Tools for standardized data collection: Speech, Language, and Hearing measurement protocols in the PhenX Toolkit.

The PhenX Toolkit (https://www.phenxtoolkit.org/) is an online catalog of recommended measurement protocols to facilitate cross-study analyses for biomedical research. An expert review panel (ERP) reviewed and updated the PhenX Toolkit Speech and Hearing domain to improve the precision and consistency of speech, language, and hearing disorder phenotypes. A three-member ERP convened in August 2018 to review the measurement protocols in the PhenX Speech and Hearing domain. Aided by three additional experts in voice assessment, vertigo, and stuttering, the ERP updated the 28 protocols to reflect the latest science and technology. ERP recommendations include six new protocols, five updated protocols (from the same source), and one retired protocol. New additions include two voice-related, three hearing-related, and two speech-related protocols. Additions reflect new phone/tablet applications for hearing and language, and clinical evaluations of voice. "Language" was added to the domain name, which is now "Speech, Language, and Hearing," to represent language-related protocols. These protocols can facilitate the assessment of speech, language, and hearing in clinical and population research. Common data elements (i.e., use of the same variables across studies) used by geneticists, otolaryngologists, audiologists, speech-language pathologists, and in other disciplines can lead to cross-study data integration and increased statistical power when studies are combined.

Integration of vestibular and hindlimb inputs by vestibular nucleus neurons: multisensory influences on postural control.

We recently demonstrated in decerebrate and conscious cat preparations that hindlimb somatosensory inputs converge with vestibular afferent input onto neurons in multiple central nervous system (CNS) locations that participate in balance control. Although it is known that head position and limb state modulate postural reflexes, presumably through vestibulospinal and reticulospinal pathways, the combined influence of the two inputs on the activity of neurons in these brainstem regions is unknown. In the present study, we evaluated the responses of vestibular nucleus (VN) neurons to vestibular and hindlimb stimuli delivered separately and together in conscious cats. We hypothesized that VN neuronal firing during activation of vestibular and limb proprioceptive inputs would be well fit by an additive model. Extracellular single-unit recordings were obtained from VN neurons. Sinusoidal whole body rotation in the roll plane was used as the search stimulus. Units responding to the search stimulus were tested for their responses to 10° ramp-and-hold roll body rotation, 60° extension hindlimb movement, and both movements delivered simultaneously. Composite response histograms were fit by a model of low- and high-pass filtered limb and body position signals using least squares nonlinear regression. We found that VN neuronal activity during combined vestibular and hindlimb proprioceptive stimulation in the conscious cat is well fit by a simple additive model for signals with similar temporal dynamics. The mean R2 value for goodness of fit across all units was 0.74 ± 0.17. It is likely that VN neurons that exhibit these integrative properties participate in adjusting vestibulospinal outflow in response to limb state.NEW & NOTEWORTHY Vestibular nucleus neurons receive convergent information from hindlimb somatosensory inputs and vestibular inputs. In this study, extracellular single-unit recordings of vestibular nucleus neurons during conditions of passively applied limb movement, passive whole body rotations, and combined stimulation were well fit by an additive model. The integration of hindlimb somatosensory inputs with vestibular inputs at the first stage of vestibular processing suggests that vestibular nucleus neurons account for limb position in determining vestibulospinal responses to postural perturbations.

Vestibular Neuroscience for the Headache Specialist.

BACKGROUND: The vestibular system is a multifaceted, integrative sensory system that is often referred to as the "multi-sensory" sense. There is an extensive literature about the vestibular sensory organs and afferent nerve pathways; however, this rich resource is often unknown to the headache specialist. AIMS: In this review, we highlight the significance of vestibular sensory processing beyond its role in the maintenance of balance. The role of the vestibular system in migraine pathophysiology is emphasized, not just in how it impacts dizziness or nausea, but also in its higher order effects on mood and cognition. How the vestibular system responds to current and new migraine therapies, such as anti-CGRP (calcitonin gene-related peptide) antibodies, is also discussed. CONCLUSIONS: The vestibular system is not just about balance; this should be taken into account by clinicians as they assess their patients' associated non-headache symptoms. There is a co-occurrence of migraine and vestibular-based problems and a confluence of disciplines relevant to vestibular migraine.

