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1.
Sci Rep ; 11(1): 13187, 2021 06 23.
Article in English | MEDLINE | ID: mdl-34162968

ABSTRACT

Electrophysiological studies show that nicotine enhances neural responses to characteristic frequency stimuli. Previous behavioral studies partially corroborate these findings in young adults, showing that nicotine selectively enhances auditory processing in difficult listening conditions. The present work extended previous work to include both young and older adults and assessed the nicotine effect on sound frequency and intensity discrimination. Hypotheses were that nicotine improves auditory performance and that the degree of improvement is inversely proportional to baseline performance. Young (19-23 years old) normal-hearing nonsmokers and elderly (61-80) nonsmokers with normal hearing between 500 and 2000 Hz received nicotine gum (6 mg) or placebo gum in a single-blind, randomized crossover design. Participants performed three experiments (frequency discrimination, frequency modulation identification, and intensity discrimination) before and after treatment. The perceptual differences were analyzed between pre- and post-treatment, as well as between post-treatment nicotine and placebo conditions as a function of pre-treatment baseline performance. Compared to pre-treatment performance, nicotine significantly improved frequency discrimination. Compared to placebo, nicotine significantly improved performance for intensity discrimination, and the improvement was more pronounced in the elderly with lower baseline performance. Nicotine had no effect on frequency modulation identification. Nicotine effects are task-dependent, reflecting possible interplays of subjects, tasks and neural mechanisms.


Subject(s)
Aging/physiology , Auditory Perception/drug effects , Nicotine/pharmacology , Non-Smokers , Affect/drug effects , Aged , Aged, 80 and over , Cross-Over Studies , Discrimination, Psychological/drug effects , Female , Humans , Male , Middle Aged , Nicotine/administration & dosage , Nicotine Chewing Gum , Non-Smokers/psychology , Oxygen/blood , Pitch Perception/drug effects , Psychomotor Performance , Receptors, Nicotinic/drug effects , Receptors, Nicotinic/physiology , Research Design , Signal-To-Noise Ratio , Single-Blind Method , Young Adult
2.
Hum Brain Mapp ; 41(17): 4982-4996, 2020 12.
Article in English | MEDLINE | ID: mdl-32820851

ABSTRACT

The concept of self and self-referential processing has a growing explanatory value in psychiatry and neuroscience, referring to the cognitive organization and perceptual differentiation of self-stimuli in health and disease. Conditions in which selfhood loses its natural coherence offer a unique opportunity for elucidating the mechanisms underlying self-disturbances. We assessed the psychoactive effects of psilocybin (230 µg/kg p.o.), a preferential 5-HT1A/2A agonist known to induce shifts in self-perception. Our placebo-controlled, double-blind, within-subject crossover experiment (n = 17) implemented a verbal self-monitoring task involving vocalizations and participant identification of real-time auditory source- (self/other) and pitch-modulating feedback. Subjective experience and task performance were analyzed, with time-point-by-time-point assumption-free multivariate randomization statistics applied to the spatiotemporal dynamics of event-related potentials. Psilocybin-modulated self-experience, interacted with source to affect task accuracy, and altered the late phase of self-stimuli encoding by abolishing the distinctiveness of self- and other-related electric field configurations during the P300 timeframe. This last effect was driven by current source density changes within the supragenual anterior cingulate and right insular cortex. The extent of the P300 effect was associated with the intensity of psilocybin-induced feelings of unity and changed meaning of percepts. Modulations of late encoding and their underlying neural generators in self-referential processing networks via 5-HT signaling may be key for understanding self-disorders. This mechanism may reflect a neural instantiation of altered self-other and relational meaning processing in a stimulus-locked time domain. The study elucidates the neuropharmacological foundation of subjectivity, with implications for therapy, underscoring the concept of connectedness.


Subject(s)
Auditory Perception/drug effects , Event-Related Potentials, P300/drug effects , Gyrus Cinguli/drug effects , Insular Cortex/drug effects , Psilocybin/pharmacology , Self Concept , Serotonin 5-HT1 Receptor Agonists/pharmacology , Serotonin 5-HT2 Receptor Agonists/pharmacology , Social Perception , Adult , Cross-Over Studies , Double-Blind Method , Electroencephalography , Executive Function/drug effects , Female , Humans , Male , Pitch Perception/drug effects , Psilocybin/administration & dosage , Psychomotor Performance/drug effects , Serotonin 5-HT1 Receptor Agonists/administration & dosage , Serotonin 5-HT2 Receptor Agonists/administration & dosage , Young Adult
4.
J Psychopharmacol ; 31(7): 861-872, 2017 07.
Article in English | MEDLINE | ID: mdl-28675114

