Role of the Basal Ganglia in the Controlof Purposive Saccadic Eye MovementsOKIHIDE HIKOSAKA, YORIKO TAKIKAWA, AND REIKO KAWAGOEDepartment of Physiology, Juntendo University, School of Medicine, Tokyo, JapanI. Introduction 954II. Concept of the Basal Ganglia 954III. General Scheme of Saccadic Eye Movement 955A. Hierarchy of oculomotor mechanisms 955B. Superior colliculus: a key station for saccade control 957IV. Mechanisms of the Basal Ganglia: Disinhibition 957A. Visuo-oculomotor activities in the substantia nigra pars reticulata 958B. Substantia nigra pars reticulata-superior colliculus projection (and its experimentalmanipulation) 958C. Caudate nucleus as an input station in the basal ganglia 958D. Visuo-oculomotor activities in the caudate nucleus 959E. Caudate nucleus-substantia nigra pars reticulata projection 959F. Disinhibition: a key feature of basal ganglia function 959G. Reversible blockade of substantia nigra pars reticulata 960V. Mechanisms of the Basal Ganglia: Enhancement of Inhibition 960A. Subthalamic nucleus as a mechanism for motor suppression 961B. Neural activity in the subthalamic nucleus 961C. Globus pallidus external segment as a mediator for enhancement of inhibition 962D. Neural activity in the globus pallidus external segment 962E. Focusing and sequencing of basal ganglia signals 962VI. Mechanisms of the Basal Ganglia: Role of Dopamine 963VII. Context Dependency of Neural Activity in the Basal Ganglia 964A. Relation to attention 964B. Relation to working memory 964C. Relation to expectation 965D. Relation to sequential procedural learning 965VIII. Reinforcement: A Key Factor for Decision Making in the Basal Ganglia 966A. Experimental approach to motivation and oculomotor action 966B. Modulation of caudate nucleus neural activity by expectation of reward 967C. Possible role of dopamine neurons 967D. Scheme of reinforcement learning 968IX. Clinical Application 969X. Conclusions 970Hikosaka, Okihide, Yoriko Takikawa, and Reiko Kawagoe. Role of the Basal Ganglia in the Control of PurposiveSaccadic Eye Movements. Physiol Rev 80: 953–978, 2000.—In addition to their well-known role in skeletal movements, thebasal ganglia control saccadic eye movements (saccades) by means of their connection to the superior colliculus (SC).The SC receives convergent inputs from cerebral cortical areas and the basal ganglia. To make a saccade to an objectpurposefully, appropriate signals must be selected out of the cortical inputs, in which the basal ganglia play a crucial role.This is done by the sustained inhibitory input from the substantia nigra pars reticulata (SNr) to the SC. This inhibition canbe removed by another inhibition from the caudate nucleus (CD) to the SNr, which results in a disinhibition of the SC.The basal ganglia have another mechanism, involving the external segment of the globus pallidus and the subthalamicnucleus, with which the SNr-SC inhibition can further be enhanced. The sensorimotor signals carried by the basal ganglianeurons are strongly modulated depending on the behavioral context, which reflects working memory, expectation, andattention. Expectation of reward is a critical determinant in that the saccade that has been rewarded is facilitatedsubsequently. The interaction between cortical and dopaminergic inputs to CD neurons may underlie the behavioraladaptation toward purposeful saccades.PHYSIOLOGICAL REVIEWSVol. 80, No. 3, July 2000Printed in U.S.A.www.physrev.physiology.org 9530031-9333/00 $15.00 Copyright © 2000 the American Physiological SocietyI. INTRODUCTIONAnimals lacking the striatum always display a certainfatuous, expressionless facies from which the eyes starevacantly and with morbid intentness.Mettler (212)Patients with basal ganglia disorders suffer from ex-cessive or retarded movements of the trunk, arms, or legs.Such movement deficits are so disabling that deficits ineye movements, if present, may remain unnoticed duringclinical tests. Notably, however, one of the diagnosticsigns of Parkinson’s disease is the expressionless face,often called “parkinsonian mask” (283), which is duepartly to the paucity of spontaneous gaze shifts (saccadiceye movements). Parkinsonian patients may make a sac-cade, on command, to a visual object with little difficulty,yet their voluntary saccades are rare. These facts suggestthat the basal ganglia are involved in the control of sac-cades, but in an intricate manner. Recent studies ontrained animals and humans have suggested that the basalganglia are related to both initiation and suppression ofsaccades in complex behavioral contexts, which we sum-marize in this review.Clinical studies have indicated that smooth pursuit isalso impaired in basal ganglia disorders (75, 326). How-ever, because to our knowledge there has been no studythat suggests how the basal ganglia contribute to thecontrol of smooth pursuit, we do not make further com-ments on this issue.This article may be divided roughly into three parts.First, we introduce you to the present topic by speculat-ing how the basal ganglia evolved to control spatial ori-enting (sects. II and III). In the second part, we summarizethe experimental evidence for the specific relation of thebasal ganglia to saccadic eye movement (sects. IV–VI). Thesecond part will, hopefully, be continued into the thirdpart smoothly, where we describe the results of recentstudies on cognitive or motivational aspects of motorcontrol (sects. VII and VIII). The issues dealt with in thethird part are not limited to the control of eye movementbut are of more global importance for brain function ingeneral.II. CONCEPT OF THE BASAL GANGLIAThe basal ganglia are considered to be necessary forvoluntary control of body movements (53). This idea isderived mainly from the clinical observations that lesionsin the basal ganglia lead to movement disorders rangingfrom the inability to initiate a movement to the inability tosuppress involuntary movements. Anatomically, the basalganglia are the aggregate of nerve cell nuclei located atthe base of the cerebrum (39). Although there are differ-ent opinions on the definition (106), the basal ganglia, asa functional entity, are composed of the caudate nucleus(CD) and putamen (PUT) (collectively called striatum),globus pallidus, substantia nigra, and subthalamic nu-cleus (STN).1The globus pallidus is further divided intothe external segment (GPe) and the internal segment(GPi); the substantia nigra is divided into the pars reticu-lata
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