A mathematical model of saccadic reaction time as a function of the fixation point brightness gain.

The gap effect refers to a reduction in saccadic reaction time (SRT) to an eccentric target, when the fixation point is removed before the target onset. Though it is known that the gap effect peaks when the fixation point is offset about 200 ms before the onset of the eccentric target, it is unknown how this effect is modulated by stimulus variations. In this paper, we propose and investigate a model of saccadic reaction time as a function of the fixation point brightness gain. The brightness gain is defined as the ratio of the final and initial intensities of the stimulus. We have conducted a typical gap effect experiment with 15 participants, where the brightness of the fixation point was manipulated under four conditions and two gap intervals, at the same time and 200 ms before the onset of the eccentric target. The conditions included removing the fixation point (offset), leaving it with constant brightness (overlap), reducing, and increasing its brightness (lower and higher brightness conditions). Experimental data showed a significant gap effect in the offset and lower brightness conditions when compared to the overlap condition. On the other hand, the SRT was significantly longer for the higher brightness condition than the SRT for the overlap condition. Linear regression analysis using ten values of brightness gain shows that our model fits the data well for the 0- and 200-ms gap, with a coefficient of determination of .89 and .94, respectively.

Low-intensity focused ultrasound modulates monkey visuomotor behavior.

In vivo feasibility of using low-intensity focused ultrasound (FUS) to transiently modulate the function of regional brain tissue has been recently tested in anesthetized lagomorphs [1] and rodents [2-4]. Hypothetically, ultrasonic stimulation of the brain possesses several advantages [5]: it does not necessitate surgery or genetic alteration but could ultimately confer spatial resolutions superior to other noninvasive methods. Here, we gauged the ability of noninvasive FUS to causally modulate high-level cognitive behavior. Therefore, we examined how FUS might interfere with prefrontal activity in two awake macaque rhesus monkeys that had been trained to perform an antisaccade (AS) task. We show that ultrasound significantly modulated AS latencies. Such effects proved to be dependent on FUS hemifield of stimulation (relative latency increases most for ipsilateral AS). These results are interpreted in terms of a modulation of saccade inhibition to the contralateral visual field due to the disruption of processing across the frontal eye fields. Our study demonstrates for the first time the feasibility of using FUS stimulation to causally modulate behavior in the awake nonhuman primate brain. This result supports the use of this approach to study brain function. Neurostimulation with ultrasound could be used for exploratory and therapeutic purposes noninvasively, with potentially unprecedented spatial resolution.

Disruption of saccadic adaptation with repetitive transcranial magnetic stimulation of the posterior cerebellum in humans.

Saccadic eye movements are driven by motor commands that are continuously modified so that errors created by eye muscle fatigue, injury, or-in humans-wearing spectacles can be corrected. It is possible to rapidly adapt saccades in the laboratory by introducing a discrepancy between the intended and actual saccadic target. Neurophysiological and lesion studies in the non-human primate as well as neuroimaging and patient studies in humans have demonstrated that the oculomotor vermis (lobules VI and VII of the posterior cerebellum) is critical for saccadic adaptation. We studied the effect of transiently disrupting the function of posterior cerebellum with repetitive transcranial magnetic stimulation (rTMS) on the ability of healthy human subjects to adapt saccadic eye movements. rTMS significantly impaired the adaptation of the amplitude of saccades, without modulating saccadic amplitude or variability in baseline conditions. Moreover, increasing the intensity of rTMS produced a larger impairment in the ability to adapt saccadic size. These results provide direct evidence for the role of the posterior cerebellum in man and further evidence that TMS can modulate cerebellar function.

The effect of electromagnetic field emitted by a mobile phone on the inhibitory control of saccades.

OBJECTIVE: To investigate whether exposure to a pulsed high-frequency electromagnetic field (pulsed EMF) emitted by a mobile phone has short-term effects on the inhibitory control of saccades. METHODS: A double-blind, counterbalanced crossover study design was employed. We assessed the performance of 10 normal subjects on antisaccade (AS) and cued saccade (CUED) tasks as well as two types of overlap saccade (OL1, OL2) task before and after 30 min of exposure to EMF emitted by a mobile phone or sham exposure. RESULTS: After EMF or sham exposure, we observed a slight but significant shortening of latency in the CUED and OL2 tasks. AS amplitude decreased as well as the saccade velocities in the AS, CUED, and OL1 tasks after exposure. These changes occurred regardless of whether exposure was real or sham. The frequencies of pro-saccades in the AS task, saccades to cue in the CUED task, and prematurely initiated saccades in the overlap (OL2) task did not change significantly after real or sham EMF exposure. CONCLUSIONS: Thirty minutes of mobile phone exposure has no significant short-term effect on the inhibitory control of saccades. SIGNIFICANCE: The cortical processing responsible for saccade inhibition is not affected by exposure to EMF emitted by a mobile phone.