Beat-to-beat control of human optokinetic nystagmus slow phase durations.

This study provides the first clear evidence that the generation of optokinetic nystagmus fast phases (FPs) is a decision process that is influenced by performance of a concurrent disjunctive reaction time task (DRT). Ten subjects performed an auditory DRT during constant velocity optokinetic stimulation. Eye movements were measured in three dimensions with a magnetic search coil. Slow phase (SP) durations were defined as the interval between FPs. There were three main findings. Firstly, human optokinetic nystagmus SP durations are consistent with a model of a Gaussian basic interval generator (a type of biological clock), such that FPs can be triggered randomly at the end of a clock cycle (mean duration: 200-250 ms). Kolmogorov-Smirnov tests could not reject the modeled cumulative distribution for any data trials. Secondly, the FP need not be triggered at the end of a clock cycle, so that individual SP durations represent single or multiple clock cycles. Thirdly, the probability of generating a FP at the end of each interval generator cycle decreases significantly during performance of a DRT. These findings indicate that the alternation between SPs and FPs of optokinetic nystagmus is not purely reflexive. Rather, the triggering of the next FP is postponed more frequently if a recently presented DRT trial is pending action when the timing cycle expires. Hence, optokinetic nystagmus FPs show dual-task interference in a manner usually attributed to voluntary movements, including saccades. NEW & NOTEWORTHY: This study provides the first clear evidence that the generation of optokinetic nystagmus (OKN) fast phases is a decision process that is influenced by performance of a concurrent disjunctive reaction time task (DRT). The slow phase (SP) durations are consistent with a Gaussian basic interval generator and multiple interval SP durations occur more frequently in the presence of the DRT. Hence, OKN shows dual-task interference in a manner observed in voluntary movements, such as saccades.

Lipid imaging within the normal rat kidney using silver nanoparticles by matrix-assisted laser desorption/ionization mass spectrometry.

The well-characterized cellular and structural components of the kidney show distinct regional compositions and distribution of lipids. In order to more fully analyze the renal lipidome we developed a matrix-assisted laser desorption/ionization mass spectrometry approach for imaging that may be used to pinpoint sites of changes from normal in pathological conditions. This was accomplished by implanting sagittal cryostat rat kidney sections with a stable, quantifiable and reproducible uniform layer of silver using a magnetron sputtering source to form silver nanoparticles. Thirty-eight lipid species including seven ceramides, eight diacylglycerols, 22 triacylglycerols, and cholesterol were detected and imaged in positive ion mode. Thirty-six lipid species consisting of seven sphingomyelins, 10 phosphatidylethanolamines, one phosphatidylglycerol, seven phosphatidylinositols, and 11 sulfatides were imaged in negative ion mode for a total of seventy-four high-resolution lipidome maps of the normal kidney. Thus, our approach is a powerful tool not only for studying structural changes in animal models of disease, but also for diagnosing and tracking stages of disease in human kidney tissue biopsies.

Imaging of lipids in rat heart by MALDI-MS with silver nanoparticles.

Lipids are a major component of heart tissue and perform several important functions such as energy storage, signaling, and as building blocks of biological membranes. The heart lipidome is quite diverse consisting of glycerophospholipids such as phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), phosphatidylinositols (PIs), phosphatidylglycerols (PGs), cardiolipins (CLs), and glycerolipids, mainly triacylglycerols (TAGs). In this study, mass spectrometry imaging (MSI) enabled by matrix implantation of ionized silver nanoparticles (AgNP) was used to map several classes of lipids in heart tissue. The use of AgNP matrix implantation was motivated by our previous work showing that implantation doses of only 10(14)/cm(2) of 2 nm gold nanoparticulates into the first 10 nm of the near surface of the tissue enabled detection of most brain lipids (including neutral lipid species such as cerebrosides) more efficiently than traditional organic MALDI matrices. Herein, a similar implantation of 500 eV AgNP(-) across the entire heart tissue section results in a quick, reproducible, solvent-free, uniform matrix concentration of 6 nm AgNP residing near the tissue surface. MALDI-MSI analysis of either positive or negative ions produce high-quality images of several heart lipid species. In negative ion mode, 24 lipid species [16 PEs, 4 PIs, 1 PG, 1 CL, 2 sphingomyelins (SMs)] were imaged. Positive ion images were also obtained from 29 lipid species (10 PCs, 5 PEs, 5 SMs, 9 TAGs) with the TAG species being heavily concentrated in vascular regions of the heart.

