Tinnitus mechanisms and the need for an objective electrophysiological tinnitus test.

Tinnitus, the perception of sound with no external auditory stimulus, is a complex, multifaceted, and potentially devastating disorder. Despite recent advances in our understanding of tinnitus, there are limited options for effective treatment. Tinnitus treatments are made more complicated by the lack of a test for tinnitus based on objectively measured physiological characteristics. Such an objective test would enable a greater understanding of tinnitus mechanisms and may lead to faster treatment development in both animal and human research. This review makes the argument that an objective tinnitus test, such as a non-invasive electrophysiological measure, is desperately needed. We review the current tinnitus assessment methods, the underlying neural correlates of tinnitus, the multiple tinnitus generation theories, and the previously investigated electrophysiological measurements of tinnitus. Finally, we propose an alternate objective test for tinnitus that may be valid in both animal and human subjects.

Prevalence and Trends of Slow Gait Speed in the United States.

Gait speed is a simple, effective indicator of age-related disease and disability. We sought to examine the prevalence and trends of slow gait speed in older Americans. Our unweighted analytic sample included 12,427 adults aged ≥ 65 years from the 2006-2016 waves of the Health and Retirement Study. Gait speed was measured in participant residences. Persons with gait speed < 0.8 or <0.6 m/s were slow. Sample weights were used to generate nationally representative estimates. The overall estimated prevalence of slow gait speed with the <0.8 m/s cut-point was 48.6% (95% confidence interval (CI): 47.4-49.8) in the 2006-2008 waves yet was 45.7% (CI: 44.3-47.1) in the 2014-2016 waves, but this downward trend was not statistically significant (p = 0.06). The estimated prevalence of slowness with the <0.6 m/s cut-point was 21.3% (CI: 20.4-22.3) for the 2006-2008 waves, 18.5% (CI: 17.5-19.4) for the 2010-2012 waves, and 19.2% (CI: 18.2-20.2) for the 2014-2016 waves, but there were again no significant trends (p = 0.61). Our findings showed that the estimated prevalence of slow gait speed in older Americans is pronounced, and different cut-points largely inform how slowness is categorized. Continued surveillance of slowness over time will help guide screening for disablement and identify sub-populations at greatest risk for targeted interventions.

The Prevalence and Trends of Instrumental Activities of Daily Living Impairments in the United States from 2008-2018.

Background: Instrumental activities of daily living (IADL) are neuropsychological-driven tasks that are linked to cognitive dysfunction. Examining population-based IADL deficits may reveal insights for the presence of these impairments in the United States. Objective: This investigation sought to evaluate the prevalence and trends of IADL impairments in Americans. Methods: A secondary analysis of data from the 2006-2018 waves of the Health and Retirement Study was conducted. The overall unweighted analytic sample included 29,764 Americans aged≥50 years. Respondents indicated their ability to perform six IADLs: manage money, manage medications, use a telephone, prepare hot meals, shop for groceries, and use a map. Persons reporting difficulty or an inability to complete an individual IADL were considered as having a task-specific impairment. Similarly, those indicating difficulty or an inability to perform any IADL were classified as having an IADL impairment. Sample weights were utilized to generate nationally-representative estimates. Results: Having an impairment in using a map (2018 wave: 15.7% (95% confidence interval (CI): 15.0-16.4) had the highest prevalence in individual IADLs regardless of wave examined. The overall prevalence of IADL impairments declined during the study period (p < 0.001) to 25.4% (CI: 24.5-26.2) in the 2018 wave. Older Americans and women had a consistently higher prevalence of IADL impairments compared to middle-aged Americans and men, respectively. The prevalence of IADL impairments was also highest among Hispanics and non-Hispanic Blacks. Conclusion: IADL impairments have declined over time. Continued surveillance of IADLs may help inform cognitive screening, identify subpopulations at risk of impairment, and guide relevant policy.

Comparison of two behavioral tests for tinnitus assessment in mice.

