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Knowledge of the number of people present in a catchment is fundamental for the assessment of spatio-temporal trends in wastewater-based epidemiology (WBE). Accurately estimating the number of people connected to wastewater catchments is challenging however, because populations are dynamic. Methods used to estimate population size can significantly influence the calculation and interpretation of population-normalised wastewater data (PNWD). This paper systematically reviews the reporting of population data in 339 WBE studies. Studies were evaluated based on their reporting of population size, the source of population data, the population calculation methods, and the uncertainties in population estimates. Most papers reported population size (96 %) and the source of population data (60 %). Fewer studies reported the uncertainties in their population data (50 %) and the methods used to calculate these estimates (28 %). This is relevant because different methods have unique strengths and limitations which can affect the accuracy of PNWD. Only 64 studies (19 %) reported all four components of population data. The reporting of population data has remained consistent in the past decade. Based on the findings, we recommend generalised reporting criteria for population data in WBE. As WBE is further mainstreamed and applied, the clear and comprehensive reporting of population data will only become increasingly important., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The life history of a parasite describes its partitioning of assimilated resources into growth, reproduction, and transmission effort, and its precise timing of developmental events. The life cycle, in contrast, charts the sequence of morphological stages from feeding to the transmission forms. Phenotypic plasticity in life history traits can reveal how parasites confront variable environments within hosts. Within the protist phylum Apicomplexa major clades include the malaria parasites, coccidians, and most diverse, the gregarines (with likely millions of species). Studies on life history variation of gregarines are rare. Therefore, life history traits were examined for the gregarine Monocystis perplexa in its host, the invasive earthworm Amynthas agrestis at three sites in northern Vermont, United States of America. An important value of this system is the short life-span of the hosts, with only seven months from hatching to mass mortality; we were thus able to examine life history variation during the entire life cycle of both host and parasite. Earthworms were collected ( N  = 968 over 33 sample periods during one host season), then parasites of all life stages were counted, and sexual and transmission stages measured, for each earthworm. All traits varied substantially among individual earthworm hosts and across the sites. Across sites, timing of first appearance of infected earthworms, date when transmission stage (oocysts packed within gametocysts) appeared, date when number of both feeding (trophic) cells and gametocysts were at maximum, and date when 100% of earthworms were infected differed from 2-8 weeks, surprising variation for a short season available for parasite development. The maximal size of mating cells varied among hosts and across sites and this is reflected in the number of oocysts produced by the gametocyst. A negative trade-off was observed for the number of oocysts and their size. Several patterns were striking: (1) Prevalence reached 100% at all sites by mid season, only one to three weeks after parasites first appeared in the earthworms. (2) The number of parasites per host was large, reaching 300 × 10 3 cells in some hosts, and such high numbers were present even when parasites first appeared in the host. (3) At one site, few infected earthworms produced any oocysts. (4) The transmission rate to reach such high density of parasites in hosts needed to be very high for a microbe, from >0.33% to >34.3% across the three sites. Monocystis was one of the first protist parasites to have its life cycle described (early 19 th century), but these results suggest the long-accepted life cycle of Monocystis could be incomplete, such that the parasites may be transmitted vertically (within the earthworm's eggs) as well as horizontally (leading to 100% prevalence) and merogony (asexual replication) could be present, not recognized for Monocystis , leading to high parasitemia even very early in the host's season., Competing Interests: The authors declare there are no competing interests., (©2024 Keller and Schall.)

Monocystis perplexa n. sp., a parasite of an important invasive Japanese earthworm in North America, Amynthas agrestis, is described from a site in Vermont. An improved standard for Monocystis species descriptions is proposed including a standard nomenclature to reduce synonymies, a standard set of biometrics and shape descriptions for living cells, and a DNA genomic sequence for the 18S rRNA (∼1,700 base pairs). Comparing morphologies of Monocystis parasites in sympatric earthworm species indicates that M. perplexa is specific to A. agrestis in the study region. Also, polymerase chain reaction primers specific to M. perplexa amplified samples of A. agrestis earthworms taken from several sites in Japan. This suggests the parasite entered North America from Japan, the origin of the invasive Amynthas earthworm, and thus M. perplexa would be the first Monocystis described from the diverse Japanese Amynthas earthworms and the first from East Asia. Monocystis perplexa was found in every population of A. agrestis surveyed in Vermont, always reaching 100% prevalence by late summer (the host has an annual life cycle in Vermont). The 18S gene sequence differed from that of Monocystis agilis from the sympatric earthworm Lumbricus terrestris (the only other sequence available for Monocystis), and a genetic similarity tree places them closest among other gregarines. Many of the 95 described species of Monocystis are very similar in morphology (based on species descriptions), so the 18S gene can act as a barcode for Monocystis species and thus will help to eliminate both synonymies and reveal cryptic species., (© American Society of Parasitologists 2020.)

Ecosystem responses to invasion are strongly influenced by interactions between invaders and native species. If native species provide biotic resistance by consuming or competing with an invader, the invasion may be slowed, and/or invasive populations may be limited. If local herbivores recognize an invasive plant as being similar to native species, they may graze it more readily. Biotic resistance is thus generally predicted to increase if the invader is phylogenetically related to natives. However, if the native species were unpalatable, then grazers may be predisposed to avoid the invader, thus reducing biotic resistance from consumption. In the marine realm, invertebrate grazers often avoid feeding on invasive algae. However, tests comparing macroalgal invaders to phylogenetically related natives have been rare. Here we present data for invertebrate grazing and habitat use of (i) invasive Agarophyton vermiculophyllum (Rhodophyta: Gracilariales: Gracilarieae), (ii) the native contribal species Gracilaria tikvahiae , and (iii) an unrelated native, Ulva sp., the most common native alga in the system. We find that grazers prefer Ulva over both Gracilarieae, both for feeding and for habitat use. These data suggest that biotic resistance from consumption is low and not enhanced by the presence of a closely related native alga.

The syntheses, properties, and broad utility of noble metal plasmonic nanomaterials are now well-established. To capitalize on this exceptional utility, mitigate its cost, and potentially expand it, non-noble metal plasmonic materials have become a topic of widespread interest. As new plasmonic materials come online, it is important to understand and assess their ability to generate comparable or complementary plasmonic properties to their noble metal counterparts, including as both sensing and photoredox materials. Here, we study plasmon-driven chemistry on degenerately doped copper selenide (Cu 2- x Se) nanoparticles. In particular, we observe plasmon-driven dimerization of 4-nitrobenzenethiol to 4,4'-dimercaptoazobenzene on Cu 2- x Se surfaces with yields comparable to those observed from noble metal nanoparticles. Overall, our results indicate that doped semiconductor nanoparticles are promising for light-driven chemistry technologies.

