The location probability effects of saccade reaction times are modulated in the frontal eye fields but not in the supplementary eye field

The visual system constantly utilizes regularities that are embedded in the environment and by doing so reduces the computational burden of processing visual information. Recent findings have demonstrated that probabilistic information can override attentional effects, such as the cost of making an eye movement away from a visual target (antisaccade cost). The neural substrates of such probability effects have been associated with activity in the superior colliculus (SC). Given the immense reciprocal connections to SC, it is plausible that this modulation originates from higher oculomotor regions, such as the frontal eye field (FEF) and the supplementary eye field (SEF). To test this possibility, the present study employed theta burst transcranial magnetic stimulation (TMS) to selectively interfere with FEF and SEF activity. We found that TMS disrupted the effect of location probability when TMS was applied over FEF. This was not observed in the SEF TMS condition. Together, these 2 experiments suggest that the FEF plays a critical role not only in initiating saccades but also in modulating the effects of location probability on saccade production.     

Posterior cingulate cortex: sensory and oculomotor properties of single neurons in behaving cat.

The posterior cingulate cortex of the cat is strongly linked to cortical areas with sensory and oculomotor functions. We have now recorded from feline posterior cingulate neurons in order to determine whether they are active in conjunction with sensory events and eye movements. The results described here are based on monitoring the electrical activity of 195 single neurons in the posterior cingulate cortex of three cats equipped with surgically implanted scleral search coils and trained to fixate visual targets. Posterior cingulate neurons carry tonic orbital position signals and are phasically active in conjunction with saccadic eye movements. Activity related to eye movements and gaze is attenuated but not abolished by the elimination of visual feedback. Posterior cingulate neurons also are responsive to visual, auditory, and somatosensory stimulation. Systematic testing with visual stimuli revealed that responses are sharply reduced due to refractoriness at rates of stimulation greater than a few per second. These results conform to the theory that posterior cingulate cortex is involved in processes underlying visuospatial cognition.     

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.     

Distinct causal influences of parietal versus frontal areas on human visual cortex: evidence from concurrent TMS-fMRI

It has often been proposed that regions of the human parietal and/or frontal lobe may modulate activity in visual cortex, for example, during selective attention or saccade preparation. However, direct evidence for such causal claims is largely missing in human studies, and it remains unclear to what degree the putative roles of parietal and frontal regions in modulating visual cortex may differ. Here we used transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) concurrently, to show that stimulating right human intraparietal sulcus (IPS, at a site previously implicated in attention) elicits a pattern of activity changes in visual cortex that strongly depends on current visual context. Increased intensity of IPS TMS affected the blood oxygen level-dependent (BOLD) signal in V5/MT+ only when moving stimuli were present to drive this visual region, whereas TMS-elicited BOLD signal changes were observed in areas V1-V4 only during the absence of visual input. These influences of IPS TMS upon remote visual cortex differed significantly from corresponding effects of frontal (eye field) TMS, in terms of how they related to current visual input and their spatial topography for retinotopic areas V1-V4. Our results show directly that parietal and frontal regions can indeed have distinct patterns of causal influence upon functional activity in human visual cortex.     

Dorsolateral prefrontal cortex prevents short-latency saccade and vergence: a TMS study

This study explores whether vergence eye movements along the median plane can be triggered with short latencies, and the role of the dorsolateral prefrontal cortex (DLPFC) in controlling such movements. We used a gap paradigm and applied transcranial magnetic stimulation (TMS) in 10 humans making saccades or vergence. TMS over the motor cortex had no effect on any eye movement parameter. TMS over DLPFC influenced eye movement initiation but not their metrics. TMS over the right DLPFC accelerated the triggering of saccades bilaterally but did not influence divergence. TMS over the left DLPFC speeded up the triggering of ipsilateral saccades and exacerbated the anticipatory mode of triggering of divergence. For convergence, TMS effects were mild: rightward TMS increased the proportion of short latencies but failed to shorten the group mean latency; leftward TMS influenced triggering in some individuals only. For saccades and convergence under TMS, some subjects showed an emerging population of short latencies in their latency distribution. Horizontal saccadic intrusions (80% of trials) and vertical saccades (recorded in one subject) intruding on vergence were unlikely to assist vergence triggering. We conclude that the prefrontal mechanisms underlying voluntary eye movement control are similar for saccades and vergence although some specificities exist.     