Transcranial magnetic stimulation over posterior parietal cortex disrupts transsaccadic memory of multiple objects.

The posterior parietal cortex (PPC) plays a role in spatial updating of goals for eye and arm movements across saccades, but less is known about its role in updating perceptual memory. We reported previously that transsaccadic memory has a capacity for storing the orientations of three to four Gabor patches either within a single fixation (fixation task) or between separate fixations (saccade task). Here, we tested the role of the PPC in transsaccadic memory in eight subjects by simultaneously applying single-pulse transcranial magnetic stimulation (TMS) over the right and left PPC, over several control sites, and comparing these to behavioral controls with no TMS. In TMS trials, we randomly delivered pulses at one of three different time intervals around the time of the saccade, or at an equivalent time in the fixation task. Controls confirmed that subjects could normally retain at least three visual features. TMS over the left PPC and a control site had no significant effect on this performance. However, TMS over the right PPC disrupted memory performance in both tasks. This TMS-induced effect was most disruptive in the saccade task, in particular when stimulation coincided more closely with saccade timing. Here, the capacity to compare presaccadic and postsaccadic features was reduced to one object, as expected if the spatial aspect of memory was disrupted. This finding suggests that right PPC plays a role in the spatial processing involved in transsaccadic memory of visual features. We propose that this process uses saccade-related feedback signals similar to those observed in spatial updating.

Time course of blood oxygenation level-dependent signal response after theta burst transcranial magnetic stimulation of the frontal eye field.

The aim of the current study was to examine the effect of theta burst repetitive transcranial magnetic stimulation (rTMS) on the blood oxygenation level-dependent (BOLD) activation during repeated functional magnetic resonance imaging (fMRI) measurements. Theta burst rTMS was applied over the right frontal eye field in seven healthy subjects. Subsequently, repeated fMRI measurements were performed during a saccade-fixation task (block design) 5, 20, 35, and 60 min after stimulation. We found that theta burst rTMS induced a strong and long-lasting decrease of the BOLD signal response of the stimulated frontal eye field at 20 and 35 min. Furthermore, less pronounced alterations of the BOLD signal response with different dynamics were found for remote oculomotor areas such as the left frontal eye field, the pre-supplementary eye field, the supplementary eye field, and both parietal eye fields. Recovery of the BOLD signal changes in the anterior remote areas started earlier than in the posterior remote areas. These results show that a) the major inhibitory impact of theta burst rTMS occurs directly in the stimulated area itself, and that b) a lower effect on remote, oculomotor areas can be induced.

Temporal patterning of saccadic eye movement signals.

Electrical microstimulation is used widely in experimental neurophysiology to examine causal links between specific brain areas and their behavioral functions and is used clinically to treat neurological and psychiatric disorders in patients. Typically, microstimulation is applied to local brain regions as a train of equally spaced current pulses. We were interested in the sensitivity of a neural circuit to a train of variably spaced pulses, as is observed in physiological spike trains. We compared the effect of fixed, decelerating, accelerating, and randomly varying microstimulation patterns on the likelihood and metrics of eye movements evoked from the frontal eye field of monkeys, while holding the mean interpulse interval constant. Our results demonstrate that the pattern of microstimulation pulses strongly influences the probability of evoking a saccade, as well as the metrics of the saccades themselves. Specifically, the pattern most closely resembling physiological spike trains (accelerating pattern) was most effective at evoking a saccade, three times more so than the least effective decelerating pattern. A saccade-triggered average of effective random trains confirmed the positive relationship between accelerating rate and efficacy. These results have important implications for the use of electrical microstimulation in both experimental and clinical settings and suggest a means to study the role of temporal pattern in the encoding of behavioral and cognitive functions.

What delay fields tell us about striate cortex.

It is well known that electrical activation of striate cortex (area V1) can disrupt visual behavior. Based on this knowledge, we discovered that electrical microstimulation of V1 in macaque monkeys delays saccadic eye movements when made to visual targets located in the receptive field of the stimulated neurons. This review discusses the following issues. First, the parameters that affect the delay of saccades by microstimulation of V1 are reviewed. Second, the excitability properties of the V1 elements mediating the delay are discussed. Third, the properties that determine the size and shape of the region of visual space affected by stimulation of V1 are described. This region is called a delay field. Fourth, whether the delay effect is mainly due to a disruption of the visual signal transmitted through V1 or whether it is a disturbance of the motor signal transmitted between V1 and the brain stem saccade generator is investigated. Fifth, the properties of delay fields are used to estimate the number of elements activated directly by electrical microstimulation of macaque V1. Sixth, these properties are used to make inferences about the characteristics of visual percepts induced by such stimulation. Seventh, the disruptive effects of V1 stimulation in monkeys and humans are compared. Eighth, a cortical mechanism to account for the disruptive effects of V1 stimulation is proposed. Finally, these effects are related to normal vision.