Threat assessment and locomotion: clinical applications of an integrated model of anxiety and postural control.

Interactions between anxiety and vestibular symptoms have been described since the late 1800s. Typically, they have been conceptualized as bidirectional effects of one condition on the other (i.e., anxiety disorders as a cause of vestibular symptoms and vestibular disorders as a cause of anxiety symptoms). Over the past 30 years, however, a steady progression of neurophysiological investigations of gait and stance under conditions of postural threat, neuroanatomical studies of connections between threat assessment and vestibular pathways in the brain, and clinical research on anxiety-related vestibular conditions has offered the building blocks of a more integrated model. In this newer concept, threat assessment is an integral component of spatial perception, postural control, and locomotion in health and disease. It is not imposed on the vestibular system from the outside or simply reactive to vestibular dysfunction, but an inherently necessary part of every aspect of mobility. In this article, the authors review evidence that supports this model and then use it to examine common neurotologic conditions in which anxiety-related processes play important roles-fear of falling, primary and secondary anxiety disorders in patients with vestibular symptoms, and chronic subjective dizziness.

Frequency dependence of coordinated pupil and eye movements for binocular disparity tracking.

Introduction: Coordinated alignment of the eyes during gaze fixation and eye movements are an important component of normal visual function. We have previously described the coordinated behavior of convergence eye movements and pupillary responses using a 0.1 Hz binocular disparity-driven sine profile and a step profile. The goal of this publication is to further characterize ocular vergence-pupil size coordination over a wider range of frequencies of ocular disparity stimulation in normal subjects. Methods: Binocular disparity stimulation is generated by presentation of independent targets to each eye on a virtual reality display, while eye movements and pupil size are measured by an embedded video-oculography system. This design allows us to study two complimentary analyses of this motion relationship. First, a macroscale analysis describes the vergence angle of the eyes in response to binocular disparity target movement and pupil area as a function of the observed vergence response. Second, a microscale analysis performs a piecewise linear decomposition of the vergence angle and pupil relationship to permit more nuanced findings. Results: These analyses identified three main features of controlled coupling of pupil and convergence eye movements. First, a near response relationship operates with increasing prevalence during convergence (relative to the "baseline" angle); the coupling is higher with increased convergence in this range. Second, the prevalence of "near response"-type coupling decreases monotonically in the diverging direction; the decrease persists after the targets move (converge back) from maximum divergence toward the baseline positions, with a minimum prevalence of near response segments near the baseline target position. Third, an opposite polarity pupil response is infrequent, but tends to be more prevalent when the vergence angles are at maximum convergence or divergence for a sinusoidal binocular disparity task. Discussion: We suggest that the latter response is an exploratory "range-validation" when binocular disparity is relatively constant. In a broader sense, these findings describe operating characteristics of the near response in normal subjects and form a basis for quantitative assessments of function in conditions such as convergence insufficiency and mild traumatic brain injury.

Statistical Considerations for Subjective Visual Vertical and Subjective Visual Horizontal Assessment in Normal Subjects.

Objectives: Judgments of the subjective visual vertical (SVV) and subjective visual horizontal (SVH) while seated upright are commonly included in standard clinical test batteries for vestibular function. We examined SVV and SVH data from retrospective control to assess their statistical distributions and normative values for magnitudes of the preset effect, sex differences, and fixed-head versus head-free device platforms for assessment. Methods: Retrospective clinical SVV and SVH data from 2 test platforms, Neuro-otologic Test Center (NOTC) and the Neurolign Dx 100 (I-Portal Portable Assessment System Nystagmograph) were analyzed statistically (SPSS and MATLAB software) for 408 healthy male and female civilians and military service members, aged 18-50 years. Results: No prominent age-related effects were observed. The preset angle effects for both SVV and SVH, and their deviations from orthogonality, agree in magnitude with previous reports. Differences attributable to interactions with device type and sex are of small magnitude. Analyses confirmed that common clinical measure for SVV and SVH, the average of equal numbers of clockwise and counterclockwise preset trials, was not significantly affected by the test device or sex of the subject. Finally, distributional analyses failed to reject the hypothesis of underlying Gaussian distributions for the clinical metrics. Conclusions: z scores based on these normative findings can be used for objective detection of outliers from normal functional limits in the clinic.

