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

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

Topographic maps of visual spatial attention in human parietal cortex

Functional magnetic resonance imaging (fMRI) was used to measure activity in human parietal cortex during performance of a visual detection task in which the focus of attention systematically traversed the visual field. Critically, the stimuli were identical on all trials (except for slight contrast changes in a fully randomized selection of the target locations) whereas only the cued location varied. Traveling waves of activity were observed in posterior parietal cortex consistent with shifts in covert attention in the absence of eye movements. The temporal phase of the fMRI signal in each voxel indicated the corresponding visual field location. Visualization of the distribution of temporal phases on a flattened representation of parietal cortex revealed at least two distinct topographically organized cortical areas within the intraparietal sulcus (IPS), each representing the contralateral visual field. Two cortical areas were proposed based on this topographic organization, which we refer to as IPS1 and IPS2 to indicate their locations within the IPS. This nomenclature is neutral with respect to possible homologies with well-established cortical areas in the monkey brain. The two proposed cortical areas exhibited relatively little response to passive visual stimulation in comparison with early visual areas. These results provide evidence for multiple topographic maps in human parietal cortex.     

Processing of Coherent Visual Motion in Topographically Organized Visual Areas in Human Cerebral Cortex

Recent imaging studies in human subjects have demonstrated representations of global visual motion in medial parieto-occipital cortex (area V6) and posterior parietal cortex, the latter containing at least seven topographically organized areas along the intraparietal sulcus (IPS0–IPS5, SPL1). In this fMRI study we used topographic mapping procedures to delineate a total of 18 visual areas in human cerebral cortex and tested their responsiveness to coherent visual motion under conditions of controlled attention and fixation. Preferences for coherent visual motion as compared to motion noise as well as hemispheric asymmetries were assessed for contralateral, ipsilateral, and bilateral visual motion presentations. Except for areas V1–V4 and IPS3-5, all other areas showed stronger responses to coherent motion with the most significant activations found in V6, followed by MT/MST, V3A, IPS0-2 and SPL1. Hemispheric differences were negligible altogether suggesting that asymmetries in parietal cortex observed in cognitive tasks do not reflect differences in basic visual response properties. Interestingly, areas V6, MST, V3A, and areas along the intraparietal sulcus showed specific representations of coherent visual motion not only when presented in the hemifield primarily covered by the given visual representation but also when presented in the ipsilateral visual field. This finding suggests that coherent motion induces a switch in spatial representation in specialized motion areas from contralateral to full-field coding.     

Spike-field activity in parietal area LIP during coordinated reach and saccade movements

The posterior parietal cortex is situated between visual and motor areas and supports coordinated visually guided behavior. Area LIP in the intraparietal sulcus contains representations of visual space and has been extensively studied in the context of saccades. However, area LIP has not been studied during coordinated movements, so it is not known whether saccadic representations in area LIP are influenced by coordinated behavior. Here, we studied spiking and local field potential (LFP) activity in area LIP while subjects performed coordinated reaches and saccades or saccades alone to remembered target locations to test whether activity in area LIP is influenced by the presence of a coordinated reach. We find that coordination significantly changes the activity of individual neurons in area LIP, increasing or decreasing the firing rate when a reach is made with a saccade compared with when a saccade is made alone. Analyzing spike-field coherence demonstrates that area LIP neurons whose firing rate is suppressed during the coordinated task have activity temporally correlated with nearby LFP activity, which reflects the synaptic activity of populations of neurons. Area LIP neurons whose firing rate increases during the coordinated task do not show significant spike-field coherence. Furthermore, LFP power in area LIP is suppressed and does not increase when a coordinated reach is made with a saccade. These results demonstrate that area LIP neurons display different responses to coordinated reach and saccade movements, and that different spike rate responses are associated with different patterns of correlated activity. The population of neurons whose firing rate is suppressed is coherently active with local populations of LIP neurons. Overall, these results suggest that area LIP plays a role in coordinating visually guided actions through suppression of coherent patterns of saccade-related activity.     