Effects of thirty-minute mobile phone exposure on saccades.

OBJECTIVE: To investigate whether exposure to pulsed high-frequency electromagnetic field (pulsed EMF) emitted by a mobile phone has short-term effects on saccade performances. METHODS: A double blind, counterbalanced crossover design was employed. In 10 normal subjects, we studied the performance of visually guided saccade (VGS), gap saccade (GAP), and memory guided saccade (MGS) tasks before and after exposure to EMF emitted by a mobile phone for thirty minutes or sham exposure. We also implemented a hand reaction time (RT) task in response to a visual signal. RESULTS: With the exception of VGS and MGS latencies, the parameters of VGS, GAP and MGS tasks were unchanged before and after real or sham EMF exposure. In addition, the latencies of VGS and MGS did not change differently after real and sham exposure. The hand RT shortened with the repetition of trials, but again this trend was of similar magnitude for real and sham exposures. CONCLUSIONS: Thirty minutes of mobile phone exposure has no significant short-term effect on saccade performances. SIGNIFICANCE: This is the first study to investigate saccade performance in relation to mobile phone exposure. No significant effect of mobile phone use was demonstrated on the performance of various saccade tasks, suggesting that the cortical processing for saccades and attention is not affected by exposure to EMF emitted by a mobile phone.

The local loop of the saccadic system closes downstream of the superior colliculus.

Models of the saccadic system differ in several respects including the signals fed back to their comparators, as well as the location and identity of the units that could serve as comparators. Some models place the comparator in the superior colliculus while others assign this role to the reticular formation. To test the plausibility of reticular models we stimulated electrically efferent fibers of the superior colliculus (SC) of alert cats along their course through the pons, in the predorsal bundle (PDB). Our data demonstrate that electrical stimulation of the PDB evokes saccades, even with stimuli of relatively low frequency (100 Hz), which are often accompanied by slow drifts. The velocity and latency of saccades are influenced by the intensity and frequency of stimulation while their amplitude depends on the intensity of stimulation and the initial position of the eyes. The dynamics of evoked saccades are comparable to those of natural, self-generated saccades of the cat and to those evoked in response to the electrical stimulation of the SC. We also show that PDB-evoked saccades are not abolished by lesions of the SC and that therefore antidromic activation of the SC is not needed for their generation. Our data clearly demonstrate that the burst generator of the horizontal saccadic system is located downstream of the SC. If it is configured as a local loop controller, as assumed by most models of the saccadic system, our data also demonstrate that its comparator is located beyond the decussation of SC efferent fibers, in the pons.

Executive control of countermanding saccades by the supplementary eye field.

The supplementary eye field registers the occurrence of conflict, errors and reward in macaque monkeys performing a saccade-countermanding task. Using intracortical microstimulation, we determined whether the supplementary eye field only monitors or can actually influence performance. Weak microstimulation of many sites in the supplementary eye field improved monkeys' performance on a 'stop signal' task by delaying saccade initiation. This effect depended on the context of the task because simple visually guided saccades were not delayed by the same stimulation. These results demonstrate that the supplementary eye field can exert contextual executive control over saccade generation.

One-Hertz transcranial magnetic stimulation over the frontal eye field induces lasting inhibition of saccade triggering.

The aim of the study was to examine the effect of low-frequency repetitive transcranial magnetic stimulation on saccade triggering. In five participants, a train of 600 pulses with a frequency of 1 Hz was applied over the right frontal eye field and--as control condition--over the vertex. After repetitive transcranial magnetic stimulation application, oculomotor performance was evaluated with an overlap paradigm. The results show that the repetitive transcranial magnetic stimulation effect was specific for frontal eye field stimulation. Saccade latencies were found to be increased bilaterally for several minutes after the stimulation, and the time course of recovery was different for the ipsilateral and contralateral sides. The results are discussed in the light of possible local and remote repetitive transcranial magnetic stimulation effects on the oculomotor network.

The role of the human posterior parietal cortex in memory-guided saccade execution: a double-pulse transcranial magnetic stimulation study.

