Publications by authors named "Richard F Lewis"

39 Publications

Effects of vestibular neurectomy and neural compensation on head movements in patients undergoing vestibular schwannoma resection.

Sci Rep 2021 Jan 12;11(1):517. Epub 2021 Jan 12.

Department of Biomedical Engineering, Johns Hopkins University, Baltimore, USA.

The vestibular system is vital for maintaining balance and stabilizing gaze and vestibular damage causes impaired postural and gaze control. Here we examined the effects of vestibular loss and subsequent compensation on head motion kinematics during voluntary behavior. Head movements were measured in vestibular schwannoma patients before, and then 6 weeks and 6 months after surgical tumor removal, requiring sectioning of the involved vestibular nerve (vestibular neurectomy). Head movements were recorded in six dimensions using a small head-mounted sensor while patients performed the Functional Gait Assessment (FGA). Kinematic measures differed between patients (at all three time points) and normal subjects on several challenging FGA tasks, indicating that vestibular damage (caused by the tumor or neurectomy) alters head movements in a manner that is not normalized by central compensation. Kinematics measured at different time points relative to vestibular neurectomy differed substantially between pre-operative and 6-week post-operative states but changed little between 6-week and > 6-month post-operative states, demonstrating that compensation affecting head kinematics is relatively rapid. Our results indicate that quantifying head kinematics during self-generated gait tasks provides valuable information about vestibular damage and compensation, suggesting that early changes in patient head motion strategy may be maladaptive for long-term vestibular compensation.
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http://dx.doi.org/10.1038/s41598-020-79756-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804855PMC
January 2021

Self-motion perception is sensitized in vestibular migraine: pathophysiologic and clinical implications.

Sci Rep 2019 10 4;9(1):14323. Epub 2019 Oct 4.

Jenks Vestibular Physiology Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA, USA.

Vestibular migraine (VM) is the most common cause of spontaneous vertigo but remains poorly understood. We investigated the hypothesis that central vestibular pathways are sensitized in VM by measuring self-motion perceptual thresholds in patients and control subjects and by characterizing the vestibulo-ocular reflex (VOR) and vestibular and headache symptom severity. VM patients were abnormally sensitive to roll tilt, which co-modulates semicircular canal and otolith organ activity, but not to motions that activate the canals or otolith organs in isolation, implying sensitization of canal-otolith integration. When tilt thresholds were considered together with vestibular symptom severity or VOR dynamics, VM patients segregated into two clusters. Thresholds in one cluster correlated positively with symptoms and with the VOR time constant; thresholds in the second cluster were uniformly low and independent of symptoms and the time constant. The VM threshold abnormality showed a frequency-dependence that paralleled the brain stem velocity storage mechanism. These results support a pathogenic model where vestibular symptoms emanate from the vestibular nuclei, which are sensitized by migraine-related brainstem regions and simultaneously suppressed by inhibitory feedback from the cerebellar nodulus and uvula, the site of canal-otolith integration. This conceptual framework elucidates VM pathophysiology and could potentially facilitate its diagnosis and treatment.
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http://dx.doi.org/10.1038/s41598-019-50803-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778132PMC
October 2019

Relationship between vestibular sensitivity and multisensory temporal integration.

J Neurophysiol 2018 10 18;120(4):1572-1577. Epub 2018 Jul 18.

Department of Otolaryngology-Head and Neck Surgery, Oregon Health and Science University , Portland, Oregon.

A single event can generate asynchronous sensory cues due to variable encoding, transmission, and processing delays. To be interpreted as being associated in time, these cues must occur within a limited time window, referred to as a "temporal binding window" (TBW). We investigated the hypothesis that vestibular deficits could disrupt temporal visual-vestibular integration by determining the relationships between vestibular threshold and TBW in participants with normal vestibular function and with vestibular hypofunction. Vestibular perceptual thresholds to yaw rotation were characterized and compared with the TBWs obtained from participants who judged whether a suprathreshold rotation occurred before or after a brief visual stimulus. Vestibular thresholds ranged from 0.7 to 16.5 deg/s and TBWs ranged from 13.8 to 395 ms. Among all participants, TBW and vestibular thresholds were well correlated ( R = 0.674, P < 0.001), with vestibular-deficient patients having higher thresholds and wider TBWs. Participants reported that the rotation onset needed to lead the light flash by an average of 80 ms for the visual and vestibular cues to be perceived as occurring simultaneously. The wide TBWs in vestibular-deficient participants compared with normal functioning participants indicate that peripheral sensory loss can lead to abnormal multisensory integration. A reduced ability to temporally combine sensory cues appropriately may provide a novel explanation for some symptoms reported by patients with vestibular deficits. Even among normal functioning participants, a high correlation between TBW and vestibular thresholds was observed, suggesting that these perceptual measurements are sensitive to small differences in vestibular function. NEW & NOTEWORTHY While spatial visual-vestibular integration has been well characterized, the temporal integration of these cues is not well understood. The relationship between sensitivity to whole body rotation and duration of the temporal window of visual-vestibular integration was examined using psychophysical techniques. These parameters were highly correlated for those with normal vestibular function and for patients with vestibular hypofunction. Reduced temporal integration performance in patients with vestibular hypofunction may explain some symptoms associated with vestibular loss.
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http://dx.doi.org/10.1152/jn.00379.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6230789PMC
October 2018

Bayesian optimal adaptation explains age-related human sensorimotor changes.

