Background: We monitor brain activities in thalamotomy for Parkinson's disease by a bipolar concentric microelectrode. Aim: The present study aimed to standardize the quantitative monitoring for targeting and for pathophysiological analysis. Methods: To show the process of data analysis, we selected 20 patients who gave informed consent for thalamotomy. The cases were divided into group I with rigidity, but no tremor (n = 10), and the group II with rigidity and tremor (n = 10). Most patients suffered from bradykinesia. We monitored the electromyograms of the neck and limb muscles. Brain activities were sampled as the electrode passed through the caudate and thalamic nuclei, divided into filtered local field potentials and multiple unit spikes, and rated at different depths by the summed periods in percent occupied by the component wavelets of field potentials at 3-7, 7-13, 13-27 and 27-80 Hz. Results: Analysis was summarized by the depth distribution histograms of dominant wavelet compositions. The 13-27-Hz activities were exaggerated in the caudate, thalamic ventroanterior and ventrolateral nuclei. The 3-7-Hz activities timelocked with tremor were exaggerated in the nucleus ventralis intermedius. Group I cases showed little 3-7-Hz activities. Thermolesion in the thalamus with those highly-rated activities alleviated tremor and rigidity, but spared most bradykinesia. Conclusion:The standardized analysis suggests that the thalamic 3-7-Hz and 13-27-Hz activities serve as the quantitative markers of pathophysiology representing tremor and rigidity, respectively.

The present study provides evidence that the saccadic signals in the caudate nucleus (caudate) are transmitted to the substantia nigra pars reticulata (SNr). We inserted two microelectrodes into the caudate and SNr of monkeys trained to perform saccade tasks. After identifying the functional characteristics of a SNr neuron recorded, we stimulated the caudate (single pulse, < 100 microA) to see whether its discharge rate changed. Among 138 SNr cells tested, 60 showed responses to stimulation of the caudate: inhibition only (n = 21), inhibition-excitation (n = 17), excitation only (n = 9), and excitation-inhibition (n = 13). The latencies were 9.0-32.5 ms (mean 16.7 ms) for the initial inhibitory responses and 6.5-35.0 ms (mean 16.7 ms) for the initial excitatory responses. Pars compacta cells (n = 10) were unresponsive. The effect of caudate stimulation was selective in terms of (1) functional type of SNr cells, (2) location of SNr cells, and (3) stimulation site within the caudate. Functional type of SNr cells: saccadic, visual, expectation-related cells were more responsive than auditory, mouth/hand/arm movement-related, and reward-related cells. Many of the cells whose functional characteristics were unidentified responded to the caudate stimulation. The preferential effects were seen among the functional subtypes: cells related to memory-guided saccades, not visually guided saccades; cells with conditioned visual responses, not simple visual responses. Location of SNr cells: the stimulus effects were seen preferentially in cells in the central part of the SNr, not in the dorsal part. Stimulus site: stronger effects, whether inhibition or excitation, were obtained when the stimulation was applied to the head-body transitional zone where visuooculomotor cells were clustered. Behaviorally contingent correlation of spike activity was found between the caudate-nigral pair of cells. For example when a SNr cell with memory-contingent saccadic activity was inhibited by the caudate stimulation, a caudate cell at or close to the stimulation site may show memory-contingent saccadic activity with a similar movement field.

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.

The synaptic organization of the saccade-related neuronal circuit between the superior colliculus (SC) and the brainstem saccade generator was examined in an awake monkey using a saccadic, midflight electrical-stimulation method. When microstimulation (50-100 microA, single pulse) was applied to the SC during a saccade, a small, conjugate contraversive eye movement was evoked with latencies much shorter than those obtained by conventional stimulation. Our results may be explained by the tonic inhibition of premotor burst neurons (BNs) by omnipause neurons that ceases during saccades to allow BNs to burst. Thus, during saccades, signals originating from the SC can be transmitted to motoneurons and seen in the saccade trajectory. Based on this hypothesis, we estimated the number of synapses intervening between the SC and motoneurons by applying midflight stimulation to the SC, the BN area, and the abducens nucleus. Eye position signals were electronically differentiated to produce eye velocity to aid in detecting small changes. The mean latencies of the stimulus-evoked eye movements were: 7.9 +/- 1.0 ms (SD; ipsilateral eye) and 7.8 +/- 0.9 ms (SD; contralateral eye) for SC stimulation; 4.8 +/- 0.5 ms (SD; ipsilateral eye) and 5.1 +/- 0.7 ms (SD; contralateral eye) for BN stimulation; and 3.6 +/- 0.4 ms (SD; ipsilateral eye) and 5.2 +/- 0.8 ms (SD; contralateral eye) for abducens nucleus stimulation. The time difference between SC- and BN-evoked eye movements (about 3 ms) was consistent with a disynaptic connection from the SC to the premotor BNs.