Biomedical subjects

Robert H Wurtz

Publications and source records attributed to Robert H Wurtz.

14 recordsLinked to original sources

PubMed2006

Influence of the thalamus on spatial visual processing in frontal cortex.

Each of our movements activates our own sensory receptors, and therefore keeping track of self-movement is a necessary part of analysing sensory input. One way in which the brain keeps track of self-movement is by monitoring an internal copy, or corollary discharge, of motor commands. This concept could explain why we perceive a stable visual world despite our frequent quick, or saccadic, eye movements: corollary discharge about each saccade would permit the visual system to ignore saccade-induced visual changes. The critical missing link has been the connection between corollary discharge and visual processing. Here we show that such a link is formed by a corollary discharge from the thalamus that targets the frontal cortex. In the thalamus, neurons in the mediodorsal nucleus relay a corollary discharge of saccades from the midbrain superior colliculus to the cortical frontal eye field. In the frontal eye field, neurons use corollary discharge to shift their visual receptive fields spatially before saccades. We tested the hypothesis that these two components-a pathway for corollary discharge and neurons with shifting receptive fields-form a circuit in which the corollary discharge drives the shift. First we showed that the known spatial and temporal properties of the corollary discharge predict the dynamic changes in spatial visual processing of cortical neurons when saccades are made. Then we moved from this correlation to causation by isolating single cortical neurons and showing that their spatial visual processing is impaired when corollary discharge from the thalamus is interrupted. Thus the visual processing of frontal neurons is spatiotemporally matched with, and functionally dependent on, corollary discharge input from the thalamus. These experiments establish the first link between corollary discharge and visual processing, delineate a brain circuit that is well suited for mediating visual stability, and provide a framework for studying corollary discharge in other sensory systems.

Animals↗

PubMed2006

Enhanced performance with brain stimulation: attentional shift or visual cue?

The premotor theory of visual spatial attention proposes that the same brain activity that prepares for saccades to one part of the visual field also facilitates visual processing at that same region of the visual field. Strong support comes from improvements in performance by electrical stimulation of presaccadic areas, including the frontal eye field and superior colliculus (SC). Interpretations of these stimulation experiments are hampered by the possibility that stimulation might be producing an internal visual flash or phosphene that attracts attention as a real flash would. We tested this phosphene hypothesis in the SC by comparing the effect of interchanging real visual stimuli and electrical stimulation. We first presented a veridical visual cue at the time SC stimulation improved performance; if a phosphene improved performance at this time, a real cue should do so in the same manner, but it did not. We then changed the time of SC visual-motor stimulation to when we ordinarily presented the veridical visual cue, and failed to improve performance. Last, we shifted the site of SC stimulation from the visual-motor neurons of the SC intermediate layers to the visual neurons of the superficial layers to determine whether stimulating visual neurons produced a larger improvement in performance, but it did not. Our experiments provide evidence that a phosphene is not responsible for the shift of attention that follows SC stimulation. This added evidence of a direct shift of attention is consistent with a key role of the SC in the premotor theory of attention.

Animals↗

PubMed2006

Saccade-related spread of activity across superior colliculus may arise from asymmetry of internal connections.

The superior colliculus (SC) receives a retinotopic projection of the contralateral visual field in which the representation of the central field is expanded with respect to the peripheral field. The visual projection forms a nonlinear, approximately logarithmic, map on the SC. Models of the SC commonly assume that the function defining the strength of neuronal connections within this map (the kernel) depends only on the distance between two neurons, and is thus isotropic and homogeneous. However, if the connection strength is based on the distance between two stimuli in sensory space, the kernel will be asymmetric because of the nonlinear projection onto the brain map. We show, using a model of the SC, that one consequence of these asymmetric intrinsic connections is that activity initiated at one point spreads across the map. We compare this simulated spread with the spread observed experimentally around the time of saccadic eye movements with respect to direction of spread, differing effects of local and global inhibition, and the consequences of localized inactivation on the SC map. Early studies suggested that the SC spread was caused by feedback of eye displacement during a saccade, but subsequent studies were inconsistent with this feedback hypothesis. In our new model, the spread is autonomous, resulting from intrinsic connections within the SC, and thus does not depend on eye movement feedback. Other sensory maps in the brain (e.g., visual cortex) are also nonlinear and our analysis suggests that the consequences of asymmetric connections in those areas should be considered.

Algorithms↗

PubMed2006

Attentional modulation of thalamic reticular neurons.

