Hidehiko Okamoto

Listening to tailor-made notched music reduces tinnitus loudness and tinnitus-related auditory cortex activity

Maladaptive auditory cortex reorganization may contribute to the generation and maintenance of tinnitus. Because cortical organization can be modified by behavioral training, we attempted to reduce tinnitus loudness by exposing chronic tinnitus patients to self-chosen, enjoyable music, which was modified (“notched”) to contain no energy in the frequency range surrounding the individual tinnitus frequency. After 12 months of regular listening, the target patient group (n = 8) showed significantly reduced subjective tinnitus loudness and concomitantly exhibited reduced evoked activity in auditory cortex areas corresponding to the tinnitus frequency compared to patients who had received an analogous placebo notched music treatment (n = 8). These findings indicate that tinnitus loudness can be significantly diminished by an enjoyable, low-cost, custom-tailored notched music treatment, potentially via reversing maladaptive auditory cortex reorganization.

Attention Improves Population-Level Frequency Tuning in Human Auditory Cortex

Attention improves auditory performance in noisy environments by either enhancing the processing of task-relevant stimuli (“gain”), suppressing task-irrelevant information (“sharpening”), or both. In the present study, we investigated the effect of focused auditory attention on the population-level frequency tuning in human auditory cortex by means of magnetoencephalography. Using complex stimuli consisting of a test tone superimposed on different band-eliminated noises during active listening or distracted listening conditions, we observed that focused auditory attention caused not only gain, but also sharpening of frequency tuning in human auditory cortex as reflected by the N1m auditory evoked response. This combination of gain and sharpening in the auditory cortex may contribute to better auditory performance during focused auditory attention.

Frequency-specific modulation of population-level frequency tuning in human auditory cortex.

BackgroundUnder natural circumstances, attention plays an important role in extracting relevant auditory signals from simultaneously present, irrelevant noises. Excitatory and inhibitory neural activity, enhanced by attentional processes, seems to sharpen frequency tuning, contributing to improved auditory performance especially in noisy environments. In the present study, we investigated auditory magnetic fields in humans that were evoked by pure tones embedded in band-eliminated noises during two different stimulus sequencing conditions (constant vs. random) under auditory focused attention by means of magnetoencephalography (MEG).ResultsIn total, we used identical auditory stimuli between conditions, but presented them in a different order, thereby manipulating the neural processing and the auditory performance of the listeners. Constant stimulus sequencing blocks were characterized by the simultaneous presentation of pure tones of identical frequency with band-eliminated noises, whereas random sequencing blocks were characterized by the simultaneous presentation of pure tones of random frequencies and band-eliminated noises. We demonstrated that auditory evoked neural responses were larger in the constant sequencing compared to the random sequencing condition, particularly when the simultaneously presented noises contained narrow stop-bands.ConclusionThe present study confirmed that population-level frequency tuning in human auditory cortex can be sharpened in a frequency-specific manner. This frequency-specific sharpening may contribute to improved auditory performance during detection and processing of relevant sound inputs characterized by specific frequency distributions in noisy environments.

Hemispheric Asymmetry of Auditory Evoked Fields Elicited by Spectral versus Temporal Stimulus Change

The investigation of functional hemispheric asymmetries regarding auditory processing in the human brain still remains a challenge. Classical lesion and recent neuroimaging studies indicated that speech is dominantly processed in the left hemisphere, whereas music is dominantly processed in the right. However, recent studies demonstrated that the functional hemispheric asymmetries were not limited to the processing of highly cognitive sound signals like speech and music but rather originated from the basic neural processing of elementary sound features, that is, spectral and temporal acoustic features. Here, in contrast to previous studies, we used carefully composed tones and pulse trains as stimuli, balanced the overall physical sound input between spectral and temporal change conditions, and demonstrated the time course of neural activity evoked by spectral versus temporal sound input change by means of magnetoencephalography (MEG). These original findings support the hypothesis that spectral change is dominantly processed in the right hemisphere, whereas temporal change is dominantly processed in the left.

