A Novel Saccadic Strategy Revealed by Suppression Head Impulse Testing of Patients with Bilateral Vestibular Loss.

OBJECTIVE: We examined the eye movement response patterns of a group of patients with bilateral vestibular loss (BVL) during suppression head impulse testing. Some showed a new saccadic strategy that may have potential for explaining how patients use saccades to recover from vestibular loss. METHODS: Eight patients with severe BVL [vestibulo-ocular reflex (VOR) gains less than 0.35 and absent otolithic function] were tested. All patients were given the Dizziness Handicap Inventory and questioned about oscillopsia during abrupt head movements. Two paradigms of video head impulse testing of the horizontal VOR were used: (1) the classical head impulse paradigm [called head impulse test (HIMPs)]-fixating an earth-fixed target during the head impulse and (2) the new complementary test paradigm-fixating a head-fixed target during the head impulse (called SHIMPs). The VOR gain of HIMPs was quantified by two algorithms. RESULTS: During SHIMPs testing, some BVL patients consistently generated an inappropriate covert compensatory saccade during the head impulse that required a corresponding large anti-compensatory saccade at the end of the head impulse in order to obey the instructions to maintain gaze on the head-fixed target. By contrast, other BVL patients did not generate this inappropriate covert saccade and did not exhibit a corresponding anti-compensatory saccade. The latencies of the covert saccade in SHIMPs and HIMPs were similar. CONCLUSION: The pattern of covert saccades during SHIMPs appears to be related to the reduction of oscillopsia during abrupt head movements. BVL patients who did not report oscillopsia showed this unusual saccadic pattern, whereas BVL patients who reported oscillopsia did not show this pattern. This inappropriate covert SHIMPs saccade may be an objective indicator of how some patients with vestibular loss have learned to trigger covert saccades during head movements in everyday life.

Sustained and Transient Vestibular Systems: A Physiological Basis for Interpreting Vestibular Function.

Otolithic afferents with regular resting discharge respond to gravity or low-frequency linear accelerations, and we term these the static or sustained otolithic system. However, in the otolithic sense organs, there is anatomical differentiation across the maculae and corresponding physiological differentiation. A specialized band of receptors called the striola consists of mainly type I receptors whose hair bundles are weakly tethered to the overlying otolithic membrane. The afferent neurons, which form calyx synapses on type I striolar receptors, have irregular resting discharge and have low thresholds to high frequency (e.g., 500 Hz) bone-conducted vibration and air-conducted sound. High-frequency sound and vibration likely causes fluid displacement which deflects the weakly tethered hair bundles of the very fast type I receptors. Irregular vestibular afferents show phase locking, similar to cochlear afferents, up to stimulus frequencies of kilohertz. We term these irregular afferents the transient system signaling dynamic otolithic stimulation. A 500-Hz vibration preferentially activates the otolith irregular afferents, since regular afferents are not activated at intensities used in clinical testing, whereas irregular afferents have low thresholds. We show how this sustained and transient distinction applies at the vestibular nuclei. The two systems have differential responses to vibration and sound, to ototoxic antibiotics, to galvanic stimulation, and to natural linear acceleration, and such differential sensitivity allows probing of the two systems. A 500-Hz vibration that selectively activates irregular otolithic afferents results in stimulus-locked eye movements in animals and humans. The preparatory myogenic potentials for these eye movements are measured in the new clinical test of otolith function-ocular vestibular-evoked myogenic potentials. We suggest 500-Hz vibration may identify the contribution of the transient system to vestibular controlled responses, such as vestibulo-ocular, vestibulo-spinal, and vestibulo-sympathetic responses. The prospect of particular treatments targeting one or the other of the transient or sustained systems is now being realized in the clinic by the use of intratympanic gentamicin which preferentially attacks type I receptors. We suggest that it is valuable to view vestibular responses by this sustained-transient distinction.

Balance in Virtual Reality: Effect of Age and Bilateral Vestibular Loss.