The major pathway for visual information reaching cerebral cortex is through the lateral geniculate nucleus (LGN) of the thalamus. Acting on this vital relay is another thalamic nucleus, the thalamic reticular nucleus (TRN). This nucleus receives topographically organized collaterals from both thalamus and cortex and sends similarly organized projections back to thalamus. The inputs to the TRN are excitatory, but the output back to the thalamic relay is inhibitory, providing an ideal organization for modulating visual activity during early processing. This functional architecture led Crick in 1984 to hypothesize that TRN serves to direct a searchlight of attention to different regions of the topographic map; however, despite the substantial influence of this hypothesis, the activity of TRN neurons has never been determined during an attention task. We have determined the nature of the response of visual TRN neurons in awake monkeys, and the modulation of that response as the monkeys shifted attention between visual and auditory stimuli. Visual TRN neurons had a strong (194 spikes/s) and fast (25 ms latency) transient increase of activity to spots of light falling in their receptive fields, as well as high background firing rate (45 spikes/s). When attention shifted to the spots of light, the amplitude of the transient visual response typically increased, whereas other neuronal response characteristics remained unchanged. Thus, as predicted previously, TRN activity is modified by shifts of visual attention, and these attentional changes could influence visual processing in LGN via the inhibitory connections back to the thalamus.

Acoustic Stimulation↗

PubMed2005

Drivers from the deep: the contribution of collicular input to thalamocortical processing.

A traditional view of the thalamus is that it is a relay station which receives sensory input and conveys this information to cortex. This sensory input determines most of the properties of first order thalamic neurons, and so is said to drive, rather than modulate, these neurons. This holds as a rule for first order thalamic nuclei, but in contrast, higher order thalamic nuclei receive much of their driver input back from cerebral cortex. In addition, higher order thalamic neurons receive inputs from subcortical movement-related centers. In the terminology popularized from studies of the sensory system, can we consider these ascending motor inputs to thalamus from subcortical structures to be modulators, subtly influencing the activity of their target neurons, or drivers, dictating the activity of their target neurons? This chapter summarizes relevant evidence from neuronal recording, inactivation, and stimulation of pathways projecting from the superior colliculus through thalamus to cerebral cortex. The study concludes that many inputs to the higher order nuclei of the thalamus from subcortical oculomotor areas - from the superior colliculus and probably other midbrain and pontine regions - should be regarded as motor drivers analogous to the sensory drivers at the first order thalamic nuclei. These motor drivers at the thalamus are viewed as being at the top of a series of feedback loops that provide information on impending actions, just as sensory drivers provide information about the external environment.

Action Potentials↗

PubMed2004

Subcortical modulation of attention counters change blindness.

Change blindness is the failure to see large changes in a visual scene that occur simultaneously with a global visual transient. Such visual transients might be brief blanks between visual scenes or the blurs caused by rapid or saccadic eye movements between successive fixations. Shifting attention to the site of the change counters this "blindness" by improving change detection and reaction time. We developed a change blindness paradigm for visual motion and then showed that presenting an attentional cue diminished the blindness in both humans and old world monkeys. We then replaced the visual cue with weak electrical stimulation of an area in the monkey's brainstem, the superior colliculus, to see if activation at such a late stage in the eye movement control system contributes to the attentional shift that counters change blindness. With this stimulation, monkeys more easily detected changes and had shorter reaction times, both characteristics of a shift of attention.

Animals↗

PubMed2004

Recovery of saccadic dysmetria following localized lesions in monkey superior colliculus.

Damage to the monkey superior colliculus (SC) produces deficits in the generation of saccadic eye movements. Recovery of the accuracy of saccades is rapid, but saccadic latency and peak velocity recover slowly or not at all. In the present experiments we revisited the issue of recovery of function following localized lesions of the SC using three methodological advances: implantation of wire recording electrodes into the SC for the duration of the experiment to ensure that we were recording from the same site on the SC map on successive days; quantification of changes in saccadic accuracy, latency, and velocity using a standard grid of target points in the visual field contralateral to the SC lesion; measurement of movement field size to quantitatively determine any changes following the lesion. We confirmed a decrease in saccadic accuracy following electrolytic lesions of the SC, and we found that this dysmetria recovered within about 4 days. Saccadic latency increased for saccades to the lesion area and this deficit persisted. Peak saccadic velocity decreased immediately after the lesion and decreased further during the 10 days to 2 weeks of the experiment. We found no indication of an expansion of the movement fields of neurons adjacent to the lesion area. This lack of reorganization suggests that movement field changes within the SC cannot mediate the recovery in accuracy of the saccade. The persistence of the latency and velocity deficits despite the recovery of amplitude deficits indicates that saccadic latency and peak velocity are dependent upon the SC whereas saccadic amplitude is not.

