Methylphenidate attenuates the response to cold pain but not to aversive auditory stimuli in healthy human: a double-blind randomized controlled study.

INTRODUCTION: We recently showed that the psycho-stimulant norepinephrine-dopamine reuptake inhibitor methylphenidate (MP) prolonged cold pain threshold and tolerance in adults with attention-deficit hyperactivity disorder (ADHD). OBJECTIVES: The objectives of the present study were to: (1) examine whether MP has antinociceptive properties in healthy men; (2) test MP's effects on responses to aversive auditory stimuli. The underlying aim was to determine whether MP exerts antinociceptive properties or more generalized, nonspecific attenuating effects on different aversive sensory modalities. METHODS: This double-blind, crossover, randomized placebo-controlled study consisted of 2 sessions one week apart from each other. In each session, pain threshold (seconds) and tolerance (seconds) in response to painful cold stimulation were measured. Additionally, threshold (dB) and tolerance (seconds) to loud aversive auditory stimuli (500 Hz, 2000 Hz and white noise) were also tested prior to and 2 hours following the administration of a single dose of either 20 mg MP or an identical looking placebo. RESULTS: Forty men, 26.1 ± 4.0 (mean ± SD) years were enrolled in the study. Wilcoxon signed-rank test analyses showed that MP, but not the placebo, produced a significant increase in cold pain threshold (from 4.1 ± 2.6 to 5.4 ± 3.1 seconds, P = 0.001 and from 4.5 ± 2.6 to 4.3 ± 2.7 seconds, P = 0.2, respectively) and tolerance (from 57.8 ± 54.0 to 73.8 ± 61.8 seconds, P = 0.001 and from 52.5 ± 53.7 sec to 57.0 ± 52.9 seconds, P = 0.1, respectively). No significant changes were found in any of the auditory parameters. CONCLUSION: These results suggest that MP has an effect on nociceptive pathways rather than a nonspecific, generalized attenuating effect on aversive sensory stimuli.

Predicting hearing thresholds in occupational noise-induced hearing loss by auditory steady state responses.

OBJECTIVES: Currently available behavioral tools for the assessment of noise-induced hearing loss (NIHL) depend on the reliable cooperation of the subject. Furthermore, in workers' compensation cases, there is considerable financial gain to be had from exaggerating symptoms, such that accurate assessment of true hearing threshold levels is essential. An alternative objective physiologic tool for assessing NIHL is the auditory steady state response (ASSR) test, which combines frequency specificity with a high level of auditory stimulation, making it applicable for the evaluation of subjects with a moderate to severe deficit. The primary aim of the study was to assess the value of the multifrequency ASSR test in predicting the behavioral warble-tone audiogram in a large sample of young subjects with NIHL of varying severity or with normal hearing. The secondary goal was to assess suprathreshold ASSR growth functions in these two groups. DESIGN: The study group included 157 subjects regularly exposed to high levels of occupational noise, who attended a university-associated audiological clinic for evaluation of NIHL from 2009 through 2011. All underwent a behavioral audiogram, and on the basis of the findings, were divided into those with NIHL (108 subjects, 216 ears) or normal hearing (49 subjects, 98 ears). The accuracy of the ASSR threshold estimations for frequencies of 500, 1000, 2000, and 4000 Hz was compared between groups, and the specificity and sensitivity of the ASSR test in differentiating ears with or without NIHL was calculated using receiver operating characteristic analysis. Linear regression analysis was used to formulate an equation to predict the behavioral warble-tone audiogram at each test frequency using ASSR thresholds. Multifrequency ASSR amplitude growth as a function of stimulus intensity was compared between the NIHL and normal-hearing groups for 1000 Hz and 4000 Hz carrier frequencies. RESULTS: In the subjects with NIHL, ASSR thresholds to various frequencies were significantly and highly correlated with the behavioral warble-tone thresholds; Pearson correlation coefficients ranged from 0.6 to 0.8 over the four frequencies tested. Differences between thresholds ranged from 10 to 13 dB. The configuration of the ASSR waveforms closely approximated the behavioral audiogram. The sensitivity for screening hearing thresholds was 92%; by frequency, sensitivity ranged between 92.7 and 98.4%, but specificity was lower, especially at the low frequencies. ASSR accurately predicted moderate and severe NIHL. The mean ASSR growth amplitude to increasing stimulus level for 1000 and 4000 Hz was significantly steeper in the NIHL than in the normal-hearing group, with no significant difference between frequencies. CONCLUSIONS: The ASSR test has a high sensitivity to detect moderate to severe hearing loss in subjects with NIHL. Its use can facilitate the early identification of noise-exposed workers with NIHL. It may also serve an important medico-legal function in cases of workers' compensation. The ASSR test is not, by itself, an appropriate tool for hearing screening in the general population.