BACKGROUND: Quantitative balance measurement is used in clinical practice to prevent falls. The conditions of the test were limited to eyes open, eyes closed, and sway-referenced vision. We developed a new visual perturbation to challenge balance using virtual reality (VR), measuring postural stability by a Wii Balance Board (WBB). METHODS: In this study, we recorded balance performance of 116 healthy subjects and of 10 bilateral vestibular loss patients using VR to assess the effect of age and the effect of total loss of vestibular function. We used several conditions: eyes open (normal visual inputs), eyes closed (no visual inputs), stable visual world (vision referenced), and perturbed visual world (visual perturbation) at different amplitudes of perturbation. Balance under these visual conditions was assessed on the WBB (stable support surface) and on the WBB plus foam rubber (unstable support surface). RESULTS: In healthy subjects, we found that the percentage of falls increased with age and with the amplitude of perturbation for both conditions: WBB or WBB + foam. Moreover, we can define a threshold for falls in each age group as the amplitude of perturbation which induced falls. For bilateral vestibular loss patients, on the WBB + foam, all of them failed with eyes closed and with perturbed visual world even at the minimal amplitude of perturbation. Finally, we observed that stable visual world induced fewer falls than eyes closed whatever the subject's group (healthy or bilateral vestibular loss) and whatever the age decade. CONCLUSION: VR allowed us to develop a useful new tool with a wide range of visual perturbations. Rather than only two levels of visual condition (eyes open and eyes closed), the VR stimulus can be continuously adjusted to produce a visual perturbation powerful enough to induce falls even in young healthy subjects and which has allowed us to determine a threshold for falls.

An Attempt of Early Detection of Poor Outcome after Whiplash.

The main concern with whiplash is that a large proportion of whiplash patients experience disabling symptoms or whiplash-associated disorders (WAD) for months if not years following the accident. Therefore, identifying early prognostic factors of WAD development is important as WAD have widespread clinical and economic consequences. In order to tackle that question, our study was specifically aimed at combining several methods of investigation in the same WAD patients at the acute stage and 6 months later. Our longitudinal, open, prospective, multi-center study included 38 whiplash patients, and 13 healthy volunteers matched for age, gender, and socio-economic status with the whiplash group. Whiplash patients were evaluated 15-21 days after road accident, and 6 months later. At each appointment, patients underwent a neuropsychological evaluation, a full clinical neurological examination, neurophysiological and postural tests, oto-neurological tests, cervical spine cord magnetic resonance imaging (MRI) with tractography (DTI). At 6 months, whiplash patients were categorized into two subgroups based on the results of the Diagnostic and Statistical Manual of Mental Disorders as having either favorable or unfavorable progression [an unfavorable classification corresponding to the presence of post-concussion symptom (PCS)] and we searched retrospectively for early prognostic factors of WAD predicting the passage to chronicity. We found that patients displaying high level of catastrophizing at the acute stage and/or post-traumatic stress disorder associated with either abnormalities in head or trunk kinematics, abnormal test of the otolithic function and at the Equitest or a combination of these syndromes, turned to chronicity. This study suggests that low-grade whiplash patients should be submitted as early as possible after the trauma to neuropsychological and motor control tests in a specialized consultation. In addition, they should be evaluated by a neuro-otologist for a detailed examination of vestibular functions, which should include cervical vestibular evoked myogenic potential. Then, if diagnosed at risk of WAD, these patients should be subjected to an intensive preventive rehabilitation program, including vestibular rehabilitation if required.

Saccadic Velocity in the New Suppression Head Impulse Test: A New Indicator of Horizontal Vestibular Canal Paresis and of Vestibular Compensation.