J Neurophysiol 2018 02 8;119(2):509-520. Epub 2017 Nov 8.

Jenks Vestibular Physiology Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts.

The brain uses information from different sensory systems to guide motor behavior, and aging is associated with simultaneous decline in the quality of sensory information provided to the brain and deterioration in motor control. Correlations between age-dependent decline in sensory anatomical structures and behavior have been demonstrated in many sensorimotor systems, and it has recently been suggested that a Bayesian framework could explain these relationships. Here we show that age-dependent changes in a human sensorimotor reflex, the vestibuloocular reflex, are explained by a Bayesian optimal adaptation in the brain occurring in response to death of motion-sensing hair cells. Specifically, we found that the temporal dynamics of the reflex as a function of age emerge from ( r = 0.93, P < 0.001) a Kalman filter model that determines the optimal behavioral output when the sensory signal-to-noise characteristics are degraded by death of the transducers. These findings demonstrate that the aging brain is capable of generating the ideal and statistically optimal behavioral response when provided with deteriorating sensory information. While the Bayesian framework has been shown to be a general neural principle for multimodal sensory integration and dynamic sensory estimation, these findings provide evidence of longitudinal Bayesian processing over the human life span. These results illuminate how the aging brain strives to optimize motor behavior when faced with deterioration in the peripheral and central nervous systems and have implications in the field of vestibular and balance disorders, as they will likely provide guidance for physical therapy and for prosthetic aids that aim to reduce falls in the elderly. NEW & NOTEWORTHY We showed that age-dependent changes in the vestibuloocular reflex are explained by a Bayesian optimal adaptation in the brain that occurs in response to age-dependent sensory anatomical changes. This demonstrates that the brain can longitudinally respond to age-related sensory loss in an ideal and statistically optimal way. This has implications for understanding and treating vestibular disorders caused by aging and provides insight into the structure-function relationship during aging.
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http://dx.doi.org/10.1152/jn.00710.2017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5867390PMC
February 2018

An Engineering Model to Test for Sensory Reweighting: Nonhuman Primates Serve as a Model for Human Postural Control and Vestibular Dysfunction.

J Biomech Eng 2018 Jan;140(1)

Departments of Otology and Laryngology and Neurology, Harvard Medical School, Boston, MA 02139.

Quantitative animal models are critically needed to provide proof of concept for the investigation of rehabilitative balance therapies (e.g., invasive vestibular prostheses) and treatment response prior to, or in conjunction with, human clinical trials. This paper describes a novel approach to modeling the nonhuman primate postural control system. Our observation that rhesus macaques and humans have even remotely similar postural control motivates the further application of the rhesus macaque as a model for studying the effects of vestibular dysfunction, as well as vestibular prosthesis-assisted states, on human postural control. Previously, system identification methodologies and models were only used to describe human posture. However, here we utilized pseudorandom, roll-tilt balance platform stimuli to perturb the posture of a rhesus monkey in normal and mild vestibular (equilibrium) loss states. The relationship between rhesus monkey trunk sway and platform roll-tilt was determined via stimulus-response curves and transfer function results. A feedback controller model was then used to explore sensory reweighting (i.e., changes in sensory reliance), which prevented the animal from falling off of the tilting platform. Conclusions involving sensory reweighting in the nonhuman primate for a normal sensory state and a state of mild vestibular loss led to meaningful insights. This first-phase effort to model the balance control system in nonhuman primates is essential for future investigations toward the effects of invasive rehabilitative (balance) technologies on postural control in primates, and ultimately, humans.
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http://dx.doi.org/10.1115/1.4038157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5676644PMC
January 2018

Postural compensation strategy depends on the severity of vestibular damage.

Heliyon 2017 Mar 22;3(3):e00270. Epub 2017 Mar 22.

Jenks Vestibular Physiology Laboratory, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114, USA; Harvard- MIT Health Sciences and Technology, 77 Massachusetts Avenue, E25-519, Cambridge, MA 02139, USA; Department of Otology and Laryngology, Harvard Medical School, 243 Charles Street Boston, MA 02114, USA.

The purpose of this study was to investigate the effects of various levels of vestibular function on balance in two, free-standing rhesus monkeys. We hypothesized that postural control strategy depended on the severity of vestibular damage. More specifically, that increased muscle stiffness (via short-latency mechanisms) was adequate to compensate for mild damage, but long-latency mechanisms must be utilized for more severe vestibular damage. One animal was studied for pre-ablated and mild vestibular dysfunction states, while a second animal was studied in a pre-ablated and severe vestibular dysfunction state. The vestibulo-ocular reflex (VOR), an eye movement reflex directly linked to vestibular function, was used to quantify the level of vestibular damage. A postural feedback controller model, previously only used for human studies, was modified to interpret non-human primate postural responses (differences observed in the measured trunk roll) for these three levels of vestibular function. By implementing a feedback controller model, we were able to further interpret our empirical findings and model results were consistent with our above hypothesis. This study establishes a baseline for future studies of non-human primate posture.
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http://dx.doi.org/10.1016/j.heliyon.2017.e00270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5367863PMC
March 2017

Vestibular implants studied in animal models: clinical and scientific implications.

Authors:
Richard F Lewis

J Neurophysiol 2016 12 19;116(6):2777-2788. Epub 2016 Oct 19.