Effect of cochlear window fixation on air- and bone-conduction thresholds.

HYPOTHESIS: In the absence of patent cochlear windows, cochlear fluid inertia depends on the presence of a "third window" as a major component of the bone-conduction response. BACKGROUND: Studies have shown conflicting results regarding changes in air and bone conduction whenever, the round window, oval window, or both windows were occluded. METHOD: The study was performed in a tertiary university-affiliated medical center. Auditory brain responses to clicks and 1-kHz tone bursts delivered by air and bone conduction were tested in 5 adult-size fat sand rats. The round window membrane (total, 7 ears) was sealed with Super Glue, and auditory brain response testing was repeated. Thereafter, the stapes footplate was firmly fixated, and auditory brain responses were recorded for a third time. RESULTS: Round-window fixation induced a significant increase in air-conduction thresholds to clicks from 36.4 ± 0.9 to 69.3 ± 4.1 dB SPL, with no significant change in bone-conduction thresholds. When the stapes footplate was immobilized as well, air conduction increased by another 20 dB, on average, with no change in bone conduction. A similar deterioration was seen in response to 1 kHz stimulus. CONCLUSION: These findings support and complement earlier studies in the same animal model, suggesting that when the pressure outlet through the cochlear windows are abolished, still bone conduction displaces the cochlear partition probably because of a functioning "third window."

Prediction of aided and unaided audiograms using sound-field auditory steady-state evoked responses.

OBJECTIVE: To assess sound field auditory thresholds of hearing-impaired adults by using auditory steady-state evoked responses (ASSRs). DESIGN: ASSRs were recorded to carrier frequencies of 500, 1000, 2000, and 4000 Hz, each uniquely modulated at a single frequency of 80-100 Hz. ASSR thresholds were compared to behavioral auditory thresholds. STUDY SAMPLE: Twenty adults (11 male, age 35.6 years) with moderate-severe sensorineural hearing loss who had used hearing aids, and 10 normal-hearing subjects (mean age 22.4 years). RESULTS: For most frequencies, behavioral sound-field thresholds were slightly lower than ASSR thresholds in both aided and unaided conditions, with a significant correlation between them. Differences between ASSR and behavioral thresholds ranged between 516 dB in the unaided and between 5-16 dB in the aided condition. The ASSR amplitude growth function to 2000 Hz was steeper in both the aided and unaided conditions than in the normal-hearing group. CONCLUSIONS: Sound-field ASSRs can predict behavioral auditory thresholds in both the unaided and aided condition, as well as behavioral functional gains. The ASSR growth function for 2000 Hz is suggested to reflect an underlying mechanism of intensity encoding common to abnormal loudness perception frequently reported in cases of cochlear hearing loss.

Superior canal dehiscence effect on hearing thresholds: animal model.

OBJECTIVE: Superior semicircular dehiscence syndrome is associated with vestibular symptoms and an air-bone gap component in the audiogram, apparently caused by the creation of a pathological bony "third window" in the superior semicircular canal. The aim of this study was to evaluate changes in auditory air- and bone-conduction thresholds to low- and high-frequency stimuli in an animal model of a bony fenestration facing the aerated mastoid cavity. STUDY DESIGN: Anatomic, audiological. SETTING: Tertiary university-affiliated medical center. ANIMALS: A small hole was drilled in the bony apical portion of the superior semicircular canal facing the mastoid bulla/cavity, with preservation of the membranous labyrinth, in 5 adult-size fat sand rats. MAIN OUTCOME MEASURES: Auditory brain stem responses to clicks and 1-kHz tone bursts delivered by air and bone conduction before surgery, after opening the bulla, and after fenestration. RESULTS: After fenestration, a significant air-bone gap was measured in response to clicks (mean ± standard deviation, 37 ± 5.8 dB) and bursts (mean ± standard deviation, 34 ± 14.5 dB). The gap was attributable solely to the significant deterioration in air-conduction thresholds, in the absence of a significant change in bone conduction thresholds. The pattern of auditory brain response changes closely resembled that reported for middle ear dysfunction, namely, an increase in absolute latency of waves I, III, and V without significant alterations in interpeak latency differences. CONCLUSIONS: Bony fenestration of the superior semicircular canal toward an aerated cavity in a rodent model mimics the auditory loss pattern of patients with superior semicircular dehiscence syndrome. The dehiscent membrane accounts for the auditory changes.

Animal model of cochlear third window in the scala vestibuli or scala tympani.