OBJECTIVE: To determine whether saccadic velocity in the suppression head impulse paradigm (SHIMP) test is a reliable indicator of vestibular loss at the acute and at the chronic stage in patients suffering from different vestibular pathologies. METHODS: Thirty-five normal subjects and 57 patients suffering from different vestibular pathologies associated with unilateral vestibular loss (UVL) or bilateral vestibular loss (BVL) were tested in the SHIMPs paradigm. SHIMPs were performed by turning the head 10 times at high velocities to the left or right side, respectively. The patients were instructed to fixate on a red spot generated by a head-fixed laser projected on the wall. In this SHIMPs paradigm, healthy subjects made a large anti-compensatory saccade at the end of the head turn (a SHIMP saccade). The peak saccadic velocity, the percentage of the trials completed with saccades in 10 trials, and the latency of the saccades were quantified in each group. A video-head impulse test (v-HIT) was systematically performed in all of our subjects as well as a caloric test. The dizziness handicap inventory questionnaire was also given to chronic UVL and BVL patients. RESULTS: At the acute stage after a complete UVL, patients had zero or a few anti-compensatory saccades for low velocity head turns toward the lesioned side. These saccades had lower velocity than the anti-compensatory saccades recorded during head rotation toward the intact side and/or compared with the saccades measured in control subjects. At the chronic stage, some of the patients recovered the ability to perform SHIMP saccades at each head turn toward the lesioned side, but very often these saccades were of significantly lower velocity. In BVL patients, no anti-compensatory saccades, or only significantly smaller ones, could be detected for head turns to both sides. CONCLUSION: SHIMP is a specific and sensitive test to detect a complete horizontal canal loss at the acute stage. In addition, it reflects the ability of patients with moderate horizontal vestibulo-ocular reflex gain decrease to generate anti-compensatory saccades in the chronic stage. In association with v-HIT, it allows determination of the residual vestibular function and to detect anti-compensatory saccades.

Dopamine Modulates Motor Control in a Specific Plane Related to Support.

At the acute stage following unilateral labyrinthectomy (UL), rats, mice or guinea pigs exhibit a complex motor syndrome combining circling (HSCC lesion) and rolling (utricular lesion). At the chronic stage, they only display circling, because proprioceptive information related to the plane of support substitutes the missing utricular information to control posture in the frontal plane. Circling is also observed following unilateral lesion of the mesencephalic dopaminergic neurons by 6- hydroxydopamine hydrobromide (6-OHDA rats) and systemic injection of apomorphine (APO rats). The resemblance of behavior induced by unilateral vestibular and dopaminergic lesions at the chronic stage can be interpreted in two ways. One hypothesis is that the dopaminergic system exerts three-dimensional control over motricity, as the vestibular system does. If this hypothesis is correct, then a unilateral lesion of the nigro-striatal pathway should induce three-dimensional motor deficits, i.e., circling and at least some sort of barrel rolling at the acute stage of the lesion. Then, compensation could also take place very rapidly based on proprioception, which would explain the prevalence of circling. In addition, barrel rolling should reappear when the rodent is placed in water, as it occurs in UL vertebrates. Alternatively, the dopaminergic network, together with neurons processing the horizontal canal information, could control the homeostasis of posture and locomotion specifically in one and only one plane of space, i.e. the plane related to the basis of support. In that case, barrel rolling should never occur, whether at the acute or chronic stage on firm ground or in water. Moreover, circling should have the same characteristics following both types of lesions. Clearly, 6-OHDA and APO-rats never exhibited barrel rolling at the acute stage. They circled at the acute stage of the lesion and continued to do so three weeks later, including in water. In contrast, UL-rats, exhibited both circling and barrel rolling at the acute stage, and then only circled on the ground. Furthermore, barrel rolling instantaneously reappeared in water in UL rats, which was not the case in 6-OHDA and APO-rats. That is, the lesion of the dopaminergic system on one side did not compromise trim in the pitch and roll planes, even when proprioceptive information related to the basis of support was lacking as in water. Altogether, these results strongly suggest that dopamine does not exert three-dimensional control of the motor system but regulates postural control in one particular plane of space, the one related to the basis of support. In contrast, as previously shown, the vestibular system exerts three-dimensional control on posture. That is, we show here for the first time a relationship between a given neuromodulator and the spatial organization of motor control.

Absence of Rotation Perception during Warm Water Caloric Irrigation in Some Seniors with Postural Instability.

