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.

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.

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.

Musical expertise is related to altered functional connectivity during audiovisual integration.

The present study investigated the cortical large-scale functional network underpinning audiovisual integration via magnetoencephalographic recordings. The reorganization of this network related to long-term musical training was investigated by comparing musicians to nonmusicians. Connectivity was calculated on the basis of the estimated mutual information of the sources' activity, and the corresponding networks were statistically compared. Nonmusicians' results indicated that the cortical network associated with audiovisual integration supports visuospatial processing and attentional shifting, whereas a sparser network, related to spatial awareness supports the identification of audiovisual incongruences. In contrast, musicians' results showed enhanced connectivity in regions related to the identification of auditory pattern violations. Hence, nonmusicians rely on the processing of visual clues for the integration of audiovisual information, whereas musicians rely mostly on the corresponding auditory information. The large-scale cortical network underpinning multisensory integration is reorganized due to expertise in a cognitive domain that largely involves audiovisual integration, indicating long-term training-related neuroplasticity.

Dissociation of Neural Networks for Predisposition and for Training-Related Plasticity in Auditory-Motor Learning.

Skill learning results in changes to brain function, but at the same time individuals strongly differ in their abilities to learn specific skills. Using a 6-week piano-training protocol and pre- and post-fMRI of melody perception and imagery in adults, we dissociate learning-related patterns of neural activity from pre-training activity that predicts learning rates. Fronto-parietal and cerebellar areas related to storage of newly learned auditory-motor associations increased their response following training; in contrast, pre-training activity in areas related to stimulus encoding and motor control, including right auditory cortex, hippocampus, and caudate nuclei, was predictive of subsequent learning rate. We discuss the implications of these results for models of perceptual and of motor learning. These findings highlight the importance of considering individual predisposition in plasticity research and applications.

Differential processing of melodic, rhythmic and simple tone deviations in musicians--an MEG study.

Rhythm and melody are two basic characteristics of music. Performing musicians have to pay attention to both, and avoid errors in either aspect of their performance. To investigate the neural processes involved in detecting melodic and rhythmic errors from auditory input we tested musicians on both kinds of deviations in a mismatch negativity (MMN) design. We found that MMN responses to a rhythmic deviation occurred at shorter latencies than MMN responses to a melodic deviation. Beamformer source analysis showed that the melodic deviation activated superior temporal, inferior frontal and superior frontal areas whereas the activation pattern of the rhythmic deviation focused more strongly on inferior and superior parietal areas, in addition to superior temporal cortex. Activation in the supplementary motor area occurred for both types of deviations. We also recorded responses to similar pitch and tempo deviations in a simple, non-musical repetitive tone pattern. In this case, there was no latency difference between the MMNs and cortical activation was smaller and mostly limited to auditory cortex. The results suggest that prediction and error detection of musical stimuli in trained musicians involve a broad cortical network and that rhythmic and melodic errors are processed in partially different cortical streams.

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.

Pharyngeal electrical stimulation can modulate swallowing in cortical processing and behavior - magnetoencephalographic evidence.

BACKGROUND: The act of swallowing is a complex neuromuscular function that is processed in a distributed network involving cortical, subcortical and brainstem structures. Difficulty in swallowing arises from a variety of neurologic diseases for which therapeutic options are currently limited. Pharyngeal electrical stimulation (PES) is a novel intervention designed to promote plastic changes in the pharyngeal motor cortex to aid dysphagia rehabilitation. In the present study we evaluate the effect of PES on cortical swallowing network activity and associated changes in swallowing performance. METHODS: In a randomized, crossover study design 10min of real (0.2-ms pulses, 5Hz, 280V, stimulation intensity at 75% of maximum tolerated threshold) or sham PES were delivered to 14 healthy volunteers in two separate sessions. Stimulation was delivered via a pair of bipolar ring electrodes mounted on an intraluminal catheter positioned in the pharynx. Before and after each intervention swallowing capacity (ml/s) was tested using a 150ml-water swallowing stress test. Event-related desynchronization (ERD) of cortical oscillatory activity during volitional swallowing was recorded applying whole-head magnetoencephalography before, immediately after and 45min past the intervention. RESULTS: A prominent reduction of ERD in sensorimotor brain areas occurred in the alpha and beta frequency ranges immediately after real PES but not after sham stimulation (p<0.05) and had faded after 45min. Volume per swallow and swallowing capacity significantly increased following real stimulation only. CONCLUSION: Attenuation of ERD following PES reflects stimulation-induced increased swallowing processing efficiency, which is associated with subtle changes in swallowing function in healthy subjects. Our data contribute evidence that swallowing network organization and behavior can effectively be modulated by PES.

