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Competing Interests: E. D. Gaier: Luminopia, Inc (advisor, patent, equity), Stoke Therapeutics, Inc (consultant). The remaining authors report no conflicts of interest.

The rostral superior colliculus (rSC) encodes position errors for multiple types of eye movements, including microsaccades, small saccades, smooth pursuit, and fixation. Here we address whether the rSC contributes to the development of neural signals that are suitable for controlling vergence eye movements. We use both single-unit recording and microstimulation techniques in monkey to answer this question. We found that vergence eye movements can be evoked using microstimulation in the rSC. Moreover, among the previously described neurons in rSC, we recorded a novel population of neurons that either increased (i.e., convergence neurons) or decreased (i.e., divergence neurons) their activity during vergence eye movements. In particular, these neurons dynamically encoded changes in vergence angle during vergence tracking, fixation in 3D space and the slow binocular realignment that occurs after disconjugate saccades, but were completely unresponsive during conjugate or the rapid component of disconjugate saccades (i.e., fast vergence) and conjugate smooth pursuit. Together, our microstimulation and single-neuron results suggest that the SC plays a role in the generation of signals required to precisely align the eyes toward targets in 3D space. We propose that accurate maintenance of 3D eye position, critical for the perception of stereopsis, may be mediated via the rSC.

A gaze-related region in the caudal midbrain tegementum, termed the central mesencephalic reticular formation (cMRF), has been designated on electrophysiological grounds in monkeys. In macaques, the cMRF correlates with an area in which reticulotectal neurons overlap with tectoreticular terminals. We examined whether a region with the same anatomical characteristics exists in cats by injecting biotinylated dextran amine into their superior colliculi. These injections showed that a cat cMRF is present. Not only do labeled tectoreticular axons overlap the distribution of labeled reticulotectal neurons, these elements also show numerous close boutonal associations, suggestive of synaptic contact. Thus, the presence of a cMRF that supplies gaze-related feedback to the superior colliculus may be a common vertebrate feature. We then investigated whether cMRF connections indicate a role in the head movement component of gaze changes. Cervical spinal cord injections in both the cat and monkey retrogradely labeled neurons in the ipsilateral, medial cMRF. In addition, they provided evidence for a spinoreticular projection that terminates in this same portion of the cMRF, and in some cases contributes boutons that are closely associated with reticulospinal neurons. Injection of the physiologically defined, macaque cMRF demonstrated that this spinoreticular projection originates in the cervical ventral horn, indicating it may provide the cMRF with an efference copy signal. Thus, the cat and monkey cMRFs have a subregion that is reciprocally connected with the ipsilateral spinal cord. This pattern suggests the medial cMRF may play a role in modulating the activity of antagonist neck muscles during horizontal gaze changes., ((c) 2008 Wiley-Liss, Inc.)

Previous single unit recordings and electrical stimulation have suggested that separate regions of the MRF participate in the control of vergence and conjugate eye movements. Neurons in the supraoculomotor area (SOA) have been found to encode symmetric vergence [Zhang, Y. et al. (1992). J. Neurophysiol., 67: 944-960] while neurons in the central MRF, the cMRF, located ventral to the SOA and lateral to the oculomotor nucleus are associated with conjugate eye movements [Waitzman, D.M. et al. (1996). J. Neurophysiol., 75(4): 1546-1572]. However, it remains unknown if cMRF neurons are strictly associated with conjugate movements since eye movements were recorded with a single eye coil in monkeys viewing visual stimuli at a distance of at least 50 cm. In the current study we addressed whether neurons in the cMRF might also encode vergence-related information. Interestingly, electrical stimulation elicited disconjugate saccades (contralateral eye moved more than the ipsilateral eye) from locations previously thought to elicit only conjugate saccades. Single unit recordings in this same area made in two rhesus monkeys trained to follow visual stimuli moved rapidly in depth along the axis of sight of an individual eye demonstrate that cMRF neurons do not simply encode conjugate information during disconjugate saccades; in fact our findings provide evidence that cMRF neurons are most closely associated with the movement of an individual eye. These results support the hypothesis that the midbrain shapes the activity of the pre-motor saccadic neurons by encoding integrated conjugate and vergence commands.

