Positron emission tomography of cortical centers of tinnitus

Human Brain Mapping, 2013

Cerebral 18 F-deoxyglucose positron emission tomography (FDG-PET) has shown altered auditory pathway activity in tinnitus. However, the corresponding studies involved only small samples and analyses were restricted to the auditory cortex in most studies. Evidence is growing that also limbic, frontal, and parietal areas are involved in the pathophysiology of chronic tinnitus. These regions are considered to mediate perceptual, attentional, and emotional processes. Thus, the aim of the present study was the systematic evaluation of metabolic brain activity in a large sample of tinnitus patients. Ninety one patients with chronic tinnitus underwent FDG-PET. The effects of tinnitus severity (assessed by a tinnitus questionnaire score), duration and laterality were evaluated with statistical parametric mapping (SPM) in whole brain analyses. In addition, region of interest analyses were performed for primary auditory areas. Tinnitus duration correlated positively with brain metabolism in right inferior frontal, right ventro-medial prefrontal, and right posterior cingulate cortex. Tinnitus distress correlated positively with activation of left and right posterior inferior temporal gyrus as well as left and right posterior parahippocampal-hippocampal interface. Region of interest analysis demonstrated an overactivation of left in contrast to right Heschl's gyrus independently from tinnitus laterality and anatomical hemispheric differences. Tinnitus duration and distress were associated with areas involved in attentional and emotional processing. This is in line with recent findings indicating the relevance of higher order areas in the pathophysiology of tinnitus. Earlier results of asymmetric activation of the auditory cortices in tinnitus were confirmed, i.e., left-sided overactivation was found independently from tinnitus laterality. Hum Brain Mapp 00:000-000,

Acta Oto-laryngologica, 2000

Subjective tinnitus is an auditory phantom perception that may arise from any aberrant signal within the auditory system. Further processing of this signal and the conscious perception of tinnitus takes place in the cerebral cortex. A few functional brain-imaging studies have been performed to elucidate the underlying cerebral mechanisms of this perception. These studies mostly concern rare types of tinnitus (e.g. tinnitus changeable by oral-facial movements), or compared tinnitus patients with healthy volunteers. These studies attributed variable activation of the primary auditory cortices, associative auditory cortices and the left hippocampus to the perception of tinnitus. Based on these heterogeneous results, no consensus on the underlying mechanisms has been reached. The aim of the present study was to obtain further details of the central perception and processing of the tinnitus signal. Positron emission tomography (PET) was used to map the tinnitus-specific central activity. By contrasting PET-images of suppressed tinnitus with PET-images of the habitual tinnitus sensation, we were able to identify a right prefrontal-temporal network associated with the perception of tinnitus. Besides the evidence of activation of associative auditory sensory regions, the results indicated that activation of cortical centres subserving attention and emotion may underlie the continuous irritability associated with severe tinnitus.

Introduction Tinnitus is an abnormal perception of sound in the absence of an external stimulus. Chronic tinnitus usually has a high impact in many aspects of patients’ lives, such as emotional stress, sleep disturbance, concentration difficulties, and so on. These strong reactions are usually attributed to central nervous system involvement. Neuroimaging has revealed the implication of brain structures in the auditory system. Objective This systematic review points out neuroimaging studies that contribute to identifying the structures involved in the pathophysiological mechanism of generation and persistence of various forms of tinnitus. Data Synthesis Functional imaging research reveals that tinnitus perception is associated with the involvement of the nonauditory brain areas, including the front parietal area; the limbic system, which consists of the anterior cingulate cortex, anterior insula, and amygdala; and the hippocampal and parahippocampal area. Conclusion The neuroimaging research confirms the involvement of the mechanisms of memory and cognition in the persistence of perception, anxiety, distress, and suffering associated with tinnitus.

Hearing Research, 2009

In this review, we highlight the contribution of advances in human neuroimaging to the current understanding of central mechanisms underpinning tinnitus and explain how interpretations of neuroimaging data have been guided by animal models. The primary motivation for studying the neural substrates of tinnitus in humans has been to demonstrate objectively its representation in the central auditory system and to develop a better understanding of its diverse pathophysiology and of the functional interplay between sensory, cognitive and affective systems. The ultimate goal of neuroimaging is to identify subtypes of tinnitus in order to better inform treatment strategies. The three neural mechanisms considered in this review may provide a basis for TI classification. While human neuroimaging evidence strongly implicates the central auditory system and emotional centres in TI, evidence for the precise contribution from the three mechanisms is unclear because the data are somewhat inconsistent. We consider a number of methodological issues limiting the field of human neuroimaging and recommend approaches to overcome potential inconsistency in results arising from poorly matched participants, lack of appropriate controls and low statistical power.

In this paper, we review studies that have investigated brain morphology in chronic tinnitus in order to better understand the underlying pathophysiology of the disorder. Current consensus is that tinnitus is a disorder involving a distributed network of peripheral and central pathways in the nervous system. However, the precise mechanism remains elusive and it is unclear which structures are involved. Given that brain structure and function are highly related, identification of anatomical differences may shed light upon the mechanism of tinnitus generation and maintenance. We discuss anatomical changes in the auditory cortex, the limbic system, and prefrontal cortex, among others. Specifically, we discuss the gating mechanism of tinnitus and evaluate the evidence in support of the model from studies of brain anatomy. Although individual studies claim significant effects related to tinnitus, outcomes are divergent and even contradictory across studies. Moreover, results are often confounded by the presence of hearing loss. We conclude that, at present, the overall evidence for structural abnormalities specifically related to tinnitus is poor. As this area of research is expanding, we identify some key considerations for research design and propose strategies for future research.

