Variants of benign paroxysmal positional vertigo in relation to head position during sleep.

BACKGROUND: Patients with posterior- and lateral-(canal)-benign paroxysmal positional vertigo (BPPV)-canalolithiasis sleep in the affected-ear-down head position. Posterior-BPPV-canalolithiasis typically affects the right than left ear; sleeping in the right-ear-down head position may be causal. OBJECTIVE: To investigate the relationship between habitual head position during sleep and the onset of BPPV variants. METHODS: Among 1,170 cases of BPPV variants with unknown etiology, the affected ears, habitual head positions during sleep based on interviews, and relationships among them were investigated. RESULTS: Posterior-BPPV-canalolithiasis and lateral-BPPV-canalolithiasis-geotropic affected the right ear significantly more often. Significantly more patients with posterior-BPPV-canalolithiasis and lateral-BPPV-canalolithiasis-apogeotropic habitually slept in the right-ear-down head position. Patients with posterior- and lateral-BPPV-canalolithiasis and light cupula were more likely to sleep habitually in the affected-ear-down position than in the healthy-ear-down head position; no relationship was observed in patients with posterior- and lateral-BPPV-cupulolithiasis. In patients with posterior-BPPV-canalolithiasis and lateral-BPPV-canalolithiasis-geotropic, the proportion of right-affected ears in those sleeping habitually in the right-ear-down head position was significantly greater than that for the left-affected ear. CONCLUSIONS: A habitual affected-ear-down head position during sleep may contribute to BPPV-canalolithiasis and light cupula onset, but not BPPV-cupulolithiasis onset. However, habitual sleeping in the right-ear-down head position cannot explain the predominance of right-affected ears.

Long-latency optical responses from the dorsal inferior colliculus of Seba's fruit bat.

We used a novel microendoscope system to record simultaneously optical activity (fluorescence of a calcium indicator dye) and electrical activity (multi-unit activity and local field potentials) from the dorsal inferior colliculus of the echolocating bat, Carollia perspicillata. Optically recorded calcium responses to wide-band noise and to frequency-modulated bursts were recorded at probe depths down to 1300 µm, with the majority of active sites encountered at more shallow depths down to 800 µm. Calcium activity exhibited long latencies, within the time span of 50-100 ms after stimulus onset, significantly longer than onset latencies of either multi-unit activity or local field potentials. Latencies and amplitude/latency trading of these electrical responses were consistent with those seen in standard electrophysiological recordings, confirming that the microendoscope was able to record both neural and optical activity successfully. Optically recorded calcium responses rose and decayed slowly and were correlated in time with long-latency negative deflections in local field potentials. These data suggest that calcium-evoked responses may reflect known, sustained inhibitory interactions in the inferior colliculus.

Real-time imaging of head and neck squamous cell carcinomas using confocal micro-endoscopy and applicable dye: A preliminary study.

OBJECTIVES: Confocal laser endomicroscopy (CLE) is a technology that enables microscopic visualization of lesions in real-time (optical biopsy) and has been successfully applied for clinical use in gastroenterology. Recently, it was also introduced for head and neck squamous cell carcinoma (HNSCC) diagnostics. We previously designed a self-made CLE, which can provide bichrome images, with topical contrast agents that are safe for use in patients. Herein, we report findings of a pilot study using our self-made CLE to image pairs of normal and cancerous tissues. This study aimed to characterize the features of HNSCC compared with normal mucosa and to establish a methodology of in vivo real-time optical biopsy of HNSCCs. METHODS: HNSCC tissues were acquired from 10 patients who underwent surgical resection. Dissected specimens were first evaluated for their auto-fluorescence spectral profiles with 473 nm laser excitation and further optical observation. While obtaining the image, auto-fluorescence spectrum and intensity of the reflectance fluorescent signals were measured in real-time by a spectrometer. Subsequently, acriflavine was applied to the specimen to fluorescently label the nuclei and observe the difference between normal and cancerous tissues with 473 nm laser excitation. Finally, double staining with acriflavine and edible Food Red No.106 was performed to observe both nuclei and the cytoplasm of normal and cancerous tissues at 473 nm and 561 nm laser excitation. RESULTS: Lower signals were detected from auto-fluorescence images of cancer tissues than normal tissues with 473 nm laser excitation. After acriflavine application, there was a clear difference between cancer and normal mucosa in the uniformity of nuclear size and shape. In normal mucosa, cells were arranged in an orderly manner, with each cell resembling a frog's egg. By contrast, in cancer tissues, the cell density was higher, and the cellular arrangement was less orderly. Using both acriflavine and Food Red No.106, images became more vivid, but more complicated because red dye staining of the cytoplasm emerged as fluorescence at different wavelengths. CONCLUSIONS: Real-time in vivo imaging using the newly developed CLE and conditions may be used to distinguish cancer tissue from normal mucosa without invasive biopsy.

