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.

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.

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.

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.

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.

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.

Third Window Syndrome: Surgical Management of Cochlea-Facial Nerve Dehiscence.

Objective: This communication is the first assessment of outcomes after surgical repair of cochlea-facial nerve dehiscence (CFD) in a series of patients. Pre- and post-operative quantitative measurement of validated survey instruments, symptoms, diagnostic findings and anonymous video descriptions of symptoms in a cohort of 16 patients with CFD and third window syndrome (TWS) symptoms were systematically studied. Study design: Observational analytic case-control study. Setting: Quaternary referral center. Patients: Group 1 had 8 patients (5 children and 3 adults) with CFD and TWS who underwent surgical management using a previously described round window reinforcement technique. Group 2 had 8 patients (2 children and 6 adults) with CFD who did not have surgical intervention. Interventions: The Dizziness Handicap Inventory (DHI) and Headache Impact Test (HIT-6) were administered pre-operatively and post-operatively. In addition, diagnostic findings of comprehensive audiometry, cervical vestibular evoked myogenic potential (cVEMP) thresholds and electrocochleography (ECoG) were studied. Symptoms before and after surgical intervention were compared. Main outcome measures: Pre- vs. post-operative DHI, HIT-6, and audiometric data were compared statistically. The thresholds and amplitudes for cVEMP in symptomatic ears, ears with cochlea-facial nerve dehiscence and ears without CFD were compared statistically. Results: There was a highly significant improvement in DHI and HIT-6 at pre- vs. post-operative (p < 0.0001 and p < 0.001, respectively). The age range was 12.8-52.9 years at the time of surgery (mean = 24.7 years). There were 6 females and 2 males. All 8 had a history of trauma before the onset of their symptoms. The mean cVEMP threshold was 75 dB nHL (SD 3.8) for the operated ear and 85.7 dB (SD 10.6) for the unoperated ear. In contrast to superior semicircular canal dehiscence, where most ears have abnormal ECoG findings suggestive of endolymphatic hydrops, only 1 of 8 operated CFD ears (1 of 16 ears) had an abnormal ECoG study. Conclusions: Overall there was a marked improvement in DHI, HIT-6 and symptoms post-operatively. Statistically significant reduction in cVEMP thresholds was observed in patients with radiographic evidence of CFD. Surgical management with round window reinforcement in patients with CFD was associated with improved symptoms and outcomes measures.

Patterns of Pupillary Activity During Binocular Disparity Resolution.

This study examined the dynamic coordination between disconjugate, vergence eye movements, and pupil size in 52 normal subjects during binocular disparity stimulation in a virtual reality display. Eye movements and pupil area were sampled with a video-oculographic system at 100 Hz during performance of two tasks, (1) fusion of a binocular disparity step (±1.5° of visual angle in the horizontal plane) and (2) pursuit of a sinusoidally varying binocular disparity stimulus (0.1 Hz, ±2.6° of visual angle in the horizontal plane). Pupil size data were normalized on the basis of responses to homogeneous illumination increments ranging from 0.42 to 65.4 cd/m2. The subjects produced robust vergence eye movements in response to disparity step shifts and high fidelity sinusoidal vergence responses (R 2 relative to stimulus profile: 0.933 ± 0.088), accompanied by changes in pupil area. Trajectory plots of pupil area as a function of vergence angle showed that the pupil area at zero vergence is altered between epochs of linear vergence angle-pupil area relations. Analysis with a modified Gath-Geva clustering algorithm revealed that the dynamic relationship between the ocular vergence angle and pupil size includes two different transient, synkinetic response patterns. The near response pattern, pupil constriction during convergence and pupil dilation during divergence, occurred ~80% of the time across subjects. An opposite, previously undescribed synkinetic pattern was pupil constriction during divergence and pupil dilatation during convergence; it occurred ~15% of the time across subjects. The remainder of the data were epochs of uncorrelated activity. The pupil size intercepts of the synkinetic segments, representing pupil size at initial tropia, had different relationships to vergence angle for the two main coordinated movement types. Hippus-like movements of the pupil could also be accompanied by vergence movements. No pupil coordination was observed during a conjugate pursuit task. In terms of the current dual interaction control model (1), findings suggest that the synkinetic eye and pupillary movements are produced by a dynamic switch of the influence of vergence related information to pupil control, accompanied by a resetting of the pupil aperture size at zero-vergence.

Mass Spectrometric Imaging of Ceramide Biomarkers Tracks Therapeutic Response in Traumatic Brain Injury.

Traumatic brain injury (TBI) is a serious public health problem and the leading cause of death in children and young adults. It also contributes to a substantial number of cases of permanent disability. As lipids make up over 50% of the brain mass and play a key role in both membrane structure and cell signaling, their profile is of particular interest. In this study, we show that advanced mass spectrometry imaging (MSI) has sufficient technical accuracy and reproducibility to demonstrate the anatomical distribution of 50 µm diameter microdomains that show changes in brain ceramide levels in a rat model of controlled cortical impact (CCI) 3 days post injury with and without treatment. Adult male Sprague-Dawley rats received one strike and were euthanized 3 days post trauma. Brain MS images showed increase in ceramides in CCI animals compared to control as well as significant reduction in ceramides in CCI treated animals, demonstrating therapeutic effect of a peptide agonist. The data also suggests the presence of diffuse changes outside of the injured area. These results shed light on the extent of biochemical and structural changes in the brain after traumatic brain injury and could help to evaluate the efficacy of treatments.

