Vanneste, Sven

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Sven Vanneste is an Associate Professor of Auditory and Integrative Neuroscience. His research interests include:

  • Neuroimaging
  • Neurophysiology
  • Invasive and non-invasive neuromodulation
  • Bayesian predictive model of the brain
  • Thalamocortical dysrhythmias
  • Obsessive compulsive spectrum disorder

Learn more about Dr. Vanneste on his BBS People and Lab for Auditory and Integrative Neuroscience pages.



Recent Submissions

Now showing 1 - 20 of 25
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    Tinnitus and Neuropathic Pain Share a Common Neural Substrate in the Form of Specific Brain Connectivity and Microstate Profiles
    (Pergamon-Elsevier Science Ltd, 2018-08-22) Vanneste, Sven; To, Wing Ting; De Ridder, Dirk; 0000-0002-9906-1836 (Vanneste, S); Vanneste, Sven; To, Wing Ting
    Tinnitus and neuropathic pain share similar pathophysiological, clinical, and treatment characteristics. In this EEG study, a group of tinnitus (n = 100) and neuropathic pain (n = 100) patients are compared to each other and to a healthy control group (n = 100). Spectral analysis demonstrates gamma band activity within the primary auditory and somatosensory cortices in patients with tinnitus and neuropathic pain, respectively. A conjunction analysis further demonstrates an overlap of tinnitus and pain related activity in the anterior and posterior cingulate cortex as well as in the dorsolateral prefrontal cortex in comparison to healthy controls. Further analysis reveals that similar states characterize tinnitus and neuropathic pain patients, two of which differ from the healthy group and two of which are shared. Both pain and tinnitus patients spend half of the time in one specific microstate. Seed-based functional connectivity with the source within the predominant microstate shows delta, alpha1, and gamma lagged phase synchronization overlap with multiple brain areas between pain and tinnitus. These data suggest that auditory and somatosensory phantom perceptions share an overlapping brain network with common activation and connectivity patterns and are differentiated by specific sensory cortex gamma activation.
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    Top-Down and Bottom-Up Regulated Auditory Phantom Perception
    (Soc Neuroscience, 2019-01-09) Vanneste, Sven; Alsalman, Ola; De Ridder, Dirk; 0000-0002-9906-1836 (Vanneste, S); Vanneste, Sven; Alsalman, Ola
    Auditory phantom percepts such as tinnitus are associated with auditory deafferentation. The idea is that auditory deafferentation limits the amount of information the brain can acquire to make sense of the world. Because of this, auditory deafferentation increases the uncertainty of the auditory environment. To minimize uncertainty, the deafferented brain will attempt to obtain or fill in the missing information. A proposed multiphase compensation model suggests two distinct types of bottom-up related tinnitus: an auditory cortex related tinnitus and a parahippocampal cortex related tinnitus. The weakness of this model is that it cannot explain why some people without hearing loss develop tinnitus, whereas conversely others with hearing loss do not develop tinnitus. In this human study, we provide evidence for a top-down type of tinnitus associated with a deficient noise-cancelling mechanism. A total of 72 participants (age: 40.96 ± 7.67 years; males: 48; females: 24) were recruited for this study. We demonstrate that top-down related tinnitus is related to a change in the pregenual anterior cingulate cortex that corresponds to increased activity in the auditory cortex. This is in accordance with the idea that tinnitus can have different generators as proposed in a recent model that suggests that different compensation mechanisms at a cortical level can be linked to phantom percepts.
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    Tinnitus Distress: A Paradoxical Attention to the Sound?