An attempt to measure the diametric relationship between slow and quick phases of nystagmus.

OBJECTIVE: To investigate whether our original method can precisely evaluate the angle between slow and quick phases of nystagmus (vector angle) and to determine whether vector angle analysis is helpful in differentiating between horizontal nystagmus and mixed nystagmus with horizontal and vertical components. METHODS: We included 20 healthy volunteers, 17 patients with horizontal nystagmus, and 15 patients with mixed nystagmus. Caloric nystagmus was recorded in healthy volunteers; positional nystagmus was recorded in each patient. We extracted the velocity of nystagmus from eye movement of each subject and analysed the vector angle. RESULTS: In caloric nystagmus, the vector angle approached 180 degrees as slow-phase velocity increased, suggesting that our vector angle measurement is more reliable with faster nystagmus. Importantly, in horizontal nystagmus from peripheral vestibular disease, the vector angle similarly approached 180 degrees as slow-phase velocity increased; in contrast, the vector angle in cases of mixed nystagmus from vertebrobasilar insufficiency or spinocerebellar degeneration significantly differed from the angle of caloric nystagmus. CONCLUSIONS: Vector angle analysis using our original algorithm can precisely evaluate the diametric relationship in vestibular nystagmus; it may be helpful in diagnosis of non-peripheral vestibular disorders.

Contribution of action potentials to the extracellular field potential in the nucleus laminaris of barn owl.

Extracellular field potentials (EFP) are widely used to evaluate in vivo neural activity, but identification of multiple sources and their relative contributions is often ambiguous, making the interpretation of the EFP difficult. We have therefore analyzed a model EFP from a simple brainstem circuit with separable pre- and postsynaptic components to determine whether we could isolate its sources. Our previous papers had shown that the barn owl neurophonic largely originates with spikes from input axons and synapses that terminate on the neurons in the nucleus laminaris (NL) (Kuokkanen PT, Wagner H, Ashida G, Carr CE, Kempter R. J Neurophysiol 104: 2274-2290, 2010; Kuokkanen PT, Ashida G, Carr CE, Wagner H, Kempter R. J Neurophysiol 110: 117-130, 2013; McColgan T, Liu J, Kuokkanen PT, Carr CE, Wagner H, Kempter R. eLife 6: e26106, 2017). To determine how much the postsynaptic NL neurons contributed to the neurophonic, we recorded EFP responses in NL in vivo. Power spectral analyses showed that a small spectral component of the evoked response, between 200 and 700 Hz, could be attributed to the NL neurons' spikes, while nucleus magnocellularis (NM) spikes dominate the EFP at frequencies ≳1 kHz. Thus, spikes of NL neurons and NM axons contribute to the EFP in NL in distinct frequency bands. We conclude that if the spectral components of source types are different and if their activities can be selectively modulated, the identification of EFP sources is possible. NEW & NOTEWORTHY Extracellular field potentials (EFPs) generate clinically important signals, but their sources are incompletely understood. As a model, we have analyzed the auditory neurophonic in the barn owl's nucleus laminaris. There the EFP originates predominantly from spiking in the afferent axons, with spectral power ≳1 kHz, while postsynaptic laminaris neurons contribute little. In conclusion, the identification of EFP sources is possible if they have different spectral components and if their activities can be modulated selectively.

In vivo calcium imaging from dentate granule cells with wide-field fluorescence microscopy.

A combination of genetically-encoded calcium indicators and micro-optics has enabled monitoring of large-scale dynamics of neuronal activity from behaving animals. In these studies, wide-field microscopy is often used to visualize neural activity. However, this method lacks optical sectioning capability, and therefore its axial resolution is generally poor. At present, it is unclear whether wide-field microscopy can visualize activity of densely packed small neurons at cellular resolution. To examine the applicability of wide-field microscopy for small-sized neurons, we recorded calcium activity of dentate granule cells having a small soma diameter of approximately 10 micrometers. Using a combination of high numerical aperture (0.8) objective lens and independent component analysis-based image segmentation technique, activity of putative single granule cell activity was separated from wide-field calcium imaging data. The result encourages wider application of wide-field microscopy in in vivo neurophysiology.