New model of superior semicircular canal dehiscence with reversible diagnostic findings characteristic of patients with the disorder.

Background: Third window syndrome is a vestibular-cochlear disorder in humans in which a third mobile window of the otic capsule creates changes to the flow of sound pressure energy through the perilymph/endolymph. The nature and location of this third mobile window can occur at many different sites (or multiple sites); however, the most common third mobile window is superior semicircular canal dehiscence (SSCD). There are two essential objective diagnostic characteristics needed to validate a model of SSCD: the creation of a pseudoconductive hearing loss and cVEMP increased amplitude and decreased threshold. Methods: Adult Mongolian gerbils (n = 36) received surgical fenestration of the superior semicircular canal of the left inner ear. ABR and c+VEMP testing were carried out prior to surgery and over acute (small 1 mm SSCD, 1-10 days) or prolonged (large 2 mm SSCD, 28 days) recovery. Because recovery of function occurred quickly, condenser brightfield stereomicroscopic examination of the dehiscence site was carried out for the small SSCD animals post-hoc and compared to both ABRs and c+VEMPs. Micro-CT analysis was also completed with representative samples of control, day 3 and 10 post-SSCD animals. Results: The SSCD created a significant worsening of hearing thresholds of the left ear; especially in the lower frequency domain (1-4 kHz). Left (EXP)/right (CTL) ear comparisons via ABR show significant worsening thresholds at the same frequency representations, which is a proxy for the human pseudoconductive hearing loss seen in SSCD. For the c+VEMP measurements, increased amplitude of the sound-induced response (N1 2.5 ms and P1 3.2 ms) was observed in animals that received larger fenestrations. As the bone regrew, the c+VEMP and ABR responses returned toward preoperative values. For small SSCD animals, micro-CT data show that progressive osteoneogenesis results in resurfacing of the SSCD without bony obliteration. Conclusion: The large (2 mm) SSCD used in our gerbil model results in similar electrophysiologic findings observed in patients with SSCD. The changes observed also reverse and return to baseline as the SSCD heals by bone resurfacing (with the lumen intact). Hence, this model does not require a second surgical procedure to plug the SSCD.

Rizatriptan reduces vestibular-induced motion sickness in migraineurs.

A previous pilot study suggested that rizatriptan reduces motion sickness induced by complex vestibular stimulation. In this double-blind, randomized, placebo-controlled study we measured motion sickness in response to a complex vestibular stimulus following pretreatment with either rizatriptan or a placebo. Subjects included 25 migraineurs with or without migraine-related dizziness (23 females) aged 21-45 years (31.0 ± 7.8 years). Motion sickness was induced by off-vertical axis rotation in darkness, which stimulates both the semicircular canals and otolith organs of the vestibular apparatus. Results indicated that of the 15 subjects who experienced vestibular-induced motion sickness when pretreated with placebo, 13 showed a decrease in motion sickness following pretreatment with rizatriptan as compared to pretreatment with placebo (P < 0.02). This significant effect was not seen when subjects were exposed to more provocative vestibular stimulation. We conclude that the serotonin agonist, rizatriptan, reduces vestibular-induced motion sickness by influencing serotonergic vestibular-autonomic projections.

Mild blast wave exposure produces intensity-dependent changes in MMP2 expression patches in rat brains - Findings from different blast severities.