Directional selectivity of BOLD activity in human posterior parietal cortex for memory-guided double-step saccades

We used functional magnetic resonance imaging (fMRI) to investigate the role of the human posterior parietal cortex (PPC) in storing target locations for delayed double-step saccades. To do so, we exploited the laterality of a subregion of PPC that preferentially responds to the memory of a target location presented in the contralateral visual field. Using an event-related design, we tracked fMRI signal changes in this region while subjects remembered the locations of two sequentially flashed targets, presented in either the same or different visual hemifields, and then saccaded to them in sequence. After presentation of the first target, the fMRI signal was always related to the side of the visual field in which it had been presented. When the second target was added, the cortical activity depended on the respective locations of both targets but was still significantly selective for the target of the first saccade. We conclude that this region within the human posterior parietal cortex not only acts as spatial storage center by retaining target locations for subsequent saccades but is also involved in selecting the target for the first intended saccade.     

Temporal processing of saccade targets in parietal cortex area LIP during visual search

We studied whether the lateral intraparietal (LIP) area-a subdivision of parietal cortex anatomically interposed between visual cortical areas and saccade executive centers-contains neurons with activity patterns sufficient to contribute to the active process of selecting saccade targets in visual search. Visually responsive neurons were recorded while monkeys searched for a color-different target presented concurrently with seven distractors evenly distributed in a circular search array. We found that LIP neurons initially responded indiscriminately to the presentation of a visual stimulus in their response fields, regardless of its feature and identity. Their activation nevertheless evolved to signal the search target before saccade initiation: an ideal observer could reliably discriminate the target from the individual activation of 60% of neurons, on average, 138 ms after stimulus presentation and 26 ms before saccade initiation. Importantly, the timing of LIP neuronal discrimination varied proportionally with reaction times. These findings suggest that LIP activity reflects the selection of both the search target and the targeting saccade during active visual search.     

Responses to auditory stimuli in macaque lateral intraparietal area. II. Behavioral modulation.

The lateral intraparietal area (LIP), a region of posterior parietal cortex, was once thought to be unresponsive to auditory stimulation. However, recent reports have indicated that neurons in area LIP respond to auditory stimuli during an auditory-saccade task. To what extent are auditory responses in area LIP dependent on the performance of an auditory-saccade task? To address this question, recordings were made from 160 LIP neurons in two monkeys while the animals performed auditory and visual memory-saccade and fixation tasks. Responses to auditory stimuli were significantly stronger during the memory-saccade task than during the fixation task, whereas responses to visual stimuli were not. Moreover, neurons responsive to auditory stimuli tended also to be visually responsive and to exhibit delay or saccade activity in the memory-saccade task. These results indicate that, in general, auditory responses in area LIP are modulated by behavioral context, are associated with visual responses, and are predictive of delay or saccade activity. Responses to auditory stimuli in area LIP may therefore be best interpreted as supramodal responses, and similar in nature to the delay activity, rather than as modality-specific sensory responses. The apparent link between auditory activity and oculomotor behavior suggests that the behavioral modulation of responses to auditory stimuli in area LIP reflects the selection of auditory stimuli as targets for eye movements.     

Nonspatial saccade-specific activation in area LIP of monkey parietal cortex

We present evidence that neurons in the lateral intraparietal area (LIP) of monkey posterior parietal cortex (PPC) are activated by the instruction to make an eye movement, even in the complete absence of a spatial target. This study employed a visually guided motor task that dissociated the type of movement to make (saccade or reach) from the location where the movement was to be made. Using this task, animals were instructed to prepare a specific type of movement prior to knowing the spatial location of the movement target. We found that 25% of the LIP neurons recorded in two animals were activated significantly more by the instruction to prepare a saccade than by the instruction to prepare a reach. This finding indicates that LIP is involved in more than merely spatial attention and provides further evidence for nonspatial effector-specific signal processing in the dorsal stream.     