The oculomotor system must convert signals representing the target of an intended eye movement into appropriate input to drive the individual extraocular muscles. Neural models propose that this transformation may involve either a decomposition of the intended eye displacement signal into horizontal and vertical components or an implicit process whereby component signals do not predominate until the level of the motor neurons. Thus decomposition models predict that premotor neurons should primarily encode component signals while implicit models predict encoding of off-cardinal optimal directions by premotor neurons. The central mesencephalic reticular formation (cMRF) and paramedian pontine reticular formation (PPRF) are two brain stem regions that likely participate in the development of motor activity since both structures are anatomically connected to nuclei that encode movement goal (superior colliculus) and generate horizontal eye movements (abducens nucleus). We compared cMRF and PPRF neurons and found they had similar relationships to saccade dynamics, latencies, and movement fields. Typically, the direction preference of these premotor neurons was horizontal, suggesting they were related to saccade components. To confirm this supposition, we studied the neurons during a series of oblique saccades that caused "component stretching" and thus allowed the vectorial (overall) saccade velocity to be dissociated from horizontal component velocity. The majority of cMRF and PPRF neurons encoded component velocity across all saccades, supporting decomposition models that suggest horizontal and vertical signals are generated before the level of the motoneurons. However, we also found novel vectorial eye velocity encoding neurons that may have important implications for saccade control.

Anatomical studies in goldfish show that the tectofugal axons provide a large number of boutons within the mesencephalic reticular formation. Electrical stimulation, reversible inactivation and cell recording in the primate central mesencephalic reticular formation have suggested that it participates in the control of rapid eye movements (saccades). Moreover, the role of this tecto-recipient area in the generation of saccadic eye movements in fish is unknown. In this study we show that the electrical microstimulation of the mesencephalic reticular formation of goldfish evoked short latency saccadic eye movements in any direction (contraversive or ipsiversive, upward or downward). Movements of the eyes were usually disjunctive. Based on the location of the sites from which eye movements were evoked and the preferred saccade direction, eye movements were divided into different groups: pure vertical saccades were mainly elicited from the rostral mesencephalic reticular formation, while oblique and pure horizontal were largely evoked from middle and caudal mesencephalic reticular formation zones. The direction and amplitude of pure vertical and horizontal saccades were unaffected by initial eye position. However the amplitude, but not the direction of most oblique saccades was systematically modified by initial eye position. At the same time, the amplitude of elicited saccades did not vary in any consistent manner along either the anteroposterior, dorsoventral or mediolateral axes (i.e. there was no topographic organization of the mesencephalic reticular formation with respect to amplitude). In addition to these groups of movements, we found convergent and goal-directed saccades evoked primarily from the anterior and posterior mesencephalic reticular formation, respectively. Finally, the metric and kinetic characteristics of saccades could be manipulated by changes in the stimulation parameters. We conclude that the mesencephalic reticular formation in goldfish shares physiological functions that correspond closely with those found in mammals.

Neurones in the central mesencephalic reticular formation (cMRF) begin to discharge prior to saccades. These long lead burst neurones interact with major oculomotor centres including the superior colliculus (SC) and the paramedian pontine reticular formation (PPRF). Three different functions have been proposed for neurones in the cMRF: (1) to carry eye velocity signals that provide efference copy information to the SC (feedback), (2) to provide duration signals from the omnipause neurones to the SC (feedback), or (3) to participate in the transformation from the spatial encoding of a target selection signal in the SC into the temporal pattern of discharge used to drive the excitatory burst neurones in the pons (feed-forward). According to each respective proposal, specific predictions about cMRF neuronal discharge have been formulated. Individual neurones should: (1) encode instantaneous eye velocity, (2) burst specifically in relation to saccade duration but not to other saccade metrics, or (3) have a spectrum of weak to strong correlations to saccade dynamics. To determine if cMRF neurones could subserve these multiple oculomotor roles, we examined neuronal activity in relation to a variety of saccade metrics including amplitude, velocity and duration. We found separate groups of cMRF neurones that have the characteristics predicted by each of the proposed models. We also identified a number of subgroups for which no specific model prediction had previously been established. We found that we could accurately predict the neuronal firing pattern during one type of saccade behaviour (visually guided) using the activity during an alternative behaviour with different saccade metrics (memory guided saccades). We suggest that this evidence of a close relationship of cMRF neuronal discharge to individual saccade metrics supports the hypothesis that the cMRF participates in multiple saccade control pathways carrying saccade amplitude, velocity and duration information within the brainstem.