Plasmonic materials show great potential for selective photocatalysis under relatively mild reaction conditions. However, the catalytic activity of these plasmonic catalysts can also depend upon the support material that stabilizes the catalysts, where the composition of the catalytic support may change the overall photocatalytic efficiency and yield. It is unknown how changes in the support material may change the plasmon-driven photocatalysis, which may be initiated by plasmon-derived hot carriers, localized heating, or enhanced electromagnetic fields. Herein, we probe the effects of catalytic supports on heating in plasmon-driven catalysis by examining various gold nanoparticle oxide systems. We use ultrafast surface-enhanced Raman thermometry to measure the effective temperature, equivalent to the vibrational kinetic energy, of reporter molecules located between plasmonic gold nanostructures and local environments ranging from ligands to mesoporous silica shells to silica shells. Upon photoexcitation, the transient effective temperature, equivalent to the energy deposited into a vibrational mode, of adsorbed molecules on the silica-coated samples increases, and the energy quickly dissipates within 3 ps. However, the baseline effective temperature that arises from the surface-enhanced Raman spectroscopy probing process depends upon the encapsulant, where the energy deposition differs by 200-300 K between the ligand-coated (citrate or CTAB) and the silica-coated samples. Adsorbates surrounded by a silica shell experience significantly higher effective temperatures than the adsorbates surrounded by ligands or solvent, likely because of the differing effective heat capacities of these media. Taken together, this work shows that a silica support impacts the localized heating of molecular adsorbates on the gold surface and may play a role in enhanced plasmonic photocatalysis because of increased thermal contributions.

Plasmonic materials efficiently convert light to various forms of energies for many applications, including photocatalysis, photovoltaics, and photothermal therapies. In particular, plasmonic photocatalysts hold incredible promise for highly selective sunlight-driven catalysis through the generation of highly energetic holes and electrons used to drive chemical reactions. However, plasmons are also known to generate heat, and the partitioning of photoexcitation energy into hot carriers and heat on molecularly relevant time scales is not well understood, yet plays a crucial role in designing and understanding these photocatalysts. Using an ultrafast surface-enhanced Raman thermometry technique, we probe the effective temperature, equivalent to the mode-specific increase of vibrational kinetic energy, of molecules adsorbed to gold nanoparticle aggregates in the most active hot spots on the picosecond time scale of chemical reactivity. This represents the first measurement of vibrational energy deposition for coupled molecular-plasmonic systems on the picosecond time scale of molecular motion. We find that upon plasmon excitation, the adsorbates in the hot spots undergo an initial energy transfer within several picoseconds that changes the effective temperature of the system by less than 100 K, even at peak flux values 10 8 times stronger than focused sunlight. The energy quickly dissipates from the adsorbates into the surroundings in less than 5 ps, even at the highest values of photoexcitation. This surprisingly modest energy transfer of the most active regions of the plasmonic materials on the ultrafast time scale decisively proves that most plasmonic photocatalysis is not primarily thermally driven.

Hot electrons generated through plasmonic excitations in metal nanostructures show great promise for efficiently driving chemical reactions with light. However, the lifetime, yield, and mechanism of action of plasmon-generated hot electrons involved in a given photocatalytic process are not well understood. Here, we develop ultrafast surface-enhanced Raman scattering (SERS) as a direct probe of plasmon-molecule interactions in the plasmon-catalyzed dimerization of 4-nitrobenzenethiol to p,p'-dimercaptoazobenzene. Ultrafast SERS probing of these molecular reporters in plasmonic hot spots reveals transient Fano resonances, which we attribute to near-field coupling of Stokes-shifted photons to hot electron-driven metal photoluminescence. Surprisingly, we find that hot spots that yield more photoluminescence are much more likely to drive the reaction, which indirectly proves that plasmon-generated hot electrons induce the photochemistry. These ultrafast SERS results provide insight into the relative reactivity of different plasmonic hot spot environments and quantify the ultrafast lifetime of hot electrons involved in plasmon-driven chemistry.

Ultrafast surface-enhanced Raman spectroscopy (SERS) with pico- and femtosecond time resolution has the ability to elucidate the mechanisms by which plasmons mediate chemical reactions. Here we review three important technological advances in these new methodologies, and discuss their prospects for applications in areas including plasmon-induced chemistry and sensing at very low limits of detection. Surface enhancement, arising from plasmonic materials, has been successfully incorporated with stimulated Raman techniques such as femtosecond stimulated Raman spectroscopy (FSRS) and coherent anti-Stokes Raman spectroscopy (CARS). These techniques are capable of time-resolved measurement on the femtosecond and picosecond time scale and can be used to follow the dynamics of molecules reacting near plasmonic surfaces. We discuss the potential application of ultrafast SERS techniques to probe plasmon-mediated processes, such as H2 dissociation and solar steam production. Additionally, we discuss the possibilities for high sensitivity SERS sensing using these stimulated Raman spectroscopies.

Surface-enhanced Raman spectroscopy (SERS) is a promising technique for in vivo bioanalyte detection, but accurate characterization of SERS biosensors can be challenging due to difficulties in differentiating resonance and surface enhancement contributions to the Raman signal. Here, we quantitate the resonance Raman cross-sections for a commonly used near-infrared SERS dye, 3,3'-diethylthiatricarbocyanine (DTTC). It is typically challenging to measure resonance Raman cross-sections for fluorescent dye molecules due to the overwhelming isoenergetic fluorescence signal. To overcome this issue, we used etalon-based femtosecond stimulated Raman spectroscopy, which is intrinsically designed to acquire a stimulated Raman signal without strong fluorescence or interference from signals resulting from other four-wave mixing pathways. Using this technique, we found that the cross-sections for most of the resonantly enhanced modes in DTTC exceed 10(-25) cm(2)/molecule. These cross-sections lead to high signal magnitude SERS signals from even weakly enhancing SERS substrates, as much of what appears to be a SERS signal is actually coming from the intrinsically strong resonance Raman signal. Our work will lead to a more accurate determination of SERS enhancement factors and SERS substrate characterization in the biologically relevant near-infrared region, ultimately leading to a more widespread use of SERS for biosensing and bioimaging applications.

Ru and Ru(x)Ni(30) dendrimer encapsulated nanoparticles (DENs) were synthesized using a redox-displacement method. DEN catalytic activity for the reduction of p-nitrophenol was evaluated and found to be dependent on the ratio of metals present.

The frontal eye fields (FEF), originally identified as an oculomotor cortex, have also been implicated in perceptual functions, such as constructing a visual saliency map and shifting visual attention. Further dissecting the area's role in the transformation from visual input to oculomotor command has been difficult because of spatial confounding between stimuli and responses and consequently between intermediate cognitive processes, such as attention shift and saccade preparation. Here we developed two tasks in which the visual stimulus and the saccade response were dissociated in space (the extended memory-guided saccade task), and bottom-up attention shift and saccade target selection were independent (the four-alternative delayed saccade task). Reversible inactivation of the FEF in rhesus monkeys disrupted, as expected, contralateral memory-guided saccades, but visual detection was demonstrated to be intact at the same field. Moreover, saccade behavior was impaired when a bottom-up shift of attention was not a prerequisite for saccade target selection, indicating that the inactivation effect was independent of the previously reported dysfunctions in bottom-up attention control. These findings underscore the motor aspect of the area's functions, especially in situations where saccades are generated by internal cognitive processes, including visual short-term memory and long-term associative memory.

