Human Frontal Eye Field Research Articles

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.

Role of human frontal and supplementary eye fields in double step saccades.

Transcranial magnetic stimulation (TMS) was applied over the frontal eye field (FEF) and the supplementary eye field (SEF) regions before execution of the first saccade in a double step task. When applied over the FEF, stimulation increased the percentage error in amplitude of the contralateral second saccade as compared to no stimulation. This was due to an interference with retinotopic but not craniotopic gain calculation. Stimulation of the SEF region interfered with saccade ordering. Thus, FEF might participate in target memorization whereas SEF is confirmed to code order information for sequential saccades even in this paradigm of only two consecutive movements.

Conjugate Eye Deviation With Head Version due to a Cortical Infarction of the Frontal Eye Field

To the Editor: Conjugate eye deviation (CED) occurs in approximately 20% of patients with cerebrovascular disease. CED is usually caused by a certain degree of hemispheric lesion subside aphasia, hemiparesis, or coma, which indicates poor prognosis.1,2⇓ The underlying mechanism of CED is thought to be a disturbance of the cortical center or subcortical pathways involved in the control of voluntary eye movements. However, the exact site of the human frontal eye field (FEF) is still controversial. In this letter we discuss the possible location of the FEF of human response to CED in a patient with localized cortical lesion. An 82-year-old woman was admitted to the hospital for acute-onset visual disturbances. She reported the sudden appearance of visual disturbance that she felt as difficulty of fixation to her left side. General examination showed arterial blood pressure of 170/100 mm Hg and pulse rate of 72 beats/min. Neurological examination showed the eyes were deviated to the right, but there was difficulty in turning the eyes and head to the left side, although both eyes responded to horizontal oculocephalic stimulation. In addition, the neck rotated to the right. Spontaneous …

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

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. 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. 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.

Event-related fMRI responses in the human frontal eye fields in a randomized pro- and antisaccade task

Event-related fMRI responses in the human frontal eye fields in a randomized pro- and antisaccade task

Involvement of the human frontal eye field and multiple parietal areas in covert visual selection during conjunction search.

Searching for a target object in a cluttered visual scene requires active visual attention if the target differs from distractors not by elementary visual features but rather by a feature conjunction. We used functional magnetic resonance imaging (fMRI) in human subjects to investigate the functional neuroanatomy of attentional mechanisms employed during conjunction search. In the experimental condition, subjects searched for a target defined by a conjunction of colour and orientation. In the baseline condition, subjects searched for a uniquely coloured target, regardless of its orientation. Eye movement recordings outside the scanner verified subjects' ability to maintain fixation during search. Reaction times indicated that the experimental condition was attentionally more demanding than the baseline condition. Differential activations between conditions were therefore ascribed to top-down modulation of neural activity. The frontal eye field, the ventral precentral sulcus and the following posterior parietal regions were consistently activated: (i) the postcentral sulcus; (ii) the posterior; and (iii) the anterior part of the intraparietal sulcus; and (iv) the junction of the intraparietal with the transverse occipital sulcus. Parietal regions were spatially distinct and displayed differential amplitudes of signal increase with a maximal amplitude in the posterior intraparietal sulcus. Less consistent activation was found in the lateral fusiform gyrus. These results suggest an involvement of the human frontal eye field in covert visual selection of potential targets during search. These results also provide evidence for a subdivision of posterior parietal cortex in multiple areas participating in covert visual selection, with a major contribution of the posterior intraparietal sulcus.

Location of the human frontal eye field as defined by electrical cortical stimulation

Electrical cortical stimulation of the human frontal gyri and the precentral gyrus has been shown to induce eye movements and it has classically been assumed that these stimulation-induced eye movements result from electrical interference with the human homologue of the monkey frontal eye field (FEF). However, amplitude of electrical current and induced type of eye movement, which are essential for the determination of eye fields in the monkey, have not been investigated systematically in man. We applied electrical cortical stimulation in the lateral frontal cortex in six epileptic patients. Sites whose stimulation resulted in eye movements were determined with respect to gyral and sulcal patterns, Talairach coordinates and neighboring functions as found by electrical cortical stimulation. Based on this approach, a restricted location of the electrically defined FEF is proposed within a larger oculomotor region on the posterior part of the middle frontal gyrus.

