Biomedical subjects

M Fetter

Publications and source records attributed to M Fetter.

At least 55 records · Page 3Linked to original sources

PubMed1996

Autosomal dominant cerebellar ataxia type I clinical features and MRI in families with SCA1, SCA2 and SCA3.

Sixty-five patients suffering from autosomal dominant cerebellar ataxia-I(ADCA-1) were subjected genotype phenotype correlation analysis using molecular genetic assignment to the spinocerebellar ataxia type 1, 2 or 3 (SCA1, -2 or -3) locus, clinical examination, eye movement recording and morphometric analysis of MRIs. Pyramidal tract signs, pale discs and dysphagia were more frequent in SCA1 compared SCA2 and SCA3 patients. Saccade velocity was reduced in 56% of SCA1 and all SCA2, but only in 30% of SCA3 patients. MRIs of SCA2 patients showed atrophy changes typical of severe olivopontocerebellar atrophy (OPCA). The morphological changes in SCA1 were similar but less pronounced. In contrast, SCA3 patients had only mild cerebellar and brain stem atrophy distinct from typical OPCA. The principal finding of this study is that mutations of the SCA2 and SCA3 gene cause phenotypes which can be distinguished in vivo by recording of eye movements and morphometric MRI analysis. Correlative plotting of saccade velocity and diameter of the middle cerebellar peduncle yields a clear separation of SCA2 and SCA3. Spinocerebellar ataxia type I falls into an intermediate range that overlaps with both SCA2 and SCA3. However, the clinical syndrome observed in SCA1 patients is different from that in SCA2 and SCA3.

Adult↗

PubMed1996

Interaction of smooth pursuit and the vestibuloocular reflex in three dimensions.

1. What is the neural mechanism of vestibuloocular reflex (VOR) cancellation when a subject fixates a target moving with the head? One theory is that the moving target evokes pursuit eye movements that add to and cancel the VOR. A recent finding with implications for this theory is that eye velocity vectors of both pursuit and the VOR vary with eye position, but in different ways, because pursuit follows Listing's law whereas the VOR obeys a "half-Listing" strategy. As a result, pursuit cannot exactly cancel the VOR in most eye positions, and so the pursuit superposition theory predicts an eye-position-dependent pattern of residual eye velocities during cancellation. To test these predictions, we measured eye velocity vectors in humans during VOR, pursuit, and cancellation in response to torsional, vertical, and horizontal stimuli with the eyes in different positions. 2. For example, if a subject is rolling clockwise (CW, frequency 0.3 Hz, maximum speed 37.5 deg/s) while looking 20 deg up, the VOR generates an eye velocity that is mainly counterclockwise (CCW), but also leftward. If we then turn on a small target light, located 20 deg up and moving with the subject, then pursuit superposition predicts that the CCW component of eye velocity will shrink and the horizontal component will reverse, from leftward to rightward. This pattern was seen in all subjects. 3. Velocities depended on eye position in the predicted way; e.g., when subjects looked 20 deg down, instead of 20 deg up, during CW roll, the reversal of horizontal eye velocity went the other way, from rightward to leftward. And when gaze was 20 deg right or left, analogous reversals occurred in the vertical eye velocity, again as predicted. 4. Analogous predictions for horizontal and vertical stimulation were also borne out by the data. For example, when subjects rotated rightward while looking 20 deg up, the VOR response was leftward and CCW. When the target light switched on, the torsional component of the response reversed, becoming CW. And analogous predictions for other eye positions and for vertical stimulation also held. 5. For all axes of stimulation and all eye positions, eye velocity during cancellation was roughly parallel with the gaze line. This alignment is predicted by pursuit superposition and has the effect of reducing retinal image slip over the fovea. 6. The fact that the complex dependence of eye velocity on the stimulation axis and eye position predicted by pursuit superposition was seen in all subjects and conditions suggests strongly that the VOR indeed is canceled additively by pursuit. However, eye velocities during cancellation were consistently smaller than predicted. This shrinkage indicates that a second mechanism, besides pursuit superposition, attenuates eye velocities during cancellation. The results can be explained if VOR gain is reduced by approximately 30%, and if, in addition, pursuit is driven by retinal slip rather than reconstructed target velocity in space.