Saccade-generating burst neurons (BN) are inhibited by omnipause neurons (OPN), except during saccades. OPN activity pauses before saccade onset and resumes at the saccade end. Microstimulation of OPN stops saccades in mid-flight, which shows that OPN can end saccades. However, OPN pause duration does not correlate well with saccade duration, and saccades are normometric after OPN lesions. We tested whether OPN were responsible for stopping saccades both in late-onset Tay-Sachs, which causes premature saccadic termination, and in individuals with cerebellar hypermetria. We studied gaze shifts between two targets at different distances aligned on one eye, which consist of a disjunctive saccade followed by vergence. High-frequency conjugate oscillations during the vergence movements that followed saccades were present in all subjects studied, indicating OPN silence. Thus, mechanisms other than OPN discharge (e.g., cerebellar caudal fastigial nucleus-promoting inhibitory BN discharge) must contribute to saccade termination., (© 2011 New York Academy of Sciences.)

pH transitions occur in hydroxyapatite (HAP) columns that are subject to step changes in salt concentration, which have been shown to be controlled by proton exchange on the HAP surface. The pH temporarily decreases before gradually returning to the feed value when the salt concentration increases, potentially compromising the stability of the HAP when either the magnitude or duration of the pH drop is excessive. The opposite happens when the salt concentration decreases. In this work we address the effects of several key variables: the flow rate, the particle size, the use of salt gradients instead of steps, the use of different co-buffers, the surface area of the HAP, and the use of a slightly alkaline wash prior to increasing the salt concentration. Flow rate and particle size were found to have virtually no effect, demonstrating that the pH transitions are equilibrium rather than kinetically driven. Salt gradients resulted in smaller pH drops compared to steps since the exchanged protons are diluted over the gradient volume. MES and histidine used as co-buffers were effective at reducing the duration of the pH transitions but did not affect their magnitude. The same result was found when comparing HAP samples with different surface areas, with the lower surface area HAP yielding much shorter duration but similar pH drops and rises. Finally, washing the HAP column with a pH 7.5 buffer prior to the salt step was found to dramatically reduce the subsequent pH drop. In general, there was good agreement between these results and predictions based on our previously developed model., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Previous studies using muscimol inactivations in the frontal eye fields (FEFs) have shown that saccades generated by recall from working memory are eliminated by these lesions, whereas visually guided saccades are relatively spared. In these experiments, we made reversible inactivations in FEFs in alert macaque monkeys and examined the effect on saccades in a choice response task. Our task required monkeys to learn arbitrary pairings between colored stimuli and saccade direction. Following inactivations, the percentage of choice errors increased as a function of the number of alternative (NA) pairings. In contrast, the percentage of dysmetric saccades (saccades that landed in the correct quadrant but were inaccurate) did not vary with NA. Saccade latency increased postlesion but did not increase with NA. We also made simultaneous inactivations in both FEFs. The results following bilateral lesions showed approximately twice as many choice errors. We conclude that the FEFs are involved in the generation of saccades in choice response tasks. The dramatic effect of NA on choice errors, but the lack of an effect of NA on motor errors or response latency, suggests that two types of processing are interrupted by FEF lesions. The first involves the formation of a saccadic intention vector from associate memory inputs, and the second, the execution of the saccade from the intention vector. An alternative interpretation of the first result is that a role of the FEFs may be to suppress incorrect responses. The doubling of choice errors following bilateral FEF lesions suggests that the effect of unilateral lesions is not caused by a general inhibition of the lesioned side by the intact side.

The behavior characterizing choice response decision-making was studied in monkeys to provide background information for ongoing neurophysiological studies of the neural mechanisms underlying saccadic choice decisions. Animals were trained to associate a specific color from a set of colored visual stimuli with a specific spatial location. The visual stimuli (colored disks) appeared briefly at equal eccentricity from a central fixation position and then were masked by gray disks. The correct target association was subsequently cued by the appearance of a colored stimulus at the fixation point. The animal indicated its choice by saccading to the remembered location of the eccentric stimulus, which had matched the color of the cue. The number of alternative associations (NA) varied from 1 to 4 and remained fixed within a block of trials. After the training period, performance (percent correct responses) declined modestly as NA increased (on average 96, 93 or 84% correct for 1, 2 or 4 NA, respectively). Response latency increased logarithmically as a function of NA, thus obeying Hick's law. The spatial extent of the learned association between color and location was investigated by rotating the array of colored stimuli that had remained fixed during the learning phase to various different angles. Error rates in choice saccades increased gradually as a function of the amount of rotation. The learned association biased the direction of the saccadic response toward the quadrant associated with the cue, but saccade direction was always toward one of the actual visual stimuli. This suggests that the learned associations between stimuli and responses were not spatially exact, but instead the association between color and location was distributed with declining strength from the trained locations. These results demonstrate that the saccade system in monkeys also displays the characteristic dependence on NA in choice response latencies, while more basic features of the eye movements are invariant from those in other tasks. The findings also provide behavioral evidence that spatially distributed regions are established for the sensory-to-motor associations during training which are later utilized for choice decisions.

Selection of identical responses may not use the same neural mechanisms when the number of alternatives (NA) for the selection changes, as suggested by Hick's law. For elucidating the choice mechanisms, frontal eye field (FEF) neurons were monitored during a color-to-location choice saccade task as the number of potential targets was varied. Visual responses to alternative targets decreased as NA increased, whereas perisaccade activities increased with NA. These modulations of FEF activities seem closely related to the choice process because the activity enhancements coincided with the timing of target selection, and the neural modulation was greater as NA increased, features expected of neural correlates for a choice process from the perspective of Hick's law. Our current observations suggest two novel notions of FEF neuronal behavior that have not been reported previously: (1) cells called "phasic visual" that do not discharge in the perisaccade interval in a delayed-saccade paradigm show such activity in a choice response task at the time of the saccade; and (2) the activity in FEF visuomotor cells display an inverse relationship between perisaccadic activity and the time of saccade triggering with higher levels of activity leading to longer saccade reaction times. These findings support the area's involvement in sensory-motor translation for target selection through coactivation and competitive interaction of neural populations that code for alternative action sets.

Saccades are rapid shifts of gaze that normally place the line of sight on a desired target with a single smooth movement. A number of disease states have been shown to result in saccadic movements that are fragmented, but still end near target position after a multi-step sequence of saccades. Among these disorders are Parkinson's disease and late-onset Tay-Sachs disease (LOTS). We have recently shown that normal human subjects and monkeys also make some two-step saccadic responses in cognitively difficult, choice response tasks. In monkeys we have been able to record neuronal responses as the animals performed a visually guided, choice saccade task. We compared the activity of neurons in the superior colliculus (SC) and the cortical frontal eye field (FEF) during the majority of trials that were accomplished with single-step saccades with those completed with two-step saccades. Several differences in discharge pattern aligned on the first saccade were uncovered. Neurons in the rostral and caudal SC were not modulated at the time of the first saccade, but a class of FEF neurons showed a burst of activity before the first saccade. If these neurons are among those known to project to the saccade generator in the brainstem, they could trigger the onset of a saccade before the remaining machinery in the saccade generator had sufficient activity to sustain the saccade. Overall the results suggest that a delicate balance of triggering and sustaining inputs are required to produce normal single-step saccades. These neural results may also help to clarify the pathology present when fragmented saccades occur in various disease states.

Saccades normally place the eye on target with one smooth movement. In late-onset Tay-Sachs (LOTS), intrasaccadic transient decelerations occur that may result from (1) premature omnipause neuron (OPN) re-activation due to malfunction of the latch circuit that inhibits OPNs for the duration of the saccade or (2) premature inhibitory burst neuron (IBN) activation due to fastigial nucleus (FN) dysregulation by the dorsal cerebellar vermis. Neuroanatomic analysis of a LOTS brain was performed. Purkinje cells were absent and gliosis of the granular cell layer was present in the dorsal cerebellar vermis. Deep cerebellar nuclei contained large inclusions. IBNs were present with small inclusions. The sample did not contain the complete OPN region; however, neurons in the OPN region contained massive inclusions. Pathologic findings suggest that premature OPN re-activation and/or inappropriate firing of IBNs may be responsible for interrupted saccades in LOTS. Cerebellar clinical dysfunction, lack of saccadic slowing, and significant loss of cerebellar cells suggest that the second cause is more likely.

