Tinnitus-frequency specific activity and connectivity: A MEG study.

Tinnitus pathophysiology has been associated with an atypical cortical network that involves functional changes in auditory and non-auditory areas. Numerous resting-state studies have replicated a tinnitus brain network to be significantly different from healthy-controls. Yet it is still unknown whether the cortical reorganization is attributed to the tinnitus frequency specifically or if it is frequency-irrelevant. Employing magnetoencephalography (MEG), the current study aimed to identify frequency-specific activity patterns by using an individual tinnitus tone (TT) and a 500 Hz-control tone (CT) as auditory stimuli, across 54 tinnitus patients. MEG data were analyzed in a data-driven approach employing a whole-head model in source space and in sources' functional connectivity. Compared to the CT, the event related source space analysis revealed a statistically significant response to TT involving fronto-parietal regions. The CT mainly involved typical auditory activation-related regions. A comparison of the cortical responses to a healthy control group that underwent the same paradigm rejected the alternative interpretation that the frequency-specific activation differences were due to the higher frequency of the TT. Overall, the results suggest frequency-specificity of tinnitus-related cortical patterns. In line with previous studies, we demonstrated a tinnitus-frequency specific network comprising left fronto-temporal, fronto-parietal and tempo-parietal junctions.

Clinical determinants and neural correlates of presbyphagia in community-dwelling older adults.

Background: "Presbyphagia" refers to characteristic age-related changes in the complex neuromuscular swallowing mechanism. It has been hypothesized that cumulative impairments in multiple domains affect functional reserve of swallowing with age, but the multifactorial etiology and postulated compensatory strategies of the brain are incompletely understood. This study investigates presbyphagia and its neural correlates, focusing on the clinical determinants associated with adaptive neuroplasticity. Materials and methods: 64 subjects over 70 years of age free of typical diseases explaining dysphagia received comprehensive workup including flexible endoscopic evaluation of swallowing (FEES), magnetoencephalography (MEG) during swallowing and pharyngeal stimulation, volumetry of swallowing muscles, laboratory analyzes, and assessment of hand-grip-strength, nutritional status, frailty, olfaction, cognition and mental health. Neural MEG activation was compared between participants with and without presbyphagia in FEES, and associated clinical influencing factors were analyzed. Presbyphagia was defined as the presence of oropharyngeal swallowing alterations e.g., penetration, aspiration, pharyngeal residue pooling or premature bolus spillage into the piriform sinus and/or laryngeal vestibule. Results: 32 of 64 participants showed swallowing alterations, mainly characterized by pharyngeal residue, whereas the airway was rarely compromised. In the MEG analysis, participants with presbyphagia activated an increased cortical sensorimotor network during swallowing. As major clinical determinant, participants with swallowing alterations exhibited reduced pharyngeal sensation. Presbyphagia was an independent predictor of a reduced nutritional status in a linear regression model. Conclusions: Swallowing alterations frequently occur in otherwise healthy older adults and are associated with decreased nutritional status. Increased sensorimotor cortical activation may constitute a compensation attempt to uphold swallowing function due to sensory decline. Further studies are needed to clarify whether the swallowing alterations observed can be considered physiological per se or whether the concept of presbyphagia may need to be extended to a theory with a continuous transition between presbyphagia and dysphagia.

Acute effect of vagus nerve stimulation (VNS) on brain function.

INTRODUCTION: VNS is a non-pharmalogical neuromodulatory treatment option for difficult-to-treat depression. A pulse generator implanted in the left chest area is connected to an electrode that is wrapped around the left vagal nerve. It is presumed, that the vagal afferent network modulates neuronal activity in key monoaminergic structures. METHODS: We performed MEG recording during active stimulation of the left vagal nerve. Our patient was a 60 years old female treated with VNS since December 2019 due to unipolar major depression. RESULTS: MEG recording and analysis were possible despite stimulation signals and the metal stimulation systems. We saw a reproducible reduction of the 10-Hz-alpha amplitude after the end of the 30 s stimulation period in wide-spread areas including parieto-occipital cortex where alpha oscillations are prominently generated. During stimulation, however, alpha oscillations remained unaffected. These findings could be reproduced in a second measurement. CONCLUSION: Increased alpha power was linked to depressive states and alterations of cortical activity. A reduction may indicate cortical activation by stimulation of the vagal nerve as a possible mechanism of action of VNS in depression.