The present study investigated the role of the right posterior parietal cortex (PPC) in the triggering of memory-guided saccades by means of double-pulse transcranial magnetic stimulation (dTMS). Shortly before saccade onset, dTMS with different interstimulus intervals (ISI; 35, 50, 65 or 80 ms) was applied. For contralateral saccades, dTMS significantly decreased saccadic latency with an ISI of 80 ms and increased saccadic gain with an ISI of 65 and 80 ms. Together with the findings of a previous study during frontal eye field (FEF) stimulation the present results demonstrate similarities and differences between both regions in the execution of memory-guided saccades. Firstly, dTMS facilitates saccade triggering in both regions, but the timing is different. Secondly, dTMS over the PPC provokes a hypermetria of contralateral memory-guided saccades that was not observed during FEF stimulation. The results are discussed within the context of recent neurophysiological findings in monkeys.

Context-dependent stimulation effects on saccade initiation in the presupplementary motor area of the monkey.

Although evidence suggests that the contribution of the presupplementary motor area (pre-SMA) to voluntary motor control is effector-nonselective, the question of how electrical stimulation of the pre-SMA affects eye movements remains unanswered. To address this issue, stimulus effects of the pre-SMA of monkeys on saccade initiation were investigated during performance of a visually guided saccade task with an instructed delay period. This report describes two major findings. First, when stimuli with currents of < or =80 microA were applied before the presentation of a go signal, the reaction time (RT) of an upcoming saccade shortened with comparable effects on ipsi- and contraversive saccades. Second, stimuli that were delivered after the go signal lengthened the RT; this resulted in greater effects on ipsiversive saccades. In addition, the stimulation yielded a mild impairment of saccade accuracy, particularly when the stimulation was delivered after the go signal. By themselves, however, these stimuli did not directly elicit eye movements. Therefore the stimulus effects appeared only in the context of the behavioral task and were dependent on the phase of the task. These findings provide additional support for the hypothesis that the involvement of the pre-SMA in motor control can be linked to either eye or arm motor system dependent on behavioral context.

Phosphene induction and the generation of saccadic eye movements by striate cortex.

The purpose of this review is to critically examine phosphene induction and saccadic eye movement generation by electrical microstimulation of striate cortex (area V1) in humans and monkeys. The following issues are addressed: 1) Properties of electrical stimulation as they pertain to the activation of V1 elements; 2) the induction of phosphenes in sighted and blind human subjects elicited by electrical stimulation using various stimulation parameters and electrode types; 3) the induction of phosphenes with electrical microstimulation of V1 in monkeys; 4) the generation of saccadic eye movements with electrical microstimulation of V1 in monkeys; and 5) the tasks involved for the development of a cortical visual prosthesis for the blind. In this review it is concluded that electrical microstimulation of area V1 in trained monkeys can be used to accelerate the development of an effective prosthetic device for the blind.

Microstimulation of V1 input layers disrupts the selection and detection of visual targets by monkeys.

Electrical microstimulation delivered to primary visual cortex (V1) concurrently with the presentation of visual targets interferes with the selection of these targets. To determine the source of this interference, we stimulated the visual input layers of V1 as rhesus monkeys generated saccadic eye movements to visual targets presented at and outside the receptive field of the stimulated neurons. Columns of cells in V1 innervated by the left and right eye are segregated according to eye dominance, such that cells within a column respond best to visual stimuli presented to the ocular dominant eye. Interference was maximal when targets were presented to the ocular dominant eye, moderate when presented to the ocular inferior eye, and negligible when presented to both eyes. Thus, electrical microstimulation of the visual input layers of V1 disrupts the flow of visual information along the geniculostriate pathway. Knowing how electrical stimulation of V1 affects visual behaviour is necessary when using monkeys to develop a visual prosthesis for the blind.

Saccadic eye movements evoked by microstimulation of striate cortex.

Experiments were performed to assess the excitability of neural elements activated while inducing saccadic eye movements electrically from different cortical layers of striate cortex (area V1) in rhesus monkeys. Excitability was assessed by measuring current thresholds, saccadic latencies, chronaxies, and the effectiveness of anode-first vs. cathode-first pulses. Minimum current thresholds for the evocation of saccades (i.e. less than 5 microA) were observed when the deepest layers of V1 were stimulated. The shortest saccadic latencies were also observed at these depths. The shortest latency at 10 times the threshold current was 49 ms on average. The chronaxies of the elements mediating saccades were less in deep V1 (i.e. 0.17 ms) than in superficial V1 (i.e. 0.23 ms). Anode-first pulses were more effective at evoking saccades from superficial V1, whereas cathode-first pulses were more effective at evoking saccades from deep V1. These results indicate that the excitability properties of superficial and deep V1 are distinct for the generation of saccades. Moreover, the excitability of elements mediating saccades in V1 of monkeys is comparable to that of elements mediating phosphenes in human V1.

