Initiation Of Saccadic Eye Movements Research Articles

Increased saccadic latency in Amblyopia: Oculomotor and attentional factors

Amblyopia is a neurodevelopmental disorder of vision that arises from disrupted binocular vision during early childhood. Delayed initiation of saccadic eye movements is an established feature of amblyopia. The present study investigated whether oculomotor and/or attentional factors contribute to increased amblyopic eye saccadic latencies. Participants with normal vision (n = 10) and amblyopia (n = 10; 4 anisometropia, 6 strabismic/mixed) performed visually-guided saccades to targets presented via a mirror haploscope. Eye movements were recorded for both eyes even under monocular viewing conditions. In Experiment 1, we measured the latency, amplitude gain and peak velocity of saccades as targets were presented binocularly, or monocularly. Saccadic latencies were significantly longer for both eyes when targets were presented to only the amblyopic eye compared to all other conditions. Saccade gain and main sequence rate constants were similar across groups for all viewing conditions. In Experiment 2, we tested the hypothesis that shifts of overt attention may be deficient when viewing with the amblyopic eye. We presented the fixation target to one eye and the subsequent peripheral target (saccadic error signal) to the other eye. Shifting saccadic targets between the eyes expedited saccadic latencies irrespective of which eye viewed the target in the amblyopia group. These findings indicate that oculomotor factors related to saccade generation are unlikely to be responsible for amblyopic eye saccadic latency delays. We propose that an impairment in the ability to disengage attention from a fixation target and orient to a peripheral target when both targets are seen by the amblyopic eye may contribute to increased saccadic latency.

Development of a test grid using Eye Movement Perimetry for screening glaucomatous visual field defects

BackgroundEye Movement Perimetry (EMP) uses Saccadic Eye Movement (SEM) responses for visual field evaluation. Previous studies have demonstrated significant delay in initiation of SEMs among glaucoma patients in comparison with healthy subjects. The aim of the current study was to develop an EMP-based screening grid to identify glaucomatous visual field defects.MethodsAn interactive test consisting of 36 locations and two stimulus contrasts (162 cd/m2 and 190 cd/m2 on a background of 140 cd/m2) was evaluated in 54 healthy subjects and 50 primary glaucoma patients. Each subject was presented a central fixation target combined with the random projection of Goldmann size III peripheral targets. Instructions were given to look at each peripheral target on detection and then re-fixate at the central fixation target while the saccades were assessed using an eye tracker. From each seen peripheral target, the Saccadic Reaction Time (SRT) was calculated for contrast level 162 cd/ m2. These values were used to plot Receiver Operating Characteristic (ROC) curves for each test locations and the Area Under the Curve (AUC) values were used to identify the locations with highest susceptibility to glaucomatous damage. Each stimulus location with an AUC less than 0.75 along with its mirrored test location around the horizontal axis were eliminated from the grid.ResultsThe mean age was 48.1 ± 16.6 years and 50.0 ± 14.5 years for healthy subjects and glaucoma patients respectively. A significant increase of SRT values by 76.5% (p < 0.001) was found in glaucoma patients in comparison with the healthy subjects. From the ROC analysis, ten out of 36 locations meeting the cut-off criteria of AUC were eliminated resulting in a new grid containing 26 test locations. SRT values were significantly different (p < 0.05) between the healthy subjects and glaucoma irrespective of the grids used.ConclusionsThe present study resulted in a screening grid consisting of 26 locations predominantly testing nasal, superior and inferior areas of the visual field. An internal validation of the modified grid showed 90.4% of screening accuracy which makes it a potential approach for population based glaucoma screening.