Comparing pure tone and narrow band noise to measure tonal tinnitus pitch-match frequency.

Tinnitus assessment is a precursor for individualized treatment and outcome measurement. In the recent years, several studies proposed two-alternative forced choice (2AFC) recursive matching as a method to determine tinnitus pitch-match frequency in a standardized reliable manner. Currently, pure tones are used as comparison stimuli to assess pitch-match frequency. In this study, we investigated the psychometric quality of the method comparing different sound types. We measured 20 chronic tinnitus patients in 2 runs on 3 days. To assess pitch-match frequency, we used 2AFC recursive matching and compared results between pure tones and narrow band noise (NBN). Test-retest reliability between runs and across sound types was high (α>0.9) and increased across days. Perceived matching difficulty and time to completion decreased over repetitions. Importantly, the difference of matched frequencies (DMF) between runs was significantly less for NBN. When patients matched the spectral bandwidth of a test tone to their tinnitus, consistency was high (α=0.86) and no patient indicated continuously a pure tone. In conclusion, we recommend using NBN sounds in 2AFC recursive matching to assess pitch-match frequency as a standardized reliable method. Such a procedure could be offered as smartphone-based application to monitor tinnitus symptomatology for individualized assessment and treatment outcome.

Targeting the sensory feedback within the swallowing network-Reversing artificially induced pharyngolaryngeal hypesthesia by central and peripheral stimulation strategies.

Pharyngolaryngeal hypesthesia is a major reason for dysphagia in various neurological diseases. Emerging neuromodulation devices have shown potential to foster dysphagia rehabilitation, but the optimal treatment strategy is unknown. Because functional imaging studies are difficult to conduct in severely ill patients, we induced a virtual sensory lesion in healthy volunteers and evaluated the effects of central and peripheral neurostimulation techniques. In a sham-controlled intervention study with crossover design on 10 participants, we tested the potential of (peripheral) pharyngeal electrical stimulation (PES) and (central) transcranial direct current stimulation (tDCS) to revert the effects of lidocaine-induced pharyngolaryngeal hypesthesia on central sensorimotor processing. Changes were observed during pharyngeal air-pulse stimulation and voluntary swallowing applying magnetoencephalography before and after the interventions. PES induced a significant (p < .05) increase of activation during swallowing in the bihemispheric sensorimotor network in alpha and low gamma frequency ranges, peaking in the right premotor and left primary sensory area, respectively. With pneumatic stimulation, significant activation increase was found after PES in high gamma peaking in the left premotor area. Significant changes of brain activation after tDCS could neither be detected for pneumatic stimulation nor for swallowing. Due to the peripheral cause of dysphagia in this model, PES was able to revert the detrimental effects of reduced sensory input on central processing, whereas tDCS was not. Results may have implications for therapeutic decisions in the clinical context.

One Step Closer towards a Reliable Tinnitus Pitch-Match Frequency Determination Using Repetitive Recursive Matching.

INTRODUCTION: The determination of the tinnitus pitch-match (PM) frequency is not straightforward but an important audiological assessment recommended for clinical and research purposes. We evaluated repetitive recursive matching using an iPod-based matching procedure as a method to estimate a patient's PM frequency without audiometric equipment. METHODS: One hundred and seventeen patients with chronic tonal tinnitus (uni- and bilateral tinnitus) measured their tinnitus in 10 sessions using a self-administered automated iPod-based procedure comprising a recursive 2 interval forced-choice test. RESULTS: Mean SD of the PM frequency of all participants across sessions was 0.41 octaves. The internal consistency measured by Cronbach's α was very high (0.8->0.95). As an example, 7 PMs obtained excellent internal consistency (α = 0.93). The exclusion of the first and/or second session led to more definite PMs with a decreased SD. Outliers were identified by PMs departing 2 SDs (i.e., 0.94 octaves) from the mean variability (n = 5). CONCLUSION: Repetitive recursive matching together with recommendations for the exclusion of initial and redundant sessions as well as outlier identification and treatment can enable a reliable estimation of the PM frequency.