Department of Otolaryngology, Harvard Medical School, Boston, Massachusetts;

Damage to the peripheral vestibular system can result in debilitating postural, perceptual, and visual symptoms. A potential new treatment for this clinical problem is to replace some aspects of peripheral vestibular function with an implant that senses head motion and provides this information to the brain by stimulating branches of the vestibular nerve. In this review I consider animal studies performed at our institution over the past 15 years, which have helped elucidate how the brain processes information provided by a vestibular (semicircular canal) implant and how this information could be used to improve the problems experienced by patients with peripheral vestibular damage.
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http://dx.doi.org/10.1152/jn.00601.2016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5148793PMC
December 2016

Vestibular ablation and a semicircular canal prosthesis affect postural stability during head turns.

Exp Brain Res 2016 11 12;234(11):3245-3257. Epub 2016 Jul 12.

Department of Otology and Laryngology, Harvard Medical School, Boston, MA, USA.

In our study, we examined postural stability during head turns for two rhesus monkeys: one animal study contrasted normal and mild bilateral vestibular ablation and a second animal study contrasted severe bilateral vestibular ablation with and without prosthetic stimulation. The monkeys freely stood, unrestrained on a balance platform and made voluntary head turns between visual targets. To quantify each animals' posture, motions of the head and trunk, as well as torque about the body's center of mass, were measured. In the mildly ablated animal, we observed less foretrunk sway in comparison with the normal state. When the canal prosthesis provided electric stimulation to the severely ablated animal, it showed a decrease in trunk sway during head turns. Because the rhesus monkey with severe bilateral vestibular loss exhibited a decrease in trunk sway when receiving vestibular prosthetic stimulation, we propose that the prosthetic electrical stimulation partially restored head velocity information. Our results provide an indication that a semicircular canal prosthesis may be an effective way to improve postural stability in patients with severe peripheral vestibular dysfunction.
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http://dx.doi.org/10.1007/s00221-016-4722-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5108089PMC
November 2016

Contribution of intravestibular sensory conflict to motion sickness and dizziness in migraine disorders.

J Neurophysiol 2016 10 6;116(4):1586-1591. Epub 2016 Jul 6.

Jenks Vestibular Physiology Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts; Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts; and Department of Neurology, Harvard Medical School, Boston, Massachusetts

Migraine is associated with enhanced motion sickness susceptibility and can cause episodic vertigo [vestibular migraine (VM)], but the mechanisms relating migraine to these vestibular symptoms remain uncertain. We tested the hypothesis that the central integration of rotational cues (from the semicircular canals) and gravitational cues (from the otolith organs) is abnormal in migraine patients. A postrotational tilt paradigm generated a conflict between canal cues (which indicate the head is rotating) and otolith cues (which indicate the head is tilted and stationary), and eye movements were measured to quantify two behaviors that are thought to minimize this conflict: suppression and reorientation of the central angular velocity signal, evidenced by attenuation ("dumping") of the vestibuloocular reflex and shifting of the rotational axis of the vestibuloocular reflex toward the earth vertical. We found that normal and migraine subjects, but not VM patients, displayed an inverse correlation between the extent of dumping and the size of the axis shift such that the net "conflict resolution" mediated through these two mechanisms approached an optimal value and that the residual sensory conflict in VM patients (but not migraine or normal subjects) correlated with motion sickness susceptibility. Our findings suggest that the brain normally controls the dynamic and spatial characteristics of central vestibular signals to minimize intravestibular sensory conflict and that this process is disrupted in VM, which may be responsible for the enhance motion intolerance and episodic vertigo that characterize this disorder.
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http://dx.doi.org/10.1152/jn.00345.2016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5144688PMC
October 2016

Abnormal Tilt Perception During Centrifugation in Patients with Vestibular Migraine.

J Assoc Res Otolaryngol 2016 06 8;17(3):253-8. Epub 2016 Mar 8.

Jenks Vestibular Physiology Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA, USA.

Vestibular migraine (VM), defined as vestibular symptoms caused by migraine mechanisms, is very common but poorly understood. Because dizziness is often provoked in VM patients when the semicircular canals and otolith organs are stimulated concurrently (e.g., tilting the head relative to gravity), we measured tilt perception and eye movements in patients with VM and in migraine and normal control subjects during fixed-radius centrifugation, a paradigm that simultaneously modulates afferent signals from the semicircular canals and otoliths organs. Twenty-four patients (8 in each category) were tested with a motion paradigm that generated an inter-aural centrifugal force of 0.36 G, resulting in a 20° tilt of the gravito-inertial force in the roll plane. We found that percepts of roll tilt developed slower in VM patients than in the two control groups, but that eye movement responses, including the shift in the eye's rotational axis, were equivalent in all three groups. These results demonstrate a change in vestibular perception in VM that is unaccompanied by changes in vestibular-mediated eye movements and suggest that either the brain's integration of canal and otolith signals or the dynamics of otolith responses are aberrant in patients with VM.
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http://dx.doi.org/10.1007/s10162-016-0559-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4854827PMC
June 2016

Cerebellar contributions to self-motion perception: evidence from patients with congenital cerebellar agenesis.

J Neurophysiol 2016 05 17;115(5):2280-5. Epub 2016 Feb 17.