    (Springer-Verlag GmbH and Co., 2019-05-31) Kandeepan, S.; Maudoux, A.; Ribeiro de Paula, D.; Zheng, J. Y.; Cabay, J. E.; Gómez, F.; Chronik, B. A.; Ridder, D.; Vanneste, Sven; Soddu, A.; 0000-0002-9906-1836 (Vanneste, S); Vanneste, Sven
    Tinnitus, the perception of sound in the absence of external stimuli, is often a disturbing symptom for which the underlying functional neuroanatomy still remains poorly understood. Most studies have focused solely on functional connectivity changes in the auditory cortex of tinnitus patients. The aim of this study was to investigate whether a correlation exists between tinnitus behavioural scores and functional brain connectivity of five resting-state networks comprising the auditory, the default mode, the external control left and right, and the salience network. For this purpose, a large sample of one hundred and thirty-five subjects underwent resting-state functional magnetic resonance imaging and their behavioural scores were obtained using clinical evaluations. Networks were extracted using independent component analysis, and functional connectivity patterns in the extracted networks were evaluated by a graph theoretical approach. The effects of tinnitus for each network were investigated by correlating the graph strength of all the regions with the tinnitus behavioural scores using stepwise fit regression analysis. Results indicated that alterations of functional interactions between key neural circuits of the brain are not limited to one single network. In particular, tinnitus distress showed a strong correlation with the connectivity pattern within and between the right executive control network and the other four resting-state networks, indicating that tinnitus distress is probably the consequence of a hyperactive attention condition. Among the behavioural scores, the strongest correlation was observed between age and hearing loss, while the tinnitus objective loudness was not correlated with any behavioural scores. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
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    Meta-Analysis of Functional Subdivisions within Human Posteromedial Cortex
    (Springer Heidelberg, 2018-10-26) Huang, Yuefeng; Hullfish, Jeffrey; De Ridder, Dirk; Vanneste, Sven; Huang, Yuefeng; Hullfish, Jeffrey; Vanneste, Sven
    The posteromedial cortex (PMC) comprising posterior cingulate cortex (PCC), retrosplenial cortex (RSC), and the precuneus (PrC) is perhaps best known for its involvement in the default mode network. There is no consensus regarding the specific functions of PMC, however, and its component regions each exhibit distinct, but partially overlapping functional profiles. To date, there has been minimal effort to disentangle the functions of these regions. In the present study, we use Neurosynth ( to conduct an unbiased meta-analysis of the PMC based on fMRI coactivation and semantic information extracted from 11,406 studies. Our analyses revealed six PMC clusters with distinct functional profiles: superior and inferior dorsal PCC, anterior and posterior PrC, ventral PCC, and RSC. We discuss these findings in the context of the existing literature and suggest several fruitful avenues for continued research.
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    Comparison of Neural Activity in Chronic Pain Patients during Tonic and Burst Spinal Cord Stimulation Using Fluorodeoxyglucose Positron Emission Tomography
    (Blackwell Publishing Inc., 2019-04-30) Yearwood, T.; De Ridder, D.; Yoo, Hye Bin; Falowski, S.; Venkatesan, L.; Ting To, W.; Vanneste, Sven; 0000-0002-9906-1836 (Vanneste, S); Yoo, Hye Bin; Vanneste, Sven
    Objective: Burst spinal cord stimulation (SCS) is a novel stimulation paradigm that seems to provide better pain relief compared to the classic tonic SCS with minimal paresthesia sensation. Based on source localized electroencephalography and clinical data, it has been proposed that burst stimulation as defined by Dirk De Ridder exerts this greater effect by not only modulating the lateral and the descending pain-inhibitory pathways (similar to tonic SCS) but also modulating the medial pain pathway, which encodes the affective, motivational aspects of pain. Material and Methods: The current study evaluates the supraspinal differences between burst and tonic stimulation with another functional imaging technique, namely fluorodeoxyglucose positron emission tomography (FGD-PET) scanning, in seven patients, who underwent both burst and tonic SCS, to confirm this notion of medial pain pathway modulation. Results: The results of the current FGD-PET study show that burst stimulation, in contrast to tonic stimulation, indeed modulates the dorsal anterior cingulate cortex (i.e., medial pain pathway) more than tonic stimulation. Discussion: Our data suggest an inherent difference in the central neural mechanisms during burst and tonic stimulation, which could potentially alter the patient's perception of pain. ©2019 International Neuromodulation Society
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    The Functional Alterations in Top-Down Attention Streams of Parkinson's Disease Measured by EEG
    (Nature Publishing Group) Bin Yoo, Hye; de la Concha, Edward Omar; De Ridder, D.; Pickut, B. A.; Vanneste, Sven; 0000-0002-9906-1836 (Vanneste, S); Bin Yoo, Hye; de la Concha, Edward Omar; Vanneste, Sven
    Early and moderate Parkinson's disease patients seem to have attention dysfunctions manifested differentially in separate attention streams: Top-down and bottom-up. With a focus on the neurophysiological underpinnings of such differences, this study evaluated source-localized regional activity and functional connectivity of regions in the top-down and bottom-up streams as well as any discordance between the two streams. Resting state electroencephalography was used for 36 Parkinson's disease patients and 36 healthy controls matched for age and gender. Parkinson's disease patients showed disproportionally higher bilateral gamma activity in the bottom-up stream and higher left alpha2 connectivity in the top-down stream when compared to age-matched controls. An additional cross-frequency coupling analysis showed that Parkinson's patients have higher alpha2-gamma coupling in the right posterior parietal cortex, which is part of the top-down stream. Higher coupling in this region was also associated with lower severity of motor symptoms in Parkinson's disease. This study provides evidence that in Parkinson's disease, the activity in gamma frequency band and connectivity in alpha2 frequency band is discordant between top-down and bottom-up attention streams. © 2018 The Author(s).
