Tatiana Pasternak - US grants

We have recently found that the visual disorder of adult cats reared in a visually restricted environment is largely reversed following motion detection training. Such recovery after prolonged visual deprivation has not been reported to occur either spontaneously or following other forms of visual training. We now propose to explore the necessary and sufficient training conditions for such recovery and the types of visual disorders which respond to such training. Three groups of visually deprived cats, reared under different conditions, will be studied. The rearing conditions were chosen to produce a severe deficit of visual motion response in one group (8 Hz strobe-reared), of spatial resolution in a second (blur-reared), and of both motion response and spatial vision in the third (dark-reared). determine which aspects of motion detection training are crucial to recovery. The importance of the speed, direction, spatial frequency content and orientation of training stimuli will be assessed. The comparison of three groups of cats will enable us to separate psychophysical effects due to neuronal abnormalities in directional and spatial properties. The training induced visual recovery will be quantified with parallel psychophysical and physiological measures of spatial contrast sensitivity and directional motion sensitivity. The proposed experiments will provide an important information about the reversibility of developmentally induced visual deficits and the type of visual training which maximizes the recovery from these deficits.

Psychophysical studies in humans and in cats have identified two classes of contrast detecting mechanisms, directionally selective and non-directional, each operating at different but overlapping spatial and temporal frequencies. This proposal describes studies in cats, that could not be done in humans, designed to elucidate the neural basis of these two mechanisms. In all proposed studies contrast sensitivity for detection of a moving grating will be compared to the sensitivity for discriminating the grating's direction. Fixation locus will be controlled behaviorally and monitored with eye coils. In the first project the major stimulus parameters that determine visibility of the direction of stimulus motion will be identified in normal cats by measuring detection and direction discrimination over a range of spatial and temporal frequencies, at several retinal eccentricities. The separate contribution of the two major cortical structures, areas 17 and 18 to the preception of motion will be examined. Focal lesions will be placed in physiologically identified portions of either area 17 or 18 and sensitivity measured for detection and direction discrimination of moving gratings in corresponding portions of the visual field. Localized lesions will also be made in the lateral suprasylvian area (LS) to examine its role in later stages of motion processing. Cats with LS lesions will be tested with simple gratings as well as with more complex motion patterns (dynamic random dots). The final project will determine the locus of directionally selective neurons, involved in the ability to discriminate opposite directions of motion. Previous behavioral studies of cats with a selective loss of directional selectivity in visual cortex (cats reared in 8 hz stroboscopic illumination), found greatly reduced contrast sensitivity for stimulus direction but nearly normal direction discrimination performance at high stimulus contrasts. Localized lesions will be made in area 17, 18 or LS in these cats to determine which of the few remaining directionally selective neurons contribute to their residual sensitivity for motion direction.

Funds are requested to support a symposium entitled "Learning and Memory in Vision", scheduled for June 8-11 at the University of Rochester. Recent experimental evidence of plasticity and learning in the adult visual cortex even at the earliest stages of processing suggests a need for the development of new approaches to the study of vision. One of the goals of the meeting is to bring together researchers whose work focuses on the plastic nature and dynamic representation of vision. Nineteen prominent scientists who approach the question of learning and memory in vision from the physiological, anatomical, behavioral and computational perspective will present 45 minute talks. Individual sessions will cover the following topics: cellular and anatomical foundations of learning and memory, adult cortical plasticity, perceptual learning, short-term memory: active observer, and visual short-term memory.

The visual cortex of the brain is an area where there now is evidence for mechanisms of plasticity and learning, even at the earliest stages of processing, and even in the adult brain. It is appropriate to consider new approaches to the study of vision in this context. This meeting brings together researchers whose work focuses on the plastic nature and dynamic representation of vision. Presentations and discussions cover physiological, anatomical, behavioral and computational perspectives. Sessions cover the topics of cellular and anatomical foundations of learning and memory; adult cortical plasticity; perceptual learning; short-term memory and attention in active observers; and visual short-term memory. The conference will have an impact on understanding how the visual system interacts with areas traditionally associated with memory, and so have an impact across neuroscience and psychology, in addition to visual science.

