Biomedical subjects

M A Frens

Publications and source records attributed to M A Frens.

At least 19 recordsLinked to original sources

PubMed2006

Visual search deficits in Williams-Beuren syndrome.

Williams-Beuren syndrome (WBS) is a rare genetic condition characterized by several physical and mental traits, such as a poor visuo-spatial processing and a relative strength in language. In this study we investigated how WBS subjects search and scan their visual environment. We presented 10 search displays on a computer screen to WBS subjects as well as control subjects, with the instruction to find a target out of several stimulus elements. We analyzed the eye movement patterns for fixation characteristics and systematicy of search. Fixations generally lasted longer in WBS subjects than in control subjects. WBS subjects made more fixations at a stimulus element they had already looked at and more fixations that were not aimed at a stimulus element at all, decreasing the efficiency of search. These outcomes lead to the conclusion that visual search of individuals with Williams-Beuren syndrome is less effective than in control subjects. This finding may be related to their motor deficits, an impaired processing of global visual information and/or deficits in working memory and could reflect impairments within the dorsal stream.

Adolescent↗

PubMed2005

Visual depth processing in Williams-Beuren syndrome.

Patients with Williams-Beuren Syndrome (WBS, also known as Williams Syndrome) show many problems in motor activities requiring visuo-motor integration, such as walking stairs. We tested to what extent these problems might be related to a deficit in the perception of visual depth or to problems in using this information in guiding movements. Monocular and binocular visual depth perception was tested in 33 patients with WBS. Furthermore, hand movements to a target were recorded in conditions with and without visual feedback of the position of the hand. The WBS group was compared to a group of control subjects. The WBS patients were able to perceive monocular depth cues that require global processing, but about 49% failed to show stereopsis. On average, patients with WBS moved their hand too far when no visual feedback on hand position was given. This was not so when they could see their hand. Patients with WBS are able to derive depth from complex spatial relationships between objects. However, they seem to be impaired in using depth information for guiding their movements when deprived of visual feedback. We conclude that the problems that WBS patients have with tasks such as descending stairs are not due to an inability to judge distance.

Adolescent↗

PubMed2005

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 tottering's 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.

Action Potentials↗

PubMed2005

Increased prevalences of left-handedness and left-eye sighting dominance in individuals with Williams-Beuren syndrome.

Handedness and eye sighting dominance were assessed in a sample of 50 individuals (25 male, 25 female; aged 5-38 years) with Williams-Beuren syndrome (WBS). The prevalences of left-handedness and left-eyedness were compared to the normative prevalences in the general population. We found significantly higher prevalences of left-handedness and left-eyedness in the WBS sample. The higher prevalences were more salient in younger than in older individuals and in male than in female individuals. We suggest that the increased prevalence of left-handedness in WBS is a consequence of a slower maturation rate, which allows deviation from a predetermined laterality pattern.

Adolescent↗

PubMed2005

The cervico-ocular reflex is increased in whiplash injury patients.

Whiplash-associated disorders (WAD) are a major problem in the Western world, which put a formidable financial burden on modern society and which evoke an emerging debate on the true nature of their origin. To date there is no generally accepted test that allows us to diagnose WAD objectively. Because whiplash injury causes dysfunction of proprioception in the neck, we investigated the characteristics of the cervico-ocular reflex (COR) of presumptive WAD patients. These patients and age-matched healthy controls were rotated at different stimulus peak velocities in the dark while their head was fixed in space. The gain values of the COR were significantly increased in the patient population at a wide range of stimulus peak velocities with maximum difference at the lower frequencies (p = 0.037, ANOVA). Hence, although larger numbers of patients should be measured, the COR gain appears to be a parameter that may permit an objective diagnosis of WAD.

Adult↗

PubMed2004

Short-term adaptation of the cervico-ocular reflex.