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    Optimization of Transcranial Direct Current Stimulation of Dorsolateral Prefrontal Cortex for Tinnitus: A Non-Linear Dose-Response Effect
    (Nature Publishing Group) Shekhawat, Giriraj Singh; Vanneste, Sven; Shekhawat, Giriraj Singh; 0000-0002-9906-1836 (Vanneste, S); Vanneste, Sven
    Neuromodulation is defined as the process of augmenting neuroplasticity via invasive or non-invasive methods. Tinnitus is the perception of sound in the absence of its external source. The objective of this study was to optimize the parameters of transcranial direct current stimulation (tDCS) of dorsolateral prefrontal cortex (DLPFC) for tinnitus suppression. The following factors were optimized in the dose-response design (n = 111): current intensity (1.5 mA or 2 mA), stimulation duration (20 min or 30 min), and number of stimulation sessions (2, 4, 6, 8, or 10), with a 3-4 day washout period between each session. Participants underwent a minimum of 2 sessions in 1 week or maximum of 10 sessions in 5 weeks' time. Tinnitus loudness was measured in pre-post design using a 10-point numeric rating scale. There was a significant reduction in tinnitus loudness after tDCS of DLPFC. There was no significant difference between the intensity and duration of stimulation. As the number of sessions increased, there was a higher reduction in the tinnitus loudness; however, this effect plateaued after 6 sessions.
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    Influencing Connectivity and Cross-Frequency Coupling by Real-Time Source Localized Neurofeedback of the Posterior Cingulate Cortex Reduces Tinnitus Related Distress
    (Elsevier Science Inc) Vanneste, Sven; Joos, Kathleen; Ost, Jan; De Ridder, Dirk; 0000-0002-9906-1836 (Vanneste, S); Vanneste, Sven
    Background: In this study we are using source localized neurofeedback to moderate tinnitus related distress by influencing neural activity of the target region as well as the connectivity within the default network. Hypothesis: We hypothesize that up-training alpha and down-training beta and gamma activity in the posterior cingulate cortex has a moderating effect on tinnitus related distress by influencing neural activity of the target region as well as the connectivity within the default network and other functionally connected brain areas. Methods: Fifty-eight patients with chronic tinnitus were included in the study. Twenty-three tinnitus patients received neurofeedback training of the posterior cingulate cortex with the aim of up-training alpha and down-training beta and gamma activity, while 17 patients underwent training of the lingual gyrus as a control situation. A second control group consisted of 18 tinnitus patients on a waiting list for future tinnitus treatment. Results: This study revealed that neurofeedback training of the posterior cingulate cortex results in a significant decrease of tinnitus related distress. No significant effect on neural activity of the target region could be obtained. However, functional and effectivity connectivity changes were demonstrated between remote brain regions or functional networks as well as by altering cross frequency coupling of the posterior cingulate cortex. Conclusion: This suggests that neurofeedback could remove the information, processed in beta and gamma, from the carrier wave, alpha, which transports the high frequency information and influences the salience attributed to the tinnitus sound. Based on the observation that much pathology is the result of an abnormal functional connectivity within and between neural networks various pathologies should be considered eligible candidates for the application of source localized EEG based neurofeedback training.