Animal research focused on chronic tinnitus associated with noise-induced hearing loss can be expensive and time-consuming as a result of the behavioral training required. Although there exist a number of behavioral tests for tinnitus; there have been few formal direct comparisons of these tests. Here, we evaluated animals in two different tinnitus assessment methods. CBA/CaJ mice were trained in an operant conditioning, active avoidance (AA) test, and a reflexive, gap-induced pre-pulse inhibition of acoustic startle (GPIAS) test, or both. Tinnitus was induced in awake mice by unilateral continuous sound exposure using a 2-kHz- or 1 2 octave-wide noise centered at 16 kHz and presented at 113- or 116-dB SPL. Tinnitus was assessed 8 weeks after sound overexposure. Most mice had evidence of tinnitus behavior in at least one of the two behaviors. Of the mice evaluated in AA, over half (55%) had tinnitus positive behavior. In GPIAS, fewer animals (13%) were positive than were identified using the AA test. Few mice were positive in both tests (10%), and only one was positive for tinnitus behavior at the same spectral frequency in both tests. When the association between tinnitus behavior and spontaneous activity recorded in the inferior colliculus was compared, animals with tinnitus behavior in AA exhibited increased spontaneous activity, while those positive in GPIAS did not. Thus, it appears that operant conditioning tests, like AA, maybe more reliable and accurate tests for tinnitus than reflexive tests.

Long-Duration Sound-Induced Facilitation Changes Population Activity in the Inferior Colliculus.

The inferior colliculus (IC) is at the midpoint of the auditory system and integrates virtually all information ascending from the auditory brainstem, organizes it, and transmits the results to the auditory forebrain. Its abundant, excitatory local connections are crucial for this task. This study describes a long duration sound (LDS)-induced potentiation in the IC that changes both subsequent tone-evoked responses and spontaneous activity. Afterdischarges, changes of spontaneous spiking following an LDS, were seen previously in single neurons. Here, we used multi-channel probes to record activity before and after a single, tetanic sound and describe the changes in a population of IC neurons. Following a 60 s narrowband-noise stimulation, a subset of recording channels (∼16%) showed afterdischarges. A facilitated response spike rate to tone pips following an LDS was also observed in ∼16% of channels. Both channels with an afterdischarge and channels with facilitated tone responses had higher firing rates in response to LDS, and the magnitude of the afterdischarges increased with increased responses to the LDS. This is the first study examining the effect of LDS stimulation on tone-evoked responses. This observed facilitation in vivo has similarities to post-tetanic potentiation in vitro as both manner of induction (strong stimulation for several seconds) as well as time-course of the facilitation (second to minute range) are comparable. Channels with and without facilitation appear to be intermixed and distributed widely in the central nucleus of IC, and this suggests a heretofore unknown property of some IC neurons or their circuits. Consequently, this sound-evoked facilitation may enhance the sound-evoked output of these neurons, while, simultaneously, most other IC neurons have reduced or unchanged output in response to the same stimulus.

FAS promoter polymorphism: outcome of childhood acute myeloid leukemia. A children's oncology group report.

PURPOSE: FAS is a cell surface receptor involved in apoptotic signal transmission. Deregulation of this pathway results in down-regulation of apoptosis and subsequent persistence of a malignant clone. A single nucleotide polymorphism resulting in guanine-to-adenine transition in the FAS promoter region (position -1377) is thought to reduce stimulatory protein 1 transcription factor binding and decrease FAS expression. Previous work has shown increased risk of developing acute myeloid leukemia (AML) in adult patients with a variant allele at this site. The same authors have shown that the presence of an adenine residue rather than a guanine residue at -1,377 bp significantly attenuates transcription factor stimulatory protein 1 binding and may contribute to a reduction in FAS expression and ultimately to the enrichment of apoptosis-resistant clones in AML. We hypothesized that FAS genotype by altering susceptibility to apoptosis might affect outcome of childhood AML therapy. EXPERIMENTAL DESIGN: Four hundred forty-four children treated for de novo AML on a uniform protocol were genotyped for FAS 1377. RESULTS: There were no significant differences in overall survival, event-free survival, treatment-related mortality, or relapse rate between patients with FAS 1377GG genotype versus 1377GA/1377AA genotypes. CONCLUSIONS: FAS 1377 genotype does not alter outcome of de novo AML in children.