Maarten A. Frens

Recording eye movements with video-oculography and scleral search coils: a direct comparison of two methods

A video-based 2D eye-tracking system (EyeLink version 2.04, SR Research Ltd/SMI) was compared with the scleral search coil technique for its performance on recording the properties of fixations and saccadic eye movements. Fixation positions and saccadic properties (amplitude, duration, and peak velocity) were calculated independently from the data of the two systems that recorded eye positions simultaneously. Fixation positions were well correlated between the video and the coil output with an average discrepancy of <1 degree over a tested range of 40 by 40 degree of visual angle. With respect to the saccade analysis, the values measured by the video system were fitted as a linear function of the values measured by the coil system. Highly correlated linear fits with slopes near one were obtained for all the saccadic parameters. Main sequence relationships (amplitudes-duration and amplitude-peak velocity) were also similar for both systems. A disadvantage of the video method is its low sample rate of 250 Hz. The relatively noisier estimate of all parameters of small saccades could be attributed to this low sampling frequency.

Increased noise level of purkinje cell activities minimizes impact of their modulation during sensorimotor control

While firing rate is well established as a relevant parameter for encoding information exchanged between neurons, the significance of other parameters is more conjectural. Here, we show that regularity of neuronal spike activities affects sensorimotor processing in tottering mutants, which suffer from a mutation in P/Q-type voltage-gated calcium channels. While the modulation amplitude of the simple spike firing rate of their floccular Purkinje cells during optokinetic stimulation is indistinguishable from that of wild-types, the regularity of their firing is markedly disrupted. The gain and phase values of totterings compensatory eye movements are indistinguishable from those of flocculectomized wild-types or from totterings with the flocculus treated with P/Q-type calcium channel blockers. Moreover, normal eye movements can be evoked in tottering when the flocculus is electrically stimulated with regular spike trains mimicking the firing pattern of normal simple spikes. This study demonstrates the importance of regularity of firing in Purkinje cells for neuronal information processing.

Visual-auditory interactions modulate saccade-related activity in monkey superior colliculus

This paper reports on single-unit activity of saccade-related burst neurons (SRBNs) in the intermediate and deep layers of the monkey superior colliculus (SC), evoked by bimodal sensory stimulation. Monkeys were trained to generate saccadic eye movements towards visual stimuli, in either a unimodal visual saccade task, or in a bimodal visual-auditory task. In the latter task, the monkeys were required to make an accurate saccade towards a visual target, while ignoring an auditory stimulus. The presentation of an auditory stimulus in temporal and spatial proximity of the visual target influenced neither the accuracy nor the kinematic properties of the evoked saccades. However, it had a significant effect on the activity of 90% (45/50) of the SRBNs. The motor-related burst increased significantly in some neurons, but was suppressed in others. In visual-movement cells, comparable bimodal interactions were observed in both the visually evoked burst and the movement-related burst. The large differences observed in the movement-related activity of SRBNs for identical saccades under different sensory conditions do not support the hypothesis that such cells encode dynamic motor error. The only behavioral parameter that was affected by the presentation of the auditory stimulus was saccade latency. Auditory stimulation caused saccade latency changes in the majority of the experiments. Meanwhile, the timing of peak collicular motor activity and saccade onset remained tightly coupled for all stimulus configurations. In addition, saccade latency varied as function of the distance between the stimuli in 36% of the recordings. Interestingly, the occurrence of a spatial latency effect covaried significantly with a similar spatial influence on the SRBNs firing rate. These cells were always most active in the bimodal task when both stimuli were in spatial register, but activity decreased with increasing stimulus separation.

