Symptom reduction in mal de débarquement syndrome with attenuation of the velocity storage contribution in the central vestibular pathways.

Background: The velocity storage mechanism of the central vestibular system is closely associated with the vestibulo-ocular reflex (VOR), but also contributes to the sense of orientation in space and the perception of self-motion. We postulate that mal de débarquement syndrome (MdDS) is a consequence of inappropriate sensory adaptation of velocity storage. The premise that a maladapted velocity storage may be corrected by spatial readaptation of the VOR has recently been translated into the development of the first effective treatment for MdDS.

Treatment of Gravitational Pulling Sensation in Patients With Mal de Debarquement Syndrome (MdDS): A Model-Based Approach.

Perception of the spatial vertical is important for maintaining and stabilizing vertical posture during body motion. The velocity storage pathway of vestibulo-ocular reflex (VOR), which integrates vestibular, optokinetic, and proprioception in the vestibular nuclei vestibular-only (VO) neurons, has spatio-temporal properties that are defined by eigenvalues and eigenvectors of its system matrix. The yaw, pitch and roll eigenvectors are normally aligned with the spatial vertical and corresponding head axes.

Predicting Vasovagal Responses: A Model-Based and Machine Learning Approach.

Vasovagal syncope () or neurogenically induced fainting has resulted in falls, fractures, and death. Methods to deal with are to use implanted pacemakers or beta blockers. These are often ineffective because the underlying changes in the cardiovascular system that lead to the syncope are incompletely understood and diagnosis of frequent occurrences of is still based on history and a tilt test, in which subjects are passively tilted from a supine position to 20° from the spatial vertical (to a 70° position) on the tilt table and maintained in that orientation for 10-15 min.

Vestibular, locomotor, and vestibulo-autonomic research: 50 years of collaboration with Bernard Cohen.

My collaboration on the vestibulo-ocular reflex with Bernard Cohen began in 1972. Until 2017, this collaboration included studies of saccades, quick phases of nystagmus, the introduction of the concept of velocity storage, the relationship of velocity storage to motion sickness, primate and human locomotion, and studies of vasovagal syncope. These studies have elucidated the functioning of the vestibuloocular reflex, the locomotor system, the functioning of the vestibulo-sympathetic reflex, and how blood pressure and heart rate are controlled by the vestibular system.

Modeling Interval Timing by Recurrent Neural Nets.

The purpose of this study was to take a new approach in showing how the central nervous system might encode time at the supra-second level using recurrent neural nets (RNNs). This approach utilizes units with a delayed feedback, whose feedback weight determines the temporal properties of specific neurons in the network architecture. When these feedback neurons are coupled, they form a multilayered dynamical system that can be used to model temporal responses to steps of input in multidimensional systems.

Coding of Velocity Storage in the Vestibular Nuclei.

Semicircular canal afferents sense angular acceleration and output angular velocity with a short time constant of ≈4.5 s. This output is prolonged by a central integrative network, velocity storage that lengthens the time constants of eye velocity.

Vestibular Activation Habituates the Vasovagal Response in the Rat.

Vasovagal syncope is a significant medical problem without effective therapy, postulated to be related to a collapse of baroreflex function. While some studies have shown that repeated static tilts can block vasovagal syncope, this was not found in other studies. Using anesthetized, male Long-Evans rats that were highly susceptible to generation of vasovagal responses, we found that repeated activation of the vestibulosympathetic reflex (VSR) with ±2 and ±3 mA, 0.

The response of the vestibulosympathetic reflex to linear acceleration in the rat.

The vestibulosympathetic reflex (VSR) increases blood pressure (BP) upon arising to maintain blood flow to the brain. The optimal directions of VSR activation and whether changes in heart rate (HR) are associated with changes in BP are still not clear. We used manually activated pulses and oscillatory linear accelerations of 0.

A Model of Blood Pressure, Heart Rate, and Vaso-Vagal Responses Produced by Vestibulo-Sympathetic Activation.

Blood Pressure (BP), comprised of recurrent systoles and diastoles, is controlled by central mechanisms to maintain blood flow. Periodic behavior of BP was modeled to study how peak amplitudes and frequencies of the systoles are modulated by vestibular activation. The model was implemented as a relaxation oscillator, driven by a central signal related to Desired BP.

Vasovagal oscillations and vasovagal responses produced by the vestibulo-sympathetic reflex in the rat.

Sinusoidal galvanic vestibular stimulation (sGVS) induces oscillations in blood pressure (BP) and heart rate (HR), i.e., vasovagal oscillations, as well as transient decreases in BP and HR, i.

The vasovagal response of the rat: its relation to the vestibulosympathetic reflex and to Mayer waves.

Vasovagal responses (VVRs) are characterized by transient drops in blood pressure (BP) and heart rate (HR) and increased amplitude of low-frequency oscillations in the Mayer wave frequency range. Typical VVRs were induced in anesthetized, male, Long-Evans rats by sinusoidal galvanic vestibular stimulation (sGVS). VVRs were also produced by single sinusoids that transiently increased BP and HR, by 70-90° nose-up tilts, and by 60° tilts of the gravitoinertial acceleration vector using translation while rotating (TWR).

Modeling spatial tuning of adaptation of the angular vestibulo-ocular reflex.

Gain adaptation of the yaw angular vestibular ocular reflex (aVOR) induced in side-down positions has gravity-independent (global) and -dependent (localized) components. When the head oscillation angles are small during adaptation, localized gain changes are maximal in the approximate position of adaptation. Concurrently, polarization vectors of canal-otolith vestibular neurons adapt their orientations during these small-angle adaptation paradigms.