ABSTRACT

Nicotine is a psychoactive substance that is commonly consumed in the context of music. However, the reason why music and nicotine are co-consumed is uncertain. One possibility is that nicotine affects cognitive processes relevant to aspects of music appreciation in a beneficial way. Here we investigated this possibility using Event-Related Potentials. Participants underwent a simple decision-making task (to maintain attentional focus), responses to which were signalled by auditory stimuli. Unlike previous research looking at the effects of nicotine on auditory processing, we used complex tones that varied in pitch, a fundamental element of music. In addition, unlike most other studies, we tested non-smoking subjects to avoid withdrawal-related complications. We found that nicotine (4.0 mg, administered as gum) increased P2 amplitude in the frontal region. Since a decrease in P2 amplitude and latency is related to habituation processes, and an enhanced ability to disengage from irrelevant stimuli, our findings suggest that nicotine may cause a reduction in habituation, resulting in non-smokers being less able to adapt to repeated stimuli. A corollary of that decrease in adaptation may be that nicotine extends the temporal window during which a listener is able and willing to engage with a piece of music.


Subject(s)
Cerebral Cortex/drug effects , Evoked Potentials, Auditory/drug effects , Habituation, Psychophysiologic/drug effects , Nicotine/pharmacology , Nicotinic Agonists/pharmacology , Pitch Perception/drug effects , Adolescent , Adult , Electroencephalography , Female , Humans , Male , Music , Nicotine/administration & dosage , Nicotinic Agonists/administration & dosage , Young Adult
5.
Ear Hear ; 34(5): 651-60, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23598724

ABSTRACT

OBJECTIVES: Animal data indicate that xylene induces cochlear dysfunction, characterized by the loss of outer hair cells. There is little evidence regarding xylene-induced ototoxicity in humans. The aim of the study was to investigate the possible adverse effects of xylene on the peripheral and central auditory system in humans. DESIGN: A total of 30 medical laboratory workers who had been exposed to a mixture of xylene isomers, together with 30 nonexposed control participants matched for gender, age, and educational level were selected. Participants of both groups were not exposed to noise levels above 85 dBA time-weighted average. All participants were evaluated with a comprehensive audiological test battery, which included measures of peripheral and central auditory function. Peripheral auditory measures included pure-tone audiometry and distortion product otoacoustic emissions. Behavioral measures of central auditory function included a pitch pattern sequence test, an adaptive test of temporal resolution, a dichotic digit test, and a masking level difference test. The auditory brainstem response was used to objectively evaluate the function of the auditory pathways at the brainstem level. Speech perception in quiet and in noise was evaluated using the Hearing In Noise Test (HINT). The xylene-exposed participants were extensively evaluated with regard to their exposure to both noise and xylene. Noise dosimetry was conducted over an 8-hr work shift to obtain noise-exposure levels for each xylene-exposed worker. Airborne xylene concentrations were obtained at 11 different workstations throughout the medical laboratories, and methyl hippuric acid levels per gram of creatinine in urine were obtained for each xylene-exposed subject. Finally, a detailed interview exploring current and past solvent and noise exposure was conducted. RESULTS: The xylene-exposed participants showed significantly worse pure-tone thresholds in comparison with the nonexposed participants. The xylene-exposed participants demonstrated significantly worse results than the control group participants for the pitch pattern sequence test, dichotic digit test, HINT, and the auditory brainstem response (absolute and interpeak latencies). No significant differences between the xylene-exposed and nonexposed participants were observed for distortion product otoacoustic emissions, adaptive test of temporal resolution, or the masking level difference test. A significant correlation between the concentrations of methyl hippuric acid in urine and pure-tone thresholds (2 to 8 kHz) was found in xylene-exposed workers. Also, participants with high cumulative dose of xylene exposure presented with poorer test results than participants with low cumulative dose of xylene exposure. CONCLUSIONS: The results of the present research suggest that xylene is associated with adverse central auditory effects and poorer sound detection abilities in humans. A major limitation of the study is that the results found among xylene-exposed participants cannot be proved to be permanent, and thus further research should be conducted to clarify this limitation. Workers exposed to this chemical should be routinely evaluated with a comprehensive audiological test battery, to detect early signs of auditory dysfunction.