Purkinje cells in awake behaving animals operate at the upstate membrane potential

To the Editor: Over the last decades, cellular bistability or multistable states of the membrane potential have been demonstrated both in vitro and in vivo for different types of neurons throughout the brain, and various functions have been proposed for this phenomenon1,2. Recently, Loewenstein et al.3 proposed that bistability in Purkinje cells has a key role in the short-term processing and storage of sensorimotor information in the cerebellar cortex and that complex spikes may act as a toggle switch to control these processes. However, all intracellular recordings of bistability to date have been obtained either in slices or in anesthetized animals4. Because anesthetics can directly or indirectly affect the membrane potential5, it remains to be seen whether the proposed functional roles of bistability are valid in normal behaving animals under physiological conditions. To confirm the occurrence of bistability in Purkinje cells, we performed whole-cell patch recordings in vivo in mice under isoflurane or ketamine/xylazine anesthesia.

Inhibition of return is not a foraging facilitator in saccadic search and free viewing

The ability to search and scan the environment effectively is a prerequisite for spatial behavior. A longstanding theory proposes that inhibition of previously attended loci (Inhibition of return; IOR) serves to facilitate exploration by increasing the likelihood to inspect new areas instead of returning to locations that have been inspected before. In this eye movement study we tested whether we could find evidence in favor of this hypothesis. Here we report that IOR does occur during search and free viewing, because we found increased fixation times preceding return saccades (eye movements that return to previously fixated locations). Meanwhile we observed no influence of IOR on the search strategy. Rather than the predicted low number we found many return saccades. Therefore, IOR does not serve as a foraging facilitator in saccadic search and free viewing. We hypothesize that IOR is an intrinsic aspect of shifting attention and gaze direction and furthermore that it is not always advantageous to prevent return saccades.

Compensatory increase of the cervico-ocular reflex with age in healthy humans

The cervico‐ocular reflex (COR) is an ocular stabilization reflex that is elicited by rotation of the neck. It works in conjunction with the vestibulo‐ocular reflex (VOR) and the optokinetic reflex (OKR) in order to prevent visual slip over the retina due to self‐motion. The gains of the VOR and OKR are known to decrease with age. We have investigated whether the COR, a reflexive eye movement elicited by rotation of the neck, shows a compensatory increase and whether a synergy exists between the COR and the other ocular stabilization reflexes. In the present study 35 healthy subjects of varying age (20–86 years) were rotated in the dark in a trunk‐to‐head manner (the head fixed in spaced with the body passively rotated under it) at peak velocities between 2.1 and 12.6 deg s−1 as a COR stimulus. Another 15 were subjected to COR, VOR and OKR stimuli at frequencies between 0.04 and 0.1 Hz. Three subjects participated in both tests. The position of the eyes was recorded with an infrared recording technique. We found that the COR‐gain increases with increasing age and that there is a significant covariation between the gains of the VOR and COR, meaning that when VOR increases, COR decreases and vice versa. A nearly constant phase lag between the COR and the VOR of about 25 deg existed at all stimulus frequencies.

Throwing darts : Timing is not the limiting factor

It has been argued that precision in throwing is limited by the precision in the timing of the release. When precision is the only goal, as in throwing darts, one could therefore expect people to throw in a way that reduces sensitivity for imprecision in timing. We show that subjects do not do so, but throw in a way that reduces the sensitivity for speed errors instead. They even appear to vary the timing of release to compensate for the errors in the hand’s movement. Thus timing does not appear to be the limiting factor.

Simple spike and complex spike activity of floccular Purkinje cells during the optokinetic reflex in mice lacking cerebellar long-term depression

Cerebellar long‐term depression (LTD) at parallel fibre–Purkinje cell (P‐cell) synapses is thought to embody neuronal information storage for motor learning. Transgenic L7‐protein kinase C inhibitor (PKCI) mice in which cerebellar LTD is selectively blocked do indeed exhibit impaired adaptation in the vestibulo‐ocular reflex (VOR) while their default oculomotor performance is unaffected. Although supportive, these data do not definitively establish a causal link between memory storage required for motor learning and cerebellar LTD. As the L7‐PKCI transgene is probably activated from the early stages of P‐cell development, an alternative could be that P‐cells develop abnormal signals in L7‐PKCI mutants, disturbing mechanisms of motor learning that rely on proper P‐cell outputs. To test this alternative hypothesis, we studied simple spike (SS) and complex spike (CS) activity of vertical axis P‐cells in the flocculus of L7‐PKCI mice and their wild‐type littermates during sinusoidal optokinetic stimulation. Both SS and CS discharge dynamics appeared to be very similar in wild‐type and transgenic P‐cells at all stimulus frequencies (0.05–0.8 Hz). The CS activity of all vertical axis cells increased with contralateral stimulus rotation and lagged ipsiversive eye velocity by 165–180°. The SS modulation was roughly reciprocal to the CS modulation and lagged ipsiversive eye velocity by ∼ 15°. The baseline SS and CS discharge characteristics were indistinguishable between the two genotypes. We conclude that the impaired VOR learning in L7‐PKCI mutants does not reflect fundamental aberrations of the cerebellar circuitry. The data thus strengthen the evidence that cerebellar LTD is implicated in rapid VOR learning but not in the development of normal default response patterns.