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    Increased Parietal Circuit-Breaker Activity in Delta Frequency Band and Abnormal Delta/Theta Band Connectivity in Salience Network in Hyperacusis Subjects
    (Public Library of Science) Han, Jae Joon; Jang, Ji Hye; De Ridder, Dirk; Vanneste, Sven; Koo, Ja-Won; Song, Jae-Jin; 0000-0002-9906-1836 (Vanneste, S); Vanneste, Sven
    Recent studies have suggested that hyperacusis, an abnormal hypersensitivity to ordinary environmental sounds, may be characterized by certain resting-state cortical oscillatory patterns, even with no sound stimulus. However, previous studies are limited in that most studied subjects with other comorbidities that may have affected cortical activity. In this regard, to assess ongoing cortical oscillatory activity in idiopathic hyperacusis patients with no comorbidities, we compared differences in resting-state cortical oscillatory patterns between five idiopathic hyperacusis subjects and five normal controls. The hyperacusis group demonstrated significantly higher electrical activity in the right auditory-related cortex for the gamma frequency band and left superior parietal lobule (SPL) for the delta frequency band versus the control group. The hyperacusis group also showed significantly decreased functional connectivity between the left auditory cortex (AC) and left orbitofrontal cortex (OFC), between the left AC and left subgenual anterior cingulate cortex (sgACC) for the gamma band, and between the right insula and bilateral dorsal anterior cingulate cortex (dACC) and between the left AC and left sgACC for the theta band versus the control group. The higher electrical activity in the SPL may indicate a readiness of circuit-breaker activity to shift attention to forthcoming sound stimuli. Also, because of the disrupted salience network, consisting of the dACC and insula, abnormally increased salience to all sound stimuli may emerge, as a consequence of decreased top-down control of the AC by the dACC and dysfunctional emotional weight attached to auditory stimuli by the OFC. Taken together, abnormally enhanced attention and salience to forthcoming sound stimuli may render hyperacusis subjects hyperresponsive to non-noxious auditory stimuli.
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    Thalamocortical Dysrhythmia Detected by Machine Learning
    (Nature Publishing Group) Vanneste, Sven; Song, Jae-Jin; De Ridder, Dirk; Vanneste, Sven
    Thalamocortical dysrhythmia (TCD) is a model proposed to explain divergent neurological disorders. It is characterized by a common oscillatory pattern in which resting-state alpha activity is replaced by cross-frequency coupling of low- and high-frequency oscillations. We undertook a data-driven approach using support vector machine learning for analyzing resting-state electroencephalography oscillatory patterns in patients with Parkinson's disease, neuropathic pain, tinnitus, and depression. We show a spectrally equivalent but spatially distinct form of TCD that depends on the specific disorder. However, we also identify brain areas that are common to the pathology of Parkinson's disease, pain, tinnitus, and depression. This study therefore supports the validity of TCD as an oscillatory mechanism underlying diverse neurological disorders.
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    Changing Brain Networks Through Non-Invasive Neuromodulation
    To, Wing Ting; De Ridder, Dirk; Hart, John, Jr.; Vanneste, Sven; Wang, Zijie; Perananthan, Sahila; Panangala, Samitha D.; Ferraris, John P.; Balkus, Kenneth J.; To, Wing Ting; Hart, John, Jr.; Vanneste, Sven
    Background/Objective: Non-invasive neuromodulation techniques, such as repetitive Transcranial Magnetic Stimulation (rTMS) and transcranial Direct Current Stimulation (tDCS), have increasingly been investigated for their potential as treatments for neurological and psychiatric disorders. Despite widespread dissemination of these techniques, the underlying therapeutic mechanisms and the ideal stimulation site for a given disorder remain unknown. Increasing evidence support the possibility of non-invasive neuromodulation affecting a brain network rather than just the local stimulation target. In this article, we present evidence in a clinical setting to support the idea that non-invasive neuromodulation changes brain networks. Method: This article addresses the idea that non-invasive neuromodulation modulates brain networks, rather than just the local stimulation target, using neuromodulation studies in tinnitus and major depression as examples. We present studies that suppo rt this hypothesis from different perspectives. Main Results/Conclusion: Studies stimulating the same brain region, such as the dorsolateral prefrontal cortex (DLPFC), have shown to be effective for several disorders and studies using different stimulation sites for the same disorder have shown similar results. These findings, as well as results from studies investigating brain network connectivity on both macro and micro levels, suggest that non-invasive neuromodulation affects a brain network rather than just the local stimulation site targeted. We propose that non-invasive neuromodulation should be approached from a network perspective and emphasize the therapeutic potential of this approach through the modulation of targeted brain networks.