Musical expertise is related to neuroplastic changes of multisensory nature within the auditory cortex.

Recent neuroscientific evidence indicates that multisensory integration does not only occur in higher level association areas of the cortex as the hierarchical models of sensory perception assumed, but also in regions traditionally thought of as unisensory, such as the auditory cortex. Nevertheless, it is not known whether expertise-induced neuroplasticity can alter the multisensory processing that occurs in these low-level regions. The present study used magnetoencephalography to investigate whether musical training may induce neuroplastic changes of multisensory processing within the human auditory cortex. Magnetoencephalography data of four different experiments were used to demonstrate the effect of long-term and short-term musical training on the integration of auditory, somatosensory and visual stimuli in the auditory cortex. The cross-sectional design of three of the experiments allowed us to infer that long-term musical training is related to a significantly different way of processing multisensory information within the auditory cortex, whereas the short-term training design of the fourth experiment allowed us to causally infer that multisensory music reading training affects the multimodal processing within the auditory cortex.

Magnetoencephalographic Correlates of Emotional Processing in Major Depression Before and After Pharmacological Treatment.

BACKGROUND: In major depressive disorder (MDD), electrophysiological and imaging studies suggest reduced neural activity in the parietal and dorsolateral prefrontal cortex regions. In the present study, neural correlates of emotional processing in MDD were analyzed for the first time in a pre-/post-treatment design by means of magnetoencephalography (MEG), allowing for detecting temporal dynamics of brain activation. METHODS: Twenty-five medication-free Caucasian in-patients with MDD and 25 matched controls underwent a baseline MEG session with passive viewing of pleasant, unpleasant, and neutral pictures. Fifteen patients were followed-up with a second MEG session after 4 weeks of antidepressant monopharmacotherapy with mirtazapine. The corresponding controls received no intervention between the measurements. The clinical course of depression was assessed using the Hamilton Depression scale. RESULTS: Prior to treatment, an overall neocortical hypoactivation during emotional processing, particularly at the parietal regions and areas at the right temporoparietal junction, as well as abnormal valence-specific reactions at the right parietal and bilateral dorsolateral prefrontal cortex (dlPFC) regions were observed in patients compared to controls. These effects occurred <150 ms, suggesting dysfunctional processing of emotional stimuli at a preconscious level. Successful antidepressant treatment resulted in a normalization of the hypoactivation at the right parietal and right temporoparietal regions. Accordingly, both dlPFC regions revealed an increase of activity after therapy. CONCLUSIONS: The present study provides neurophysiological evidence for dysfunctional emotional processing in a fronto-parieto-temporal network, possibly contributing to the pathogenesis of MDD. These activation patterns might have the potential to serve as biomarkers of treatment success.

Multisensory integration during short-term music reading training enhances both uni- and multisensory cortical processing.

The human ability to integrate the input of several sensory systems is essential for building a meaningful interpretation out of the complexity of the environment. Training studies have shown that the involvement of multiple senses during training enhances neuroplasticity, but it is not clear to what extent integration of the senses during training is required for the observed effects. This study intended to elucidate the differential contributions of uni- and multisensory elements of music reading training in the resulting plasticity of abstract audiovisual incongruency identification. We used magnetoencephalography to measure the pre- and posttraining cortical responses of two randomly assigned groups of participants that followed either an audiovisual music reading training that required multisensory integration (AV-Int group) or a unisensory training that had separate auditory and visual elements (AV-Sep group). Results revealed a network of frontal generators for the abstract audiovisual incongruency response, confirming previous findings, and indicated the central role of anterior prefrontal cortex in this process. Differential neuroplastic effects of the two types of training in frontal and temporal regions point to the crucial role of multisensory integration occurring during training. Moreover, a comparison of the posttraining cortical responses of both groups to a group of musicians that were tested using the same paradigm revealed that long-term music training leads to significantly greater responses than the short-term training of the AV-Int group in anterior prefrontal regions as well as to significantly greater responses than both short-term training protocols in the left superior temporal gyrus (STG).

Mismatch negativity to acoustical illusion of beat: how and where the change detection takes place?

