Larry E. Roberts

The neuroscience of tinnitus

Tinnitus is an auditory phantom sensation (ringing of the ears) experienced when no external sound is present. Most but not all cases are associated with hearing loss induced by noise exposure or aging. Neuroscience research has begun to reveal how tinnitus is generated by the brain when hearing loss occurs, and to suggest new avenues for management and prevention of tinnitus following hearing injuries. Downregulation of intracortical inhibition induced by damage to the cochlea or to auditory projection pathways highlights neural processes that underlie the sensation of phantom sound.

Increased auditory cortical representation in musicians.

Acoustic stimuli are processed throughout the auditory projection pathway, including the neocortex, by neurons that are aggregated into ‘tonotopic’ maps according to their specific frequency tunings. Research on animals has shown that tonotopic representations are not statically fixed in the adult organism but can reorganize after damage to the cochlea or after training the intact subject to discriminate between auditory stimuli. Here we used functional magnetic source imaging (single dipole model) to measure cortical representations in highly skilled musicians. Dipole moments for piano tones, but not for pure tones of similar fundamental frequency (matched in loudness), were found to be enlarged by about 25% in musicians compared with control subjects who had never played an instrument. Enlargement was correlated with the age at which musicians began to practise and did not differ between musicians with absolute or relative pitch. These results, when interpreted with evidence for modified somatosensory representations of the fingering digits in skilled violinists, suggest that use-dependent functional reorganization extends across the sensory cortices to reflect the pattern of sensory input processed by the subject during development of musical skill.

Ringing Ears: The Neuroscience of Tinnitus

Tinnitus is a phantom sound (ringing of the ears) that affects quality of life for millions around the world and is associated in most cases with hearing impairment. This symposium will consider evidence that deafferentation of tonotopically organized central auditory structures leads to increased neuron spontaneous firing rates and neural synchrony in the hearing loss region. This region covers the frequency spectrum of tinnitus sounds, which are optimally suppressed following exposure to band-limited noise covering the same frequencies. Cross-modal compensations in subcortical structures may contribute to tinnitus and its modulation by jaw-clenching and eye movements. Yet many older individuals with impaired hearing do not have tinnitus, possibly because age-related changes in inhibitory circuits are better preserved. A brain network involving limbic and other nonauditory regions is active in tinnitus and may be driven when spectrotemporal information conveyed by the damaged ear does not match that predicted by central auditory processing.

Timbre-specific enhancement of auditory cortical representations in musicians

Neural imaging studies have shown that the brains of skilled musicians respond differently to musical stimuli than do the brains of non-musicians, particularly for musicians who commenced practice at an early age. Whether brain attributes related to musical skill are attributable to musical practice or are hereditary traits that influence the decision to train musically is a subject of controversy, owing to its pedagogic implications. Here we report that auditory cortical representa- tions measured neuromagnetically for tones of different timbre (violin and trumpet) are enhanced compared to sine tones in violinists and trumpeters, preferentially for timbres of the instrument of training. Timbre specificity is predicted by a principle of use-dependent plasticity and imposes new requirements on nativistic accounts of brain attributes associated with musical skill.

A high-precision magnetoencephalographic study of human auditory steady-state responses to amplitude-modulated tones

The cerebral magnetic field of the auditory steady-state response (SSR) to sinusoidal amplitude-modulated (SAM) tones was recorded in healthy humans. The waveforms of underlying cortical source activity were calculated at multiples of the modulation frequency using the method of source space projection, which improved the signal-to-noise ratio (SNR) by a factor of 2 to 4. Since the complex amplitudes of the cortical source activity were independent of the sensor position in relation to the subjects head, a comparison of the results across experimental sessions was possible. The effect of modulation frequency on the amplitude and phase of the SSR was investigated at 30 different values between 10 and 98 Hz. At modulation frequencies between 10 and 20 Hz the SNR of harmonics near 40 Hz were predominant over the fundamental SSR. Above 30 Hz the SSR showed an almost sinusoidal waveform with an amplitude maximum at 40 Hz. The amplitude decreased with increasing modulation frequency but was significantly different from the magnetoencephalographic (MEG) background activity up to 98 Hz. Phase response at the fundamental and first harmonic decreased monotonically with increasing modulation frequency. The group delay (apparent latency) showed peaks of 72 ms at 20 Hz, 48 ms at 40 Hz, and 26 ms at 80 Hz. The effects of stimulus intensity, modulation depth, and carrier frequency on amplitude and phase of the SSR were also investigated. The SSR amplitude decreased linearly when stimulus intensity or the modulation depth were decreased in logarithmic steps. SSR amplitude decreased by a factor of 3 when carrier frequency increased from 250 to 4000 Hz. From the phase characteristics, time delays were found in the range of 0 to 6 ms for stimulus intensity, modulation depth, and carrier frequency, which were maximal at low frequencies, low intensities, or maximal modulation depth.

