogous to torsional responses to roll tilt. A related but more complete assessment of the tilt-translation parsing problem in the LVOR was performed in squirrel monkeys. Both true tilt and translational accelerations were used, over a broad frequency bandwidth (0.01D4.0 Hz). The unique properties of our rotating linear sled were required to accomplish this task. We demonstrated that both horizontal and torsional responses occur in response to both true roll tilt and interanral translation, reflecting the physical ambiguity of otolith response properties (they respond to all forms of acceleration equally). However, the horizontal responses operate with high-pass characteristics while the torsional responses operate with low-pass characteristics. This confirms our contention that the brain parses otolith input into tilt and translational functions through simple frequency-dependent filtering. Modeling efforts have illustrated that all VOR response characteristics can be well simulated by a straightforward linear systems model with simple dynamic elements in a canal-driven AVOR pathway, and two otolith-driven pathways, a high-pass translational LVOR, and a low-path tilt LVOR.

Localization of objects requires that spatial information are the same regardless of the type of sensory input. For example, if a pedestrian approaches an intersection and a car honks, the pedestrian must identify the source of the sound cue in space and link it accurately to a corresponding visual cue in order to avoid confusion (there may be many cars) if not disaster (he may be in danger of collision). Thus the two sensory inputs must be in concordance. In the process of orienting toward the car, an eye and head movement are generated, thereby providing additional sensory cues from proprioceptive (neck) and vestibular (head) origin. These must be accurately registered internally so that the brain's depiction of the car in space remains correct. Having realized that the light had not changed, the pedestrian might then reorient toward the crosswalk button and guide his hand to press this new target. Though simple in concept, this set of behaviors requires that the brain integrate auditory, visual, proprioceptive, and vestibular inputs accurately and synchronously. All inputs must be spatially concordant; that is, the sense of a particular target location must be the same for the auditory and visual inputs. These must be integrated with internal signals conveying where the eyes are in the head, where the head is in space, where the head is on the body (neck position), and where the body is relative to the ground. Errors in these various components (sensory or motor) will result in inaccurate localization of external targets, and therefore erroneous behavior. New methods, such as "virtual reality" technology, will be used to control and shape the visual and auditory world, while new motion control devices will allow manipulation of vestibular and somatic variables. A visual display panel within arm's reach, a virtual auditory stimulus capability, and a head and finger tracking device will be added to our sled/rotator laboratory. The sled/rotator permits precise control of subject motion in space (vestibular stimuli). The addition of virtual auditory stimuli allows us to coordinate and manipulate vestibular and auditory spatial cues smoothly and independently. Visual target presentation capabilities will allow us to also independently manipulate spatial visual targets in space. These combined features will provide true multisensory stimulus capabilities across three sensory modalities, with which we can assess each influence in isolation or in combination. This past year, we have set up a development lab (light tight and near anechoic) in order to instrument and test auditory and visual stimulus methods and tasking procedures. We have begun to assess virtual auditory techniques in direct comparison with real stimuli. We are also testing auditory-visual concordance paradigms and reaching tasks before porting the system to the sled-rotator lab.

Individuated movementsDthose in which one or more body parts move relatively independently of the movement or posture of other body partsDimpart a rich flexibility to the human behavioral repertoire. The individuated movements used in many forms of cognitive expression, such as speaking, dancing, or playing a musical instrument, contrast significantly with the phylogenetically older movements of the same body parts used, respectively, in eating, walking or grasping. In neurologic patients, individuated movements are the first lost and last recovered when lesions of any sort injure the motor cortex or corticospinal tract. Given the importance of individuated finger movements in so many aspects of human functionDfrom buttoning buttons to playing the pianosurprisingly few studies have quantitatively examined the ability of normal humans to individuate finger movements, or to recover this ability after nervous system injury. This reflects an underlying assumption that humans make perfectly independent movements of each finger, with any lack of independence being attributable to connections between the tendons to different fingers. Independent finger movements are assumed to be controlled by different parts of the primary motor cortex (Ml), and produced by separatemuscles moving each finger. Recent studies in non-human primates have shown, however, that individuated finger movements are controlled by overlapping neuronal populations in Ml, and are produced by multitendoned extrinsic muscles that put tension on more than one finger at a time. In humans, recent evidence indicates: (i) that Ml territories controlling different fingers overlap extensively; (ii) that motoneurons in different human finger muscles receive common input from the same premotor neurons; and (iii) that human multitendoned finger musclesDsuch as flexor digitorum profundusDmay not have separate functional subdivisions for each finger.

