N1m Responses Research Articles

Neuromagnetic representation of musical roundness in chord progressions.

Musical roundness perception relies on consonance/dissonance within a rule-based harmonic context, but also on individual characteristics of the listener. The present work tackles these aspects in a combined psychoacoustic and neurophysiological study, taking into account participant's musical aptitude. Our paradigm employed cadence-like four-chord progressions, based on Western music theory. Chord progressions comprised naturalistic and artificial sounds; moreover, their single chords varied regarding consonance/dissonance and harmonic function. Thirty participants listened to the chord progressions while their cortical activity was measured with magnetoencephalography; afterwards, they rated the individual chord progressions with respect to their perceived roundness. Roundness ratings differed according to the degree of dissonance in the dominant chord at the progression's third position; this effect was pronounced in listeners with high musical aptitude. Interestingly, a corresponding pattern occurred in the neuromagnetic N1m response to the fourth chord (i.e., at the progression's resolution), again with somewhat stronger differentiation among musical listeners. The N1m magnitude seemed to increase during chord progressions that were considered particularly round, with the maximum difference after the final chord; here, however, the musical aptitude effect just missed significance. The roundness of chord progressions is reflected in participant's psychoacoustic ratings and in their transient cortical activity, with stronger differentiation among listeners with high musical aptitude. The concept of roundness might help to reframe consonance/dissonance to a more holistic, gestalt-like understanding that covers chord relations in Western music.

Possibility of additive effects by the presentation of visual information related to distractor sounds on the contra-sound effects of the N100m responses

Auditory-evoked responses can be affected by different types of contralateral sounds or by attention modulation. The present study examined the additive effects of presenting visual information about contralateral sounds as distractions during dichotic listening tasks on the contralateral effects of N100m responses in the auditory-evoked cortex in 16 subjects (12 males and 4 females). In magnetoencephalography, a tone-burst of 500 ms duration at a frequency of 1000 Hz was played to the left ear at a level of 70 dB as a stimulus to elicit the N100m response, and a movie clip was used as a distractor stimulus under audio-only, visual-only, and audio-visual conditions.Subjects were instructed to pay attention to the left ear and press the response button each time they heard a tone-burst stimulus in their left ear. The results suggest that the presentation of visual information related to the contralateral sound, which worked as a distractor, significantly suppressed the amplitude of the N100m response compared with only the contralateral sound condition. In contrast, the presentation of visual information related to contralateral sound did not affect the latency of the N100m response. These results suggest that the integration of contralateral sounds and related movies may have resulted in a more perceptually loaded stimulus and reduced the intensity of attention to tone-bursts. Our findings suggest that selective attention and saliency mechanisms may have cross-modal effects on other modes of perception.

Different contra-sound effects between noise and music stimuli seen in N1m and psychophysical responses

Auditory-evoked responses can be affected by the sound presented to the contralateral ear. The different contra-sound effects between noise and music stimuli on N1m responses of auditory-evoked fields and those on psychophysical response were examined in 12 and 15 subjects, respectively. In the magnetoencephalographic study, the stimulus to elicit the N1m response was a tone burst of 500 ms duration at a frequency of 250 Hz, presented at a level of 70 dB, and white noise filtered with high-pass filter at 2000 Hz and music stimuli filtered with high-pass filter at 2000 Hz were used as contralateral noise. The contralateral stimuli (noise or music) were presented in 10 dB steps from 80 dB to 30 dB. Subjects were instructed to focus their attention to the left ear and to press the response button each time they heard burst stimuli presented to the left ear. In the psychophysical study, the effects of contralateral sound presentation on the response time for detection of the probe sound of a 250 Hz tone burst presented at a level of 70 dB were examined for the same contra-noise and contra-music used in the magnetoencephalographic study. The amplitude reduction and latency delay of N1m caused by contra-music stimuli were significantly larger than those by contra-noise stimuli in bilateral hemisphere, even for low level of contra-music near the psychophysical threshold. Moreover, this larger suppressive effect induced by contra-music effects was also observed psychophysically; i.e., the change in response time for detection of the probe sound was significantly longer by adding contralateral music stimuli than by adding contra-noise stimuli. Regarding differences in effect between contra-music and contra-noise, differences in the degree of saliency may be responsible for their different abilities to disturb auditory attention to the probe sound, but further investigation is required to confirm this hypothesis.