Micro-endoscopic system for functional assessment of neural circuits in deep brain regions: Simultaneous optical and electrical recordings of auditory responses in mouse's inferior colliculus.

In vivo Ca2+ imaging is a powerful method for the functional assessment of neural circuits. Although multi-photon excitation fluorescence microscopy has been widely used, observation of circuits in deep brain regions remains challenging. Recently, observing these deep regions has become possible via an endoscope consisting of an optical fiber bundle or gradient-index lens. We have designed a micro-endoscope system that enables simultaneous optical recording of fluorescence and electrical recording of neural activity. Using this system, we recorded auditory responses by simultaneously detecting changes in the fluorescence intensity of a Ca2+ indicator dye, multi-unit activities (MUA), and local field potentials (LFP) in the mouse's inferior colliculus (IC). Such simultaneous optical and electrical recordings enabled detailed comparison of electrically recorded phenomena (MUA and LFP) and optically recorded Ca2+ response. By systematically changing sound frequency and intensity, we determined the frequency tuning of the recording site. The best frequency shifted higher as the probe advanced more deeply, demonstrating that the system is capable of optically measuring the dorso-ventral organization of IC (i.e., tonotopicity). Thus, our new micro-endoscope system will be useful in the neurophysiological studies of a wide range of brain circuits, including those within the auditory system.

Regenerative therapy for vestibular disorders using human induced pluripotent stem cells (iPSCs): neural differentiation of human iPSC-derived neural stem cells after in vitro transplantation into mouse vestibular epithelia.

OBJECTIVES: Vestibular ganglion cells, which convey sense of motion from vestibular hair cells to the brainstem, are known to degenerate with aging and after vestibular neuritis. Thus, regeneration of vestibular ganglion cells is important to aid in the recovery of balance for associated disorders. METHODS: The present study derived hNSCs from induced pluripotent stem cells (iPSCs) and transplanted these cells into mouse utricle tissues. After a 7-day co-culture period, histological and electrophysiological examinations of transplanted hNSCs were performed. RESULTS: Injected hNSC-derived cells produced elongated axon-like structures within the utricle tissue that made contact with vestibular hair cells. A proportion of hNSC-derived cells showed spontaneous firing activities, similar to those observed in cultured mouse vestibular ganglion cells. However, hNSC-derived cells around the mouse utricle persisted as immature neurons or occasionally differentiated into putative astrocytes. Moreover, electrophysiological examination showed hNSC-derived cells around utricles did not exhibit any obvious spontaneous firing activities. CONCLUSIONS: Injected human neural stem cells (hNSCs) showed signs of morphological maturation including reconnection to denervated hair cells and partial physiological maturation, suggesting hNSC-derived cells possibly differentiated into neurons.

Htr2a-Expressing Cells in the Central Amygdala Control the Hierarchy between Innate and Learned Fear.

Fear is induced by innate and learned mechanisms involving separate pathways. Here, we used an olfactory-mediated innate-fear versus learned-fear paradigm to investigate how these pathways are integrated. Notably, prior presentation of innate-fear stimuli inhibited learned-freezing response, but not vice versa. Whole-brain mapping and pharmacological screening indicated that serotonin-2A receptor (Htr2a)-expressing cells in the central amygdala (CeA) control both innate and learned freezing, but in opposing directions. In vivo fiber photometry analyses in freely moving mice indicated that innate but not learned-fear stimuli suppressed the activity of Htr2a-expressing CeA cells. Artificial inactivation of these cells upregulated innate-freezing response and downregulated learned-freezing response. Thus, Htr2a-expressing CeA cells serve as a hierarchy generator, prioritizing innate fear over learned fear.

Role of PKA signaling in D2 receptor-expressing neurons in the core of the nucleus accumbens in aversive learning.

The nucleus accumbens (NAc) serves as a key neural substrate for aversive learning and consists of two distinct subpopulations of medium-sized spiny neurons (MSNs). The MSNs of the direct pathway (dMSNs) and the indirect pathway (iMSNs) predominantly express dopamine (DA) D1 and D2 receptors, respectively, and are positively and negatively modulated by DA transmitters via Gs- and Gi-coupled cAMP-dependent protein kinase A (PKA) signaling cascades, respectively. In this investigation, we addressed how intracellular PKA signaling is involved in aversive learning in a cell type-specific manner. When the transmission of either dMSNs or iMSNs was unilaterally blocked by pathway-specific expression of transmission-blocking tetanus toxin, infusion of PKA inhibitors into the intact side of the NAc core abolished passive avoidance learning toward an electric shock in the indirect pathway-blocked mice, but not in the direct pathway-blocked mice. We then examined temporal changes in PKA activity in dMSNs and iMSNs in behaving mice by monitoring Förster resonance energy transfer responses of the PKA biosensor with the aid of microendoscopy. PKA activity was increased in iMSNs and decreased in dMSNs in both aversive memory formation and retrieval. Importantly, the increased PKA activity in iMSNs disappeared when aversive memory was prevented by keeping mice in the conditioning apparatus. Furthermore, the increase in PKA activity in iMSNs by aversive stimuli reflected facilitation of aversive memory retention. These results indicate that PKA signaling in iMSNs plays a critical role in both aversive memory formation and retention.