Sound processing hierarchy within human auditory cortex

Both attention and masking sounds can alter auditory neural processes and affect auditory signal perception. In the present study, we investigated the complex effects of auditory-focused attention and the signal-to-noise ratio of sound stimuli on three different auditory evoked field components (auditory steady-state response, N1m, and sustained field) by means of magnetoencephalography. The results indicate that the auditory steady-state response originating in primary auditory cortex reflects the signal-to-noise ratio of physical sound inputs (bottom–up process) rather than the listeners attentional state (top–down process), whereas the sustained field, originating in nonprimary auditory cortex, reflects the attentional state rather than the signal-to-noise ratio. The N1m was substantially influenced by both bottom–up and top–down neural processes. The differential sensitivity of the components to bottom–up and top–down neural processes, contingent on their level in the processing pathway, suggests a stream from bottom–up driven sensory neural processing to top–down driven auditory perception within human auditory cortex.

Music-induced cortical plasticity and lateral inhibition in the human auditory cortex as foundations for tonal tinnitus treatment

Over the past 15 years, we have studied plasticity in the human auditory cortex by means of magnetoencephalography (MEG). Two main topics nurtured our curiosity: the effects of musical training on plasticity in the auditory system, and the effects of lateral inhibition. One of our plasticity studies found that listening to notched music for 3 h inhibited the neuronal activity in the auditory cortex that corresponded to the center-frequency of the notch, suggesting suppression of neural activity by lateral inhibition. Subsequent research on this topic found that suppression was notably dependent upon the notch width employed, that the lower notch-edge induced stronger attenuation of neural activity than the higher notch-edge, and that auditory focused attention strengthened the inhibitory networks. Crucially, the overall effects of lateral inhibition on human auditory cortical activity were stronger than the habituation effects. Based on these results we developed a novel treatment strategy for tonal tinnitus—tailor-made notched music training (TMNMT). By notching the music energy spectrum around the individual tinnitus frequency, we intended to attract lateral inhibition to auditory neurons involved in tinnitus perception. So far, the training strategy has been evaluated in two studies. The results of the initial long-term controlled study (12 months) supported the validity of the treatment concept: subjective tinnitus loudness and annoyance were significantly reduced after TMNMT but not when notching spared the tinnitus frequencies. Correspondingly, tinnitus-related auditory evoked fields (AEFs) were significantly reduced after training. The subsequent short-term (5 days) training study indicated that training was more effective in the case of tinnitus frequencies ≤ 8 kHz compared to tinnitus frequencies >8 kHz, and that training should be employed over a long-term in order to induce more persistent effects. Further development and evaluation of TMNMT therapy are planned. A goal is to transfer this novel, completely non-invasive and low-cost treatment approach for tonal tinnitus into routine clinical practice.

Short and intense tailor-made notched music training against tinnitus: the tinnitus frequency matters.

Tinnitus is one of the most common diseases in industrialized countries. Here, we developed and evaluated a short-term (5 subsequent days) and intensive (6 hours/day) tailor-made notched music training (TMNMT) for patients suffering from chronic, tonal tinnitus. We evaluated (i) the TMNMT efficacy in terms of behavioral and magnetoencephalographic outcome measures for two matched patient groups with either low (≤8 kHz, N = 10) or high (>8 kHz, N = 10) tinnitus frequencies, and the (ii) persistency of the TMNMT effects over the course of a four weeks post-training phase. The results indicated that the short-term intensive TMNMT took effect in patients with tinnitus frequencies ≤8 kHz: subjective tinnitus loudness, tinnitus-related distress, and tinnitus-related auditory cortex evoked activity were significantly reduced after TMNMT completion. However, in the patients with tinnitus frequencies >8 kHz, significant changes were not observed. Interpreted in their entirety, the results also indicated that the induced changes in auditory cortex evoked neuronal activity and tinnitus loudness were not persistent, encouraging the application of the TMNMT as a longer-term training. The findings are essential in guiding the intended transfer of this neuro-scientific treatment approach into routine clinical practice.