N100m latency shortening caused by selective attention

The N100m response to a specific same-sound stimulus may be altered by the degree of attention paid to the stimulus. When participants selectively pay attention to the stimulus, the N100m amplitude increases; however, minimal effects are observed on the N100m latency. In this study, we examined the effects of selective special attention (motivation) to extract the frequency (or pitch) information from a probe tone on the N100m response to the probe tone. We compared the N100m latencies and amplitudes using magnetoencephalography, with the following three experimental conditions: 1) vocalization task protocol (vocalize in tune with the pitch of the probe tone after the presentation of the probe tone), 2) hearing task protocol (just listen to the probe tone), and 3) imagining (just imagine the vocalization in tune with the probe tone). The results indicated that the N100m latency in response to the probe tone was significantly shortened in the vocalization and imagining tasks compared with the hearing task in the right hemisphere of the brain. The amplitude was significantly increased in the vocalization task compared with the imagining and hearing tasks in the right hemisphere, and in the vocalization task compared with the hearing task in the left hemisphere of the brain; that is, the attention and/or motivation required to extract the information from the stimulus tones may have caused N100m latency shortening. To our knowledge, this study is the first to demonstrate that the N100m latency may be shortened under particular attentional conditions in response to a simple tone.

Modulation change detection in human auditory cortex: Evidence for asymmetric, non-linear edge detection.

Changes in modulation rate are important cues for parsing acoustic signals, such as speech. We parametrically controlled modulation rate via the correlation coefficient (r) of amplitude spectra across fixed frequency channels between adjacent time frames: broadband modulation spectra are biased toward slow modulate rates with increasing r, and vice versa. By concatenating segments with different r, acoustic changes of various directions (e.g., changes from low to high correlation coefficients, that is, random-to-correlated or vice versa) and sizes (e.g., changes from low to high or from medium to high correlation coefficients) can be obtained. Participants listened to sound blocks and detected changes in correlation while MEG was recorded. Evoked responses to changes in correlation demonstrated (a) an asymmetric representation of change direction: random-to-correlated changes produced a prominent evoked field around 180ms, while correlated-to-random changes evoked an earlier response with peaks at around 70 and 120ms, whose topographies resemble those of the canonical P50m and N100m responses, respectively, and (b) a highly non-linear representation of correlation structure, whereby even small changes involving segments with a high correlation coefficient were much more salient than relatively large changes that did not involve segments with high correlation coefficients. Induced responses revealed phase tracking in the delta and theta frequency bands for the high correlation stimuli. The results confirm a high sensitivity for low modulation rates in human auditory cortex, both in terms of their representation and their segregation from other modulation rates.

A simple magnetoencephalographic auditory paradigm may aid in confirming left-hemispheric language dominance in epilepsy patients.

ObjectiveThe intracarotid amobarbital procedure (IAP) is the current “gold standard” in the preoperative assessment of language lateralization in epilepsy surgery candidates. It is, however, invasive and has several limitations. Here we tested a simple noninvasive language lateralization test performed with magnetoencephalography (MEG).MethodsWe recorded auditory MEG responses to pairs of vowels and pure tones in 16 epilepsy surgery candidates who had undergone IAP. For each individual, we selected the pair of planar gradiometer sensors with the strongest N100m response to vowels in each hemisphere and—from the vector sum of signals of this gradiometer pair—calculated the vowel/tone amplitude ratio in the left (L) and right (R) hemisphere and, subsequently, the laterality index: LI = (L–R)/(L+R). In addition to the analysis using a single sensor pair, an alternative analysis was performed using averaged responses over 18 temporal sensor pairs in both hemispheres.ResultsThe laterality index did not correlate significantly with the lateralization data obtained from the IAP. However, an MEG pattern of stronger responses to vowels than tones in the left hemisphere and stronger responses to tones than vowels in the right hemisphere was associated with left-hemispheric language dominance in the IAP in all the six patients who showed this pattern. This results in a specificity of 100% and a sensitivity of 67% of this MEG pattern in predicting left-hemispheric language dominance (p = 0.01, Fisher's exact test). In the analysis using averaged responses over temporal channels, one additional patient who was left-dominant in IAP showed this particular MEG pattern, increasing the sensitivity to 78% (p = 0.003).SignificanceThis simple MEG paradigm shows promise in feasibly and noninvasively confirming left-hemispheric language dominance in epilepsy surgery candidates. It may aid in reducing the need for the IAP, if the results are confirmed in larger patient samples.

Modulation of Auditory Evoked Magnetic Fields Elicited by Successive Frequency-Modulated (FM) Sweeps.

