Charles Marshall Gray - US grants

In the proposed research, we plan to employ a relatively new experimental paradigm-termed "free viewing"-in which a monkey freely views a collection of natural images, to investigate the firing patterns of pairs of simultaneously recorded neurons in striate cortex under conditions approximating those occurring naturally. Our goal is to obtain answers to three categories of questions. First, are the receptive field properties of V1 neurons, measured during free viewing, consistent with the receptive field properties of the same cells measured using classical techniques? An answer to this question will help us to determine the extent to which classically measured receptive field properties can account for the behavior of primary visual cortex under natural conditions. Second, is the activity of V1 neurons during free viewing consistent with the predictions of a hypothesis for sparse coding of natural images? In this framework, an efficient code for natural scenes is achieved by representing visual images with the smallest number of simultaneously active cells. The free viewing paradigm will provide an opportunity to test several specific predictions of this hypothesis. Third, do simultaneously recorded neurons in V1 exhibit synchronous responses to natural image features that are consistent with a hypothesis for perceptual grouping? A large body of evidence has demonstrated that cortical neurons engage in stimulus dependent synchronous firing. The proposed experiment will determine if, and in response to what stimulus features, synchronous activity occurs during the free viewing of natural images. To answer these questions, we will conduct two types of measurements from pairs of single units in area V1 of awake behaving macaques monkeys. First, while the animals perform a simple fixation task, we will quantitatively map each cell's receptive field properties using i) drifting sinewave gratings, and ii) the methods of reverse correlation analysis. Second, while the animals perform a match-to-sample task, in which they visually scan a set of natural images to identify a cued object, we will measure the joint activity of pairs of neurons in response to these stimuli. These data will allow us to address the questions posed above, and thus improve our understanding of the behavior of primary visual cortex under natural conditions.

0118406
Gray

This Americas Program award will support a workshop organized by Dr. Charles M. Gray, Montana State University, and Dr. Pedro E. Maldonado of the University of Chile, to be held in Pucon, Chile in March 2002. The workshop will focus on the theoretical and experimental foundations of cooperative cortical dynamics with the goal of discussing different and complementary approaches to improve our understanding of brain function.

Participants will discuss theoretical and empirical approaches to characterizing and modeling neuronal activity in different structures of the nervous system, using a variety of methods ranging from electrophysiological techniques for the recording of large numbers of neurons to the mathematical analysis of spike trains. An added benefit of this activity will be the introduction of advances in systems neuroscience and techniques employed to examine cortical function to students from the U.S. and throughout Latin America.

[unreadable] DESCRIPTION (provided by applicant): The long-term objective of the proposed research is to understand the neuronal mechanisms underlying scene segmentation by the mammalian visual system. In this process, the visual system is thought to parse a scene into its component objects by identifying relationships among common features. A critical step in segmentation is the grouping of oriented features into contours that form the boundaries of objects. Current evidence indicates that striate cortex makes a fundamental contribution to this process of contour integration, but the underlying neuronal representations are not fully understood. In the proposed research, we plan to monitor the activity of groups of neurons at two or more sites in striate cortex of behaving macaque monkeys, in order to test three specific hypotheses for the neuronal correlate of contour integration. We will conduct two sets of experiments in which we will establish the relations between contour salience, neuronal activity and behavioral performance. In the first experiment, the animals will be required to signal their detection of a peripheral contour embedded in a background by making a saccadic eye movement to its location after a central fixation target is extinguished. In the second experiment, the animals will be cued to select one of two adjacent contours embedded in a background by making a saccadic eye movement to the cued contour after a central fixation target is extinguished. In both experiments, the contour salience, and hence the task difficulty, will be controlled by varying the orientation of the elements comprising the contour. The visual stimuli will be composed of arrays of randomly oriented Gabor patches, in which one or two subsets of the patches will be aligned to form a closed contour. Elements of the contour(s) or background will be positioned over the cellular receptive fields to activate the recorded neurons. This paradigm will enable us to keep the local stimuli activating the cells constant while systematically manipulating the figure/ground relationships, the perceptual salience and the behavioral relevance of the contours. We will analyze the resulting activities to determine if contour integration is correlated with specific changes in firing rates, temporal correlations, response latencies or some combination of these variables. Together, these experiments will enable us to investigate the neuronal correlate of contour integration in striate cortex, and advance our understanding of scene segmentation processes in general.

This award provides funding for the development of a multichannel recording device that can be used to monitor activity of multiple individual neurons in the mammalian brain. Although it is now accepted by most neuroscientists that most brain functions reflect the concerted efforts of many neurons, direct demonstrations have been hampered by the limitations of currently available technology for single-cell recording from the brain, including the lack of automation in electrode placement, a relatively low number of electrodes that can be used simultaneously, and a relatively high cost. The device to be developed should significantly improve on the technical limitations of existing hardware, while not increasing the cost of the equipment needed . Important features include a low cost manipulator system that can position up to 64 electrodes independently of each other, a feedback control system that will couple positioning of the electrodes to the signals detected by the electrodes, and an implant device that allows implanted electrodes to be left in place for long-term recording.