In case of binaural presentation of two tones with slightly different frequencies the structures of brainstem can no longer follow the interaural time differences (ITD) resulting in an illusionary perception of beat corresponding to frequency difference between the two prime tones. Hence, the beat-frequency does not exist in the prime tones presented to either ear. This study used binaural beats to explore the nature of acoustic deviance detection in humans by means of magnetoencephalography (MEG). Recent research suggests that the auditory change detection is a multistage process. To test this, we employed 26 Hz-binaural beats in a classical oddball paradigm. However, the prime tones (250 Hz and 276 Hz) were switched between the ears in the case of the deviant-beat. Consequently, when the deviant is presented, the cochleae and auditory nerves receive a "new afferent", although the standards and the deviants are heard identical (26 Hz-beats). This allowed us to explore the contribution of auditory periphery to change detection process, and furthermore, to evaluate its influence on beats-related auditory steady-state responses (ASSRs). LORETA-source current density estimates of the evoked fields in a typical mismatch negativity time-window (MMN) and the subsequent difference-ASSRs were determined and compared. The results revealed an MMN generated by a complex neural network including the right parietal lobe and the left middle frontal gyrus. Furthermore, difference-ASSR was generated in the paracentral gyrus. Additionally, psychophysical measures showed no perceptual difference between the standard- and deviant-beats when isolated by noise. These results suggest that the auditory periphery has an important contribution to novelty detection already at sub-cortical level. Overall, the present findings support the notion of hierarchically organized acoustic novelty detection system.

Encoding of nested levels of acoustic regularity in hierarchically organized areas of the human auditory cortex.

Our auditory system is able to encode acoustic regularity of growing levels of complexity to model and predict incoming events. Recent evidence suggests that early indices of deviance detection in the time range of the middle-latency responses (MLR) precede the mismatch negativity (MMN), a well-established error response associated with deviance detection. While studies suggest that only the MMN, but not early deviance-related MLR, underlie complex regularity levels, it is not clear whether these two mechanisms interplay during scene analysis by encoding nested levels of acoustic regularity, and whether neuronal sources underlying local and global deviations are hierarchically organized. We registered magnetoencephalographic evoked fields to rapidly presented four-tone local sequences containing a frequency change. Temporally integrated local events, in turn, defined global regularities, which were infrequently violated by a tone repetition. A global magnetic mismatch negativity (MMNm) was obtained at 140-220 ms when breaking the global regularity, but no deviance-related effects were shown in early latencies. Conversely, Nbm (45-55 ms) and Pbm (60-75 ms) deflections of the MLR, and an earlier MMNm response at 120-160 ms, responded to local violations. Distinct neuronal generators in the auditory cortex underlay the processing of local and global regularity violations, suggesting that nested levels of complexity of auditory object representations are represented in separated cortical areas. Our results suggest that the different processing stages and anatomical areas involved in the encoding of auditory representations, and the subsequent detection of its violations, are hierarchically organized in the human auditory cortex.

Tones and numbers: a combined EEG-MEG study on the effects of musical expertise in magnitude comparisons of audiovisual stimuli.

This study investigated the cortical responses underlying magnitude comparisons of multisensory stimuli and examined the effect that musical expertise has in this process. The comparative judgments were based on a newly learned rule binding the auditory and visual stimuli within the context of magnitude comparisons: "the higher the pitch of the tone, the larger the number presented." The cortical responses were measured by simultaneous MEG\EEG recordings and a combined source analysis with individualized realistic head models was performed. Musical expertise effects were investigated by comparing musicians to non-musicians. Congruent audiovisual stimuli, corresponding to the newly learned rule, elicited activity in frontotemporal and occipital areas. In contrast, incongruent stimuli activated temporal and parietal regions. Musicians when compared with nonmusicians showed increased differences between congruent and incongruent stimuli in a prefrontal region, thereby indicating that music expertise may affect multisensory comparative judgments within a generalized representation of analog magnitude.

Study protocol: Münster tinnitus randomized controlled clinical trial-2013 based on tailor-made notched music training (TMNMT).