Jenks Vestibular Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts; Department of Neurology, Harvard Medical School, Boston, Massachusetts; Department of Otolaryngology, Harvard Medical School, Boston, Massachusetts

The cerebellum was historically considered a brain region dedicated to motor control, but it has become clear that it also contributes to sensory processing, particularly when sensory discrimination is required. Prior work, for example, has demonstrated a cerebellar contribution to sensory discrimination in the visual and auditory systems. The cerebellum also receives extensive inputs from the motion and gravity sensors in the vestibular labyrinth, but its role in the perception of head motion and orientation has received little attention. Drawing on the lesion-deficit approach to understanding brain function, we evaluated the contributions of the cerebellum to head motion perception by measuring perceptual thresholds in two subjects with congenital agenesis of the cerebellum. We used a set of passive motion paradigms that activated the semicircular canals or otolith organs in isolation or combination, and compared results of the agenesis patients with healthy control subjects. Perceptual thresholds for head motion were elevated in the agenesis subjects for all motion protocols, most prominently for paradigms that only activated otolith inputs. These results demonstrate that the cerebellum increases the sensitivity of the brain to the motion and orientation signals provided by the labyrinth during passive head movements.
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http://dx.doi.org/10.1152/jn.00763.2015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4922453PMC
May 2016

Vestibular Prostheses Investigated in Animal Models.

Authors:
Richard F Lewis

ORL J Otorhinolaryngol Relat Spec 2015 15;77(4):219-226. Epub 2015 Sep 15.

Loss of peripheral vestibular function results in debilitating postural, perceptual, and visual symptoms. A new approach to treating this clinical problem is to replace some aspects of peripheral vestibular function with a prosthesis that senses head motion and provides this information to the brain by stimulating the vestibular nerve. In this paper, I review studies done in animals over the past 15 years which lay the groundwork for transferring this approach to human patients with severe peripheral vestibular damage. The animal studies demonstrate that the visual and perceptual defects associated with peripheral vestibular damage can be improved with a vestibular implant, but the data on postural control remain less conclusive at this point in time.
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http://dx.doi.org/10.1159/000433551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792791PMC
September 2015

Advances in the diagnosis and treatment of vestibular disorders: psychophysics and prosthetics.

Authors:
Richard F Lewis

J Neurosci 2015 Apr;35(13):5089-96

Department of Otology and Laryngology and Department of Neurology, Harvard Medical School, Boston, Massachusetts 02114

Although vestibular disorders are common and often disabling, they remain difficult to diagnose and treat. For these reasons, considerable interest has been focused on developing new ways to identify peripheral and central vestibular abnormalities and on new therapeutic options that could benefit the numerous patients who remain symptomatic despite optimal therapy. In this review, I focus on the potential utility of psychophysical vestibular testing and vestibular prosthetics. The former offers a new diagnostic approach that may prove to be superior to the current tests in some circumstances; the latter may be a way to provide the brain with information about head motion that restores some elements of the information normally provided by the vestibular labyrinth.
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http://dx.doi.org/10.1523/JNEUROSCI.3922-14.2015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380990PMC
April 2015

Clinical vestibular testing assessed with machine-learning algorithms.

JAMA Otolaryngol Head Neck Surg 2015 Apr;141(4):364-72

Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts4Department of Neurology, Harvard Medical School, Boston, Massachusetts.

Importance: Dizziness and imbalance are common clinical problems, and accurate diagnosis depends on determining whether damage is localized to the peripheral vestibular system. Vestibular testing guides this determination, but the accuracy of the different tests is not known.

Objective: To determine how well each element of the vestibular test battery segregates patients with normal peripheral vestibular function from those with unilateral reductions in vestibular function.

Design, Setting, And Participants: Retrospective analysis of vestibular test batteries in 8080 patients. Clinical medical records were reviewed for a subset of individuals with the reviewers blinded to the vestibular test data.

Interventions: A group of machine-learning classifiers were trained using vestibular test data from persons who were "manually" labeled as having normal vestibular function or unilateral vestibular damage based on a review of their medical records. The optimal trained classifier was then used to categorize patients whose diagnoses were unknown, allowing us to determine the information content of each element of the vestibular test battery.

Main Outcomes And Measures: The information provided by each element of the vestibular test battery to segregate individuals with normal vestibular function from those with unilateral vestibular damage.

Results: The time constant calculated from the rotational test ranked first in information content, and measures that were related physiologically to the rotational time constant were 10 of the top 12 highest-ranked variables. The caloric canal paresis ranked eighth, and the other elements of the test battery provided minimal additional information. The sensitivity of the rotational time constant was 77.2%, and the sensitivity of the caloric canal paresis was 59.6%; the specificity of the rotational time constant was 89.0%, and the specificity of the caloric canal paresis was 64.9%. The diagnostic accuracy of the vestibular test battery increased from 72.4% to 93.4% when the data were analyzed with the optimal machine-learning classifier.

Conclusions And Relevance: Rotational testing should be considered the primary test to diagnose unilateral peripheral vestibular damage in patients with dizziness or imbalance. Most physicians, however, continue to rely on caloric tests to guide their diagnoses. Our results support a significant shift in the approach used to determine diagnoses in patients with vestibular symptoms.
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http://dx.doi.org/10.1001/jamaoto.2014.3519DOI Listing
April 2015

Central Integration of Canal and Otolith Signals is Abnormal in Vestibular Migraine.

Front Neurol 2014 10;5:233. Epub 2014 Nov 10.

