Using Auditory Steady State Responses to Outline the Functional Connectivity in the Tinnitus Brain

BACKGROUND: Tinnitus is an auditory phantom perception that is most likely generated in the central nervous system. Most of the tinnitus research has concentrated on the auditory system. However, it was suggested recently that also non-auditory structures are involved in a global network that encodes subjective tinnitus. We tested this assumption using auditory steady state responses to entrain the tinnitus network and investigated long-range functional connectivity across various non-auditory brain regions. METHODS AND FINDINGS: Using whole-head magnetoencephalography we investigated cortical connectivity by means of phase synchronization in tinnitus subjects and healthy controls. We found evidence for a deviating pattern of long-range functional connectivity in tinnitus that was strongly correlated with individual ratings of the tinnitus percept. Phase couplings between the anterior cingulum and the right frontal lobe and phase couplings between the anterior cingulum and the right parietal lobe showed significant condition x group interactions and were correlated with the individual tinnitus distress ratings only in the tinnitus condition and not in the control conditions. CONCLUSIONS: To the best of our knowledge this is the first study that demonstrates existence of a global tinnitus network of long-range cortical connections outside the central auditory system. This result extends the current knowledge of how tinnitus is generated in the brain. We propose that this global extend of the tinnitus network is crucial for the continuos perception of the tinnitus tone and a therapeutical intervention that is able to change this network should result in relief of tinnitus

Central Crosstalk for Somatic Tinnitus: Abnormal Vergence Eye Movements

Frequent oulomotricity problems with orthoptic testing were reported in patients with tinnitus. This study examines with objective recordings vergence eye movements in patients with somatic tinnitus patients with ability to modify their subjective tinnitus percept by various movements, such as jaw, neck, eye movements or skin pressure.Vergence eye movements were recorded with the Eyelink II video system in 15 (23–63 years) control adults and 19 (36–62 years) subjects with somatic tinnitus.1) Accuracy of divergence but not of convergence was lower in subjects with somatic tinnitus than in control subjects. 2) Vergence duration was longer and peak velocity was lower in subjects with somatic tinnitus than in control subjects. 3) The number of embedded saccades and the amplitude of saccades coinciding with the peak velocity of vergence were higher for tinnitus subjects. Yet, saccades did not increase peak velocity of vergence for tinnitus subjects, but they did so for controls. 4) In contrast, there was no significant difference of vergence latency between these two groups.The results suggest dysfunction of vergence areas involving cortical-brainstem-cerebellar circuits. We hypothesize that central auditory dysfunction related to tinnitus percept could trigger mild cerebellar-brainstem dysfunction or that tinnitus and vergence dysfunction could both be manifestations of mild cortical-brainstem-cerebellar syndrome reflecting abnormal cross-modality interactions between vergence eye movements and auditory signals

Enhancing Inhibition-Induced Plasticity in Tinnitus – Spectral Energy Contrasts in Tailor-Made Notched Music Matter

Chronic tinnitus seems to be caused by reduced inhibition among frequency selective neurons in the auditory cortex. One possibility to reduce tinnitus perception is to induce inhibition onto over-activated neurons representing the tinnitus frequency via tailor-made notched music (TMNM). Since lateral inhibition is modifiable by spectral energy contrasts, the question arises if the effects of inhibition-induced plasticity can be enhanced by introducing increased spectral energy contrasts (ISEC) in TMNM. Eighteen participants suffering from chronic tonal tinnitus, pseudo randomly assigned to either a classical TMNM or an ISEC-TMNM group, listened to notched music for three hours on three consecutive days. The music was filtered for both groups by introducing a notch filter centered at the individual tinnitus frequency. For the ISEC-TMNM group a frequency bandwidth of 3/8 octaves on each side of the notch was amplified, additionally, by about 20 dB. Before and after each music exposure, participants rated their subjectively perceived tinnitus loudness on a visual analog scale. During the magnetoencephalographic recordings, participants were stimulated with either a reference tone of 500 Hz or a test tone with a carrier frequency representing the individual tinnitus pitch. Perceived tinnitus loudness was significantly reduced after TMNM exposure, though TMNM type did not influence the loudness ratings. Tinnitus related neural activity in the N1m time window and in the so called tinnitus network comprising temporal, parietal and frontal regions was reduced after TMNM exposure. The ISEC-TMNM group revealed even enhanced inhibition-induced plasticity in a temporal and a frontal cortical area. Overall, inhibition of tinnitus related neural activity could be strengthened in people affected with tinnitus by increasing spectral energy contrast in TMNM, confirming the concepts of inhibition-induced plasticity via TMNM and spectral energy contrasts