In our daily life, we are successively exposed to frequency-modulated (FM) sounds that play an important role in speech and species-specific communication. Previous studies demonstrated that repetitive exposure to identical pure tones resulted in decreased neural activity. However, the effects of repetitively presented FM sounds on neural activity in the human auditory cortex remain unclear. In the present study, we used magnetoencephalography to investigate auditory evoked N1m responses elicited by four successive temporally repeated and superimposed FM sweeps in three sequences: (1) four FM sweeps were identical, (2) four FM sweeps had the same FM direction and rate, but different carrier frequencies, (3) four FM sweeps differed with respect to the FM rate and/or direction and their carrier frequencies. In contrast to our expectations, the results obtained demonstrated that N1m responses were maximal when the four FM sweeps were identical and minimal when they were distinct. These results suggest that the neural processing of repetitive FM sweeps in the human auditory cortex may differ from that of repetitive pure tones.

Impact of Audio-Visual Asynchrony on Lip-Reading Effects -Neuromagnetic and Psychophysical Study.

The effects of asynchrony between audio and visual (A/V) stimuli on the N100m responses of magnetoencephalography in the left hemisphere were compared with those on the psychophysical responses in 11 participants. The latency and amplitude of N100m were significantly shortened and reduced in the left hemisphere by the presentation of visual speech as long as the temporal asynchrony between A/V stimuli was within 100 ms, but were not significantly affected with audio lags of -500 and +500 ms. However, some small effects were still preserved on average with audio lags of 500 ms, suggesting similar asymmetry of the temporal window to that observed in psychophysical measurements, which tended to be more robust (wider) for audio lags; i.e., the pattern of visual-speech effects as a function of A/V lag observed in the N100m in the left hemisphere grossly resembled that in psychophysical measurements on average, although the individual responses were somewhat varied. The present results suggest that the basic configuration of the temporal window of visual effects on auditory-speech perception could be observed from the early auditory processing stage.

Auditory evoked fields elicited by repetitive gaps embedded within a continuous tone

The N1m response, which is a prominent auditory evoked component with a latency of around 100 ms, elicited by sound onset is known to decrease with the repetition of identical sound stimuli. Previous studies demonstrated that a silent gap embedded within a continuous sound could also elicit the N1m responses; however, it remains elusive whether the N1m decrement occurs with a repetition of silent gaps. In the present study, we investigated the decrement of N1m responses elicited by five repetitive pure tones presented in silence and by five repetitive silent gaps embedded within a continuous tone using magnetoencephalography. The results obtained demonstrated that the N1m responses elicited by the repetitive pure tones decreased from the 1st to the 2nd and remained constant from the 2nd to the 5th, whereas those elicited by the repetitive gaps in a continuous tone gradually decreased from the 1st to the 5th. Those results indicate that neural refractoriness appears to mainly contribute to the decrement of the N1m responses elicited by repetitive pure tones, while habituation may play an additional role in the decrement of the N1m responses elicited by repetitive gaps in a continuous tone.

Encoding of frequency-modulation (FM) rates in human auditory cortex.

Frequency-modulated sounds play an important role in our daily social life. However, it currently remains unclear whether frequency modulation rates affect neural activity in the human auditory cortex. In the present study, using magnetoencephalography, we investigated the auditory evoked N1m and sustained field responses elicited by temporally repeated and superimposed frequency-modulated sweeps that were matched in the spectral domain, but differed in frequency modulation rates (1, 4, 16, and 64 octaves per sec). The results obtained demonstrated that the higher rate frequency-modulated sweeps elicited the smaller N1m and the larger sustained field responses. Frequency modulation rate had a significant impact on the human brain responses, thereby providing a key for disentangling a series of natural frequency-modulated sounds such as speech and music.

Extractions of steady-state auditory evoked fields in normal subjects and tinnitus patients using complementary ensemble empirical mode decomposition.