Prior studies of the central portion of the mesencephalic reticular formation (cMRF) have shown that in head-restrained monkeys, neurons discharge prior to saccades. Here, we provide a systematic analysis of the patterns of activity in cMRF neurons during head unrestrained gaze shifts. Two types of cMRF neurons were found: presaccadic neurons began to discharge before the onset of gaze movements, while postsaccadic neurons began to discharge after gaze shift onset and typically after the end of the gaze shift. Presaccadic neuronal responses were well correlated with gaze movements, while the discharge of postsaccadic neurons was more closely associated with head movements. The activity of presaccadic neurons was organized into gaze movement fields, while the activity of postsaccadic neurons was better organized into movement fields associated with head displacement. We found that cMRF neurons displayed both open and closed movement field responses. Neurons with closed movement fields discharged before a specific set of gaze (presaccadic) or head (postsaccadic) movement amplitudes and directions and had a clear distal boundary. Neurons with open movement fields discharged for gaze or head movements of a specific direction and also for movement amplitudes up to the limit of measurement (70 degrees). A subset of open movement field neurons displayed an increased discharge with increased gaze shift amplitudes, similar to pontine burst neurons, and were called monotonically increasing open movement field neurons. In contrast, neurons with non-monotonically open movement fields demonstrated activity for all gaze shift amplitudes, but their activity reached a plateau or declined gradually for gaze shifts beyond specific amplitudes. We suggest that presaccadic neurons with open movement fields participate in a descending pathway providing gaze signals to medium-lead burst neurons in the paramedian pontine reticular formation, while presaccadic closed movement field neurons may participate in feedback to the superior colliculus. The previously unrecognized group of postsaccadic cMRF neurons may provide signals of head position or velocity to the thalamus, cerebellum, or spinal cord.

The accompanying paper demonstrated two distinct types of central mesencephalic reticular formation (cMRF) neuron that discharged before or after the gaze movement: pre-saccadic or post-saccadic. The movement fields of pre-saccadic neurons were most closely associated with gaze displacement. The movement fields of post-saccadic neurons were most closely associated with head displacement. Here we examine the relationships of the discharge patterns of these cMRF neurons with the temporal aspects of gaze or head movement. For pre-saccadic cMRF neurons with monotonically open movement fields, we demonstrate that burst duration correlated closely with gaze duration. In addition, the peak discharge of the majority of pre-saccadic neurons was closely correlated with peak gaze velocity. In contrast, discharge parameters of post-saccadic neurons were best correlated with the time of peak head velocity. However, the duration and peak discharge of post-saccadic discharge was only weakly related to the duration and peak velocity of head movement. As a result, for the majority of post-saccadic neurons the discharge waveform poorly correlated with the dynamics of head movement. We suggest that the discharge characteristics of pre-saccadic cMRF neurons with monotonically open movement fields are similar to that of direction long-lead burst neurons found previously in the paramedian portion of the pontine reticular formation (PPRF; Hepp and Henn 1983). In light of their anatomic connections with the PPRF, these pre-saccadic neurons could form a parallel pathway that participates in the transformation from the spatial coding of gaze in the superior colliculus (SC) to the temporal coding displayed by excitatory burst neurons of the PPRF. In contrast, closed and non-monotonically open movement field pre-saccadic neurons could play a critical role in feedback to the SC. The current data do not support a role for post-saccadic cMRF neurons in the direct control of head movements, but suggest that they may serve a feedback or reafference function, providing a signal of current head amplitude to upstream regions involved in head control.

