Biomedical subjects
Publications and source records attributed to S Glasauer.
Intracellular granules containing ferric and ferrous iron formed in Shewanella putrefaciens CN32 during dissimilatory reduction of solid-phase ferric iron. It is the first in situ detection at high resolution (150 nm) of a mixed-valence metal particle residing within a prokaryotic cell. The relationship of the internal particles to Fe(III) reduction may indicate a respiratory role.
To investigate how visual and vestibular cues are integrated for the perception of gravity during passive self-motion, we measured the ability to maintain a handheld object vertical relative to gravity without visual feedback during sinusoidal roll-tilt stimulation. Visual input, either concordant or discordant with actual dynamic roll-tilt, was delivered by a head-mounted display showing the laboratory. The four visual conditions were darkness, visual-vestibular concordance, stationary visual scene, and a visual scene 180 degrees phase-shifted relative to actual tilt. Tilt-indication performance using a solid, cylindrical joystick was better in the presence of concordant visual input relative to the other visual conditions. In addition, we compared performance when indicating the vertical by the joystick or a full glass of water. Subjects indicated the direction of gravity significantly better when holding the full glass of water than the joystick. Matching the inertial characteristics, including fluid properties, of the handheld object to the glass of water did not improve performance. There was no effect of visual input on tilt performance when using the glass of water to indicate gravitational vertical. The gain of object tilt motion did not change with roll-tilt amplitude and frequency (+/-7.5 degrees at 0.25 Hz, +/-10 degrees at 0.16 Hz, and +/-20 degrees at 0.08 Hz), however, the phase of object tilt relative to subject tilt showed significant phase-leads at the highest frequency tested (0.25 Hz). Comparison of the object and visual effects observed suggest that the task-dependent behavior change may be due to an attentional shift and/or shift in strategy.
The authors evaluated floccular activity with fMRI during the performance of vertical smooth pursuit eye movements in four patients with downbeat nystagmus (DBN) due to cerebellar degeneration and in 16 healthy controls. Region of interest analysis revealed a significantly diminished activation of both floccular lobes during downward but not upward pursuit in DBN. These imaging data support the view that a functional deficiency of the flocculi in downward pursuit causes DBN.
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The increased postural sway of patients with disorders of the vestibular system improves with vision. The suppression of pathologic nystagmus also reduces sway. Because the latter effect cannot be attributed to retinal slip as a relevant feedback for postural control, the authors investigated how eye movements rather than retinal slip affect balance. They found that slow eye movements increase sway, possibly by an efference copy, which explains why spontaneous nystagmus causes postural imbalance.
The effect of the potassium channel blocker 4-aminopyridine (4-AP) on spontaneous upbeat nystagmus (UBN) was investigated with the search coil technique during fixation in different gaze positions and smooth pursuit in a patient before and after ingestion of 10 mg 4-AP. UBN was reduced from 8.6 deg/s to 2.0 deg/s by 4-AP causing subjective relief from distressing oscillopsia, and impaired upward smooth pursuit was restored (gains: before medication 0.38; after medication 0.86). In the dark, UBN was slightly stronger and not affected by 4-AP. We propose that 4-AP improved the function of cerebellar pathways that mediate gaze holding and smooth pursuit by intensifying the excitability of cerebellar Purkinje cells.
BACKGROUND: In a recent study, the authors found that blinks in healthy volunteers always triggered ocular torsion quick phases during dynamic roll movements of the head. On the basis of this observation, they hypothesized that blinks in patients with a vestibular tone imbalance would also trigger torsional quick phases. METHODS: Using video-oculography with a fixation target, the authors recorded the ocular torsion position of the left eye of 37 participants while they made voluntary blinks once every 6 to 10 seconds. The participants were recruited from four groups: two age groups of healthy volunteers with a mean +/- SD age of 32 +/- 4 (n = 9) and 65 +/- 11 y (n = 9); patients with a unilateral vestibular disorder in an acute state (n = 12, 53 +/- 17 y); and those in a persisting state in which spontaneous nystagmus had already faded (n = 9, 65 +/- 13 y). RESULTS: In the control groups of healthy volunteers, blinks triggered no or only small quick phases on the order of 0.1 deg. In both patient groups blinks always triggered quick phases with significantly higher amplitudes of 1.85 +/- 1.02 deg and were followed by exponentially decaying slow-phases with time constants on the order of 1 to 2 seconds. Patients in the persisting state clearly differed from patients in the acute state in that their torsional spontaneous nystagmus had already vanished due to vestibular compensation. But surprisingly, these two groups did not show a large difference in terms of the effect of blinks on ocular torsion. The authors always observed torsional quick phases with the upper pole of the eye beating away from the side of the lesion. CONCLUSIONS: Blinks are able to trigger torsional quick phases in patients with both acute and persisting vestibular disorders. The side of the impairment can be determined from the direction in which the eye is rotated after a blink. Thus, ocular torsion recordings during blinks can be used as a simple clinical test for a vestibular tone imbalance, particularly during a persisting failure in which spontaneous nystagmus has resolved and can therefore no longer be used for diagnosis.