Subject(s)
Auditory Diseases, Central/chemically induced , Auditory Diseases, Central/physiopathology , Occupational Exposure/adverse effects , Pitch Perception/drug effects , Speech Perception/drug effects , Xylenes/adverse effects , Adult , Audiometry, Pure-Tone , Auditory Diseases, Central/diagnosis , Auditory Threshold/drug effects , Auditory Threshold/physiology , Dichotic Listening Tests , Female , Humans , Male , Middle Aged , Noise, Occupational/adverse effects , Otoacoustic Emissions, Spontaneous/drug effects , Otoacoustic Emissions, Spontaneous/physiology , Pitch Perception/physiology , Solvents/adverse effects , Sound Localization/drug effects , Sound Localization/physiology , Speech Perception/physiology , Young Adult
7.
J Otolaryngol Head Neck Surg ; 40(6): 446-52, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22420430

ABSTRACT

OBJECTIVE: The frequency characteristics of the vestibular organ have gained notice in recent years, but the morphologic basis was unknown. This study investigated the gentamicin-induced damage of frequency-selective perception of the horizontal semicircular canal and its morphologic basis. METHODS: Eighty guinea pigs were randomly divided into four groups, one control group and three experimental groups. The experimental animals received gentamicin subcutaneously for 1 to 3 weeks. Short-latency vestibular evoked potentials evoked by 0.5 and 10 Hz step rotation stimuli following drug administration were recorded, and then the crista ampullaris of the horizontal semicircular canals was investigated by scanning and transmission electron microscopy. RESULTS: Damage to hair cells of the crista ampullaris is concentrated at the apex area first and then extends to the peripheral area of the vestibular crista ampullaris when the gentamicin administration time increased. When only the hair cells at the apex area are damaged, the high-frequency (10 Hz) rotation perception of the crista ampullaris of the horizontal semicircular canal was injured, but perceptions to 0.5 Hz step rotation stimulation remained normal. CONCLUSION: Gentamicin mainly affects the high-frequency perception function of the crista ampullaris of the horizontal semicircular canal. The hair cells at the central apex area of the crista ampullaris might be responsible for high-frequency rotation perception function.


Subject(s)
Anti-Bacterial Agents/toxicity , Gentamicins/toxicity , Pitch Perception/drug effects , Semicircular Canals/drug effects , Animals , Disease Models, Animal , Dose-Response Relationship, Drug , Guinea Pigs , Hair Cells, Ampulla/drug effects , Hair Cells, Ampulla/pathology , Injections, Subcutaneous , Microscopy, Electron, Scanning , Microscopy, Electron, Transmission , Reaction Time/drug effects , Semicircular Canals/pathology , Semicircular Ducts/drug effects , Semicircular Ducts/pathology , Vestibular Evoked Myogenic Potentials/drug effects , Vestibular Function Tests
8.
Percept Mot Skills ; 111(2): 589-607, 2010 Oct.
Article in English | MEDLINE | ID: mdl-21162458

ABSTRACT

The purpose of this study is to examine the effects of various levels of alcohol consumption on human response to auditory and visual stimuli in terms of reaction time, movement time, total reaction time, and error rate. Placebo level and three low-level alcohol doses were randomly assigned to 20 male university student volunteers. 30 min. after consuming the alcohol or placebo, participants responded to either auditory or visual stimuli. Total reaction time increased significantly at the mid-low dose of alcohol (0.3 g/kg). For alcohol doses less than .5 g/kg, the change in total reaction time was confined to reaction time, i.e., the processing time between onset of stimulus and onset of movement. Effects of alcohol were significantly more pronounced in the choice-type tests. Notably, the effects of alcohol on total reaction time and error rate were significant for auditory but not visual stimuli.


Subject(s)
Alcohol Drinking/psychology , Auditory Perception/drug effects , Ethanol/pharmacology , Psychomotor Performance/drug effects , Reaction Time/drug effects , Visual Perception/drug effects , Choice Behavior/drug effects , Color Perception/drug effects , Dose-Response Relationship, Drug , Humans , Male , Orientation/drug effects , Pattern Recognition, Visual/drug effects , Pitch Perception/drug effects , Young Adult
9.
J Neurosci ; 30(9): 3473-81, 2010 Mar 03.
Article in English | MEDLINE | ID: mdl-20203207

ABSTRACT

Cisplatin is a chemotherapeutic agent that is widely used in the treatment of solid tumors. Ototoxicity is a common side effect of cisplatin therapy and often leads to permanent hearing loss. The sensory organs of the avian ear are able to regenerate hair cells after aminoglycoside ototoxicity. This regenerative response is mediated by supporting cells, which serve as precursors to replacement hair cells. Given the antimitotic properties of cisplatin, we examined whether the avian ear was also capable of regeneration after cisplatin ototoxicity. Using cell and organ cultures of the chick cochlea and utricle, we found that cisplatin treatment caused apoptosis of both auditory and vestibular hair cells. Hair cell death in the cochlea occurred in a unique pattern, progressing from the low-frequency (distal) region toward the high-frequency (proximal) region. We also found that cisplatin caused a dose-dependent reduction in the proliferation of cultured supporting cells as well as increased apoptosis in those cells. As a result, we observed no recovery of hair cells after ototoxic injury caused by cisplatin. Finally, we explored the potential for nonmitotic hair cell recovery via activation of Notch pathway signaling. Treatment with the gamma-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester failed to promote the direct transdifferentiation of supporting cells into hair cells in cisplatin-treated utricles. Taken together, our data show that cisplatin treatment causes maintained changes to inner ear supporting cells and severely impairs the ability of the avian ear to regenerate either via proliferation or by direct transdifferentiation.