In late-onset Tay-Sachs disease (LOTS), saccades are interrupted by one or more transient decelerations. Some saccades reaccelerate and continue on before eye velocity reaches zero, even in darkness. Intervals between successive decelerations are not regularly spaced. Peak decelerations of horizontal and vertical components of oblique saccades in LOTS is more synchronous than those in control subjects. We hypothesize that these decelerations are caused by dysregulation of the fastigial nuclei (FN) of the cerebellum, which fire brain stem inhibitory burst neurons (IBNs).

Recent evidence implicates the superior colliculus (SC) in cognitive processes, such as target selection and control of spatial attention, in addition to the execution of saccadic eye movements. We report here the presence of a cognitive response in some cells in the SC in a task that requires the long-term association of spatial location with an arbitrary color. In this study, using a visual choice response task, we demonstrate that visuomotor neurons in the SC were activated by the appearance of a central symbolic cue delivered outside of the visual response fields of the recorded neurons. This procedure ensures that cognitively generated activity in these SC cells is not confounded with modulation of activity from previous visual stimuli that appeared in the response field of the neurons. The experiments suggest that cognitive signals can activate SC cells by themselves instead of only being able to modulate activities already evoked by visual events. Furthermore, a substantial fraction of these cells accurately reflected cue-aligned target selection in advance of saccade initiation. Our results add further support to other studies that have demonstrated that internally generated signals exist in SC cells.

The discharge of neurons in the deeper layers of the superior colliculus (SC) was studied while monkeys performed two visual discrimination tasks that required different amounts of cognitive processing. In a search paradigm the animal's task was to saccade to the location of an odd-colored stimulus located in an array of distractors of uniform color (pop-out visual search). The visual stimuli remained on the screen as the discrimination process distinguished target from distractors. In a choice response task the color of a central cue signaled which stimulus from a previously presented array of colored stimuli was to be the target of a saccade. The stimulus array was turned off well before the central cue was presented. Most neurons showed activity aligned on both the visual input and the motor response in single-target tasks. Many of these same neurons showed additional discharge that was correlated with the required higher-level decision processes in both of these more natural visual tasks. In the case of pop-out search the SC has been shown to be functionally involved in the decision processes. The cue-aligned activity in SC in the choice response task is surprising because no transient visual stimulus appeared in the response field of the neuron.

Since Hick's original description, many subsequent studies have confirmed the logarithmic relationship that exists between response time and the number of alternatives (NA) for a choice response. In the present study a novel paradigm was used to quantify saccade response time as a function of NA. Normal subjects were required to make a saccade to the remembered location of a visual target whose color was specified by a centrally located cue. The paradigm thus required a stimulus-response transformation similar to that used by Hick. The results show that, when such a transformation was required, a logarithmic relationship was found for saccadic response time. The use of a color-to-location paradigm to study saccade choice response time produced an unexpected additional result that may provide insight into the neural organization of the saccadic system. When the number of alternative choice responses was large (4 or 8), subjects frequently made a two-saccade response instead of a single saccade to the correct location. The first movement in such a sequence was in the correct direction, but was hypometric. A second movement then followed which moved the eyes onto the correct location. These results suggest dynamic dissociations in the mechanisms underlying the triggering of saccades and the specification of their metrics.

Variable saccade trajectories are produced in visual search paradigms in which multiple potential target stimuli are present. These variable trajectories provide a rich source of information that may lead to a deeper understanding of the basic control mechanisms of the saccadic system. We have used published behavioral observations and neural recordings in the superior colliculus (SC), gathered in monkeys performing visual search paradigms, to guide the construction of a new distributed model of the saccadic system. The new model can account for many of the variations in saccade trajectory produced by the appearance of multiple visual stimuli in a search paradigm. The model uses distributed feedback about current eye motion from the brainstem to the SC to reduce activity there at physiologically realistic rates during saccades. The long-range lateral inhibitory connections between SC cells used in previous models have been eliminated to match recent physiological evidence. The model features interactions between visually activated multiple populations of cells in the SC and distributed and topologically organized inhibitory input to the SC from the SNr to produce some of the types of variable saccadic trajectories, including slightly curved and averaging saccades, observed in visual search tasks. The distributed perisaccadic disinhibition of SC from the substantia nigra (SNr) is assumed to have broad spatial tuning. In order to produce the strongly curved saccades occasionally recorded in visual search, the existence of a parallel input to the saccadic burst generators in addition to that provided by the distributed input from the SC is required. The spatiotemporal form of this additional parallel input is computed based on the assumption that the input from the model SC is realistic. In accordance with other recent models, it is assumed that the parallel input comes from the cerebellum, but our model predicts that the parallel input is delayed during highly curved saccadic trajectories.

Background: Late-onset Tay-Sachs disease (LOTS) is an adult-onset, autosomal recessive, progressive variant of GM2 gangliosidosis, characterized by involvement of the cerebellum and anterior horn cells., Objective: To determine the range of visual and ocular motor abnormalities in LOTS, as a prelude to evaluating the effectiveness of novel therapies., Methods: Fourteen patients with biochemically confirmed LOTS (8 men; age range 24 to 53 years; disease duration 5 to 30 years) and 10 age-matched control subjects were studied. Snellen visual acuity, contrast sensitivity, color vision, stereopsis, and visual fields were measured, and optic fundi were photographed. Horizontal and vertical eye movements (search coil) were recorded, and saccades, pursuit, vestibulo-ocular reflex (VOR), vergence, and optokinetic (OK) responses were measured., Results: All patients showed normal visual functions and optic fundi. The main eye movement abnormality concerned saccades, which were "multistep," consisting of a series of small saccades and larger movements that showed transient decelerations. Larger saccades ended earlier and more abruptly (greater peak deceleration) in LOTS patients than in control subjects; these changes can be attributed to premature termination of the saccadic pulse. Smooth-pursuit and slow-phase OK gains were reduced, but VOR, vergence, and gaze holding were normal., Conclusions: Patients with late-onset Tay-Sachs disease (LOTS) show characteristic abnormalities of saccades but normal afferent visual systems. Hypometria, transient decelerations, and premature termination of saccades suggest disruption of a "latch circuit" that normally inhibits pontine omnipause neurons, permitting burst neurons to discharge until the eye movement is completed. These measurable abnormalities of saccades provide a means to evaluate the effects of novel treatments for LOTS.

Saccades are rapid eye movements that orient gaze toward areas of interest in the visual scene. Neural activity correlated with saccade target selection has been identified in several brain regions, including the superior colliculus (SC), but it is not known whether the SC is directly involved in target selection, or whether the SC merely receives selection-related signals from cortex in preparation for the execution of eye movements. In monkeys, we used focal reversible inactivation to test the functional contributions of the SC to target selection during visual search, and found that inactivation resulted in clear deficits. When a target appeared in the inactivated field, saccades were often misdirected to distractor stimuli. Control tasks showed that this deficit was not caused by low-level visual or motor impairments. Our results indicate that, in addition to its well-established involvement in movement execution, the SC has an important functional role in target selection.