The cervico-ocular reflex (COR) works in conjunction with the vestibulo-ocular reflex (VOR) and the optokinetic reflex (OKR) in order to prevent visual slip over the retina during head movement. The COR induces eye movements in response to proprioceptive signals from the neck. We investigated whether the COR gain can be adapted by inducing a mismatch between vision and neck proprioception, in analogy to VOR adaptation. Thirteen healthy subjects were rotated in the dark in a trunk-to-head manner (the head fixed in space while the body passively rotated sinusoidally with a peak velocity of 1.25 degrees /s). Eye movements were recorded with infrared video-oculography under various adaptive conditions. Analysis showed a small but significant reduction in COR gain in the suppression conditions. This means that the cervico-ocular reflex can be modified after only 10 min of concurrent visual and cervical stimulation.

Adaptation, Physiological↗

PubMed2004

Saccade dysmetria in Williams-Beuren syndrome.

Numerous studies have described the poor visuo-spatial processing capacities of subjects with Williams-Beuren syndrome (WBS), a genetically based developmental disorder. Since visual perception and eye movements are closely related we hypothesized that the poor visuo-spatial processing capacities of subjects with WBS might be related to a poor saccadic control. Thereto, we recorded horizontal and vertical saccadic eye movements to targets using infrared video-oculography in 27 subjects with WBS and eight healthy controls. In the WBS group saccadic gains were highly variable, both between and within individual subjects, and they often needed more than one correction saccade to reach the target. Ten (out of a subgroup of 22) WBS subjects showed a large number of hypometric and/or hypermetric saccades, and, also a left-right asymmetry in saccadic gains was observed in WBS. We conclude that the observed impairments in saccadic control are likely to affect the proper processing of visuo-spatial information.

Adolescent↗

PubMed2004

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 degrees. The SS modulation was roughly reciprocal to the CS modulation and lagged ipsiversive eye velocity by approximately 15 degrees. 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.

Action Potentials↗

PubMed2003

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.

Adult↗

PubMed2003

Three-dimensional vestibular eye and head reflexes of the chameleon: characteristics of gain and phase and effects of eye position on orientation of ocular rotation axes during stimulation in yaw direction.

We investigated gaze-stabilizing reflexes in the chameleon using the three-dimensional search-coil technique. Animals were rotated sinusoidally around an earth-vertical axis under head-fixed and head-free conditions, in the dark and in the light. Gain, phase and the influence of eye position on vestibulo-ocular reflex rotation axes were studied. During head-restrained stimulation in the dark, vestibulo-ocular reflex gaze gains were low (0.1-0.3) and phase lead decreased with increasing frequencies (from 100 degrees at 0.04 Hz to < 30 degrees at 1 Hz). Gaze gains were larger during stimulation in the light (0.1-0.8) with a smaller phase lead (< 30 degrees) and were close to unity during the head-free conditions (around 0.6 in the dark, around 0.8 in the light) with small phase leads. These results confirm earlier findings that chameleons have a low vestibulo-ocular reflex gain during head-fixed conditions and stimulation in the dark and higher gains during head-free stimulation in the light. Vestibulo-ocular reflex eye rotation axes were roughly aligned with the head's rotation axis and did not systematically tilt when the animals were looking eccentrically, up- or downward (as predicted by Listing's Law). Therefore, vestibulo-ocular reflex responses in the chameleon follow a strategy, which optimally stabilizes the entire retinal images, a result previously found in non-human primates.

Adaptation, Physiological↗

PubMed2002

Inhibition of saccade initiation by preceding smooth pursuit.

In this study, we investigated the influence of smooth-pursuit eye movements on saccade initiation in response to a sudden jump of a continuously moving target. We replicated the finding by Tanaka et al. (1998) that saccadic eye movements in the direction opposite to preceding pursuit have longer latencies than those in the same direction. We confirmed that this asymmetry is indeed due to an inhibitory effect of smooth pursuit on saccade initiation in the opposite direction rather than facilitation of saccade initiation in the same direction. The inhibitory effect decreased strongly when subjects knew the jump direction in advance. This supports the notion that the prolonged latencies of backward saccades are not due to orbital mechanics or low-level motor processing. Furthermore, we found that the range of saccade directions inhibited by a pursuit movement is broad, covering all directions that did not have the same horizontal component as the pursuit direction. This is in contrast with the predictions of "Inhibition of Saccade Return" (ISR, Hooge and Frens 2000), which is restricted to a smaller confined area.