Adult↗

PubMed1996

Friedreich's ataxia with retained tendon reflexes: molecular genetics, clinical neurophysiology, and magnetic resonance imaging.

Lower limb areflexia is generally regarded as an essential criterion for the diagnosis of Friedreich's ataxia (FRDA). We describe a family with a recessive form of early-onset ataxia in which one member had a phenotype typical of FRDA whereas another, with retained tendon reflexes in the lower limbs, did not have electrophysiologic evidence of the usual severe afferent axonal neuropathy of FRDA. In contrast, somatosensory evoked potentials, eye-movement recordings, and MRI of the head and cervical cord provided results highly suggestive of FRDA in both patients. We performed genetic linkage analysis in this family, using markers tightly linked to the FRDA locus on chromosome 9. Inheritance of identical paternal and maternal genotypes by the affected members, but not by their unaffected siblings, provided supporting evidence that this disorder may result from mutation within the FRDA gene or is tightly linked to the investigated loci on chromosome 9.

Adult↗

PubMed1995

Fixation instability and oculomotor abnormalities in Friedreich's ataxia.

Eye movements were studied in 13 patients with Friedreich's ataxia and correlated with MRI findings to investigate whether oculomotor abnormalities can be traced to cerebellar disturbances in this disease. One of the most prominent eye signs was fixation instability (square-wave jerks, SWJ.). Besides SWJ the patients showed various combinations of cerebellar, vestibular and brain-stem oculomotor signs. Our patients did not comprise a homogeneous group with regard to their oculomotor findings. There was no correlation between the severity of any of the so-called cerebellar oculomotor disturbances and the number of SWJ. We tried to correlate the extent of oculomotor disturbances with floccular atrophy and atrophy of the dorsal vermis on MRI in seven of the patients. None of the oculomotor features (including SWJ) correlated with flocculus or dorsal vermis size. Furthermore, floccular and vermal measurements on MRI were normal. Accordingly, we think it unlikely that the oculomotor disturbances, including SWJ, are attributable to cerebellar pathology per se.

Adult↗

PubMed1995

Ocular space exploration in the dark and its relation to subjective and objective body orientation in neglect patients with parietal lesions.

Eye movements of neglect patients with right parietal lesions were recorded during ocular searching for a (non-existent) target in complete darkness. With respect to the objective orientation of the sagittal midplane, ocular exploration was biased toward the ipsilesional side. However, in relation to the patients' subjective localization of the sagittal midplane in space, exploratory eye movements were symmetrically distributed to the subjective "left" and "right" as observed in non-brain-damaged controls. The present results further support the hypothesis that the essential aspect leading to spatial neglect is a disturbance of those cortical structures that are crucial for computing egocentric, body-centred coordinates that allow use to determine our body position in space and that are necessary for visuomotor coordination and exploration of space. In neglect patients the central coordinate transformation seems to work with a systematic error resulting in a deviation of the spatial reference frame to the ipsilesional side. Consequences of this deviation are a displacement of subjective localization of body orientation and--to the same degree--of the spatial area in which motor behavior (here exploratory eye movements) is executed.

Aged↗

PubMed1995

Three-dimensional (3-D) eye movement analysis in patients with positioning nystagmus.

Benign paroxysmal positioning vertigo (BPPV), and nystagmus (BPPN) is the commonest type of rotational vertigo. Typical BPPN is generally believed to arise from one posterior semicircular canal. If this is true, the syndrome would offer the unique possibility to study vestibular responses when just one single semicircular canal is excited. In this study we used search coils to measure 3-D eye positions in 3 patients with BPPN. We present a complete 3-D description of the eye movements induced in BPPN. We found that in our patients the eyes rotate rather precisely in the plane of one posterior semicircular canal, suggesting that BPPN in our cases is indeed solely produced by the posterior semicircular canal.