Animals↗

PubMed2004

Identifying corollary discharges for movement in the primate brain.

The brain keeps track of the movements it makes so as to process sensory input accurately and coordinate complex movements gracefully. In this chapter we review the brain's strategies for keeping track of fast, saccadic eye movements. One way it does this is by monitoring copies of saccadic motor commands, or corollary discharges. It has been difficult to identify corollary discharge signals in the primate brain, although in some studies the influence of corollary discharge, for example on visual processing, has been found. We propose four criteria for identifying corollary discharge signals in primate brain based on our experiences studying a pathway from superior colliculus, in the brainstem, through mediodorsal thalamus to frontal eye field, in the prefrontal cortex. First, the signals must originate from a brain structure involved in generating movements. Second, they must begin just prior to movements and represent spatial attributes of the movements. Third, eliminating the signals should not impair movements in simple tasks not requiring corollary discharge. Fourth, eliminating the signals should, however, disrupt movements in tasks that require corollary discharge, such as a double-step task in which the monkey must keep track of one saccade in order to correctly generate another. Applying these criteria to the pathway from superior colliculus to frontal eye field, we concluded that it does indeed convey corollary discharge signals. The extent to which cerebral cortex actually uses these signals, particularly in the realm of sensory perception, remains unknown pending further studies. Moreover, many other ascending pathways from brainstem to cortex remain to be explored in behaving monkeys, and some of these, too, may carry corollary discharge signals.

Animals↗

PubMed2003

What the brain stem tells the frontal cortex. I. Oculomotor signals sent from superior colliculus to frontal eye field via mediodorsal thalamus.

Neuronal processing in cerebral cortex and signal transmission from cortex to brain stem have been studied extensively, but little is known about the numerous feedback pathways that ascend from brain stem to cortex. In this study, we characterized the signals conveyed through an ascending pathway coursing from the superior colliculus (SC) to the frontal eye field (FEF) via mediodorsal thalamus (MD). Using antidromic and orthodromic stimulation, we identified SC source neurons, MD relay neurons, and FEF recipient neurons of the pathway in Macaca mulatta. The monkeys performed oculomotor tasks, including delayed-saccade tasks, that permitted analysis of signals such as visual activity, delay activity, and presaccadic activity. We found that the SC sends all of these signals into the pathway with no output selectivity, i.e., the signals leaving the SC resembled those found generally within the SC. Visual activity arrived in FEF too late to contribute to short-latency visual responses there, and delay activity was largely filtered out in MD. Presaccadic activity, however, seemed critical because it traveled essentially unchanged from SC to FEF. Signal transmission in the pathway was fast ( approximately 2 ms from SC to FEF) and topographically organized (SC neurons drove MD and FEF neurons having similarly eccentric visual and movement fields). Our analysis of identified neurons in one pathway from brain stem to frontal cortex thus demonstrates that multiple signals are sent from SC to FEF with presaccadic activity being prominent. We hypothesize that a major signal conveyed by the pathway is corollary discharge information about the vector of impending saccades.

Animals↗

PubMed2003

What the brain stem tells the frontal cortex. II. Role of the SC-MD-FEF pathway in corollary discharge.

One way we keep track of our movements is by monitoring corollary discharges or internal copies of movement commands. This study tested a hypothesis that the pathway from superior colliculus (SC) to mediodorsal thalamus (MD) to frontal eye field (FEF) carries a corollary discharge about saccades made into the contralateral visual field. We inactivated the MD relay node with muscimol in monkeys and measured corollary discharge deficits using a double-step task: two sequential saccades were made to the locations of briefly flashed targets. To make second saccades correctly, monkeys had to internally monitor their first saccades; therefore deficits in the corollary discharge representation of first saccades should disrupt second saccades. We found, first, that monkeys seemed to misjudge the amplitudes of their first saccades; this was revealed by systematic shifts in second saccade end points. Thus corollary discharge accuracy was impaired. Second, monkeys were less able to detect trial-by-trial variations in their first saccades; this was revealed by reduced compensatory changes in second saccade angles. Thus corollary discharge precision also was impaired. Both deficits occurred only when first saccades went into the contralateral visual field. Single-saccade generation was unaffected. Additional deficits occurred in reaction time and overall performance, but these were bilateral. We conclude that the SC-MD-FEF pathway conveys a corollary discharge used for coordinating sequential saccades and possibly for stabilizing vision across saccades. This pathway is the first elucidated in what may be a multilevel chain of corollary discharge circuits extending from the extraocular motoneurons up into cerebral cortex.

