The basal ganglia contribute to the suppression and initiation of saccadic eye movements through the inhibitory connection from the substantia nigra pars reticulata (SNr) to the superior colliculus. This mechanism consists of serial and parallel connections, which are mostly inhibitory and GABAergic. Dopamine is known to exert powerful modulatory effects on the basal ganglia function, but its nature and mechanism are still unclear, especially in relation to voluntary behavior. The purpose of this series of investigation was to study the role of dopamine in the control of saccadic eye movements. We examined, in the monkey, whether and how the deficiency of the nigrostriatal dopaminergic innervation affects saccadic eye movements. The present article is focused on spontaneous saccades that the monkey made with no incentive to obtain reward; the next paper will describe task-specific saccades. Using an osmotic minipump we infused 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine (MPTP) unilaterally into the head-body junction of the caudate nucleus of monkeys where presaccadic neurons were clustered. Tyrosine hydroxylase activity, visualized using an immunohistochemical method, decreased locally around the injection site with some effects extending into the ipsilateral putamen and locally in the ipsilateral substantia nigra. Changes of eye movements started to appear 3–5 d after starting the infusion. Spontaneous saccades became less frequent. The area scanned by the saccades became narrower and shifted to the hemifield ipsilateral to the infusion site. The saccade amplitudes and peak velocities decreased; durations were prolonged. These effects were more prominent for saccades directed toward the side contralateral to the infusion site. These monkeys showed no obvious skeletomotor symptoms. These results suggest that the local deprivation of the dopaminergic innervation in the caudate nucleus facilitates neuronal activity of the SNr leading to suppression of saccadic eye movements.

Unilateral infusion of MPTP into the monkey caudate nucleus produced deficits in task-specific saccades, in addition to the deficits in spontaneous eye movements (preceding article). We trained three monkeys to perform two kinds of saccade tasks: (1) saccade task for eliciting visually guided saccades and (2) delayed saccade task for eliciting memory-guided saccades. After the MPTP infusion, dopaminergic function, estimated by tyrosine hydroxylase (TH) immunoreactivity, was shown to be decreased locally around the infusion site at the head-body junction of the caudate. We found that the deficits were prominent in the saccades directed to the side contralateral to the infusion (contralateral saccades). Memory-guided saccades were sometimes misdirected to the ipsilateral side even when the cue stimulus was presented on the contralateral side. Among the parameters of saccades, a selective change was found in the saccade latency: the latency was prolonged consistently in contralateral memory-guided saccades. The amplitude and velocity of saccades decreased in contralateral saccades, either memory guided or visually guided. The duration of saccades tended to increase in visually-guided saccades and memory-guided saccades, in both directions. Only one monkey, in which the decrease in TH activity included a large part of the putamen and the head of the caudate, showed prolongation of manual reaction time for lever release.

1. Measurements were made in four normal human subjects of the accuracy of saccades to remembered locations of targets that were flashed on a 20 x 30 deg random dot display that was either stationary or moving horizontally and sinusoidally at +/-9 deg at 0.3 Hz. During the interval between the target flash and the memory-guided saccade, the "memory period" (1.4 s), subjects either fixated a stationary spot or pursued a spot moving vertically sinusoidally at +/-9 deg at 0.3 Hz. 2. When saccades were made toward the location of targets previously flashed on a stationary background as subjects fixated the stationary spot, median saccadic error was 0.93 deg horizontally and 1.1 deg vertically. These errors were greater than for saccades to visible targets, which had median values of 0.59 deg horizontally and 0.60 deg vertically. 3. When targets were flashed as subjects smoothly pursued a spot that moved vertically across the stationary background, median saccadic error was 1.1 deg horizontally and 1.2 deg vertically, thus being of similar accuracy to when targets were flashed during fixation. In addition, the vertical component of the memory-guided saccade was much more closely correlated with the "spatial error" than with the "retinal error"; this indicated that, when programming the saccade, the brain had taken into account eye movements that occurred during the memory period. 4. When saccades were made to targets flashed during attempted fixation of a stationary spot on a horizontally moving background, a condition that produces a weak Duncker-type illusion of horizontal movement of the primary target, median saccadic error increased horizontally to 3.2 deg but was 1.1 deg vertically. 5. When targets were flashed as subjects smoothly pursued a spot that moved vertically on the horizontally moving background, a condition that induces a strong illusion of diagonal target motion, median saccadic error was 4.0 deg horizontally and 1.5 deg vertically; thus the horizontal error was greater than under any other experimental condition. 6. In most trials, the initial saccade to the remembered target was followed by additional saccades while the subject was still in darkness. These secondary saccades, which were executed in the absence of visual feedback, brought the eye closer to the target location. During paradigms involving horizontal background movement, these corrections were more prominent horizontally than vertically. 7. Further measurements were made in two subjects to determine whether inaccuracy of memory-guided saccades, in the horizontal plane, was due to mislocalization at the time that the target flashed, misrepresentation of the trajectory of the pursuit eye movement during the memory period, or both. 8. The magnitude of the saccadic error, both with and without corrections made in darkness, was mislocalized by approximately 30% of the displacement of the background at the time that the target flashed. The magnitude of the saccadic error also was influenced by net movement of the background during the memory...

Cutaneous facial inputs influencing head movement were examined in the conscious and anaesthetised cat. EMG recordings were made in neck muscles of conscious, unrestrained cats in which an unexpected light cutaneous stimulus was applied to the glabrous skin of the planum nasale (PN). These observations established that head aversion movements were associated with synchronised activation of both deep and superficial dorsal neck muscles. In anaesthetised cats in which activity in the motoneurons of the large dorsal neck muscles was examined, mechanical stimulation of the PN or electrical stimulation of the infraorbital nerve (ION) produced a short latency, reflex activation. The reflex could be elicited by excitation of low threshold, rapidly conducting fibres in the ION. Intracellular recording from neck motoneurons showed that there is a short latency, probably disynaptic, excitatory pathway from low threshold nerves in the ION to neck motoneurons, but discharge of neck motoneurons occurred several milliseconds later, presumably as a result of activity in a longer multisynaptic pathway.

Macrosaccadic oscillations of eyes (MSO) are regarded as a form of saccadic dysmetria secondary to cerebellar dysfunction. They are usually conjugate, horizontal, and symmetric in both directions of gaze. Using magnetic search coils, we studied a patient with MSO that developed five years following head injury and involved synchronously horizontal, vertical, and torsional planes. The MSO were characterized by directional pre-ponderance and were associated with ipsilateral pontine lesion. We propose a disturbance of fixation mechanisms due to unilateral disinhibition of saccadic burst neurons in three planes. This could arise from either primary or secondary dysfunction of omnipause neurons due to impaired input from the contralateral superior colliculus. The delayed onset is suggestive of denervation supersensitivity as the underlying pathophysiology.