Adult↗

PubMed1995

Three-dimensional eye movement analysis in benign paroxysmal positioning vertigo and nystagmus.

Benign paroxysmal positioning vertigo (BPPV) and nystagmus (BPPN) is the commonest type of rotational vertigo, but its origin is not fully understood. In this study we used search coils to measure 3-D eye position in 5 patients with BPPN. We present for the first time a complete three-dimensional description of the eye movements induced in BPPN. By calculating the eye movement direction in head co-ordinates we are able to relate the elicited nystagmus very precisely to a particular canal and thereby localize the lesion.

Adult↗

PubMed1994

The interactive contribution of neck muscle proprioception and vestibular stimulation to subjective "straight ahead" orientation in man.

Seventeen normal subjects were asked to direct a laser point to the position they felt to lie exactly straight ahead of their body. Subjects were seated in complete darkness in an approximately spherical cabin in an upright position with the orientation of the trunk and head aligned. For both the horizontal and vertical plane, "straight ahead" judgements were closely scattered around the objective straight ahead body position. Posterior neck muscle vibration as well as caloric vestibular stimulation with ice water led to (1) an apparent motion and horizontal displacement of a stationary visual target to the side opposite to stimulation and (2) a horizontal deviation of subjective "straight ahead" perception toward the side of stimulation. Only those subjects who experienced an illusion of target motion also showed a deviation of their subjective body orientation. No systematic effect of a displacement of subjective body orientation in the vertical plane was detected. When vestibular stimulation and neck muscle vibration were combined their effects were additive, i.e. the horizontal deviation of subjective body orientation observed when either type of stimulation was applied in isolation, was linearly combined either by summation or by cancellation. The present results clearly support the assumption that afferent visual, vestibular and proprioceptive input converge to the neural generation of an egocentric, body-centred coordinate system that allows us to determine our body position with respect to visual space.

Adult↗

PubMed1994

Oculomotor abnormalities and MRI findings in idiopathic cerebellar ataxia.

Extensive oculomotor testing and quantitative MRI evaluation was performed in seven patients with idiopathic cerebellar ataxia without extracerebellar symptoms (IDCA-C) and in ten patients with additional extracerebellar symptoms (IDCA-P). The most severe oculomotor deficits were disturbed smooth pursuit, optokinetic nystagmus and suppression of the vestibulo-ocular reflex (VOR). The symptoms correlated well and consistently with the amount of atrophy of the flocculus and the dorsal vermis. These correlations, however, were not specific, and deficits also correlated with the amount of atrophy of other cerebellar structures. No correlation was found between saccade velocity and brainstem atrophy or between saccade metrics and atrophy of the dorsal vermis. Although patients with IDCA-P had more severe oculomotor deficits than patients with IDCA-C, the pattern of the oculomotor disturbances was the same for both groups. Thus, eye movement analysis alone is not sufficient to distinguish between patients with pure cerebellar ataxia and those with additional extracerebellar symptoms.

Adult↗

PubMed1994

The influence of gravity on Donders' law for head movements.

Three-dimensional (3-D) head rotations were examined in seven human subjects when their bodies were inclined +/- 45 degrees in pitch and roll. The selection of 3-D orientations of the head while subjects looked at visual targets was similar to that seen previously for the eye: there was a small static counter pitch and counter roll of approx. 10%. Thus rotations of the head relative to the trunk are largely independent of the trunk's position relative to gravity and the head's torsional orientation is primarily dependent on its horizontal and vertical position relative to the trunk.

Eye Movements↗

PubMed1994

Testing models of the oculomotor velocity-to-position transformation.

