Winfried Schlee

Top-down modulation of the auditory Steady State Response in a task-switch paradigm

Auditory selective attention is an important mechanism for top-down selection of the vast amount of auditory information our perceptual system is exposed to. In the present study, the impact of attention on auditory steady-state responses is investigated. This issue is still a matter of debate and recent findings point to a complex pattern of attentional effects on the auditory steady state response (aSSR). The present study aimed at shedding light on the involvement of ipsilateral and contralateral activations to the attended sound taking into account hemispheric differences and a possible dependency on modulation frequency. In aid of this, a dichotic listening experiment was designed using amplitude-modulated tones that were presented to the left and right ear simultaneously. Participants had to detect target tones in a cued ear while their brain activity was assessed using MEG. Thereby, a modulation of the aSSR by attention could be revealed, interestingly restricted to the left hemisphere and 20 Hz responses: contralateral activations were enhanced while ipsilateral activations turned out to be reduced. Thus, our findings support and extend recent findings, showing that auditory attention can influence the aSSR, but only under specific circumstances and in a complex pattern regarding the different effects for ipsilateral and contralateral activations.

High-frequency tinnitus without hearing loss does not mean absence of deafferentation

A broad consensus within the neuroscience of tinnitus holds that this audiologic condition is triggered by central deafferentation, mostly due to cochlear damage. The absence of audiometrically detectable hearing loss however poses a challenge to this rather generalizing assumption. The aim of this study was therefore to scrutinize cochlear functioning in a sample of tinnitus subjects audiometrically matched to a normal hearing control group. Two tests were applied: the Threshold Equalizing Noise (TEN) test and a pitch scaling task. To perform well on both tasks relatively normal functioning of inner hair cells is a requirement. In the TEN test the tinnitus group revealed a circumscribed increment of thresholds partially overlapping with the tinnitus spectrum. Abnormal slopes were observed in the pitch scaling task which indicated that tinnitus subjects, when presented with a high-frequency stimulus, relied heavily on input derived from lower-frequency inner hair cells (off-frequency listening). In total both results argue for the presence of a deafferentation also in tinnitus subjects with audiometrically normal thresholds and therefore favour the deafferentation assumption posed by most neuroscientific theories.

Abnormal resting-state cortical coupling in chronic tinnitus

BackgroundSubjective tinnitus is characterized by an auditory phantom perception in the absence of any physical sound source. Consequently, in a quiet environment, tinnitus patients differ from control participants because they constantly perceive a sound whereas controls do not. We hypothesized that this difference is expressed by differential activation of distributed cortical networks.ResultsThe analysis was based on a sample of 41 participants: 21 patients with chronic tinnitus and 20 healthy control participants. To investigate the architecture of these networks, we used phase locking analysis in the 1–90 Hz frequency range of a minute of resting-state MEG recording. We found: 1) For tinnitus patients: A significant decrease of inter-areal coupling in the alpha (9–12 Hz) band and an increase of inter-areal coupling in the 48–54 Hz gamma frequency range relative to the control group. 2) For both groups: an inverse relationship (r = -.71) of the alpha and gamma network coupling. 3) A discrimination of 83% between the patient and the control group based on the alpha and gamma networks. 4) An effect of manifestation on the distribution of the gamma network: In patients with a tinnitus history of less than 4 years, the left temporal cortex was predominant in the gamma network whereas in patients with tinnitus duration of more than 4 years, the gamma network was more widely distributed including more frontal and parietal regions.ConclusionIn the here presented data set we found strong support for an alteration of long-range coupling in tinnitus. Long-range coupling in the alpha frequency band was decreased for tinnitus patients while long-range gamma coupling was increased. These changes discriminate well between tinnitus and control participants. We propose a tinnitus model that integrates this finding in the current knowledge about tinnitus. Furthermore we discuss the impact of this finding to tinnitus therapies using Transcranial Magnetic Stimulation (TMS).

Mapping cortical hubs in tinnitus

BackgroundSubjective tinnitus is the perception of a sound in the absence of any physical source. It has been shown that tinnitus is associated with hyperactivity of the auditory cortices. Accompanying this hyperactivity, changes in non-auditory brain structures have also been reported. However, there have been no studies on the long-range information flow between these regions.ResultsUsing Magnetoencephalography, we investigated the long-range cortical networks of chronic tinnitus sufferers (n = 23) and healthy controls (n = 24) in the resting state. A beamforming technique was applied to reconstruct the brain activity at source level and the directed functional coupling between all voxels was analyzed by means of Partial Directed Coherence. Within a cortical network, hubs are brain structures that either influence a great number of other brain regions or that are influenced by a great number of other brain regions. By mapping the cortical hubs in tinnitus and controls we report fundamental group differences in the global networks, mainly in the gamma frequency range. The prefrontal cortex, the orbitofrontal cortex and the parieto-occipital region were core structures in this network. The information flow from the global network to the temporal cortex correlated positively with the strength of tinnitus distress.ConclusionWith the present study we suggest that the hyperactivity of the temporal cortices in tinnitus is integrated in a global network of long-range cortical connectivity. Top-down influence from the global network on the temporal areas relates to the subjective strength of the tinnitus distress.

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.

Controversy: Does repetitive transcranial magnetic stimulation/ transcranial direct current stimulation show efficacy in treating tinnitus patients?