Subject(s)
Cisplatin/toxicity , Ear, Inner/drug effects , Nerve Degeneration/chemically induced , Nerve Regeneration/drug effects , Neurotoxins/toxicity , Amyloid Precursor Protein Secretases/antagonists & inhibitors , Animals , Antineoplastic Agents/toxicity , Apoptosis/drug effects , Apoptosis/physiology , Cell Differentiation/drug effects , Cell Differentiation/physiology , Cell Proliferation/drug effects , Cells, Cultured , Chick Embryo , Deafness/chemically induced , Deafness/pathology , Deafness/physiopathology , Disease Models, Animal , Dose-Response Relationship, Drug , Ear, Inner/pathology , Ear, Inner/physiopathology , Enzyme Inhibitors/pharmacology , Hair Cells, Auditory/drug effects , Hair Cells, Auditory/pathology , Hair Cells, Vestibular/drug effects , Hair Cells, Vestibular/pathology , Labyrinth Supporting Cells/drug effects , Labyrinth Supporting Cells/pathology , Nerve Degeneration/pathology , Nerve Degeneration/physiopathology , Nerve Regeneration/physiology , Organ Culture Techniques , Pitch Perception/drug effects , Pitch Perception/physiology , Receptors, Notch/drug effects , Receptors, Notch/metabolism
10.
Dev Psychobiol ; 51(3): 289-300, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19145592

ABSTRACT

Behavioral thresholds to pure tones were obtained from adult rhesus monkeys that had been exposed to lead during early development and unexposed cohort controls. Thresholds were elevated (by 2-9 dB) for the previously lead exposed monkeys at all frequencies tested (125-8,000 Hz in octave steps). Although the magnitude and direction of the differences were similar to significant effects reported for children, the more difficult task and much smaller sample sizes in this study of monkeys may have precluded obtaining significant differences at the same magnitude of effects observed in children. Thresholds for one lead-exposed monkey were significantly elevated at midrange frequencies in agreement with electrophysiological results obtained in another study [Lasky, Maier, Snodgrass, Hecox, and Laughlin [1995] Neurotoxicology and Teratology, 17, 633-644]. Behavioral measurements during the threshold task indicated less engagement for lead exposed monkeys than for controls. In addition, the lead exposed monkeys completed testing at significantly fewer frequencies and were significantly more difficult to test than control monkeys by tester ratings. These results are consistent with reports concerning the behavior of lead exposed children.


Subject(s)
Auditory Threshold/drug effects , Lead Poisoning/physiopathology , Organometallic Compounds/toxicity , Prenatal Exposure Delayed Effects/physiopathology , Animals , Association Learning/drug effects , Attention/drug effects , Audiometry, Pure-Tone , Conditioning, Operant/drug effects , Cooperative Behavior , Disease Models, Animal , Female , Macaca mulatta , Male , Motivation , Pitch Perception/drug effects , Pregnancy
11.
Neurobiol Learn Mem ; 90(2): 443-54, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18573347

ABSTRACT

Although the cholinergic system has long been implicated in the formation of memory, there had been no direct demonstration that activation of this system can actually induce specific behavioral memory. We have evaluated the "cholinergic-memory" hypothesis by pairing a tone with stimulation of the nucleus basalis (NB), which provides acetylcholine to the cerebral cortex. We found that such pairing induces behaviorally-validated auditory memory. NB-induced memory has the key features of natural memory: it is associative, highly-specific and rapidly induced. Moreover, the level of NB stimulation controls the amount of detail in memory about the tonal conditioned stimulus. While consistent with the hypothesis that properly-timed release of acetylcholine (ACh) during natural learning is sufficient to induce memory, pharmacological evidence has been lacking. This study asked whether scopolamine, a muscarinic antagonist, impairs or prevents the formation of NB-induced memory. Adult male rats were first tested for responses (disruption of ongoing respiration) to tones (1-15 kHz), constituting a pre-training behavioral frequency generalization gradient (BFGG). Then, they received a single session of 200 trials of a tone (8.00 kHz, 70 dB, 2 s) paired with electrical stimulation of the NB (100 Hz, 0.2 s). Immediately after training, they received either scopolamine (1.0 mg/kg, i.p.) or saline. Twenty-four hours later, they were tested for specific memory by obtaining post-training BFGGs. The saline group developed CS-specific memory, manifested by maximum increase in response specific to the CS frequency band. In contrast, the scopolamine group exhibited no such memory. These findings indicate that NB-induced specific associative behavioral memory requires the action of intrinsic acetylcholine at muscarinic receptors, and supports the hypothesis that natural memory formation engages the nucleus basalis and muscarinic receptors.