Purpose: It has been shown that mutations in the optineurin (OPTN) gene are involved in the etiology of adult-onset primary open-angle glaucoma (POAG). In view of close similarities between human and nonhuman primate ocular development and function, the rhesus monkey is considered a suitable model for human visual system research. Therefore, this study was conducted to clone the orthologue of the human OPTN gene in the rhesus monkey (Rh-OPTN) and to determine its genomic organization. A further purpose was to establish Rh-OPTN protein expression profiles and tissue distribution in the rhesus anterior segment, retina, and optic nerve., Methods: The Rh-OPTN gene was cloned and its genomic structure determined. The mRNA expression pattern was examined by Northern blot analysis. The protein's cellular localization, ocular expression, and tissue distribution were established by immunolabeling., Results: The Rh-OPTN gene has 13 exons and encodes for a 571-amino-acid protein. Both cDNA and amino acid sequences are 96% identical with the human OPTN. Northern blot analysis revealed prominent expression of two different transcripts in heart, brain, kidney, lung, spleen, skeletal muscle, and small intestine. Cellular and tissue distribution of Rh-OPTN protein were highly similar to its human and mouse homologous proteins., Conclusions: The optineurin gene and protein are evolutionary conserved between humans and the rhesus monkey. High similarity of ocular expression and tissue distribution between the two optineurin proteins suggests that this nonhuman primate is a suitable model for the pathophysiology and treatment of human glaucomatous optic neuropathy.

Purpose: To report results of treatment with a monoclonal antibody (infliximab) directed against tumor necrosis factor alpha in seven patients with chronic and difficult-to-control idiopathic orbital inflammation (orbital myositis)., Design: Observational case series., Methods: Retrospective data were collected from seven patients who had idiopathic orbital inflammation and who were evaluated at three medical centers. All patients were treated with infliximab after the failure of traditional therapy, which included corticosteroids, radiotherapy, or anti-inflammatory chemotherapeutic agents., Results: All seven patients had a favorable response to treatment with infliximab. One patient with Behcet disease required supplemental oral corticosteroids. Pain, swelling, and need for concomitant corticosteroids were the primary measures of treatment success. Symptoms of comorbid disease in four patients also improved (Crohn disease in two, Behcet disease in one, and psoriasis in one). There were no untoward effects of treatment after a mean follow-up of 15.7 months (range, 4 to 31 months)., Conclusions: Treatment with infliximab appears to offer another therapeutic option in cases of recalcitrant or recurrent idiopathic orbital inflammation in which conventional treatment fails.

Converging lines of evidence support a role for the intermediate and deep layers of the superior colliculus (SC) and the mesencephalic reticular formation (MRF) in the control of combined head and eye movements (i.e., gaze). Recent microstimulation, single-cell recording, and lesion experiments are reviewed in which monkeys are free to move their heads. Cells in the SC discharge in advance of combined head and eye movements and most likely provide a gaze error signal to downstream structures. In contrast, the neurons in the MRF are of at least two types. Eye cells have features that are similar to neurons in the rostral portion of the SC, but fire before the onset of horizontal eye movments. A second group of MRF neurons begin to fire after the onset of the gaze shift and are most closely associated with movements of the head. The peak discharge of these late-onset MRF neurons occurs near the peak head velocity. Stimulation in the rostral SC generates eye movements with fixed amplitude and direction. A similar response is noted after stimulation of the more dorsal portion of the caudal MRF. Stimulation in the caudal portion of the SC produces combined head and eye movements of fixed amplitude. Electrical activation of the more ventral portions of the caudal MRF generates goal-directed and centering eye movements. Temporary inactivation of the SC with the GABA agonist muscimol generated hypometria and curved trajectories of contralateral eye movements. Inactivation of the caudal MRF produced contralateral hypermetria and ipsilateral hypometria of saccades. Release of the monkey's head demonstrated a profound contralateral head tilt. Taken together, these data suggest that the gaze signal generated in the SC is filtered by neurons in the MRF to generate a feedback signal of eye motor error. The head signal found in the MRF could cancel a portion of the gaze signal coming from the SC in the form of head velocity feedback.

