Competition in working memory reduces frontal guidance of visual selection

Working memory (WM) representations can bias visual selection to matching stimuli in the field. WM biases can, however, be modulated by the level of cognitive load, with WM guidance reduced as memory load increases. Here, we used functional magnetic resonance imaging to distinguish between competing hypotheses for the reduction of WM guidance under load: 1) poor neural representations of memory contents under high load, 2) strategic control at high loads to direct attention away from search distracters matching the WM content, and 3) reduction of frontal top-down biasing of visual areas with increasing memory loads. We show that matching between WM contents and the visual display appeared to be well represented in visual areas under high memory loads, despite a lack of WM guidance at the behavioral level. There was little engagement of "cognitive control" areas in the prefrontal cortex during search at high loads. More importantly, WM guidance at low loads engaged a set of frontal regions in the superior and inferior ventral frontal cortex. Functional connectivity analyses revealed frontal regions working in concert with occipital areas at low memory loads, but this coupling was disrupted by increased memory load. We discuss the implications for understanding the mechanisms supporting the interplay between WM and attention.     

Neuronal activity in the caudal frontal eye fields of monkeys during memory-based smooth pursuit eye movements: comparison with the supplementary eye fields

Recently, we examined the neuronal substrate of predictive pursuit during memory-based smooth pursuit and found that supplementary eye fields (SEFs) contain signals coding assessment and memory of visual motion direction, decision not-to-pursue ("no-go"), and preparation for pursuit. To determine whether these signals were unique to the SEF, we examined the discharge of 185 task-related neurons in the caudal frontal eye fields (FEFs) in 2 macaques. Visual motion memory and no-go signals were also present in the caudal FEF but compared with those in the SEF, the percentage of neurons coding these signals was significantly lower. In particular, unlike SEF neurons, directional visual motion responses of caudal FEF neurons decayed exponentially. In contrast, the percentage of neurons coding directional pursuit eye movements was significantly higher in the caudal FEF than in the SEF. Unlike SEF inactivation, muscimol injection into the caudal FEF did not induce direction errors or no-go errors but decreased eye velocity during pursuit causing an inability to compensate for the response delays during sinusoidal pursuit. These results indicate significant differences between the 2 regions in the signals represented and in the effects of chemical inactivation suggesting that the caudal FEF is primarily involved in generating motor commands for smooth-pursuit eye movements.     

TMS evidence for smooth pursuit gain control by the frontal eye fields

Smooth pursuit eye movements are used to continuously track slowly moving visual objects. A peculiar property of the smooth pursuit system is the nonlinear increase in sensitivity to changes in target motion with increasing pursuit velocities. We investigated the role of the frontal eye fields (FEFs) in this dynamic gain control mechanism by application of transcranial magnetic stimulation. Subjects were required to pursue a slowly moving visual target whose motion consisted of 2 components: a constant velocity component at 4 different velocities (0, 8, 16, and 24 deg/s) and a superimposed high-frequency sinusoidal oscillation (4 Hz, +/-8 deg/s). Magnetic stimulation of the FEFs reduced not only the overall gain of the system, but also the efficacy of the dynamic gain control. We thus provide the first direct evidence that the FEF population is significantly involved in the nonlinear computation necessary for continuously adjusting the feedforward gain of the pursuit system. We discuss this with relation to current models of smooth pursuit.     

Localization of human frontal eye fields: anatomical and functional findings of functional magnetic resonance imaging and intracerebral electrical stimulation.

OBJECT: The goal of this study was to investigate the anatomical localization and functional role of human frontal eye fields (FEFs) by comparing findings from two independently conducted studies. METHODS: In the first study, 3-tesla functional magnetic resonance (fMR) imaging was performed in 14 healthy volunteers divided into two groups: the first group executed self-paced voluntary saccades in complete darkness and the second group repeated newly learned or familiar sequences of saccades. In the second study, intracerebral electrical stimulation (IES) was performed in 38 patients with epilepsy prior to surgery, and frontal regions where stimulation induced versive eye movements were identified. These studies showed that two distinct oculomotor areas (OMAs) could be individualized in the region classically corresponding to the FEFs. One OMA was consistently located at the intersection of the superior frontal sulcus with the fundus of the superior portion of the precentral sulcus, and was the OMA in which saccadic eye movements could be the most easily elicited by electrical stimulation. The second OMA was located more laterally, close to the surface of the precentral gyrus. The fMR imaging study and the IES study demonstrated anatomical and stereotactic agreement in the identification of these cortical areas. CONCLUSIONS: These findings indicate that infracentimetric localization of cortical areas can be achieved by measuring the vascular signal with the aid of 3-tesla fMR imaging and that neuroimaging and electrophysiological recording can be used together to obtain a better understanding of the human cortical functional anatomy.     

