Canceling planned action: an FMRI study of countermanding saccades

We investigated the voluntary control of motor behavior by studying the process of deciding whether or not to execute a movement. We imaged the human dorsal cortex while subjects performed a countermanding task that allowed us to manipulate the probability that subjects would be able to cancel a planned saccade in response to an imperative stop signal. We modeled the behavioral data as a race between gaze-shifting mechanisms and gaze-holding mechanisms towards a finish line where a saccade is generated or canceled, and estimated that saccade cancelation took approximately 160 ms. The frontal eye fields showed greater activation on stop signal trials regardless of successful cancelation, suggesting coactivation of saccade and fixation mechanisms. The supplementary eye fields, however, distinguished between successful and unsuccessful cancelation, suggesting a role in monitoring performance. These oculomotor regions play distinct roles in the decision processes mediating saccadic choice.     

Strength of figure-ground activity in monkey primary visual cortex predicts saccadic reaction time in a delayed detection task

When and where are decisions made? In the visual system a saccade, which is a fast shift of gaze toward a target in the visual scene, is the behavioral outcome of a decision. Current neurophysiological data and reaction time models show that saccadic reaction times are determined by a build-up of activity in motor-related structures, such as the frontal eye fields. These structures depend on the sensory evidence of the stimulus. Here we use a delayed figure-ground detection task to show that late modulated activity in the visual cortex (V1) predicts saccadic reaction time. This predictive activity is part of the process of figure-ground segregation and is specific for the saccade target location. These observations indicate that sensory signals are directly involved in the decision of when and where to look.     

Impairment of gaze-centered updating of reach targets in bilateral parietal-occipital damaged patients

Recent studies have suggested that internal updating of visuospatial targets in humans occurs in gaze-centered coordinates and takes place in the parietal and extrastriate cortices. We explored how information for reaching is updated in two patients with bilateral lesions in these areas. Subjects performed two visuomotor tasks: (i) a fixation reaching task, which began with the appearance of one of five fixation positions (varying eye positions) followed by a central reaching target. Subjects reached to the target while fixating on the presented fixation position (relative to gaze the target was always presented in the periphery); and (ii) a saccade reaching task, in which subjects foveated on the central reaching target, then made a saccade to the presented fixation position before reaching to the central target. In both tasks, subjects reached to targets after a 500 or 5000 ms delay. Gaze-centered updating predicts similarities in reaching errors between fixation and saccade trials. Control subjects showed evidence for gaze-centered updating during both 500 and 5000 ms delay conditions. In contrast, patient AT, who had extensive occipital-parietal damage, only showed signs of gaze-centered representation after 5 s. Patient IG, with a more focal lesion in the parietal cortices, showed partial updating in gaze-centered coordinates when reaching with the small memory delay but recovered a complete gaze-centered representation after the longer delay. This suggests that patients with bilateral occipital-parietal lesions may rely on non-gaze-centered frames to store immediate target locations in reaching space but, given enough time, this information may be rerouted to access other gaze-centered motor cortical mechanisms.     

MEG tomography of human cortex and brainstem activity in waking and REM sleep saccades

We recorded the magnetoencephalographic (MEG) signal from three subjects before, during and after eye movements cued to a tone, self-paced, awake and during rapid eye movement (REM) sleep. During sleep we recorded the MEG signal throughout the night together with electroencephalographic (EEG) and electromyographic (EMG) channels to construct a hypnogram. While awake, just prior to and during eye movements, the expected well time-locked physiological activations were imaged in pontine regions, with early 3 s priming. Activity in the frontal eye fields (FEF) was identified in the 300 ms before the saccade onset. Visual cortex activation occurred 200 ms after saccades. During REM, compared to the eyes closed awake condition, activity was higher in supplementary motor area (SMA) and lower in inferior parietal and precuneus cortex. Electro-occulographic (EOG) activity just prior to REM saccades correlated with bilateral pontine and FEF activity some 250-400 ms before REM saccade onset, which in turn was preceded 200 ms earlier by reciprocal activation of the pons and FEF. An orbitofrontal-amygdalo-parahippocampal-pontine sequence, possibly related to emotional activation during REM sleep, was identified in the last 100 ms leading to the REM saccade, but not linked to saccade initiation.     