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    Pairing Sound with Vagus Nerve Stimulation Modulates Cortical Synchrony and Phase Coherence in Tinnitus: An Exploratory Retrospective Study
    (Nature Publishing Group) Vanneste, Sven; Martin, Jeffrey S.; Rennaker, Robert L.; Kilgard, Michael P.; 0000 0001 2879 2132 (Rennaker, RL); 0000 0001 3852 473X (Kilgard, MP); 0000-0002-9906-1836 (Vanneste, S); Vanneste, Sven; Martin, Jeffrey S.; Rennaker, Robert L.; Kilgard, Michael P.
    Recent research has shown that vagus nerve stimulation (VNS) paired with tones or with rehabilitative training can help patients to achieve reductions in tinnitus perception or to expedite motor rehabilitation after suffering an ischemic stroke. The rationale behind this treatment is that VNS paired with experience can drive neural plasticity in a controlled and therapeutic direction. Since previous studies observed that gamma activity in the auditory cortex is correlated with tinnitus loudness, we assessed resting-state source-localized EEG before and after one to three months of VNS-tone pairing in chronic tinnitus patients. VNS-tone pairing reduced gamma band activity in left auditory cortex. VNStone pairing also reduced the phase coherence between the auditory cortex and areas associated with tinnitus distress, including the cingulate cortex. These results support the hypothesis that VNS-tone pairing can direct therapeutic neural plasticity. Targeted plasticity therapy might also be adapted to treat other conditions characterized by hypersynchronous neural activity.
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    The Neural Correlates of the Unified Percept of Alcohol-Related Craving: A fMRI and EEG Study
    Huang, Yuefeng; Mohan, Anusha; De Ridder, Dirk; Sunaert, Stefan; Vanneste, Sven; Huang, Yuefeng; Mohan, Anusha; Vanneste, Sven
    Alcohol addiction is accompanied by aberrant neural activity. Previously, task-based fMRI and resting-state EEG studies have revealed that craving, a critical component of addiction, is linked to abnormal activity in cortical regions including the dorsal anterior cingulate cortex (dACC), nucleus accumbens (NAcc), posterior cingulate cortex (PCC) and pregenual anterior cingulate cortex (pgACC), etc. In this study, we combine these two imaging techniques to investigate a group of alcohol-addicted patients and provide convergent evidence for the neural correlates of craving not only in alcohol but substance abuse in general. We observe abnormal BOLD signal levels in the dACC, NAcc, pgACC, PCC, amygdala, and parahippocampus (PHC) in a cue-reactivity fMRI experiment. These findings are consistent with increased beta-band activity in the dACC and pgACC in resting-state EEG. We further observe desynchronization characterized by decreased functional connectivity in cue-based fMRI and hypersynchronization characterized by increased functional connectivity between these regions in the theta frequency band. The results of our study show a consistent pattern of alcohol craving elicited by external cues and internal desires. Given the advantage of superior spatial and temporal resolution, we hypothesize a "central craving network" that integrates the different aspects of alcohol addiction into a unified percept.