Specialization of reach function in human posterior parietal cortex

Posterior parietal cortex (PPC) plays an important role in the planning and control of goal-directed action. Single-unit studies in monkeys have identified reach-specific areas in the PPC, but the degree of effector and computational specificity for reach in the corresponding human regions is still under debate. Here, we review converging evidence spanning functional neuroimaging, parietal patient and transcranial magnetic stimulation studies in humans that suggests a functional topography for reach within human PPC. We contrast reach to saccade and grasp regions to distinguish functional specificity and also to understand how these different goal-directed actions might be coordinated at the cortical level. First, we present the current evidence for reach specificity in distinct modules in PPC, namely superior parietal occipital cortex, midposterior intraparietal cortex and angular gyrus, compared to saccade and grasp. Second, we review the evidence for hemispheric lateralization (both for hand and visual hemifield) in these reach representations. Third, we review evidence for computational reach specificity in these regions and finally propose a functional framework for these human PPC reach modules that includes (1) a distinction between the encoding of reach goals in posterior–medial PPC as opposed to reach movement vectors in more anterior–lateral PPC regions, and (2) their integration within a broader cortical framework for reach, grasp and eye–hand coordination. These findings represent both a confirmation and extension of findings that were previously reported for the monkey.     

The functional organization of the intraparietal sulcus in humans and monkeys

In macaque monkeys, the posterior parietal cortex (PPC) is concerned with the integration of multimodal information for constructing a spatial representation of the external world (in relation to the macaque's body or parts thereof), and planning and executing object-centred movements. The areas within the intraparietal sulcus (IPS), in particular, serve as interfaces between the perceptive and motor systems for controlling arm and eye movements in space. We review here the latest evidence for the existence of the IPS areas AIP (anterior intraparietal area), VIP (ventral intraparietal area), MIP (medial intraparietal area), LIP (lateral intraparietal area) and CIP (caudal intraparietal area) in macaques, and discuss putative human equivalents as assessed with functional magnetic resonance imaging. The data suggest that anterior parts of the IPS comprising areas AIP and VIP are relatively well preserved across species. By contrast, posterior areas such as area LIP and CIP have been found more medially in humans, possibly reflecting differences in the evolution of the dorsal visual stream and the inferior parietal lobule. Despite interspecies differences in the precise functional anatomy of the IPS areas, the functional relevance of this sulcus for visuomotor tasks comprising target selections for arm and eye movements, object manipulation and visuospatial attention is similar in humans and macaques, as is also suggested by studies of neurological deficits (apraxia, neglect, Bálint's syndrome) resulting from lesions to this region.     

Cortical control of saccades

Saccadic eye movements are controlled by a cortical network composed of several oculomotor areas that are now accurately localized. Clinical and experimental studies have enabled us to understand their specific roles better. These areas are: (1) the parietal eye field (PEF) located in the intraparietal sulcus involved in visuospatial integration and in reflexive saccade triggering; (2) the frontal eye field (FEF), located in the precentral gyrus, involved in the preparation and the triggering of purposive saccades; and (3) the supplementary eye field (SEF) on the medial wall of the frontal lobe, probably involved in the temporal control of sequences of visually guided saccades and in eye-hand coordination. A putative cingulate eye field (CEF), located in the anterior cingulate cortex, would be involved in motivational modulation of voluntary saccades. Besides these motor areas, the dorsolateral prefrontal cortex (dlPFC) in the midfrontal gyrus is involved in reflexive saccade inhibition and visual shortterm memory.     

Memory activity of LIP neurons for sequential eye movements simulated with neural networks

Many neurons in macaque lateral intraparietal cortex (LIP) maintain elevated activity induced by visual or auditory targets during tasks in which monkeys are required to withhold one or more planned eye movements. We studied the mechanisms for such memory activity with neural network modeling. Recurrent connections among simulated LIP neurons were used to model memory responses of LIP neurons. The connection weights were computed using an optimization procedure to produce desired outputs in memory-saccade tasks. One constraint for the training process is the "single-purpose" rule, which mimics the fact that once LIP neurons hold the memory activity of a saccade, they are insensitive to further stimuli until the motor action is completed. After training, excitatory connections were developed between units with similar preferred saccade directions, while inhibitory connections were formed between units with dissimilar directions. This "push-pull" mechanism enables the network to encode the next intended eye movement and is essential for programming sequential saccades. In simulating double saccades, the push-pull connections locked the on-going activity in the network for the first saccade until the saccade was made, then a new population of units became active to prepare for the second saccade. The simulated LIP neurons exhibited sensory responses and memory activities similar to those recorded in LIP neurons. We propose that push-pull recurrent connections might be the basic structure mediating the memory activity of area LIP in planning sequential eye movements.     