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 visual environment of an active observer is constantly changing, even though its individual features may remain constant. To preserve continuity of visual stimulation, the observer has to not only encode visual information, but also preserve it over brief periods of time. This research is aimed at examining properties of this temporary storage mechanism. We will also explore the role of selected extrastriate cortical areas in storing one of the fundamental features of the visual stimulus, its direction of motion. We chose this feature because its neural coding is well understood and some cortical areas involved in its processing have been identified. These studies will provide important new information concerning the possible participation of visual cortical areas in circuitry subserving visual short-term memory. Proposed experiments will use psychophysical measures, microstimulation and lesions of physiologically identified regions in selected extrastriate cortical areas to investigate the temporary storage (i.e. short-term memory) of directional information. I. Psychophysical properties of mechanisms mediating short-term memory for stimulus motion - The first group of experiments will explore the nature of the process underlying the storage of motion information, in particular its spatio-temporal and directional tuning, retinotopy, and the efficacy of different types of stimulus noise in degrading storage. The monkeys will be tested in a visual task in which two visual stimuli, the sample and the test, separated in time will be judged as the same or different. These studies will provide a better understanding of the mechanisms mediating the retention of motion information, help determine the level of cortical processing at which visual information is stored and set the stage for subsequent studies of neural substrates underlying visual memory. II. The role of areas MT, V3 and V4 in discrimination and storage of stimulus direction and orientation - The goal of this portion of the project is to determine the role of visual areas identified with motion analysis, areas V3 and MT, in the processing and storage of information about stimulus direction. We will use intracortical microstimulation of physiologically identified sites and the lesion approach. To determine the specificity of the effects produced by these manipulations, we will also use non-motion tasks requiring discrimination and retention of stimulus orientation, and apply the same manipulations to localized portions of area V4, which has been identified with form processing. This will help clarify how hierarchical and parallel cortical streams mediate both perception and recall of stimulus features.

SUBPROJECT ABSTRACT NOT PROVIDED

DESCRIPTION (provided by applicant): The ability to briefly retain visual information is fundamental to successfully executing visually guided behaviors. This is a renewal application to study the circuitry underlying the active maintenance of sensory representation, i.e. sensory working memory. The overriding goal is to provide a link between cortical areas traditionally associated with processing of visual motion and regions identified with working memory and cognitive control of visually guided behaviors. We will focus on cortical areas MT and MST, important for motion processing, and on prefrontal cortex (RFC) strongly associated with working memory and cognitive control. Our recent work revealed that during the performance of a memory for visual motion task, MT neurons carry memory-related signals and are affected by the demands of the behavioral task. Recordings from PFC also revealed memory related activity and of activity strongly modulated by the behavioral state of the animal. Furthermore, they revealed responses selective for visual motion, similar to those characteristic of neurons in areas MT &MST. The presence of memory signals and the similarity of sensory responses in motion processing areas and in PFC during the same behavioral task suggests a potential functional link between these 2 regions and their participation in the circuitry sub-serving the ability to remember visual motion. During the next grant period we will examine the nature of recently discovered memory-related directional motion signals in areas MT (Aim 1.1), MST (Aim 1.2) and PFC (Aim 2). We will also focus on the interactions between the 2 regions by determining whether PFC is a source of memory signals and modulation by task demands, recorded in MT and MST (Aim 3). For all experiments, we will use a task in which the monkeys compare the directions of 2 moving stimuli separated by memory delay. We will combine recordings of activity of single neurons and local field potentials, microstimulation and reversible inactivation with psychophysical measures of visual working memory. These studies will shed light on the involvement of neurons in PFC and in cortical areas processing sensory signals used in working memory and the way they coordinate their activity to support successful execution of memory tasks. The knowledge of the neural circuitry underlying short-term storage of sensory information will contribute to the understanding and treatment of diseases characterized by working memory impairments, such as Alzheimer's, Parkinson's and Schizophrenia.

The interactions between vision, cognition and action are much more extensive than previously believed. This is the central motivation for the 26th Symposium of the Center for Visual Science (CVS), entitled "Blurring the Borders Between Vision, Cognition and Action," scheduled for May 29-31, 2008 at the University of Rochester. Twenty researchers who work with neurophysiological, anatomical, behavioral or computational perspectives will participate. Topics will include: Visual and Cognitive Circuits, Visual Signals in Cognitive Circuits, Cognitive Influences on Visual Processing (including attention, context and learning) and Vision During Action. To attract younger scientists, ten travel fellowships will be awarded to graduate students or postdoctoral students who will present their work in a poster session.

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There has been an explosion of information in molecular, cellular, circuit and systems neuroscience but little of that information has made significant inroads into our understanding of cognitive function. This Gordon Research Conference on the Neurobiology of Cognition should help bridge the gap, at the very least by identifying the avenues for connection that have the most potential for near-term traction and by linking scientist from disparate fields.