Laser Desorption/Ionization Mass Spectrometric Imaging of Endogenous Lipids from Rat Brain Tissue Implanted with Silver Nanoparticles.

Mass spectrometry imaging (MSI) of tissue implanted with silver nanoparticulate (AgNP) matrix generates reproducible imaging of lipids in rodent models of disease and injury. Gas-phase production and acceleration of size-selected 8 nm AgNP is followed by controlled ion beam rastering and soft landing implantation of 500 eV AgNP into tissue. Focused 337 nm laser desorption produces high quality images for most lipid classes in rat brain tissue (in positive mode: galactoceramides, diacylglycerols, ceramides, phosphatidylcholines, cholesteryl ester, and cholesterol, and in negative ion mode: phosphatidylethanolamides, sulfatides, phosphatidylinositol, and sphingomyelins). Image reproducibility in serial sections of brain tissue is achieved within <10% tolerance by selecting argentated instead of alkali cationized ions. The imaging of brain tissues spotted with pure standards was used to demonstrate that Ag cationized ceramide and diacylglycerol ions are from intact, endogenous species. In contrast, almost all Ag cationized fatty acid ions are a result of fragmentations of numerous lipid types having the fatty acid as a subunit. Almost no argentated intact fatty acid ions come from the pure fatty acid standard on tissue. Graphical Abstract ᅟ.

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.

What is nausea? A historical analysis of changing views.

The connotation of "nausea" has changed across several millennia. The medical term 'nausea' is derived from the classical Greek terms ναυτια and ναυσια, which designated the signs and symptoms of seasickness. In classical texts, nausea referred to a wide range of perceptions and actions, including lethargy and disengagement, headache (migraine), and anorexia, with an awareness that vomiting was imminent only when the condition was severe. However, some recent articles have limited the definition to the sensations that immediately precede emesis. Defining nausea is complicated by the fact that it has many triggers, and can build-up slowly or rapidly, such that the prodromal signs and symptoms can vary. In particular, disengagement responses referred to as the "sopite syndrome" are typically present only when emetic stimuli are moderately provocative, and do not quickly culminate in vomiting or withdrawing from the triggering event. This review considers how the definition of "nausea" has evolved over time, and summarizes the physiological changes that occur prior to vomiting that may be indicative of nausea. Also described are differences in the perception of nausea, as well as the accompanying physiological responses, that occur with varying stimuli. This information is synthesized to provide an operational definition of nausea.

Distribution of 5-HT1F Receptors in Monkey Vestibular and Trigeminal Ganglion Cells.

BACKGROUND: Evidence of serotonergic involvement in vestibular pathway contributions to migraine and balance disorders is compelling. Serotonergic 5-HT1B and 5-HT1D receptors are expressed extensively in inner ear ganglia of monkeys and rats. The serotonergic 5-HT1F receptor is also a target of triptans. This study describes its distribution in vestibular and trigeminal ganglia of monkeys. METHODS: Using primary polyclonal antibodies raised against oligopeptides specific for the human 5-HT1F receptor, neuronal somatic area and intensity of immunoreactive vestibular and trigeminal ganglia were quantified. RESULTS AND DISCUSSION: Virtually all vestibular and considerable trigeminal ganglia showed positive 5-HT1F receptor immunoreactivity. Inferior and superior vestibular ganglia staining appeared confined to distinct cell regions, varying considerably among cells of different sizes: more intense in small, punctate in some medium and regionally polarized in some large cells. Analyses of average somatic vestibular neuronal immunoreactive intensity identified mainly medium sized cells with high standard deviation of intensity corresponding to punctately stained cells. Less variability occurred in somatic intensity staining and cellular distribution among 5-HT1F receptor immunopositive trigeminal ganglia. Most exhibited similar punctate staining patterns, higher mean somatic immunoreactive intensity and larger neuronal somatic size proportions per size distribution subpopulation compared to vestibular ganglia size distribution populations. Centrally directed vestibular ganglion neuronal processes, cochlear inner hair cells, vestibular hair cells and blood vessels in vestibular maculae and cristae were immunoreactive. The 5-HT1F receptor expression in vestibular ganglia shows complex variable staining intensity patterns associated with cell size of immunopositive neurons, not seen in immunopositive trigeminal ganglia and not previously evident with 5-HT1B and 5-HT1D receptor subtype immunoreactivity in vestibular ganglia. These data motivate exploration of 5-HT1 receptor oligomerization and ligand functional selectivity in differential serotonergic involvement in co-morbidity of migraine and balance disorders. Similar findings in cochlear inner hair cell afferents are applicable to migraine-related tinnitus or hypercusis (phonophobia).

Mass spectrometry imaging of rat brain lipid profile changes over time following traumatic brain injury.