Subject(s)
Acetylcholine/physiology , Auditory Perception/drug effects , Basal Nucleus of Meynert/drug effects , Mental Recall/drug effects , Scopolamine/pharmacology , Acoustic Stimulation , Animals , Association Learning/drug effects , Cerebral Cortex/drug effects , Electric Stimulation , Electroencephalography/drug effects , Male , Pitch Perception/drug effects , Rats , Rats, Sprague-Dawley , Sound Spectrography
12.
Exp Brain Res ; 187(4): 613-21, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18340440

ABSTRACT

Previous studies have demonstrated the importance of both kinesthetic and auditory feedback for control of voice fundamental frequency (F0). In the present study, a possible interaction between auditory feedback and kinesthetic feedback for control of voice F0 was tested by administering local anesthetic to the vocal folds in the presence of perturbations in voice pitch feedback. Responses to pitch-shifted voice feedback were larger when the vocal fold mucosa was anesthetized than during normal kinesthesia. A mathematical model incorporating a linear combination of kinesthesia and pitch feedback simulated the main aspects of our experimental results. This model indicates that a feasible explanation for the increase in response magnitude with vocal fold anesthesia is that the vocal motor system uses both pitch and kinesthesia to stabilize voice F0 shortly after a perturbation of voice pitch feedback has been perceived.


Subject(s)
Feedback/physiology , Pitch Perception/physiology , Speech Acoustics , Voice , Adult , Anesthesia/methods , Female , Humans , Kinetics , Male , Mathematics , Middle Aged , Models, Biological , Phonation , Pitch Perception/drug effects
13.
Eur J Neurosci ; 26(9): 2613-26, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17970728

ABSTRACT

Song perception in songbirds, just as music and speech perception in humans, requires processing the spectral and temporal structure found in the succession of song-syllables. Using functional magnetic resonance imaging and synthetic songs that preserved exclusively either the temporal or the spectral structure of natural song, we investigated how vocalizations are processed in the avian forebrain. We found bilateral and equal activation of the primary auditory region, field L. The more ventral regions of field L showed depressed responses to the synthetic songs that lacked spectral structure. These ventral regions included subarea L3, medial-ventral subarea L and potentially the secondary auditory region caudal medial nidopallium. In addition, field L as a whole showed unexpected increased responses to the temporally filtered songs and this increase was the largest in the dorsal regions. These dorsal regions included L1 and the dorsal subareas L and L2b. Therefore, the ventral region of field L appears to be more sensitive to the preservation of both spectral and temporal information in the context of song processing. We did not find any differences in responses to playback of the bird's own song vs other familiar conspecific songs. We also investigated the effect of three commonly used anaesthetics on the blood oxygen level-dependent response: medetomidine, urethane and isoflurane. The extent of the area activated and the stimulus selectivity depended on the type of anaesthetic. We discuss these results in the context of what is known about the locus of action of the anaesthetics, and reports of neural activity measured in electrophysiological experiments.


Subject(s)
Auditory Pathways/physiology , Auditory Perception/physiology , Evoked Potentials/physiology , Finches/physiology , Prosencephalon/physiology , Vocalization, Animal/physiology , Acoustic Stimulation , Anesthetics/pharmacology , Animals , Auditory Cortex/anatomy & histology , Auditory Cortex/drug effects , Auditory Cortex/physiology , Auditory Pathways/anatomy & histology , Auditory Perception/drug effects , Brain Mapping , Cerebrovascular Circulation/physiology , Evoked Potentials/drug effects , Evoked Potentials, Auditory/drug effects , Evoked Potentials, Auditory/physiology , Finches/anatomy & histology , Magnetic Resonance Imaging , Male , Pitch Perception/drug effects , Pitch Perception/physiology , Prosencephalon/anatomy & histology , Prosencephalon/drug effects , Sexual Behavior, Animal/physiology , Species Specificity , Telencephalon/anatomy & histology , Telencephalon/drug effects , Telencephalon/physiology , Time Perception/drug effects , Time Perception/physiology
14.
Brain Res ; 1167: 80-91, 2007 Sep 05.
Article in English | MEDLINE | ID: mdl-17689505

ABSTRACT

In acoustic communication, animals must extract biologically relevant signals that are embedded in noisy environment. The present study examines how weak noise may affect the auditory sensitivity of neurons in the central nucleus of the mouse inferior colliculus (IC) which receives convergent excitatory and inhibitory inputs from both lower and higher auditory centers. Specifically, we studied the frequency sensitivity and minimum threshold of IC neurons using a pure tone probe and a weak white noise masker under forward masking paradigm. For most IC neurons, probe-elicited response was decreased by a weak white noise that was presented at a specific gap (i.e. time window). When presented within this time window, weak noise masking sharpened the frequency tuning curve and increased the minimum threshold of IC neurons. The degree of weak noise masking of these two measurements increased with noise duration. Sharpening of the frequency tuning curve and increasing of the minimum threshold of IC neurons during weak noise masking were mostly mediated through GABAergic inhibition. In addition, sharpening of frequency tuning curve by the weak noise masker was more effective at the high than at low frequency limb. These data indicate that in the real world the ambient noise may improve frequency sensitivity of IC neurons through GABAergic inhibition while inevitably decrease the frequency response range and sensitivity of IC neurons.