The enigma of Bálint's syndrome: neural substrates and cognitive deficits

The enigma of Bálint's syndrome: neural substrates and cognitive deficits

Cross-frequency coupling of eye-movement related LFP activities of freely viewing monkeys

Living organisms do not only passively receive sensory stimuli from the external world, but also actively explore their surroundings using their sensory organs such as sniffing for odor sensation, whisking for touch sensation, and eye-movements for visual sensation. While neuronal activities underlying active sensing in olfaction and vibrissa sensation have been studied in detail, the activities related to active vision have remained largely unknown. In a recent study, we studied spike synchrony between neurons recorded from the primary visual cortex (V1) of monkeys while they perform visual exploration of natural scene images with self-paced, voluntary eye-movements and found that the V1 cells show excess synchrony around the onset of their response to visual fixation [1]. In the subsequent study, we further examined LFP activities recorded simultaneously with the spike data and found the evidence that the oscillatory LFP activity in the beta frequency band (10-25 Hz) related to the initiation of saccadic eye-movements modulates the timing of single spikes and supports the occurrence of spike synchrony of the V1 cells [2]. It has widely been recognized that brain activities show oscillations on multiple time scales [3]. While previous studies tended to focus on a single, specific frequency band, recent studies have reported strong interactions between activities in different frequency bands [4]. Such interaction is referred to as cross-frequency coupling, and the most common type of coupling is phase-amplitude coupling, also known as nested oscillations [5], where the phase of the slower oscillations modulates the amplitude of the faster oscillations. In the present study, we investigate cross-frequency coupling of eye-movement related LFPs of freely viewing monkeys. We identify three distinct frequency components characterized by different types of temporal locking to the onset of saccadic eye-movements: A delta-theta band component which is phase-locked to fixation-onset, a beta-gamma band component that is evoked by saccade-onset, and an induced component in the high gamma band. We find that the slowest frequency component (δ–θ (2-8 Hz) frequency band) covaries with the self-initiated, exploratory eye movements. Interactions between this slow component and the other faster components are studied in terms of phase-amplitude coupling measured by the modulation index (MI) [6]. We show that the amplitudes of the faster frequency components (α–β (8-32 Hz) and high-γ (>100 Hz) frequency bands) are modulated by the phase of the slow component (δ band), as reflected in high MI values for the respective frequencies. Furthermore, we find positive correlations between the degree of the phase-amplitude coupling and the amplitude of the slow component. These results represent the first evidence of mutual entrainment of different LFP frequency components during natural, active viewing behavior. Spontaneous, self-initiated eye-movements are accompanied by a reset of slow oscillations and by evoked beta oscillations, which modulate the high-gamma oscillations induced by visual input. This suggests a structuring role of slow oscillations in the processing of external visual stimuli.

Basal Ganglia Mechanisms of Reward‐Oriented Eye Movement

Expectation of reward facilitates motor behaviors that enable the animal to approach a location in space where the reward is expected. It is now known that the same expectation of reward profoundly modifies sensory, motor, and cognitive information processing in the brain. However, it is still unclear which brain regions are responsible for causing the reward-approaching behavior. One candidate is the dorsal striatum where cortical and dopaminergic inputs converge. We tested this hypothesis by injecting dopamine antagonists into the caudate nucleus (CD) while the monkey was performing a saccade task with a position-dependent asymmetric reward schedule. We previously had shown that: (1) serial GABAergic connections from the CD to the superior colliculus (SC) via the substantia nigra pars reticulata (SNr) exert powerful control over the initiation of saccadic eye movement and (2) these GABAergic neurons encode target position and are strongly influenced by expected reward, while dopaminergic neurons in the substantia nigra pars compacta (SNc) encode only reward-related information. Before injections of dopamine antagonists the latencies of saccades to a given target were shorter when the saccades were followed by a large reward than when they were followed by a small reward. After injections of dopamine D1 receptor antagonist the reward-dependent latency bias became smaller. This was due to an increase in saccade latency on large-reward trials. After injections of D2 antagonist the latency bias became larger, largely due to an increase in saccade latency on small-reward trials. These results indicate that: (1) dopamine-dependent information processing in the CD is necessary for the reward-dependent modulation of saccadic eye movement and (2) D1 and D2 receptors play differential roles depending on the positive and negative reward outcomes.