Segregation of visual selection and saccades in human frontal eye fields

The premotor theory of attention suggests that target processing and generation of a saccade to the target are interdependent. Temporally precise transcranial magnetic stimulation (TMS) was delivered over the human frontal eye fields, the area most frequently associated with the premotor theory in association with eye movements, while subjects performed a visually instructed pro-/antisaccade task. Visual analysis and saccade preparation were clearly separated in time, as indicated by 2 distinct time points of TMS delivery that resulted in elevated saccade latencies. These results show that visual analysis and saccade preparation, although frequently enacted together, are dissociable processes.     

Population vector analysis of primate prefrontal activity during spatial working memory

Population vectors were used to examine information represented by a population of prefrontal activity and its temporal change during spatial working memory processes while monkeys performed ODR and R-ODR tasks. In the ODR task, monkeys made a saccade to the cue location after the delay, whereas in the R-ODR task, they made a saccade 90 degrees clockwise from the cue location. We first constructed population vectors using cue- and response-period activity. The directions of population vectors were similar to the cue directions and the saccade target directions, respectively, indicating that population vectors correctly represented information regarding directions of visual cues and saccade targets. We then calculated population vectors during a 250 ms time-window from the cue presentation to the end of the response period. In the ODR task, all population vectors were directed toward the cue direction. However, in the R-ODR task, the population vector gradually rotated during the delay period from the cue direction to the saccade direction. These results indicate that spatial information represented by a population of prefrontal activity can be shown as the direction of the population vector and that its temporal change during spatial working memory tasks can be depicted as the temporal change of the vector's direction.     

Decomposing the neural correlates of antisaccade eye movements using event-related FMRI

The antisaccade task is a model of the conflict between an unwantedreflexive response (which must be inhibited) and a complex volitionalresponse (which must be generated). The present experiment aimedto investigate separately the neural correlates of these cognitivecomponents using a delayed saccade paradigm to dissociate saccadeinhibition from generation. Seventeen healthy volunteers completedevent-related functional magnetic resonance imaging at 1.5 Tduring saccades to and away from a peripheral visual target(prosaccades and antisaccades, respectively). Saccades wererequested in response to an auditory go signal on average 12s after peripheral target appearance. It was found that theright supramarginal gyrus showed significantly greater activationduring the inhibition phase than the generation phase of theparadigm for both antisaccade and prosaccade trials, suggestinga role in saccade inhibition or stimulus detection. On the otherhand, the right lateral frontal eye field and bilateral intraparietalsulcus showed evidence of selective involvement in antisaccadegeneration. Ventrolateral and dorsolateral prefrontal corticesshowed comparable levels of activation in both phases of thetask. These areas likely fulfill a more general supervisoryrole in the volitional control of eye movements, such as stimulusappraisal, task set, and decision making.     

Temporal evolution and strength of neural activity in parietal cortex during eye and hand movements

The role of area 7a in eye-hand movement was studied by recording from individual neurons while monkeys performed 7 different tasks, aimed at assessing the relative influence of retinal, eye, and hand information on neural activity. Parietal cell activity was modulated by visuospatial signals about target location, as well as by information concerning eye and/or hand movement, and position. The highest activity was elicited when the hand moved to the fixation point. The population activities across different memory tasks showed common temporal peaks when aligned to the visual instruction (visuospatial peak) or Go signal (motor peak) for eye, hand, and coordinated eye-hand movement. The motor peak was higher for coordinated eye-hand movement, and it was absent in a No-Go task. Two activation maxima were also observed during visual reaching. They had the same latency of the visuospatial and motor peaks seen in the memory tasks. Therefore, area 7a seems to operate through a common neural mechanism underlying eye, hand, or combined eye-hand movement. This mechanism is revealed by invariant temporal activity profiles and is independent from the effector selected and from the presence or absence of a visible target during movement. For comparative purposes, we have studied the temporal evolution of the population activity in the superior parietal lobule (SPL) during the same reaching tasks and during a saccade task. In SPL, the population activity was characterized by a single peak, time locked to the Go signal for eye, hand, or combined eye-hand movement. As in IPL, the time of occurrence of this peak was effector independent. The population activity remained unchanged when the position of the eye changed, suggesting that SPL is mostly devoted to the hand motor behavior.     

A cortico-subcortical model for generation of spatially accurate sequential saccades.