Circuit-dependent striatal PKA and ERK signaling underlies rapid behavioral shift in mating reaction of male mice.

The selection of reward-seeking and aversive behaviors is controlled by two distinct D1 and D2 receptor-expressing striatal medium spiny neurons, namely the direct pathway MSNs (dMSNs) and the indirect pathway MSNs (iMSNs), but the dynamic modulation of signaling cascades of dMSNs and iMSNs in behaving animals remains largely elusive. We developed an in vivo methodology to monitor Förster resonance energy transfer (FRET) of the activities of PKA and ERK in either dMSNs or iMSNs by microendoscopy in freely moving mice. PKA and ERK were coordinately but oppositely regulated between dMSNs and iMSNs by rewarding cocaine administration and aversive electric shocks. Notably, the activities of PKA and ERK rapidly shifted when male mice became active or indifferent toward female mice during mating behavior. Importantly, manipulation of PKA cascades by the Designer Receptor recapitulated active and indifferent mating behaviors, indicating a causal linkage of a dynamic activity shift of PKA and ERK between dMSNs and iMSNs in action selection.

Minimal conductance-based model of auditory coincidence detector neurons.

Sound localization is a fundamental sensory function of a wide variety of animals. The interaural time difference (ITD), an important cue for sound localization, is computed in the auditory brainstem. In our previous modeling study, we introduced a two-compartment Hodgkin-Huxley type model to investigate how cellular and synaptic specializations may contribute to precise ITD computation of the barn owl's auditory coincidence detector neuron. Although our model successfully reproduced fundamental physiological properties observed in vivo, it was unsuitable for mathematical analyses and large scale simulations because of a number of nonlinear variables. In the present study, we reduce our former model into three types of conductance-based integrate-and-fire (IF) models. We test their electrophysiological properties using data from published in vivo and in vitro studies. Their robustness to parameter changes and computational efficiencies are also examined. Our numerical results suggest that the single-compartment active IF model is superior to other reduced models in terms of physiological reproducibility and computational performance. This model will allow future theoretical studies that use more rigorous mathematical analysis and network simulations.

Bedside evaluation of smooth pursuit eye movements in acute sensory stroke patients.

BACKGROUND AND PURPOSE: Unilateral saccadic pursuit is reported to be suggestive of a pontine lesion in sensory stroke patients. We attempted to verify this eye sign in just-hospitalized pontine sensory stroke patients. METHODS: Horizontal smooth pursuit eye movements were evaluated upon hospital arrival in 4 pontine sensory stroke patients and were compared with those in 6 thalamic sensory stroke patients. Eye movements were evaluated with the patient lying down on the emergency room or stroke care unit bed by means of a newly developed video-oculography-based eye movement recording system equipped to project a moving laser pointer onto the ceiling. RESULTS: Laterality of horizontal smooth pursuit gain in pontine sensory stroke patients was evident upon arrival; in thalamic sensory stroke patients, horizontal smooth pursuit gain was equal in both directions. These characteristics were easily detected at bedside. CONCLUSION: Unilateral saccadic pursuit in pontine sensory stroke patients may be a practical diagnostic sign that can be detected even in the emergency room. The video-oculography-based recording system equipped to project a moving laser pointer onto the ceiling may be useful for detecting this eye sign.

One-third of vertiginous episodes during the follow-up period are caused by benign paroxysmal positional vertigo in patients with Meniere's disease.

