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Biomedical subjects

Daniel M Merfeld

Publications and source records attributed to Daniel M Merfeld.

11 recordsLinked to original sources

Roll rotation cues influence roll tilt perception assayed using a somatosensory technique.

We investigated how the nervous system processes ambiguous cues from the otolith organs by measuring roll tilt perception elicited by two motion paradigms. In one paradigm (tilt), eight subjects were sinusoidally tilted in roll with the axis of rotation near ear level. Stimulus frequencies ranged from 0.005 to 0.7 Hz, and the peak amplitude of tilt was 20 degrees . During this paradigm, subjects experienced a sinusoidal variation of interaural gravitational force with a peak of 0.34 g. The second motion paradigm (translation) was designed to yield the same sinusoidal variation in interaural force but did not include a roll canal cue. This was achieved by sinusoidally translating the subjects along their interaural axis. For the 0.7-Hz translation trial, the subjects were simply translated from side to side. A centrifuge was used for the 0.005- to 0.5-Hz translation trials; the subjects were rotated in yaw at 250 degrees /s for 5 min before initiating sinusoidal translations yielding an interaural otolith stimulus composed of both centrifugal and radial acceleration. Using a somatosensory task to measure roll tilt perception, we found substantial differences in tilt perception during the two motion paradigms. Because the primary difference between the two motion paradigms was the presence of roll canal cues during roll tilt trials, these perceptual differences suggest that canal cues influence tilt perception. Specifically, rotational cues provided by the semicircular canals help the CNS resolve ambiguous otolith cues during head tilt, yielding more accurate tilt perception.

Adult↗

Visual mental imagery during caloric vestibular stimulation.

We investigated high-resolution mental imagery and mental rotation, while the participants received caloric vestibular stimulation. High-resolution visual mental imagery tasks have been shown to activate early visual cortex, which is deactivated by vestibular input. Thus, we predicted that vestibular stimulation would disrupt high-resolution mental imagery; this prediction was confirmed. In addition, mental rotation tasks have been shown to activate posterior parietal cortex, which is also engaged in the processing of vestibular stimulation. As predicted, we also found that mental rotation is impaired during vestibular stimulation. In contrast, such stimulation did not affect performance of a low-imagery control task. These data document previously unsuspected interactions between the vestibular system and the high-level visual system.

Adult↗

Acclimation to chronic constant-rate peripheral stimulation provided by a vestibular prosthesis.

We are developing two types of vestibular prosthetics that electrically stimulate afferent neurons. One type replaces absent sensory function by providing stimulation that modulates above and below a baseline established with the head stationary. The other type provides constant stimulation and is turned on only when necessary, for example, to override unnatural variations like those experienced by patients suffering from Ménère's syndrome; this prosthesis does not provide motion information. Both prostheses require neural plasticity, which we investigated by providing chronic constant-rate stimulation to semicircular canal neurons in three guinea pigs. The stimulation was alternately switched on or off for eight consecutive weeks before being switched daily. A brisk horizontal nystagmus was measured when the stimulation was first turned on and then dissipated over the course of a day. The nystagmus demonstrated an after-effect in the opposite direction when the stimulation was turned off. The nystagmus that we measured after just a few (2 to 5) off-to-on transitions returned to baseline more rapidly than when first turned on. In fact, after many such off-to-on or on-to-off transitions, little nystagmus was evoked by turning the stimulation on or off. These findings show that the brain acclimates to constant-rate stimulation.

Acclimatization↗

Vestibular perception and action employ qualitatively different mechanisms. I. Frequency response of VOR and perceptual responses during Translation and Tilt.

To investigate the neural mechanisms that humans use to process the ambiguous force measured by the otolith organs, we measured vestibuloocular reflexes (VORs) and perceptions of tilt and translation. One primary goal was to determine if the same, or different, mechanisms contribute to vestibular perception and action. We used motion paradigms that provided identical sinusoidal inter-aural otolith cues across a broad frequency range. We accomplished this by sinusoidally tilting (20 degrees, 0.005-0.7 Hz) subjects in roll about an earth-horizontal, head-centered, rotation axis ("Tilt") or sinusoidally accelerating (3.3 m/s2, 0.005-0.7 Hz) subjects along their inter-aural axis ("Translation"). While identical inter-aural otolith cues were provided by these motion paradigms, the canal cues were substantially different because roll rotations were present during Tilt but not during Translation. We found that perception was dependent on canal cues because the reported perceptions of both roll tilt and inter-aural translation were substantially different during Translation and Tilt. These findings match internal model predictions that rotational cues from the canals influence the neural processing of otolith cues. We also found horizontal translational VORs at frequencies >0.2 Hz during both Translation and Tilt. These responses were dependent on otolith cues and match simple filtering predictions that translational VORs include contributions via simple high-pass filtering of otolith cues. More generally, these findings demonstrate that internal models govern human vestibular "perception" across a broad range of frequencies and that simple high-pass filters contribute to human horizontal translational VORs ("action") at frequencies above approximately 0.2 Hz.