Jenks Vestibular Physiology Laboratory, Massachusetts Eye and Ear Infirmary , Boston, MA , USA ; Department of Otology and Laryngology, Harvard Medical School , Boston, MA , USA ; Department of Neurology, Harvard Medical School , Boston, MA , USA.

Vestibular migraine (VM), a common cause of vestibular symptoms within the general population, is a disabling and poorly understood form of dizziness. We sought to examine the underlying pathophysiology of VM with three studies, which involved the central synthesis of canal and otolith cues, and present preliminary results from each of these studies: (1) VM patients appear to have reduced motion perception thresholds when canal and otolith signals are modulated in a co-planar manner during roll tilt; (2) percepts of roll tilt appear to develop more slowly in VM patients than in control groups during a centrifugation paradigm that presents conflicting, orthogonal canal and otolith cues; and (3) eye movement responses appear to be different in VM patients when studied with a post-rotational tilt paradigm, which also presents a canal-otolith conflict, as the shift of the eye's rotational axis was larger in VM and the relationship between the axis shift and tilt suppression of the vestibulo-ocular reflex differed in VM patients relative to control groups. Based on these preliminary perceptual and eye movement results obtained with three different motion paradigms, we present a hypothesis that the integration of canal and otolith signals by the brain is abnormal in VM and that this abnormality could be cerebellar in origin. We provide potential mechanisms that could underlie these observations, and speculate that one of more of these mechanisms contributes to the vestibular symptoms and motion intolerance that are characteristic of the VM syndrome.
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http://dx.doi.org/10.3389/fneur.2014.00233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226145PMC
November 2014

Motion Perception in Patients with Idiopathic Bilateral Vestibular Hypofunction.

Otolaryngol Head Neck Surg 2014 06 19;150(6):1040-2. Epub 2014 Mar 19.

Department of Otology & Laryngology, Harvard Medical School, Boston, Massachusetts, USA Jenks Vestibular Physiology Laboratory, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA Department of Neurology, Harvard Medical School, Boston, Massachusetts, USA

We measured vestibular perceptual thresholds in patients with idiopathic bilateral vestibulopathy to assess the distribution of peripheral vestibular damage in this disorder. Thresholds were measured with standard psychometric techniques in 4 patients and compared with thresholds in normal subjects and patients with completely absent peripheral vestibular function. Motion paradigms included yaw rotation (testing the lateral canals), interaural translation (testing the utricles), superior-inferior translation (testing the saccules), and roll tilt (testing the vertical semicircular canals and the otolith organs). We found that perceptual thresholds were abnormally elevated in the patients with idiopathic bilateral vestibulopathy for yaw rotation at all frequencies and for interaural translation at only the lower frequencies. Thresholds were normal for the other 2 motion paradigms. The results demonstrate that the distribution of vestibular dysfunction in this disorder is not uniform but, rather, can affect lateral canal and utricular thresholds while relatively sparing vertical canal and saccular function.
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http://dx.doi.org/10.1177/0194599814526557DOI Listing
June 2014

Electrical stimulation of semicircular canal afferents affects the perception of head orientation.

J Neurosci 2013 May;33(22):9530-5

Jenks Vestibular Physiology Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts 02114, USA.

Patients with vestibular dysfunction have visual, perceptual, and postural deficits. While there is considerable evidence that a semicircular canal prosthesis that senses angular head velocity and stimulates canal ampullary nerves can improve vision by augmenting the vestibulo-ocular reflex, no information is available regarding the potential utility of a canal prosthesis to improve perceptual deficits. In this study, we investigated the possibility that electrical stimulation of canal afferents could be used to modify percepts of head orientation. Two rhesus monkeys were trained to align a light bar parallel to gravity, and were tested in the presence and absence of electrical stimulation provided by an electrode implanted in the right posterior canal. While the monkeys aligned the light bar close to the true earth-vertical without stimulation, when the right posterior canal was stimulated their responses deviated toward their left ear, consistent with a misperception of head tilt toward the right. The deviation of the light bar from the earth-vertical exceeded the torsional deviation of the eyes, indicating that the perceptual changes were not simply visual in origin. Eye movements recorded during electrical stimulation in the dark were consistent with isolated activation of right posterior canal afferents, with no evidence of otolith stimulation. These results demonstrate that electrical stimulation of canal afferents affects the perception of head orientation, and therefore suggest that motion-modulated stimulation of canal afferents by a vestibular prosthesis could potentially improve vestibular percepts in patients lacking normal vestibular function.
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http://dx.doi.org/10.1523/JNEUROSCI.0112-13.2013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3718451PMC
May 2013

Adaptation of vestibular tone studied with electrical stimulation of semicircular canal afferents.

J Assoc Res Otolaryngol 2013 Jun 20;14(3):331-40. Epub 2013 Feb 20.

Jenks Vestibular Physiology Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA, USA.