BackgroundAuditory steady-state response (ASSR) induced by repetitive auditory stimulus is commonly used for audiometric testing. ASSR can be measured using electro-encephalography (EEG) and magnetoencephalography (MEG), referred to as steady-state auditory evoked potential (SSAEP) and steady-state auditory evoked field (SSAEF), respectively. However, the signal level of SSAEP and SSAEF are weak so that signal processing technique is required to increase its signal-to-noise ratio. In this study, a complementary ensemble empirical mode decomposition (CEEMD)-based approach is proposed in MEG study and the extraction of SSAEF has been demonstrated in normal subjects and tinnitus patients.MethodsThe CEEMD utilizes noise assisted data analysis (NADA) approach by adding positive and negative noise to decompose MEG signals into complementary intrinsic mode functions (IMF). Ten subjects (five normal and five tinnitus patients) were studied. The auditory stimulus was designed as 1 kHz carrier frequency with 37 Hz modulation frequency. Two channels in the vicinities of right and left temporal areas were chosen as channel-of-interests (COI) and decomposed into IMFs. The spatial distribution of each IMF was correlated with a pair of left- and right-hemisphere spatial templates, designed from each subject’s N100m responses in pure-tone auditory stimulation. IMFs with spatial distributions highly correlated with spatial templates were identified using K-means and those SSAEF-related IMFs were used to reconstruct noise-suppressed SSAEFs.ResultsThe current strengths estimated from CEEMD processed SSAEF showed neural activities greater or comparable to those processed by conventional filtering method. Both the normal and tinnitus groups showed the phenomenon of right-hemisphere dominance. The mean current strengths of auditory-induced neural activities in tinnitus group were larger than the normal group.ConclusionsThe present study proposes an effective method for SSAEF extraction. The enhanced SSAEF in tinnitus group echoes the decreased inhibition in tinnitus’s central auditory structures as reported in previous studies.

Computational modelling suggests that temporal integration results from synaptic adaptation in auditory cortex.

Incoming sounds are represented in the context of preceding events, and this requires a memory mechanism that integrates information over time. Here, it was demonstrated that response adaptation, the suppression of neural responses due to stimulus repetition, might reflect a computational solution that auditory cortex uses for temporal integration. Adaptation is observed in single-unit measurements as two-tone forward masking effects and as stimulus-specific adaptation (SSA). In non-invasive observations, the amplitude of the auditory N1m response adapts strongly with stimulus repetition, and it is followed by response recovery (the so-called mismatch response) to rare deviant events. The current computational simulations described the serial core-belt-parabelt structure of auditory cortex, and included synaptic adaptation, the short-term, activity-dependent depression of excitatory corticocortical connections. It was found that synaptic adaptation is sufficient for columns to respond selectively to tone pairs and complex tone sequences. These responses were defined as combination sensitive, thus reflecting temporal integration, when a strong response to a stimulus sequence was coupled with weaker responses both to the time-reversed sequence and to the isolated sequence elements. The temporal complexity of the stimulus seemed to be reflected in the proportion of combination-sensitive columns across the different regions of the model. Our results suggest that while synaptic adaptation produces facilitation and suppression effects, including SSA and the modulation of the N1m response, its functional significance may actually be in its contribution to temporal integration. This integration seems to benefit from the serial structure of auditory cortex.

Human cortical sensitivity to interaural time difference in high-frequency sounds

Human sound source localization relies on various acoustical cues one of the most important being the interaural time difference (ITD). ITD is best detected in the fine structure of low-frequency sounds but it may also contribute to spatial hearing at higher frequencies if extracted from the sound envelope. The human brain mechanisms related to this envelope ITD cue remain unexplored. Here, we tested the sensitivity of the human auditory cortex to envelope ITD in magnetoencephalography (MEG) recordings. We found two types of sensitivity to envelope ITD. First, the amplitude of the auditory cortical N1m response was smaller for zero envelope ITD than for long envelope ITDs corresponding to the sound being in opposite phase in the two ears. Second, the N1m response amplitude showed ITD-specific adaptation for both fine-structure and for envelope ITD. The auditory cortical sensitivity was weaker for envelope ITD in high-frequency sounds than for fine-structure ITD in low-frequency sounds but occurred within a range of ITDs that are encountered in natural conditions. Finally, the participants were briefly tested for their behavioral ability to detect envelope ITD. Interestingly, we found a correlation between the behavioral performance and the neural sensitivity to envelope ITD. In conclusion, our findings show that the human auditory cortex is sensitive to ITD in the envelope of high-frequency sounds and this sensitivity may have behavioral relevance.