The vestibular system uses organs of the inner ear called the semicircular canals and the otolith organs to detect gravity and movements of the head. It is a system with extensive influence on eye movement, head position, and control of locomotion and posture. This international conference brings together active researchers in this field to discuss recent results and their implications from biological, biomedical and bioengineering perspectives. Emphasis in this conference will be on the interactions of vestibular input with visual, auditory and other sensory modalities, and on the integrated behavior of spatial orientation in animals and humans.
The meeting will have an impact on the participating students and young investigators by involving them with other researchers at the leading edge of the field, and will have an impact on other areas of neuroscience and physiology by the integrated perspective.

This proposal requests support for a meeting entitled, "Vestibular Influences on Spatial Orientation,"a satellite to the ninth Annual Meeting of th Society for the Neural Control of Movement. The meeting will be held April 16-19, 1999, at the Princeville Resort in Kauai, Hawaii. This will be a unique meeting on vestibular function. Although there have been several meetings in recent years covering the vestibular system, all have followed a similar pattern-they generally start with the labyrinth and then progress centrally. This meeting will chart exactly the opposite course. The key issues will center around how vestibular inputs are employed during natural behavior, and the selective advantages conveyed by evolution in the system's structure and function. The meeting will focus on central processes, including perception. Indeed, the sequnce of sessions will begin with the perception of spatial orientation, gravity, and motion, and will progress toward behavioral responses to vestibular and multisensory spatial inputs and their underlying neural mechanisms. Exciting new developments in vestibular and multisensory interactions in cortex, the cerebellum, and the brainstem will be explored and discussed, Head/neck as well as oculomotor control will be emphasized in targeted sessions, as will compensation and adaptive plasticity, leading finally to cellular and sub-cellular mechanisms that support neural function and plasticity, in vestibular pathways. This novel approach will fill a logical hole left fallow by other conferences on the vesibular system. Traditional areas will also be represented, however, in the interest of maintaining breadth and scope for the meeting. This will ensure fruitful discussions and interactions among attendees, spanning multiple levels of scientific inquiry. Additional topics include progress in labyrinthine function, influences of postural mechanisms on head and gaze stability, advances in clinical and age-related dysfunction, and contributions of modeling and computational approaches to our under- standing of spatial orientation. Session leaders are all acknowledged leaders in their respective disciplines. They will govern the content of their sessions and select the subtopics and contributors in conjunction with the PI. Both workshop/symposium sessions snd poster presentations will be included, with deliberate emphasis on dedicated discussions and interactions between participants throughout the meeting. Students and post-doctoral fellows are specifically encouraged to attend and participate, and a scholarship program will target and enhance this important aspect of the meeting.