Falls in seniors are a major public health problem. Falls lead to fear of falling, reduced mobility, and decreased quality of life. Vestibular dysfunction is one of the fall risk factors. The relationship between objective measures of vestibular responses and age has been studied. However, the effects of age on vestibular perception during caloric stimulation have not been studied. Twenty senior subjects were included in the study, and separated in two groups: 10 seniors reporting postural instability (PI) and exhibiting absence of vestibular perception when they tested with caloric stimulation and 10 sex- and age-matched seniors with no such problems (controls). We assessed vestibular perception on a binary rating scale during the warm irrigation of the caloric test. The function of the various vestibular receptors was assessed using video head impulse test (vHIT), caloric tests, and cervical and ocular vestibular-evoked myogenic potentials. The Equitest was used to evaluate balance. No horizontal canal dysfunction assessed using both caloric test and vHIT was detected in either group. No significant difference was detected between PI and control groups for the peak SPV of caloric-induced ocular nystagmus or for the HVOR gain. All the controls perceived rotation when the maximal SPV during warm irrigation was equal to or ≥15°/s. None of the subjects in the PI group perceived rotation even while the peak SPV exceeded 15°/s, providing objective evidence of normal peripheral horizontal canal function. All the PI group had abnormal Equitest results, particularly in the two last conditions. These investigations show for the first time that vestibular perception can be absent during a caloric test despite normal horizontal canal function. We call this as dissociation vestibular neglect. Patients with poor vestibular perception may not be aware of postural perturbations and so will not correct for them. Thus, falls in the elderly may result, among other factors, from a vestibular neglect due to an inappropriate central processing of normal vestibular peripheral inputs. That is, failure to perceive rotation during caloric testing when the SPV is >15°/s, should prompt the clinician to envisage preventive actions to avoid future falls such as rehabilitation.

Maintaining Balance when Looking at a Virtual Reality Three-Dimensional Display of a Field of Moving Dots or at a Virtual Reality Scene.

EXPERIMENTAL OBJECTIVE: To provide a safe, simple, relatively inexpensive, fast, accurate way of quantifying balance performance either in isolation, or in the face of challenges provided by 3D high definition moving visual stimuli as well as by the proprioceptive challenge from standing on a foam pad. This method uses the new technology of the Wii balance board to measure postural stability during powerful, realistic visual challenges from immersive virtual reality. LIMITATIONS OF CURRENT TECHNIQUES: Present computerized methods for measuring postural stability are large, complex, slow, and expensive, and do not allow for testing the response to realistic visual challenges. PROTOCOL: Subjects stand on a 6 cm thick, firm, foam pad on a Wii balance board. They wear a fast, high resolution, low persistence, virtual reality head set (Oculus Rift DK2). This allows displays of varying speed, direction, depth, and complexity to be delivered. The subject experiences a visual illusion of real objects fixed relative to the world, and any of these displays can be perturbed in an unpredictable fashion. A special app (BalanceRite) used the same procedures for analyzing postural analysis as used by the Equitest. POWER OF THE TECHNIQUE: Four simple "proof of concept" experiments demonstrate that this technique matches the gold standard Equitest in terms of the measurement of postural stability but goes beyond the Equitest by measuring stability in the face of visual challenges, which are so powerful that even healthy subjects fall. The response to these challenges presents an opportunity for predicting falls and for rehabilitation of seniors and patients with poor postural stability. SIGNIFICANCE FOR THE FIELD: This new method provides a simpler, quicker, cheaper method of measurement than the Equitest. It may provide a new mode of training to prevent falls, by maintaining postural stability in the face of visual and proprioceptive challenges similar to those encountered in life.

The role of cervical and ocular vestibular evoked myogenic potentials in the assessment of patients with vestibular schwannomas.