Animals↗

PubMed2003

Sequential activity of simultaneously recorded neurons in the superior colliculus during curved saccades.

The visual world presents multiple potential targets that can be brought to the fovea by saccadic eye movements. These targets produce activity at multiple sites on a movement map in the superior colliculus (SC), an area of the brain related to saccade generation. The saccade made must result from competition between the populations of neurons representing these many saccadic goals, and in the present experiments we used multiple moveable microelectrodes to follow this competition. We recorded simultaneously from two sites on the SC map where each site was related to a different saccade target. The two targets appeared in rapid sequence, and the monkey was rewarded for making a saccade toward the one appearing first. Our study concentrated on trials in which the monkey made strongly curved saccades that were directed first toward one target and then toward the other. These curved saccades activated both sites on the SC map as they veered from one target to the other. The major finding was that the strongly curved saccades were preceded by sequential activity in the two neurons as indicated by three observations: the firing rate for the neuron related to the first target reached its peak earlier than did the rate of the neuron for the second target; the timing of the peak activity of the two neurons was related to the beginning and end of the saccade curvature; a weighted vector-average model based on the activity of the two neurons predicted the timing of saccade curvature. Straight averaging saccades ended between the targets so that they did not go to either target, and they were accompanied by simultaneous rather than sequential activation of the two neurons. Thus when multiple populations of neurons are active on the SC movement map, the resulting saccade is determined by the relative timing of the activity in the populations as well as their magnitude. In contrast, SC activity at the two sites did not predict the final direction of the saccade, and several control experiments found insufficient activity at other sites on the SC map to account for that final direction. We conclude that the SC neuronal activity predicts the timing of the saccade curvature, but not the final direction of the trajectory. These observations are consistent with SC activity being critical in selecting the goal of the saccade, but not in determining the exact trajectory.

Action Potentials↗

PubMed2002

A pathway in primate brain for internal monitoring of movements.

It is essential to keep track of the movements we make, and one way to do that is to monitor correlates, or corollary discharges, of neuronal movement commands. We hypothesized that a previously identified pathway from brainstem to frontal cortex might carry corollary discharge signals. We found that neuronal activity in this pathway encodes upcoming eye movements and that inactivating the pathway impairs sequential eye movements consistent with loss of corollary discharge without affecting single eye movements. These results identify a pathway in the brain of the primate Macaca mulatta that conveys corollary discharge signals.

Animals↗

PubMed2002

Neuronal activity in substantia nigra pars reticulata during target selection.

Complex visual scenes require that a target for an impending saccadic eye movement be selected from a number of possible targets. We investigated whether changing the number of stimuli from which a target would be identified altered the activity of substantia nigra pars reticulata (SNr) neurons of the basal ganglia (BG) and how such changes might contribute to changes we observed previously in the superior colliculus (SC). One, two, four, or eight visual stimuli appeared on random trials while monkeys fixated a centrally located spot. After a delay, one of the stimuli in the array changed luminance, indicating that it was the saccade target. We found that SNr neurons that had a pause in tonic activity after target onset and when the saccade was made to the target showed a modulation of activity during the multitarget task. Because the number of stimuli in the array increased from one to eight, the initial pause after the onset of the visual stimulus decreased. Activity during the preselection delay was reduced but was independent of the number of possible targets present. When one of the stimuli was identified as the saccade target, but before the saccade was made, we found a sharp decline in activity. This decline was related to the monkey's selecting the target rather than the luminance change identifying the target, because on error trials, when the luminance changed but a saccade was not made to the target, the activity did not decline. The decline for the preferred target location was also accompanied by a lesser decline for adjacent locations. Our findings indicate that SNr activity changes with target selection as it does with saccade initiation and that the SNr could make substantial, direct contributions to the SC at both times. The pause in SNr activity with target selection is consistent with the hypothesis that BG provide a disinhibition for the selection of desired movements.

Action Potentials↗

PubMed2002

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

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

Animals↗