The Pathological Mechanisms and Treatments of Tinnitus.

Tinnitus is defined as the ringing, hissing, clicking or roaring sounds an individual consciously perceives in the absence of an external auditory stimulus. Currently, the literature on the mechanism of tinnitus pathology is multifaceted, ranging from tinnitus generation at the cellular level to its perception at the system level. Cellular level mechanisms include increased neuronal synchrony, neurotransmission changes and maladaptive plasticity. At the system level, the role of auditory structures, non-auditory structures, changes in the functional connectivities in higher regions and tinnitus networks have been investigated. The exploration of all these mechanisms creates a holistic view on understanding the changes the pathophysiology of tinnitus undertakes. Although tinnitus percept may start at the level of cochlear nerve deafferentation, the neuronal changes in the central auditory system to the neuronal and connectivity changes in non-auditory regions, such as the limbic system, become cardinal in chronic tinnitus generation. At the present moment, some tinnitus generation mechanisms are well established (e.g., increased neuronal synchrony) whereas other mechanisms have gained more traction recently (e.g., tinnitus networks, tinnitus-distress networks) and therefore, require additional investigation to solidify their role in tinnitus pathology. The treatments and therapeutics designed for tinnitus are numerous, with varied levels of success. They are generally two-fold: some treatments focus on tinnitus cessation (including cochlear implants, deep brain stimulation, transcranial direct current stimulation and transcranial magnetic stimulation) whereas the other set focuses on tinnitus reduction or masking (including hearing aids, sound therapy, cognitive behavioral therapy, tinnitus retraining therapy, and tailor made notched musical training).  Tinnitus management has focused on implementing tinnitus masking/reducing therapies more than tinnitus cessation, since cessation treatments are still lacking in streamlined treatment protocols and long-term sustainability and efficacy of the treatment. This review will focus on concisely exploring the current and most relevant tinnitus pathophysiology mechanisms, treatments and therapeutics.