OBJECTIVES: To investigate the clinical utility of VEMPs in patients suffering from unilateral vestibular schwannoma (VS) and to determine the optimal stimulation parameter (air conducted sound, bone conducted vibration) for evaluating the function of the vestibular nerve. METHODS: Data were obtained in 63 patients with non-operated VS, and 20 patients operated on VS. Vestibular function was assessed by caloric, cervical and ocular VEMP testing. 37/63 patients with conclusive ACS ocular VEMPs responses were studied separately. RESULTS: In the 63 non-operated VS patients, cVEMPs were abnormal in 65.1% of patients in response to AC STB and in 49.2% of patients to AC clicks. In the 37/63 patients with positive responses from the unaffected side, oVEMPs were abnormal in 75.7% of patients with ACS, in 67.6% with AFz and in 56.8% with mastoid BCV stimulation. In 16% of the patients, VEMPs were the only abnormal test (normal caloric and normal hearing). Among the 26 patients who did not show oVEMP responses on either side with ACS, oVEMPs responses could be obtained with AFz (50%) and with mastoid stimulation (89%). CONCLUSIONS: The VEMP test demonstrated significant clinical value as it yielded the only abnormal test results in some patients suffering from a unilateral vestibular schwannoma. For oVEMPs, we suggest that ACS stimulation should be the initial test. In patients who responded to ACS and who had normal responses, BCV was not required. In patients with abnormal responses on the affected side using ACS, BCV at AFz should be used to confirm abnormal function of the superior vestibular nerve. In patients who exhibited no responses on either side to ACS, BCV was the only approach allowing assessment of the function of the superior vestibular nerve. We favor using AFz stimulation first because it is easier to perform in clinical practice than mastoid stimulation.

Lithium enhances remyelination of peripheral nerves.

Glycogen synthase kinase 3ß (GSK3ß) inhibitors, especially the mood stabilizer lithium chloride, are also used as neuroprotective or anti-inflammatory agents. We studied the influence of LiCl on the remyelination of peripheral nerves. We showed that the treatment of adult mice with LiCl after facial nerve crush injury stimulated the expression of myelin genes, restored the myelin structure, and accelerated the recovery of whisker movements. LiCl treatment also promoted remyelination of the sciatic nerve after crush. We also demonstrated that peripheral myelin gene MPZ and PMP22 promoter activities, transcripts, and protein levels are stimulated by GSK3ß inhibitors (LiCl and SB216763) in Schwann cells as well as in sciatic and facial nerves. LiCl exerts its action in Schwann cells by increasing the amount of ß-catenin and provoking its nuclear localization. We showed by ChIP experiments that LiCl treatment drives ß-catenin to bind to T-cell factor/lymphoid-enhancer factor response elements identified in myelin genes. Taken together, our findings open perspectives in the treatment of nerve demyelination by administering GSK3ß inhibitors such as lithium.

Auditory outcomes after implantation and electrical stimulation of the lateral ampullar nerve in guinea pig.

OBJECTIVE: To determine in a guinea pig model the factors of invasiveness of a bipolar electrode implanted in the horizontal semicircular canal (HSC) and to evaluate the consequences on hearing of electrical stimulation of the ampullary nerve. DESIGN: Sixteen guinea pigs divided into four groups underwent surgical opening of the HSC of one ear as follows: control (group 1), cyanoacrylate glue application on the HSC opening (group 2), electrode implantation with cyanoacrylate glue on the HSC opening (group 3), and electrode implantation with electrical stimulation (1 hr/day) for 9 days (group 4). Auditory brainstem responses were recorded before and after surgery and after electrical stimulation. The effectiveness of electrical stimulation in producing a horizontal vestibulo-ocular reflex was evaluated by recording eye movement with video-oculography. RESULTS: Group 1 animals showed hearing loss, and in group 2, sealing the HSC opening with cyanoacrylate glue preserved the hearing thresholds. After electrode implantation, seven of the eight animals showed hearing loss compared with preoperative values. Electrical stimulation did not induce additional hearing loss. CONCLUSION: Electrode implantation at the canal level entailed a risk of hearing loss in an animal model, but electrical stimulation of the horizontal ampullary nerve did not further alter hearing function.

Probing residual vestibular function with galvanic stimulation in vestibular loss patients.

INTRODUCTION: Galvanic vestibular stimulation (GVS) was used to probe the residual vestibular function in unilateral vestibular loss. METHODS: 39 control subjects, 60 patients areflexic to caloric tests, 21 patients with pre-operative acoustic neurinoma, and 26 patients with surgical deafferentation were tested with 4mA trapezoidal GVS. Horizontal slow phase velocity and vertical slow phase velocity components of the slow phase of induced nystagmus were recorded with videonystagmography. RESULTS: All patients had lower horizontal slow phase velocity compared with intact subject. In caloric areflexic patients, the intact ear responded similarly to controls. The lesioned ear was less excitable but could be inhibited as in controls. In patients with acoustic neurinoma, the intact ear was normally excitable but less sensitive to inhibition. The lesioned ear, although not excitable, could be inhibited. In patients with surgical deafferentation, the intact ear could be barely excited and not inhibited. The lesioned ear could not be excited but slightly inhibited. These results fit well with previous data in animal models after unilateral vestibular loss. CONCLUSION: Unilateral vestibular patients exhibit a progressive deterioration of the horizontal canal function, corresponding to 4 different patterns of GVS response. This study confirms that GVS is useful to probe evolution of the residual vestibular function in patients.