The conference will take place in Newry, ME on July 20-25, 2014. The emphasis of the workshop is to facilitate in-depth discussion between scientists working in divergent fields whose integration is essential to understanding the neurobiology of cognition. NSF support will enable graduate students and postdoctoral trainees to participate in this high-profile workshop and will allow early stage investigators (non-tenured) to attend as speakers and full participants.

All human experiences of the world - our perceptions, actions, emotions, and decisions - are products of the brain. Neurobiologists attempt to comprehend this fact by studying the brain's anatomical and functional organizing principles. As a community, they investigate the brain at multiple levels simultaneously, with different subgroups focusing on the chemical communication between single cells, or cell-type specificity within neural pathways, or the temporal coordination of activity among brain-wide networks. The knowledge that results from these and many other lines of inquiry must then be integrated and shared throughout the community, which requires meeting opportunities to explain, inquire, discuss, and offer healthy skepticism. Neuroscientific findings are most useful when they shed light on aspects of human behavior, as this is the most immediate and familiar measure of brain function. In the long run, this is particularly important, because a central goal of neuroscience research is to identify mechanisms underlying behavioral deficits in neurological and psychiatric illness. Technical advances in the past decade, including multi-electrode technology, optical methods, and functional magnetic resonance imaging, have enabled researchers to rapidly extract new and expanded information from the brain of humans and animal models. The Gordon Research Conference (GRC) on the Neurobiology of Cognition was established in 2010 to provide a forum through which top researchers are able to report unpublished data, receive feedback from colleagues inside and outside their immediate field, and hold rich and substantive discussions. The 2016 GRC will feature work from top scientists, as well as the most promising young scientists and trainees, who study core aspects of human cognition, including memory, attention, and social perception. In fitting with the spirit of the GRC organization, the aim is catalyze discussion and debate and to share information across partially overlapping fields of neurobiology. Importantly, the conference is arranged to invite young and underrepresented scientists to participate fully in the discussion and establish connections in the field of neurobiology.

The meeting will take place over five days, beginning the first evening with two keynote lectures presenting perspectives on the human brain provided by functional imaging and studies of brain damaged patients. Eight half-day sessions will then explore topics related to the neurobiology of cognition that have shown particular progress in the last years. Among these are sessions dedicated to cognitive influences on sensory processing, the neurobiology of social interaction, prefrontal cortex function, and the brain's production and maintenance of consciousness. Speakers contributing to each session are selected to provide a mix of results from experimental animals and those from human volunteers and patients in an effort to promote the sharing of ideas between groups using different methodologies. As the infusion of new scientists and new ideas is central to the mission of the GRC conferences, an important theme of the meeting is the inclusion of early career investigators and trainees, as well as women and minorities. Diversity is the key to the success of the meeting, which aims to capture and integrate unique perspectives on the neurobiology of cognition. In addition to the sessions, the format includes scheduled periods of open discussion, as well as many opportunities for small groups or one-on-one discussions. This format is particularly conducive to the fostering of new collaborations that cut across established planes of neuroscientific inquiry, promoting discussion between theorists, experimentalists, and clinicians. It is only through such active efforts to share and integrate information that the field of neuroscience as a whole can harness and integrate the many new results and insights that together shape our understanding of the neurobiology of cognition.

?DESCRIPTION (provided by applicant): This proposal requests partial support for the fourth Gordon Research Conference (GRC) on the Neurobiology of Cognition and for its associated Gordon Research Seminar (GRS) for trainees. The driving force behind the GRC is the rapid pace of convergent findings in molecular, cellular circuit and systems neuroscience, augmented by technical developments in simultaneously monitoring and manipulating activity across wide brain regions during complex cognitive tasks. These developments combined with genetic manipulations allowing cell-targeting and computational approaches provide the basis for evolving descriptions of neuronal circuits and dynamics, neurophysiological processes and computational principles underlying cognitive functions. The goal of this GRC is to continue promoting communication and collaboration across relevant levels of analysis among empirical scientists and theoreticians working in the field, emphasizing the most recent findings. The associated GRS, held just prior to the GRC, is designed to provide opportunities for doctoral and post-doctoral trainees to communicate their most recent findings and perspectives, and to prepare them for more in-depth participation in the parent GRC that immediately follows. One of the important features of this GRC is participation of several leading clinician-scientists with unique clinical perspective on a variety of cognitive disorders caused by brain damage and insights into normal cognitive function their work provides. Overall, the program is highly interdisciplinary, bringing together behavioral, neuroimaging, electrophysiological techniques and manipulations targeting specific cell types with computational approaches aimed at constructing realistic models of cognitive operations. The format of the meeting promotes intensive interactions among investigators and trainees from different perspectives and analytic levels, and in particular, between clinicians, experimentalists and theorists.