Daniel J. Bosnyak

Residual Inhibition Functions Overlap Tinnitus Spectra and the Region of Auditory Threshold Shift

Animals exposed to noise trauma show augmented synchronous neural activity in tonotopically reorganized primary auditory cortex consequent on hearing loss. Diminished intracortical inhibition in the reorganized region appears to enable synchronous network activity that develops when deafferented neurons begin to respond to input via their lateral connections. In humans with tinnitus accompanied by hearing loss, this process may generate a phantom sound that is perceived in accordance with the location of the affected neurons in the cortical place map. The neural synchrony hypothesis predicts that tinnitus spectra, and heretofore unmeasured “residual inhibition functions” that relate residual tinnitus suppression to the center frequency of masking sounds, should cover the region of hearing loss in the audiogram. We confirmed these predictions in two independent cohorts totaling 90 tinnitus subjects, using computer-based tools designed to assess the psychoacoustic properties of tinnitus. Tinnitus spectra and residual inhibition functions for depth and duration increased with the amount of threshold shift over the region of hearing impairment. Residual inhibition depth was shallower when the masking sounds that were used to induce residual inhibition showed decreased correspondence with the frequency spectrum and bandwidth of the tinnitus. These findings suggest that tinnitus and its suppression in residual inhibition depend on processes that span the region of hearing impairment and not on mechanisms that enhance cortical representations for sound frequencies at the audiometric edge. Hearing thresholds measured in age-matched control subjects without tinnitus implicated hearing loss as a factor in tinnitus, although elevated thresholds alone were not sufficient to cause tinnitus.

Residual inhibition functions in relation to tinnitus spectra and auditory threshold shift

Conclusions: Psychoacoustic functions relating the depth and duration of tinnitus suppression (‘residual inhibition’) to the center frequency of band-passed noise masking sounds appear to span the region of hearing loss, as do psychoacoustic measurements of the tinnitus spectrum. The results (1) suggest that cortical map reorganization induced by hearing loss is not the principal source of the tinnitus sensation and (2) provide a necessary baseline for optimizing residual inhibition in individual cases. Objective: To measure residual inhibition functions and tinnitus spectra using sounds spanning the region of hearing loss. Materials and methods: Three subject-driven, computer-based tools were developed and applied to measure psychoacoustic properties of tinnitus and residual inhibition in 32 subjects with chronic tonal, ringing, or hissing tinnitus. Residual inhibition functions were measured with band-passed noise sounds varying in center frequency up to 12.0 kHz. Results: The depth and duration of residual inhibition increased with the center frequency of the band-passed noise stimuli. Near-elimination of tinnitus for up to 45 s was reported by 8/24 (33%) subjects at center frequencies above 3 kHz (these cases distributed across tinnitus types). Tinnitus spectra covered the region of hearing loss with no preponderance of frequencies near the audiometric edge of normal hearing.

Re-examining the relationship between audiometric profile and tinnitus pitch

Abstract Objective: We explored the relationship between audiogram shape and tinnitus pitch to answer questions arising from neurophysiological models of tinnitus: ‘Is the dominant tinnitus pitch associated with the edge of hearing loss?’ and ‘Is such a relationship more robust in people with narrow tinnitus bandwidth or steep sloping hearing loss?’ Design: A broken-stick fitting objectively quantified slope, degree and edge of hearing loss up to 16 kHz. Tinnitus pitch was characterized up to 12 kHz. We used correlation and multiple regression analyses for examining relationships with many potentially predictive audiometric variables. Study Sample: 67 people with chronic bilateral tinnitus (43 men and 24 women, aged from 22 to 81 years). Results: In this ample of 67 subjects correlation failed to reveal any relationship between the tinnitus pitch and the edge frequency. The tinnitus pitch generally fell within the area of hearing loss. The pitch of the tinnitus in a subset of subjects with a narrow tinnitus bandwidth (n = 23) was associated with the audiometric edge. Conclusions: Our findings concerning subjects with narrow tinnitus bandwidth suggest that this can be used as an a priori inclusion criterion. A large group of such subjects should be tested to confirm these results. Sumario Objetivo: Exploramos la relación entre la forma del audiograma y el tono del acufeno para responder a preguntas provenientes de modelos neurofisiológicos del acúfeno: ‘Es el tono dominante del acúfeno asociado con el borde de la hipoacusia?’y ‘Será tal relación más robusta en personas con un acúfeno de banda angosta o con una hipoacusia de caída abrupta?’ Diseño: Una pendiente tipo “palo roto” objetivamente cuantificada, con severidad y borde de la hipoacusia hasta 16 kHz. El tono del acúfeno fue caracterizado hasta 12 kHz. Utilizamos un análisis de correlación y regresión múltiple para examinar la relación con muchas de las variables potencialmente predictivas. Muestra del estudio: 67 personas con acúfeno bilateral crónico (43 hombres y 24 mujeres con edades entre 22 y 81 años). Resultados: En esta amplia muestra de 67 sujetos, la correlación no demostró ninguna relación entre el acúfeno y el borde de la frecuencia. El tono del acúfeno generalmente cayó dentro del área de la hipoacusia. En un subgrupo de sujetos, que tenían un acúfeno de banda angosta (n=23), si hubo asociación con el borde audiométrico. Conclusiones: Nuestros hallazgos que corresponden a los sujetos con un acúfeno de banda angosta, sugieren que esto puede ser utilizado a priori como un criterio de inclusión. Un grupo grande de sujetos debe ser examinado para confirmar estos resultados.