DESCRIPTION (provided by applicant): The long-term goal of the proposed research is to test the hypothesis that the maintenance of information about object identity and/or location in working memory involves the cooperative interaction of populations of neurons located in a distributed network that includes dorsolateral prefrontal, posterior parietal and inferior temporal cortical regions. To accomplish this goal, we plan to develop and implement three essential methodologies and then test the feasibility of combining them in a single experimental paradigm. First, we will train macaque monkeys to perform an oculomotor Go/No-Go delayed match-to-sample task. The task requires the animals to flexibly integrate and retain information about the identity and/or spatial location of complex visual objects, and use this information to form a rule-based behavioral decision. Second, we have designed a new type of micromanipulator that enables the semi-chronic recording of neuronal activity from up to 36 independently moveable microelectrodes housed within a single recording chamber. We plan to construct, test and optimize these devices, and then use them to record spatio-temporal patterns of neuronal activity in the dorsolateral prefrontal, posterior parietal, and inferior temporal cortical areas while the animals perform the behavioral task. Third, we have developed a comprehensive approach to the statistical quantification of neuronal correlations on a fast time scale. We plan to collect an initial body of experimental data and use these analytic methods to investigate the statistical relations of activity in these three areas at both the field potential and single unit levels. This research plan constitutes the initial phase of a long-term project to study the cortical mechanisms underlying visual cognition. For several reasons, it is particularly well suited to the goals of the R21 program. A variety of new techniques will be developed to conduct the experiments, including innovations in surgical, mechanical, electrophysiological and behavioral methods. New analytical methods will be incorporated to evaluate and interpret the resulting data. And, completion of this initial phase of the research plan will form the basis for future applications.

[unreadable] DESCRIPTION (provided by applicant): The goal of the proposed research is to advance our understanding of higher brain functions by developing a new class of instrumentation that will enable investigators to simultaneously monitor neuronal activity from tens to hundreds of independently movable microelectrodes that are semi-chronically implanted in widespread regions of the brains of awake, behaving monkeys. To accomplish this objective, we plan to design and build an integrated system, consisting of a form-fitting chamber and a modular, replaceable guide array and microdrive, for implanting and independently manipulating up to 240 microelectrodes in the brains of alert macaque monkeys. The system will provide high density electrophysiological access to an entire cerebral hemisphere and enable simultaneous recording of unit and local field potential activity from many cortical and/or subcortical locations for periods lasting many weeks or months. We will implant and test the system in three macaque monkeys in order to i) optimize the design of the system and minimize the time and expense required for its manufacture, ii) determine the most effective design of the system to facilitate its surgical implantation, insure its mechanical stability, reduce the chances of intracranial infection, and provide for the best possible care of the wound margins surrounding the implant, iii) evaluate the long-term quality and stability of the electrophysiological recordings, and iv) evaluate the effects of the implanted electrodes and guide tubes on the histological structure of the brain tissue. This approach will insure that the system is both generic and modular in its design while optimizing its capabilities and minimizing the costs for its manufacture. When completed, the proposed system will provide the research community with a new technology for long-term monitoring of neuronal activity from distributed locations in the brain of non-human primates. This technological advance will open up vast new opportunities for studying the neural basis of higher brain functions. [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): The goal of the proposed research is to advance our understanding of the storage, maintenance, and retrieval of information in visual working memory. Our guiding hypothesis is that these functions involve the synchronous, and causal, interactions of neuronal populations located in prefrontal, posterior parietal, and inferior temporal cortical regions. Our research plan, based on an extensive body of preliminary studies supported by a previous R21 award, consists of two sets of experiments addressing three specific aims. In the first experiment, we will train macaque monkeys to perform an oculomotor delayed match-to-sample task in which memory load will be manipulated by changes in task duration and the inclusion of distractors. This study will enable us to test specific hypotheses regarding the neural mechanisms mediating the storage and maintenance of information in visual working memory. In the second experiment, another set of monkeys will be trained to perform a delayed match-to-sample task in which they must actively retrieve either the shape or the color of a sample object following a rule-based cue. This experiment will enable us to test specific hypotheses regarding the neural mechanisms mediating the active retrieval of information from visual working memory. In both experiments, we will perform long-term measurements of neuronal activity (i.e. unit activity and local field potentials) from up to 32 independently movable microelectrodes in prefrontal, posterior parietal, and inferior temporal cortical areas while the monkeys perform the behavioral tasks. Once the data are collected, we will apply a comprehensive battery of statistical analyses to test specific hypotheses regarding the storage, maintenance and retrieval of information in visual working memory. These analyses will characterize the spatiotemporal statistical relations between groups of simultaneously recorded neurons, between neurons and local field potentials, and between local field potentials. The results will allow us to test hypotheses concerning the synchronous neuronal interactions that occur both within and between cortical areas in support of visual working memory function. We anticipate that the proposed studies will produce new insights into the dynamics of synchronous activity thought to underlie the representation and utilization of visual information in working memory. The knowledge gained from these studies will provide an important framework for understanding synchronous functional relations in the brain that may be important in the diagnosis of pathological conditions, such as Alzheimer's disease, autism, and schizophrenia, in which these relations have already been demonstrated to be deficient. PUBLIC HEALTH RELEVANCE: Disturbances of attention and working memory, and the changes in synchronous cortical activity that accompany them, are a hallmark of human psychiatric conditions including Alzheimer's disease, Autism, Attention Deficit Hyperactivity Disorder, and Schizophrenia. Analyses of disturbances in cortico-cortical synchronization hold the promise of providing critical diagnostic measures for a wide variety of cognitive disturbances. Hence, an improved understanding of the neural mechanisms mediating working memory and the task-dependent synchronization of cortical activity will have a significant impact on the development of treatments for a wide variety of neuropsychiatric disorders.