BACKGROUND: Tinnitus is a result of hyper-activity/hyper-synchrony of auditory neurons coding the tinnitus frequency, which has developed to synchronous mass activity owing the lack of inhibition. We assume that removal of exactly these frequency components from an auditory stimulus will cause the brain to reorganize around tonotopic regions coding the tinnitus frequency. Based on this assumption a novel treatment for tonal tinnitus - tailor-made notched music training (TMNMT) (Proc Natl Acad Sci USA 107:1207-1210, 2010; Ann N Y Acad Sci 1252:253-258, 2012; Frontiers Syst Neurosci 6:50, 2012) has been introduced and will be tested in this clinical trial on a large number of tinnitus patients. METHODS AND DESIGN: A randomized controlled trial (RCT) in parallel group design will be performed in a double-blinded manner. The choice of the intervention we are going to apply is based on two "proof of concept" studies in humans (Proc Natl Acad Sci USA 107:1207-1210, 2010; Ann N Y Acad Sci 1252:253-258, 2012; Frontiers Syst Neurosci 6:50, 2012; PloS One 6(9):e24685, 2011) and on a recent animal study (Front Syst Neurosci 7:21, 2013).The RCT includes 100 participants with chronic, tonal tinnitus who listened to tailor-made notched music (TMNM) for two hours a day for three months. The effect of TMNMT is assessed by the tinnitus handicap questionnaire and visual analogue scales (VAS) measuring perceived tinnitus loudness, distress and handicap. DISCUSSION: This is the first randomized controlled trial applying TMNMT on a larger number of patients with tonal tinnitus. Our data will verify more securely and reliably the effectiveness of this kind of completely non-invasive and low-cost treatment approach on tonal tinnitus. TRIAL REGISTRATION: Current Controlled Trials ISRCTN04840953.

Evidence for adaptive cortical changes in swallowing in Parkinson's disease.

Dysphagia is a relevant symptom in Parkinson's disease, whose pathophysiology is poorly understood. It is mainly attributed to degeneration of brainstem nuclei. However, alterations in the cortical contribution to deglutition control in the course of Parkinson's disease have not been investigated. Here, we sought to determine the patterns of cortical swallowing processing in patients with Parkinson's disease with and without dysphagia. Swallowing function in patients was objectively assessed with fiberoptic endoscopic evaluation. Swallow-related cortical activation was measured using whole-head magnetoencephalography in 10 dysphagic and 10 non-dysphagic patients with Parkinson's disease and a healthy control group during self-paced swallowing. Data were analysed applying synthetic aperture magnetometry, and group analyses were done using a permutation test. Compared with healthy subjects, a strong decrease of cortical swallowing activation was found in all patients. It was most prominent in participants with manifest dysphagia. Non-dysphagic patients with Parkinson's disease showed a pronounced shift of peak activation towards lateral parts of the premotor, motor and inferolateral parietal cortex with reduced activation of the supplementary motor area. This pattern was not found in dysphagic patients with Parkinson's disease. We conclude that in Parkinson's disease, not only brainstem and basal ganglia circuits, but also cortical areas modulate swallowing function in a clinically relevant way. Our results point towards adaptive cerebral changes in swallowing to compensate for deficient motor pathways. Recruitment of better preserved parallel motor loops driven by sensory afferent input seems to maintain swallowing function until progressing neurodegeneration exceeds beyond the means of this adaptive strategy, resulting in manifestation of dysphagia.

Playing and listening to tailor-made notched music: cortical plasticity induced by unimodal and multimodal training in tinnitus patients.

BACKGROUND. The generation and maintenance of tinnitus are assumed to be based on maladaptive functional cortical reorganization. Listening to modified music, which contains no energy in the range of the individual tinnitus frequency, can inhibit the corresponding neuronal activity in the auditory cortex. Music making has been shown to be a powerful stimulator for brain plasticity, inducing changes in multiple sensory systems. Using magnetoencephalographic (MEG) and behavioral measurements we evaluated the cortical plasticity effects of two months of (a) active listening to (unisensory) versus (b) learning to play (multisensory) tailor-made notched music in nonmusician tinnitus patients. Taking into account the fact that uni- and multisensory trainings induce different patterns of cortical plasticity we hypothesized that these two protocols will have different affects. RESULTS. Only the active listening (unisensory) group showed significant reduction of tinnitus related activity of the middle temporal cortex and an increase in the activity of a tinnitus-coping related posterior parietal area. CONCLUSIONS. These findings indicate that active listening to tailor-made notched music induces greater neuroplastic changes in the maladaptively reorganized cortical network of tinnitus patients while additional integration of other sensory modalities during training reduces these neuroplastic effects.

