Smooth pursuit-related information processing in frontal eye field neurons that project to the NRTP

The cortical pursuit system begins the process of transforming visual signals into commands for smooth pursuit (SP) eye movements. The frontal eye field (FEF), located in the fundus of arcuate sulcus, is known to play a role in SP and gaze pursuit movements. This role is supported, at least in part, by FEF projections to the rostral nucleus reticularis tegmenti pontis (rNRTP), which in turn projects heavily to the cerebellar vermis. However, the functional characteristics of SP-related FEF neurons that project to rNRTP have never been described. Therefore, we used microelectrical stimulation (ES) to deliver single pulses (50-200 microA, 200-micros duration) in rNRTP to antidromically activate FEF neurons. We estimated the eye or retinal error motion sensitivity (position, velocity, and acceleration) of FEF neurons during SP using multiple linear regression modeling. FEF neurons that projected to rNRTP were most sensitive to eye acceleration. In contrast, FEF neurons not activated following ES of rNRTP were often most sensitive to eye velocity. In similar modeling studies, we found that rNRTP neurons were also biased toward eye acceleration. Therefore, our results suggest that neurons in the FEF-rNRTP pathway carry signals that could play a primary role in initiation of SP.     

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.     

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.     

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.     

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.     

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.     

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.     

Brain and behavior: a task-dependent eye movement study

Recent electrophysiological and behavioral studies have found similarities in the neurology of pursuit and saccadic eye movements. In a previous study on eye movements using closely matched paradigms for pursuit and saccades, we revealed that both exhibit bimodal distributions of latency to predictable (PRD) and randomized (RND) stimuli; however, the latency to each type of stimulus was different, and there was more segregation of latencies in saccades than pursuit (Burke MR, Barnes GR. 2006. Quantitative differences in smooth pursuit and saccadic eye movements in humans. Exp Brain Res. 175(4):596-608). To investigate the brain areas involved in these tasks, and to search for correlates of behavior, we used functional magnetic resonance imaging during equivalent PRD and RND target presentations. In the contrast pursuit > saccades, which reflects velocity-dependent versus position-dependent activities, respectively, we found higher activation in the dorsolateral prefrontal cortex (DLPFC) for pursuit and in the frontopolar region for saccades. In the contrast RND > PRD, which principally reflects activation related to visually driven versus memory-driven responses, respectively, we found a higher sustained level of activation in the frontal eye fields during visually guided eye movements. The reverse contrast revealed higher activity for the memory-guided responses in the supplementary eye fields and the superior parietal lobe. In addition, we found learning-related activation during the PRD condition in visual area V5, the DLPFC, and the cerebellum.     

Convergence insufficiency in brain-injured patients

Disorders of eye movements are relatively common in brain-injured patients. Some of these disturbances are caused by direct trauma to the orbital content, cranial nerves and other brain areas. Convergence, which is a part of the near-vision complex and depends on the integrative function of the cortical and subcortical areas, is commonly affected by traumatic brain injury. Intact vergence needs the integrative function of brain structures associated with acquisition of information on one side and intact mesencephalic function, including function of a vergence integrator, and their interconnections. Clinical investigation of vergence function in 26 traumatically brain-injured patients examined as early as possible after trauma revealed disturbances in over a third of the examinees. A follow-up of 72 patients some 3 years after injury revealed vergence insufficiency in 42%. Convergence insufficiency was associated with longer periods of coma (p less than 0.001), presence of cognitive disturbances (p less than 0.005) and patients' failing to find work in the open market (p less than 0.01). It is suggested that the presence of disturbed vergence several years after trauma, and its close association with prolonged coma and cognitive disturbances, is an expression of permanent damage to mesencephalic and cortical brain structures and can serve as an important aid in evaluation of these patients. This paper describes the close relationship between vergence state and over-all rehabilitation outcome as evaluated by patients' occupational status.     

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.     

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.     

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.     

Area MST and heading perception in macaque monkeys

The macaque medial superior temporal area (MST) is proposed to be specialized for analyzing complex 'optic flow' information. Such space-varying motion patterns provide a rich source of information about self motion, scene structure and object shape. We report the performance of rhesus macaques on a two-alternative 'heading' task, in which they reported whether horizontally varying, simulated trajectories were to left or right of center. Monkeys were sensitive to small heading angles; thresholds averaged 1.5-3 degrees. Heading estimates were stable in the face of changing stimulus location and smooth pursuit eye movements. In addition, we tested the role of area MST in heading judgements by electrically activating columns of neurons in this area while the monkeys performed the heading task. Activation of MST frequently affected performance, usually causing choice biases. These induced biases were often large and usually concordant with the preference of the neurons being activated. In addition, the induced biases were often larger in the presence of smooth pursuit eye movements. These results favor the hypothesis that MST is involved in recovering self-motion direction from optic flow cues and in the process by which heading perception is compensated for ongoing eye movements.     