Plastic changes in the auditory cortex induced by intensive frequency discrimination training

The slow auditory evoked (wave Nlm) and mismatch field (MMF) elicited by sequences of pure tones of 1000 Hz and deviant tones of 1050, 1010 and 1005 Hz were measured before, during and 3 weeks after subjects were trained at frequency discrimination for 15 sessions (over 3 weeks) using an odd-ball procedure. The task of the subject was to detect deviants differing by progressively smaller frequency shifts from the standard stimulus. Frequency discrimination improved rapidly in the first week and was followed by small but constant improvements thereafter. Nlm and MMF responses to the deviant stimuli increased in amplitude during training. This enhancement persisted until training was finished, but decreased 3 weeks later. The results suggest a plastic reorganization of the cortical representation for the trained frequencies.

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 auditory cortical development by musical experience in children.

Auditory evoked potentials (AEPs) express the development of mature synaptic connections in the upper neocortical laminae known to occur between 4 and 15 years of age. AEPs evoked by piano, violin, and pure tones were measured twice in a group of 4- to 5-year-old children enrolled in Suzuki music lessons and in non-musician controls. P1 was larger in the Suzuki pupils for all tones whereas P2 was enhanced specifically for the instrument of practice (piano or violin). AEPs observed for the instrument of practice were comparable to those of non-musician children about 3 years older in chronological age. The findings set into relief a general process by which the neocortical synaptic matrix is shaped by an accumulation of specific auditory experiences.

Frequency organization of the 40-Hz auditory steady-state response in normal hearing and in tinnitus

We used the 40-Hz auditory steady-state response (SSR) to compare for the first time tonotopic frequency representations in the region of primary auditory cortex (PAC) between subjects with chronic tinnitus and hearing impairment and normal hearing controls. Frequency representations were measured in normal hearing (n=17) and tinnitus (n=28) subjects using eight carrier frequencies between 384 and 6561 Hz, each amplitude modulated (AM) at 40-Hz on trials of 3 min duration under passive attention. In normal hearing subjects, frequency gradients were observed in the medial-lateral, anterior-posterior, and inferior-superior axes, which were consistent with the orientation of Heschls gyrus and with functional organization revealed by fMRI investigations. The frequency representation in the right hemisphere was approximately 5 mm anterior and approximately 7 mm lateral to that in the left hemisphere, corroborating with MEG measurements hemispheric asymmetries reported by cytoarchitectonic studies of the PAC and by MRI morphometry. In the left hemisphere, frequency gradients were inflected near 2 kHz in normal hearing subjects. These SSR frequency gradients were attenuated in both hemispheres in tinnitus subjects. Dipole power was also elevated in tinnitus, suggesting that more neurons were entrained synchronously by the AM envelope. These findings are consistent with animal experiments reporting altered tonotopy and changes in the response properties of auditory cortical neurons after hearing loss induced by noise exposure. Degraded frequency representations in tinnitus may reflect a loss of intracortical inhibition in deafferented frequency regions of the PAC after hearing injury.

Music training leads to the development of timbre-specific gamma band activity

Oscillatory gamma band activity (GBA, 30-100 Hz) has been shown to correlate with perceptual and cognitive phenomena including feature binding, template matching, and learning and memory formation. We hypothesized that if GBA reflects highly learned perceptual template matching, we should observe its development in musicians specific to the timbre of their instrument of practice. EEG was recorded in adult professional violinists and amateur pianists as well as in 4- and 5-year-old children studying piano in the Suzuki method before they commenced music lessons and 1 year later. The adult musicians showed robust enhancement of induced (non-time-locked) GBA, specifically to their instrument of practice, with the strongest effect in professional violinists. Consistent with this result, the children receiving piano lessons exhibited increased power of induced GBA for piano tones with 1 year of training, while children not taking lessons showed no effect. In comparison to induced GBA, evoked (time-locked) gamma band activity (30-90 Hz, approximately 80 ms latency) was present only in adult groups. Evoked GBA was more pronounced in musicians than non-musicians, with synchronization equally exhibited for violin and piano tones but enhanced for these tones compared to pure tones. Evoked gamma activity may index the physical properties of a sound and is modulated by acoustical training, while induced GBA may reflect higher perceptual learning and is shaped by specific auditory experiences.