1. Do neural computations in premotor circuits mirror the physical properties of the systems they control? In 1987, Tweed and Vilis showed that oculomotor theories where a neural integrator converts eye angular velocity commands into position commands cannot be correct, because angular position is not the integral of angular velocity. Recently Schnabolk and Raphan proposed that an angular velocity integrator is nevertheless used to generate tonic commands in the oculomotor system. Here we test the Schnabolk-Raphan (S-R) model against Tweed and Vilis's quaternion (Q) model of the velocity to position transformation. 2. The S-R model predicts large (up to 7 degrees) transient (approximately 700 ms) deviations ("blips") in torsional eye position during attempted horizontal and vertical saccades. The Q model predicts no blips. Search coil recordings of saccades by 7 normal human subjects showed no large blips. 3. For approximately 200 saccades by each subject, we plotted the area under the torsional blip versus the product of saccade eccentricity and magnitude. According to the S-R model, this graph should form a straight line with slope 1.00. According to the Q model, the slope should be zero. Measured slopes averaged 0.016 (range -0.073 to 0.061) for saccade targets at 20 degrees eccentricity and 0.040 (range 0.004-0.076) for targets at 40 degrees. 4. No parameter change can significantly improve the S-R model, but lowering one parameter eradicates the tiny inaccuracy in the Q model. We show that the fundamental reason for the S-R model's failure is its use of a commutative controller to steer a noncommutative plant.

Attention↗

PubMed1994

Rotational kinematics of the human vestibuloocular reflex. I. Gain matrices.

1. This series of three papers aims to describe the three-dimensional, kinematic input-output relations of the rotational vestibuloocular reflex (VOR) in humans, and to identify the functional advantages of these relations. In this first paper the response to sinusoidal rotation in darkness at 0.3 Hz, maximum speed 37.5%/s, was quantified by the use of the three-dimensional analogue of VOR gain: a 3 x 3 matrix where each element describes the dependence of one component (torsional, vertical, or horizontal) of eye velocity on one component of head velocity. 2. The three matrix elements indicating collinear gains (i.e., dependence of torsional eye velocity on torsional head velocity, vertical on vertical, and horizontal on horizontal) were smaller than the -1's required for optimal retinal image stabilization. Of these three the torsional gain was weakest: -0.37 for rotation about an earth-vertical axis, versus -0.73 and -0.64 for vertical and horizontal gains. Matrix elements indicating cross talk were mostly negligible. There was a tendency to leftward eye rotation in response to clockwise head motion, but this was not statistically significant. 3. VOR responses were compared for rotation about earth-vertical and earth-horizontal axes. The varying otolith input due to the rotation of the gravity vector relative to the head during earth-horizontal axis rotation made no difference to the collinear gains. 4. There were no consistent phase leads or lags except for a torsional phase lead of up to 10 degrees, usually more marked for clock-wise head rotation versus counterclockwise, and for oblique axis rotations versus purely torsional. 5. Torsional gain was magnified, averaging -0.52, when the torsional component of head rotation was only a small part of a predominantly vertical or horizontal rotation, i.e., when the axis of head rotation was near the frontal plane. Because most natural head rotations occur about such axes, the torsional VOR is probably somewhat stronger than the response to pure torsion would suggest. 6. The speed of eye rotation in response to a given stimulus varied widely among subjects, but the direction of rotation was much more uniform. For head rotations about oblique axes out of the frontal plane, there was a systematic misalignment of eye and head axes, with eye axes tilted toward the frontal plane. These findings can be explained on the basis of a strategy where the VOR balances the muscular effort of rotating the eyes against the cost of retinal slip.

Acceleration↗

PubMed1994

Rotational kinematics of the human vestibuloocular reflex. II. Velocity steps.

