Tinnitus and hyperacusis: Contributions of paraflocculus, reticular formation and stress

Abstract

Tinnitus and hyperacusis are common and potentially serious hearing disorders associated with noise-, age- or drug-induced hearing loss. Accumulating evidence suggests that tinnitus and hyperacusis are linked to excessive neural activity in a distributed brain network that not only includes the central auditory pathway, but also brain regions involved in arousal, emotion, stress and motor control. Here we examine electrophysiological changes in two novel non-auditory areas implicated in tinnitus and hyperacusis: the caudal pontine reticular nucleus (PnC), involved in arousal, and the paraflocculus lobe of the cerebellum (PFL), implicated in head-eye coordination and gating tinnitus and we measure the changes in corticosterone stress hormone levels. Using the salicylate-induced model of tinnitus and hyperacusis, we found that long-latency (>10 ms) sound-evoked response components in both the brain regions were significantly enhanced after salicylate administration, while the short-latency responses were reduced, likely reflecting cochlear hearing loss. These results are consistent with the central gain model of tinnitus and hyperacusis, which proposes that these disorders arise from the amplification of neural activity in central auditory pathway plus other regions linked to arousal, emotion, tinnitus gating and motor control. Finally, we demonstrate that salicylate results in an increase in corticosterone level in a dose-dependent manner consistent with the notion that stress may interact with hearing loss in tinnitus and hyperacusis development. This increased stress response has the potential to have wide-ranging effects on the central nervous system and may therefore contribute to brain-wide changes in neural activity.

Increased Resting-State Cerebellar-Cerebral Functional Connectivity Underlying Chronic Tinnitus

“…After auditory nerve transection, the phantom experience of tinnitus still does not disappear (Jackler and Whinney, 2001 ). It has been demonstrated that tinnitus involves aberrant neural activity in not only auditory regions but also non-auditory structures such as the prefrontal cortex, parahippocampal gyrus (PHG), amygdala, and cerebellum, which have been confirmed to be important in the development or progression of tinnitus (Rauschecker et al, 2010 ; Leaver et al, 2011 ; Langguth et al, 2013 ; Chen et al, 2015a , 2017a , b , c ; Brozoski et al, 2017 ).…”

Characteristics of somatic tinnitus patients with and without hyperacusis

“…Hyperacusis is also associated with anxiety, depression, schizophrenia and sleep disorders [ 3 , 15 , 16 ]. Approximately 40% of patients with tinnitus also suffer from hyperacusis whereas up to 80% of patients with hyperacusis also have tinnitus, suggesting that these disorders may share a common pathophysiology [ 8 , 9 , 17 ]. While hyperacusis and tinnitus are often associated with hearing loss [ 18 – 20 ], some individuals with hyperacusis and/or tinnitus have clinically normal audiograms [ 15 , 21 ].…”

“…Many studies have focused on the association between hyperacusis and tinnitus [ 8 , 9 , 17 – 20 , 42 – 44 ]; however, much less is known about the association between hyperacusis and somatic tinnitus, although the former has been shown to be associated with disordered perceptions involving the somatosensory domain. Some report an increased prevalence of hyperacusis in somatic tinnitus patients [ 45 ] while others have not [ 46 ].…”

Somatic Tinnitus

“…The increased prevalence of somatic modulation found by the authors in hyperacusis patients could be due to increased peripheral somatic activation or central hypersensitivity to somatic inputs. The latter is supported by neurophysiological findings that show increased sensitivity to multisensory stimuli in patients with hyperacusis, which may be linked to a hypervigilance network [80][81][82][83][84] . Also, Schecklmann 79 and Gilles 85 found worse tinnitus and depression scores in patients with hyperacusis than in those without.…”