In vitro activities of ABT-492, ciprofloxacin, levofloxacin, trovafloxacin, moxifloxacin, gatifloxacin, and gemifloxacin were compared. ABT-492 was more potent against quinolone-susceptible and -resistant gram-positive organisms, had activity similar to that of ciprofloxacin against certain members of the family Enterobacteriaceae, and had comparable activity against quinolone-susceptible, nonfermentative, gram-negative organisms. Bactericidal activity of ABT-492 was also evaluated.

Important insights into the neural organization of the saccadic system have been gained when the usually stereotyped movement trajectories of saccades have been altered by experimental manipulation. In the present study we produced trajectory variability in monkeys by using a visual search task in which both the location and color of an odd-colored target were changed randomly trial by trial, and the number of distractors was varied on each trial. We wished to determine whether increasing the number of distractors also increased the movement trajectory variation, i.e., the amount of initial directional deviation, endpoint deviation (averaging), and curvature of saccades. Overall, saccade latencies and the proportion of saccades directed to distractors decreased as the number of homogenous distractors increased. We also found that saccades have much more dispersion in their initial direction when distractors are present in comparison to the case when only a single target without distractors appears. However, initial dispersion decreases systematically as the number of distractors increases. The percentage of averaging saccades produced in the search task was not consistently dependent on the number of distractors. A significant fraction of averaging saccades still occurred for much wider spatial separations of stimuli than in previous studies using two visual stimuli with no specified target. The curvature of saccade trajectories increased dramatically when distractors were present, but the amount of curvature was not systematically affected by the number of distractors. Errors present in saccade trajectory in the search task were only poorly compensated. We conclude that these variable saccade trajectories result from incomplete or inaccurate specification of the target when competing stimuli are present and that a smaller number of more widely spread distractors facilitate saccade variability, perhaps due to the greater difficulty of target selection.

When multiple competing visual stimuli are present, saccades show more trajectory variations than those produced by single-target stimuli. In particular, variable trajectories including curved and averaging saccades are observed when visual search is required to select and make a saccade to a target. In this paper, based on our behavioral observations and neural recordings in the superior colliculus (SC) in monkeys, we propose a new, distributed SC and cerebellum (CBM) model that accounts for the saccade trajectory variations produced by the presence of multiple visual stimuli. The long-range lateral inhibitory connections between SC units are replaced by local excitatory connections and short-range inhibition. The inhibition to the SC from the substantia nigra (SNr) is assumed to have distributed spatial tuning. The interactions between visually activated populations of SC units and the distributed SNr inhibition produce variable initial directions of saccadic trajectories and these directional variations are partially compensated by the CBM feedback system.

A long-standing belief holds that the saccadic and smooth-pursuit eye movement systems are composed of largely separate premotor circuits, at least in the brainstem. One crucial prediction predicated on this belief is that the tonic discharge of omnipause neurons (OPNs), which are thought to be part of only the saccadic system, should not be modulated during pursuit eye movements. This report shows that the discharge of OPNs, in contradiction, is modulated downward during pursuit movements. In contrast to their behavior during saccades, where they pause completely for the duration of the movement, the downward modulation during pursuit did not totally silence OPNs. The depth of the downward modulation was correlated with the speed of the ongoing pursuit movement. Another type of cell, which we have named saccade/pursuit neurons, was recorded in the paramedian pontine reticular formation near the location of OPNs. This subpopulation of burst cells discharged a cascade of spikes for saccades in a preferred direction. They also displayed a lower-frequency sustained discharge of spikes for the duration of pursuit in the same preferred direction. These data suggest a new type of combined model for the organization of the brainstem saccade/pursuit system. In this new combined model, the OPNs form a common inhibitory mechanism for both types of movements, and the saccade/pursuit neurons participate in the eye-velocity modulation of OPN discharge or membrane polarization during either type of movement.

When saccadic eye movements are made in a search task that requires selecting a target from distractors, the movements show greater curvature in their trajectories than similar saccades made to single stimuli. To test the hypothesis that this increase in curvature arises from competitive interactions between saccade goals occurring near the time of movement onset, we performed single-unit recording and microstimulation experiments in the superior colliculus (SC). We found that saccades that ended near the target but curved toward a distractor were accompanied by increased presaccadic activity of SC neurons coding the distractor site. This increased activity occurred approximately 30 ms before saccade onset and was abruptly quenched on saccade initiation. The magnitude of increased activity at the distractor site was correlated with the amount of curvature toward the distractor. In contrast, neurons coding the target location did not show any significant difference in discharge for curved versus straight saccades. To determine whether this pattern of SC discharge is causally related to saccade curvature, we performed a second series of experiments using electrical microstimulation. Monkeys made saccades to single visual stimuli presented without distractors, and we stimulated sites in the SC that would have corresponded to distractor sites in the search task. The stimulation was subthreshold for evoking saccades, but when its temporal structure mimicked the activity recorded for curved saccades in search, the subsequent saccades to the visual target showed curvature toward the location coded by the stimulation site. The effect was larger for higher stimulation frequencies and when the stimulation site was in the same colliculus as the representation of the visual target. These results support the hypothesis that the increased saccade curvature observed in search arises from rivalry between target and distractor goals and are consistent with the idea that the SC is involved in the competitive neural interactions underlying saccade target selection.

Because real-world scenes typically contain many different potential objects of interest, selecting one goal from many is clearly a fundamental problem faced by the saccadic system. We recorded from visual, movement, and visuo-movement (VM) neurons in the superior colliculus (SC) of monkeys performing a reaction-time visual-search task requiring them to make saccades to an odd-colored target presented with distractors. First, we compared the responses of SC neurons in search with their responses when a single target was presented without distractors (single-stimulus task). Consistent with earlier reports, initial visual activity was smaller in search than in the single-stimulus task, while movement-related activity in the two tasks was comparable. Further experiments showed that much of the reduction in the initial visual response during search was due to lateral inhibition, although a top-down task-related component was also evident. Although the initial visual activity did not discriminate the target from the distractors, some neurons showed a biphasic pattern of visual activity. In VM burst neurons, the second phase of this activity was significantly larger when the target, rather than a distractor, was in the response field. We traced the time course of target/distractor discrimination using receiver operating characteristic (ROC) analysis and found that VM burst neurons, VM prelude neurons, and pure movement neurons discriminated the target from distractors before saccade onset but that phasic and tonic pure visual neurons did not. We also examined the relationship between target/distractor discrimination time and saccade latency. Discrimination in VM burst neurons having a biphasic pattern of visual activity and in many VM prelude neurons occurred after a consistent delay that did not depend on saccade latency, suggesting that these neurons are involved in target selection as well as movement initiation. In contrast, VM burst neurons lacking a biphasic pattern of visual activity, pure movement neurons, and a subset of VM prelude neurons discriminated the target at a time that was well correlated with saccade latency, suggesting that this latter group of neurons is involved in triggering movement execution but not in target selection. Thus a mix of signals likely related to target selection and movement initiation co-exists in different groups of SC neurons. This suggests that certain types of SC neurons participate in the target selection process and that the SC as a whole represents a gateway for target selection signals to be converted into a saccadic command.

