Auditory thalamus dysfunction and pathophysiology in tinnitus: a predictive network hypothesis

Abstract

Tinnitus is the perception of a ‘ringing’ sound without an acoustic source. It is generally accepted that tinnitus develops after peripheral hearing loss and is associated with altered auditory processing. The thalamus is a crucial relay in the underlying pathways that actively shapes processing of auditory signals before the respective information reaches the cerebral cortex. Here, we review animal and human evidence to define thalamic function in tinnitus. Overall increased spontaneous firing patterns and altered coherence between the thalamic medial geniculate body (MGB) and auditory cortices is observed in animal models of tinnitus. It is likely that the functional connectivity between the MGB and primary and secondary auditory cortices is reduced in humans. Conversely, there are indications for increased connectivity between the MGB and several areas in the cingulate cortex and posterior cerebellar regions, as well as variability in connectivity between the MGB and frontal areas regarding laterality and orientation in the inferior, medial and superior frontal gyrus. We suggest that these changes affect adaptive sensory gating of temporal and spectral sound features along the auditory pathway, reflecting dysfunction in an extensive thalamo-cortical network implicated in predictive temporal adaptation to the auditory environment. Modulation of temporal characteristics of input signals might hence factor into a thalamo-cortical dysrhythmia profile of tinnitus, but could ultimately also establish new directions for treatment options for persons with tinnitus.

Evidence of a Neuroinflammatory Model of Tinnitus

“…The medial geniculate body is a known intermediary between the auditory cortex and the inferior colliculus in the classical auditory pathway; however, its role in tinnitus has not been well-examined [48]. Roberts [19] suggests following hyperactivity in the inferior colliculus, thalamic neurons switch from tonal firing to burst firing in the medial geniculate body.…”

“…Roberts [19] suggests following hyperactivity in the inferior colliculus, thalamic neurons switch from tonal firing to burst firing in the medial geniculate body. This change is caused by membrane hyperpolarization, which activates calcium channels causing thalamic neurons to carry less well-defined nonlinear inputs [48]. This may lead to low-frequency oscillations propagating to the auditory cortex [19].…”

“…The GPIAS is commonly used to determine the presence of tinnitus in animals; however, the GPIAS has not been proven to be a valid measure of tinnitus in humans [29]. It is also not possible to distinguish between subtypes of subjective tinnitus based on the presentation in animals [48].…”

The role of the medial geniculate body of the thalamus in the pathophysiology of tinnitus and implications for treatment

“…Rauschecker et al, 2010). The MGB is thought to gate and transform auditory information as it is passed to the auditory cortex (AC) (Brinkmann et al, 2021;Sherman 2012). The MGB also extensively connects with limbic structures that are likely impacting emotional responses to tinnitus (LeDoux 2007).…”

The Effect of Noise Trauma and Deep Brain Stimulation of the Medial Geniculate Body on Tissue Activity in the Auditory Pathway

“…However, the optimal DBS target for effective treatment of tinnitus remains to be determined. The role of the auditory thalamus, particularly the MGB, in tinnitus pathology is also attracting more interest [ 10 ]. Findings in both human and animal studies suggest the auditory thalamus has a prominent role in the altered auditory system in tinnitus [ 11 , 12 ].…”