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    Bi-Modal Stimulation in the Treatment of Tinnitus: A Study Protocol for an Exploratory Trial to Optimise Stimulation Parameters and Patient Subtyping
    (BMJ Publishing Group) D'Arcy, Shona; Hamilton, Caroline; Hughes, Stephen; Hall, Deborah A.; Vanneste, Sven; Langguth, Berthold; Conlon, Brendan; Vanneste, Sven
    INTRODUCTION: Tinnitus is the perception of sound in the absence of a corresponding external acoustic stimulus. Bimodal neuromodulation is emerging as a promising treatment for this condition. The main objectives of this study are to investigate the relevance of interstimulus timing and the choices of acoustic and tongue stimuli for a proprietary bimodal (auditory and somatosensory) neuromodulation device, as well as to explore whether specific subtypes of patients are differentially responsive to this novel intervention for reducing the symptoms of chronic tinnitus. METHODS AND ANALYSIS: This is a two-site, randomised, triple-blind, exploratory study of a proprietary neuromodulation device with a pre-post and 12-month follow-up design. Three different bimodal stimulation parameter sets will be examined. The study will enrol 342 patients, split 80: 20 between two sites (Dublin, Ireland and Regensburg, Germany), to complete 12 weeks of treatment with the device. Patients will be allocated to one of three arms using a stepwise stratification according to four binary categories: tinnitus tonality, sound level tolerance (using loudness discomfort level of <60 dB SL as an indicator for hyperacusis), hearing thresholds and presence of a noise-induced audiometric profile. The main indicators of relative clinical efficacy for the three different parameter sets are two patient-reported outcomes measures, the Tinnitus Handicap Inventory and the Tinnitus Functional Index, after 12 weeks of intervention. Clinical efficacy will be further explored in a series of patient subtypes, split by the stratification variables and by presence of a somatic tinnitus. Evidence for sustained effects on the psychological and functional impact of tinnitus will be followed up for 12 months. Safety data will be collected and reported. A number of feasibility measures to inform future trial design include: reasons for exclusion, completeness of data collection, attrition rates, patient's adherence to the device usage as per manufacturer's instructions and evaluation of alternative methods for estimating tinnitus impact and tinnitus loudness. ETHICS AND DISSEMINATION: This study protocol is approved by the Tallaght Hospital/St. James's Hospital Joint Research Ethics Committee in Dublin, Ireland, and by the Ethics Committee of the University Clinic Regensburg, Germany. Findings will be disseminated to relevant research, clinical, health service and patient communities through publications in peer-reviewed and popular science journals and presentations at scientific and clinical conferences.
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    A Quantitative Electroencephalography Study on Cochlear Implant-Induced Cortical Changes in Single-Sided Deafness with Tinnitus
    (Frontiers Media SA) Song, Jae-Jin; Kim, Kyungsoo; Sunwoo, Woongsang; Mertens, Griet; Van de Heyning, Paul; De Ridder, Dirk; Vanneste, Sven; Lee, Sang-Youp; Park, Kyung-Joon; Choi, Hongsoo; Choi, Ji-Woong; Vanneste, Sven
    The mechanism of tinnitus suppression after cochlear implantation (CI) in single-sided deafness (SSD) is not fully understood. In this regard, by comparing pre-and post-CI quantitative electroencephalography (qEEG), we explored cortical changes relevant to tinnitus improvement. In SSD patients who underwent CI, qEEG data were collected: (1) before CI, (2) 6 months post-operatively with CI-on, and (3) 30 min after CI-off and source-localized cortical activity/functional connectivity analyses were performed. Compared to the pre-operative baseline, the CI-on condition demonstrated significantly decreased activity in the right auditory-and orbitofrontal cortices (OFC) for the delta frequency band as well as decreased connectivity between the auditory cortex/posterior cingulate cortex for the delta/beta2 bands. Meanwhile, compared to the CI-off condition, the CI-on condition displayed decreased activity in the right auditory cortices/OFC for the delta band, and in bilateral auditory cortices, left inferior frontal cortex/OFC for the gamma band. However, qEEG analyses showed no significant differences between the CI-off and baseline conditions. CI induced overall decreased cortical activity and functional connectivity. However, judging from no differences between the CI-off and baseline conditions, CI-induced cortical activity and functional connectivity changes are not by cortical plastic changes, but by dynamic peripheral reafferentation.