CONCLUSION: In the present study, about one-third of patients with Meniere's disease developed benign paroxysmal positional vertigo (BPPV)-like attacks. Additionally, more than one-third of all vertigo attacks were BPPV-like attacks. Thus, vertigo attacks in patients with Meniere's disease must be carefully treated because the therapy for such vertigo attacks is totally different from the therapy for BPPV. OBJECTIVE: Physicians sometimes encounter patients with previously diagnosed Meniere's disease who develop BPPV attacks during the course of clinical follow-up. In this study, we explored the frequency with which BPPV was involved in all vertiginous episodes among patients with Meniere's disease. METHODS: This retrospective study involved 296 patients with Meniere's disease who visited Kyoto University Hospital. The diagnosis of Meniere's disease was based on the guidelines for the diagnosis of Meniere's disease proposed by the Committee on Hearing and Equilibrium. We judged the cause of vertigo as one of the following five types: (1) definite Meniere's disease attack, (2) suspicious Meniere's disease attack, (3) definite BPPV attack, (4) suspicious BPPV attack, or (5) unknown. RESULTS: In all, 96 patients (32.8%) developed BPPV-like attacks, and 187 vertiginous episodes (37.9%) were caused by BPPV. The lateral semicircular canal was the most frequently involved canal.

Enhanced stability of hippocampal place representation caused by reduced magnesium block of NMDA receptors in the dentate gyrus.

BACKGROUND: Voltage-dependent block of the NMDA receptor by Mg2+ is thought to be central to the unique involvement of this receptor in higher brain functions. However, the in vivo role of the Mg2+ block in the mammalian brain has not yet been investigated, because brain-wide loss of the Mg2+ block causes perinatal lethality. In this study, we used a brain-region specific knock-in mouse expressing an NMDA receptor that is defective for the Mg2+ block in order to test its role in neural information processing. RESULTS: We devised a method to induce a single amino acid substitution (N595Q) in the GluN2A subunit of the NMDA receptor, specifically in the hippocampal dentate gyrus in mice. This mutation reduced the Mg2+ block at the medial perforant path-granule cell synapse and facilitated synaptic potentiation induced by high-frequency stimulation. The mutants had more stable hippocampal place fields in the CA1 than the controls did, and place representation showed lower sensitivity to visual differences. In addition, behavioral tests revealed that the mutants had a spatial working memory deficit. CONCLUSIONS: These results suggest that the Mg2+ block in the dentate gyrus regulates hippocampal spatial information processing by attenuating activity-dependent synaptic potentiation in the dentate gyrus.

Role of granule-cell transmission in memory trace of cerebellum-dependent optokinetic motor learning.

Adaptation of the optokinetic response (OKR) is an eye movement enhanced by repeated motion of a surrounding visual field and represents a prototype of cerebellum-dependent motor learning. Purkinje cells and vestibular nuclei (VN) receive optokinetic and retinal slip signals via the mossy fiber-granule cell pathway and climbing-fiber projections, respectively. To explore the neural circuits and mechanisms responsible for OKR adaptation, we adopted the reversible neurotransmission-blocking (RNB) technique, in which granule-cell transmission to Purkinje cells was selectively and reversibly blocked by doxycycline-dependent expression of transmission-blocking tetanus toxin in granule cells. Blockade of granule-cell inputs abolished both short-term and long-term OKR adaptation induced by repeated OKR training, but normal levels of both responses were immediately evoked in the pretrained RNB mice by OKR retraining once granule-cell transmission had recovered. Importantly, eye movement elicited by electrical stimulation of the cerebellar focculus was elevated by long-term but not by short-term OKR training in adaptive OKR-negative RNB mice. Furthermore, when the flocculus of adaptive OKR-negative RNB mice was electrically excited in-phase with OKR stimulation, these mice exhibited long-term adaptive OKR. These results indicate that convergent information to the VN was critical for acquisition and storage of long-term OKR adaptation with conjunctive action of Purkinje cells for OKR expression. Interestingly, in contrast to conditioned eyeblink memory, the expression of once acquired adaptive long-term OKR was not abrogated by blockade of granule-cell transmission, suggesting that distinct forms of neural plasticity would operate in different forms of cerebellum-dependent motor learning.

Aversive behavior induced by optogenetic inactivation of ventral tegmental area dopamine neurons is mediated by dopamine D2 receptors in the nucleus accumbens.

Dopamine (DA) transmission from the ventral tegmental area (VTA) is critical for controlling both rewarding and aversive behaviors. The transient silencing of DA neurons is one of the responses to aversive stimuli, but its consequences and neural mechanisms regarding aversive responses and learning have largely remained elusive. Here, we report that optogenetic inactivation of VTA DA neurons promptly down-regulated DA levels and induced up-regulation of the neural activity in the nucleus accumbens (NAc) as evaluated by Fos expression. This optogenetic suppression of DA neuron firing immediately evoked aversive responses to the previously preferred dark room and led to aversive learning toward the optogenetically conditioned place. Importantly, this place aversion was abolished by knockdown of dopamine D2 receptors but not by that of D1 receptors in the NAc. Silencing of DA neurons in the VTA was thus indispensable for inducing aversive responses and learning through dopamine D2 receptors in the NAc.