Patients with episodic ataxia type 2 (EA2) can often be successfully treated with acetazolamide. The authors report three patients with EA2 (two with proven mutations in the CACNA1A gene) whose attacks were prevented with the potassium channel blocker 4-aminopyridine (4-AP; 5 mg tid). Attacks recurred after treatment was stopped; subsequent treatment alleviated the symptoms (mean follow-up time 6 months). These effects might be due to an improvement of the impaired functioning of Purkinje cells.
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A patient with anterior semicircular canal dehiscence syndrome underwent surgical patching that caused an isolated dysfunction of the left anterior semicircular canal postoperatively. He exhibited significant ocular torsion toward the side of the affected labyrinth (17 degrees excyclotropia of the ipsilateral eye), but no displacement of the subjective visual vertical. This dissociation suggests that an isolated ocular torsion may occur after an anterior semicircular canal lesion. A combined ocular torsion and subjective visual vertical tilt, which is usually seen with vestibular lesions, requires an associated otolith dysfunction.
Downbeat nystagmus (DN), a fixation nystagmus with the fast phases directed downward, is usually caused by cerebellar lesions, but the precise etiology is not known. A disorder of the smooth-pursuit system or of central vestibular pathways has been proposed. However, both hypotheses fail to explain why DN is usually accompanied by gaze-holding nystagmus, which implies a leaky neural velocity-to-position integrator. Because three-dimensional (3-D) analysis of nystagmus slow phases provides an excellent means for testing both hypotheses, we examined 19 patients with DN during a fixation task and compared them with healthy subjects. We show that the presentation of DN patients is not uniform; they can be grouped according to their deficits: DN with vertical integrator leakage, DN with vertical and horizontal integrator leakage, and DN without integrator leakage. The 3-D analysis of the slow phases of DN patients revealed that DN is most likely neither caused by damage to central vestibular pathways carrying semicircular canal information nor by a smooth pursuit imbalance. We propose that the observed effects can be explained by partial damage of a brain stem-cerebellar loop that augments the time constant of the neural velocity to position integrators in the brain stem and neurally adjusts the orientation of Listing's plane.
The rostral fastigial nucleus contains vestibular neurons, which presumably are involved in spinal mechanisms (neck, gait, posture) and which are not modulated with individual eye movements. Single-unit recordings in the alert behaving monkey during natural stimulus conditions reveal that virtually all neurons demonstrate integration of several sensory inputs. This applies not only for canal-canal and canal-otolith interaction, but also for otolith-otolith interaction. There is also some evidence that most neurons receive not only an utriculus but also a sacculus input. Furthermore, most neurons also respond to large-field optokinetic stimulation, reflecting visual-vestibular interaction. Neurons are also affected by the head on trunk position, which would allow these neurons to operate in a body-centered rather than a head-centered reference frame. These complex, multisensory features could permit fastigial nucleus neurons to rather specifically affect spinal motor functions.
The eye movement component that rotates around the line of sight, i.e., the ocular torsion, is in many aspects different from horizontal and vertical eye movements. While ocular torsion is mediated only by reflexive pathways like the torsional vestibulo-ocular and optokinetic reflexes (TVOR and OKN, respectively), horizontal and vertical components are also subject to intentional control mechanisms that are mediated by the saccadic and the pursuit systems. Dynamic properties of torsional eye movements are also very distinct. While horizontal and vertical VOR components show a gain close to unity and a small neural integration leakage with a time constant around pi=30 s, the TVOR shows a smaller gain of 0.4 and also a greater leakage with pi=2 s. During slow head rotations in roll, the TVOR is even less compensatory. At small stimulation levels the gain drops to a value of 0.2 and proves thus to be nonlinear, i.e., to depend on the stimulus magnitude. In a recent study, we hypothesized that this nonlinearity might be the result of a nonlinear processing of nystagmus quick phases rather than a nonlinearity in direct or integrator TVOR pathways. In the present study, we experimentally tested this hypothesis by measuring ocular torsion responses at different head rotation speeds. In addition to the conventional approach of analyzing slow-phase velocity (SPV) gains, we also analyzed properties of nystagmus quick phases. This method proved to be suitable for determining whether nonlinear processing of nystagmus frequency is responsible for the TVOR nonlinearity.
While we walk through the environment, we constantly receive inputs from different sensory systems. For us to accomplish a given task, for example to reach a target location, the sensory information has to be integrated to update our knowledge of self-position and self-orientation with respect to the target so that we can correctly plan and perform the remaining trajectory. As has been shown previously, vestibular information plays a minor role in the performance of linear goal-directed locomotion when walking blindfolded toward a previously seen target within a few meters. The present study extends the question of whether vestibular information is a requirement for goal-directed locomotion by studying a more complex task that also involves rotation: walking a triangular path. Furthermore, studying this task provides information about how we walk a given trajectory, how we move around corners, and whether we are able to return to the starting point. Seven young male, five labyrinthine-defective (LD) and five age- and gender-matched control subjects were asked to walk a previously seen triangular path, which was marked on the ground, first without vision (EC) and then with vision (EO). Each subject performed three clockwise (CW) and three counterclockwise (CCW) walks under the EC condition and one CW and CCW walk under the EO condition. The movement of the subjects was recorded by means of a 3D motion analysis system. Analysis of the data showed that LD subjects had, in the EC condition, a significantly larger final arrival error, which was due to increased directional errors during the turns. However, there was no difference between the groups as regards the overall path length walked. This shows that LD subjects were able to plan and execute the given trajectory without vision, but failed to turn correctly around the corners. Hence, the results demonstrate that vestibular information enhances the ability to perform a planned trajectory incorporating whole body rotations when no visual feedback is available.