Activity of neurons in the lateral intraparietal area of the monkey during an antisaccade task.

The close relationship between saccadic eye movements and vision complicates the identification of neural responses associated with each function. Visual and saccade-related responses are especially closely intertwined in a subdivision of posterior parietal cortex, the lateral parietal area (LIP). We analyzed LIP neurons using an antisaccade task in which monkeys made saccades away from a salient visual cue. The vast majority of neurons reliably signaled the location of the visual cue. In contrast, most neurons had only weak, if any, saccade-related activity independent of visual stimulation. Thus, whereas the great majority of LIP neurons reliably encoded cue location, only a small minority encoded the direction of the upcoming saccade.     

A comparison of frontoparietal fMRI activation during anti-saccades and anti-pointing

An anti-saccade, which is a saccade directed toward a mirror-symmetrical position in the opposite visual field relative to the visual stimulus, involves at least three separate operations: covert orienting, response suppression, and coordinate transformation. The distinction between pro- and anti-saccades can also be applied to pointing. We used fMRI to compare patterns of brain activation during pro- and anti-movements, to determine whether or not additional areas become active during the production of anti-movements. In parietal cortex, an inferior network was active during both saccades and pointing that included three foci along the intraparietal sulcus: 1) a posterior superior parietal area (pSPR), more active during the anti-tasks; 2) a middle inferior parietal area (mIPR), active only during the anti-tasks; and 3) an anterior inferior parietal area (aIPR), equally active for pro- and anti-movement. A superior parietal network was active during pointing but not saccades and included the following: 1) a medial region, active during anti- but not pro-pointing (mSPR); 2) an anterior and medial region, more active during pro-pointing (aSPR); and 3) an anterior and lateral region, equally active for pro- and anti-pointing (lSPR). In frontal cortex, areas selectively active during anti-movement were adjacent and anterior to areas that were active during both the anti- and pro-tasks, i.e., were anterior to the frontal eye field and the supplementary motor area. All saccade areas were also active during pointing. In contrast, foci in the dorsal premotor area, the anterior superior frontal region, and anterior cingulate were active during pointing but not saccades. In summary, pointing with central gaze activates a frontoparietal network that includes the saccade network. The operations required for the production of anti-movements recruited additional frontoparietal areas.     

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.     

Transcranial magnetic stimulation disrupts eye-hand interactions in the posterior parietal cortex

Recent neurophysiological studies have started to shed some light on the cortical areas that contribute to eye-hand coordination. In the present study we investigated the role of the posterior parietal cortex (PPC) in this process in normal, healthy subjects. This was accomplished by delivering single pulses of transcranial magnetic stimulation (TMS) over the PPC to transiently disrupt the putative contribution of this area to the processing of information related to eye-hand coordination. Subjects made open-loop pointing movements accompanied by saccades of the same required amplitude or by saccades that were substantially larger. Without TMS the hand movement amplitude was influenced by the amplitude of the corresponding saccade; hand movements accompanied by larger saccades were larger than those accompanied by smaller saccades. When TMS was applied over the left PPC just prior to the onset of the saccade, a marked reduction in the saccadic influence on manual motor output was observed. TMS delivered at earlier or later periods during the response had no effect. Taken together, these data suggest that the PPC integrates signals related to saccade amplitude with limb movement information just prior to the onset of the saccade.     

Integration of retinal disparity and fixation-distance related signals toward an egocentric coding of distance in the posterior parietal cortex of primates

For those movements that are directed toward objects located in extrapersonal space, it is necessary that visual inputs are first remapped from a retinal coordinate system to a body-centered one. The posterior parietal cortex (PPC) most likely integrates retinal and extraretinal information to determine the egocentric distance of an object located in three-dimensional (3-D) space. This determination requires both a retinal disparity signal and a parallel estimate of the fixation distance. We recorded from the lateral intraparietal area (LIP) to see if single neurons respond to both vergence angle and retinal disparity and if these two signals are integrated to encode egocentric distance. Monkeys were trained to make saccades to real targets in 3-D space. When both fixation distance and disparity of visual stimuli were varied, the disparity tuning of individual neurons display a fixation-distance modulation. We propose that the observed modulation contributes to a spatial coding domain intermediate between retinal and egocentric because the disparity tuning shifts in a systematic way with changes in fixation distance.     