Biophysical basis of the sound analog membrane potential that underlies coincidence detection in the barn owl.

Interaural time difference (ITD), or the difference in timing of a sound wave arriving at the two ears, is a fundamental cue for sound localization. A wide variety of animals have specialized neural circuits dedicated to the computation of ITDs. In the avian auditory brainstem, ITDs are encoded as the spike rates in the coincidence detector neurons of the nucleus laminaris (NL). NL neurons compare the binaural phase-locked inputs from the axons of ipsi- and contralateral nucleus magnocellularis (NM) neurons. Intracellular recordings from the barn owl's NL in vivo showed that tonal stimuli induce oscillations in the membrane potential. Since this oscillatory potential resembled the stimulus sound waveform, it was named the sound analog potential (Funabiki et al., 2011). Previous modeling studies suggested that a convergence of phase-locked spikes from NM leads to an oscillatory membrane potential in NL, but how presynaptic, synaptic, and postsynaptic factors affect the formation of the sound analog potential remains to be investigated. In the accompanying paper, we derive analytical relations between these parameters and the signal and noise components of the oscillation. In this paper, we focus on the effects of the number of presynaptic NM fibers, the mean firing rate of these fibers, their average degree of phase-locking, and the synaptic time scale. Theoretical analyses and numerical simulations show that, provided the total synaptic input is kept constant, changes in the number and spike rate of NM fibers alter the ITD-independent noise whereas the degree of phase-locking is linearly converted to the ITD-dependent signal component of the sound analog potential. The synaptic time constant affects the signal more prominently than the noise, making faster synaptic input more suitable for effective ITD computation.

Theoretical foundations of the sound analog membrane potential that underlies coincidence detection in the barn owl.

A wide variety of neurons encode temporal information via phase-locked spikes. In the avian auditory brainstem, neurons in the cochlear nucleus magnocellularis (NM) send phase-locked synaptic inputs to coincidence detector neurons in the nucleus laminaris (NL) that mediate sound localization. Previous modeling studies suggested that converging phase-locked synaptic inputs may give rise to a periodic oscillation in the membrane potential of their target neuron. Recent physiological recordings in vivo revealed that owl NL neurons changed their spike rates almost linearly with the amplitude of this oscillatory potential. The oscillatory potential was termed the sound analog potential, because of its resemblance to the waveform of the stimulus tone. The amplitude of the sound analog potential recorded in NL varied systematically with the interaural time difference (ITD), which is one of the most important cues for sound localization. In order to investigate the mechanisms underlying ITD computation in the NM-NL circuit, we provide detailed theoretical descriptions of how phase-locked inputs form oscillating membrane potentials. We derive analytical expressions that relate presynaptic, synaptic, and postsynaptic factors to the signal and noise components of the oscillation in both the synaptic conductance and the membrane potential. Numerical simulations demonstrate the validity of the theoretical formulations for the entire frequency ranges tested (1-8 kHz) and potential effects of higher harmonics on NL neurons with low best frequencies (<2 kHz).

Benign paroxysmal positional vertigo and head position during sleep.

To determine whether any particular head positions during sleep are associated with BPPV, head position during sleep was monitored for 3 days in 50 BPPV patients after the disappearance of positional nystagmus and in 25 normal control subjects. A gravity sensor was attached to the center of the subject's forehead at home. The positional angle of the head was measured at 5-second intervals during sleep. In BPPV, the posterior semicircular canal was involved in 40 patients and the lateral semicircular canal in 10 patients. Recurrence was found in 22 of 50 BPPV patients. BPPV patients with recurrence were significantly more likely to sleep in the affected-ear-down 45-degree head position than were patients with no history of recurrence (P< 0.02). When the head is in the affected-ear-down 45-degree head position, the non-ampullated half of the posterior semicircular canal and the non-ampullated half of the lateral semicircular canal are nearly in the earth-vertical position, making it easier for detached otoconia to fall into the posterior or lateral semicircular canal and to agglomerate and attain a certain size in the lowest portion of each semicircular canal. Our findings showed that the affected-ear-down 45-degree head position during sleep could be an etiological factor of BPPV, more particularly in patients with recurrent BPPV.