Magnetoencephalographic study of the cortical activity elicited by human voice

In an attempt to identify voice-specific neural activities in auditory cortex in humans, we recorded cortical magnetic responses. Volunteers were instructed to listen to vocal and instrumental sounds matched in fundamental-frequency, duration, temporal envelope and average root mean square power. The stimuli were sounds produced by four singers and four musical instruments at each of two fundamental frequencies: 220 Hz (musical note A3) and 261.9 Hz (C3). Two components of the evoked responses were analyzed, one at approximately 100 ms (N1m) and the other 400 ms after the stimulus onset (sustained field, SF). The source locations of equivalent current dipoles for both components were estimated around the Heschls gyrus in both hemispheres. Compared with the instrumental sound, the source strength of the SF component for the voice was significantly larger.

Combining Transcranial Direct Current Stimulation and Tailor-Made Notched Music Training to Decrease Tinnitus-Related Distress – A Pilot Study

The central auditory system has a crucial role in tinnitus generation and maintenance. Curative treatments for tinnitus do not yet exist. However, recent attempts in the therapeutic application of both acoustic stimulation/training procedures and electric/magnetic brain stimulation techniques have yielded promising results. Here, for the first time we combined tailor-made notched music training (TMNMT) with transcranial direct current stimulation (tDCS) in an effort to modulate TMNMT efficacy in the treatment of 32 patients with tonal tinnitus and without severe hearing loss. TMNMT is characterized by regular listening to so-called notched music, which is generated by digitally removing the frequency band of one octave width centered at the individual tinnitus frequency. TMNMT was applied for 10 subsequent days (2.5 hours of daily treatment). During the initial 5 days of treatment and the initial 30 minutes of TMNMT sessions, tDCS (current strength: 2 mA; anodal (N = 10) vs. cathodal (N = 11) vs. sham (N = 11) groups) was applied simultaneously. The active electrode was placed on the head surface over left auditory cortex; the reference electrode was put over right supra-orbital cortex. To evaluate treatment outcome, tinnitus-related distress and perceived tinnitus loudness were assessed using standardized tinnitus questionnaires and a visual analogue scale. The results showed a significant treatment effect reflected in the Tinnitus Handicap Questionnaire that was largest after 5 days of treatment. This effect remained significant at the end of follow-up 31 days after treatment cessation. Crucially, tDCS did not significantly modulate treatment efficacy - it did not make a difference whether anodal, cathodal, or sham tDCS was applied. Possible explanations for the findings and functional modifications of the experimental design for future studies (e.g. the selection of control conditions) are discussed.

Asymmetric lateral inhibitory neural activity in the auditory system: a magnetoencephalographic study

BackgroundDecrements of auditory evoked responses elicited by repeatedly presented sounds with similar frequencies have been well investigated by means of electroencephalography and magnetoencephalography (MEG). However the possible inhibitory interactions between different neuronal populations remains poorly understood. In the present study, we investigated the effect of proceeding notch-filtered noises (NFNs) with different frequency spectra on a following test tone using MEG.ResultsThree-second exposure to the NFNs resulted in significantly different N1m responses to a 1000 Hz test tone presented 500 ms after the offset of the NFNs. The NFN with a lower spectral edge closest to the test tone mostly decreased the N1m amplitude.ConclusionThe decrement of the N1m component after exposure to the NFNs could be explained partly in terms of lateral inhibition. The results demonstrated that the amplitude of the N1m was more effectively influenced by inhibitory lateral connections originating from neurons corresponding to lower rather than higher frequencies. We interpret this effect of asymmetric lateral inhibition in the auditory system as an important contribution to reduce the asymmetric neural activity profiles originating from the cochlea.