The premotor pathways subserving saccades and smooth-pursuit eye movements are usually thought to be different. Indeed, saccade and smooth-pursuit eye movements have different dynamics and functions. In particular, a group of midline cells in the pons called omnipause neurons (OPNs) are considered to be part of the saccadic system only. It has been established that OPNs keep premotor neurons for saccades under constant inhibition during fixation periods. Saccades occur only when the activity of OPNs has completely stopped or paused. Accordingly, electrical stimulation in the region of OPNs inhibits premotor neurons and interrupts saccades. The premotor relay for smooth pursuit is thought to be organized differently and omnipause neurons are not supposed to be involved in smooth-pursuit eye movements. To investigate this supposition, OPNs were recorded during saccades and during smooth pursuit in the monkey (Macaca mulatta). Unexpectedly, we found that neuronal activity of OPNs decreased during smooth pursuit. The resulting activity reduction reached statistical significance in approximately 50% of OPNs recorded during pursuit of a target moving at 40 degrees /s. On average, activity was reduced by 34% but never completely stopped or paused. The onset of activity reduction coincided with the onset of smooth pursuit. The duration of activity reduction was correlated with pursuit duration and its intensity was correlated with eye velocity. Activity reduction was observed even in the absence of catch-up saccades that frequently occur during pursuit. Electrical microstimulation in the OPNs' area induced a strong deceleration of the eye during smooth pursuit. These results suggest that OPNs form an inhibitory mechanism that could control the time course of smooth pursuit. This inhibitory mechanism is part of the fixation system and is probably needed to avoid reflexive eye movements toward targets that are not purposefully selected. This study shows that saccades and smooth pursuit, although they are different kinds of eye movements, are controlled by the same inhibitory system.

Neural studies of oculomotor function in the past have been conducted with the use of very simple visual stimuli. More recently there has been a new emphasis on using more natural stimuli to extend our knowledge of oculomotor organization. Visual search paradigms are an example of the use of these more natural visual surrounds. In search a subject must locate and saccade to a target that appears simultaneously with an array of distractors. When monkeys are used in this paradigm, it is possible to record from neurons located in various central structures in the brain while the initial visual response, subsequent discrimination processes and final saccadic movement unfold. In the present study we used an array of four visual stimuli, and the target was distinguished by its odd color from three distractors of uniform color. Location of the target within the array and its color were randomly selected on each trial. Neurons located in the deeper layers of the superior colliculus (SC) were recorded by standard methods in blocks of search trials. We found several new features in the discharge of SC neurons using this search paradigm that have not previously been reported in studies using single-target visual displays. (1) In contrast to the "winner take all" behavior previously reported for the SC, we found evidence of concurrent processing of alternative movement vectors. When incorrect movements were made to distractor locations, this concurrent activity was associated with significantly shorter intersaccadic intervals. (2) The discharge profile of the visual response in many units was modified by the appearance of a second prominent peak which followed the initial phasic visual response, but which was clearly differentiated from a third burst in activity associated with a saccade into the cell's response field. In some neurons, the activity in this second peak was discriminatory for the impending saccade vector. That is, it was larger when the target appeared in the response field of the cell than when it contained a distractor. This target selection signal was thus distinct from the burst normally associated with saccades into the movement fields of SC neurons. (3) Some saccades in search had a curved trajectory bowing toward the location of a distractor. These saccades were accompanied by an elevated discharge of neurons coding that distractor.

Saccades are typically separated by inter-saccadic fixation intervals (ISFIs) of > or =125 ms. During this time, the saccadic system selects a goal and completes the preparatory processes required prior to executing the subsequent movement. However, in tasks in which competing stimuli are presented, two sequentially executed movements to different goals can be separated by much shorter ISFIs. This suggests that the saccadic system is capable of completing many of the preparatory requirements for a second saccade concurrently with the execution of an initial movement. We recorded single neurons in the superior colliculus (SC) during rapid saccade sequences made by rhesus monkeys performing a search task. We found that during the execution of an initial saccade, activity related to the goal of a quickly following second saccade can be simultaneously maintained in the SC motor map. This activity appears to signal the selection or increased salience of the second saccade goal even before the initial saccade has ended. For movements separated by normal ISFIs (> or =125 ms), we did not observe activity related to concurrent processing, presumably because for these longer ISFI responses, the goal of the second saccade is not selected until after the end of the first saccade. These results indicate that, at the time of an initial saccade, the SC does not necessarily act as a strict winner-take-all network. Rather it appears that the salience of a second visual goal can be simultaneously maintained in the SC. This provides evidence that selection or preparatory activity related to the goal of a second saccade can overlap temporally with activity related to an initial saccade and indicates that such concurrent processing is present even in a structure which is fairly close to the motor output.

Several alternative methods for decoding the desired motor command vector from neural networks containing distributed, place-coded information have been suggested. The two most widely discussed candidate mechanisms are vector summation (VS) and a center-of-mass (CM) computation. The latter mechanism has also been called vector averaging. The present paper compares the operation of these two methods in a model of an experimentally well-studied neural structure, the superior colliculus (SC). The SC is one structure that has been shown to be responsible for generating saccadic command vectors in the form of distributed neural activity that is topologically arranged across its surface. It has been suggested that the pattern of eye-movement errors obtained following the placement of a collicular lesion can distinguish between these two mechanisms. As a result of this suggestion, the pattern of saccadic errors produced by lesions in the SC have been widely cited to support the CM hypothesis. In the present paper the placement of a discrete lesion is simulated in a recurrent (dynamic) neural network model of the SC. These dynamic connections in the model SC network produce a systematic shift of the locus of distributed activity away from the site of the lesion. The spatiotemporal shift in the location of SC activity then produces a pattern of saccadic errors that appear to support the CM hypothesis, even though ensemble activity in our model colliculus is decoded by VS. This result demonstrates that, when ensemble activity on the SC motor map is dynamically modulated over space and time by intrinsic collicular circuitry, an explicit CM computation is not needed to reproduce the pattern of physiological results that follow focal SC lesions.

In human subjects, two mechanisms for improving the efficiency of saccades in visual search have recently been described: color priming and concurrent processing of two saccades. Since the monkey provides an important model for understanding the neural underpinnings of target selection in visual search, we sought to explore the degree to which the saccadic system of monkeys uses these same mechanisms. Therefore, we recorded the eye movements of rhesus monkeys performing a simple color-oddity pop-out search task, similar to that used previously with human subjects. The monkeys were rewarded for making a saccade to the odd-colored target, which was presented with an array of three distractors. The target and distractors were randomly chosen to be red or green in each trial. Similar to what was previously observed for humans, we found that monkeys show the influence of a cumulative, short-term priming mechanism which facilitates saccades when the color of the search target happens to repeat from trial to trial. Furthermore, we found that like humans, when monkeys make an erroneous initial saccade to a distractor, they are capable of executing a second saccade to the target after a very brief inter-saccadic interval, suggesting that the two saccades have been programmed concurrently (i.e. in parallel). These results demonstrate a close similarity between human and monkey performance. We also made a new observation: we found that when monkeys make such two-saccade responses, the trajectory of the initial saccade tends to curve toward the goal of the subsequent saccade. This provides evidence that the two saccade goals are simultaneously represented on a common motor map, supporting the idea that the movements are processed concurrently. It also indicates that concurrent processing is not limited to brain areas involved in higher-level planning; rather, such parallel programming apparently occurs at a low enough level in the saccadic system that it can affect saccade trajectory.