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    The Neural Correlates of Chronic Symptoms of Vertigo Proneness in Humans
    (Public Library of Science) Alsalman, Ola (UT Dallas); Ost, J.; Vanspauwen, R.; Blaivie, C.; De Ridder, D.; Vanneste, Sven (UT Dallas); 0000-0002-9906-1836 (Vanneste, S)
    Vestibular signals are of significant importance for variable functions including gaze stabilization, spatial perception, navigation, cognition, and bodily self-consciousness. The vestibular network governs functions that might be impaired in patients affected with vestibular dysfunction. It is currently unclear how different brain regions/networks process vestibular information and integrate the information into a unified spatial percept related to somatosensory awareness and whether people with recurrent balance complaints have a neural signature as a trait affecting their development of chronic symptoms of vertigo. Pivotal evidence points to a vestibular-related brain network in humans that is widely distributed in nature. By using resting state source localized electroencephalography in non-vertiginous state, electrophysiological changes in activity and functional connectivity of 23 patients with balance complaints where chronic symptoms of vertigo and dizziness are among the most common reported complaints are analyzed and compared to healthy subjects. The analyses showed increased alpha2 activity within the posterior cingulate cortex and the precuneues/cuneus and reduced beta3 and gamma activity within the pregenual and subgenual anterior cingulate cortex for the subjects with balance complaints. These electrophysiological variations were correlated with reported chronic symptoms of vertigo intensity. A region of interest analysis found reduced functional connectivity for gamma activity within the vestibular cortex, precuneus, frontal eye field, intra-parietal sulcus, orbitofrontal cortex, and the dorsal anterior cingulate cortex. In addition, there was a positive correlation between chronic symptoms of vertigo intensity and increased alpha-gamma nesting in the left frontal eye field. When compared to healthy subjects, there is evidence of electrophysiological changes in the brain of patients with balance complaints even outside chronic symptoms of vertigo episodes. This suggests that these patients have a neural signature or trait that makes them prone to developing chronic balance problems.
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    Tinnitus: A Large VBM-EEG Correlational Study
    (Public Library of Science) Vanneste, Sven (UT Dallas); Van de Heyning, Paul (UT Dallas); De Ridder, Dirk
    A surprising fact in voxel-based morphometry (VBM) studies performed in tinnitus is that not one single region is replicated in studies of different centers. The question then rises whether this is related to the low sample size of these studies, the selection of non-representative patient subgroups, or the absence of stratification according to clinical characteristics. Another possibility is that VBM is not a good tool to study functional pathologies such as tinnitus, in contrast to pathologies like Alzheimer's disease where it is known the pathology is related to cell loss. In a large sample of 154 tinnitus patients VBM and QEEG (Quantitative Electroencephalography) was performed and evaluated by a regression analysis. Correlation analyses are performed between VBM and QEEG data. Uncorrected data demonstrated structural differences in grey matter in hippocampal and cerebellar areas related to tinnitus related distress and tinnitus duration. After control for multiple comparisons, only cerebellar VBM changes remain significantly altered. Electrophysiological differences are related to distress, tinnitus intensity, and tinnitus duration in the subgenual anterior cingulate cortex, dorsal anterior cingulate cortex, hippocampus, and parahippocampus, which confirms previous results. The absence of QEEG-VBM correlations suggest functional changes are not reflected by co-occurring structural changes in tinnitus, and the absence of VBM changes (except for the cerebellum) that survive correct statistical analysis in a large study population suggests that VBM might not be very sensitive for studying tinnitus.