Muscimol-induced inactivation of monkey frontal eye field: effects on visually and memory-guided saccades.

Muscimol-induced inactivation of the monkey frontal eye field: effects on visually and memory-guided saccades. Although neurophysiological, anatomic, and imaging evidence suggest that the frontal eye field (FEF) participates in the generation of eye movements, chronic lesions of the FEF in both humans and monkeys appear to cause only minor deficits in visually guided saccade generation. Stronger effects are observed when subjects are tested in tasks with more cognitive requirements. We tested oculomotor function after acutely inactivating regions of the FEF to minimize the effects of plasticity and reallocation of function after the loss of the FEF and gain more insight into the FEF contribution to the guidance of eye movements in the intact brain. Inactivation was induced by microinjecting muscimol directly into physiologically defined sites in the FEF of three monkeys. FEF inactivation severely impaired the monkeys' performance of both visually guided and memory-guided saccades. The monkeys initiated fewer saccades to the retinotopic representation of the inactivated FEF site than to any other location in the visual field. The saccades that were initiated had longer latencies, slower velocities, and larger targeting errors than controls. These effects were present both for visually guided and for memory-guided saccades, although the memory-guided saccades were more disrupted. Initially, the effects were restricted spatially, concentrating around the retinotopic representation at the center of the inactivated site, but, during the course of several hours, these effects spread to flanking representations. Predictability of target location and motivation of the monkey also affected saccadic performance. For memory-guided saccades, increases in the time during which the monkey had to remember the spatial location of a target resulted in further decreases in the accuracy of the saccades and in smaller peak velocities, suggesting a progressive loss of the capacity to maintain a representation of target location in relation to the fovea after FEF inactivation. In addition, the monkeys frequently made premature saccades to targets in the hemifield ipsilateral to the injection site when performing the memory task, indicating a deficit in the control of fixation that could be a consequence of an imbalance between ipsilateral and contralateral FEF activity after the injection. There was also a progressive loss of fixation accuracy, and the monkeys tended to restrict spontaneous visual scanning to the ipsilateral hemifield. These results emphasize the strong role of the FEF in the intact monkey in the generation of all voluntary saccadic eye movements, as well as in the control of fixation.

Visual activity in the human frontal eye field.

Although visual information processing in the monkey frontal eye field (FEF) has been well demonstrated, the contribution of its human homologue to vision is still unknown. Here we report a study of intracranial visual evoked potentials (VEPs) recorded from the human FEF which was identified by electrical cortical stimulation. Electrical stimulations and EEG recordings were carried out via subdural grid electrodes placed over the frontal cortex in three epileptic patients. Evoked eye movements were mainly horizontal and always directed to the hemispace contralateral to the stimulation site. Intracranial VEPs showed responses predominately to stimuli in the contralateral visual field. Our findings demonstrate a close relationship between the direction of the electrically elicited eye movements and the visual stimulus location which predominantly leads to neural responses in the FEF. These findings provide evidence for the functional role of the human FEF in the analysis of visual stimuli from the contralateral visual field as well as in the generation of eye movements towards these conspicuous targets.

Localization of the human frontal eye fields and motor hand area with transcranial magnetic stimulation and magnetic resonance imaging

We localized the neuroanatomical correlates for control of saccadic eye movements and for finger movements using a combined transcranial magnetic stimulation (TMS) and magnetic resonance imaging (MRI) approach. Two participants underwent TMS while performing an endogenous saccade task. The motor hand area was localized by TMS and the region anterior to it was mapped to identify the borders of a region where TMS produced delays in generating contralateral saccades. MRI scans were then obtained with fiducial markers placed over the motor hand area and 2 cm anterior to it, the common cortical region that produced saccadic delays in these two subjects. It was also shown that the structural anatomy of the hand area, physiologically defined by visible contractions of the contralateral hand following TMS, corresponded to the knob-like structure recently reported [18, 19]. These results demonstrate that TMS can be a precise, non-invasive tool for neuroanatomical mapping of cortical structures when combined with structural images of the brain.