This article provides a systems framework for the analysis of cortical and subcortical interactions in the control of saccadic eye movements, A major thesis of this model is that a topography of saccade direction and amplitude is preserved through multiple projections between brain regions until they are finally transformed into a temporal pattern of activity that drives the eyes to the target. The control of voluntary saccades to visual and remembered targets is modeled in terms of interactions between posterior parietal cortex, frontal eye fields, the basal ganglia (caudate and substantia nigra), superior colliculus, mediodorsal thalamus, and the saccade generator of the brainstem. Interactions include the modulation of eye movement motor error maps by topographic inhibitory projections, dynamic remapping of spatial target representations in saccade motor error maps, and sustained neural activity that embodies spatial memory. Models of these mechanisms implemented in our Neural Simulation Language simulate behavior and neural activity described in the literature, and suggest new experiments.     

Effects of low-dose isoflurane on saccadic eye movement generation

The effects of 0.15% quasi-steady-state end-tidal isoflurane on two saccadic eye-movement tests were examined in five volunteers using a newly devised computer-based recording system. The tests were saccadic latency and a countermanding task, the latter being an indicator of the highest levels of conscious performance. A moving light-emitting diode target was displayed on a screen and in the saccadic-latency task the latency of eye movement to the target was measured. In all five subjects the latency increased with anaesthetic by an amount which varied from 8 to 45 ms. This result was significantly different (p < 0.05) from subjects without anaesthetic. In the countermanding task, the subject had to voluntarily inhibit movement to the target. Again anaesthetic increased the latency of response, which varied from 6 to 33 ms. This result was significantly different (p < 0.05) from subjects without anaesthetic. In these studies it appeared that two tasks, one a simple latency test and the other, the countermanding task, requiring higher cortical processing were equally impaired at subanaesthetic concentrations of isoflurane.     

Modulation of antisaccades by transcranial magnetic stimulation of the human frontal eye field

It has been suggested that the frontal eye field (FEF), which is involved with the inhibition and generation of saccades, is engaged to a different degree in pro- and antisaccades. Pro- and antisaccades are often assessed in separate experimental blocks. In such cases, saccade inhibition is required for antisaccades but not for prosaccades. To more directly assess the role of the FEF in saccade inhibition and generation, a new paradigm was used in which inhibition was necessary on pro- and antisaccade trials. Participants looked in the direction indicated by a target ('<' or '>') that appeared in the left or right visual field. When the pointing direction and the location were congruent, prosaccades were executed; otherwise antisaccades were required. Saccadic latencies were measured in blocks without and with single pulse transcranial magnetic stimulation (TMS) to the right FEF or a right posterior control site. Results showed that antisaccades generated into the hemifield ipsilateral to the TMS were significantly delayed after TMS over the FEF, but not the posterior control site. This result is interpreted in terms of a modulation of saccade inhibition to the contralateral visual field due to disruption of processing in the FEF.     

Functional brain mapping of the macaque related to spatial working memory as revealed by PET

To define the cortical areas that subserve spatial working memory in a nonhuman primate, we measured regional cerebral blood flow (rCBF) with [(15)O]H(2)O and positron emission tomography while monkeys performed a visually guided saccade (VGS) task and an oculomotor delayed-response (ODR) task. Both Statistical Parametric Mapping and regions of interest-based analyses revealed an increase of rCBF in the area surrounding the principal sulcus (PS), the superior convexity, the anterior bank of the arcuate sulcus (AS), the lateral orbitofrontal cortex (lOFC), the frontal pole (FP), the anterior cingulate cortex (ACC), the lateral bank of the intraparietal sulcus (lIPS) and the prestriate cortex. In the prefrontal cortex (PS, superior convexity, AS, lOFC and FP), rCBF values correlated positively with ODR task performance scores. From the hippocampus, rCBF values correlated negatively with ODR task performance. From the AS, superior convexity, lOFC, FP, ACC and lIPS, rCBF values of the PS correlated positively with rCBF values and negatively with hippocampus rCBF values. These results suggest that neural circuitry in the prefrontal cortex directly contributes the spatial working memory processes and that, in spatial working memory processes, the posterior parietal cortex and hippocampus have a different role to the prefrontal cortex.     

