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Motor Learning and Memory in Health and Disease

$467,864R56FY2007NSNIH

Johns Hopkins University, Baltimore MD

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Abstract

Abstract The neural basis of how people adapt their movements to novel conditions is poorly understood, and yet adaptation is fundamental to our ability to perform calibrated and accurate movements. From a theoretical standpoint, motor adaptation appears to depend on plasticity in regions of the brain that learn to associate motor commands and sensory consequences. Where are these regions? In the past funding cycle we found converging evidence from cerebellar and Huntington's disease patients, from neuroimaging studies on normal volunteers, and from ventrolateral thalamic stimulation in Essential Tremor patients that the key subcortical structure responsible for reach adaptation is the cerebellum and not the basal ganglia. However, neurophysiological and imaging studies also indicate that in response to error, anterior parietal cortex and frontal motor areas are engaged to adaptively change motor commands. Here we suggest that a possible reason why multiple regions are engaged during adaptation may be that the motor output is a sum of two or more distinct processes that simultaneously adapt to motor error but have different computational properties. Using examples from both reach and saccade adaptation, we propose that motor error engages one system that is highly sensitive to error but tends to rapidly forget, and another system that has poor sensitivity to error but has a much slower forgetting rate. We propose that the new theory can account for a host of observations in reach and saccade adaptation. Our aim is to perform experiments that test behavioral predictions of this hypothesis, and search for their neural correlates. Our search for neural correlates benefits from a number of innovations: we propose to use thalamic deep brain stimulation to investigate contribution of subcortical networks to motor adaptation. We propose to use fMRI compatible robots and brain imaging to investigate neural correlates of the fast and slow motor learning system. Finally, we propose to record from single cells in the human ventrolateral thalamus during reaching in patients that undergo functional neurosurgery and to quantify response of these cells to reach errors during adaptation.

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