Distance Perception↗

PubMed2002

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.

Eye Movements↗

PubMed2002

Scleral search coils influence saccade dynamics.

The scleral search coil technique is commonly used for recording eye movements. The goal of this paper is to investigate to what extent the placement of scleral search coils onto the eyes influences the kinematics of saccades. To that end saccadic eye movements of human subjects were recorded with an infrared video system, while they wore coils and we compared the main sequence properties with recordings in which no coils were mounted on the eyes. It was found that saccades last longer (by about 8%) and become slower (by about 5%) when both eyes wear coils. This is truly due to the fact that the coils are on the eyes and not due to other factors that are part of this method, such as the scleral anesthesia. The influence of coils in both eyes was also observed when one coil was mounted on one eye only. Therefore the effect that the coils have on the eye movements cannot be attributed to purely mechanical factors, such as inertial load on the eyeball or increased friction. Rather the coils appear to change the oculomotor command signals that drive the saccadic eye movements.

Biotechnology↗

PubMed2001

Expression of protein kinase C inhibitor blocks cerebellar long-term depression without affecting Purkinje cell excitability in alert mice.

A longstanding but still controversial hypothesis is that long-term depression (LTD) of parallel fiber-Purkinje cell synapses in the cerebellum embodies part of the neuronal information storage required for associative motor learning. Transgenic mice in which LTD is blocked by Purkinje cell-specific inhibition of protein kinase C (PKC) (L7-PKCI mutants) do indeed show impaired adaptation of their vestibulo-ocular reflex, whereas the dynamics of their eye movement performance are unaffected. However, because L7-PKCI mutants have a persistent multiple climbing fiber innervation at least until 35 d of age and because the baseline discharge of the Purkinje cells in the L7-PKCI mutants is unknown, factors other than a blockage of LTD induction itself may underlie their impaired motor learning. We therefore investigated the spontaneous discharge of Purkinje cells in alert adult L7-PKCI mice as well as their multiple climbing fiber innervation beyond the age of 3 months. We found that the simple spike and complex spike-firing properties (such as mean firing rate, interspike interval, and spike count variability), oscillations, and climbing fiber pause in the L7-PKCI mutants were indistinguishable from those in their wild-type littermates. In addition, we found that multiple climbing fiber innervation does not occur in cerebellar slices obtained from 3- to 6-month-old mutants. These data indicate (1) that neither PKC inhibition nor the subsequent blockage of LTD induction disturbs the spontaneous discharge of Purkinje cells in alert mice, (2) that Purkinje cell-specific inhibition of PKC detains rather than prevents the developmental conversion from multiple to mono-innervation of Purkinje cells by climbing fibers, and (3) that as a consequence the impaired motor learning as observed in older adult L7-PKCI mutants cannot be attributable either to a disturbance in the baseline simple spike and complex spike activities of their Purkinje cells or to a persistent multiple climbing fiber innervation. We conclude that cerebellar LTD is probably one of the major mechanisms underlying motor learning, but that deficits in LTD induction and motor learning as observed in the L7-PKCI mutants may only be reflected in differences of the Purkinje cell signals during and/or directly after training.

Action Potentials↗

PubMed2001

Heading and path percepts from visual flow and eye pursuit signals.