Auditory Categorization of Man-Made Sounds Versus Natural Sounds by Means of MEG Functional Brain Connectivity.

Previous neuroimaging studies have shown that sounds can be discriminated due to living-related or man-made-related characteristics and involve different brain regions. However, these studies have mainly provided source space analyses, which offer simple maps of activated brain regions but do not explain how regions of a distributed system are functionally organized under a specific task. In the present study, we aimed to further examine the functional connectivity of the auditory processing pathway across different categories of non-speech sounds in healthy adults, by means of MEG. Our analyses demonstrated significant activation and interconnection differences between living and man-made object sounds, in the prefrontal areas, anterior-superior temporal gyrus (aSTG), posterior cingulate cortex (PCC), and supramarginal gyrus (SMG), occurring within 80-120 ms post-stimulus interval. Current findings replicated previous ones, in that other regions beyond the auditory cortex are involved during auditory processing. According to the functional connectivity analysis, differential brain networks across the categories exist, which proposes that sound category discrimination processing relies on distinct cortical networks, a notion that has been strongly argued in the literature also in relation to the visual system.

Maladaptive alterations of resting state cortical network in Tinnitus: A directed functional connectivity analysis of a larger MEG data set.

The present study used resting state MEG whole-head recordings to identify how chronic tonal tinnitus relates to altered functional connectivity of brain's intrinsic cortical networks. Resting state MEG activity of 40 chronic tinnitus patients and 40 matched human controls was compared identifying significant alterations in intrinsic networks of the tinnitus population. Directed functional connectivity of the resting brain, at a whole cortex level, was estimated by means of a statistical comparison of the estimated phase Transfer Entropy (pTE) between the time-series of cortical activations, as reconstructed by LORETA. As pTE identifies the direction of the information flow, a detailed analysis of the connectivity differences between tinnitus patients and controls was possible. Results indicate that the group of tinnitus patients show increased connectivity from right dorsal prefrontal to right medial temporal areas. Our results go beyond previous findings by indicating that the role of the left para-hippocampal area is dictated by a modulation from dmPFC; a region that is part of the dorsal attention network (DAN), as well as implicated in the regulation of emotional processing. Additionally, this whole cortex analysis showed a crucial role of the left inferior parietal cortex, which modulated the activity of the right superior temporal gyrus, providing new hypotheses for the role of this area within the context of current tinnitus models. Overall, these maladaptive alterations of the structure of intrinsic cortical networks show a decrease in efficiency and small worldness of the resting state network of tinnitus patients, which is correlated to tinnitus distress.

Choice of test stimulus matters for pitch matching performance: Comparison between pure tone and narrow band noise.

Chronic tinnitus, a symptom of high prevalence, is a persistent hearing sensation in the absence of an external sound source. Recent electrophysiological studies indicate that tinnitus generation is to a high degree the result of maladaptive plasticity in the central auditory pathway. The pitch of the tinnitus sensation can be assessed by performing a pitch matching procedure. In the most frequent "tonal tinnitus" type pure tones are used as test stimuli. However, in the case of tonal tinnitus not a single malfunctioning neuron, but rather a population of neighbouring neurons is involved in the generation process of tinnitus and patients typically perceive their tinnitus as a sound having a prominent centre frequency with some spectral extent. Thus, the question arises, why not to use narrow band noise (NBN) instead of pure tones as test stimuli in pitch matching procedures? To investigate this, we first evaluated the pitch matching performance of healthy subjects. In a recursive two alternative choice testing, driven by a computer based automated procedure, the subjects were asked to match the pitch of two sounds. In a crosswise design, NBNs and pure tones were used both as target and as test stimuli. We were able to show that across all four possible combinations the pitch matching performance was least favourable when a sinusoidal sound had to be matched to an NBN target. Even though matching two sinusoidal sounds results in the lowest error, considering that the tinnitus percept typically includes some spectral extent, an NBN should be preferably used as a test stimulus against a pure tone.

The effect of stimulation type, head modeling, and combined EEG and MEG on the source reconstruction of the somatosensory P20/N20 component.

