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, customtailored notched music treatment, potentially via reversing maladaptive auditory cortex reorganization.cortical plasticity | human auditory cortex | lateral inhibition | magnetoencephalography | MEG S ubjective tinnitus (1) is among the most prevalent symptoms of hearing disorders in industrialized countries (2, 3). Tinnitus loudness can be considered as the most tangible tinnitus characteristic. In 1-3% of the general population, the tinnitus sensation is loud enough to affect the quality of life (4). Causal treatment strategies for tinnitus are not yet available.The lack of treatment strategies is due to incomplete knowledge concerning the mechanisms of tinnitus generation and maintenance. However, recent neurophysiological studies have shown that tinnitus is presumably caused by maladaptive auditory cortex reorganization (4-6) (similar phenomena were observed also in somatosensory cortex; refs. 7-9). For instance, magnetoencephalography (MEG) studies have demonstrated that auditory cortical map areas corresponding to the tinnitus frequency were distorted; the amount of distortion correlated positively with perceived tinnitus strength (10). Moreover, auditory cortex activity corresponding to the tinnitus frequency was shown to be enhanced and related to perceived tinnitus intrusiveness (11).To date, widely used tinnitus treatment strategies (e.g., tinnitus retraining therapy; ref. 12) are merely symptom management approaches. Therefore, there is a great demand for causal treatment approaches targeting the tinnitus percept more directly. Recent neurophysiological studies indicate that behavioral training can be a powerful means to reverse maladaptive cortical reorganization (7, 13).A previous study (14) demonstrated that listening to spectrally "notched" music can reduce cortical activity corresponding to the notch center frequency, possibly through lateral inhibition. Motivated by this finding, we developed an innovative tinnitus treatment strategy aimed at reducing tinnitus loudness. The treatment regimen consists of regular listening to enjoyable, custom-tailored notched music. Here, we evaluate and report results of the treatment from a longitudinal double-blinded ...

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.

The goal of this study was to compare the lateral inhibition and the habituation in the human auditory cortex, two important physiological effects during auditory processing that can be reliably measured by means of magnetoencephalography when recording auditory evoked fields. Applying 40-Hz amplitude-modulated stimuli allowed us to record simultaneously the slow transient evoked and the steady-state fields and thus to characterize the lateral inhibition and the habituation effect in primary and non-primary auditory cortical structures. The main finding of the study is that the lateral inhibition effect of non-primary auditory areas as measured on the major component of the slow transient auditory evoked field (N1) is significantly stronger than the corresponding habituation effect. By contrast, this effect was not observed for the 40-Hz steady-state fields, characterizing the activation of the primary auditory cortex in humans. The results might be interpreted as (i) evidence that the inhibition mediated by lateral connections is stronger than the habituation of excitatory neurons in the non-primary auditory cortex and (ii) the processing hierarchy in the human auditory cortex is demonstrated by the different behaviour of lateral inhibition and habituation in primary and non-primary auditory cortical structures.

Background: Under 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 bandeliminated noises during two different stimulus sequencing conditions (constant vs. random) under auditory focused attention by means of magnetoencephalography (MEG).

Although anatomical, histochemical and electrophysiological findings in both animals and humans have suggested a parallel and serial mode of auditory processing, precise activation timings of each cortical area are not well known, especially in humans. We investigated the timing of arrival of signals to multiple cortical areas using magnetoencephalography in humans. Following click stimuli applied to the left ear, activations were found in six cortical areas in the right hemisphere: the posteromedial part of Heschl's gyrus (HG) corresponding to the primary auditory cortex (PAC), the anterolateral part of the HG region on or posterior to the transverse sulcus, the posterior parietal cortex (PPC), posterior and anterior parts of the superior temporal gyrus (STG), and the planum temporale (PT). The mean onset latencies of each cortical activity were 17.1, 21.2, 25.3, 26.2, 30.9 and 47.6 ms respectively. These results suggested a serial model of auditory processing along the medio-lateral axis of the supratemporal plane and, in addition, implied the existence of several parallel streams running postero-superiorly (from the PAC to the belt region and then to the posterior STG, PPC or PT) and anteriorly (PAC-belt-anterior STG).

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.

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.

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.