Contributions of prefrontal cue-, delay-, and response-period activity to the decision process of saccade direction in a free-choice ODR task

To examine how the dorsolateral prefrontal cortex (DLPFC) contributes to the decision process of the saccade direction, we recorded single-neuron activity while two monkeys performed two oculomotor delayed-response (ODR) tasks. In an ordinary ODR task, monkeys were required to make a memory-guided saccade to the cue location after a 3-s delay. In a self-selection version of the ODR task (S-ODR), four identical visual cues were presented simultaneously at the cue period, and monkeys were required to make a saccade toward any one of four directions after a 3-s delay. By comparing the same neuron's activity between two tasks, we found (1) neurons having directional cue-period activity in the ODR task did not show directionally selective activity in the S-ODR task, (2) neurons having directional pre-saccadic activity showed highly similar directional preferences in two tasks and exhibited temporal coupling between the onset of pre-saccadic activity and the initiation of saccadic eye movements, (3) neurons with directional delay-period activity in the ODR task exhibited similar directional preferences and showed gradual increase in the strength of the directional selectivity toward the end of the delay period in the S-ODR task. These results suggest that directional delay-period activity contributes to the decision process of the saccade direction in the S-ODR task, while directional cue-period and pre-saccadic activities do not. The gradual increase of the directional selectivity in delay-period activity might correspond to neural correlates of the decision process of the saccade direction in the S-ODR task.

Crossmodal Integration in the Primate Superior Colliculus Underlying the Preparation and Initiation of Saccadic Eye Movements

Saccades to combined audiovisual stimuli often have reduced saccadic reaction times (SRTs) compared with those to unimodal stimuli. Neurons in the intermediate/deep layers of the superior colliculus (dSC) are capable of integrating converging sensory inputs to influence the time to saccade initiation. To identify how neural processing in the dSC contributes to reducing SRTs to audiovisual stimuli, we recorded activity from dSC neurons while monkeys generated saccades to visual or audiovisual stimuli. To evoke crossmodal interactions of varying strength, we used auditory and visual stimuli of different intensities, presented either in spatial alignment or to opposite hemifields. Spatially aligned audiovisual stimuli evoked the shortest SRTs. In the case of low-intensity stimuli, the response to the auditory component of the aligned audiovisual target increased the activity preceding the response to the visual component, accelerating the onset of the visual response and facilitating the generation of shorter-latency saccades. In the case of high-intensity stimuli, the auditory and visual responses occurred much closer together in time and so there was little opportunity for the auditory stimulus to influence previsual activity. Instead, the reduction in SRT for high-intensity, aligned audiovisual stimuli was correlated with increased premotor activity (activity after visual burst but preceding saccade-aligned burst). These data provide a link between changes in neural activity related to stimulus modality with changes in behavior. They further demonstrate how crossmodal interactions are not limited to the initial sensory activity but can also influence premotor activity in the SC.

Comparison of cortico-cortical and cortico-collicular signals for the generation of saccadic eye movements.