1. Gain matrices were used to quantify the three-dimensional vestibuloocular reflex (VOR) in five human subjects who were accelerated over 1 s and then spun at a constant 150 degrees/s for 29 s in darkness. Rotations were torsional, vertical and horizontal, about earth-vertical and earth-horizontal axes. 2. Elements on the main diagonal of the gain matrices were much smaller than the optimal value of -1, and torsional gain was weaker than vertical or horizontal. Off-diagonal elements, indicating cross talk, were minimal except for a small but consistent horizontal response to torsional head rotation. 3. Downward slow phases were more than twice as fast as upward at the start of rotation about both earth-vertical and earth-horizontal axes, but the asymmetry vanished later in the rotation. 4. During earth-vertical-axis rotation, all matrix elements decayed to zero. The main-diagonal torsional and vertical gains waned with time constants close to that of the cupula (6.7 and 7.3 s). Velocity storage prolonged the horizontal response to horizontal head rotation (time constant 14.2 s) but not the horizontal response to torsion (7.7 s). A simple explanation is that velocity storage acts on a central estimate of head motion that accurately distinguishes horizontal from torsional and that the inappropriate horizontal eye velocity response to torsion occurs because of cross talk downstream from velocity storage. 5. During earth-horizontal-axis rotation, the torsional, vertical, and horizontal main-diagonal elements declined, with time constants of 7.6, 8.2, and 7.9 s, to maintained nonzero values, all equal to about -0.1. Off-diagonal elements, including the horizontal response to torsion, decayed to zero, so that the otolith-driven reflex, late in the rotation, was equally strong in all dimensions and almost free of detectable cross talk. 6. The difference between gain curves over the course of earth-vertical- and earth-horizontal-axis rotations was not constant but increased with time, suggesting that the VOR response to earth-horizontal-axis rotation is not a simple sum of canal and otolith reflexes.

Acceleration↗

PubMed1994

Rotational kinematics of the human vestibuloocular reflex. III. Listing's law.

1. Do slow phase eye velocities generated by the vestibuloocular reflex (VOR) depend on eye position? If the purpose of the VOR is simply to stabilize the retinal image, there can be no such dependence, because eye velocity must always be equal and opposite to head velocity. But if the VOR tolerates some retinal slip to achieve other goals, such as reducing eye velocity or following Listing's law, then one should see specific patterns of dependence. We examined VOR responses of human subjects to yaw, pitch, and roll rotation looking in various directions to quantify how the input-output properties of the VOR vary with eye position. 2. Eye rotation axes during yaw and pitch tilted in the same direction as the gaze line but only one-quarter as far on average. Thus, during yaw head rotation, the axis of eye rotation was roughly aligned with the head axis when the subject looked straight ahead, but tilted up when the gaze direction was up, and down when gaze was down. The amount of tilt varied between subjects, but on average a 30 degrees change in eye position caused a 7.5 degrees tilt in the eye rotation axis. During pitch, the eye axis tilted right when gaze was right and left when gaze was left, also moving 7.5 degrees on average for a 30 degrees change in the gaze direction. 3. During roll stimulation, the axis of eye rotation tilted in the opposite direction to the gaze line, and about one-half as far. On average, when the gaze line moved 30 degrees down, the eye rotation axis tilted 12.0 degrees up; when the gaze moved 30 degrees left, the eye axis tilted 15.3 degrees right. 4. It is often argued that the torsional VOR is weak because head rotation about the line of sight causes little image displacement on the fovea. But the line of sight is collinear with the torsional axis only when the subject looks straight ahead. Does the "weak axis" of the VOR stay collinear with the gaze line when the subject looks eccentrically? We calculated the axis of head rotation for which the VOR response is weakest and found that it does vary with eye position, but does not stay parallel with the gaze direction. When subjects looked straight ahead, the weak axis was roughly collinear with the gaze line; when gaze shifted eccentrically, the weak axis shifted in the same direction but only about one-half as far.(ABSTRACT TRUNCATED AT 400 WORDS)

Acceleration↗

PubMed1994

Head position dependent adjustment of the three-dimensional human vestibuloocular reflex.