HYPOTHESIS: The auditory impact of a cochlear third window differs by its location in the scala vestibuli or scala tympani. BACKGROUND: Pathologic third window has been investigated primarily in the vestibular apparatus of animals and humans. Dehiscence of the superior semicircular canal is the clinical model. METHODS: Fat sand rats (n = 11) have a unique inner-ear anatomy that allows easy surgical access. A window was drilled in the bony labyrinth over the scala vestibuli in 1 group (12 ears) and over the scala tympani in another (7 ears) while preserving the membranous labyrinth. Auditory brain stem responses to high- and low-frequency stimuli delivered by air and bone conduction were recorded before and after the procedure. RESULTS: Scala vestibuli group: preoperative air-conduction thresholds to clicks and tone-bursts averaged 8.3 and 9.6 dB, respectively, and bone-conduction thresholds, 4.6 and 3.3 dB, respectively; after fenestration, air-conduction thresholds averaged 40.4 and 41.8 dB, respectively, and bone-conduction thresholds, -1 and 5.6 dB, respectively. Scala tympani group: preoperative air-conduction thresholds to clicks and tone-bursts averaged 8.6 dB each, and bone-conduction thresholds, 7.9 dB and 7.1 dB, respectively; after fenestration, air-conduction thresholds averaged 11.4 and 9.3 dB, respectively, and bone-conduction thresholds, 9.3 and 4.2 dB, respectively. The changes in air- (p = 0.0001) and bone-conduction (p = 0.04) thresholds were statistically significant only in the scala vestibuli group. CONCLUSION: The presence of a cochlear third window over the scala vestibuli, but not over the scala tympani, causes a significant increase in air-conduction auditory thresholds. These results agree with the theoretic model and clinical findings and contribute to our understanding of vestibular dehiscence.

A third window of the posterior semicircular canal: an animal model.

OBJECTIVES/HYPOTHESIS: A third window in the vestibular apparatus has been investigated in both animals and humans, specifically in superior semicircular canal dehiscence. There are as yet no animal model studies of the effect of a third vestibular window of the posterior semicircular canal. STUDY DESIGN: Original basic research study. METHODS: A fenestration was drilled in the bony labyrinth over the posterior semicircular canal, preserving the membranous labyrinth, in seven healthy, 6-month-old, fat sand rats (total 10 ears). Auditory brain stem responses to low- and high-frequency acoustic stimuli delivered by air conduction and bone conduction were recorded before and after fenestration. RESULTS: On the preoperative auditory brainstem recordings, air-conduction thresholds to clicks and tone bursts averaged, respectively, 6.5 dB and 7.5 dB, and bone-conduction thresholds, 8 dB and 4.5 dB. Postoperatively, air-conduction thresholds averaged 14.5 dB, and bone-conduction thresholds 10.5 dB and 5 dB. The change in air-conduction thresholds was statistically significant (P < .01), whereas the bone conduction thresholds remained unchanged. CONCLUSIONS: A vestibular third window in the posterior semicircular canal decreases the sensitivity to air-conducted sound stimuli, raising the air-conduction threshold. There is no change in the bone-conduction threshold. These findings agree with the theoretical model and clinical findings.

Otologic and audiologic lesions due to blast injury.

AIM: To evaluate the effect of blast injury on the otologic and hearing state over time. SETTING: Otology unit of a tertiary referral center. METHODS: Seventy-three patients aged 16 to 73 years who sustained physical trauma from an explosion underwent otologic and audiologic examination 3-4 months and one year later. RESULTS: At the first examination, high-frequency sensorineural hearing loss was detected in 57 patients (78%), mixed hearing loss in 13 (19%), and low-tone conductive hearing loss in two (3%). Conductive hearing loss had improved by one year, while the cochlear hearing loss, in most cases, did not. Only 7% of the patients with tinnitus reported improvement after one year. CONCLUSIONS: The permanent otologic damage caused by blast injury cannot be determined before one year after the traumatic event.

Psychoacoustic tests for central auditory processing: normative data.

The comprehension of spoken language is based on the analysis of complex acoustic signals by the central auditory system, Direct relationships between gradual, spectrotemporal modifications of speech sounds and the impairment of the comprehension of such altered sounds have been found in many psychophysical studies. Thus, it is reasonable to assume that deficits in the understanding of speech seen in patients with acquired brain lesions may, to a certain degree, result from impaired central processing of acoustic signals. We report normative data collected from 94 young normal-hearing subjects on a battery of psychoacoustic tests designed to evaluate signal processing at different levels of the central auditory system. Monaural pure tone thresholds were used to evaluate the performance of peripheral hearing. The integrity of auditory brainstem processing was evaluated by quantifying masking level difference (MLD) values and gap detection (GD) thresholds. Three monaural speech tests (time-compressed speech [CS], filtered speech [FS] and speech in noise [SIN]) were conducted to evaluate the processing of distorted speech materials by cortical auditory processing mechanisms. Evaluating performance of naïve, young normal-hearing subjects, as we did here, is indispensable for (a) evaluating the effectiveness of potential tests, (b) evaluating their suitability for the examination of patients, and (c) the revision and further development of central auditory tests.