Activation of the human right frontal eye field by unexpected visual input

Activation of the human right frontal eye field by unexpected visual input

Transcranial Magnetic Stimulation of the Prefrontal Cortex Delays Contralateral Endogenous Saccades

The contributions of the superior prefrontal cortex (SPFC) and the superior parietal lobule (SPL) in generating voluntary endogenous and reflexive visually guided saccades were investigated using transcranial magnetic stimulation (TMS). Subjects made choice saccades to the left or right visual field in response to a central arrowhead (endogenous go signal) or a peripheral asterisk (exogenous go signal) that were presented along with a single TMS pulse at varying temporal intervals. TMS over the SPFC increased latencies for saccades made in response to an endogenous go signal toward the contralateral hemifield. No effects were observed when the go signal was exogenous and TMS was over the SPFC or when TMS was over the SPL for either saccade type. The delayed contralateral endogenous saccades observed in this study are likely a consequence of disruption in the normal operations of the human frontal eye field.

Dissociation of saccade-related and pursuit-related activation in human frontal eye fields as revealed by fMRI.

The location of the human frontal eye fields (FEFs) underlying horizontal visually guided saccadic and pursuit eye movements was investigated with the use of functional magnetic resonance imaging in five healthy humans. Execution of both saccadic and pursuit eye movements induced bilateral FEF activation located medially at the junction of the precentral sulcus and the superior frontal sulcus and extending laterally to the precentral gyrus. These findings extend previous functional imaging studies by providing the first functional imaging evidence of a specific activation in the FEF during smooth pursuit eye movements in healthy humans. FEF activation during smooth pursuit performance was smaller than during saccades. This finding, which may reflect the presence of a smaller pursuit-related region area in human FEF than the saccade-related region, is consistent with their relative size observed in the monkey. The mean location of the pursuit-related FEF was more inferior and lateral than the location of the saccade-related FEF. These results provide the first evidence that there are different subregions in the human FEF that are involved in the execution of two different types of eye movements, namely saccadic and pursuit eye movements. Moreover, this study provides additional evidence that the human FEF is located in Brodmann's area 6, unlike the monkey FEF which is located in the posterior part of Brodmann's area 8.

Rapid-rate transcranial magnetic stimulation of human frontal cortex can evoke saccades under facilitating conditions

Rapid-rate transcranial magnetic stimulation (rTMS) of a localized area within premotor frontal cortex elicited short-latency, multistep eye movements during a double-step saccade task in 3 of 9 subjects. These evoked saccades occurred in 14–32% of trials when rTMS was delivered over premotor regions located 5–7 cm lateral and 2–4 cm anterior to the vertex. In trials without rTMS or when rTMS was delivered medial or posterior to these sites, multistep saccades occurred in less than 2% of trials. In two subjects, rTMS of the right premotor cortex evoked contraversive saccades. In a third subject, rTMS of the left premotor cortex evoked saccades whose trajectory depended on the direction of the double-step targets. The amplitude and likelihood of occurrence of evoked saccades varied between rTMS trials. The intervals between evoked saccades were proportional to the intervals between rTMS pulses delivered at 16, 20 or 25 Hz. rTMS did not elicit saccades during fixation on a stationary target or during straight-ahead gaze in darkness, suggesting that the double-step saccade task facilitated the activation of a discrete premotor area consistent with the human frontal eye fields.

Transcranial magnetic stimulation of the human frontal eye field

The region of cortex over which transcranial magnetic stimulation (TMS) can delay saccadic eye movement was investigated. With TMS delivered in the reaction time foreperiod of auditory-triggered saccades, saccade onset could be delayed by up to 60 ms. The area of cortex over which TMS could delay saccade onset was located near the inter-aural line, approximately 6 cm lateral to the vertex, and was situated between areas over which TMS could generate motor evoked potentials in muscles of the hand and face. It is concluded that this area corresponds to the human frontal eye field and is closely associated with the motor strip, at a level between the representations of the hand and the face, and that stimulation of this region can interfere with the programming and execution of externally triggered saccades.