BACKGROUND: Mild traumatic brain injury (TBI) is a common public health issue that may contribute to chronic degenerative disorders. Membrane lipids play a key role in tissue responses to injury, both as cell signals and as components of membrane structure and cell signaling. This study demonstrates the ability of high resolution mass spectrometry imaging (MSI) to assess sequences of responses of lipid species in a rat controlled cortical impact model for concussion. NEW METHOD: A matrix of implanted silver nanoparticles was implanted superficially in brain sections for matrix-assisted laser desorption (MALDI) imaging of 50µm diameter microdomains across unfixed cryostat sections of rat brain. Ion-mobility time-of-flight MS was used to analyze and map changes over time in brain lipid composition in a rats after Controlled Cortical Impact (CCI) TBI. RESULTS: Brain MS images showed changes in sphingolipids near the CCI site, including increased ceramides and decreased sphingomyelins, accompanied by changes in glycerophospholipids and cholesterol derivatives. The kinetics differed for each lipid class; for example ceramides increased as early as 1 day after the injury whereas other lipids changes occurred between 3 and 7 days post injury. COMPARISON WITH EXISTING METHOD(S): Silver nanoparticles MALDI matrix is a sensitive new tool for revealing previously undetectable cellular injury response and remodeling in neural, glial and vascular structure of the brain. CONCLUSIONS: Lipid biochemical and structural changes after TBI could help highlighting molecules that can be used to determine the severity of such injuries as well as to evaluate the efficacy of potential treatments.

Longitudinal Cognitive and Neurobehavioral Functional Outcomes Before and After Repairing Otic Capsule Dehiscence.

OBJECTIVE: Patients with peripheral vestibular dysfunction because of gravitational receptor asymmetries display signs of cognitive dysfunction and are assumed to have neurobehavioral sequelae. This was tested with pre- and postoperatively quantitative measurements in three cohort groups with superior semicircular canal dehiscence syndrome (SSCDS) symptoms with: 1) superior canal dehiscence (SCD) repaired via a middle cranial fossa craniotomy and canal plugging only; 2) otic capsule defects not visualized with imaging (no-iOCD) repaired with round window reinforcement (RWR) only; or 3) both SCD plugging and subsequent development of no-iOCD followed by RWR. STUDY DESIGN: Prospective patient series. SETTING: Tertiary referral center. PATIENTS: There were 13 adult and 4 pediatric patients with SSCDS who had completion of neuropsychology test batteries pre- and every 3 months postoperatively. Eight patients had no-iOCD and RWR exclusively, 5 had SCD and plugging exclusively, and 4 had both SCD plugging and then development of no-iOCD with RWR. These cohorts included SSCDS with 2 different dehiscence locations. INTERVENTIONS: Completion of a neuropsychology test battery preoperatively and at 3, 6, 9, and 12 months postoperatively that included: Beck Depression Inventory-II (BDI); Wide Range Intelligence Test (WRIT FSIQ) including average verbal (crystallized intelligence) and visual (fluid intelligence); Wide Range Assessment of Memory and Learning (WRAML), including the four domains of verbal memory, visual memory, attention/concentration, and working memory; and Delis-Kaplan Executive Function System (D-KEFS). The Dizziness Handicap Inventory (DHI) and the Headache Impact Test (HIT-6) were also completed to assess the impact of their disease on activities pre- and postoperatively. MAIN OUTCOME MEASURES: Quantitative and statistical analysis of their cognitive and neurobehavioral function. RESULTS: The pattern of differences between the SCD group and the no-iOCD group from WRAML verbal, visual, and attention test performance indicate different postoperative clinical trajectories. For the WRAML, there was a statistically significant improvement for visual memory and verbal memory for the no-iOCD only and both (SCD and subsequent no-iOCD) groups, but no mean improvement for the SCD only group. By contrast, the no-iOCD group had significantly lower scores on the WRAML attention test preoperatively, but they recovered postoperatively to match the other groups. The preoperative findings and postoperative outcomes did not differ significantly among patient groups on the WRAML working memory test, D-KEFS motor scores, D-KEFS number and letter scores, or Wide Range Intelligence Test scores. There was a significant decrease in the BDI for all groups. The IQ scores were unchanged. There was a statistically significant improvement in the DHI and HIT-6 scores postoperatively in all groups. CONCLUSIONS: There was a marked overall improvement in cognitive and neurobehavioral function postoperatively. Variability may result from duration of underlying disease before intervention. The initial decrement or delay in performance improvement measured in several patients may represent brain reorganization. Greater longitudinal data and greater subject numbers are necessary to better understand and optimize cognitive recovery.

Early Diagnosis and Treatment of Traumatic Vestibulopathy and Postconcussive Dizziness.

Mild traumatic brain injury (mTBI) is a common health condition in amateur and professional sports and in military operations but can occur in everyday life. Dizziness is the most common disorder seen after mTBI followed closely by headache. This article examines the diagnosis and treatment of vestibular disorders after mTBI. Data are included from the literature, and conclusions are drawn from the literature review and the experience of the authors. Much of what is known about this disorder comes from recent military experience, but the link to more common civilian injuries is detailed in this article.