Direct projections from the superior colliculus (SC) to the paramedian pontine reticular formation (PPRF) have been demonstrated anatomically. The PPRF contains cells called excitatory burst neurons (EBNs) that execute the final premotoneuronal processing for saccadic eye movements, as well as other burst cells called long-lead burst neurons (LLBNs). Previous electrophysiological tests in monkey have failed to find evidence for monosynaptic connections from the SC to EBNs, but have shown that direct projections to LLBNs exist. The validity of these results has been questioned because EBNs are known to be inhibited during periods of fixation by cells called omnipause neurons (OPNs). In later experiments in cat, the stimulus in the SC was triggered during saccades (when OPNs are off) and direct connections to EBNs were found. The present experiments were conducted to determine whether direct connections from the SC to EBNs could be demonstrated in monkey. LLBNs located near EBNs were also recorded. Single-pulse stimuli were delivered at sites in the SC at current levels well above those required to evoke saccades with pulse train stimuli. The stimuli were triggered shortly after the onset of ipsilateral or contralateral saccades and also slightly after the end of saccades. A sample of 21 EBNs was recorded and none were activated by postsaccadic stimulation or during contralateral saccades. The high spontaneous discharge rates of EBNs during ipsilateral saccades made activation of these cells more difficult to detect; however, when the results were quantified by peristimulus time histograms aligned on stimulus onset, only 1/21 EBNs showed evidence of activation in the monosynaptic range of latencies (<1.6 ms), 13 EBNs were activated at di- or polysynaptic latencies, and 7 were not activated. In contrast, 15/21 LLBNs were activated with latencies in the monosynaptic range. Further evidence supporting the absence of direct connections to EBNs was obtained by realigning the peristimulus time histograms for a subset of EBNs with similar firing rates on the time of occurrence of the last spike before stimulus onset. A subset of EBNs was also studied during drowsy ipsilaterally directed eye drifts, during which these cells were firing at low spontaneous rates and OPNs were off. No evidence for direct connections to EBNs was found in this behavioral state. The variance in results obtained for cat and monkey may be due to a species difference that reflects the more complex signal processing required in the monkey's saccadic system.

The activity of neurons located in the deep intermediate and adjacent deep layers (hereafter called just deep intermediate layer neurons) of the superior colliculus (SC) in monkeys was recorded during saccades interrupted by electrical stimulation of the brainstem omnipause neuron (OPN) region. The goal of the experiment was to determine if these neurons maintained their discharge during the saccadic interruption, and thus, could potentially provide a memory trace for the intended movement which ends accurately on target in spite of the perturbation. The collicular neurons recorded in the present study were located in the rostral three-fifths of the colliculus. Most of these cells tended to show considerable presaccadic activity during a delayed saccade paradigm, and, therefore, probably overlap with the population of SC cells called buildup neurons or prelude bursters in previous studies. The effect of electrical stimulation in the OPN region (which interrupted ongoing saccades) on the discharge of these neurons was measured by computing the percentage reduction in a cell's activity compared to that present during non-interrupted saccades. During saccade interruption about 70% of deep intermediate layer neurons experienced a major reduction (30% or greater) in their activity, but discharge recovered quickly after the termination of the stimulation as the eyes resumed their movement to finish the saccade on the target. Therefore, the pattern of activity recorded in most of the deep intermediate layer neurons during interrupted saccades qualitatively resembled that previously reported for the saccade-related burst neurons which tend to be located more dorsally in the intermediate layer. In contrast, some of our cells (30%) showed little or no perturbation in their activity caused by the saccade interrupting stimulation. Because all the more dorsally located burst neurons and the majority of our deep intermediate layer neurons show a total or major suppression in their discharge during interrupted saccades, it seems unlikely that the colliculus by itself could maintain an accurate memory of the desired saccadic goal or the remaining dynamic motor error required to account for the accuracy of the resumed movement which occurs following the interruption. However, it remains possible that the smaller proportion of our neurons whose activity was not perturbed during interrupted movements could play a role in the mechanisms underlying saccade accuracy in the interrupted saccade paradigm. Interrupted saccades have longer durations than normal saccades to the same target. Therefore, we investigated whether the discharge of our deeper collicular cells was also necessarily prolonged during interrupted saccades, and, if so, how the prolongation compared to the prolongation of the saccade. Sixty percent of our sample neurons showed a prolongation in discharge that was approximately the same as the prolongation in saccade duration (difference < 15 ms in magnitude). The, observation that temporal discharge in our neurons was perturbed to roughly match saccadic temporal perturbation suggests that dynamic feedback about ongoing saccadic motion is provided to the colliculus, but does not necessarily imply that this structure is the site responsible for the computation of dynamic motor error.

Interrupted saccades, movements that are perturbed in mid-flight by pulsatile electrical stimulation in the omnipause neuron region, are known to achieve final eye displacements with accuracies that are similar to normal saccades even in the absence of visual input following the perturbation. In an attempt to explain the neurophysiological basis for this phenomenon, the present paper describes a model of the saccadic system that represents the superior colliculus as a dynamic two-dimensional, topographically arranged array of laterally interconnected units. A distributed feedback pathway to the colliculus from downstream elements, providing both eye position and velocity signals is incorporated in the model. With the help of a training procedure based on a genetic algorithm and gradient descent, the model is optimized to produce both the normal as well as slow saccades with similar accuracy. The slow movements are included in the training set to mimic the accurate saccades that occur despite alterations in alertness, as well as following various degenerative oculomotor diseases. Although interrupted saccades were not included in the training set, the model is able to produce accurate movement of this type as an emergent property for a wide range of perturbed eye velocity trajectories. Our model demonstrates for the first time, that by means of an appropriate feedback mechanism, a single-layered dynamic network can be made to retain a distributed memory of the remaining ocular displacement error even for interrupted and slow saccades. These results support the hypothesis that saccades are controlled by error feedback of signals that code efference copies of eye motion, and further, suggest a possible answer to a long standing question about the kind of the feedback signal, if any, that is received by the superior colliculus during saccadic eye movements.

Over the past decade, considerable research efforts have been focused on the role of the rostral superior colliculus (SC) in control of saccades. The most recent theory separates the deeper intermediate layers of the SC into two functional regions: the rostral pole of these layers constitutes a fixation zone and the caudal region comprises the saccade zone. Sustained activity of fixation neurons in the fixation zone is argued to maintain fixation and help prevent saccade generation by exciting the omnipause neurons (OPNs) in the brain stem. This hypothesis is in contrast to the traditional view that the SC contains a topographic representation of the saccade motor map on which the rostral pole of the SC encodes signals for generating small saccades (<2 degrees ) instead of preventing them. There is therefore an unresolved controversy about the specific role on the most rostral region of the SC, and we reexamined its functional contribution by quantifying and comparing spatial and temporal trajectories of 30 degrees saccades perturbed by electrical stimulation of the rostral pole and more caudal regions in the SC and of the OPN region. If the rostral pole serves to preserve fixation, then saccades perturbed by stimulation should closely resemble interrupted saccades produced by stimulation of the OPN region. If it also contributes to saccade generation, then the disrupted movements would better compare with redirected saccades observed after stimulation of the caudal SC. Our experiments revealed two significant findings: 1) the locus of stimulation was the primary factor determining the perturbation effect. If the directions of the target-directed saccade and stimulation-evoked saccade were aligned and if the stimulation was delivered within approximately the rostral 2 mm (<10 degrees amplitude) of SC, the ongoing saccade stopped in midflight but then resumed after stimulation end to reach the original visually specified goal with close to normal accuracy. When stimulation was applied at more caudal sites, the ongoing saccade directly reached the target location without stopping at an intermediate position. If the directions differed considerably, both initial and resumed components were typically observed for all stimulation sites. 2) A quantitative analysis of the saccades perturbed from the fixation zone showed significant deviations from their control spatial trajectories. Thus they resembled redirected saccades induced by caudal SC stimulation and differed significantly from interrupted saccades produced by OPN stimulation. The amplitude of the initial saccade, latency of perturbation, and spatial redirection were greatest for the most caudal sites and decreased gradually for rostral sites. For stimulation sites within the rostral pole of SC, the measures formed a smooth continuation of the trends observed in the saccade zone. As these results argue for the saccade zone concept, we offer reinterpretations of the data used to support the fixation zone model. However, we also discuss scenarios that do not allow an outright rejection of the fixation zone hypothesis.