Musical expertise induces audiovisual integration of abstract congruency rules.

Perception of everyday life events relies mostly on multisensory integration. Hence, studying the neural correlates of the integration of multiple senses constitutes an important tool in understanding perception within an ecologically valid framework. The present study used magnetoencephalography in human subjects to identify the neural correlates of an audiovisual incongruency response, which is not generated due to incongruency of the unisensory physical characteristics of the stimulation but from the violation of an abstract congruency rule. The chosen rule-"the higher the pitch of the tone, the higher the position of the circle"-was comparable to musical reading. In parallel, plasticity effects due to long-term musical training on this response were investigated by comparing musicians to non-musicians. The applied paradigm was based on an appropriate modification of the multifeatured oddball paradigm incorporating, within one run, deviants based on a multisensory audiovisual incongruent condition and two unisensory mismatch conditions: an auditory and a visual one. Results indicated the presence of an audiovisual incongruency response, generated mainly in frontal regions, an auditory mismatch negativity, and a visual mismatch response. Moreover, results revealed that long-term musical training generates plastic changes in frontal, temporal, and occipital areas that affect this multisensory incongruency response as well as the unisensory auditory and visual mismatch responses.

Magnetoencephalographic evidence for the modulation of cortical swallowing processing by transcranial direct current stimulation.

Swallowing is a complex neuromuscular task that is processed within multiple regions of the human brain. Rehabilitative treatment options for dysphagia due to neurological diseases are limited. Because the potential for adaptive cortical changes in compensation of disturbed swallowing is recognized, neuromodulation techniques like transcranial direct current stimulation (tDCS) are currently considered as a treatment option. Here we evaluate the effect of tDCS on cortical swallowing network activity and behavior. In a double-blind crossover study, anodal tDCS (20 min, 1 mA) or sham stimulation was administered over the left or right swallowing motor cortex in 21 healthy subjects in separate sessions. Cortical activation was measured using magnetoencephalography (MEG) before and after tDCS during cued "simple", "fast" and "challenged" swallow tasks with increasing levels of difficulty. Swallowing response times and accuracy were measured. Significant bilateral enhancement of cortical swallowing network activation was found in the theta frequency range after left tDCS in the fast swallow task (p=0.006) and following right tDCS in the challenged swallow task (p=0.007), but not after sham stimulation. No relevant behavioral effects were observed on swallow response time, but swallow precision improved after left tDCS (p<0.05). Anodal tDCS applied over the swallowing motor cortex of either hemisphere was able to increase bilateral swallow-related cortical network activation in a frequency specific manner. These neuroplastic effects were associated with subtle behavioral gains during complex swallow tasks in healthy individuals suggesting that tDCS deserves further evaluation as a treatment tool for dysphagia.

Affect-specific modulation of the N1m to shock-conditioned tones: magnetoencephalographic correlates.

Despite its fundamental relevance for representing the emotional world surrounding us, human affective neuroscience research has widely neglected the auditory system, at least in comparison to the visual domain. Here, we have investigated the spatiotemporal dynamics of human affective auditory processing using time-sensitive whole-head magnetoencephalography. A novel and highly challenging affective associative learning procedure, 'MultiCS conditioning', involving multiple conditioned stimuli (CS) per affective category, was adopted to test whether previous findings from intramodal conditioning of multiple click-tones with an equal number of auditory emotional scenes (Bröckelmann et al., 2011 J. Neurosci., 31, 7801) would generalise to crossmodal conditioning of multiple click-tones with an electric shock as single aversive somatosensory unconditioned stimulus (UCS). Event-related magnetic fields were recorded in response to 40 click-tones before and after four contingent pairings of 20 CS with a shock and the other half remaining unpaired. In line with previous findings from intramodal MultiCS conditioning we found an affect-specific modulation of the auditory N1m component 100-150 ms post-stimulus within a distributed frontal-temporal-parietal neural network. Increased activation for shock-associated tones was lateralised to right-hemispheric regions, whereas unpaired safety-signalling tones were preferentially processed in the left hemisphere. Participants did not show explicit awareness of the contingent CS-UCS relationship, yet behavioural conditioning effects were indicated on an indirect measure of stimulus valence. Our findings imply converging evidence for a rapid and highly differentiating affect-specific modulation of the auditory N1m after intramodal as well crossmodal MultiCS conditioning and a correspondence of the modulating impact of emotional attention on early affective processing in vision and audition.