Modeling and experimental parameters influence the Electro- (EEG) and Magnetoencephalography (MEG) source analysis of the somatosensory P20/N20 component. In a sensitivity group study, we compare P20/N20 source analysis due to different stimulation type (Electric-Wrist [EW], Braille-Tactile [BT], or Pneumato-Tactile [PT]), measurement modality (combined EEG/MEG - EMEG, EEG, or MEG) and head model (standard or individually skull-conductivity calibrated including brain anisotropic conductivity). Considerable differences between pairs of stimulation types occurred (EW-BT: 8.7 ± 3.3 mm/27.1° ± 16.4°, BT-PT: 9 ± 5 mm/29.9° ± 17.3°, and EW-PT: 9.8 ± 7.4 mm/15.9° ± 16.5° and 75% strength reduction of BT or PT when compared to EW) regardless of the head model used. EMEG has nearly no localization differences to MEG, but large ones to EEG (16.1 ± 4.9 mm), while source orientation differences are non-negligible to both EEG (14° ± 3.7°) and MEG (12.5° ± 10.9°). Our calibration results show a considerable inter-subject variability (3.1-14 mS/m) for skull conductivity. The comparison due to different head model show localization differences smaller for EMEG (EW: 3.4 ± 2.4 mm, BT: 3.7 ± 3.4 mm, and PT: 5.9 ± 6.8 mm) than for EEG (EW: 8.6 ± 8.3 mm, BT: 11.8 ± 6.2 mm, and PT: 10.5 ± 5.3 mm), while source orientation differences for EMEG (EW: 15.4° ± 6.3°, BT: 25.7° ± 15.2° and PT: 14° ± 11.5°) and EEG (EW: 14.6° ± 9.5°, BT: 16.3° ± 11.1° and PT: 12.9° ± 8.9°) are in the same range. Our results show that stimulation type, modality and head modeling all have a non-negligible influence on the source reconstruction of the P20/N20 component. The complementary information of both modalities in EMEG can be exploited on the basis of detailed and individualized head models.

Constrained maximum intensity optimized multi-electrode tDCS targeting of human somatosensory network.

Transcranial direct current stimulation (tDCS) is a noninvasive method that delivers current through the scalp to enhance or suppress brain activity. The standard way of applying tDCS is by the use of two large rectangular sponge electrodes on the scalp. The resulting currents often stimulate a broad region of the brain distributed over brain networks. In order to address this issue, recently, multi-electrode transcranial direct current stimulation with optimized montages has been used to stimulate brain regions of interest (ROI) with improved trade-off between focality and intensity of the electrical current at the target brain region. However, in many cases only the location of target region is considered and not the orientation. Here we emphasize the importance of calculating the individualized target location and orientation by combined electroencephalography and magnetoencephalography (EMEG) source analysis in individualized skull-conductivity calibrated finite element method (FEM) head models and stimulate the target region by four different tDCS montages. We have chosen the generator of the P20/N20 component, located at Brodmann area 3b and oriented mainly from posterior to anterior directions as our target for stimulation because it can be modeled as a single dipole source with a fixed position and orientation. The simulations will deliver optimized excitatory and inhibitory electrode montages that are in future investigations compared to standard and sham tDCS in a somatosensory experiment. We also present a new constrained maximum intensity (CMI) optimization approach that better distributes the currents over multiple electrodes, therefore should lead to less tingling and burning sensations at the skin, and thus allows an easier realization of the sham condition significantly reducing the current intensity parallel to the target.

Statistical learning of multisensory regularities is enhanced in musicians: An MEG study.

The present study used magnetoencephalography (MEG) to identify the neural correlates of audiovisual statistical learning, while disentangling the differential contributions of uni- and multi-modal statistical mismatch responses in humans. The applied paradigm was based on a combination of a statistical learning paradigm and a multisensory oddball one, combining an audiovisual, an auditory and a visual stimulation stream, along with the corresponding deviances. Plasticity effects due to musical expertise were investigated by comparing the behavioral and MEG responses of musicians to non-musicians. The behavioral results indicated that the learning was successful for both musicians and non-musicians. The unimodal MEG responses are consistent with previous studies, revealing the contribution of Heschl's gyrus for the identification of auditory statistical mismatches and the contribution of medial temporal and visual association areas for the visual modality. The cortical network underlying audiovisual statistical learning was found to be partly common and partly distinct from the corresponding unimodal networks, comprising right temporal and left inferior frontal sources. Musicians showed enhanced activation in superior temporal and superior frontal gyrus. Connectivity and information processing flow amongst the sources comprising the cortical network of audiovisual statistical learning, as estimated by transfer entropy, was reorganized in musicians, indicating enhanced top-down processing. This neuroplastic effect showed a cross-modal stability between the auditory and audiovisual modalities.