Population vector analysis of primate mediodorsal thalamic activity during oculomotor delayed-response performance

To understand functional roles of the thalamic mediodorsal nucleus (MD) in sensory-to-motor information transformation during spatial working memory performance and compare with those of the dorsolateral prefrontal cortex (DLPFC), we calculated population vectors using a population of MD activities recorded during 2 tasks. In the oculomotor delayed-response (ODR) task, monkeys needed to make a memory-guided saccade to the cue location, whereas in the rotatory oculomotor delayed-response (R-ODR) task, they needed to make a memory-guided saccade 90 degrees clockwise from the cue direction. The directions of population vectors calculated from populations of cue- and response-period activities were similar to the cue and saccade target directions, respectively, which confirmed that population vectors represent information regarding the directions of the visual cue and the saccade target. We then calculated population vectors of delay-period activity using a sliding 250-ms time window. In the ODR task, population vectors were directed toward the cue direction throughout the delay. However, in the R-ODR task, they gradually rotated from the cue direction to the saccade target direction. Based on a comparison with the results obtained from DLPFC neurons, the rotation of population vectors started earlier in the MD than in the DLPFC, suggesting that the motor information regarding forthcoming saccade is provided from the MD.     

Simultaneous representation of saccade targets and visual onsets in monkey lateral intraparietal area

The monkey's lateral intraparietal area (LIP) has been associated with attention and saccades. LIP neurons have visual on-responses to objects abruptly appearing in their receptive fields (RFs) and sustained activity preceding saccades to the RF. We studied the relationship between the on-responses and delay activity in LIP using a 'stable-array' task. Monkeys viewed eight distinct, continuously illuminated objects, arranged in a circle with at least one object in the RF. A cue flashed instructing the monkey to make a saccade, after a delay, to the stable object physically matching the cue. The location of the cue was fixed in trial blocks, either in or out of the RF. If the cue was outside the RF, neurons developed delay-period activity tuned for the direction of the saccade target at approximately 190 ms after cue onset. If the cue appeared in the RF, neurons initially responded to cue onset and developed tuning for saccade direction only toward the end of the delay period, 390 ms after cue onset. The cue- and saccade-target responses coexisted throughout a significant portion of the delay period. The results show that visual-on responses and delay-period activity in LIP are functionally separable, and that, although highly selective, the salience representation in LIP can contain more than one object at a time.     

Activation of Human Prefrontal Cortex during Spatial and Nonspatial Working Memory Tasks Measured by Functional MRI

Separate working memory domains for spatial location, and forobjects, faces, and patterns, have been identified in the prefrontalcortex (PFC) of nonhuman primates. We have used functional magneticresonance imaging to examine whether spatial and nonspatialvisual working memory processes are similarly dissociable inhuman PFC. Subjects performed tasks which required them to remembereither the location or shape of successive visual stimuli. Wefound that the mnemonic component of the working memory tasksaffected the hemispheric pattern of PFC activation. The spatial(LOCATION) working memory task preferentially activated themiddle frontal gyrus (MFG) in the right hemisphere, while thenonspatial (SHAPE) working memory task activated the NIFG inboth hemispheres. Furthermore, the area of activation in theleft hemisphere extended into the inferior frontal gyrus forthe nonspatial SHAPE task. A perceptual target (DOT) detectiontask also activated the MFG bilaterally, but at a level approximatelyhalf that of the working memory tasks. The activation in theMFG occurred within 3–6 s of task onset and declined followingtask offset. Time-course analysis revealed a different patternfor the cingulate gyrus, in which activation occurred upon taskcompletion. Cingulate activation was greatest following theSHAPE task and was greater in the left hemisphere. The presentresults support the prominent role of the PFC and, specifically,the MFG in working memory, and indicate that the mnemonic contentof the task affects the relative weighting of hemispheric activation.     

Central effects of sildenafil (Viagra) on auditory selective attention and verbal recognition memory in humans: a study with event-related brain potentials

The purpose of this study was to assess possible central side-effects of sildenafil (Viagra) on attention and memory functions. Sildenafil and placebo were administered in young male subjects in a double-blind balanced cross-over design. Behavioral patterns and event-related brain potentials (ERP) were recorded in a spatial auditory attention and a visual word recognition task. While behavioral patterns did not reveal any overt effects of sildenafil, auditory ERPs were indicative of an enhanced ability to focus attention (amplitude enhancement of Nd-effect) and to select relevant target stimuli in the sildenafil condition (P3 component). In the memory task, CNS-effects of sildenafil were evident in a reduction of a negativity in the 150–250 ms range. No overt effects on behavior were observed. Nevertheless, the data reveal CNS-effects of sildenafil necessitating further studies.     