Many neurons in the frontal eye field (FEF) and lateral intraparietal (LIP) areas of cerebral cortex are active during the visual-motor events preceding the initiation of saccadic eye movements: they respond to visual targets, increase their activity before saccades, and maintain their activity during intervening delay periods. Previous experiments have shown that the output neurons from both LIP and FEF convey the full range of these activities to the superior colliculus (SC) in the brain stem. These areas of cerebral cortex also have strong interconnections, but what signals they convey remains unknown. To determine what these cortico-cortical signals are, we identified the LIP neurons that project to FEF by antidromic activation, and we studied their activity during a delayed-saccade task. We then compared these cortico-cortical signals to those sent subcortically by also identifying the LIP neurons that project to the intermediate layers of the SC. Of 329 FEF projection neurons and 120 SC projection neurons, none were co-activated by both FEF and SC stimulation. FEF projection neurons were encountered more superficially in LIP than SC projection neurons, which is consistent with the anatomical projection of many cortical layer III neurons to other cortical areas and of layer V neurons to subcortical structures. The estimated conduction velocities of FEF projection neurons (16.7 m/s) were significantly slower that those of SC projection neurons (21.7 m/s), indicating that FEF projection neurons have smaller axons. We identified three main differences in the discharge properties of FEF and SC projection neurons: only 44% of the FEF projection neurons changed their activity during the delayed-saccade task compared with 69% of the SC projection neurons; only 17% of the task-related FEF projection neurons showed saccadic activity, whereas 42% of the SC projection neurons showed such increases; 78% of the FEF projection neurons had a visual response but no saccadic activity, whereas only 55% of the SC projection neurons had similar activity. The FEF and SC projection neurons had three similarities: both had visual, delay, and saccadic activity, both had stronger delay and saccadic activity with visually guided than with memory-guided saccades, and both had broadly tuned responses for disparity stimuli, suggesting that their visual receptive fields have a three-dimensional configuration. These observations indicate that the activity carried between parietal and frontal cortical areas conveys a spectrum of signals but that the preponderance of activity conveyed might be more closely related to earlier visual processing than to the later saccadic stages that are directed to the SC.

Progression in neuronal processing for saccadic eye movements from parietal cortex area lip to superior colliculus.

Neurons in both the lateral intraparietal area (LIP) of the monkey parietal cortex and the intermediate layers of the superior colliculus (SC) are activated well in advance of the initiation of saccadic eye movements. To determine whether there is a progression in the covert processing for saccades from area LIP to SC, we systematically compared the discharge properties of LIP output neurons identified by antidromic activation with those of SC neurons collected from the same monkeys. First, we compared activity patterns during a delayed saccade task and found that LIP and SC neurons showed an extensive overlap in their responses to visual stimuli and in their sustained activity during the delay period. The saccade activity of LIP neurons was, however, remarkably weaker than that of SC neurons and never occurred without any preceding delay activity. Second, we assessed the dependence of LIP and SC activity on the presence of a visual stimulus by contrasting their activity in delayed saccade trials in which the presentation of the visual stimulus was either sustained (visual trials) or brief (memory trials). Both the delay and the presaccadic activity levels of the LIP neuronal sample significantly depended on the sustained presence of the visual stimulus, whereas those of the SC neuronal sample did not. Third, we examined how the LIP and SC delay activity relates to the future production of a saccade using a delayed GO/NOGO saccade task, in which a change in color of the fixation stimulus instructed the monkey either to make a saccade to a peripheral visual stimulus or to withhold its response and maintain fixation. The average delay activity of both LIP and SC neuronal samples significantly increased by the advance instruction to make a saccade, but LIP neurons were significantly less dependent on the response instruction than SC neurons, and only a minority of LIP neurons was significantly modulated. Thus despite some overlap in their discharge properties, the neurons in the SC intermediate layers showed a greater independence from sustained visual stimulation and a tighter relationship to the production of an impending saccade than the LIP neurons supplying inputs to the SC. Rather than representing the transmission of one processing stage in parietal cortex area LIP to a subsequent processing stage in SC, the differences in neuronal activity that we observed suggest instead a progressive evolution in the neuronal processing for saccades.

The role of the superior colliculus in saccade initiation: a study of express saccades and the gap effect

Neural mechanisms underlying the initiation of saccadic eye movements were studied by recording the activity of neurons in the superior colliculus of rhesus monkeys that had extensive experience on the gap task using targets restricted to one visual field. The superposition of visual activation upon the increased excitability occurring on gap trials facilitates the occurrence of a motor burst with extremely short latency; the motor burst is tightly coupled to saccade onset for the full range of saccadic reactions times, both regular and express. We found no evidence that express saccades are a special class of saccades triggered directly by visual responses. The low frequency activity, necessary for the occurrence of express saccades, neither initiates express saccades nor serves as an accurate predictor of the direction or latency of saccades. Based upon these findings, the hypothesis that the motor burst of collicular neurons serves as a signal for triggering saccade onset can now be extended to express saccades.

