Participation of the Anterior Cingulate Cortex in Sodium Salicylate-induced Tinnitus

Hypothesis: The anterior cingulate cortex (ACC) participates in sodium salicylate (SS)-induced tinnitus through alteration of the disordered neural activity and modulates the neuronal changes in the auditory cortex (AC). Background: Although the mechanism underlying tinnitus remains unclear, the crucial roles of the auditory center and limbic system in this process have been elucidated. Recent reports suggest that dysfunction of the ACC, an important component of the limbic system that regulates and controls the conduction of multiple sensations, is involved in tinnitus. Although altered functional connectivity between the ACC and the auditory system has been observed in humans with tinnitus, the underlying neuronal mechanism remains unexplored. Methods: SS (350 mg/kg, 10%, i.p.) was used to yield tinnitus model in rats, followed by comparison of the alteration in the spontaneous firing rate (SFR), local field potential (LFP), and extracellular glutamic acid in the ACC. The responses of neurons in the AC to electrical stimulation from the ACC were also observed. Results: We determined significant increases in the neuronal SFR and extracellular glutamate level in the ACC after SS injection ( p < 0.05). These effects were accompanied by decreased alpha band activity and increased beta and gamma band activity ( p < 0.05). In the majority of AC neurons, the SFR decreased in response to ACC stimulation ( p < 0.05). Conclusions: Our results demonstrated that disordered neural activity in the ACC contributes to SS-induced tinnitus and that ACC activation can modulate AC activity.