Stocktaking on the development of posturography for clinical use.

This report identifies fundamental problems to be addressed in order to build relevant clinical tests of human balance while standing. The stated purpose of these tests is identification of lesion site and/or definition of functional balance deficits in a specific patient. During a recent consensus meeting (ESCEBD), 60 researchers and experienced clinical users of posturography (14 European countries, 9 different disciplines) inventoried and critically analyzed the various methodologies of posturography currently used for clinical evaluation. To complement posturography, alternative methods of assessment of balance control were considered. The indications for the clinical use of posturography were defined as well as recommendations regarding measurement parameters, type of perturbations and signal analysis techniques to improve assessment of balance control. Consensus was reached that a force platform cannot be considered as a technique which is sufficient on its own to perform a clinically relevant test for the assessment of neuro-otological and musculo-skeletal conditions, evaluation of compensation or treatment (rehabilitation) or prediction of falls. It should be supported by complementary methods, such as segment motion analysis, body-fixed 2D or 3D accelerometer-gyroscope or electromyography. At present, no generally applicable posturography test is available with reasonable sensitivity and specificity for the diagnosis of balance disorders. Perturbation techniques are most likely needed to enhance the diagnostic yield of posturography.

Ocular and cervical VEMPs: a study of 74 patients suffering from peripheral vestibular disorders.

OBJECTIVE: This study compared the results of ocular and cervical vestibular evoked myogenic potentials (VEMPs) tests for healthy subjects with those for patients suffering from vestibular diseases to try to determine the clinical usefulness of combined ocular and cervical STB VEMP testing. METHODS: Thirty-two healthy volunteers and 74 patients with unilateral vestibular dysfunction underwent tests for ocular and cervical VEMPs induced by AC 100 dB nHL 500 Hz STB combined with caloric and audiometric tests. RESULTS: In healthy subjects, the mean P13-N23 peak-to-peak amplitude of cervical VEMPs was much larger than the mean n1-p1 peak-to-peak amplitude of ocular VEMPs. In patients, cervical and ocular VEMPs may be dissociated. The peak-to-peak amplitude of both cervical and ocular tests was abnormally in most of patients suffering from vestibular lesions. No correlations were found between VEMPs, the degree of hearing loss and/or of horizontal canalar paresis. CONCLUSIONS: Ocular and cervical VEMPs provide complementary information about saccular and utricular otolithic function. SIGNIFICANCE: Testing of ocular and cervical VEMPs allows the crossed vestibulo-ocular reflex and ipsilateral sacculo-collic reflex to be determined. These tests can help describe vestibular lesions and assess the effects of treatment and should therefore be used clinically.

The effects of the Chinese herbal medicine EMF01 on salicylate-induced tinnitus in rats.

AIM OF THE STUDY: Traditional Chinese medicine (TCM) has been reported to successfully alleviate tinnitus, although well-controlled studies have not been conducted. In this study, we attempted to test a TCM, Er Ming Fang (EMF01) containing Rehmannia glutinosa, Cornus officinalis, Salvia mittiorrhiza, Pueraria, Schisandra chinensis, Poria cocos and Platycodon grandiflorum, on salicylate-induced tinnitus in rats, using a conditioned lick suppression paradigm. MATERIALS AND METHODS: A pilot study examined the effect of 8.75 g/kg and 17.5 g/kg EMF01 (delivered by oral gavage for 20 days) and showed a slight decrease in the suppression ratio (SR) in the 8.75 g/kg group. In order to confirm the possible effect of EMF01 on tinnitus at 8.75 g/kg, a further study was carried out with a larger sample size. RESULTS: While there were statistically significant differences between the treatment groups, post hoc tests revealed that EMF01 did not have any significant effect on salicylate-induced tinnitus. CONCLUSIONS: While this study does not support the efficacy of EMF01 in the treatment of salicylate-induced tinnitus, further studies should be conducted to determine if it alleviates tinnitus associated with acoustic trauma.