Visual motion responses in the posterior cingulate sulcus: a comparison to V5/MT and MST

Motion processing regions apart from V5+/MT+ are still relatively poorly understood. Here, we used functional magnetic resonance imaging to perform a detailed functional analysis of the recently described cingulate sulcus visual area (CSv) in the dorsal posterior cingulate cortex. We used distinct types of visual motion stimuli to compare CSv with V5/MT and MST, including a visual pursuit paradigm. Both V5/MT and MST preferred 3D flow over 2D planar motion, responded less yet substantially to random motion, had a strong preference for contralateral versus ipsilateral stimulation, and responded nearly equally to contralateral and to full-field stimuli. In contrast, CSv had a pronounced preference to 2D planar motion over 3D flow, did not respond to random motion, had a weak and nonsignificant lateralization that was significantly smaller than that of MST, and strongly preferred full-field over contralateral stimuli. In addition, CSv had a better capability to integrate eye movements with retinal motion compared with V5/MT and MST. CSv thus differs from V5+/MT+ by its unique preference to full-field, coherent, and planar motion cues. These results place CSv in a good position to process visual cues related to self-induced motion, in particular those associated to eye or lateral head movements.     

An autopsy case of multicentric glioma of multiple histopathology

An autopsy case is described of an 66-year-old man with multicentric glioma of multiple histopathology, i.e. protoplasmic astrocytoma and glioblastoma. Enhanced CT scan revealed three separate lesions in the right cerebral hemisphere, pons, and cerebellar vermis. Initial diagnosis by CT included metastatic and primary brain tumor, multiple abscess, fungal infection, parasites, tuberculoma, and so on. Biopsy of the right frontal mass revealed astrocytoma grade-2. An autopsy revealed gelatinous, clear marginal mass in the right frontal, parietooccipital and cerebellar vermis; an opaque marginal mass with necrosis in dorsal pons was found. At microscopic examination, the right frontal tumor exhibited continuity with both the paraventricular and the right parietooccipital tumor. The right cerebral hemisphere and cerebellar vermis tumors showed protoplasmic astrocytoma; the dorsal pons tumor showed glioblastoma. CSF examination revealed no tumor cells. Tumor invasion of the internal capsule and the meninges was also not found. Accordingly, we diagnosed as multicentric astrocytoma of multiple histopathology. Only 11 case reports of multicentric glioma were recorded in Japan; only one of which was of multiple histopathology. Worldwide, only 7 case reports of multicentric glioma of multiple histopathology were recorded; this is the first case of protoplasmic astrocytoma and glioblastoma. Seen in terms of pathogenesis of multicentric glioma, this case is thought to be very interesting.     

Enhancement of eye motor response and electrical brain activity during noise and vibration in rabbits

The relationship between electroencephalogram (EEG) and eye movements was studied in rabbits during optokinetic, vestibular, and optovestibular tests. EEG was recorded through permanently implanted electrodes. Exposure to noise and vibration increased the frequency and the velocity of optokinetic nystagmus (OKN). The increase was greater during vibration but greatest during combined noise and vibration. EEG activity was closely linked to changes in OKN and was particularly evident with the appearance of theta waves in the dorsal hippocampus. Also, rotation of the rabbit produced considerable activation in the EEG.     

Cortical mechanisms for shifting and holding visuospatial attention

Access to visual awareness is often determined by covert, voluntary deployments of visual attention. Voluntary orienting without eye movements requires decoupling attention from the locus of fixation, a shift to the desired location, and maintenance of attention at that location. We used event-related functional magnetic resonance imaging to dissociate these components while observers shifted attention among 3 streams of letters and digits, one located at fixation and 2 in the periphery. Compared with holding attention at the current location, shifting attention between the peripheral locations was associated with transient increases in neural activity in the superior parietal lobule (SPL) and frontal eye fields (FEF), as in previous studies. The supplementary eye fields and separate portions of SPL and FEF were more active for decoupling attention from fixation than for shifting attention to a new location. Large segments of precentral sulcus (PreCS) and posterior parietal cortex (PPC) were more active when attention was maintained in the periphery than when it was maintained at fixation. We conclude that distinct subcomponents of the dorsal frontoparietal network initiate redeployments of covert attention to new locations and disengage attention from fixation, while sustained activity in lateral regions of PPC and PreCS represents sustained states of peripheral attention.     

A neural model of motion processing and visual navigation by cortical area MST

Cells in the dorsal medial superior temporal cortex (MSTd) process optic flow generated by self-motion during visually guided navigation. A neural model shows how interactions between well-known neural mechanisms (log polar cortical magnification, Gaussian motion-sensitive receptive fields, spatial pooling of motion-sensitive signals and subtractive extraretinal eye movement signals) lead to emergent properties that quantitatively simulate neurophysiological data about MSTd cell properties and psychophysical data about human navigation. Model cells match MSTd neuron responses to optic flow stimuli placed in different parts of the visual field, including position invariance, tuning curves, preferred spiral directions, direction reversals, average response curves and preferred locations for stimulus motion centers. The model shows how the preferred motion direction of the most active MSTd cells can explain human judgments of self-motion direction (heading), without using complex heading templates. The model explains when extraretinal eye movement signals are needed for accurate heading perception, and when retinal input is sufficient, and how heading judgments depend on scene layouts and rotation rates.     

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.