Apostolos P. Georgopoulos - US grants

DESCRIPTION (Adapted from applicant's abstract): The overall goal of the research proposed in this application is to determine the brain activation patterns during performance of specific perceptual motor cognitive tasks, as revealed by high field strength (4 Tesla) functional magnetic resonance imaging (fMRI). Healthy women and men will be studied. The tasks are designed to test hypothesis of how some higher order motor functions are represented in the brain. These functions include predictive motor control, such as intercepting a moving target, and tasks reflecting praxis, namely complex purposeful motor actions, such as copying figures from visual templates, finding exit routes in mazes, and constructing objects from component parts. The potential achievement of these objectives is within reach, due to the adequate resolution afforded by the fMRI even for individual subjects. The hypotheses will be tested (a) that each one of the tasks above involves the cooperative interaction of specific brain areas, (b) that there is an overlap in the pattern of this activation, and (c) that this overlap corresponds to the common functional core shared by these tasks. The data acquired will be analyzed using both traditional as well as modern multivariate statistical techniques, such as hierarchical tree analysis. The results to be obtained are expected to provide novel insights into how the brain deals with dynamic visuomotor processes that are commonly disturbed in patients suffering from constructional apraxia. Finally, the general hypothesis will be tested that two genders do not differ in the functional brain activation patterns underlying the tasks above; if significant differences are found, these will be identified and will lead to the generation of new hypotheses about the brain processing of visuo spatial and visuo constructive information by women and men.

male; female; cognition; magnetic resonance imaging; nervous system; human subject; biomedical resource;

This collaborative effort is an extension of work supported by a grant funded for monkey studies (RO1 NS17413-20, 7/1/96 - 6/30/2001). It is conducted in a synergistic fashion together with similar and parallel experiments to be carried out with humans using. The general goal of this research is to understand the neural mechanisms underlying praxis, that is complex, purposeful motor actions; these mechanisms are largely unknown. In the monkey studies, rhesus monkeys are trained to perform tasks commonly used to determine the presence of constructional apraxia in brain-damaged human patients, including copying simple geometrical figures, assembling objects out of component parts, and route finding in a maze. The activity of single cells during task performance is recorded in key cortical areas of the monkey brain using a 7-microelectrode system. We have started examining in human subjects using fMRI at 4 Tesla which regions are activated during identical or analogous tasks. Extensive preliminary data has been collected demonstrating that activity is primarily in the frontal cortex, a finding that was unexpected.

DESCRIPTION (provided by the applicant): The general goal or this research is to understand the neural mechanisms underlying spatial cognition and to investigate the role of the right hemisphere in this function. For that purpose, rhesus monkeys will be trained to perform tasks commonly used to determine the spatial capacities of adult human subjects and children during development. These tasks include memorizing locations of visual stimuli, categorizing space explicitly (e.g. "high"/"low"), making comparative spatial judgments (e.g. about "higher/lower"), estimating relative distances (with respect to a reference point, or not), and using Cartesian coordinate axes. Each monkey will be trained in all tasks. The activity of single cells during task performance will be recorded in posterior parietal cortex using 16-microelectrode systems. Posterior parietal cortex is known to be intimately involved in spatial operations and, therefore, we expect cell activity to be modulated involved in the aforementioned tasks and to provide valuable Information concerning their neural mechanisms. In addition, we will test the hypothesis that parietal cortex in the right hemisphere is specialized for spatial operations, a hypothesis based on the differential effects of brain damage on spatial abilities of human patients. For that purpose, we will record simultaneously from symmetric posterior parietal sites of the two hemispheres during performance of all the tasks. The data to be obtained will be analyzed using uni- and multivariate statistical methods to determine the control of these tasks by singe cells and neuronal populations, and to delineate the specific contribution of each one of the cortical areas above to this control. By analyzing normal brain mechanisms, we hope to discover some basic principles of organization underlying spatial deficits observed in brain-damaged people.

[unreadable] DESCRIPTION (provided by applicant): The overall goal of the research proposed in this application is to determine the brain activation patterns in the human frontal and parietal lobes during performance of specific spatial cognitive tasks, as revealed by high field strength (4 Tesla) functional magnetic resonance imaging (fMRI). Healthy women and men will be studied. The tasks are designed to test hypotheses of how some higher order spatial cognitive processes are represented in the frontoparietal cortex. The research proposed is centered on route-tracing. This function crucially depends on the integrity of this cortex, as evidenced by its disturbance following cortical damage, e.g. after stroke. The processes involved in route-tracing comprise tracing of route segments as well as turning from one segment to the next. We will test five hypotheses concerning the neural representation of these processes and their specific aspects for which parietal cortex might be instrumental. The first hypothesis is that the direction of tracing of a straight route segment is represented in an orderly fashion, such that there is an orderly map of the direction of tracing. The second hypothesis is that tracing of a complex route (i.e. a route composed of multiple segments) is a spatially distributed process that sequentially engages distinct parts of the frontoparietal cortex, as the process unfolds in time. The third hypothesis is that turning from one segment to the next involves a process of mental rotation between these two segments, such that the intensity of activation will depend on the angle of rotation. The fourth hypothesis is that this dependence of the activation on the angle of directional change will be qualitatively and quantitatively similar to the dependence observed in a stand-alone mental rotation paradigm. Finally, the fifth hypothesis concerns differences between women and men with respect to the brain activation patterns associated with tracing complex sequences and the dependence of activation on the turning angle and mental rotation. The potential achievement of these objectives is within reach, due to the adequate resolution afforded by the fMRI at high magnetic field, even for individual subjects. The data acquired will be analyzed using both traditional as well as specialized spatial statistical techniques. The results to be obtained are expected to provide novel insights into how the brain deals with dynamic, cognitive, visuomotor processes that are commonly disturbed in patients suffering from cortical damage, e.g. after stroke. In addition, they will provide an insight into possible hemispheric asymmetries and differences between women and men, especially with respect to the performance of sequential movement and mental rotation tasks [unreadable] [unreadable]