Control of recurrent inhibition of the lateral posterior-pulvinar complex by afferents from the deep layers of the superior colliculus of the rabbit.

We investigated the effect of stimulation of the deep layers of the superior colliculus (SC) on the recurrent inhibition of the lateral posterior-pulvinar complex (LP) in anesthetized rabbits. Intracellular recordings from 23 relay cells in LP showed that they responded to SC stimulation with a long-lasting (140.2 +/- 19.6 ms; mean +/- SD) inhibitory postsynaptic potential (IPSP), which sometimes was followed by a rebound burst of spikes. The same SC stimulation evoked a burst of spikes in extracellular recordings from 31 recurrent inhibitory interneurons in the LP-cortical pathway, which were located in the ventral part of the visual sector of the thalamic reticular nucleus. The mean latency of the burst in reticular cells was 1.6 ms shorter than that of the IPSP in LP relay cells, suggesting that the IPSP in LP cells was mediated by these reticular cells. Intracellular recordings from nine reticular cells showed that the burst of spikes evoked by SC stimulation resulted from an excitatory postsynaptic potential that was always followed by a long-lasting (143.3 +/- 24.0 ms) IPSP. Stimulation of the contralateral predorsal bundle, the main output pathway of deep SC neurons, elicited similar responses in LP cells or reticular neurons with latencies longer than those from SC stimulation. The latency difference between the responses to predorsal bundle and SC stimulation is equal to the antidromic conduction time of predorsal bundle fibers, suggesting that the inhibition in LP originates from the activation of predorsal bundle-projecting neurons. The response characteristics of the inhibitory circuit of LP and of the lateral geniculate nucleus to SC stimulation are strikingly similar, implying that a similar circuit is used by predorsal bundle-projecting neurons to control the recurrent inhibition in both lateral geniculate nucleus and LP. Because the predorsal bundle-projecting neurons are believed to be involved in the initiation of saccadic eye movements, we suggest that the inhibitory circuits may play an important role in modulating ascending visual information during saccadic eye movements.

Neuronal Activity in Monkey Superior Colliculus Related to the Initiation of Saccadic Eye Movements

The introduction of a temporal gap between the disappearance of an initially fixated target and the appearance of an eccentric saccadic target results in a general reduction of saccadic reaction times (SRTs)-the gap effect-and often in the production of express saccades, the latencies of which approach the conduction time of the shortest neural pathways from the retina to the eye muscles. We investigated saccade initiation by recording neuronal activity in the superior colliculus in monkeys performing the gap paradigm. Fixation-related neurons reduced their discharge rate during the gap period, regardless of the SRT. This reduction in activity is consistent with the hypothesized release of ocular fixation that facilitates premotor processes and may contribute to the gap effect. In addition to saccade-related discharges, many saccade-related neurons displayed phasic target-related responses and/or low-frequency preparatory activity during the gap period. The level of this preparatory activity correlated with both SRT and express saccade occurrence when the saccade was made into the response field of the neuron. Evidence indicates that advanced motor preparation is required for express saccade generation, which may be subserved by specific increases in the preparatory activity of saccade-related neurons. Increased preparatory activity may allow the target-related responses to trigger short-latency express saccades directly. This study provides insights into the functional mechanism of saccade initiation and may be relevant to the generation of all voluntary motor responses.