Stimulation by cochlear implant in unilaterally deaf rats reverses the decrease of inhibitory transmission in the inferior colliculus.

In the last decade, numerous studies have investigated synaptic transmission changes in various auditory nuclei after unilateral cochlear injury. However, few data are available concerning the potential effect of electrical stimulation of the deafferented auditory nerve on the inhibitory neurotransmission in these nuclei. We report here for the first time the effect of chronic electrical stimulation of the deafferented auditory nerve on alpha1 subunit of the glycinergic receptor (GlyRalpha1) and glutamic acid decarboxylase (GAD)67 expression in the central nucleus of inferior colliculus (CIC). Adult rats were unilaterally cochleectomized by intracochlear neomycin sulphate injection. Fifteen days later, the ipsilateral auditory nerve was chronically stimulated either 4, 8 or 22 h daily, for 5 days using intracochlear bipolar electrodes. GlyRalpha1 and GAD67 mRNA and protein were quantified in the CIC using in situ hybridization and immunohistofluorescence methods. Our data showed that as after surgical ablation, GlyRalpha1 and GAD67 expression were strongly decreased in the contralateral CIC after unilateral chemical cochleectomy. Most importantly, these postlesional down-modulations were significantly reversed by chronic electrical stimulation of the deafferented auditory nerve. This recovery, however, did not persist for more than 5 days after the cessation of the deafferented auditory nerve electrical stimulation. Thus, downregulations of GlyRalpha1 and GAD67 may be involved both in the increased excitability observed in the CIC after unilateral deafness and consequently in the tinnitus frequently observed in unilateral adult deaf patients. Electrical stimulation of the deafferented auditory nerve in patients may be a potential new approach for treating tinnitus with unilateral hearing loss.

Behavioral effects of a deletion in Kcnn2, the gene encoding the SK2 subunit of small-conductance Ca2+-activated K+ channels.

Small-conductance Ca(2+)-activated potassium (SK) channels are heteromeric complexes of SK alpha-subunits and calmodulin that modulate membrane excitability, are responsible for part of the after-hyperpolarization (AHP) following action potentials, and thus control the firing patterns and excitability of most central neurons. An engineered knockout allele for the SK2 subunit has previously been reported. The hippocampal neurons of these mice lacked the medium latency component of the AHP, but the animals were not described as presenting any overt behavioral phenotype. In this report, we describe a deletion in the 5' region of the Kcnn2 gene encoding the SK2 subunit in the mouse neurological frissonnant (fri) mutant. The frissonnant mutant phenotype is characterized by constant rapid tremor and locomotor instability. It has been suggested, based merely on its phenotype, as a potential model for human Parkinson disease. We used a positional cloning strategy to identify the mutation underlying the frissonnant phenotype. We narrowed the genetic disease interval and identified a 3,441-bp deletion in the Kcnn2 gene, one of the three candidate genes present in the interval. Expression studies showed complete absence of normal Kcnn2 transcripts while some tissue-specific abnormal truncated variants were detected. Intracellular electrophysiological recordings of central vestibular neurons revealed permanent alterations of the AHP and firing behavior that might cause the tremor and associated locomotor deficits. Thus, the fri mutation suggests a new, potentially important physiological role, which had not been described, for the SK2 subunit of small-conductance Ca(2+)-activated potassium channels.

Relationship between dynamic balance and self-reported handicap in patients who have unilateral peripheral vestibular loss.