The effect of transcranial magnetic stimulation on the latencies of vertical saccades

In this study, we investigated the effect of transcranial magnetic stimulation (TMS) over the right posterior parietal cortex (PPC) on the latency of two different types of visually-guided vertical saccades: reflexive saccades triggered by the sudden onset of a target, and saccades towards target locations known in advance. For this reason, we used two oculomotor tasks: a gap and a delay task, respectively. Nine normal subjects performed vertical saccades at ±7.5 and ±15°. TMS was applied at 80 and 100 ms after target onset in the gap task, and after fixation offset in the delay task. Without TMS, we confirmed a latency asymmetry in the gap task favouring upward saccades at the lower eccentricity (7.5°), and a latency symmetry in the delay task. TMS increased the latencies of all saccades in the delay task, when delivered at 100 ms. This effect was mostly pronounced for downward saccades at 7.5°. As a result, saccade latencies showed an asymmetry in this condition, similar to the one observed in the gap task without TMS. The gap task with TMS resulted in a variable latency distribution and no significant overall effect on saccade latency. Our results indicate that the right PPC is involved in the initiation of vertical saccades in the delay task, and that this involvement appears to be enhanced for downward saccades. A conclusion for the involvement of this area in the gap task could not be drawn from this study.     

Memory-guided saccade processing in visual form agnosia (patient DF)

According to Milner and Goodale’s model (The visual brain in action, Oxford University Press, Oxford, 2006) areas in the ventral visual stream mediate visual perception and off-line actions, whilst regions in the dorsal visual stream mediate the on-line visual control of action. Strong evidence for this model comes from a patient (DF), who suffers from visual form agnosia after bilateral damage to the ventro-lateral occipital region, sparing V1. It has been reported that she is normal in immediate reaching and grasping, yet severely impaired when asked to perform delayed actions. Here we investigated whether this dissociation would extend to saccade execution. Neurophysiological studies and TMS work in humans have shown that the posterior parietal cortex (PPC), on the right in particular (supposedly spared in DF), is involved in the control of memory-guided saccades. Surprisingly though, we found that, just as reported for reaching and grasping, DF’s saccadic accuracy was much reduced in the memory compared to the stimulus-guided condition. These data support the idea of a tight coupling of eye and hand movements and further suggest that dorsal stream structures may not be sufficient to drive memory-guided saccadic performance.     

Microstimulation of the lateral wall of the intraparietal sulcus compared with the frontal eye field during oculomotor tasks

We compared the effects of intracortical microstimulation (ICMS) of the lateral wall of the intraparietal sulcus (LIP) with those of ICMS of the frontal eye field (FEF) on monkeys performing oculomotor tasks. When ICMS was applied during a task that involved fixation, contraversive saccades evoked in the LIP and FEF appeared similar. When ICMS was applied to the FEF at the onset of voluntary saccades, the evoked saccades collided with the ongoing voluntary saccade so that the trajectory of voluntary saccade was compensated by the stimulus. Thus the resultant saccade was redirected and came close to the endpoint of saccades evoked from the fixation point before the start of voluntary saccade. In contrast, when ICMS was applied to the LIP at the onset of voluntary saccades, the resultant saccade followed a trajectory that was different from that evoked from the FEF. In that case, the colliding saccades were redirected toward an endpoint that was close to the endpoint of saccades evoked when animals were already fixating at the target of the voluntary saccade. This finding suggests that the colliding saccade was directed toward an endpoint calculated with reference to the target of the voluntary saccade. We hypothesize that, shortly before initiation of voluntary saccades, a dynamic process occurs in the LIP so that the reference point for calculating the saccade target shifts from the fixation point to the target of a voluntary saccade. Such predictive updating of reference points seems useful for immediate reprogramming of upcoming saccades that can occur in rapid succession.