Damage to one vestibular labyrinth or nerve causes a central tone imbalance, reflected by prominent spontaneous nystagmus. Central adaptive mechanisms eliminate the nystagmus over several days, and the mechanisms underlying this process have received extensive study. The characteristics of vestibular compensation when the tone imbalance is presented gradually or repeatedly have never been studied. We used high-frequency electrical stimulation of semicircular canal afferents to generate a vestibular tone imbalance and recorded the nystagmus produced when the stimulation was started abruptly or gradually and when it was repeatedly cycled on and off. In the acute-onset protocol, brisk nystagmus occurred when stimulation started, gradually resolved within 1 day, and reversed direction when the stimulation was stopped after 1 week. Repeated stimulation cycles resulted in progressively smaller nystagmus responses. In the slow-onset protocol, minimal nystagmus occurred while the stimulation ramped-up to its maximum rate over 12 h, but a reversal still occurred when the stimulation was stopped after 1 week, and repeated stimulation cycles did not affect this pattern. The absence of nystagmus during the 12 h ramp of stimulation demonstrates that central vestibular tone can rebalance relatively quickly, and the reduction in the stimulation-off nystagmus with repeated cycles of the acute-onset but not the slow-onset stimulation suggests that dual-state adaptation may have occurred with the former paradigm but not the latter.
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http://dx.doi.org/10.1007/s10162-013-0376-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3642268PMC
June 2013

Vestibular labyrinth contributions to human whole-body motion discrimination.

J Neurosci 2012 Sep;32(39):13537-42

Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts 02114, USA.

To assess the contributions of the vestibular system to whole-body motion discrimination in the dark, we measured direction recognition thresholds as a function of frequency for yaw rotation, superior-inferior translation ("z-translation"), interaural translation ("y-translation"), and roll tilt for 14 normal subjects and for 3 patients following total bilateral vestibular ablation. The patients had significantly higher average threshold measurements than normal (p < 0.01) for yaw rotation (depending upon frequency, 5.4× to 15.7× greater), z-translation (8.3× to 56.8× greater), y-translation (1.7× to 4.5× greater), and roll tilt (1.3× to 3.0× greater)--establishing the predominant contributions of the vestibular system for these motions in the dark.
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http://dx.doi.org/10.1523/JNEUROSCI.2157-12.2012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3467969PMC
September 2012

Replacing semicircular canal function with a vestibular implant.

Curr Opin Otolaryngol Head Neck Surg 2012 Oct;20(5):386-92

Jenks Vestibular Physiology Laboratory, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA.

Purpose Of Review: To summarize the recent progress in the development of vestibular implants. The review is timely because of the recent advances in the field and because MED-EL has recently announced that they are developing a vestibular implant for clinical applications.

Recent Findings: The handicap experienced by patients suffering from bilateral vestibulopathy has a strong negative impact on physical and social functioning that appears to justify a surgical intervention. Two different surgical approaches to insert electrodes to stimulate ampullary neurons have been shown to be viable. The three-dimensional vestibulo-ocular reflex in rhesus monkeys produced with a three-dimensional vestibular implant showed gains that were relatively normal during acute stimulation. Rotation cues provided by an implant interact with otolith cues in a qualitatively normal manner. The brain appears to adapt plastically to the cues provided via artificial electrical stimulation.

Summary: Research to date includes just a few human studies, but available data from both humans and animals support the technological and physiological feasibility of vestibular implants. Although vestibular implant users should not expect normal vestibular function - any more than cochlear implant users should expect normal hearing - data suggest that significant functional improvements are possible.
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http://dx.doi.org/10.1097/MOO.0b013e328357630fDOI Listing
October 2012

Responses evoked by a vestibular implant providing chronic stimulation.

J Vestib Res 2012 ;22(1):11-5

Jenks Vestibular Physiology Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA, USA.

Patients with bilateral vestibular loss experience dehabilitating visual, perceptual, and postural difficulties, and an implantable vestibular prosthesis that could improve these symptoms would be of great benefit to these patients. In previous work, we have shown that a one-dimensional, unilateral canal prosthesis can improve the vestibulooccular reflex (VOR) in canal-plugged squirrel monkeys. In addition to the VOR, the potential effects of a vestibular prosthesis on more complex, highly integrative behaviors, such as the perception of head orientation and posture have remained unclear. We tested a one-dimensional, unilateral prosthesis in a rhesus monkey with bilateral vestibular loss and found that chronic electrical stimulation partially restored the compensatory VOR and also that percepts of head orientation relative to gravity were improved. However, the one-dimensional prosthetic stimulation had no clear effect on postural stability during quiet stance, but sway evoked by head-turns was modestly reduced. These results suggest that not only can the implementation of a vestibular prosthesis provide partial restitution of VOR but may also improve perception and posture in the presence of bilateral vestibular hypofunction (BVH). In this review, we provide an overview of our previous and current work directed towards the eventual clinical implementation of an implantable vestibular prosthesis.
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http://dx.doi.org/10.3233/VES-2012-0442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4041130PMC
October 2012

Spatial and temporal properties of eye movements produced by electrical stimulation of semicircular canal afferents.

J Neurophysiol 2012 Sep 6;108(5):1511-20. Epub 2012 Jun 6.

Department of Otolaryngology, Harvard Medical School, Boston, MA, USA.