Subject(s)
Auditory Threshold/physiology , Inferior Colliculi/metabolism , Neural Inhibition/physiology , Neurons/metabolism , Pitch Perception/physiology , gamma-Aminobutyric Acid/metabolism , Acoustic Stimulation , Animals , Auditory Pathways/anatomy & histology , Auditory Pathways/drug effects , Auditory Pathways/metabolism , Auditory Threshold/drug effects , Evoked Potentials, Auditory/drug effects , Evoked Potentials, Auditory/physiology , Excitatory Postsynaptic Potentials/drug effects , Excitatory Postsynaptic Potentials/physiology , GABA Antagonists/pharmacology , Hearing Loss, Noise-Induced/physiopathology , Inferior Colliculi/anatomy & histology , Inferior Colliculi/drug effects , Inhibitory Postsynaptic Potentials/drug effects , Inhibitory Postsynaptic Potentials/physiology , Mice , Neural Inhibition/drug effects , Neurons/drug effects , Noise , Perceptual Masking/physiology , Pitch Perception/drug effects , Sound Localization/drug effects , Sound Localization/physiology , Synaptic Transmission/drug effects , Synaptic Transmission/physiology , Time Factors
15.
HNO ; 55(4): 299-306, 2007 Apr.
Article in German | MEDLINE | ID: mdl-16437215

ABSTRACT

BACKGROUND: Slight high frequency hearing loss following cisplatin chemotherapy can be proof of an ototoxic effect even when hearing ability is not yet clinically affected. To answer scientific questions, such as the relationship between cisplatin ototoxicity and drug regime or individual tolerance, early detection of ototoxicity and a classification relating to intensity and the affected frequencies are required. A search for relevant literature resulted the WHO-classification (1991) describing clinically relevant hearing loss and two high frequency hearing loss classifications published by Khan et al. (1982) and Brock et al. (1991). Their application is compared to a new, proprietary classification. PATIENTS AND METHODS: 55 patients (32 boys, 23 girls) undergoing cisplatin chemotherapy at Muenster University Hospital from 1999 to 2004 underwent audiometric tests in our department. From this data we developed a grading system, that was based on the WHO classification, but paid special attention to early ototoxic effects, to intensity of hearing loss and to the frequencies affected: Grade 0 (normal hearing) includes hearing loss of not more than 10 dB in all frequencies. Grade 1 (beginning hearing loss) encompasses > 10 dB up to 20 dB in at least one frequency or tinnitus. Grade 2 (moderate impairment) describes hearing loss > or = 4 kHz and differentiates 2a (> 20 to 40 dB), 2b (> 40 to 60 dB) and 2c (> 60 dB). Hearing loss < 4 kHz > 20 dB in grade 3 (severe impairment, hearing aids needed) is further classified according to grade 2 in a, b and c. Grade 4 (loss of function) finally describes average hearing loss < 4 kHz of at least 80 dB. This classification is compared to the two high frequency hearing loss classifications (Khan et al. and Brock et al.). RESULTS: The Muenster classification, compared to Khan et al. and Brock et al., demonstrated the best results in the early detection of hearing loss: All children with hearing loss of at least 20 dB after therapy had already shown pathological audiograms during treatment, when those audiograms were assessed by our classification. All children whose audiograms were flagged as pathological by our classification finally developed hearing loss. In terms of the prediction of hearing loss, our classification evaluated processing audiograms with a sensitivity, specificity and efficiency of 1.0. Progressive hearing loss was detected in 45 patients (Khan et al. 30, Brock et al. 38). Therefore our classification showed a better suitability for monitoring hearing loss than the other classifications. CONCLUSION: The Muenster classification is a suitable new basis for scientific questions concerning cisplatin ototoxicity. It detects hearing loss earlier and maps progression of hearing loss more precisely than the existing high frequency classifications (Khan et al. and Brock et al.).