The contribution of the human FEF and SEF to smooth pursuit initiation

Smooth pursuit eye movements function to keep moving targets foveated. Behavioral studies have shown that pursuit is particularly effective for predictable target motion. There is evidence that both the frontal eye field (FEF) and supplementary eye field (SEF) (also known as the dorsomedial frontal cortex) contribute to pursuit control. The goal of the current experiment was to determine whether these 2 areas made different contributions to the initiation of pursuit in response to predictable compared with unpredictable target motion. Transcranial magnetic stimulation (TMS) was used in 5 healthy human participants to temporarily disrupt each area around the time of target motion onset. TMS over the FEF delayed contraversive pursuit markedly more than ipsiversive pursuit and this direction-dependent difference was more deeply modulated during pursuit of unpredictable than predictable target motion. By contrast, TMS over the SEF resulted in a much more muted modulation of pursuit latency that was similar across both predictable and unpredictable conditions. Taken together, we conclude that the human FEF, but not the SEF, makes a significant contribution to the processing required during the preparation of contraversive pursuit responses to unpredictable target motion and this contribution is less vital during pursuit to predictable target motion.     

Distribution of activity across the monkey cerebral cortical surface, thalamus and midbrain during rapid, visually guided saccades

To examine the distribution of visual and oculomotor activity across the macaque brain, we performed functional magnetic resonance imaging (fMRI) on awake, behaving monkeys trained to perform visually guided saccades. Two subjects alternated between periods of making saccades and central fixations while blood oxygen level dependent (BOLD) images were collected [3 T, (1.5 mm)3 spatial resolution]. BOLD activations from each of four cerebral hemispheres were projected onto the subjects' cortical surfaces and aligned to a surface-based atlas for comparison across hemispheres and subjects. This surface-based analysis revealed patterns of visuo-oculomotor activity across much of the cerebral cortex, including activations in the posterior parietal cortex, superior temporal cortex and frontal lobe. For each cortical domain, we show the anatomical position and extent of visuo-oculomotor activity, including evidence that the dorsolateral frontal activation, which includes the frontal eye field (on the anterior bank of the arcuate sulcus), extends anteriorly into posterior principal sulcus (area 46) and posteriorly into part of dorsal premotor cortex (area 6). Our results also suggest that subcortical BOLD activity in the pulvinar thalamus may be lateralized during voluntary eye movements. These findings provide new neuroanatomical information as to the complex neural substrates that underlie even simple goal-directed behaviors.     

Priming of motion direction and area V5/MT: a test of perceptual memory

Presentation of supraliminal or subliminal visual stimuli that can (or cannot) be detected or identified can improve the probability of the same stimulus being detected over a subsequent period of seconds, hours or longer. The locus and nature of this perceptual priming effect was examined, using suprathreshold stimuli, in subjects who received repetitive pulse transcranial magnetic stimulation over the posterior occipital cortex, the extrastriate motion area V5/MT or the right posterior parietal cortex during the intertrial interval of a visual motion direction discrimination task. Perceptual priming observed in a control condition was abolished when area V5/MT was stimulated but was not affected by magnetic stimulation over striate or parietal sites. The effect of transcranial magnetic stimulation (TMS) on priming was specific to site (V5/MT) and to task - colour priming was unaffected by TMS over V5/MT. The results parallel, in the motion domain, recent demonstrations of the importance of macaque areas V4 and TEO for priming in the colour and form domains.     