Age- and Sex-Related Differences in Contrast Sensitivity in C57Bl/6 Mice

PURPOSE To measure contrast sensitivity in C57BL/6, the most commonly used mouse in behavioral neuroscience, and to study the effect of sex, age, and miotic drugs on the contrast sensitivity function. In addition, the authors tested a mutant in which plasticity in the cerebellum is impaired by expressing a protein kinase C inhibitor. This inhibitor is also expressed in the retina, possibly affecting vision. METHODS The gain of the optokinetic reflex (OKR) decreases as stimuli become more difficult to see. Recording OKR gains evoked by moving sine gratings shows whether the stimulus was distinguished from a homogeneous background and how well the stimulus was distinguished. RESULTS Female mice have lower OKR gains than male mice (both groups: n = 10, P = 0.001). A similar difference was observed between 4-month-old (n = 10) and 9-month-old (n = 5) C57Bl/6 mice (P = 0.001). These differences could not be detected with earlier dichotomic tests. C57BL/6 mice are able to see contrasts as low as 1%, well below the previously reported 5% threshold. Pilocarpine had no significant effect on contrast sensitivity (both groups: n = 10, P = 0.89). Vision in L7-PKCi mutants was unaffected (both groups: n = 10, P = 0.82). CONCLUSIONS OKR gains decrease as stimuli become more difficult to see, making the OKR a powerful tool to quantify contrast sensitivity. In C57BL/6 these response magnitudes vary greatly between sexes and between mice that differ only a few months in age. Therefore, it is important to match groups according to age and sex in experiments that require unimpaired vision. Otherwise, impaired vision can be misinterpreted as a learning or motor problem.

Transcranial Magnetic Stimulation and Motor Plasticity in Human Lateral Cerebellum: Dual Effect on Saccadic Adaptation

The cerebellum is a key area for movement control and sensory‐motor plasticity. Its medial part is considered as the exclusive cerebellar center controlling the accuracy and adaptive calibration of saccadic eye movements. However, the contribution of other zones situated in its lateral part is unknown. We addressed this question in healthy adult volunteers by using magnetic resonance imaging (MRI)‐guided transcranial magnetic stimulation (TMS). The double‐step target paradigm was used to adaptively lengthen or shorten saccades. TMS pulses over the right hemisphere of the cerebellum were delivered at 0, 30, or 60 ms after saccade detection in separate recording sessions. The effects on saccadic adaptation were assessed relative to a fourth session where TMS was applied to Vertex as a control site. First, TMS applied upon saccade detection before the adaptation phase reduced saccade accuracy. Second, TMS applied during the adaptation phase had a dual effect on saccadic plasticity: adaptation after‐effects revealed a potentiation of the adaptive lengthening and a depression of the adaptive shortening of saccades. For the first time, we demonstrate that TMS on lateral cerebellum can influence plasticity mechanisms underlying motor performance. These findings also provide the first evidence that the human cerebellar hemispheres are involved in the control of saccade accuracy and in saccadic adaptation, with possibly different neuronal populations concerned in adaptive lengthening and shortening. Overall, these results require a reappraisal of current models of cerebellar contribution to oculomotor plasticity. Hum Brain Mapp, 2011.