Electrical microstimulation and single-unit recording have suggested that a group of long-lead burst neurons (LLBNs) in the mesencephalic reticular formation (MRF) just lateral to the interstitial nucleus of Cajal (INC) (the peri-INC MRF, piMRF) may play a role in the generation of vertical rapid eye movements. Inactivation of this region with muscimol (a GABA(A) agonist) rapidly produced vertical saccade hypometria (6 injections). In three of six injections, there was a marked reduction in the velocity of vertical saccades out of proportion to saccade amplitude (i.e., saccades fell below the main sequence). This was associated with a moderate increase in saccade duration. Inadvertent inactivation of the INC could not account for these observations because vertical, postsaccadic drift was not observed. Similarly, pure downward saccade hypometria, the hallmark of rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) inactivation, was always preceded by loss of upward saccades in our experiments. We also found a downward and ipsiversive displacement of initial eye position and evidence of a contraversive head tilt following piMRF injections. Saccade latency was shorter after two of six injections. Simulation of a local feedback model provided three possible explanations for vertical saccade hypometria: 1) a shift in the input to the model to request smaller saccades, 2) a reduction of LLBN input to the vertical saccade medium lead burst neurons (MLBNs), or 3) an increase in the gain of the feedback pathway. However, when the second hypothesis was coupled to a shortened duration of the saccade trigger (i.e., the discharge of the omnipause neurons), the physiological observations of piMRF inactivation could be replicated. This suggested that muscimol had targeted structures that provided both long-lead burst activity to the MLBNs in the riMLF and were critical for reactivation of the omnipause neurons. Evidence of markedly reduced vertical saccade amplitude, curved saccade trajectories, increased saccade duration, and saccades that fall below the amplitude/velocity main sequence in these monkeys closely parallels the oculomotor findings of patients with progressive supranuclear palsy (PSP).

Single-neuron recording and electrical microstimulation suggest three roles for the mesencephalic reticular formation (MRF) in oculomotor control: 1) saccade triggering, 2) computation of the horizontal component of saccade amplitude (a feed-forward function), and 3) feedback of an eye velocity signal from the paramedian zone of the pontine reticular formation (PPRF) to higher structures. These ideas were tested using reversible inactivation of the MRF with pressure microinjection of muscimol, a GABA(A) agonist, in four rhesus monkeys prepared for chronic single-neuron and eye movement recording. Reversible inactivation revealed two subregions of the MRF: ventral-caudal and rostral. The ventral-caudal region, which corresponds to the central MRF, the cMRF, or nucleus subcuneiformis, is the focus of this paper and is located lateral to the oculomotor nucleus and caudal to the posterior commissure (PC). Inactivation of the cMRF produced contraversive, upward saccade hypermetria. In three of eight injections, the velocity of hypermetric saccades was too fast for a given saccade amplitude, and saccade duration was shorter. The latency for initiation of most contraversive saccades was markedly reduced. Fixation was also destabilized with the development of macrosaccadic square-wave jerks that were directed toward a contraversive goal in the hypermetric direction. Spontaneous saccades collected in total darkness were also directed toward the same orbital goal, up and to the contraversive side. Three of eight muscimol injections were associated with a shift in the initial position of the eyes. A contralateral head tilt was also observed in 5 out of 8 caudal injections. All ventral-caudal injections with head tilt showed no evidence of vertical postsaccadic drift. This suggested that the observed changes in head movement and posture resulted from inactivation of the caudal MRF and not spread of the muscimol to the interstitial nucleus of Cajal (INC). Evidence of hypermetria strongly supports the idea that the ventral-caudal MRF participates in the feedback control of saccade accuracy. However, development of goal-directed eye movements, as well as a shift in the initial position following some of the cMRF injections, suggest that this region also contributes to the generation of an estimate of target or eye position coded in craniotopic coordinates. Last, the observed reduction in contraversive saccade latency and development of macrosaccadic square-wave jerks supports a role of the MRF in saccade triggering.