The percept of self-motion through the environment is supported by visual motion signals and eye movement signals. The interaction between these signals by decoupling of the eye movement and the pattern of retinal motion during brief simulated ego-movement on straight or circular trajectories was studied. A new response method enabled subjects to report perceived destination and perceived curvature of their future path simultaneously. Various combinations of simulated gaze rotation in the retinal flow and eye pursuit were investigated. Simulated gaze rotation ranged from consistent and larger than, to opponent and larger than eye pursuit. It was found that the perceived destination shifts non-linearly with the mismatch between simulated gaze rotation and eye pursuit. The non-linearity is also revealed in the perceived tangent heading direction and perceived path curvature, although to different extent in different subjects. For the same retinal flow, eye pursuit that is consistent with the simulated gaze rotation reduces heading error and the perceived path straightens out. In contrast, perceived path and/or heading do not become more curved or more biased in the direction opposite to pursuit when the eye -in-head rotation is opposite to the simulated gaze rotation. These observations point to modulation of the effect of the extra-retinal pursuit signal by the visual evidence for eye rotation. In a second experiment, one presented to a stationary eye the sum of a component of simulated gaze rotation and radial flow. It was found that the bi-circular flow component, that characterizes the change in pattern of flow directions by the gaze rotation, induces a shift of perceived heading without appreciable perceived path curvature. Conversely, the complementary component of simulated gaze rotation (bi-radial flow) evokes a percept of motion on a curved path with a small tangent heading error. It was suggested that bi-circular and bi-radial flow components contribute primarily to percepts of heading and path curvature, respectively.

Humans↗

PubMed2001

Chameleon eye position obeys Listing's law.

Listing's law (LL) states that 3D-eye positions lie in a plane, when they are described as single-axis rotations from the primary position. This implies that the degrees of freedom of eye movements are reduced from three to two. Various hypotheses exist, regarding the implementation of LL. These include facilitation of binocular vision, optimization of oculomotor control, and mechanical constraints in the orbit. We recorded the 3D-eye position during saccadic scanning in the chameleon, to investigate whether LL is valid in an animal with different anatomical and behavioral characteristics compared to primates. We show that in chameleons, the eye position obeys LL with a high precision. Since the anatomical arrangement of the orbit in chameleons is very different from that in primates, and binocular fused vision is virtually absent, we suggest that in the chameleon, LL mainly optimizes oculomotor control.

Animals↗

PubMed2001

Floccular complex spike response to transparent retinal slip.

The flocculus of the rabbit is involved in the plasticity of compensatory eye movements. It is generally assumed that the climbing fiber input to floccular Purkinje cells encodes "retinal slip," which in turn would be a measure for the oculomotor performance error. To test this, we used transparent motion stimuli, creating a retinal slip signal that broke up this relation. We recorded the ensuing oculomotor behavior and complex spike activity of floccular Purkinje cells. Complex spike modulation in response to transparent stimulation was identical to that of a single optokinetic pattern, despite considerably different retinal slip. These results suggest that the climbing fiber code may be effectively related to the eye movement performance error, rather than to retinal slip.

Action Potentials↗

PubMed2000

Effects of cholinergic neuromodulation in cerebellar flocculus on transparent motion processing in the rabbit.

The way a rabbit moves its eyes in response to a stimulus consisting of two moving random dot patterns largely depends on the relative luminances of the two patterns. Concurrent rotation of the animal enhances the response to the visual pattern that represents the same head movement as the vestibular stimulation. In this paper we investigate the role that the flocculus plays in this behaviour. We injected the non-selective acetylcholine agonist carbachol into the flocculus. These injections are known to increase the gain of the optokinetic reflex, but have a smaller effect on the vestibulo-ocular reflex. We investigated the effect on the oculomotor response to (vestibulo-) transparent stimuli, where one pattern oscillated sinusoidally and the other pattern was stable with respect to the head. We found that the injections caused a higher response gain at a lower luminance of the oscillating pattern. Furthermore the influence of concurrent vestibular stimulation decreased. These findings agree with a role of the flocculus that is downstream of the visual normalisation, but upstream of the visual-vestibular interaction.

Acetylcholine↗