Reciprocal connections between the zona incerta and the pretectum and superior colliculus of the cat

The goal of the present experiments was to examine the relationships of the zona incerta with two structures associated with visuomotor behavior, the superior colliculus and pretectum. The experiments were carried out in the cat, a species commonly used in studies of visuomotor integration, and utilized wheat germ agglutinin–horseradish peroxidase and biocytin as retrograde and anterograde neuronal tracers. Retrograde axonal transport demonstrated that most cells in the ventral subdivision of the zona incerta project to the superior colliculus. Anterograde tracers demonstrated that the incertotectal terminal field is most dense in the intermediate gray layer, which is the primary source of the descending pathway from the superior colliculus to brainstem gaze centers. Further experiments showed that scattered cells within the intermediate gray layer give rise to a reciprocal pathway that terminates in both the dorsal and ventral subdivisions of the zona incerta. The distribution of both labeled incertotectal cells and tectoincertal terminals extends dorsolateral to the zona incerta proper, between the reticular thalamic nucleus and the external medullary lamina. Electron microscopic examination of labeled tectoincertal terminals demonstrated that they contain mainly spherical vesicles and have slightly asymmetric to symmetric synaptic densities. Labeled terminals were observed contacting labeled cells in the zona incerta, suggesting that the reciprocal pathway may be monosynaptic. The zona incerta is also reciprocally interconnected with the pretectum. The anterior pretectal nucleus provides a dense projection to the ventral part of the zona incerta and receives a sparse reciprocal projection. The posterior pretectal nucleus and nucleus of the optic tract may also project to the zona incerta. The pretectoincertal fibers form terminals that contain primarily spherical vesicles and make distinctly asymmetric synaptic contacts. In summary, these results indicate that the deep layers of the superior colliculus, which are important for controlling saccades, are the target of a projection from the ventral subdivision of the zona incerta. Like the substantia nigra, the zona incerta may play a permissive role in the tectal initiation of saccadic eye movements. The incertotectal terminal field in the cat is less dense than that observed previously in the rat, suggesting species differences in the development of this pathway. An additional finding of this study is that one of the main sources of input to these incertotectal cells is the anterior pretectal nucleus. This pretectal–incertal–tectal pathway is likely to play a role in the guidance of tectally initiated saccades by somatosensory stimuli.

Transient motion of visual texture delays saccadic eye movements

Neurophysiological research has established that a transient stimulus, spatially located outside the receptive field of visual cells, can activate some cells and inhibit firing in others. However, the significance of this phenomenon for behavioural responses in man is unclear. This study investigated the effect of a transient peripheral event on the initiation of saccadic eye movements to a luminance increment. In Experiment 1 human saccadic eye movements to targets that varied in luminance were compared on ‘shift’ trials, in which the saccadic target was timed to coincide with a step displacement of a vertical grating in the background, and on ‘no-shift’ trials, when the background remained stationary. The results showed a significant delay in mean saccadic latencies on ‘shift trials’ compared to ‘no-shift’ trials. Saccadic latencies were reduced in both conditions with increasing target intensity. Measurement of visual sensitivity showed a small non-significant increase in thresholds in the background ‘shift’ condition. A second experiment manipulated visuo-temporal information by varying both target duration and intensity. This experiment revealed significant effects of target duration and signal intensity on saccadic latency; and a 3-way interaction showing that saccades suffered the greatest delay in the background ‘shift’ condition at the lowest duration and intensity targets. These results show that the peripheral motion of visual texture delays the programming of saccadic eye movements and there is a particularly marked effect for targets of low signal strength.