Introduction: Medical treatment of macroprolactinomas with dopamine agonists decreases tumor mass and improves visual defects. We report an unusual complication of a macroprolactinoma responding to bromocriptine: a visual field defect caused by downward herniation of the optic chiasm., Materials and Methods: A 64-year-old woman was found to have a 4.5 cm macroprolactinoma with superior displacement of the optic chiasm, bitemporal hemianopia, and serum prolactin concentration (P) of 17,060 micrograms/L. Bromocriptine was initiated at 2.5 mg/day and increased to 7.5 mg/day over 2 months., Results: After 2 months, visual fields improved significantly and tumor height decreased to 3 cm with resolution of the optic chiasm displacement. P decreased to 1,180 micrograms/L. After 5 months of therapy, visual fields were normal, and P was 8 micrograms/L. After 8 months of therapy, new bilateral visual defects were observed. Magnetic resonance imaging (MRI) revealed further decrease of the tumor height to 1.5 cm, and inferior and leftward traction of the optic chiasm as the probable mechanism for the new visual field deficit. P was < 1 microgram/L. Bromocriptine was decreased to 5 mg/day to allow reduced traction on the optic chiasm and its blood supply. Over the next 4 months, visual field abnormalities resolved., Conclusions: We report the development of a visual field abnormally that is explained by chiasmal herniation caused by a shrinking macroprolactinoma. This complication resolved with a decrease in the bromocriptine dose. We suggest that patients undergoing bromocriptine therapy for macroprolactinomas be followed for this potential complication.

Background: Computed tomography (CT) and magnetic resonance imaging (MR) are commonly used neuroimaging modalities for patients with signs or symptoms of neuro-ophthalmic disorders. Understanding the technology and clinical uses of these modalities is vital in patient management., Methods/results: Basic instrument design and technology are presented together with a discussion of indications and contraindications to the use of these imaging techniques. Case reports are presented to illustrate the usefulness in diagnosis of orbital and neuro-ophthalmic disease., Conclusions: A basic knowledge of CT and MR helps the optometrist correlate imaging with clinical signs and symptoms of disease. This understanding also results in more effective communication with other health care providers and patients.

1. Recent studies of the monkey superior colliculus (SC) have identified several types of cells in the intermediate layers (including burst, buildup, and fixation neurons) and the sequence of changes in their activity during the generation of saccadic eye movements. On the basis of these observations, several hypotheses about the organization of the SC leading to saccade generation have placed the SC in a feedback loop controlling the amplitude and direction of the impending saccade. We tested these hypotheses about the organization of the SC by perturbing the system while recording the activity of neurons within the SC. 2. We applied a brief high-frequency train of electrical stimulation among the fixation cells in the rostral pole of the SC. This momentarily interrupted the saccade in midflight: after the initial eye acceleration, the eye velocity decreased (frequently to 0) and then again accelerated. Despite the break in the saccade, these interrupted saccades were of about the same amplitude as normal saccades. The postinterruption saccades were usually initiated immediately after the termination of stimulation and occurred regardless of whether the saccade target was visible or not. The velocity-amplitude relationship of the preinterruption component of the saccade fell slightly above the main sequence for control saccades of that amplitude, whereas postinterruption saccades fell near the main sequence. 3. Collicular burst neurons are silent during fixation and discharge a robust burst of action potentials for saccades to a restricted region of the visual field that define a closed movement field. During the stimulation-induced saccadic interruption, these burst neurons all showed a pause in their high-frequency discharge. During an interrupted saccade to a visual target, the typical saccade-related burst was broken into two parts: the first part of the burst began before the initial preinterruption saccade; the second burst began before the postinterruption saccade. 4. We quantified three aspects of the resumption of activity of burst neurons following saccade interruption: 1) the total number of spikes in the pre- and postinterruption bursts, was very similar to the total number of spikes in the control saccade burst; 2) the increase in total duration of the burst (preinterruption period + interruption + postinterruption period) was highly correlated with the increase in total saccade duration (preinterruption saccade + interruption + postinterruption saccade); and 3) the time course of the postinterruption saccade and the resumed cell discharge both followed the same monotonic trajectory as the control saccade in most cells. 5. The same population of burst neurons was active for both the preinterruption and the postinterruption saccades, provided that the stimulation was brief enough to allow the postinterruption saccade to occur immediately. If the postinterruption saccade was delayed by > 100 ms, then burst neurons at a new and more rostral locus related to such smaller saccades became active in association with the smaller remaining saccade. We interpret this shift in active locations within the SC as a termination of the initial saccadic error command and the triggering of a new one. 6. Buildup neurons usually had two aspects to their discharge: a high-frequency burst for saccades of the optimal amplitude and direction (similar to burst neurons), and a low-frequency discharge for saccades of optimal direction whose amplitudes were equal to or greater than the optimal (different from burst neurons). The stimulation-induced interruption in saccade trajectory differentially affected these two components of buildup neuron discharge. The high-frequency burst component was affected in a manner very similar to the burst neurons.(ABSTRACT TRUNCATED)