The cross-modal interaction between pain-related and saccade-related cerebral activation: a preliminary study by event-related functional magnetic resonance imaging

Pain-related cerebral activation in functional magnetic resonance imaging shows less consistent signals that decay earlier than in conventional task-related activation. This may result from pain's top-down inhibition mediated by cognitive or hemodynamic interaction that could affect activation by other modalities. Using event-related functional magnetic resonance imaging, we examined whether pain affects cerebral activation by a saccade task through such cross-modal interaction. Six right-handed volunteers underwent whole-brain echo-planar imaging on a 3.0 T magnetic resonance imaging scanner while they received thermal pain stimulus at 50 degrees C on the right forearm (P; n = 6), performed a visually guided saccade task (V; n = 6), and went through a simultaneous pain-plus-saccade paradigm (PV; n = 5). Averaged functional activation maps were synthesized and signal time courses were analyzed at activation clusters. P activated the bilateral secondary somatosensory cortex (S2). V activated the posterior, supplementary, frontal eye fields, and visual areas. PV enhanced the S2 activation and activated additional pain-related areas, including the bilateral premotor area, right insula, anterior, and posterior cingulate cortices. In contrast, V-related activation was attenuated in PV. We propose that pain caused cross-modal suppression on the oculomotor activity and that an oculomotor task enhanced pain-related activation by triggering attention toward pain. IMPLICATIONS: Pain-related cerebral activation is enhanced by attention toward pain. It may involve top-down suppression over the unrelated neural networks of saccade.     

Dissociable functional cortical topographies for working memory maintenance of voice identity and location

In order to ascertain whether the neural system for auditory working memory exhibits a functional dissociation for spatial and nonspatial information, we used functional magnetic resonance imaging and a single set of auditory stimuli to study working memory for the location and identity of human voices. The subjects performed a delayed recognition task for human voices and voice locations and an auditory sensorimotor control task. Several temporal, parietal, and frontal areas were activated by both memory tasks in comparison with the control task. However, during the delay periods, activation was greater for the location than for the voice identity task in dorsal prefrontal (SFS/PreCG) and parietal regions and, conversely, greater for voices than locations in ventral prefrontal cortex and the anterior portion of the insula. This preferential response to the voice identity task in ventral prefrontal cortex continued during the recognition test period, but the double dissociation was observed only during maintenance, not during encoding or recognition. Together, the present findings suggest that, during auditory working memory, maintenance of spatial and nonspatial information modulates activity preferentially in a dorsal and a ventral auditory pathway, respectively. Furthermore, the magnitude of this dissociation seems to be dependent on the cognitive operations required at different times during task performance.     

Roles of attention, memory, and motor preparation in modulating human brain activity in a spatial working memory task

Neuronal activity of the human brain was studied with magnetoencephalography (MEG) in a spatial working memory task similar to those commonly used with nonhuman primates. The subject was required to remember target positions for 3 s and make a same-different judgement with a finger lift comparing the position of the probed target with the probe or to execute a memory-guided saccade to the probed target. In this type of task single-unit studies have shown attention- and memory-related activities independent of movement type during the retention interval in a large number of cortical areas of the primates, including the parietal and prefrontal areas. Consistent with these results, there were strong stimulus-driven transient and sustained responses and modulations of oscillatory activity during the retention period. Although we did not determine the source locations, coarse estimates of the currents responsible for the MEG signals showed activity over a wide area of the cortex, most prominently over the Rolandic, parietal and occipital areas, but also over the frontal area. Some of the activities in these cortical areas reflect processes that may be identified with attention and memory, while others were related to preparation of the overt movements.      

V1 activation in congenitally blind humans is associated with episodic retrieval

Recently we showed that the occipital cortex of congenitally blind humans is activated during verbal-memory tasks. Activation was found in regions corresponding to the retinotopic visual areas of sighted humans, including the calcarine sulcus (V1). No such occipital activation was found in sighted humans. One year later, the same blind subjects participated in a second fMRI scan, to study the contribution of semantic elements and episodic memory to the occipital activation. The subjects performed an episodic-memory task, requiring recognition of words that were originally presented in the first scan. We demonstrate here that the magnitude of V1 activation during the recognition task is correlated with memory performance, assessed during the scan. Across the blind, the better-remembered set of words elicited greater V1 activation than words from the poorly-remembered set, although the semantic components and the behavioral task were similar in the two sets. This indicates that on top of semantic processing (suggested previously), V1 activation in the blind is probably associated with long-term episodic memory. Indeed, within the blind, those who showed better recognition-memory performance had greater V1 activation compared with the poorer performers. We conclude that the posterior occipital cortex (including V1) of the congenitally blind is likely to be involved in episodic retrieval.