Subject(s)
Audiometry, Pure-Tone/methods , Cisplatin/adverse effects , Hearing Loss/chemically induced , Hearing Loss/diagnosis , Severity of Illness Index , Adolescent , Antineoplastic Agents/adverse effects , Child , Child, Preschool , Female , Hearing Loss/classification , Humans , Male , Pitch Perception/drug effects , Reproducibility of Results , Sensitivity and Specificity
16.
Auris Nasus Larynx ; 34(2): 147-54, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17064865

ABSTRACT

OBJECTIVES: To investigate the interaction between welding fumes and noise in causation of hearing impairment. METHODS: Groups of rabbits (n=6) were exposed to noise, welding fumes or combination of both prior to Distortion Product Otoacoustic-Emissions (DPOAEs) analysis. The function of outer hair cells (OHCs) was examined by DPOAE assessment over a broad range of frequencies. Variations in DPOAE amplitude were compared between control (n=6) and exposed (n=18) groups. RESULTS: The DPOAEs levels measured at different frequencies (1379-6299 Hz) were found to decrease significantly (P<0.05) in rabbits exposed to 110 dB sound pressure level (SPL) broadband noise (8h/day, 12 days). In rabbits, exposed to carbon-steel welding fumes alone (157 mg/m(3)), the threshold shift was limited to the high frequencies (2759-6299 Hz), whereas, mixed exposure to noise and fumes resulted in reduction of DPOAEs at all the frequencies. Changes in DPOAEs were associated with increased susceptibility of erythrocytes to oxidation (P<0.05). Exposure to noise or fumes alone or simultaneously, suppressed total antioxidant ability of plasma as measured by ferric reducing ability of plasma (FRAP). Noise alone or in combination with fumes resulted in depletion of blood glutathione (GSH). Despite suppression of FRAP in the exposed groups, GSH was found to remain unchanged due to welding fumes suggesting that antioxidants other than GSH are affected by toxicants present in metal welding fumes. CONCLUSION: Exposure to very high levels of welding fumes can increase noise-related effects on OHC function by extending hearing threshold shift to wide band frequencies.


Subject(s)
Air Pollutants, Occupational/toxicity , Antioxidants/metabolism , Hair Cells, Auditory, Outer/drug effects , Noise/adverse effects , Otoacoustic Emissions, Spontaneous/drug effects , Welding , Animals , Glutathione/blood , Hearing Loss, Noise-Induced/etiology , Lipid Peroxidation/drug effects , Male , Pitch Perception/drug effects , Rabbits , Threshold Limit Values
17.
Acta Otolaryngol ; 126(5): 452-9, 2006 May.
Article in English | MEDLINE | ID: mdl-16698693

ABSTRACT

CONCLUSIONS: Brain-derived neurotrophic factor (BDNF) supply to the inner ear does not improve the time course or the extent of functional recovery after hair cell regeneration. Specifically it does not improve the residual threshold elevation observed after the completion of spontaneous recovery. OBJECTIVE: The avian inner ear is capable of hair cell regeneration and substantial functional recovery, but residual hearing deficits remain. We investigated whether functional recovery can be improved by intracochlear application of BDNF, which plays an important role in auditory ontogenesis and maintenance during adult life. METHODS: Hair cells in adult pigeons were destroyed by local application of gentamicin. After 3 days either BDNF or control solution was administered to the scala tympani by implanted osmotic minipumps for 8 weeks. Auditory brain stem responses (ABR) to tone pips were used to assess recovery of hearing thresholds in both groups. RESULTS: The application of gentamicin caused a frequency-dependent hearing loss that ranged from 24.8 dB SPL at low frequencies to 66.2 dB SPL at high frequencies. After day 10 substantial recovery was observed, but a significant threshold shift remained. The time course of recovery in the control and BDNF-treated groups was similar, without significant residual threshold differences in any frequency range.


Subject(s)
Auditory Threshold/drug effects , Brain-Derived Neurotrophic Factor/pharmacology , Deafness/physiopathology , Hair Cells, Auditory/drug effects , Nerve Regeneration/drug effects , Administration, Topical , Animals , Auditory Threshold/physiology , Cochlea/drug effects , Cochlea/physiopathology , Columbidae , Disease Models, Animal , Evoked Potentials, Auditory, Brain Stem/drug effects , Evoked Potentials, Auditory, Brain Stem/physiology , Gentamicins/toxicity , Hair Cells, Auditory/physiopathology , Loudness Perception/drug effects , Loudness Perception/physiology , Nerve Regeneration/physiology , Pitch Perception/drug effects , Pitch Perception/physiology
18.
J Neurophysiol ; 95(6): 3756-69, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16554513