Stimulation of the rostral approximately 2 mm of the superior colliculus (SC) during a large, visual target-initiated saccade produces a spatial deviation of the ongoing saccade and then stops it in midflight. After the termination of the stimulation, the saccade resumes and ends near the location of the flashed target. The density of collicular projections to the omnipause neuron (OPN) region is greatest from the rostral SC and decreases gradually for the more caudal regions. It has been hypothesized that the microstimulation excites the OPNs through these direct connections, and the reactivation of OPNs, which are normally silent during saccades, stops the initial component in midflight by gating off the saccadic burst generator. Two predictions emerge from this hypothesis: 1) for microstimulation triggered on the onset of large saccades, the time from stimulation onset to resumption of OPN discharge should decrease as the stimulation site is moved rostral and 2) the lead time from reactivation of OPNs to the end of the initial saccade on stimulation trials should be equal to the lead time of pause end with respect to the end of control saccades. We tested this hypothesis by recording OPN activity during saccades perturbed by stimulation of the rostral approximately 2 mm of the SC. The distance of the stimulation site from the most rostral extent of the SC and the time of reactivation with respect to stimulation onset were not significantly correlated. The mean lead of reactivation of OPNs relative to the end of the initial component of perturbed saccades (6.5 ms) was significantly less than the mean lead with respect to the end of control (9.6 ms) and resumed saccades (10.4 ms). These results do not support the notion that the excitatory input from SC neurons-in particular, the fixation neurons in the rostral SC-provide the major signal to reactivate OPNs and end saccades. An alternative, conceptual model to explain the temporal sequence of events induced by stimulation of the SC during large saccades is presented. Other OPN activity parameters also were measured and compared for control and stimulation conditions. The onset of pause with respect to resumed saccade onset was larger and more variable than the onset of pause with respect to control saccades, whereas pause end with respect to the end of resumed and control saccades was similar. The reactivated discharge of OPNs during the period between the end of the initial and the onset of the resumed saccades was at least as strong as that following control movements. This latter observation is interpreted in terms of the resettable neural integrator hypothesis.

We report a method using radial basis function (RBF) networks to estimate the time evolution of population activity in topologically organized neural structures from single-neuron recordings. This is an important problem in neuroscience research, as such estimates may provide insights into systems-level function of these structures. Since single-unit neural data tends to be unevenly sampled and highly variable under similar behavioral conditions, obtaining such estimates is a difficult task. In particular, a class of cells in the superior colliculus called buildup neurons can have very narrow regions of saccade vectors for which they discharge at high rates but very large surround regions over which they discharge at low, but not zero, levels. Estimating the dynamic movement fields for these cells for two spatial dimensions at closely spaced timed intervals is a difficult problem, and no general method has been described that can be applied to all buildup cells. Estimation of individual collicular cells' spatiotemporal movement fields is a prerequisite for obtaining reliable two-dimensional estimates of the population activity on the collicular motor map during saccades. Therefore, we have developed several computational-geometry-based algorithms that regularize the data before computing a surface estimation using RBF networks. The method is then expanded to the problem of estimating simultaneous spatiotemporal activity occurring across the superior colliculus during a single movement (the inverse problem). In principle, this methodology could be applied to any neural structure with a regular, two-dimensional organization, provided a sufficient spatial distribution of sampled neurons is available.

To help understand how complex visual stimuli are processed into short-latency saccade motor programs, the activity of visuomotor neurons in the deeper layers of the superior colliculus was recorded while two monkeys made express saccades to one target and to two targets. It has been shown previously that the visual response and perimotor discharge characteristic of visuomotor neurons temporally coalesce into a single burst of discharge for express saccades. Here we seek to determine whether the distributed visual response to two targets spatially coalesces into a command appropriate for the resulting saccade. Two targets were presented at identical radial eccentricities separated in direction by 45 degrees. A gap paradigm was used to elicit express saccades. Express saccades were more likely to land in between the two targets than were saccades of longer latency. The speeds of express saccades to two targets were similar to those of one target of similar vector, as were the trajectories of saccades to one and two targets. The movement fields for express saccades to two targets were more broad than those for saccades to one target for all neurons studied. For most neurons, the spatial pattern of discharge for saccades to two targets was better explained as a scaled version of the visual response to two spatially separate targets than as a scaled version of the perimotor response accompanying a saccade to a single target. Only the discharge of neurons with large movement fields could be equally well explained as a visual response to two targets or as a perimotor response for a one-target saccade. For most neurons, the spatial properties of discharge depended on the number of targets throughout the entire saccade-related burst. These results suggest that for express saccades to two targets the computation of saccade vector is not complete at the level of the superior colliculus for most neurons and an explicit process of target selection is not necessary at this level for the programming of an express saccade.

The two-dimensional distribution of population activity in the superior colliculus (SC) during saccadic eye movements in the monkey was estimated using radial basis functions. To make these ensemble activity estimates, cells in the deeper layers of the SC were recorded over much of the rostrocaudal (caudal to 3.8 mm from the rostral tip), mediolateral extent of this structure. The dynamic movement field of each cell was determined at 2-ms intervals around the time of saccades for a wide variety of horizontal and oblique movements. Collicular neurons were divided into partially overlapping dorsal and ventral cell layers on the basis of recorded depth in SC. The pattern of presaccadic activity was used as an additional discriminant to sort the cells in the two layers into separate burst (dorsal) and buildup (ventral) cell classes. Rostrocaudal and medioventral cell location on the colliculus was estimated from the optimal target vector for a cell's visual response rather than from the optimal motor vector. The former technique was more reliable for locating some buildup neurons because it produced locations that compared better with the locations suggested by electrical stimulation. From the movement field data and from the estimates of each cell's anatomic location, a similar algorithm was used to compute the two-dimensional population activity in the two layers of the SC during horizontal and oblique saccades. A subset of the sample of neurons, located near the horizontal meridian of the SC, first was used to compute one-dimensional dynamic population activity estimates for horizontal saccades to allow partial comparison to previous studies. Statistical analyses on the one-dimensional data were limited to saccades of

One proposed role of the superior colliculus (SC) in oculomotor control is to suppress or excite the activity of brain stem omnipause neurons (OPNs) to initiate or terminate saccades, respectively. Although connections from the SC to the OPNs have been demonstrated, the spatial distribution and discharge characteristics of the projecting neurons from the SC remain unknown. We mapped the spatial distribution of the deeper-layer neurons of the SC by stimulating the region of the OPNs to identify antidromic projections and found that the density of direct projections from the SC to the OPNs was greatest in the most rostral region and decreased gradually for more caudal sites. On the basis of saccade-related discharge characteristics, the antidromically driven neurons were predominantly fixation and buildup neurons. The spatially distributed SC projections to the OPNs and the discharge characteristics of the SC neurons suggest that the direct projections from SC to OPNs are excitatory. Finally, we propose how excitation and disfacilitation from SC activity can contribute to modulation of OPN response and control saccades.