Orientation adaptation of eye movement-related vestibular neurons due to prolonged head tilt.

Sixteen neurons, including vestibular-only (VO), eye-head velocity (EHV), and position-vestibular-pause (PVP) neurons sensitive to head tilt were recorded in the rostromedial and in superior vestibular nuclei. Projection of the otolith polarization vector to the horizontal plane (response vector orientation [RVO]) was determined before and after prolonged head orientation in side-down position. The RVO of VO neurons shifted toward alignment with the axis of gravity when the head was in the position of adaptation.

Motion sickness on tilting trains.

Trains that tilt on curves can go faster, but passengers complain of motion sickness. We studied the control signals and tilts to determine why this occurs and how to maintain speed while eliminating motion sickness. Accelerometers and gyros monitored train and passenger yaw and roll, and a survey evaluated motion sickness.

Sinusoidal galvanic vestibular stimulation (sGVS) induces a vasovagal response in the rat.

Blood pressure (BP) and heart rate (HR) were studied in isoflurane-anesthetized Long-Evans rats during sinusoidal galvanic vestibular stimulation (sGVS) and sinusoidal oscillation in pitch to characterize vestibular influences on autonomic control of BP and HR. sGVS was delivered binaurally via Ag/AgCl needle electrodes inserted over the mastoids at stimulus frequencies 0.008-0.

Spatial orientation of the angular vestibulo-ocular reflex (aVOR) after semicircular canal plugging and canal nerve section.

We investigated spatial responses of the aVOR to small and large accelerations in six canal-plugged and lateral canal nerve-sectioned monkeys. The aim was to determine whether there was spatial adaptation after partial and complete loss of all inputs in a canal plane. Impulses of torques generated head thrusts of ≈ 3,000°/s².

Prolonged reduction of motion sickness sensitivity by visual-vestibular interaction.

The angular vestibulo-ocular reflex (aVOR) and optokinetic nystagmus (OKN) were elicited simultaneously at low frequencies to study effects of habituation of the velocity storage time constant in the vestibular system on motion sickness. Twenty-nine subjects, eleven of whom were susceptible to motion sickness from common transportation, were habituated by sinusoidal rotation at 0.017 Hz at peak velocities from 5 to 20°/s, while they watched a full-field OKN stimulus.

Complementary gain modifications of the cervico-ocular (COR) and angular vestibulo-ocular (aVOR) reflexes after canal plugging.

To determine whether the COR compensates for the loss of aVOR gain, independent of species, we studied cynomolgus and rhesus monkeys in which all six semicircular canals were plugged. Gains and phases of the aVOR and COR were determined at frequencies ranging from 0.02 to 6 Hz and fit with model-based transfer functions.

Motion sickness induced by off-vertical axis rotation (OVAR).

We tested the hypothesis that motion sickness is produced by an integration of the disparity between eye velocity and the yaw-axis orientation vector of velocity storage. Disparity was defined as the magnitude of the cross product between these two vectors. OVAR, which is known to produce motion sickness, generates horizontal eye velocity with a bias level related to velocity storage, as well as cyclic modulations due to re-orientation of the head re gravity.

Frequency-velocity mismatch: a fundamental abnormality in parkinsonian gait.

Gait dysfunction and falling are major sources of disability for patients with advanced Parkinson's disease (PD). It is presently thought that the fundamental defect is an inability to generate normal stride length. Our data suggest, however, that the basic problem in PD gait is an impaired ability to match step frequency to walking velocity.

Dependence of the roll angular vestibuloocular reflex (aVOR) on gravity.

Little is known about the dependence of the roll angular vestibuloocular reflex (aVOR) on gravity or its gravity-dependent adaptive properties. To study gravity-dependent characteristics of the roll aVOR, monkeys were oscillated about a naso-occipital axis in darkness while upright or tilted. Roll aVOR gains were largest in the upright position and decreased by 7-15% as animals were tilted from the upright.

Effects of the linear vestibulo-ocular reflex on accommodative vergence eye movements.

The aim of the study was to determine whether accommodation to the relative motion of a target along the visual axis of one eye during fore-aft movement of the head could induce accurate vergence over a wide range of viewing distances and frequencies of oscillation, despite lack of vision in the second eye. This was compared to the vergence when both eyes viewed the target. Two rhesus monkeys were trained to fixate a visual target located 216-336 mm in front and along the visual axis of one eye, while being sinusoidally translated in the fore-aft direction.

Adaptation of orientation of central otolith-only neurons.

Otolith-only neurons were recorded extracellularly in the vestibular nuclei before and after cynomolgus monkeys were held on-side for up to 3 hr. The aim was to determine whether the polarization vectors of these neurons reorient toward the spatial vertical as do canal-otolith convergent neurons. Otolith input was characterized by tilting the animal 30 degrees from the upright position while positioning the head in different directions in yaw.

Effect of canal plugging on quadrupedal locomotion in monkey.

The vestibular system plays an important role in controling gait, but where in the labyrinths relevant activity arises is largely unknown. After the semicircular canals are plugged, low frequency (0.01-2 Hz) components of the angular vestibulo-ocular reflex (aVOR) and angular vestibulo-collic reflex (aVCR) are lost, but high frequency (3-20 Hz) components remain.

Modification of the cervico-ocular reflex by canal plugging.

The cervico-ocular reflex (COR) has a low gain in normal animals. In this study, we determined whether COR gain increases were specific to the low/midband frequency range, which is the range over which the angular vestibulo-ocular reflex (aVOR) is compromised by plugging. The gain and phase of the yaw and pitch COR and aVOR were compared in normal monkeys and those with all six semicircular canals or only the lateral canal plugged.