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    Thalamocortical Dysrhythmia: A Theoretical Update in Tinnitus
    (Frontiers Research Foundation) De Ridder, Dirk; Vanneste, Sven (UT Dallas); Langguth, Berthold; Llinas, Rodolfo
    Tinnitus is the perception of a sound in the absence of a corresponding external sound source. Pathophysiologically it has been attributed to bottom-up deafferentation and/or top-down noise-cancelling deficit. Both mechanisms are proposed to alter auditory -thalamocortical signal transmission, resulting in thalamocortical dysrhythmia (TCD). In deafferentation, TCD is characterized by a slowing down of resting state alpha to theta activity associated with an increase in surrounding gamma activity, resulting in persisting cross-frequency coupling between theta and gamma activity. Theta burst-firing increases network synchrony and recruitment, a mechanism, which might enable long-range synchrony, which in turn could represent a means for finding the missing thalamocortical information and for gaining access to consciousness. Theta oscillations could function as a carrier wave to integrate the tinnitus-related focal auditory gamma activity in a consciousness enabling network, as envisioned by the global workspace model. This model suggests that focal activity in the brain does not reach consciousness, except if the focal activity becomes functionally coupled to a consciousness enabling network, aka the global workspace. In limited deafferentation, the missing information can be retrieved from the auditory cortical neighborhood, decreasing surround inhibition, resulting in TCD. When the deafferentation is too wide in bandwidth, it is hypothesized that the missing information is retrieved from theta-mediated parahippocampal auditory memory. This suggests that based on the amount of deafferentation TCD might change to parahippocampocortical persisting and thus pathological theta-gamma rhythm. From a Bayesian point of view, in which the brain is conceived as a prediction machine that updates its memory-based predictions through sensory updating, tinnitus is the result of a prediction error between the predicted and sensed auditory input. The decrease in sensory updating is reflected by decreased alpha activity and the prediction error results in theta-gamma and beta-gamma coupling. Thus, TCD can be considered as an adaptive mechanism to retrieve missing auditory input in tinnitus.;
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    Dysfunctional Noise Cancelling of the Rostral Anterior Cingulate Cortex in Tinnitus Patients
    (Public Library of Science) Song, Jae Jin; Vanneste, Sven; De Ridder, Dirk
    Background Peripheral auditory deafferentation and central compensation have been regarded as the main culprits of tinnitus generation. However, patient-to-patient discrepancy in the range of the percentage of daytime in which tinnitus is perceived (tinnitus awareness percentage, 0 - 100%), is not fully explicable only by peripheral deafferentation, considering that the deafferentation is a stable persisting phenomenon but tinnitus is intermittently perceived in most patients. Consequently, the involvement of a dysfunctional noise cancellation mechanism has recently been suggested with regard to the individual differences in reported tinnitus awareness. By correlating the tinnitus awareness percentage with resting-state source-localized electroencephalography findings, we may be able to retrieve the cortical area that is negatively correlated with tinnitus awareness percentage, and then the area may be regarded as the core of the noise cancelling system that is defective in patients with tinnitus. Methods and Findings Using resting-state cortical oscillation, we investigated 80 tinnitus patients by correlating the tinnitus awareness percentage with their source-localized cortical oscillatory activity and functional connectivity. The activity of bilateral rostral anterior cingulate cortices (ACCs), left dorsal-and pregenual ACCs for the delta band, bilateral rostral/pregenual/subgenual ACCs for the theta band, and left rostral/pregenual ACC for the beta 1 band displayed significantly negative correlations with tinnitus awareness percentage. Also, the connectivity between the left primary auditory cortex (A1) and the rostral ACC, as well as between the left A1 and the subgenual ACC for the beta 1 band, were negatively correlated with tinnitus awareness percentage. Conclusions These results may designate the role of the rostral ACC as the core of the descending noise cancellation system, and thus dysfunction of the rostral ACC may result in perception of tinnitus. The present study also opens a possibility of tinnitus modulation by neuromodulatory approaches targeting the rostral ACC.
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    Auditory Cortex tACS and tRNS for Tinnitus: Single Versus Multiple Sessions
    Claes, Laura; Stamberger, Hannah; de Heyning, Paul Van; De Ridder, Dirk; Vanneste, Sven; 0000-0002-9906-1836 (Vanneste, S); Lab for Clinical & Integrative Neuroscience
    Tinnitus is the perception of a sound in the absence of an external acoustic source, which often exerts a significant impact on the quality of life. Currently there is evidence that neuroplastic changes in both neural pathways are involved in the generation and maintaining of tinnitus. Neuromodulation has been suggested to interfere with these neuroplastic alterations. In this study we aimed to compare the effect of two upcoming forms of transcranial electrical neuromodulation: alternating current stimulation (tACS) and random noise stimulation (tRNS), both applied on the auditory cortex. A database with 228 patients with chronic tinnitus who underwent noninvasive neuromodulation was retrospectively analyzed. The results of this study show that a single session of tRNS induces a significant suppressive effect on tinnitus loudness and distress, in contrast to tACS. Multiple sessions of tRNS augment the suppressive effect on tinnitus loudness but have no effect on tinnitus distress. In conclusion this preliminary study shows a possibly beneficial effect of tRNS on tinnitus and can be a motivation for future randomized placebo-controlled clinical studies with auditory tRNS for tinnitus. Auditory alpha-modulated tACS does not seem to be contributing to the treatment of tinnitus.

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