To investigate the characteristics of eye movements produced by electrical stimulation of semicircular canal afferents, we studied the spatial and temporal features of eye movements elicited by short-term lateral canal stimulation in two squirrel monkeys with plugged lateral canals, with the head upright or statically tilted in the roll plane. The electrically induced vestibuloocular reflex (eVOR) evoked with the head upright decayed more quickly than the stimulation signal provided by the electrode, demonstrating an absence of the classic velocity storage effect that improves the dynamics of the low-frequency VOR. When stimulation was provided with the head tilted in roll, however, the eVOR decayed more rapidly than when the head was upright, and a cross-coupled vertical response developed that shifted the eye's rotational axis toward alignment with gravity. These results demonstrate that rotational information provided by electrical stimulation of canal afferents interacts with otolith inputs (or other graviceptive cues) in a qualitatively normal manner, a process that is thought to be mediated by the velocity storage network. The observed interaction between the eVOR and graviceptive cues is of critical importance for the development of a functionally useful vestibular prosthesis. Furthermore, the presence of gravity-dependent effects (dumping, spatial orientation) despite an absence of low-frequency augmentation of the eVOR has not been previously described in any experimental preparation.
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http://dx.doi.org/10.1152/jn.01029.2011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544955PMC
September 2012

Dynamic tilt thresholds are reduced in vestibular migraine.

J Vestib Res 2011 ;21(6):323-30

Department of Otology, Harvard Medical School, Boston MA, USA.

Vestibular symptoms caused by migraine, referred to as vestibular migraine, are a frequently diagnosed but poorly understood entity. Based on recent evidence that normal subjects generate vestibular-mediated percepts of head motion and reflexive eye movements using different mechanisms, we hypothesized that percepts of head motion may be abnormal in vestibular migraine. We therefore measured motion detection thresholds in patients with vestibular migraine, migraine patients with no history of vestibular symptoms, and normal subjects using the following paradigms: roll rotation while supine (dynamically activating the semicircular canals); quasi-static roll tilt (statically activating the otolith organs); and dynamic roll tilt (dynamically activating the canals and otoliths). Thresholds were determined while patients were asymptomatic using a staircase paradigm, whereby the peak acceleration of the motion was decreased or increased based on correct or incorrect reports of movement direction. We found a dramatic reduction in motion thresholds in vestibular migraine compared to normal and migraine subjects in the dynamic roll tilt paradigm, but normal thresholds in the roll rotation and quasi-static roll tilt paradigms. These results suggest that patients with vestibular migraine may have enhanced perceptual sensitivity (e.g. increased signal-to-noise ratio) for head motions that dynamically modulate canal and otolith inputs together.
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http://dx.doi.org/10.3233/VES-2011-0422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3767296PMC
June 2012

Vestibular prosthesis tested in rhesus monkeys.

Annu Int Conf IEEE Eng Med Biol Soc 2011 ;2011:2277-9

Jenks Vestibular Physiology Laboratory, Massachusetts Eye and Ear Infirmary, Department of Otology and Laryngology at the Harvard Medical School, Boston, MA 02114, USA.

We are studying the effectiveness of a semicircular canal prosthesis to improve postural control, perception of spatial orientation, and the VOR in rhesus monkeys with bilateral vestibular hypofunction. Balance is examined by measuring spontaneous sway of the body during quiet stance and postural responses evoked by head turns and rotation of the support surface; perception is measured with a task derived from the subjective visual vertical (SVV) test during static and dynamic rotation in the roll plane; and the angular VOR is measured during rotation about the roll, pitch, and yaw axes. After the normal responses are characterized, bilateral vestibular loss is induced with intratympanic gentamicin, and then multisite stimulating electrodes are chronically implanted into the ampullae of all three canals in one ear. The postural, perceptual, and VOR responses are then characterized in the ablated state, and then bilateral, chronic electrical stimulation is applied to the ampullary nerves using a prosthesis that senses angular head velocity in three-dimensions and uses this information to modulate the rate of current pulses provided by the implanted electrodes. We are currently characterizing two normal monkeys with these paradigms, and vestibular ablation and electrode implantation are planned for the near future. In one prior rhesus monkey tested with this approach, we found that a one-dimensional (posterior canal) prosthesis improved balance during head turns, perceived head orientation during roll tilts, and the VOR in the plane of the instrumented canal. We therefore predict that the more complete information provided by a three-dimensional prosthesis that modulates activity in bilaterally-paired canals will exceed the benefits provided by the one-dimensional, unilateral approach used in our preliminary studies.
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http://dx.doi.org/10.1109/IEMBS.2011.6090573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3594774PMC
June 2012

Frequency dependence of vestibuloocular reflex thresholds.

J Neurophysiol 2012 Feb 9;107(3):973-83. Epub 2011 Nov 9.

Jenks Vestibular Physiology Laboratory, Massachusetts Eye and Ear Infirmary, and Otology and Laryngology, Harvard Medical School, Boston, Massachusetts, USA.

How the brain processes signals in the presence of noise impacts much of behavioral neuroscience. Thresholds provide one way to assay noise. While perceptual thresholds have been widely investigated, vestibuloocular reflex (VOR) thresholds have seldom been studied and VOR threshold dynamics have never, to our knowledge, been reported. Therefore, we assessed VOR thresholds as a function of frequency. Specifically, we measured horizontal VOR thresholds evoked by yaw rotation in rhesus monkeys, using standard signal detection approaches like those used in earlier human vestibular perceptual threshold studies. We measured VOR thresholds ranging between 0.21 and 0.76°/s; the VOR thresholds increased slightly with frequency across the measured frequency range (0.2-3 Hz). These results do not mimic the frequency response of human perceptual thresholds that have been shown to increase substantially as frequency decreases below 0.5 Hz. These reported VOR threshold findings could indicate a qualitative difference between vestibular responses of humans and nonhuman primates, but a more likely explanation is an additional dynamic neural mechanism that does not influence the VOR but, rather, influences perceptual thresholds via a decision-making process included in direction recognition tasks.
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http://dx.doi.org/10.1152/jn.00451.2011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3289464PMC
February 2012

Abnormal motion perception in vestibular migraine.