A statistical method for analyzing and comparing spatiotemporal cortical activation patterns.

Information in the cortex is encoded in spatiotemporal patterns of neuronal activity, but the exact nature of that code still remains elusive. While onset responses to simple stimuli are associated with specific loci in cortical sensory maps, it is completely unclear how the information about a sustained stimulus is encoded that is perceived for minutes or even longer, when discharge rates have decayed back to spontaneous levels. Using a newly developed statistical approach (multidimensional cluster statistics (MCS)) that allows for a comparison of clusters of data points in n-dimensional space, we here demonstrate that the information about long-lasting stimuli is encoded in the ongoing spatiotemporal activity patterns in sensory cortex. We successfully apply MCS to multichannel local field potential recordings in different rodent models and sensory modalities, as well as to human MEG and EEG data, demonstrating its universal applicability. MCS thus indicates novel ways for the development of powerful read-out algorithms of spatiotemporal brain activity that may be implemented in innovative brain-computer interfaces (BCI).

Targeting Heterogeneous Findings in Neuronal Oscillations in Tinnitus: Analyzing MEG Novices and Mental Health Comorbidities.

Tinnitus is a prevalent phenomenon and bothersome for people affected by it. Its occurrence and maintenance have a clear neuroscientific tie and one aspect are differences in the neuronal oscillatory pattern, especially in auditory cortical areas. As studies in this field come to different results, the aim of this study was to analyze a large number of participants to achieve more stable results. Furthermore, we expanded our analysis to two variables of potential influence, namely being a novice to neuroscientific measurements and the exclusion of psychological comorbidities. Oscillatory brain activity of 88 subjects (46 with a chronic tinnitus percept, 42 without) measured in resting state by MEG was investigated. In the analysis based on the whole group, in sensor space increased activity in the delta frequency band was found in tinnitus patients. Analyzing the subgroup of novices, a significant difference in the theta band emerged additionally to the delta band difference (sensor space). Localizing the origin of the activity, we found a difference in theta and gamma band for the auditory regions for the whole group and the same significant difference in the subgroup of novices. However, no differences in oscillatory activity were observed between tinnitus and control groups once subjects with mental health comorbidity were excluded. Against the background of previous studies, the study at hand underlines the fragility of the results in the field of neuronal cortical oscillations in tinnitus. It supports the body of research arguing for low frequency oscillations and gamma band activity as markers associated with tinnitus.

Introducing a Virtual Lesion Model of Dysphagia Resulting from Pharyngeal Sensory Impairment.

BACKGROUND/AIMS: Performing neurophysiological and functional imaging studies in severely affected patients to investigate novel neurostimulation techniques for the treatment of neurogenic dysphagia is difficult. Therefore, basic research needs to be conducted in healthy subjects. Swallowing is a motor function highly dependent on sensory afferent input. Here we propose a virtual peripheral sensory lesion model to mimic pharyngeal sensory impairment, which is known as a major contributor to dysphagia in neurological disease. METHODS: In this randomized crossover study on 11 healthy volunteers, cortical activation during pneumatic pharyngeal stimulation was measured applying magnetoencephalography in two separate sessions, with and without pharyngeal surface anesthesia. RESULTS: Stimulation evoked bilateral event-related desynchronization (ERD) mainly in the caudolateral pericentral cortex. In comparison to the no-anesthesia condition, topical anesthesia led to a reduction of ERD in beta (13-30 Hz) and low gamma (30-60 Hz) frequency ranges (p<0.05) in sensory but also motor cortical areas. CONCLUSIONS: Withdrawal of sensory afferent information by topical anesthesia leads to reduced response to pneumatic pharyngeal stimulation in a distributed cortical sensorimotor network in healthy subjects. The proposed paradigm may serve to investigate the effect of neuromodulatory treatments specifically on pharyngeal sensory impairment as relevant cause of neurogenic dysphagia.