Matrix metalloproteinase 2 (MMP2) is a gelatinase with multiple functions at the neurovascular interface, including local modification of the glia limitans to facilitate access of immune cells into the brain and amyloid-beta degradation during responses to injury or disease. This study examines regional changes in immunoreactive MMP2 in the rat brain after a single mild (2.7-7.9 psi peak) or moderate (13-17.5 psi peak) blast overpressure (BOP) exposure. Immunopositive MMP2 expression was examined quantitatively in histological sections of decalcified rat heads as a marker at 2, 24, and 72 h after BOP. The MMP2 immunoreactivity was isolated to patchy deposits in brain parenchyma surrounding blood vessels. Separate analyses were conducted for the cerebellum, brain stem caudal to the thalamo-mesencephalic junction, and the cerebrum (including diencephalon). The deposits varied in number, size, staining homogeneity (standard deviation of immunopositive region), and a cumulative measure, the product of size, average intensity and number, as a function of blast intensity and time. The sequences of changes in MMP2 spots from sham control animals suggested that the mild BOP exposure differences normalized within 72 h. However, the responses to moderate exposure revealed a delayed response at 72 h in the subtentorial brain stem and the cerebrum, but not the cerebellum. Hence, local MMP2 responses may be a contextual biomarker for locally regulated responses to widely distributed brain injury foci.

Peripheral vestibular system: Age-related vestibular loss and associated deficits.

Given the interdependence of multiple factors in age-related vestibular loss (e.g., balance, vision, cognition), it is important to examine the individual contributions of these factors with ARVL. While the relationship between the vestibular and visual systems has been well studied (Bronstein et al., 2015), little is known about the association of the peripheral vestibular system with neurodegenerative disorders (Cronin et al., 2017). Further, emerging research developments implicate the vestibular system as an opportunity for examining brain function beyond balance, and into other areas, such as cognition and psychological functioning. Additionally, the bidirectional impact of psychological functioning is understudied in ARVL. Recognition of ARVL as part of a multifaceted aging process will help guide the development of integrated interventions for patients who remain at risk for decline. In this review, we will discuss a wide variety of characteristics of the peripheral vestibular system and ARVL, how it relates to neurodegenerative diseases, and correlations between ARVL and balance, vision, cognitive, and psychological dysfunction. We also discuss clinical implications as well as future directions for research, with an emphasis on improving care for patients with ARVL.

Portable eye-tracking as a reliable assessment of oculomotor, cognitive and reaction time function: Normative data for 18-45 year old.

Eye movements measured by high precision eye-tracking technology represent a sensitive, objective, and non-invasive method to probe functional neural pathways. Oculomotor tests (e.g., saccades and smooth pursuit), tests that involve cognitive processing (e.g., antisaccade and predictive saccade), and reaction time tests have increasingly been showing utility in the diagnosis and monitoring of mild traumatic brain injury (mTBI) in research settings. Currently, the adoption of these tests into clinical practice is hampered by a lack of a normative data set. The goal of this study was to construct a normative database to be used as a reference for comparing patients' results. Oculomotor, cognitive, and reaction time tests were administered to male and female volunteers, aged 18-45, who were free of any neurological, vestibular disorders, or other head injuries. Tests were delivered using either a rotatory chair equipped with video-oculography goggles (VOG) or a portable virtual reality-like VOG goggle device with incorporated infrared eye-tracking technology. Statistical analysis revealed no effects of age on test metrics when participant data were divided into pediatric (i.e.,18-21 years, following FDA criteria) and adult (i.e., 21-45 years) groups. Gender (self-reported) had an effect on auditory reaction time, with males being faster than females. Pooled data were used to construct a normative database using 95% reference intervals (RI) with 90% confidence intervals on the upper and lower limits of the RI. The availability of these RIs readily allows clinicians to identify specific metrics that are deficient, therefore aiding in rapid triage, informing and monitoring treatment and/or rehabilitation protocols, and aiding in the return to duty/activity decision. This database is FDA cleared for use in clinical practice (K192186).

Normative data for ages 18-45 for ocular motor and vestibular testing using eye tracking.

