Memory Networks in Tinnitus: A Functional Brain Image Study

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.

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.

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.

Cerebral Cortex, 2005

Tinnitus is a common but poorly understood disorder characterized by ringing or buzzing in the ear. Central mechanisms must play a crucial role in generating this auditory phantom sensation as it persists in most cases after severing the auditory nerve. One hypothesis states that tinnitus is caused by a reorganization of tonotopic maps in the auditory cortex, which leads to an overrepresentation of tinnitus frequencies. Moreover, the participation of the limbic system in generating tinnitus has been postulated.

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.

2018

Background and Aim: Tinnitus, the phantom perception of sound, in which many cortical and subcortical areas are involved has become one of the popular subjects of neuroscience research. Neuroimaging studies have introduced the tinnitus network model to explain the involvement of auditory and non-auditory areas in this perception. In such a model, the cognitive and emotional aspects of tinnitus can be interpreted conveniently. Therefore, this paper aimed to review the neural basis of tinnitus networks, including data from neuroimaging studies, and discuss the clinical implication of this concept, as well. Recent Findings: The data from neuroimaging studies were reviewed and discussed in order to complete the overall image of tinnitus network and its correlates such as the distress network, attentional network and other cognitive mechanisms. In addition to the auditory system, the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC) were considered to be important hubs in tinnitus distress network, especially for having important connectivity

Human brain mapping, 2017

The phantom sound of tinnitus is believed to be triggered by aberrant neural activity in the central auditory pathway, but since this debilitating condition is often associated with emotional distress and anxiety, these comorbidities likely arise from maladaptive functional connections to limbic structures such as the amygdala and hippocampus. To test this hypothesis, resting-state functional magnetic resonance imaging (fMRI) was used to identify aberrant effective connectivity of the amygdala and hippocampus in tinnitus patients and to determine the relationship with tinnitus characteristics. Chronic tinnitus patients (n = 26) and age-, sex-, and education-matched healthy controls (n = 23) were included. Both groups were comparable for hearing level. Granger causality analysis utilizing the amygdala and hippocampus as seed regions were used to investigate the directional connectivity and the relationship with tinnitus duration or distress. Relative to healthy controls, tinnitus pat...

Although a peripheral auditory (bottom-up) deficit is an essential prerequisite for the generation of tinnitus, central cognitive (top-down) impairment has also been shown to be an inherent neuropatho-logical mechanism. Using an auditory oddball paradigm (for top-down analyses) and a passive listening paradigm (for bottom-up analyses) while recording electroencephalograms (EEGs), we investigated whether top-down or bottom-up components were more critical in the neuropathology of tinnitus, independent of peripheral hearing loss. We observed significantly reduced P300 amplitudes (reflecting fundamental cognitive processes such as attention) and evoked theta power (reflecting top-down regulation in memory systems) for target stimuli at the tinnitus frequency of patients with tinnitus but without hearing loss. The contingent negative variation (reflecting top-down expectation of a subsequent event prior to stimulation) and N100 (reflecting auditory bottom-up selective attention) were different between the healthy and patient groups. Interestingly, when tinnitus patients were divided into two subgroups based on their P300 amplitudes, their P170 and N200 components, and annoyance and distress indices to their tinnitus sound were different. EEG theta-band power and its Granger causal neurodynamic results consistently support a double dissociation of these two groups in both top-down and bottom-up tasks. Directed cortical connectivity corroborates that the tinnitus network involves the anterior cingulate and the parahippocampal areas, where higher-order top-down control is generated. Together, our observations provide neurophysiological and neurodynamic evidence revealing a differential engagement of top-down impairment along with deficits in bottom-up processing in patients with tinnitus but without hearing loss.

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.