1. One hundred twenty neurons were recorded in the central mesencephalic reticular formation (cMRF) of four rhesus monkeys, trained to make visually guided and targeted saccadic eye movements. Eye movements were recorded with the head fixed, using electrooculography (EOG) or subconjunctival scleral search coils. Seventy-six percent (92/120) of cells discharged before and during contraversive visually guided or targeted rapid eye movements, and 76% of these (70/92) responded during contraversive spontaneous saccades in the dark. cMRF neurons had large contraversive movement fields and either a high (> 10 spikes/s) or low background level of spontaneous activity in the dark. The optimal movement vectors (i.e., saccades with greatest response) were predominantly horizontal, although many had a vertical component. Cells with optimal movement vectors within +/- 25 degrees of pure vertical were more rostral in the MRF and were excluded from the analysis. 2. A subgroup of cMRF neurons (31 of 92) that discharged before and during visually guided saccades were examined for visual sensitivity. Slightly less than one-half of these cells (42%, 13/31) were visuomotor units, i.e., they responded to visual targets in the absence of eye movement. The other 58% (n = 18) did not discharge during the visual probe trial; they were movement-related cells. 3. Microstimulation (threshold 40-60 microA at 333 Hz) at the sites of many of these cMRF neurons produced contraversive saccadic eye movements at short latency (< 40 ms). The amplitude and direction of the elicited saccades were similar to the optimal movement vector determined from single-unit recording. This suggested that cMRF cells recorded at the same locus of electrical microstimulation participated in the network responsible for the production and control of rapid eye movements. 4. The 92 saccade-related neurons were divided into two groups on the basis of their background discharge rate. Firing rates for both low background (28%, n = 26) and high background (72%, n = 66) cells increased approximately 30 ms before contraversive saccades and reached a peak discharge just before saccade onset. The low background neurons had either no activity or generated a few spikes just before the end of ipsiversive saccades. The steady rate of discharge (> 10 spikes/s) of high background neurons was inhibited from approximately 20 ms before ipsiversive saccades until just before saccade end. 5. Cells were also subdivided on the basis of how their discharge rates fell at the end of saccades. Clipped cells (38%, n = 35) had activity that fell sharply with saccade offset. Partially clipped cells (62%, n = 57) had persistent firing in the 100 ms following the saccade that was > 20% higher than the firing during the 100 ms before the saccade. 6. Latencies between the 90% point on the rising edge of the peak discharge and the start of the saccade were < or = 5.3 ms for eye movement-related cells in two monkeys. Longer latencies (11-19 ms) were found when measured between the 10% point on the rising edge of the peak discharge and saccade onset. These latencies were equal to or shorter than those obtained for eye movement-related burst neurons in the intermediate and deep layers of the superior colliculus analyzed similarly. Delays between the peak discharge and peak eye velocity were 13.6-15.1 ms for the same group of cMRF eye movement-related cells. These were significantly shorter than the delays measured for eye movement neurons in the superior colliculus (SC) of one of the monkeys. These findings suggest that the buildup discharge of cMRF neurons occurs early enough before saccades to contribute to saccade triggering. The peak discharge, however, occurs with or after the burst in the SC, suggesting that this portion of the discharge serves a function other than saccade triggering. 7. The number of spikes in bursts associated with eye movement was correlated with saccade parameters.