A distributed model of the saccadic system: The effects of internal noise

A neural network model for the saccadic control system was proposed recently. In this model, the superior colliculus (SC) was represented as a two-layered neural network, with the second (motor) layer having extensive lateral interconnections. The SC network then provided a distributed dynamic control signal to a lumped model of the brainstem burst generator. In this paper, the saccadic model is modified so that it more closely reproduces the behavior measured experimentally in the primate saccadic system. The burst generator in the earlier model was replaced by a modified version that bears a stronger resemblance to the primate burst generator. The artificial trigger signal of the earlier work was replaced by a more neurophysiologically plausible mechanism, in which temporal initiation of saccadic eye movements is achieved through the output of the SC network itself. With the help of a new training algorithm that simultaneously updated all feedforward and feedback connection strengths, the revised model was trained not only to elicit realistic horizontal and oblique simulated saccades, but also to produce more realistic activity in the model's motor layer units. Finally, temporal noise was incorporated into our model and further changes were made so that discharges of the motor layer units had the same amount of variability as that recorded in neural discharges in the primate SC. The performance of the model in the presence of the injected noise was analyzed for different saccadic paradigms. In each case, the degree of scatter in the simulated eye movements resembled that recorded in monkey under similar behavioral conditions. Based on our results, we draw some potentially important inferences about the operation of the actual saccadic eye movement control system.

Chapter 3 Neurochemical microcircuitry underlying visual and oculomotor function in the cat superior colliculus

The cat superior colliculus (SC) plays an important role in visual and oculomotor functions, including the initiation of saccadic eye movements. We have studied the organization of neurochemical specific circuits in SC that underly these functions. In this chapter we have reviewed three microcircuits that can be identified by cell type, chemical content, and synaptic input from specific afferents. The first is located within the upper sgl and is related to the W retinal pathway to this region of SC. This circuit includes relay and interneurons that contain the calcium binding protein calbindin (CB), GABA containing presynaptic dendrites, and retinal terminals that have a distribution and size typical of W retinal terminals in the cat SC. This circuit is a typical synaptic triad that mediates feedforward inhibition, possibly to regulate outflow of the W pathway to the lateral geniculate nucleus. CB neurons in SC and other structures may be uniquely related to low threshold calcium currents in these neurons. The second microcircuit consists of neurons that contain parvalbumin (PV), another calcium binding protein. These neurons are located in a dense tier with the deep sgl and upper ol and they receive input from retinal terminals that are likely from 'Y' retinal ganglion cells. Some of these neurons also project to the lateral posterior nucleus and some colocalize glutamate. We speculate that these neurons also receive cortical 'Y' input although we have yet to prove this experimentally. The role of PV in these cells is unknown, but PV has been shown to be contained in fast spiking, non-accomodating neurons in visual cortex which have very rapid spike discharges that are also characteristic of SC neurons innervated by 'Y' input. The third microcircuit consists of a group of clustered neurons within the igl of the cat SC that overlaps the patch-like innervation of afferents to this region that come from the pedunculopontine tegmental and lateral dorsal tegmental nuclie, the substantia nigra, and the cortical frontal eye fields. These clustered neurons project through the tectopontobulbar pathway and terminate within the cuneiform region (CFR) of the midbrain tegmentum. They transiently express NOS during development. Ongoing studies in our laboratory suggest that these cells receive synaptic inputs directly from the PPTN and SN and may represent functional modules involved in the initiation of saccadic eye movements.

Relationship of presaccadic activity in frontal eye field and supplementary eye field to saccade initiation in macaque: Poisson spike train analysis

The purpose of this study was to investigate the temporal relationship between presaccadic neuronal discharges in the frontal eye fields (FEF) and supplementary eye fields (SEF) and the initiation of saccadic eye movements in macaque. We utilized an analytical technique that could reliably identify periods of neuronal modulation in individual spike trains. By comparing the observed activity of neurons with the random Poisson distribution generated from the mean discharge rate during the trial period, the period during which neural activity was significantly elevated with a predetermined confidence level was identified in each spike train. In certain neurons, bursts of action potentials were identified by determining the period in each spike train in which the activation deviated most from the expected Poisson distribution. Using this method, we related these defined periods of modulation to saccade initiation in specific cell types recorded in FEF and SEF. Cells were recorded in SEF while monkeys made saccades to targets presented alone. Cells were recorded in FEF while monkeys made saccades to targets presented alone or with surrounding distractors. There were no significant differences in the time-course of activity of the population of FEF presaccadic movement cells prior to saccades generated to singly presented or distractor-embedded targets. The discharge of presaccadic movement cells in FEF and SEF could be subdivided quantitatively into an early prelude followed by a high-rate burst of activity that occurred at a consistent interval before saccade initiation. The time of burst onset relative to saccade onset in SEF presaccadic movement cells was earlier and more variable than in FEF presaccadic movement cells. The termination of activity of another population of SEF neurons, known as preparatory set cells, was time-locked to saccade initiation. In addition, the cessation of SEF preparatory set cell activity coincided precisely with the beginning of the burst of SEF presaccadic movement cells. This finding raises the possibility that SEF preparatory set cells may be involved in saccade initiation by regulating the activation of SEF presaccadic movement cells. These results demonstrate the utility of the Poisson spike train analysis to relate periods of neuronal modulation to behavior.