To determine the contribution of the otoliths as well as the horizontal and vertical semicircular canals to the response of "vestibular only" neurons in the rostral fastigial nucleus of the alert monkey, we applied natural sinusoidal vestibular stimuli (0.6 Hz; +/-15 deg) around different axes. During the experiment the monkey sat erect in a primate chair with the head immobile. Semicircular canal responses were investigated during tilted yaw stimulation around an earth vertical axis. The tilt angle was varied by 30 deg and included the optimal plane for horizontal canal stimulation (15 deg nose down from the stereotactic plane). The otoliths and mainly the vertical canals made contributions during stimulation around an earth-fixed horizontal axis (vertical stimulation). Head orientation was also slowly altered (2-3 deg/s) over a range of 180 deg under both stimulus conditions (tilted yaw and vertical stimulation). Neuronal data for each paradigm were fitted by a least squares best-sine function. Computation of the hypothetical contributions made by all three pairs of semicircular canals and the otoliths to these responses showed that 74% of the 46 neurons investigated received an otolith input; in most instances it was combined with a canal input. Neurons most often received input from the horizontal and vertical canals as well as the otoliths. Only a minority of neurons received a purely otolith (13%), vertical canal (13%), or horizontal canal (4%) input. Conventional criteria (head position-related activity, spatiotemporal convergence, STC) failed to detect an otolith contribution in several such instances. Thus, canal-otolith convergence is the general rule at this central stage of vestibular information processing in the fastigial nucleus. The large variety of response types allows these neurons to participate in multiple tasks of vestibulospinal movement control.
Grip force adjustments to fluctuations of inertial loads induced by vertical arm movements with a grasped object were analysed during normal and impaired finger sensibility. Normally grip force is modulated in a highly economical way in parallel with fluctuations of load force. Two subjects performed vertical up and down movements of a grasped object, both with normal finger sensibility and then cutaneously anaesthetized finger sensibility. Short breaks were taken in between single movements, during which the object was held stationary. After digital anaesthesia was applied to the grasping fingers, both subjects substantially increased the grip force. The grip force amplitude and timing still anticipated changes in load force, although the established grip force had already overcome movement-induced load force peaks. This implies that the increase of grip force and consequently the elevated force ratio between maximum grip and maximum load force are not processed to alter the feedforward system of grip force control. Cutaneous afferent information from the grasping digits appears to be necessary for economic scaling of the grip force level, but it plays a subordinate role in the precise anticipatory temporal coupling of grip and load forces during voluntary object manipulation.
Previous models of ocular counterroll assumed that static eye position was controlled by direct brainstem pathways from the vestibular nuclei via the ocular motor nuclei to the extraocular eye muscles. However, recent experimental evidence has shown that the interstitial nucleus of Cajal (INC), known as the vertical-torsional velocity-to-position integrator, plays a crucial role in torsional otolith-dependent eye position, i.e. for the modification of Listing's plane by static head tilts. To evaluate possible mechanisms by which otolithic input may influence eye position via the INC, we constructed a 3D mathematical model of saccade and nystagmus generation. The model includes the burst generators located in the rostral interstitial nucleus of the medial longitudinal fasciculus (MLF) and paramedian pontine reticular formation and the velocity-to-position integrators located in the INC and prepositus hypoglossi. The model simulations suggest that otolith pathways to the neural integrator that adjust Listing's plane may involve the cerebellum.
We investigated the quality of predictive grip force control during gravity changes induced by parabolic flight maneuvers. During these maneuvers gravity varied: There were 2 periods of hypergravity, in which terrestrial gravity nearly doubled, and a 20-s period of microgravity, during which a manipulated object was virtually weightless. We determined grip and load forces during vertical point-to-point movements of an instrumented object. Point-to-point movements were a combination of static (stationary holding) and dynamic (continuous movements) task conditions, which were separately analyzed in our previous studies. Analysis of the produced grip forces revealed that grip adjustments were closely linked to load force fluctuations under each gravity condition. In particular, grip force maxima coincided closely in time with load force peaks, although these occurred at different phases of the movement depending on the gravity level. However, quantitative analysis of the ratio of maximum grip force to the corresponding load force peak revealed an increased force ratio during microgravity when compared to that during normal and hypergravity. We hypothesize that the impaired precision of force coupling with respect to force magnitude during microgravity results from reduced feedback information about the object's mass during the stationary holding of the object in between each movement. The results indicate that the temporal grip force regulation is highly automatized and stable, whereas economical planning of force magnitude is more flexible and might reflect changes of the external loading condition.