OBJECTIVE: Eye tracking technology has been employed in assessing ocular motor and vestibular function following vestibular and neurologic conditions, including traumatic brain injury (TBI). Assessments include tests that provide visual and motion (rotation) stimuli while recording horizontal, vertical, and torsional eye movements. While some of these tests have shown diagnostic promise in previous studies, their use in clinical practice is limited by the lack of normative data. The goal of this study was to construct normative reference ranges to be used when comparing patients' results. METHODS: Optokinetic response, subjective visual horizontal and vertical, and rotation tests were administered to male and female volunteers, ages 18-45, who were free from neurological, vestibular disorders, or other head injuries. Tests were administered using either a rotatory chair or a portable virtual reality-like goggle equipped with video-oculography. RESULTS: Reference values for eye movements in response to different patterns of stimuli were analyzed from 290 to 449 participants. Analysis of gender (self-reported) or age when grouped as pediatric (late adolescent; 18-21 years of age) and adult (21-45 years of age) revealed no effects on the test metrics. Data were pooled and presented for each test metric as the 95% reference interval (RI) with 90% confidence intervals (CI) on upper and lower limits of the RI. CONCLUSIONS: This normative database can serve as a tool to aid in diagnosis, treatment, and/or rehabilitation protocols for vestibular and neurological conditions, including mild TBI (mTBI). This database has been cleared by the FDA for use in clinical practice (K192186). LEVEL OF EVIDENCE: 2b.

Parabrachial nucleus neuronal responses to off-vertical axis rotation in macaques.

The caudal aspect of the parabrachial nucleus (PBN) contains neurons responsive to whole body, periodic rotational stimulation in alert monkeys (Balaban et al. in J Neurophysiol 88:3175-3193, 2002). This study characterizes the angular and linear motion-sensitive response properties of PBN unit responses during off-vertical axis rotation (OVAR) and position trapezoid stimulation. The OVAR responses displayed a constant firing component which varied from the firing rate at rest. Nearly two-thirds of the units also modulated their discharges with respect to head orientation (re: gravity) during constant velocity OVAR stimulation. The modulated response magnitudes were equal during ipsilateral and contralateral OVARs, indicative of a one-dimensional accelerometer. These response orientations during OVAR divided the units into three spatially tuned populations, with peak modulation responses centered in the ipsilateral ear down, contralateral anterior semicircular canal down, and occiput down orientations. Because the orientation of the OVAR modulation response was opposite in polarity to the orientation of the static tilt component of responses to position trapezoids for the majority of units, the linear acceleration responses were divided into colinear dynamic linear and static tilt components. The orientations of these unit responses formed two distinct population response axes: (1) units with an interaural linear response axis and (2) units with an ipsilateral anterior semicircular canal-contralateral posterior semicircular canal plane linear response axis. The angular rotation sensitivity of these units is in a head-vertical plane that either contains the linear acceleration response axis or is perpendicular to the linear acceleration axis. Hence, these units behave like head-based ('strapdown') inertial guidance sensors. Because the PBN contributes to sensory and interoceptive processing, it is suggested that vestibulo-recipient caudal PBN units may detect potentially dangerous anomalies in control of postural stability during locomotion. In particular, these signals may contribute to the range of affective and emotional responses that include panic associated with falling, malaise associated with motion sickness and mal-de-debarquement, and comorbid balance and anxiety disorders.

Distinctive Convergence Eye Movements in an Acquired Neurosensory Dysfunction.

In late 2016, diplomats in Havana, Cuba, began presenting with a unique symptom complex after perceiving a strange noise and/or feeling a pressure field in their domicile. This report is a retrospective, quantitative analysis of video-oculography data of pupillary light reflex performance and binocular disparity-driven eye and pupil movements during the acute time period after the reported exposure. The patterns of response in these 19 individuals are markedly different than those seen in a group of individuals with the usual acute mild traumatic brain injury (17 subjects) and from 62 control subjects (21-60 years old) with no injury. Non-linear least squares regression was used to estimate the model parameters from the eye movement and the pupil measurements (1). Linear discriminant analysis was then used to identify a classifier for an objective discrimination of the groups with >91% accuracy and no confusion between the acute neurosensory findings among the members of the Havana diplomatic community and the subjects with acute mild traumatic brain injury. This pattern difference in eye and pupil behavior may be a useful screen to help objectively distinguish blunt trauma from Havana-type effects in the future and to guide the affected individuals to appropriate care.

Blunt and blast head trauma: different entities.