Randomized trial of transcranial direct current stimulation for poststroke dysphagia.

OBJECTIVE: We evaluated whether transcranial direct current stimulation (tDCS) is able to enhance dysphagia rehabilitation following stroke. Besides relating clinical effects with neuroplastic changes in cortical swallowing processing, we aimed to identify factors influencing treatment success. METHODS: In this double-blind, randomized study, 60 acute dysphagic stroke patients received contralesional anodal (1mA, 20 minutes) or sham tDCS on 4 consecutive days. Swallowing function was thoroughly assessed before and after the intervention using the validated Fiberoptic Endoscopic Dysphagia Severity Scale (FEDSS) and clinical assessment. In 10 patients, swallowing-related brain activation was recorded applying magnetoencephalography before and after the intervention. Voxel-based statistical lesion pattern analysis was also performed. RESULTS: Study groups did not differ according to demographic data, stroke characteristics, or baseline dysphagia severity. Patients treated with tDCS showed greater improvement in FEDSS than the sham group (1.3 vs 0.4 points, mean difference = 0.9, 95% confidence interval [CI] = 0.4-1.4, p < 0.0005). Functional recovery was accompanied by a significant increase of activation (p < 0.05) in the contralesional swallowing network after real but not sham tDCS. Regarding predictors of treatment success, for every hour earlier that treatment was initiated, there was greater improvement on the FEDSS (adjusted odds ratio = 0.99, 95% CI = 0.98-1.00, p < 0.05) in multivariate analysis. Stroke location in the right insula and operculum was indicative of worse response to tDCS (p < 0.05). INTERPRETATION: Application of tDCS over the contralesional swallowing motor cortex supports swallowing network reorganization, thereby leading to faster rehabilitation of acute poststroke dysphagia. Early treatment initiation seems beneficial. tDCS may be less effective in right-hemispheric insulo-opercular stroke. Ann Neurol 2018;83:328-340.

Clinical trial on tonal tinnitus with tailor-made notched music training.

BACKGROUND: Tinnitus is a result of hyper-activity/hyper-synchrony of auditory neurons coding the tinnitus frequency, which has developed due to synchronous mass activity owing to the lack of inhibition. We assume that removal of exactly these frequencies from a complex auditory stimulus will cause the brain to reorganize around tonotopic regions coding the tinnitus frequency through inhibition-induced plasticity. Based on this assumption, a novel treatment for tonal tinnitus--tailor-made notched music training (TMNMT)--has been introduced and was tested in this clinical trial. METHODS: A randomized controlled trial in parallel group design was performed in a double-blinded manner. We included 100 participants with chronic, tonal tinnitus who listened to tailor-made notched music for two hours a day for three consecutive months. Our primary outcome measures were the Tinnitus Handicap Questionnaire and Visual Analog Scales measuring perceived tinnitus loudness, awareness, distress and handicap. Participants rated their tinnitus before and after the training as well as one month after cessation of the training. RESULTS: While no effect was found for the primary outcome measures, tinnitus distress, as measured by the Tinnitus Questionnaire, a secondary outcome measure, developed differently in the two groups. The treatment group showed higher distress scores while the placebo group revealed lower distress scores after the training. However, this effect did not reach significance in post-hoc analysis and disappeared at follow-up measurements. At follow-up, tinnitus loudness in the treatment group was significantly reduced as compared to the control group. Post hoc analysis, accounting for low reliability scores in the Visual Analog Scales, showed a significant reduction of the overall Visual Analog Scale mean score in the treatment group even at the post measurement. CONCLUSION: This is the first study on TMNMT that was planned and conducted following the CONSORT statement standards for clinical trials. The current work is one more step towards a final evaluation of TMNMT. Already after three months the effect of training with tailor-made notched music is observable in the most direct rating of tinnitus perception - the tinnitus loudness, while more global measures of tinnitus distress do not show relevant changes. TRIAL REGISTRATION: Current Controlled Trials ISRCTN04840953; Trial registration date: 17.07.2013.

