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.

Cortical plasticity in 4-month-old infants: specific effects of experience with musical timbres.

Animal models suggest that the brain is particularly neuroplastic early in development, but previous studies have not systematically controlled the auditory environment in human infants and observed the effects on auditory cortical representations. We exposed 4-month-old infants to melodies in either guitar or marimba timbre (infants were randomly assigned to exposure group) for a total of ~160 min over the course of a week, after which we measured electroencephalogram (EEG) responses to guitar and marimba tones at pitches not previously heard during the exposure phase. A frontally negative response with a topography consistent with generation in auditory areas, peaking around 450 ms, was significantly larger for guitar than marimba tones in the guitar-exposed group but significantly larger for marimba than guitar tones in the marimba-exposed group. This indicates that experience with tones in a particular timbre affects representations for that timbre, and that this effect generalizes to tones not previously experienced during exposure. Furthermore, mismatch responses to occasional small 3% changes in pitch were larger for tones in guitar than marimba timbre only for infants exposed to guitar tones. Together these results indicate that a relatively small amount of passive exposure to a particular timbre in infancy enhances representations of that timbre and leads to more precise pitch processing for that timbre.

Re-examining the relationship between audiometric profile and tinnitus pitch.

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.

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.

Enhancement of neuroplastic P2 and N1c auditory evoked potentials in musicians.

P2 and N1c components of the auditory evoked potential (AEP) have been shown to be sensitive to remodeling of the auditory cortex by training at pitch discrimination in nonmusician subjects. Here, we investigated whether these neuroplastic components of the AEP are enhanced in musicians in accordance with their musical training histories. Highly skilled violinists and pianists and nonmusician controls listened under conditions of passive attention to violin tones, piano tones, and pure tones matched in fundamental frequency to the musical tones. Compared with nonmusician controls, both musician groups evidenced larger N1c (latency, 138 msec) and P2 (latency, 185 msec) responses to the three types of tonal stimuli. As in training studies with nonmusicians, N1c enhancement was expressed preferentially in the right hemisphere, where auditory neurons may be specialized for processing of spectral pitch. Equivalent current dipoles fitted to the N1c and P2 field patterns localized to spatially differentiable regions of the secondary auditory cortex, in agreement with previous findings. These results suggest that the tuning properties of neurons are modified in distributed regions of the auditory cortex in accordance with the acoustic training history (musical- or laboratory-based) of the subject. Enhanced P2 and N1c responses in musicians need not be considered genetic or prenatal markers for musical skill.

Evidence for differential modulation of primary and nonprimary auditory cortex by forward masking in tinnitus.

It has been proposed that tinnitus is generated by aberrant neural activity that develops among neurons in tonotopic of regions of primary auditory cortex (A1) affected by hearing loss, which is also the frequency region where tinnitus percepts localize (Eggermont and Roberts 2004; Roberts et al., 2010, 2013). These models suggest (1) that differences between tinnitus and control groups of similar age and audiometric function should depend on whether A1 is probed in tinnitus frequency region (TFR) or below it, and (2) that brain responses evoked from A1 should track changes in the tinnitus percept when residual inhibition (RI) is induced by forward masking. We tested these predictions by measuring (128-channel EEG) the sound-evoked 40-Hz auditory steady-state response (ASSR) known to localize tonotopically to neural sources in A1. For comparison the N1 transient response localizing to distributed neural sources in nonprimary cortex (A2) was also studied. When tested under baseline conditions where tinnitus subjects would have heard their tinnitus, ASSR responses were larger in a tinnitus group than in controls when evoked by 500 Hz probes while the reverse was true for tinnitus and control groups tested with 5 kHz probes, confirming frequency-dependent group differences in this measure. On subsequent trials where RI was induced by masking (narrow band noise centered at 5 kHz), ASSR amplitude increased in the tinnitus group probed at 5 kHz but not in the tinnitus group probed at 500 Hz. When collapsed into a single sample tinnitus subjects reporting comparatively greater RI depth and duration showed comparatively larger ASSR increases after masking regardless of probe frequency. Effects of masking on ASSR amplitude in the control groups were completely reversed from those in the tinnitus groups, with no change seen to 5 kHz probes but ASSR increases to 500 Hz probes even though the masking sound contained no energy at 500 Hz (an "off-frequency" masking effect). In contrast to these findings for the ASSR, N1 amplitude was larger in tinnitus than control groups at both probe frequencies under baseline conditions, decreased after masking in all conditions, and did not relate to RI. These results suggest that aberrant neural activity occurring in the TFR of A1 underlies tinnitus and its modulation during RI. They indicate further that while neural changes occur in A2 in tinnitus, these changes do not reflect the tinnitus percept. Models for tinnitus and forward masking are described that integrate these findings within a common framework.

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.

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.

Distributed auditory cortical representations are modified when non-musicians are trained at pitch discrimination with 40 Hz amplitude modulated tones.

Several functional brain attributes reflecting neocortical activity have been found to be enhanced in musicians compared to non-musicians. Included are the N1m evoked magnetic field, P2 and right-hemispheric N1c auditory evoked potentials, and the source waveform of the magnetically recorded 40 Hz auditory steady state response (SSR). We investigated whether these functional brain attributes measured by EEG are sensitive to neuroplastic remodeling in non-musician subjects. Adult non-musicians were trained for 15 sessions to discriminate small changes in the carrier frequency of 40 Hz amplitude modulated pure tones. P2 and N1c auditory evoked potentials were separated from the SSR by signal processing and found to localize to spatially differentiable sources in the secondary auditory cortex (A2). Training enhanced the P2 bilaterally and the N1c in the right hemisphere where auditory neurons may be specialized for processing of spectral information. The SSR localized to sources in the region of Heschl's gyrus in primary auditory cortex (A1). The amplitude of the SSR (assessed by bivariate T2 in 100 ms moving windows) was not augmented by training although the phase of the response was modified for the trained stimuli. The P2 and N1c enhancements observed here and reported previously in musicians may reflect new tunings on A2 neurons whose establishment and expression are gated by input converging from other regions of the brain. The SSR localizing to A1 was more resistant to remodeling, suggesting that its amplitude enhancement in musicians may be an intrinsic marker for musical skill or an early experience effect.