Evidence for modality-specific but not frequency-specific modulation of human primary auditory cortex by attention

We used the stimulus-driven 40-Hz auditory steady-state response (ASSR) that localizes tonotopically to the region of primary auditory cortex (A1) to study modulation of this region by top-down attention. Experiment 1 presented amplitude modulated (AM) auditory and visual stimuli simultaneously (AM at 40 Hz and 16 Hz, respectively) while participants responded to targets in one modality or the other. ASSR amplitude increased from an unattended passive baseline during auditory but not visual attention demonstrating modality-specific auditory attention, when attention was required for brief (1 s) but not long (2 min) time intervals. Modality-specific visual attention occurred at both time intervals. Experiment 2 asked whether attention directed to one or the other of two simultaneous auditory streams (carrier frequencies of 250 and 4100 Hz AM at 37 and 41 Hz respectively, counterbalanced) increased ASSR amplitude for the attended stream (frequency-specific auditory attention). Behaviour was strongly controlled by carrier frequency (overall target rate 1.7 Hz), and the cortical sources of the two carriers were resolved by inverse modeling. Despite these conditions favourable to frequency specificity, frequency-specific modulation of ASSR amplitude was not found at either time interval. Frequency-specific modulation of A1 may require re-entrant feedback to the auditory core from auditory percepts that possess distinct spectral attributes and are attended in higher regions of the auditory system.

Acoustic experience but not attention modifies neural population phase expressed in human primary auditory cortex

We studied the effect of auditory training on the 40-Hz auditory steady-state response (ASSR) known to localize tonotopically to the region of primary auditory cortex (A1). The stimulus procedure was designed to minimize competitive interactions among frequency representations in A1 and delivered target events at random times in a training window, to increase the likelihood that neuroplastic changes could be detected. Experiment 1 found that repeated exposure to this stimulus advanced the phase of the ASSR (shortened the time delay between the 40-Hz response and stimulus waveforms). The phase advance appeared at the outset of the second of two sessions separated by 24-72 h, did not require active training, and was not accompanied by changes in ASSR amplitude over this time interval. Experiment 2 applied training for 10 sessions to reveal further advances in ASSR phase and also an increase in ASSR amplitude, but the amplitude effect lagged that on phase and did not correlate with perceptual performance while the phase advance did. A control group trained for a single session showed a phase advance but no amplitude enhancement when tested 6 weeks later (retention). In both experiments attention to auditory signals increased ASSR amplitude but had no effect on ASSR phase. Our results reveal a persistent form of neural plasticity expressed in the phase of ASSRs generated from the region of A1, which occurs either in A1 or in subcortical nuclei projecting to this region.

Neural plasticity expressed in central auditory structures with and without tinnitus

Sensory training therapies for tinnitus are based on the assumption that, notwithstanding neural changes related to tinnitus, auditory training can alter the response properties of neurons in auditory pathways. To assess this assumption, we investigated whether brain changes induced by sensory training in tinnitus sufferers and measured by electroencephalography (EEG) are similar to those induced in age and hearing loss matched individuals without tinnitus trained on the same auditory task. Auditory training was given using a 5 kHz 40-Hz amplitude-modulated (AM) sound that was in the tinnitus frequency region of the tinnitus subjects and enabled extraction of the 40-Hz auditory steady-state response (ASSR) and P2 transient response known to localize to primary and non-primary auditory cortex, respectively. P2 amplitude increased over training sessions equally in participants with tinnitus and in control subjects, suggesting normal remodeling of non-primary auditory regions in tinnitus. However, training-induced changes in the ASSR differed between the tinnitus and control groups. In controls the phase delay between the 40-Hz response and stimulus waveforms reduced by about 10° over training, in agreement with previous results obtained in young normal hearing individuals. However, ASSR phase did not change significantly with training in the tinnitus group, although some participants showed phase shifts resembling controls. On the other hand, ASSR amplitude increased with training in the tinnitus group, whereas in controls this response (which is difficult to remodel in young normal hearing subjects) did not change with training. These results suggest that neural changes related to tinnitus altered how neural plasticity was expressed in the region of primary but not non-primary auditory cortex. Auditory training did not reduce tinnitus loudness although a small effect on the tinnitus spectrum was detected.

Modulation of electrocortical brain activity by attention in individuals with and without tinnitus.

