Pathophysiology of smooth pursuit eye movements in central neurologic disorders

In the last two decades, lesion studies and functional imaging studies have identified the human homologues of some of the ocular pursuit areas originally described in monkeys. However, the circuitry of pursuit is still not completely understood, and the neural substrates for some of the functional elements identified by pursuit models are not known. In this thesis, pursuit in normal subjects was compared with pursuit in a wide variety of patients with focal brain lesions or neurologic disorders with the aim of associating pursuit deficits with lesion sites. The subjects were 72 patients with focal cerebral lesions, 12 patients with cerebellar ataxia, 7 patients with Parkinson's disease and 25 control subjects. Pursuit gain and phase were studied using conventional sinusoidal pursuit paradigms, while predictive and non-predictive pursuit were studied using intermittently illuminated constant velocity targets. Eye movements were recorded using an infrared limbus reflection technique. The results showed that lesions confined to the V5 area of the occipito-temporal cortex or region of the limbs of the internal capsule were associated with ipsidirectional pursuit deficit. Lesions involving the cortical network for directed attention, including the posterior parietal cortex, frontal eye fields and thalamus were predominantly associated with symmetric bidirectional pursuit deficit. Extensive lesions produced varying degrees of asymmetric bidirectional pursuit deficit. Right hemispheric lesions produced more devastating deficits than similar lesions on the left. Cerebellar or basal ganglia lesions reduced the gain of pursuit. Cerebral lesions impaired both the velocity gain and displacement gain of pursuit whereas cerebellar lesions impaired only the velocity gain. Cerebellar lesions, subcortical striatal-capsular lesions and some focal cerebral lesions delayed the onset of anticipatory pursuit but did not completely abolish prediction. Parkinson's disease was associated with progressive bradykinesia and hypokinesia of ocular pursuit. A putative smooth pursuit pathway was constructed based on the results of this study and the current body of knowledge