Modulation of visual responses in macaque frontal eye field during covert tracking of invisible targets

The purpose of this study was to investigate the interaction between internal representations of invisible moving targets and visual responses of neurons in frontal eye fields (FEFs). Monkeys were trained to make saccades to the extrapolated position of a target that was temporarily rendered invisible for variable durations as if it had passed behind an occluder. Flashed, task-irrelevant visual probe stimuli were used to study the visual responsiveness of FEF neurons during this task. Probes were flashed at various times and locations during the occlusion interval. Net changes in neuronal activity were obtained by comparing the activity on trials with probes with randomly interleaved trials without any probe. Most neurons showed an increase in firing rate in response to the probe, but some showed a decrease. Both types of responses were enhanced when the invisible target moved toward the receptive field (RF) as compared with trials on which the target moved away from the RF. Some neurons showed a spatial shift in the visual response during the occlusion interval. For cells that were excited by the probe, the shift tended to be correlated with the direction of motion of the target, whereas for cells that were inhibited the shift tended to be in the opposite direction. These results suggest that the role of FEF in predicting invisible target motion includes a sensory/perceptual component.     

Pursuit and saccadic eye movement subregions in human frontal eye field: a high-resolution fMRI investigation.

Recent positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) studies in humans have localized the frontal eye field (FEF) to the precentral sulcus (PCS). In macaque monkeys, low-threshold microstimulation and single unit recording studies have located a saccadic subregion of FEF in a restricted area along the anterior wall of the arcuate sulcus and a pursuit subregion located deeper in the sulcus close to the fundus. The functional organization and anatomical location of these two FEF subregions are still to be defined in humans. In the present study, we used fMRI with high spatial resolution image acquisition at 3.0 Tesla to map the saccade- and pursuit-related areas of FEF within the two walls of the PCS in 11 subjects. We localized the saccade-related area to the upper portion of the anterior wall of the precentral sulcus and the pursuit-related area to a deeper region along the anterior wall, extending in some subjects to the fundus or deep posterior wall. These findings localize distinct pursuit and saccadic subregions of FEF in humans and demonstrate a high degree of homology in the organization of these FEF subregions in the human and the macaque monkey.     

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.     

Receptive fields in human visual cortex mapped with surface electrodes

Most of our understanding of the functional organization of human visual cortex comes from lesion and functional imaging studies and by extrapolation from results obtained by neuroanatomical and neurophysiological studies in nonhuman primates. Although some single-unit and field potential recordings have been made in human visual cortex, none has provided quantitative characterization of spatial receptive fields (RFs) of individual sites. Here we use subdural electrodes implanted for clinical purposes to quantitatively measure response properties in different regions of human visual cortex. We find significant differences in RF size, response latency, and response magnitude for sites in early visual areas, versus sites in later stages of both the dorsal and ventral streams. In addition, we use this technique to estimate the cortical magnification factor in early human visual cortex. The spatial and temporal resolution of cortical surface recordings suggest that this technique is well suited to examine further issues in visual processing in humans.     

Theta-burst stimulation over human frontal cortex distorts perceptual stability across eye movements

We perceive a stable outside world despite the constant changes of visual input induced by our eye movements. Internal monitoring of a corollary discharge associated with oculomotor commands may help to anticipate the perceptual consequences of impending eye movements. The primate frontal eye fields have repeatedly been presumed to participate in the maintenance of perceptual stability across eye movements. However, a direct link between integrity of frontal oculomotor areas and perceptual stability is missing so far. Here, we show that transcranial magnetic stimulation (TMS) over the right human frontal cortex impairs the integration of visual space across eye movements. We asked 9 healthy subjects to report the direction of transsaccadic stimulus displacements and applied TMS before the actual experiment in a novel offline stimulation protocol, continuous theta-burst stimulation (cTBS). A systematic perceptual distortion was observed after stimulation over the right frontal cortex that was best explained by an internal underestimation of executed eye movement amplitudes. cTBS apparently disturbed an internal prediction process for contraversive saccades, while the metrics of associated oculomotor actions remained unchanged. Our findings suggest an important role of the frontal cortex in the internal monitoring of oculomotor actions for the perceptual integration of space across eye movements.     

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.     

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.     