Seminars in Hearing, 2008

Because subjective tinnitus is typically localized to the ear with hearing loss, tinnitus was traditionally thought to originate from neural hyperactivity in the damaged ear. However, most studies have found that hearing loss reduces the neural outputs from the damaged cochlea. These negative findings led to the hypothesis that rinnitus arises from aberrant neural activity in the central auditory system. Positron emission tomography imaging studies performed on tinnitus patients that could modulate their tinnitus provide evidence showing that the aberrant neural activity that gives rise to tinnitus resides in the central auditory pathway. To investigate the biological basis of tinnitus in more detail, an animal model was developed that allowed behavioral measures of tinnitus to be obtained from individual rats after inducing tinnitus with high doses of salicylate or high-intensity noise. This behavioral model was used to test the efficacy of memantine, an N-methyl-D-aspartate antagonist, and scopolamine, an anticholinergic, in suppressing salicylate-induced tinnitus. Neither drug completely suppressed salicylate-induced tinnitus. To detect the physiological changes associated with tinnitus, chronic microwire electrodes were implanted in the auditory cortex and measurements were obtained from the auditory cortex before and after salicylate and noise exposures known to induce tinnitus. High doses of salicylate or high-level noise exposure generally resulted in soundevoked hyperactivity in the electrophysiological responses recorded from the auditory cortex of awake-animals. However, anesthetic tended to suppress or abolish the hyperactivity.

Hearing Research, 2013

Chronic tinnitus affects approximately 5% of the population. Severe distress due to the phantom noise is experienced by 20% of the tinnitus patients. This distress cannot be predicted by psychoacoustic features of the tinnitus. It is commonly assumed that negative cognitive emotional evaluation of the tinnitus and its expected consequences is a major factor that determines the impact of tinnitus-related distress. Models of tinnitus distress and recently conducted research propose differences in limbic, frontal and parietal processing between highly and low distressed tinnitus patients. An experimental paradigm using verbal material to stimulate cognitive emotional processing of tinnitus-related information was conducted. Age and sex matched highly (n ¼ 16) and low (n ¼ 16) distressed tinnitus patients and healthy controls (n ¼ 16) underwent functional magnetic resonance imaging (fMRI) while sentences with neutral, negative or tinnitus-related content were presented. A random effects group analysis was performed on the basis of the general linear model. Tinnitus patients showed stronger activations to tinnitus-related sentences in comparison to neutral sentences than healthy controls in various limbic/ emotion processing areas, such as the anterior cingulate cortex, midcingulate cortex, posterior cingulate cortex, retrosplenial cortex and insula and also in frontal areas. Highly and low distressed tinnitus patients differed in terms of activation of the left middle frontal gyrus. A connectivity analysis and correlational analysis between the predictors of the general linear model of relevant contrasts and tinnitus-related distress further supported the idea of a fronto-parietal-cingulate network, which seems to be more active in highly distressed tinnitus patients. This network may present an aspecific distress network. Based on the findings the left middle frontal gyrus and the right medial frontal gyrus are suggested as target regions for neuromodulatory approaches in the treatment of tinnitus. For future studies we recommend the use of idiosyncratic stimulus material.

NeuroImage, 2009

Tinnitus, the phantom perception of sound, is a frequent disorder that causes significant morbidity. The pathophysiological mechanisms involved in tinnitus generation are still under exploration. Electrophysiological and functional neuroimaging studies give increasing evidence for abnormal functioning both within the central auditory system and in non-auditory brain areas. However, observed changes show great variability, hence lacking a conclusive picture. Recently, structural alterations in the central nervous system have been detected in tinnitus patients by voxel-based morphometry (VBM). Here we aimed to replicate these findings in an independent study sample. We performed structural MRI scans in 28 tinnitus patients with normal audiometry and used VBM to compare results with a control group, matched for age, sex and hearing status. As major results we found significant grey matter decreases in the tinnitus group in the right inferior colliculus and in the left hippocampus. However, neither changes in the subcallosal area nor in the thalamus as described recently have been observed. Our results underscore that (1.) VBM allows to detect structural alterations in tinnitus patients, which seem to be related to tinnitus pathophysiology. (2.) Both, areas in the auditory and the limbic system are involved giving further evidence for the important role of the limbic system in the pathophysiology of tinnitus. (3.) Even groups with similar clinical characteristics might differ in the underlying neurobiological changes.

Neuroradiology, 2012

Journal of Cerebral Blood Flow and Metabolism, 2010

Tinnitus is often defined as the perception of sounds or noise in the absence of any external auditory stimuli. The pathophysiology of subjective idiopathic tinnitus remains unclear. The aim of this study was to investigate the functional brain activities and possible involved cerebral areas in subjective idiopathic tinnitus patients by means of single photon emission computerized tomography (SPECT) coincidence imaging, which was fused with magnetic resonance imaging (MRI). In this cross-sectional study, 56 patients (1 subject excluded) with subjective tinnitus and 8 healthy controls were enrolled. After intravenous injection of 5 mCi F18-FDG (fluorodeoxyglucose), all subjects underwent a brain SPECT coincidence scan, which was then superimposed on their MRIs. In the eight regions of interest (middle temporal, inferotemporal, medial temporal, lateral temporal, temporoparietal, frontal, frontoparietal, and parietal areas), the more pronounced values were represented in medial temporal, inferotemporal, and temporoparietal areas, which showed more important proportion of associative auditory cortices in functional attributions of tinnitus than primary auditory cortex. Brain coincidence SPECT scan, when fused on MRI is a valuable technique in the assessment of patients with tinnitus and could show the significant role of different regions of central nervous system in functional attributions of tinnitus.