Statistical learning of music- and language-like sequences and tolerance for spectral shifts

In our previous study (Daikoku, Yatomi, & Yumoto, 2014), we demonstrated that the N1m response could be a marker for the statistical learning process of pitch sequence, in which each tone was ordered by a Markov stochastic model. The aim of the present study was to investigate how the statistical learning of music- and language-like auditory sequences is reflected in the N1m responses based on the assumption that both language and music share domain generality. By using vowel sounds generated by a formant synthesizer, we devised music- and language-like auditory sequences in which higher-ordered transitional rules were embedded according to a Markov stochastic model by controlling fundamental (F0) and/or formant frequencies (F1–F2). In each sequence, F0 and/or F1–F2 were spectrally shifted in the last one-third of the tone sequence. Neuromagnetic responses to the tone sequences were recorded from 14 right-handed normal volunteers. In the music- and language-like sequences with pitch change, the N1m responses to the tones that appeared with higher transitional probability were significantly decreased compared with the responses to the tones that appeared with lower transitional probability within the first two-thirds of each sequence. Moreover, the amplitude difference was even retained within the last one-third of the sequence after the spectral shifts. However, in the language-like sequence without pitch change, no significant difference could be detected. The pitch change may facilitate the statistical learning in language and music. Statistically acquired knowledge may be appropriated to process altered auditory sequences with spectral shifts. The relative processing of spectral sequences may be a domain-general auditory mechanism that is innate to humans.

Neural adaptation to silence in the human auditory cortex: a magnetoencephalographic study.

IntroductionPrevious studies demonstrated that a decrement in the N1m response, a major deflection in the auditory evoked response, with sound repetition was mainly caused by bottom-up driven neural refractory periods following brain activation due to sound stimulations. However, it currently remains unknown whether this decrement occurs with a repetition of silences, which do not induce refractoriness.MethodsIn the present study, we investigated decrements in N1m responses elicited by five repetitive silences in a continuous pure tone and by five repetitive pure tones in silence using magnetoencephalography.ResultsRepetitive sound stimulation differentially affected the N1m decrement in a sound type-dependent manner; while the N1m amplitude decreased from the 1st to the 2nd pure tone and remained constant from the 2nd to the 5th pure tone in silence, a gradual decrement was observed in the N1m amplitude from the 1st to the 5th silence embedded in a continuous pure tone.ConclusionsOur results suggest that neural refractoriness may mainly cause decrements in N1m responses elicited by trains of pure tones in silence, while habituation, which is a form of the implicit learning process, may play an important role in the N1m source strength decrements elicited by successive silences in a continuous pure tone.

Implicit and explicit statistical learning of tone sequences across spectral shifts

We investigated how the statistical learning of auditory sequences is reflected in neuromagnetic responses in implicit and explicit learning conditions. Complex tones with fundamental frequencies (F0s) in a five-tone equal temperament were generated by a formant synthesizer. The tones were subsequently ordered with the constraint that the probability of the forthcoming tone was statistically defined (80% for one tone; 5% for the other four) by the latest two successive tones (second-order Markov chains). The tone sequence consisted of 500 tones and 250 successive tones with a relative shift of F0s based on the same Markov transitional matrix. In explicit and implicit learning conditions, neuromagnetic responses to the tone sequence were recorded from fourteen right-handed participants. The temporal profiles of the N1m responses to the tones with higher and lower transitional probabilities were compared. In the explicit learning condition, the N1m responses to tones with higher transitional probability were significantly decreased compared with responses to tones with lower transitional probability in the latter half of the 500-tone sequence. Furthermore, this difference was retained even after the F0s were relatively shifted. In the implicit learning condition, N1m responses to tones with higher transitional probability were significantly decreased only for the 250 tones following the relative shift of F0s. The delayed detection of learning effects across the sound-spectral shift in the implicit condition may imply that learning may progress earlier in explicit learning conditions than in implicit learning conditions. The finding that the learning effects were retained across spectral shifts regardless of the learning modality indicates that relative pitch processing may be an essential ability for humans.

Modulatory Effects of Spectral Energy Contrasts on Lateral Inhibition in the Human Auditory Cortex: An MEG Study