Adult↗

Vestibular perception and action employ qualitatively different mechanisms. II. VOR and perceptual responses during combined Tilt&Translation.

To compare and contrast the neural mechanisms that contribute to vestibular perception and action, we measured vestibuloocular reflexes (VOR) and perceptions of tilt and translation. We took advantage of the well-known ambiguity that the otolith organs respond to both linear acceleration and tilt with respect to gravity and investigated the mechanisms by which this ambiguity is resolved. A new motion paradigm that combined roll tilt with inter-aural translation ("Tilt&Translation") was used; subjects were sinusoidally (0.8 Hz) roll tilted but with their ears above or below the rotation axis. This paradigm provided sinusoidal roll canal cues that were the same across trials while providing otolith cues that varied linearly with ear position relative to the earth-horizontal rotation axis. We found that perceived tilt and translation depended on canal cues, with substantial roll tilt and inter-aural translation perceptions reported even when the otolith organs measured no inter-aural force. These findings match internal model predictions that rotational cues from the canals influence the neural processing of otolith cues. We also found horizontal translational VORs that varied linearly with radius; a minimal response was measured when the otolith organs transduced little or no inter-aural force. Hence, the horizontal translational VOR was dependent on otolith cues but independent of canal cues. These findings match predictions that translational VORs are elicited by simple filtering of otolith signals. We conclude that internal models govern human perception of tilt and translation at 0.8 Hz and that high-pass filtering governs the human translational VOR at this same frequency.

Acceleration↗

Tilt psychophysics measured in nonhuman primates.

A method to measure tilt psychophysics in nonhuman primates has been developed and tested. Two rhesus monkeys were trained to orient a light bar parallel to the direction of gravity by rotating a small steering wheel attached to the primate chair. After adequate training, they performed this task during motion paradigms that rotated the gravitoinertial force (GIF) in the roll plane. The animals accurately aligned the light bar with the direction of gravity during and following roll tilts. Subtle aspects of perceived roll tilt previously recorded in human subjects were also observed in the monkeys. During centrifugation and linear translation, an interaural inertial force rotates the GIF in the roll plane. Similar to humans, the animals' perceived direction of gravity shifted toward alignment with the GIF during these paradigms, and the dynamics of these shifts demonstrated an interaction between the otolith afferents that transduce the GIF and rotational cues from the semicircular canals. Finally, optokinetic roll stimulation induced an illusion of roll tilt that was dependent on head orientation, similar to results described in human subjects. Taken together, these findings validate the methodology employed to measure tilt psychophysics; the monkeys' responses were qualitatively similar to those described in human subjects and also recapitulated subtle aspects of the perceptual response observed in humans. This new methodology sets the stage for innovative experimental approaches that will help to elucidate the neural mechanisms underlying the perception of spatial orientation.

Animals↗

Human ocular torsion and perceived roll responses to linear acceleration.

We investigated if human ocular torsion (OT) and perceived roll (PR) are elicited in response to either dynamic interaural linear acceleration or dynamic roll tilt of the gravito-inertial force (GIF). We expanded a previous study [26] that measured only OT across a limited frequency-range (from 0.35 Hz to 1 Hz) by simultaneously measuring OT and PR at three very low (0.01, 0.02 and 0.05 Hz) and one high (1 Hz) frequencies. Three experimental conditions were investigated: (1) Y-Upright with acceleration along the interaural (Y) axis while upright, (2) Y-Supine with acceleration along the Y-axis while supine, and (3) Z-RED with acceleration along the rostro-caudal Z) axis with right-ear-down (RED). OT was measured by video-oculography, while PR was measured by use of a somatosensory bar. OT and PR were qualitatively different. Large OT responses were measured for Y-Upright and Y-Supine, while large perceived roll responses were observed for Y-Upright and Z-RED. OT for Z-RED was small, and PR for Y-Supine was absent. In conclusion, OT and PR appear governed by qualitatively different neural mechanisms. OT appears mostly influenced by central low-pass filtering of interaural graviceptor cues, while PR appears mostly influenced by roll tilt of the GIF.

Acceleration↗

Origin of orientation-dependent asymmetries in vestibulo-ocular reflexes evoked by caloric stimulation.