Insights Into Auditory Cortex Dynamics From Non-invasive Brain Stimulation

Non-invasive brain stimulation (NIBS) has been widely used as a research tool to modulate cortical excitability of motor as well as non-motor areas, including auditory or language-related areas. NIBS, especially transcranial magnetic stimulation (TMS) and transcranial direct current stimulation, have also been used in clinical settings, with however variable therapeutic outcome, highlighting the need to better understand the mechanisms underlying NIBS techniques. TMS was initially used to address causality between specific brain areas and related behavior, such as language production, providing non-invasive alternatives to lesion studies. Recent literature however suggests that the relationship is not as straightforward as originally thought, and that TMS can show both linear and non-linear modulation of brain responses, highlighting complex network dynamics. In particular, in the last decade, NIBS studies have enabled further advances in our understanding of auditory processing and its underlying functional organization. For instance, NIBS studies showed that even when only one auditory cortex is stimulated unilaterally, bilateral modulation may result, thereby highlighting the influence of functional connectivity between auditory cortices. Additional neuromodulation techniques such as transcranial alternating current stimulation or transcranial random noise stimulation have been used to target frequency-specific neural oscillations of the auditory cortex, thereby providing further insight into modulation of auditory functions. All these NIBS techniques offer different perspectives into the function and organization of auditory cortex. However, further research should be carried out to assess the mode of action and long-term effects of NIBS to optimize their use in clinical settings

The thalamus and tinnitus:Bridging the gap between animal data and findings in humans

The neuronal mechanisms underlying tinnitus are yet to be revealed. Tinnitus, an auditory phantom sensation, used to be approached as a purely auditory domain symptom. More recently, the modulatory impact of non-auditory brain regions on the percept and burden of tinnitus are explored. The thalamus is uniquely situated to facilitate the communication between auditory and non-auditory subcortical and cortical structures. Traditionally, animal models of tinnitus have focussed on subcortical auditory structures, and research with human participants has been concerned with cortical activity in auditory and non-auditory areas. Recently, both research fields have investigated the connectivity between subcortical and cortical regions and between auditory and non-auditory areas. We show that even though the different fields employ different methods to investigate the activity and connectivity of brain areas, there is consistency in the results on tinnitus between these different approaches. This consistency between human and animals research is observed for tinnitus with peripherally instigated hearing damage, and for results obtained with salicylate and noise-induced tinnitus. The thalamus integrates input from limbic and prefrontal areas and modulates auditory activity via its connections to both subcortical and cortical auditory areas. Reported altered activity and connectivity of the auditory, prefrontal, and limbic regions suggest a more systemic approach is necessary to understand the origins and impact of tinnitus. (c) 2021 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/

Physiological regulation of chronic tinnitus: A new methodological approach

Decrease of auditory alpha-rhythm might lead to tinnitus which it calls a rehabilitation strategy using training to increase auditory alpha in chronic tinnitus patients. A novel auditory alpha monitoring method was devised to circumvent the inverse problem of standard EEG source localization methods. To prevent projection of alpha from somatosensory and occipital cortex, alpha-blockade of these two regions using tactile and visual stimulations is integrated in an EEG neurofeedback set-up. The monitoring online source method’s results showed rigorous tracking of auditory alpha activity purely from the sensor-level while the up-regulation of auditory alpha activity was very difficult for tinnitus patients. Therefore, only contingent feedback was applied instead of using a control condition or control group. Although the neurofeedback training exerted a positive effect on the tinnitus symptoms, this effect was not a consequence of neurophysiological changes, but it was probably the effect of positive expectancy and the reduction of cognitive dissonance related to the attribution of concentration and effort. Different reasons could be responsible for this lack of covariation between neurophysiology and behavior like short training time for up-regulation of alpha activity or permanent neuronal reorganization. However, the developed on-line neurofeedback of localized alpha allows systematic replication and variation of the determining variables of neurofeedback training in tinnitus in future larger clinical trials