Laryngoscope 2011 May;121(5):1124-5

Department of Otology and Laryngology, Harvard Medical School, Boston, Masshachusetts, USA.

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http://dx.doi.org/10.1002/lary.21723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3804168PMC
May 2011

Potential solutions to several vestibular challenges facing clinicians.

J Vestib Res 2010 ;20(1):71-7

Jenks Vestibular Physiology Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA.

Among other problems, patients with vestibular problems suffer imbalance, spatial disorientation, and blurred vision. These problems lead to varying degrees of disability and can be debilitating. Unfortunately, a large number of patients with vestibular complaints cannot be diagnosed with the clinical tests available today. Nor do we have treatments for all patients that we can diagnose. These clinical problems provide challenges to and opportunities for the field of vestibular research. In this paper, we discuss some new diagnostic and treatment options that could become available for tomorrow's patients. As a new diagnostic, we have begun measuring patient's perceptual direction-detection thresholds. Preliminary results appear encouraging; patients diagnosed with bilateral loss have yaw rotation thresholds almost ten times greater than normals, while patients diagnosed with migraine associated vertigo have roll tilt thresholds well below normal at 0.1 Hz. As a new treatment, we have performed animal studies looking at responses evoked by electrical stimulation provided by a vestibular prosthesis. Results measuring the VOR demonstrate promise and preliminary studies of balance and perception are also encouraging. While electrical stimulation is a standard means of stimulation, optical stimulation is also being investigated as a way to improve prosthetic stimulation specificity.
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http://dx.doi.org/10.3233/VES-2010-0347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2888506PMC
September 2010

Vestibuloocular reflex adaptation investigated with chronic motion-modulated electrical stimulation of semicircular canal afferents.

J Neurophysiol 2010 Feb 16;103(2):1066-79. Epub 2009 Dec 16.

Department of Otolaryngology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston MA 02114, USA.

To investigate vestibuloocular reflex (VOR) adaptation produced by changes in peripheral vestibular afference, we developed and tested a vestibular "prosthesis" that senses yaw-axis angular head velocity and uses this information to modulate the rate of electrical pulses applied to the lateral canal ampullary nerve. The ability of the brain to adapt the different components of the VOR (gain, phase, axis, and symmetry) during chronic prosthetic electrical stimulation was studied in two squirrel monkeys. After characterizing the normal yaw-axis VOR, electrodes were implanted in both lateral canals and the canals were plugged. The VOR in the canal-plugged/instrumented state was measured and then unilateral stimulation was applied by the prosthesis. The VOR was repeatedly measured over several months while the prosthetic stimulation was cycled between off, low-sensitivity, and high-sensitivity stimulation states. The VOR response initially demonstrated a low gain, abnormal rotational axis, and substantial asymmetry. During chronic stimulation the gain increased, the rotational axis improved, and the VOR became more symmetric. Gain changes were augmented by cycling the stimulation between the off and both low- and high-sensitivity states every few weeks. The VOR time constant remained low throughout the period of chronic stimulation. These results demonstrate that the brain can adaptively modify the gain, axis, and symmetry of the VOR when provided with chronic motion-modulated electrical stimulation by a canal prosthesis.
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http://dx.doi.org/10.1152/jn.00241.2009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2822686PMC
February 2010

Atypical voluntary nystagmus.

Neurology 2009 Feb;72(5):467-9

Department of Otology and Laryngology, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA.

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http://dx.doi.org/10.1212/01.wnl.0000341876.76523.99DOI Listing
February 2009

Roll tilt psychophysics in rhesus monkeys during vestibular and visual stimulation.

J Neurophysiol 2008 Jul 16;100(1):140-53. Epub 2008 Apr 16.

Department of Otolaryngology, Harvard Medical School, Boston, Massachusetts, USA.

How does the brain calculate the spatial orientation of the head relative to gravity? Psychophysical measurements are critical to investigate this question, but such measurements have been limited to humans. In non-human primates, behavioral measures have focused on vestibular-mediated eye movements, which do not reflect percepts of head orientation. We have therefore developed a method to measure tilt perception in monkeys, derived from the subjective visual vertical (SVV) task. Two rhesus monkeys were trained to align a light bar parallel to gravity and performed this task during roll tilts, centrifugation, and roll optokinetic stimulation. The monkeys accurately aligned the light bar with gravity during static roll tilts but also demonstrated small orientation-dependent misperceptions of the tilt angle analogous to those measured in humans. When the gravito-inertial force (GIF) rotated dynamically in the roll plane, SVV responses remained closely aligned with the GIF during roll tilt of the head (coplanar canal rotational cues present), lagged slightly behind the GIF during variable-radius centrifugation (no canal cues present), and shifted gradually during fixed-radius centrifugation (orthogonal yaw canal cues present). SVV responses also deviated away from the earth-vertical during roll optokinetic stimulation. These results demonstrate that rotational cues derived from the semicircular canals and visual system have prominent effects on psychophysical measurements of roll tilt in rhesus monkeys and therefore suggest that a central synthesis of graviceptive and rotational cues contributes to percepts of head orientation relative to gravity in non-human primates.
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http://dx.doi.org/10.1152/jn.01012.2007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2493487PMC
July 2008