Parietal damage dissociates saccade planning from presaccadic perceptual facilitation

A well-known theory in the field of attention today is the premotor theory of attention which suggests that the mechanisms involved in eye movements are the same as those for spatial attention shifts. We tested a parietal damaged patient with unilateral optic ataxia and 4 controls on a dual saccade/attentional task and show a dissociation between saccadic eye movements and presaccadic perceptual enhancement at the saccade goal. Remarkably, though the patient was able to make the appropriate saccades to the left, impaired visual field (undistinguishable from saccades to his right, intact visual field), he was unable to discriminate the letter at the saccade goal (whereas his performance was like controls for letter discrimination in his right visual field). This suggests that saccade planning and presaccadic perceptual facilitation are separable--planning a saccade to a location does not necessitate that the processing of this location is enhanced. Based on these results, we suggest that the parietal cortex is necessary for the coupling between saccade planning and presaccadic perceptual facilitation.     

Monocular visual deprivation suppresses excitability in adult human visual cortex

The adult visual cortex maintains a substantial potential for plasticity in response to a change in visual input. For instance, transcranial magnetic stimulation (TMS) studies have shown that binocular deprivation (BD) increases the cortical excitability for inducing phosphenes with TMS. Here, we employed TMS to trace plastic changes in adult visual cortex before, during, and after 48 h of monocular deprivation (MD) of the right dominant eye. In healthy adult volunteers, MD-induced changes in visual cortex excitability were probed with paired-pulse TMS applied to the left and right occipital cortex. Stimulus-response curves were constructed by recording the intensity of the reported phosphenes evoked in the contralateral visual field at range of TMS intensities. Phosphene measurements revealed that MD produced a rapid and robust decrease in cortical excitability relative to a control condition without MD. The cortical excitability returned to preinterventional baseline levels within 3 h after the end of MD. The results show that in contrast to the excitability increase in response to BD, MD acutely triggers a reversible decrease in visual cortical excitability. This shows that the pattern of visual deprivation has a substantial impact on experience-dependent plasticity of the human visual cortex.     

FEF TMS affects visual cortical activity

We tested whether the frontal eye field (FEF) is critical in controlling visual processing in posterior visual brain areas during the orienting of spatial attention. Short trains (5 pulses at 10 Hz) of transcranial magnetic stimulation (TMS) were applied to the right FEF during the cueing period of a covert attentional task while event-related potentials (ERPs) were simultaneously recorded from lateral posterior electrodes, where visual components are prominent. FEF TMS significantly affected the neural activity evoked by visual stimuli, as well as the ongoing neural activity recorded during earlier anticipation of the visual stimuli. The effects of FEF TMS started earlier and were greatest for brain activity recorded ipsilaterally to FEF TMS and contralaterally to the visual stimulus. The TMS-induced effect on visual ERPs occurred at the same time as ERPs were shown to be modulated by visual attention. Importantly, no similar effects were observed after TMS of a control site that was physically closer but not anatomically interconnected to the recording sites. The results show that the human FEF has a causal influence over the modulation of visual activity in posterior areas when attention is being allocated.     

Human cortical networks for new and familiar sequences of saccades.

Visual exploration is organized in sequences of saccadic eye movements that depend on both perceptual and cognitive context. Using functional magnetic resonance imaging, we studied the neural basis of sequential oculomotor behavior and its dependence on different types of memory by analyzing cerebral activity during performance of newly learned and familiar sequences of eye movements. Compared to a resting condition, both types of sequences activated a common fronto-parietal network, including frontal and supplementary eye fields, and several parietal areas. Within this network, newly learned sequences induced stronger activation than familiar sequences, probably reflecting higher attentional demands. In addition, specific regions were recruited for the performance of new sequences, including pre-supplementary eye fields, the precuneus and the caudate nucleus. This indicates that in addition to attentional modulation, novelty of saccadic sequences requires specific cortical resources, probably related to effortful sequence preparation and coordination as well as to spatial working memory. For familiar sequences, recalled from long-term memory, we observed specific right medial temporo-occipital activation in the vicinity of the boundary between the parahippocampal and lingual gyri, as well as an activation site in the parieto-occipital fissure. We conclude that neuronal resources recruited by the gaze system can change with the familiarity of the scanpath to be executed. This study is important to better understand how the brain implements memorized scanpaths for visual exploration and orienting.     