Mild traumatic brain injury (mTBI) caused by blast-related and blunt head trauma is frequently encountered in clinical practice. Understanding the nuances between these two distinct types of injury leads to a more focused approach by clinicians to develop better treatment strategies for patients. In this study, we evaluated two separate cohorts of mTBI patients to ascertain whether any difference exists in vestibular-ocular reflex (VOR) testing (n = 55 enrolled patients: 34 blunt, 21 blast) and vestibular-spinal reflex (VSR) testing (n = 72 enrolled patients: 33 blunt, 39 blast). The VOR group displayed a preponderance of patients with blunt mTBI, demonstrating normal to high-frequency phase lag on rotational chair testing, whereas patients experiencing mTBI from blast-related causes revealed a trend toward low-frequency phase lag on evaluation. The VSR cohort showed that patients with posttraumatic migraine-associated dizziness tended to test higher on posturography. However, an indepth look at the total patient population in this second cohort reveals that a higher percentage of blast-exposed patients exhibited a significantly increased latency on motor control testing as compared to patients with blunt head injury (p < .02). These experiments identify a distinct difference between blunt-injury and blast-injury mTBI patients and provide evidence that treatment strategies should be individualized on the basis of each mechanism of injury.

Towards a Mechanistic-Driven Precision Medicine Approach for Tinnitus.

In this position review, we propose to establish a path for replacing the empirical classification of tinnitus with a taxonomy from precision medicine. The goal of a classification system is to understand the inherent heterogeneity of individuals experiencing and suffering from tinnitus and to identify what differentiates potential subgroups. Identification of different patient subgroups with distinct audiological, psychophysical, and neurophysiological characteristics will facilitate the management of patients with tinnitus as well as the design and execution of drug development and clinical trials, which, for the most part, have not yielded conclusive results. An alternative outcome of a precision medicine approach in tinnitus would be that additional mechanistic phenotyping might not lead to the identification of distinct drivers in each individual, but instead, it might reveal that each individual may display a quantitative blend of causal factors. Therefore, a precision medicine approach towards identifying these causal factors might not lead to subtyping these patients but may instead highlight causal pathways that can be manipulated for therapeutic gain. These two outcomes are not mutually exclusive, and no matter what the final outcome is, a mechanistic-driven precision medicine approach is a win-win approach for advancing tinnitus research and treatment. Although there are several controversies and inconsistencies in the tinnitus field, which will not be discussed here, we will give a few examples, as to how the field can move forward by exploring the major neurophysiological tinnitus models, mostly by taking advantage of the common features supported by all of the models. Our position stems from the central concept that, as a field, we can and must do more to bring studies of mechanisms into the realm of neuroscience.

Acute findings in an acquired neurosensory dysfunction.

BACKGROUND: In the Autumn of 2016, diplomatic personnel residing in Havana began to present with symptoms of dizziness, ear pain, and tinnitus that emerged after perception of high frequency noise and/or a pressure sensation. Understanding the acute symptoms of this disorder is important for better defining the disorder and developing optimal diagnostic, preventive, and treatment algorithms. OBJECTIVES: To define the presenting symptoms in a cohort of patients in the acute time period after perceiving a noise/pressure exposure in Havana. DESIGN/SETTINGS/PARTICIPANTS: Review of 25 symptomatic individuals who reported a localized sensation of noise/pressure and 10 asymptomatic individuals (roommates of those affected) who did not experience the sound/pressure. RESULTS: Immediately after the exposure, the majority of individuals reported intense ear pain in one or both ears and experienced tinnitus. All of the individuals noticed unsteadiness and features of cognitive impairment. On presentation to our center, dizziness (92%) and cognitive complaints (56%) were the most common symptoms. Formal testing revealed that 100% of individuals had an otolithic abnormality and evidence of cognitive dysfunction. CONCLUSION AND RELEVANCE: This study focuses on the acute presentation of a phenomenon in which symptoms emerge after perception of a localized noise/pressure and in which the acute symptomology includes the universal nature of vestibular injuries and select cognitive deficits. The findings presented in this acute group of patients begin to provide a better picture of the initial injury pattern seen after this exposure and may allow for more accurate diagnosis of this disorder in future cases. LEVEL OF EVIDENCE: Retrospective review.