We investigated the modulation of lateral inhibition in the human auditory cortex by means of magnetoencephalography (MEG). In the first experiment, five acoustic masking stimuli (MS), consisting of noise passing through a digital notch filter which was centered at 1 kHz, were presented. The spectral energy contrasts of four MS were modified systematically by either amplifying or attenuating the edge-frequency bands around the notch (EFB) by 30 dB. Additionally, the width of EFB amplification/attenuation was varied (3/8 or 7/8 octave on each side of the notch). N1m and auditory steady state responses (ASSR), evoked by a test stimulus with a carrier frequency of 1 kHz, were evaluated. A consistent dependence of N1m responses upon the preceding MS was observed. The minimal N1m source strength was found in the narrowest amplified EFB condition, representing pronounced lateral inhibition of neurons with characteristic frequencies corresponding to the center frequency of the notch (NOTCH CF) in secondary auditory cortical areas. We tested in a second experiment whether an even narrower bandwidth of EFB amplification would result in further enhanced lateral inhibition of the NOTCH CF. Here three MS were presented, two of which were modified by amplifying 1/8 or 1/24 octave EFB width around the notch. We found that N1m responses were again significantly smaller in both amplified EFB conditions as compared to the NFN condition. To our knowledge, this is the first study demonstrating that the energy and width of the EFB around the notch modulate lateral inhibition in human secondary auditory cortical areas. Because it is assumed that chronic tinnitus is caused by a lack of lateral inhibition, these new insights could be used as a tool for further improvement of tinnitus treatments focusing on the lateral inhibition of neurons corresponding to the tinnitus frequency, such as the tailor-made notched music training.

Activation of Auditory Cortex by Anticipating and Hearing Emotional Sounds: An MEG Study

To study how auditory cortical processing is affected by anticipating and hearing of long emotional sounds, we recorded auditory evoked magnetic fields with a whole-scalp MEG device from 15 healthy adults who were listening to emotional or neutral sounds. Pleasant, unpleasant, or neutral sounds, each lasting for 6 s, were played in a random order, preceded by 100-ms cue tones (0.5, 1, or 2 kHz) 2 s before the onset of the sound. The cue tones, indicating the valence of the upcoming emotional sounds, evoked typical transient N100m responses in the auditory cortex. During the rest of the anticipation period (until the beginning of the emotional sound), auditory cortices of both hemispheres generated slow shifts of the same polarity as N100m. During anticipation, the relative strengths of the auditory-cortex signals depended on the upcoming sound: towards the end of the anticipation period the activity became stronger when the subject was anticipating emotional rather than neutral sounds. During the actual emotional and neutral sounds, sustained fields were predominant in the left hemisphere for all sounds. The measured DC MEG signals during both anticipation and hearing of emotional sounds implied that following the cue that indicates the valence of the upcoming sound, the auditory-cortex activity is modulated by the upcoming sound category during the anticipation period.

Positive auditory cortical responses in patients with absent brainstem response

ObjectiveTo compare the detectability of the different auditory evoked responses in patients with retrocochlear lesion. MethodsThe 40-Hz auditory steady state response (ASSR) and the N1m auditory cortical response were examined by magnetoencephalography in 4 patients with vestibular schwannoma, in whom the auditory brainstem response (ABR) was absent. ResultsApparent N1m responses were observed despite total absence of the ABR or absence except for small wave I in all patients, although the latency of N1m was delayed in most patients. On the other hand, clear ASSFs could be observed only in one patient. Very small 40-Hz ASSFs could be detected in 2 patients (amplitude less than 1fT), but no apparent ASSFs were observed in one patient, in whom maximum speech intelligibility was extremely low and the latency of N1m was most prolonged. ConclusionThe N1m response and 40-Hz ASSR could be detected in patients with absent ABR, but the N1m response appeared to be more detectable than the 40-Hz ASSR. SignificanceCombined assessment with several different evoked responses may be useful to evaluate the disease conditions of patients with retrocochlear lesions.

Transcutaneous vagus nerve stimulation in tinnitus: a pilot study

Conclusions: This pilot study shows that transcutaneous vagus nerve stimulation (tVNS), if combined with sound therapy (ST), reduces the severity of tinnitus and tinnitus-associated distress. Our magnetoencephalography (MEG) results show that auditory cortical activation can be modulated by the application of tVNS. Thus, tVNS might offer a new avenue to treat tinnitus and tinnitus-associated distress. Objectives: Recent studies suggest that tinnitus can be improved by tailored ST or by VNS plus ST. Our aims were to study whether tVNS has therapeutic effects on patients with tinnitus and, additionally, if tVNS has effects on acoustically evoked neuronal activity of the auditory cortex. Methods: The clinical efficacy was studied by a short-term tVNS plus ST trial in 10 patients with tinnitus using disease-specific and general well-being questionnaires. tVNS was delivered to the left tragus. The acute effects of tVNS were evaluated in eight patients in the MEG study in which the N1m response was analyzed in terms of source level amplitude and latency in the presence or absence of tVNS. Results: The treatment with tVNS plus ST produced improved mood and decreased tinnitus handicap scores, indicating reduced tinnitus severity. The application of tVNS decreased the amplitude of auditory N1m responses in both hemispheres.