Smooth-pursuit eye movement representation in the primate frontal eye field.

Physiological and behavioral data reported here show an involvement of the primate frontal eye field (FEF) cortex in smooth-pursuit eye movements, in addition to its well-established role in saccadic eye movements. Microstimulation just ventral to the small saccade representation of the FEF elicits eye movements that, in contrast to elicited saccades, have low velocities, continue smoothly without interruption during prolonged stimulation, and are usually directed ipsilaterally to the stimulated hemisphere. Neurons in this region respond in association with smooth-pursuit eye movements and visual motion. Tracking deficits following experimental lesions of the FEF depend critically upon the status of this ventral region: superficial lesions sparing it leave smooth-pursuit eye movements intact, whereas lesions removing it produce substantial deficits in the anticipatory initiation, motion-induced acceleration, asymptotic velocity, and predictive continuation of ipsilateral smooth pursuit.     

On the functional relevance of frontal cortex for passive and voluntarily controlled bistable vision

In bistable vision, one constant ambiguous stimulus leads to 2 alternating conscious percepts. This perceptual switching occurs spontaneously but can also be influenced through voluntary control. Neuroimaging studies have reported that frontal regions are activated during spontaneous perceptual switches, leading some researchers to suggest that frontal regions causally induce perceptual switches. But the opposite also seems possible: frontal activations may themselves be caused by spontaneous switches. Classically implicated in attentional processes, these same regions are also candidates for the origins of voluntary control over bistable vision. Here too, it remains unknown whether frontal cortex is actually functionally relevant. It is even possible that spontaneous perceptual switches and voluntarily induced switches are mediated by the same top-down mechanisms. To directly address these issues, we here induced "virtual lesions," with transcranial magnetic stimulation, in frontal, parietal, and 2 lower level visual cortices using an established ambiguous structure-from-motion stimulus. We found that dorsolateral prefrontal cortex was causally relevant for voluntary control over perceptual switches. In contrast, we failed to find any evidence for an active role of frontal cortex in passive bistable vision. Thus, it seems the same pathway used for willed top-down modulation of bistable vision is not used during passive bistable viewing.     

Right parietal cortex plays a critical role in change blindness

There is increasing evidence from functional magnetic resonance imaging (fMRI) that visual awareness is not only associated with activity in ventral visual cortex but also with activity in the parietal cortex. However, due to the correlational nature of neuroimaging, it remains unclear whether this parietal activity plays a causal role in awareness. In the experiment presented here we disrupted activity in right or left parietal cortex by applying repetitive transcranial magnetic stimulation (rTMS) over these areas while subjects attempted to detect changes between two images separated by a brief interval (i.e. 1-shot change detection task). We found that rTMS applied over right parietal cortex but not left parietal cortex resulted in longer latencies to detect changes and a greater rate of change blindness compared with no TMS. These results suggest that the right parietal cortex plays a critical role in conscious change detection.     

The perceptual and functional consequences of parietal top-down modulation on the visual cortex

The posterior parietal cortex (PPC) has been proposed to play a critical role in exerting top-down influences on occipital visual areas. By inducing activity in the PPC (angular gyrus) using transcranial magnetic stimulation (TMS), and using the phosphene threshold as a measure of visual cortical excitability, we investigated the functional role of this region in modulating the activity of the visual cortex. When triple-pulses of TMS were applied over the PPC unilaterally, the intensity of stimulation required to elicit a phosphene from the visual cortex (area V1/V2) was reduced, indicating an increase in visual cortical excitability. The increased excitability that was observed with unilateral TMS was abolished when TMS was applied over the PPC bilaterally. Our results provide a demonstration of the top-down modulation exerted by the PPC on the visual cortex and show that these effects are subject to interhemispheric competition.     

