Dysregulation of Limbic and Auditory Networks in Tinnitus

Abstract

Summary Tinnitus is a common disorder characterized by ringing in the ear in the absence of sound. Converging evidence suggests that tinnitus pathophysiology involves damage to peripheral and/or central auditory pathways. However, whether auditory system dysfunction is sufficient to explain chronic tinnitus is unclear, especially in light of evidence implicating other networks, including the limbic system. Using functional magnetic resonance imaging and voxel-based morphometry, we assessed tinnitus-related functional and anatomical anomalies in auditory and limbic networks. Moderate hyperactivity was present in the primary and posterior auditory cortices of tinnitus patients. However, the nucleus accumbens exhibited the greatest degree of hyperactivity, specifically to sounds frequency-matched to patients’ tinnitus. Complementary structural differences were identified in ventromedial prefrontal cortex, another limbic structure heavily connected to the nucleus accumbens. Furthermore, tinnitus-related anomalies were intercorrelated in the two limbic regions and between limbic and primary auditory areas, indicating the importance of auditory-limbic interactions in tinnitus.

Pathogenic plasticity of Kv7.2/3 channel activity is essential for the induction of tinnitus

“…Recent studies show that cortical reorganization (6, 7) and aberrant thalamocortical rhythms (48) (thalamocortical dysrythmia) may underlie the expression of tinnitus; thalamocortical dysrythmia, by promoting stimulus-independent γ oscillations could maintain the conscious perception. Moreover, although it is evident that auditory system dysfunction is necessary for the generation of tinnitus, the maintenance of chronic tinnitus may involve pathological interactions between auditory and nonauditory structures, such as the limbic system (49,50). Thus, our findings suggest that KCNQ-mediated, subcortical hyperactivity may be triggering cortical reorganization and thalamocortical dysrythmia, which, in combination with changes in the limbic system, lead to the maintenance of the perception of phantom sound.…”

Bilateral Low-Frequency Repetitive Transcranial Magnetic Stimulation of the Auditory Cortex in Tinnitus Patients Is Not Effective: A Randomised Controlled Trial

“…Even though there are many differences across studies, a general trend can be seen that neural activity across several centres of the central auditory system is enhanced [Lanting et al, 2009]. That tinnitus is not solely caused by abnormal hyperactivity in the auditory cortex is shown by abnormal activity in non-auditory areas such as the frontal areas, the limbic system and the cerebellum, which was found in neuroimaging studies [Lanting et al, 2009;Leaver et al, 2011].…”

Differential tinnitus-related neuroplastic alterations of cortical thickness and surface area

“…The number of studies that scrutinized the neuroanatomical changes in the brain structure of TI is smaller, but for the time being, the results are notably inconsistent and 50 heterogeneous [26,27,28,29,30,31,32] (for a review, see [33]). The range of brain regions that appear to undergo structural changes either as a function or as a catalyst of chronic noise perception includes the supratemporal, the lateral (pre-)frontal cortex, medial frontal, cingulate, temporal, subcallosal and parietal cortex as well as a number of subcortical nuclei.…”

“…Furthermore, evidence for confined "structural abnormalities specifically related to tinnitus is sparse" [33, p. 119], and this fact makes it difficult to test specific anatomical hypotheses. The results obtained from studies that used the standard VBM approach [27,28,29,30,32,1,35] 70 are difficult to reconcile due to their heterogeneity. Thus the question arises whether the inconsistency of available results may be related to methodological limitations of VBM measurements [33].…”

“…In the absence of any reasonable and appropriate coping strategies, these persons consider the permanent sound to be extremely detrimental [21]. 30 It has been suggested that the neural thalamo-cortical circuit that maintains the phantom sound connects increasingly with attentional circuits, and that this neural loop, being further accelerated by aversive emotional attributions, is continuously updated, eventually becoming chronically established [8,22]. Thus, chronic subjective tinnitus could be considered a disorder that results 35 from the maladaption of several overlapping brain systems that bind together in a 'vicious cycle' guided by principles of neural learning mechanisms.…”