DESCRIPTION (provided by applicant): The most compelling features of daily life include the ability to navigate through our environment and to communicate with each other. These functions are fundamental to survival, but are also among the first to encounter trouble in the diseased or aging nervous system. The University of Rochester holds a set of NIH-supported research programs dedicated to the sensory, motor, integrative, and cellular mechanisms underlying navigation and communication. Research ranges from molecular and genetic approaches to cellular neurophysiology in awake animals to human perception, and includes strong translational and clinical elements. These characteristics provide a compelling framework for our P-30, Center for Navigation and Communication Sciences (CNCS). New this past grant period, the CNCS is now operating at a steady-state that exceeds all expectations, largely due to committed leadership matched by a dedicated and engaged faculty and staff, cooperative and shared Core services, a strong advisory and quality assurance process, and an infrastructure and community that has proven attractive to new collaborations and new investigators. The CNCS allows investigators to efficiently share costly, time-consuming, essential but cumbersome, and innovative research services. The CNCS includes three Cores: 1) a Human Subjects Core to consolidate and coordinate the recruitment, screening, scheduling, and databasing of subjects across projects;2) a Research Services Core that includes a Histology &Imaging Unit (tissue preparation, image analysis &reconstruction), an Electronic/Mechanical Shop (repair and construction of lab components and devices), an Animal Research Unit (mutant and knockout preparations, husbandry and screening), and a Proteomics Unit (specialized protein analysis);and 3) a Technology and Computation Core, including a Lab Technology Unit (automated lab systems for stimulus and behavioral control, data and analysis) and a Computation Unit to support PC and network operations, software library, web support, and staff training. Some service Units share support with the Department of Neurobiology &Anatomy, the Center for Visual Science (an NEI-P30), and two program projects (an NIA-P01 and an NINDS-P01). The CNCS exploits our inherently collegiate ecology and augments our lab capabilities through outstanding Core personnel and facilities in dedicated space. All Cores and Units operate efficiently and balance the combined goals of providing both needed though sometimes-mundane services as well as novel and innovative solutions that transform into tomorrow's capabilities. This ensures high-quality, efficient, and diverse services to all, in a robust infrastructure that enriches the productivity of our research, promotes collaborations among investigators, attracts new faculty and students to our research mission, facilitates further institutional support, and ultimately contributes to the health of the community and the nation.

DESCRIPTION (provided by applicant): This proposal requests support for a meeting entitled, "Multisensory Interactions Subserving Orienting Behavior," a satellite to the twelfth Annual Meeting of the Society for the Neural Control of Movement. The meeting will be held April 14-16, 2002, at the Naples Beach Hotel in Naples, Florida. There has never been a meeting on multisensory behavior flanking the NCM meeting. The meeting will allow participants to easily participate in both the satellite and the main NCM meeting, as the last day of the symposium ends Tuesday evening, in tandem with the registration and reception for the main NCM meeting. The satellite centers on how inputs from different sensory modalities (visual, auditory, vestibular, & somatosensory) are combined at different stages in the CNS of different animal species to guide purposeful spatial behavior. It will provide a unique opportunity to bring together top researchers in the field. Dedicated meetings on multisensory orienting behavior have been rare. A notable exception was the satellite to the IBRO World Conference on Neuroscience (Niigata, Japan, 1995) many years ago. More recently, the International Multisensory Research Forum has organized two meetings (Oxford, UK, 1999, and Tarrytown, NY, 2000) which emphasized largely perception rather than spatial behavior. Our symposium will begin with a keynote lecture by Barry Stein. His seminal work on the neurophysiological and developmental aspects of multisensory integration in the cat superior colliculus, and in several of its cortical input areas, touches the very heart of the problems addressed in this satellite. The meeting will then progress over 2 days, organized as three symposium sessions per day. The first day deals with subcortical and cortical mechanisms underlying multisensory orienting, as well as multisensory 'exotica.' The second day covers developmental and plasticity phenomena, clinical aspects, and multisensory-evoked behavior. A dedicated Poster and Demonstration session on Computational Models will be held on the second day. In addition, two general poster sessions are planned at the end of the two afternoon breaks, though posters will be on display during the entire meeting to allow ample access. Symposium sessions will typically be 2 1/2 hours long, during which four speakers will have a half-hour (including 5-10 mins. discussion), leaving ample time for a general discussion between the audience and the session participants. Session leaders are all acknowledged leaders in their respective disciplines. They will govern the content of their sessions and select the subtopics and contributors in conjunction with the organizers. Students and post-doctoral fellows are specifically encouraged to attend and participate, and a scholarship program will target and enhance this important aspect of the meeting.