1. The locus of activity within the superior colliculus (SC) is related to the desired displacement of the eye. Current hypotheses suggest that the location of this locus of activity determines the amplitude of the saccade and that the level of activity at this locus determines eye velocity. We present evidence that suggests that, although the locus determines the amplitude of the saccade, the level of activity in the colliculus encodes dynamic motor error (the difference between desired and current eye displacement). 2. We categorized 86 neurons in the intermediate and deep layers of the superior colliculus of two rhesus monkeys by their activity in relation to the end of saccadic eye movements. In 36% of the cells (n = 31), activity was completely cut off by the end of the saccade (clipped cells). For 53% of cells (n = 46), the major burst of activity ceased by the end of the saccade, but activity continued for 30-100 ms after the end of the movement (partially clipped cells). The remaining 10% of the cells (n = 9) had no clear burst of activity (unclipped cells) but rather had activity that increased gradually before the saccade and then slowly decreased for up to 100 ms after the saccade. These categories were part of a continuum of cell types rather than discrete classes of cells. 3. We first determined whether this new categorization of cells revealed a special relation between the discharge of clipped and partially clipped cells and saccadic amplitude and peak velocity. As expected, we found a steady increase in spike count as saccadic amplitude increased up to the center of the movement field, and an increase in peak spike discharge as peak velocity increased up to a maximum radial eye velocity. Variability in the cell discharge was substantially greater than the variability of saccadic amplitude or peak velocity. We concluded that these single point or averaged measures did not reveal any new functional relationship of these cells. 4. We then examined the relationship of the temporal pattern of discharge of clipped and partially clipped cells to instantaneous changes in radial error and radial velocity. There was a monotonic decay in spike discharge with declining radial error. In contrast, there was a complex, multivalued relationship between spike discharge and radial velocity; collicular cells produced two different values of spike discharge for the same velocity, one during acceleration and the other during deceleration of the eye during a saccade.(ABSTRACT TRUNCATED AT 400 WORDS)

Recordings from single units in kitten primary visual cortex show that a reversible blockade of the discharge activities of cortical neurons and geniculocortical afferent terminals by intracortical infusion of the sodium channel blocker tetrodotoxin (TTX) completely prevented the ocular dominance shift that would normally be seen after monocular deprivation. The blockade of cortical plasticity, like the blockade of discharge activity, was reversible, and plasticity was restored following recovery from the effects of TTX. These results extend previous work suggesting involvement of electrical activity at the level of the cortex in the phenomenon of cortical plasticity by demonstrating an absolute requirement for discharge activities in the primary visual cortex.

Within a 5-month period, 2 homosexual men with persistent lymphadenopathy developed clinical findings consistent with herpes simplex virus (HSV) encephalitis. These signs included abrupt change in mental status, seizures, cerebrospinal fluid pleocytosis, and localized electroencephalographic abnormalities showing temporal lobe involvement. Initial computed tomographic scans were unremarkable. Treatment with adenine arabinoside was instituted and temporal lobe biopsies were performed. Although virus-specific antigens were detectable in only 1 patient, cultures of biopsy tissue from both patients yielded HSV type 2 organisms. Spiking fevers persisted and the patients failed to improve, prompting administration of acyclovir. Both patients recovered gradually after their second course of antiviral therapy and survived with severe neurological deficits. These patients should raise concerns about an increased incidence of type 2 encephalitic illness among homosexual men with persistent lymphadenopathy or acquired immune deficiency syndrome. In addition, the importance of using HSV type 2 antibody in the immunofluorescence test of brain biopsy tissue for rapid diagnosis of the disease is emphasized.

Studies of the intermediate layers of the superior colliculus have suggested that it provides a desired change in eye position signal (delta E) for the generation of saccadic eye movements. Recent evidence, however, has shown that some neurons in these layers may be related to the velocity of saccades. We present single cell recordings from the intermediate layers of monkey superior colliculus that are consistent with the hypothesis that many superior colliculus neurons provide instead a motor error signal, em. Our hypothesis about the function of these cells places them inside the local feedback loop controlling the waveform of the saccade.