OBJECTIVE: The purpose of this study was to investigate whether Dizziness Handicap Inventory (DHI) score is related to postural performance as assessed by dynamic posturography. STUDY DESIGN: Retrospective study. SETTING: Outpatient in a tertiary referral center. PATIENTS: Ninety-two complete unilateral vestibular loss patients, categorized into 3 groups according to the postlesion stage: 1 to 2 months (n = 32; age, 47.6 +/- 10.7 yr), 4 to 7 months (n= 23; 47.1 +/- 8.37 yr), and 1 year and older (n = 37; 49.2 +/- 9.5 yr). MAIN OUTCOME MEASURES: Dizziness Handicap Inventory and dynamic balance measured with a seesaw platform moving either in the anterior-posterior or in the mediolateral direction. RESULTS: The mean DHI score was 25.8 +/- 18.7 and the range was 0 to 68. Dizziness Handicap Inventory scores did not differ significantly between the different unilateral vestibular loss groups studied. No difference was detected between the groups for the 3 subscores (emotional, functional, and physical), except that the older-than-1-year group had a significantly higher physical score than the 2 others. No correlation was found between DHI scores and postural indicators for either direction of the platform. However, patients unable to maintain balance when the seesaw platform moved in the mediolateral direction had significantly higher DHI scores than those who did not fall. CONCLUSION: Even if they are not directly related, we suggest that DHI and dynamic posturography are complementary approaches for appreciating the vestibular compensation process and are thus useful for postoperative counseling for vestibular loss patients.

Relationship Between Dynamic Balance and Self-Reported Handicap in Patients Who Have Unilateral Peripheral Vestibular Loss.

OBJECTIVE:: The purpose of this study was to investigate whether Dizziness Handicap Inventory (DHI) score is related to postural performance as assessed by dynamic posturography. STUDY DESIGN:: Retrospective study. SETTING:: Outpatient in a tertiary referral center. PATIENTS:: Ninety-two complete unilateral vestibular loss patients, categorized into 3 groups according to the postlesion stage: 1 to 2 months (n = 32; age, 47.6 +/- 10.7 yr), 4 to 7 months (n= 23; 47.1 +/- 8.37 yr), and 1 year and older (n = 37; 49.2 +/- 9.5 yr). MAIN OUTCOME MEASURES:: Dizziness Handicap Inventory and dynamic balance measured with a seesaw platform moving either in the anterior-posterior or in the mediolateral direction. RESULTS:: The mean DHI score was 25.8 +/- 18.7 and the range was 0 to 68. Dizziness Handicap Inventory scores did not differ significantly between the different unilateral vestibular loss groups studied. No difference was detected between the groups for the 3 subscores (emotional, functional, and physical), except that the older-than-1-year group had a significantly higher physical score than the 2 others. No correlation was found between DHI scores and postural indicators for either direction of the platform. However, patients unable to maintain balance when the seesaw platform moved in the mediolateral direction had significantly higher DHI scores than those who did not fall. CONCLUSION:: Even if they are not directly related, we suggest that DHI and dynamic posturography are complementary approaches for appreciating the vestibular compensation process and are thus useful for postoperative counseling for vestibular loss patients.

Saccular stimulation of the human cortex: a functional magnetic resonance imaging study.

Recent imaging studies have reported the projection of semicircular canal signals onto wide regions of the cerebral cortex but little is known about otolith projections onto the cerebral cortex. We used functional magnetic resonance imaging (fMRI) to investigate the activation of the cortex by loud clicks that selectively stimulate the sacculus. Twelve normal volunteers were presented with auditory stimuli via an earphone containing a piezo electric element. High-intensity [maximum volume of 120 dB (SPL)] or low-intensity [maximum volume of 110 dB (SPL)] clicks were delivered at a frequency of 1 Hz and lasted 1 ms. We first checked that the high-intensity, but not low-intensity, clicks stimulated the sacculus by determining the vestibular evoked myogenic potentials. We then analyzed two task conditions (high- and low-intensity clicks) in a boxcar paradigm. We obtained gradient echo echo-planar images by using a 1.5 T MRI system. We analyzed the fMRI time series data with SPM2. High-intensity clicks activated wide areas of the cortex, namely, the frontal lobe (prefrontal cortex, premotor cortex, and frontal eye fields), parietal lobe (the region around the intraparietal sulcus, temporo-parietal junction, and paracentral lobule), and cingulate cortex. These areas are similar to those reported in previous imaging studies that analyzed the cortical responses to the activation of the semicircular canals. Thus, semicircular canal and otolith/saccular signals may be processed in similar regions of the human cortex.