ABSTRACT

The responses of primary auditory cortex (A1) neurons to pure tones in anesthetized animals are usually described as having mostly narrow, unimodal frequency tuning and phasic responses. Thus A1 neurons are believed not to carry much information about pure tones beyond sound onset. In awake cats, however, tuning may be wider and responses may have substantially longer duration. Here we analyze frequency-response areas (FRAs) and temporal-response patterns of 1,828 units in A1 of halothane-anesthetized cats. Tuning was generally wide: the total bandwidth at 40 dB above threshold was 4 octaves on average. FRA shapes were highly variable and many were diffuse, not fitting into standard classification schemes. Analyzing the temporal patterns of the largest responses of each unit revealed that only 9% of the units had pure onset responses. About 40% of the units had sustained responses throughout stimulus duration (115 ms) and 13% of the units had significant and informative responses lasting 300 ms and more after stimulus offset. We conclude that under halothane anesthesia, neural responses show many of the characteristics of awake responses. Furthermore, A1 units maintain sensory information in their activity not only throughout sound presentation but also for hundreds of milliseconds after stimulus offset, thus possibly playing a role in sensory memory.


Subject(s)
Auditory Cortex/physiology , Evoked Potentials, Auditory/physiology , Halothane/administration & dosage , Nerve Net/physiology , Neurons/physiology , Pitch Perception/physiology , Acoustic Stimulation/methods , Anesthetics/administration & dosage , Animals , Auditory Cortex/drug effects , Cats , Computer Simulation , Models, Neurological , Neurons/drug effects , Pitch Perception/drug effects
19.
Hear Res ; 210(1-2): 85-92, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16181754

ABSTRACT

Octave-circular pitch perception, the repetition of pitch scale qualities when surpassing the octave interval, has been observed in behavioral data from humans and monkeys, but the underlying anatomy and physiology is still unknown. Here we analyze octave circularity in a concert pianist with absolute pitch, both under medication with the neurotropic drug carbamazepine (CBZ) and without medication. Analysis of 4619 responses in a pitch identification task revealed an internal tone-scale representation, based on the norm-tone scale re A4=440 Hz, with an octave-circular pattern of strongly and weakly represented tones. CBZ caused a global down-shift of pitch (ca. 1 semitone at 500 Hz), but no down-shift of the octave-circular pattern of tone characteristics. This pattern was similar in the six tested octave ranges (32.7-2093 Hz), both under the control and the CBZ condition. Pattern repetition always occurred at octave intervals and did not reflect the stretched octaves of piano tuning. The results indicate that CBZ influences pitch detection peripheral of an octave-circular pitch representation. Thus they support previous evidence for pitch detection in the auditory midbrain and for octave-circular pitch mapping in the auditory thalamus.


Subject(s)
Carbamazepine/adverse effects , Pitch Perception/drug effects , Acoustic Stimulation , Adult , Central Nervous System Agents/adverse effects , Female , Geniculate Bodies/drug effects , Geniculate Bodies/physiology , Humans , Inferior Colliculi/drug effects , Inferior Colliculi/physiology , Music , Pitch Discrimination/drug effects , Pitch Discrimination/physiology , Pitch Perception/physiology
20.
Psychopharmacology (Berl) ; 177(4): 366-72, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15290001

ABSTRACT

RATIONALE: Alcohol has been shown to impair involuntary attention studied by event-related potentials using mismatch negativity (MMN) and P3a. OBJECTIVES: However, no studies have investigated whether alcohol affects the magnetic counterparts of N1 (N1m), MMN (MMNm) and P3a (P3am). METHODS: Auditory evoked potentials and magnetic fields elicited by infrequent deviant tones differing in frequency (5% and 20% change) and novel sounds were recorded with whole-head magnetoencephalography (MEG) and electroencephalography (EEG). Stimuli were presented separately to the left and right ear. Eleven right-handed subjects were studied in a double-blind, placebo-controlled (0.8 g/kg ethanol or juice), cross-over design. N1m, MMNm, and P3am were calculated from the channel pair at the temporal cortex showing the strongest responses in the hemisphere contralateral to the stimulation. N1, MMN and P3a were analyzed from 12 electrodes at the midline frontocentral area. RESULTS: Alcohol reduced bilaterally N1, N1m, MMN and MMNm amplitudes. P3a amplitudes, but not P3am amplitudes were also significantly decreased. No effects of alcohol on the latencies of N1, MMN and P3a or their magnetic counterparts were observed. CONCLUSIONS: Alcohol impairs the processing of tones, frequency change and novel sounds at different phases of auditory processing similarly in both hemispheres. MEG provides us with additional information unobtainable with EEG about the effects of alcohol on the neural correlates of cognition.


Subject(s)
Auditory Perception/drug effects , Central Nervous System Depressants/pharmacology , Electroencephalography/drug effects , Ethanol/pharmacology , Magnetoencephalography/drug effects , Pitch Perception/drug effects , Acoustic Stimulation , Adult , Algorithms , Attention/drug effects , Cross-Over Studies , Data Interpretation, Statistical , Double-Blind Method , Evoked Potentials, Auditory/drug effects , Female , Humans , Male
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