Contributions of the PPC to online control of visually guided reaching movements assessed with fMRI-guided TMS

The posterior parietal cortex (PPC) plays an important role in controlling voluntary movements by continuously integrating sensory information about body state and the environment. We tested which subregions of the PPC contribute to the processing of target- and body-related visual information while reaching for an object, using a reaching paradigm with 2 types of visual perturbation: displacement of the visual target and displacement of the visual feedback about the hand position. Initially, functional magnetic resonance imaging (fMRI) was used to localize putative target areas involved in online corrections of movements in response to perturbations. The causal contribution of these areas to online correction was tested in subsequent neuronavigated transcranial magnetic stimulation (TMS) experiments. Robust TMS effects occurred at distinct anatomical sites along the anterior intraparietal sulcus (aIPS) and the anterior part of the supramarginal gyrus for both perturbations. TMS over neighboring sites did not affect online control. Our results support the hypothesis that the aIPS is more generally involved in visually guided control of movements, independent of body effectors and nature of the visual information. Furthermore, they suggest that the human network of PPC subregions controlling goal-directed visuomotor processes extends more inferiorly than previously thought. Our results also point toward a good spatial specificity of the TMS effects.     

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.     

The role of rostral Brodmann area 6 in mental-operation tasks: an integrative neuroimaging approach

Recent evidence indicates that classical 'motor' areas may also have cognitive functions. We performed three neuroimaging experiments to investigate the functional neuroanatomy underlying three types of nonmotor mental-operation tasks: numerical, verbal, and spatial. (i) Positron emission tomography showed that parts of the posterior frontal cortex, which are consistent with the pre-supplementary motor area (pre-SMA) and the rostral part of the dorsolateral premotor cortex (PMdr), were active during all three tasks. We also observed activity in the posterior parietal cortex and cerebellar hemispheres during all three tasks. Electrophysiological monitoring confirmed that there were no skeletomotor, oculomotor or articulatory movements during task performance. (ii) Functional magnetic resonance imaging (fMRI) showed that PMdr activity during the mental-operation tasks was localized in the depths of the superior precentral sulcus, which substantially overlapped the region active during complex finger movements and was located dorsomedial to the presumptive frontal eye fields. (iii) Single-trial fMRI showed a transient increase in activity time-locked to the performance of mental operations in the pre-SMA and PMdr. The results of the present study suggest that the PMdr is important in the rule-based association of symbolic cues and responses in both motor and nonmotor behaviors.     

Keeping memory for intentions: a cTBS investigation of the frontopolar cortex

The present study aimed to investigate the role of frontopolar cortex in prospective memory (PM) by means of inhibitory theta-burst stimulation (cTBS). "Experiment 1"-8 volunteers were evaluated after inhibitory cTBS over left Brodmann area (BA) 10, right BA10, and Cz. In the PM procedure, sequences of 4 words each were presented. During the intersequence delay, subjects had to repeat the sequence in the observed order (ongoing task forward) or in the reverse order (backward). At the occurrence of a target word, subjects had to press a key on the keyboard (PM task). Recall and recognition of the target words were also tested. PM accuracy was lower after cTBS over left BA10 compared with Cz (P = 0.012), whereas it was comparable in right BA10 and Cz conditions. No other significant differences between the 3 conditions were found. "Experiment 2"-8 subjects were administered the same experimental PM procedure as above after inhibitory cTBS over left BA46 and Cz. In this case, none of the tested effects were significant. Our findings corroborate the hypothesis that within the prefrontal cortex, the left BA10 is specifically involved in the mediation of processes related to the execution of delayed intentions.