The most compelling features of daily life include the ability to navigate through our environment and to communicate with each other. These functions are fundamental to survival, but are also among the first to encounter trouble in the diseased or aging nervous system. The University of Rochester holds a set of NIHsupported research programs dedicated to the sensory, motor, integrative, and cellular mechanisms underlying navigation and communication. Research ranges from molecular and genetic approaches to cellular neurophysiology in awake animals to human perception, and includes strong translational and clinical elements. These characteristics provide a compelling framework for our P-30, Center for Navigation and Communication Sciences (CNCS). New this past grant period, the CNCS is now operating at a steadystate that exceeds all expectations, largely due to committed leadership matched by a dedicated and engaged faculty and staff, cooperative and shared core services, a strong advisory and quality assurance process, and an infrastructure and community that has proven attractive to new collaborations and new investigators. The CNCS allows investigators to efficiently share costly, time-consuming, essential but cumbersome, and innovative research services. The CNCS includes three cores: 1) a Human Subjects Core to consolidate and coordinate the recruitment, screening, scheduling, and databasing of subjects across projects;2) a Research Services Core that includes a Histology &Imaging Unit (tissue preparation, image analysis & reconstruction), an Electronic/Mechanical Shop (repair and construction of lab components and devices), an Animal Research Unit (mutant and knockout preparations, husbandry and screening), and a Proteomics Unit (specialized protein analysis);and 3) a Technology and Computation Core, including a Lab Technology Unit (automated lab systems for stimulus and behavioral control, data acquisition, and data analysis) and a Computation Unit to support PC and network operations, software library, web support, and staff training. Some service units share support with the Department of Neurobiology &Anatomy, the Center for Visual Science (an NEI-P30), and two program projects (an NIA-P01 and an NINDS-P01). The CNCS exploits our inherently collegiate ecology and augments our lab capabilities through outstanding core personnel and facilities in dedicated space. All cores and units operate efficiently and balance the combined goals of providing both needed though sometimes mundane services as well as novel and innovative solutions that transform into tomorrow's capabilities. This ensures high-quality, efficient, and diverse services to all, in a robust infrastructure that enriches the productivity of our research, promotes collaborations among investigators, attracts new faculty and students to our research mission, facilitates further institutional support, and ultimately contributes to the health of the community and the nation.

The Technology and Computation Core includes: 1) an innovative Lab Technology Unit that has developed a new automated lab control system, has implemented custom installations in several labs within the Core-Center with ongoing migration to others;and 2) a complementary Computation Unit that maintains PC functions, networking, backup, and communications across CNCS labs, as well as database applications for the other cores of the CNCS. These Units will pursue the following goals. The Lab Technology Unit will continue to implement lab hardware/software solutions to stimulus and behavioral control, data acquisition, and data analysis across the CNCS. The Unit uses a modular, embedded PC-based architecture (LabView-Real-Time by National Instruments [Nl]) that includes a standardized set of real-time hardware and software tools to be interfaced to specific devices within each lab. The overall scheme ensures flexibility and modularity, while maintaining the specificity required by individual labs. A clear and reliable upgrade path from Nl ensures advancement and longevity. We have implemented the system in five labs, and will propagate the system across others, while at the same time upgrading all over time. New faculty and new labs, together with incremental needs of others, creates a fertile ecology for our new stateof- the-art lab control system. One result is a set of labs that share key attributes that in turn allow researchers at any level to rapidly equilibrate to any one of them despite different research goals or systems under study. The Computation Unit provides common office and lab PC and software solutions across the Core-Center, in concert with the Medical Center's extensive domain and more basic services (firewalls, security). Our labs are highly automated. PCs have supplanted many analog devices in our racks and are ubiquitous on desktops. Communications between labs and research personnel are essential. All of us are in need of new PC hardware and software over time, maintenance, training and support, and data backup, though such needs are rarely met effectively. The Computation Unit corrects these shortcomings to the benefit of our research productivity and efficiency. The Unit also supports CNCS web and intranet functions, including powerful database structures in other CNCS cores. In sum, the two Core Units serve crucial needs of all CNCS personnel. The environment established across the Core-Center has, and will continue to, catalyze new interactions and collaborations, and attract students and faculty to our research mission.

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