We studied the influence of static head position relative to the rotation axis on the three-dimensional (3-D) vestibuloocular reflex (VOR). By means of a 3-D rotating chair and a 3-D magnetic search-coil system, eye movements were recorded in 6 normal human subjects during sinusoidal rotation about an earth-vertical axis (yaw) with the head positioned at different pitch angles and about an earth-horizontal axis (pitch) with the head positioned at different yaw angles. We confirmed that torsional VOR gain is about 2/3 of horizontal and vertical VOR gain leading to non-collinear axes of eye and head rotation whenever torsional head movement components were present with eye movement axes tilting away from the torsional direction. Despite this non-collinearity of stimulus and eye movement rotation axes there was close to perfect adjustment of the different VOR components depending on the angle between gaze direction and stimulation axis, indicating a vectorial summation of gains obtained for rotations in the major body axes (roll, pitch and yaw). The horizontal and vertical eye movement components followed a cosine function of the angle between the plane of rotation and gaze direction. The torsional component followed a sine function.

Adult↗

PubMed1993

Late-onset Friedreich's ataxia. Molecular genetics, clinical neurophysiology, and magnetic resonance imaging.

OBJECTIVE--To clarify the nosological classification of late-onset Friedreich's ataxia (LOFA), ie, patients who have later onset of Friedreich's ataxia (FRDA), often after 25 years of age. DESIGN--Comparison of clinical examination data, nerve conduction studies, electronystagmographic recording, and magnetic resonance imaging of a family with LOFA with a group of patients with FRDA. Genetic linkage analysis was performed in the family with LOFA. SETTING--Referral center. PATIENTS--Thirteen patients satisfied classic diagnostic criteria of FRDA, and three patients from one family satisfied all diagnostic criteria of FRDA but with disease onset after 25 years. RESULTS--Results of nerve conduction studies, electronystagmographic recording, and magnetic resonance imaging in patients with LOFA closely corresponded to observations made in patients with FRDA. In addition, genetic linkage analysis using markers tightly linked to the FRDA locus on chromosome 9 showed that all affected members of the LOFA family, but not their unaffected siblings, had inherited identical paternal and maternal genotypes. CONCLUSIONS--Data suggest that LOFA may also result from mutation within the FRDA locus.

Adolescent↗

PubMed1993

Vestibular perception of passive whole-body rotation about horizontal and vertical axes in humans: goal-directed vestibulo-ocular reflex and vestibular memory-contingent saccades.

This study was aimed at complementing the existing knowledge about vestibular perception of self-motion in humans. Both goal-directed vestibulo-ocular reflex and vestibular memory-contingent saccade (VMCS) tasks were used, respectively as concurrent and retrospective magnitude estimators for passive whole-body rotation. Rotations were applied about the earth-vertical and earth-horizontal axes to study the effect of the otolith signal in self-rotation evaluation, and both in yaw and pitch to examine the horizontal and vertical semi-circular canals. Two different magnitudes of constant angular acceleration (50 degrees/s2 and 100 degrees/s2) were used. The main findings were (1) strong correlation between both oculomotor responses of both tasks, (2) greater accuracy with rotations about the earth-vertical than the earth: -horizontal axis, (3) greater accuracy for yaw than for pitch rotations, (4) greater accuracy for high acceleration than for low, and (5) no effect of the delay (2 s or 12 s) in the VMCS task. Adequacy of both tasks as subjective magnitude estimators of vestibular perception of self-motion is discussed.

Adult↗

PubMed1993

The influence of gravity on vestibular nystagmus in humans.

Traditionally the human vestibular system is tested by accelerations and decelerations in a rotating chair, stimulating the horizontal semicircular canals. This kind of testing provides no information about the performance or the two pairs of vertical (anterior and posterior) canals and the two pairs of otoliths. Testing the vestibulo-ocular reflex (VOR) in its entirety requires rotations around the 3 axis of the head (yaw, pitch and roll) as well as rotations where the axis is not aligned with gravity. The data presented here are, to our knowledge, the first measurements of the VOR in normal humans obtained with 3-dimensional high resolution recording techniques.

Eye Movements↗