Age and hearing-level matched tinnitus and control groups were presented with a 40 Hz AM sound using a carrier frequency of either 5 kHz (in the tinnitus frequency region of the tinnitus subjects) or 500 Hz (below this region). On attended blocks subjects pressed a button after each sound indicating whether a single 40 Hz AM pulse of variable increased amplitude (target, probability 0.67) had or had not occurred. On passive blocks subjects rested and ignored the sounds. The amplitude of the 40 Hz auditory steady-state response (ASSR) localizing to primary auditory cortex (A1) increased with attention in control groups probed at 500 Hz and 5 kHz and in the tinnitus group probed at 500 Hz, but not in the tinnitus group probed at 5 kHz (128 channel EEG). N1 amplitude (this response localizing to nonprimary cortex, A2) increased with attention at both sound frequencies in controls but at neither frequency in tinnitus. We suggest that tinnitus-related neural activity occurring in the 5 kHz but not the 500 Hz region of tonotopic A1 disrupted attentional modulation of the 5 kHz ASSR in tinnitus subjects, while tinnitus-related activity in A1 distributing nontonotopically in A2 impaired modulation of N1 at both sound frequencies.

Neuroplastic Adaptations of the Auditory System in Musicians and Nonmusicians

The human ear has been adapted by evolutionary processes to respond to sound frequencies that are present in the environment and convey information relevant to survival and reproductive fitness. However, the specific features of most sounds that we hear on a second-by-second basis (for example, the harmonic structure, loudness, and temporal shape of a particular voice, language, or musical note) and the meaning attached to these sounds are unique for each individual and cannot be anticipated by a genetic code. The evolutionary response to this limitation on natural selection has been the development of mechanisms that represent the detailed features of sensory input (sensory maps) and update those representations on a millisecond time scale (neural plasticity). We describe two experiments which used auditory evoked potentials (AEPs) to study these processes in the human brain.

Evidence for fusion and segregation induced by 21 Hz multiple-digit stimulation in humans.

Subjects were trained to detect changes in the frequency of 21 Hz tactile stimulation applied to digits 2 + 3 + 4 (fusion group) or 2 + 4 (segregation group) of the right hand. The 21 Hz steady-state response for digit 3 was measured by 64 channel EEG on mapping trials before and after training. Discrimination improved over 3 days, confirming that subjects attended to the training stimuli. The 21 Hz response was larger on training than on mapping trials, indicating sensitivity of the response to the strength of cortical activation. Under these conditions the 21 Hz response for digit 3 decreased after training in both groups on day 1. On day 3 this effect reversed in a subset of fusion subjects while segregation continued to yield decreases. The findings suggest that somatosensory representations are dynamically modified by the sensory input experienced on a task.

Simultaneously-evoked auditory potentials (SEAP): A new method for concurrent measurement of cortical and subcortical auditory-evoked activity

&NA; Recent electrophysiological work has evinced a capacity for plasticity in subcortical auditory nuclei in human listeners. Similar plastic effects have been measured in cortically‐generated auditory potentials but it is unclear how the two interact. Here we present Simultaneously‐Evoked Auditory Potentials (SEAP), a method designed to concurrently elicit electrophysiological brain potentials from inferior colliculus, thalamus, and primary and secondary auditory cortices. Twenty‐six normal‐hearing adult subjects (mean 19.26 years, 9 male) were exposed to 2400 monaural (right‐ear) presentations of a specially‐designed stimulus which consisted of a pure‐tone carrier (500 or 600 Hz) that had been amplitude‐modulated at the sum of 37 and 81 Hz (depth 100%). Presentation followed an oddball paradigm wherein the pure‐tone carrier was set to 500 Hz for 85% of presentations and pseudo‐randomly changed to 600 Hz for the remaining 15% of presentations. Single‐channel electroencephalographic data were recorded from each subject using a vertical montage referenced to the right earlobe. We show that SEAP elicits a 500 Hz frequency‐following response (FFR; generated in inferior colliculus), 80 (subcortical) and 40 (primary auditory cortex) Hz auditory steady‐state responses (ASSRs), mismatch negativity (MMN) and P3a (when there is an occasional change in carrier frequency; secondary auditory cortex) in addition to the obligatory N1‐P2 complex (secondary auditory cortex). Analyses showed that subcortical and cortical processes are linked as (i) the latency of the FFR predicts the phase delay of the 40 Hz steady‐state response, (ii) the phase delays of the 40 and 80 Hz steady‐state responses are correlated, and (iii) the fidelity of the FFR predicts the latency of the N1 component. The SEAP method offers a new approach for measuring the dynamic encoding of acoustic features at multiple levels of the auditory pathway. As such, SEAP is a promising tool with which to study how relationships between subcortical and cortical processes change through early development and auditory learning as well as by hearing loss and aging. HighlightsSEAP permits concurrent measurement of subcortical and cortical AEPs.Onsets of subcortical steady‐state responses correlate with onset of cortical 40 Hz ASSR.Stimulus fidelity at FFR generators is related to advanced N1 onset.