Eye-pursuit and reafferent head movement signals carried by pursuit neurons in the caudal part of the frontal eye fields during head-free pursuit

Eye and head movements are coordinated during head-free pursuit. To examine whether pursuit neurons in frontal eye fields (FEF) carry gaze-pursuit commands that drive both eye-pursuit and head-pursuit, monkeys whose heads were free to rotate about a vertical axis were trained to pursue a juice feeder with their head and a target with their eyes. Initially the feeder and target moved synchronously with the same visual angle. FEF neurons responding to this gaze-pursuit were tested for eye-pursuit of target motion while the feeder was stationary and for head-pursuit while the target was stationary. The majority of pursuit neurons exhibited modulation during head-pursuit, but their preferred directions during eye-pursuit and head-pursuit were different. Although peak modulation occurred during head movements, the onset of discharge usually was not aligned with the head movement onset. The minority of neurons whose discharge onset was so aligned discharged after the head movement onset. These results do not support the idea that the head-pursuit-related modulation reflects head-pursuit commands. Furthermore, modulation similar to that during head-pursuit was obtained by passive head rotation on stationary trunk. Our results suggest that FEF pursuit neurons issue gaze or eye movement commands during gaze-pursuit and that the head-pursuit-related modulation primarily reflects reafferent signals resulting from head movements.     

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.     

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.     

An anatomical landmark for the supplementary eye fields in human revealed with functional magnetic resonance imaging.

Together with the frontal and parietal eye fields, the supplementary eye field (SEF) is involved in the performance and control of voluntary and reflexive saccades and of ocular pursuit. This region was first described in non-human primates and is rather well localized on the dorsal surface of the medial frontal cortex. In humans the site of the SEF is still ill-defined. Functional imaging techniques have allowed investigation of the location and function of the SEF. However, there is great variability with regard to the published standardized coordinates of this area. We used here the spatial precision of functional magnetic resonance imaging (fMRI) in order to better localize the SEF in individuals. We identified as the SEF a region on the medial wall that was significantly activated when subjects executed self-paced horizontal saccades in darkness as compared to rest. This region appeared to be predominantly activated in the left hemisphere. We found that, despite a discrepancy of >2 cm found in the standardized Talairach coordinates, the location of this SEF-region could be precisely and reliably described by referring to a sulcal landmark found in each individual: the upper part of the paracentral sulcus.     

Polypropylene in the human eye

Scanning electron microscopy of 10-0 polypropylene sutures removed from eyes at intervals from 2 months to 5.5 years shows a very slow surface degradation with linear and circumferential surface cracks, and flaking. The clinical significance of these findings in intraocular sutures is speculative, but the changes are much more pronounced, and of obvious significance, in sutures that have been buried in actively metabolizing tissue such as the limbus.     

The functional and temporal characteristics of top-down modulation in visual selection

Perceptual load of an attended task influences the processing of irrelevant background stimuli. In a series of behavioral, functional magnetic resonance (fMRI) and electroencephalography (EEG) experiments we examined the influence of working memory (WM) load related to a relevant visual stimulus on the processing of irrelevant backgrounds. We further addressed two open questions about the mechanism of load-dependent modulation: (i) is this modulation dependent on regional activity (i.e. phasic)? (ii) At what processing stage does this modulation take place? Load was manipulated by a WM task and concurrently the processing of irrelevant visual objects was assessed with fMRI and EEG. To examine the dependency of this modulation on intrinsic activity, we varied the activity level of visual areas by presenting objects with different levels of degradation. Activity in the lateral occipital complex (LOC) increased with object visibility and was phasically modulated by WM load. Event related potentials revealed that this phasic modulation occurred approximately 170 ms after stimulus onset, indicative of an early selection under high load. The results indicate a phasic modulatory effect of WM load on visual object processing in the LOC that is comparable to the effects found for perceptual load manipulations.     

Similar frontal and distinct posterior cortical regions mediate visual and auditory perceptual awareness

Activity in ventral visual cortex is a consistent neural correlate of visual consciousness. However, activity in this area seems insufficient to produce awareness without additional involvement of frontoparietal regions. To test the generality of the frontoparietal response, neural correlates of auditory awareness were investigated in a paradigm that previously has revealed frontoparietal activity during conscious visual perception. A within-experiment comparison showed that frontal regions were related to both visual and auditory awareness, whereas parietal activity was correlated with visual awareness and superior temporal activity with auditory awareness. These results indicate that frontal regions interact with specific posterior regions to produce awareness in different sensory modalities.