[Microperimetry and reading saccades in retinopathia solaris. Follow-up with the scanning laser ophthalmoscope]. / Mikroperimetrie und Lesesakkaden bei Retinopathia solaris. Verlaufsuntersuchungen mit dem Scanning Laser Ophthalmoskop.

UNLABELLED: Patients with solar retinopathy often complain of minute central scotomas and are handicapped when reading. The purpose of this study was to verify scotomas that are too small to be detected by standard perimeters and to analyze patients' reading patterns. METHODS: Nineteen patients (12 female, 7 male, aged 5-46 years) with acute solar retinopathy after watching a solar eclipse on 12 October 1996 underwent scanning laser ophthalmoscope (SLO) microperimetry within 10 days after exposure using stimulus size Goldmann I (0.11 degree) with the 20 degrees field. Size and depth of scotomas were measured. Eye movements during reading were recorded on videotape. Follow-up was at 1 and 6 months. RESULTS: Thirty-one eyes (7 patients unilateral, 12 bilateral) showed scotomas. Four eyes showed anatomic changes in the retinal pigment epithelium but no functional loss. VA was 0.16 to 0.5 in 5 eyes, 26 had VA of 0.8-1.2. Scotomas could be detected in all eyes with subjective impairment. Scotoma size varied from 0.3 to 1.7 degrees (1 patient 6 degrees). Forty-four percent were deep scotomas (0 dB). All defects improved at 1 and at 6 months; 25% were no longer detectable. Reading speed was reduced in 75% of eyes (42% at 6 months): 200-560 signs/min, median: 510, normal > or = 660 (at 6 months: 350-920 signs/min, median 670). This was especially due to increased number of regressions (in 81% of eyes, 21% at 6 months). The frequency and width of saccades were no different from normal subjects. CONCLUSION: Minute scotomas (diameter = 0.3 degree) can be detected with the SLO. All patients showed objective improvement of their field defect up to 6 months, even when this was not noted by the patient or thought to be due to habituation. Small scotomas can dramatically reduce reading performance.

Influence of transcranial magnetic stimulation on the execution of memorised sequences of saccades in man.

Memorised sequences of saccades are cortically controlled by the supplementary motor area (SMA), as shown in animal experiments and in humans with isolated SMA lesions. We applied transcranial magnetic stimulation (TMS) in eight healthy subjects executing memorised sequences of saccades. Sequences of three targets were presented. Then, upon a go-signal, the subjects had to execute the appropriate sequences. Ten to fifteen sequences were performed in each experiment, and the number of errors were counted. The number of errors increased significantly if TMS was given 80 ms before or 60 ms after the go-signal, with the stimulation coil overlying the SMA. There was no significant increase in errors if different stimulation intervals were chosen (160 ms and 120 ms before the go-signal; 100 ms, 140 ms or 240 ms after the go-signal), if the coil was positioned inappropriately (e.g. over the occipital cortex), or if the stimulator output was too low. We conclude that TMS can interfere specifically with the function of the SMA during a critical time interval close to the go-signal.

[The otoneurological assessment of radiotherapy-induced brain stem involvement in patients with rhinopharyngeal neoplasms]. / Valutazione otoneurologica della sofferenza troncoencefalica radioindotta in pazienti con neoplasie della rinofaringe.

The authors report a study in which otoneurological tests were employed in order to determine the possibility of radio-induced alterations in the brainstem of patients with a rhinopharyngeal carcinoma, which extended to basicranial structures, who had undergone radiotherapy. The case report includes 16 patients; 10 males and 6 females, aged from 37 to 82, all with rhinopharyngeal tumors. All the subjects underwent Co 60 radiotherapy (44-68 Gy); the brainstem received from 40 to 100% of the total dose. Otoneurological evaluation prior to and following radiotherapy was performed employing pure tone audiometry, ABR, rotatory tests, saccadic eye movements, smooth pursuit. After RT treatment, ABR analysis revealed an abnormal wave I-V interpeak interval in 40% of the cases and pathologic in 37%. Smooth pursuit, saccades and sinusoidal rotation analysis showed important alterations respectively in 21%, 6% and 12% of the subjects. The most significant variations were in patients who received more than 60 Gy. The data gathered regarding abnormalities of otoneurological parameters indicate a probable close relationship between these modifications and precocious radio-induced brainstem damage.