Eye movements in monkeys with local dopamine depletion in the caudate nucleus. I. Deficits in spontaneous saccades

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.

Organization of the zona incerta in the macaque: a Nissl and Golgi study.

The zona incerta has been implicated in the control of the initiation of saccadic eye movements in the primate. Complex interactions within the zona incerta must take place to integrate its varied inputs and to produce a coherent efferent signal in order for this function to occur. However, whether the anatomical substrates exist within the zona incerta to allow this integration to take place has not been established. The zona incerta in monkeys (Macaca mulatta) was examined in frontally, horizontally, and sagittally sectioned preparations stained for Nissl, myelinated fibers, or cytochrome oxidase, or impregnated by the Golgi technique. This nucleus can be separated into dorsal and ventral laminae on the basis of staining and morphological differences between these two subdivisions. Neurons are more densely packed, more darkly stained, and larger in the ventral lamina. In addition, the neuropil of the ventral lamina is much more intensely stained after cytochrome oxidase histochemistry. Two neuronal types, principal cells and interneurons, were identified on the basis of neuronal cell body, dendritic, and axonal features in Golgi-impregnated preparations. Principal cells have fusiform or polygonal somata (long axis from 18 to 40 microns) and dendrites that extend for up to 750 microns within the lamina in which the cell bodies are located. Putative local interneurons have small (12-16 microns), round or oval cell bodies with wavy dendrites (up to 400 microns). Numerous multilobed appendages and axon-like processes originate from these dendrites and make apparent contacts with other interneurons or with dendrites of principal cells. Dendrites of most neurons in both laminae are oriented preferentially along the principal axis, dorsolateral-to-ventromedial, of the nucleus. Therefore, within the limits of light microscopy, the zona incerta appears to possess the morphological heterogeneity to form complex intrinsic interactions. These interactions are hypothesized to form the integrative substrate for the large array of incertal inputs that are utilized to produce an efferent signal involved in the initiation of saccadic eye movements.

A follow-up study of isolated cases of suspected Huntington's disease.

We reviewed 49 patients in whom a diagnosis of Huntington's disease (HD) seemed possible on clinical grounds, but who gave no history of definitely affected relatives. In 32 with the typical clinical features of HD (progressive chorea and dementia, postural instability, abnormal initiation of saccadic eye movements), the diagnosis was confirmed in 7 patients who had had autopsies, affected relatives were found in 5 others, and HD remained probable in a further 13 who were reexamined. In the 17 with a less typical clinical picture, a diagnosis of HD appeared most likely in 2; other causes for chorea such as cerebrovascular disease, neuroacanthocytosis, recrudescence of Sydenham's chorea, and drug-induced tardive dyskinesia could be invoked in the remainder. We conclude that the likelihood of HD in a patient with the typical clinical features of this disorder but no history of affected relatives is at least 75%, which for practical purposes implies a risk to their children hardly less than in familial HD. The most plausible explanations for seemingly sporadic patients with HD are nonpaternity and mild, late-onset disease that is overlooked by other family members.