A caloric stimulus evokes primarily a horizontal vestibulo-ocular reflex (VOR) when subjects are in a supine or prone orientation with the horizontal semicircular canal plane oriented vertically. In both monkeys and humans, the magnitude of VOR eye movements is greater in the supine than in the prone orientation, indicating that some factor or factors, other than the conventionally accepted convective stimulation of the horizontal canals, contributes to the generation of the VOR. We used long-duration caloric irrigations and mathematical models of canal-otolith interactions to investigate factors contributing to the prone/supine asymmetry. Binaural caloric irrigations were applied for 7.5 or 9.5 min with subjects in a null orientation with horizontal canals in the earth-horizontal plane (control trial), or with the subject's pitch orientation periodically changing between null, supine, and prone positions with each orientation held for 30 s (caloric step trial). The control trial responses identified a small response attributable to a direct thermal effect on vestibular afferent activity that accounted for only 15% of the observed prone/supine asymmetry. We show that the gravito-inertial force resolution hypothesis for sensory integration of canal and otolith information predicts that the central processing of canal and otolith information produces an internal estimate of motion that includes both a rotational motion component and a linear acceleration component. These components evoke a horizontal angular VOR and linear VOR, which combine additively in the supine orientation, but subtract in the prone orientation, thus accounting for the majority of the observed prone/supine asymmetry.

Adult↗

Rotation otolith tilt-translation reinterpretation (ROTTR) hypothesis: a new hypothesis to explain neurovestibular spaceflight adaptation.

Normally, the nervous system must process ambiguous graviceptor (e.g., otolith) cues to estimate tilt and translation. The neural processes that help perform these estimation processes must adapt upon exposure to weightlessness and readapt upon return to Earth. In this paper we present a review of evidence supporting a new hypothesis that explains some aspects of these adaptive processes. This hypothesis, which we label the rotation otolith tilt-translation reinterpretation (ROTTR) hypothesis, suggests that the neural processes resulting in spaceflight adaptation include deterioration in the ability of the nervous system to use rotational cues to help accurately estimate the relative orientation of gravity ("tilt"). Changes in the ability to estimate gravity then also influence the ability of the nervous system to estimate linear acceleration ("translation"). We explicitly hypothesize that such changes in the ability to estimate "tilt" and "translation" will be measurable upon return to Earth and will, at least partially, explain the disorientation experienced when astronauts return to Earth. In this paper, we present the details and implications of ROTTR, review data related to ROTTR, and discuss the relationship of ROTTR to the influential otolith tilt-translation reinterpretation (OTTR) hypothesis as well as discuss the distinct differences between ROTTR and OTTR.

Adaptation, Physiological↗

System design and performance of a unilateral horizontal semicircular canal prosthesis.

We have reported preliminary results regarding a prototype semicircular canal prosthesis and concluded that it can provide rotational cues to the nervous system. This paper presents the system design of the prosthesis, and also reports the prosthesis system performance and effectiveness. The prosthesis delivers electrical pulses to the nerve branch innervating the horizontal semicircular canal on one side via implanted electrodes. To allow us to encode both directions of angular velocity, the baseline stimulation pulse frequency was set at 150 Hz, which is somewhat higher than the average firing rate of afferents innervating the semicircular canals in normal guinea pigs (approximately 60Hz). A sensor measures angular velocity to modulate (increase or decrease) the pulse rate. The prosthetic system was provided to a guinea pig whose horizontal canals were surgically plugged. The animal responded to the baseline stimulation initially and adapted to the baseline stimulation in roughly one day. After this baseline adaptation the animal responded to yaw rotation, showing that the function of the canals was partially restored. The experiments also show that the nervous system adapts to the artificial rotational cue provided via electrical stimulation.

Animals↗

Vestibular adaptation studied with a prosthetic semicircular canal.

We have developed and tested a prosthetic semicircular canal that senses angular head velocity and uses this information to modulate the rate of current pulses applied to the vestibular nerve via a stimulating electrode. In one squirrel monkey, the lateral canals were plugged bilaterally and the prosthesis was secured to the animal's head with the angular velocity sensor parallel to the axis of the lateral canals. In the first experiment, the stimulating electrode was placed near the ampullary nerve of one lateral canal. Over a period of two weeks, the gain of the horizontal VOR during yaw axis rotation gradually increased, although the response magnitude remained relatively small. In the second experiment, the stimulating electrode was placed near the ampullary nerve of the posterior canal, but the orientation of the velocity sensor remained parallel to the axis of the lateral canals. Over a one-week period, the axis of the VOR response gradually shifted towards alignment with the (yaw) axis of head rotation. Chronic patterned stimulation of the eighth nerve can therefore provide adequate information to the brain to generate a measurable VOR response, and this can occur even if the prosthetic yaw rotation cue is provided via a branch of the VIIIth nerve that doesn't normally carry yaw rotational cues. The results provided by this pilot study suggest that it may be feasible to study central adaptation by chronically modifying the afferent vestibular cue with a prosthetic semicircular canal.

Adaptation, Physiological↗