Modulatory Effects of Attention on Lateral Inhibition in the Human Auditory Cortex.

Reduced neural processing of a tone is observed when it is presented after a sound whose spectral range closely frames the frequency of the tone. This observation might be explained by the mechanism of lateral inhibition (LI) due to inhibitory interneurons in the auditory system. So far, several characteristics of bottom up influences on LI have been identified, while the influence of top-down processes such as directed attention on LI has not been investigated. Hence, the study at hand aims at investigating the modulatory effects of focused attention on LI in the human auditory cortex. In the magnetoencephalograph, we present two types of masking sounds (white noise vs. withe noise passing through a notch filter centered at a specific frequency), followed by a test tone with a frequency corresponding to the center-frequency of the notch filter. Simultaneously, subjects were presented with visual input on a screen. To modulate the focus of attention, subjects were instructed to concentrate either on the auditory input or the visual stimuli. More specific, on one half of the trials, subjects were instructed to detect small deviations in loudness in the masking sounds while on the other half of the trials subjects were asked to detect target stimuli on the screen. The results revealed a reduction in neural activation due to LI, which was larger during auditory compared to visual focused attention. Attentional modulations of LI were observed in two post-N1m time intervals. These findings underline the robustness of reduced neural activation due to LI in the auditory cortex and point towards the important role of attention on the modulation of this mechanism in more evaluative processing stages.

The Relevance of Interoception in Chronic Tinnitus: Analyzing Interoceptive Sensibility and Accuracy.

In order to better understand tinnitus and distress associated with tinnitus, psychological variables such as emotional and cognitive processing are a central element in theoretical models of this debilitating condition. Interoception, that is, the perception of internal processes, may be such a psychological factor relevant to tinnitus. Against this background, 20 participants suffering from chronic tinnitus and 20 matched healthy controls were tested with questionnaires, assessing interoceptive sensibility, and participated in two tasks, assessing interoceptive accuracy: the Schandry task, a heartbeat estimation assignment, and a skin conductance fluctuations perception task assessing the participants' ability to perceive phasic increases in sympathetic activation were used. To test stress reactivity, a construct tightly connected to tinnitus onset, we also included a stress induction. No differences between the groups were found for interoceptive accuracy and sensibility. However, the tinnitus group tended to overestimate the occurrence of phasic activation. Loudness of the tinnitus was associated with reduced interoceptive performance under stress. Our results indicate that interoceptive sensibility and accuracy do not play a significant role in tinnitus. However, tinnitus might be associated with a tendency to overestimate physical changes.

Impact of Spectral Notch Width on Neurophysiological Plasticity and Clinical Effectiveness of the Tailor-Made Notched Music Training.

Tinnitus, the ringing in the ears that is unrelated to any external source, causes a significant loss in quality of life, involving sleep disturbance and depression for 1 to 3% of the general population. While in the first place tinnitus may be triggered by damage to the inner ear cells, the neural generators of subjective tinnitus are located in central regions of the nervous system. A loss of lateral inhibition, tonotopical reorganization and a gain-increase in response to the sensory deprivation result in hypersensitivity and hyperactivity in certain regions of the auditory cortex. In the tailor-made notched music training (TMNMT) patients listen to music from which the frequency spectrum of the tinnitus has been removed. This evokes strong lateral inhibition from neurons tuned to adjacent frequencies onto the neurons involved in the tinnitus percept. A reduction of tinnitus loudness and tinnitus-related neural activity was achieved with TMNMT in previous studies. As the effect of lateral inhibition depends on the bandwidth of the notch, in the current study we altered the notch width to find the most effective notch width for TMNMT. We compared 1-octave notch width with ½-octave and »-octave. Participants chose their favorite music for the training that included three month of two hours daily listening. The outcome was measured by means of standardized questionnaires and magnetoencephalography. We found a general reduction of tinnitus distress in all administered tinnitus questionnaires after the training. Additionally, tinnitus-related neural activity was reduced after the training. Nevertheless, notch width did not have an influence on the behavioral or neural effects of TMNMT. This could be due to a non-linear resolution of lateral inhibition in high frequencies.