BACKGROUNDnTinnitus affects 10% of the population, its pathophysiology remains incompletely understood, and treatment is elusive. Functional imaging has demonstrated a relationship between the intensity of tinnitus and the degree of reorganization in the auditory cortex. Experimental studies have further shown that tinnitus is associated with synchronized hyperactivity in the auditory cortex. Therefore, targeted modulation of auditory cortex has been proposed as a new therapeutic approach for chronic tinnitus.nnnMETHODSnRepetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are noninvasive methods that can modulate cortical activity. These techniques have been applied in different ways in patients with chronic tinnitus. Single sessions of high-frequency rTMS over the temporal cortex have been successful in reducing the intensity of tinnitus during the time of stimulation and could be predictive for treatment outcome of chronic epidural stimulation using implanted electrodes.nnnRESULTSnAnother approach that uses rTMS as a treatment for tinnitus is application of low-frequency rTMS in repeated sessions, to induce a lasting change of neuronal activity in the auditory cortex beyond the duration of stimulation. Beneficial effects of this treatment have been consistently demonstrated in several small controlled studies. However, results are characterized by high interindividual variability and only a moderate decrease of the tinnitus. The role of patient-related (for example, hearing loss, tinnitus duration, age) and stimulation-related (for example, stimulation site, stimulation protocols) factors still remains to be elucidated.nnnCONCLUSIONSnEven in this early stage of investigation, there is a convincing body of evidence that rTMS represents a promising tool for pathophysiological assessment and therapeutic management of tinnitus. Further development of this technique will depend on a more detailed understanding of the neurobiological effects mediating the benefit of TMS on tinnitus perception. Moreover clinical studies with larger sample sizes and longer follow-up periods are needed.

Neurofeedback for treating tinnitus.

Many individuals with tinnitus have abnormal oscillatory brain activity. Led by this finding, we have developed a way to normalize such pathological activity by neurofeedback techniques (Weisz et al. (2005). PLoS Med., 2: e153). This is achieved mainly through enhancement of tau activity, i.e., oscillatory activity produced in perisylvian regions within the alpha frequency range (8-12 Hz) and concomitant reduction in delta power range (0.5-4 Hz). This activity is recorded from electrodes placed on the frontal scalp. We have found that modification of the tau-to-delta ratio significantly reduces tinnitus intensity. Participants who successfully modified their oscillatory pattern profited from the treatment to the extent that the tinnitus sensation became completely abolished. Overall, this neurofeedback training was significantly superiorin reducing tinnitus-related distress than frequency discrimination training.

Rapid increases of gamma power in the auditory cortex following noise trauma in humans

Tinnitus is an auditory perception in the absence of any external sound source. It has been suggested that tinnitus is related to enhanced synchronization of neuronal activity in the auditory cortex. Usually a hearing damage can be identified suggesting auditory deprivation to central auditory regions to be fundamental for neurophysiological processes related to tinnitus. Until now, human research has been conducted on patients with chronic tinnitus (>u20036u2003months). However, neuronal activity accompanying auditory deprivation and putatively tinnitus may not remain constant over time, making it difficult to directly relate outcomes of current animal studies (acute tinnitus) to chronic tinnitus in humans, and vice versa. We investigated 14 amateur rock musicians who frequently reported a short‐term tinnitus immediately after band practice. Magnetoencephalographic resting‐state recordings, audiometry and tinnitus testing were performed at two separate occasions: with and without previous exposure to loud music. Analyses revealed that transient tinnitus was accompanied by temporary hearing loss in both ears and increased gamma activity in the right auditory cortex in 13 out of 14 cases. Additionally, tinnitus frequency was strongly correlated to hearing loss. Analogous to animal studies, our results show for the first time in humans that noise trauma leads rapidly to increased neuronal synchrony in the auditory cortex. Importantly, the strongly right‐lateralized effect implies that it does not reflect tinnitus percept per se. This could rather have been triggered by greater discontinuities of hearing loss at high frequencies that were particularly pronounced in the left ear.

Loss of alpha power is related to increased gamma synchronization—A marker of reduced inhibition in tinnitus?

Tinnitus is the perception of sound in the absence of any external auditory stimulus. Based on previous research we have proposed a framework which postulates that the reduction of ongoing inhibitory alpha activity in tinnitus subjects favors a synchronization of neurons in the gamma frequency range while in a resting state. In the present work we are validating the existence of an inverse relationship between auditory gamma and alpha activity in tinnitus and control subjects using Magnetoencephalography. Tinnitus subjects exhibited a significantly steeper slope of the regression line compared to controls, presumably because a greater number of subjects concurrently exhibited low alpha and high gamma power. Therefore, the role of the alpha-gamma pattern is discussed regarding its possible implication for the generation of tinnitus.

A Global Brain Model of Tinnitus

1. n nSubjective tinnitus is characterized by the perception of a phantom sound in the absence of any physical source. n n n n n2. n nWhile transient tinnitus usually lasts only a couple of seconds to a few hours, chronic tinnitus is an ongoing conscious perception of sound for more than 6 months with low incidence of spontaneous remissions. n n n n n3. n nEmpirical studies in animals and humans often show enhancement of cortical excitability in the auditory areas associated with the tinnitus. n n n n n4. n nTheoretical and experimental studies suggest an additional involvement of extra-auditory cortical regions, especially the frontal cortex, the parietal cortex, and the cingulum. n n n n n5. n nUsing magnetoencephalograpic recordings, we found that these areas are functionally connected with each other and form a global fronto–parietal–cingulate network. n n n n n6. n nThe top–down influence of this global network on auditory areas is associated with the distress that is perceived by many individuals with tinnitus. n n n n n7. n nWe suggest that both entities – the enhanced excitability of the central auditory system and the integration with a global cortical network – are important to generate and maintain a conscious percept of tinnitus. n n n n n8. n nThis chapter will concentrate on how a conscious perception of tinnitus is formed and maintained throughout a lifetime.