Endogenously Generated and Visually Guided Saccades after Lesions of the Human Frontal Eye Fields

Abstract Nine patients with chronic, unilateral lesions of the dorso-lateral prefrontal cortex including the frontal eye fields (FEF) made saccades toward contralesional and ipsilesional fields. The saccades were either voluntarily directed in response to arrows in the center of a visual display, or were reflexively summoned by a peripheral visual signal. Saccade latencies were compared to those made by seven neurologic control patients with chronic, unilateral lesions of dorsolateral prefrontal cortex sparing the FEF, and by 13 normal control subjects. In both the normal and neurologic control subjects, reflexive saccades had shorter Latencies than voluntary saccades. In the FEF lesion patients, voluntary saccades had longer latencies toward the contralesional field than toward the ipsilesional field. The opposite pattern was found for reflexive saccades: latencies of saccades to targets in the contralesional field were shorter than saccades summoned to ipsilesional targets. Reflexive saccades toward the ipsilesional field had abnormally prolonged latencies; they were comparable to the latencies observed for voluntary Saccades. The effect of FEF lesions on saccacles contrasted with those observed in a second experiment requiring a key press response: FEF lesion patients were slower in making key press responses to signals detected in the contralesional field. To assess covert attention and preparatory set the effects of precues providing advance information were measured in both saccade and key press experiments. Neither patient group showed any deficiency in using precues to shift attention or to prepare saccades. The FEF facilitates the generation of voluntary saccatles and also inhibits reflexive saccades to exogenous signals. FEF lesions may disinhibit the ipsilesional midbrain which in turn may inhibit the opposite colliculus to slow reflexive saccades toward the ipsilesional field.

Transcranial stimulation of the human frontal eye field by magnetic pulses

Single transcranial magnetic pulsed stimuli were applied over the cortical area of the putative right frontal eye field (FEF) in 11 healthy subjects. An especially designed figure of eight shaped twin coil was used, to focus the stimulus, the strength of which was adjusted to the individual motor threshold of the left hand muscles. Eye positions and movements were recorded by an infrared reflection technique. Three different experiments were performed: 1. Stimulation during different primary gaze position did not evoke any discernible eye movement. 2. Stimulation just prior to visually elicited horizontal saccades did not cause a significant alteration of the latency, velocity, or amplitude of the saccades. 3. Only stimulation during an antisaccade task induced a significant latency prolongation, when the stimulus was applied between 50 to 90 ms after the target flashed up. This latency prolongation was found in all subjects for the antisaccades to the right, with a statistically significant average latency difference of +66 +/- 55.5 ms. In contrast, the antisaccades to the left were prolonged in the female subjects only by an average of +98 +/- 41.8 ms (p = 0.0064), whereas in the male subjects they did not alter with stimulation (average difference: -3 +/- 41.9 ms, p = 0.753). Significant latency prolongations were only obtained when the magnetic FEF stimuli were applied within a vulnerable period, which varied from subject to subject.

Cortical activation pattern during saccadic eye movements in humans: Localization by focal cerebral blood flow increases

Regional cerebral blood flow (rCBF) was measured in human subjects during saccadic eye movements by a 254-channel dynamic gamma camera. Focal rCBF increases were repeatedly observed in an area within the middle precentral and premotor regions which corresponds to the frontal eye field in humans. Our findings suggest that this region is localized between the "face" and "hand" areas in the precentral gyrus and extends anteriorly out of the primary motor strip into the adjacent premotor zone. In addition, saccades were associated with focal blood flow increases in regions corresponding to the frontal supplementary motor area and to the posterior temporooccipital visual association cortex. Similar changes in patterns of rCBF occurred during contralateral and ipsilateral horizontal saccades and also during vertical saccades, and did not differ between the right and left hemispheres. Focal rCBF increases were observed in the frontal eye field during several additional test procedures including ocular fixation and visual perception of a nonmoving target, auditory stimulation with closed eyes, and reading. It is presumed that these focal flow increases reflect increased localized neuronal activity and metabolic rate and therefore permit visualization of the cortical activation pattern associated with saccadic eye movements in humans.

Observations on stimulation of the human frontal eye field.

Observations on stimulation of the human frontal eye field.