Subjective tinnitus is the conscious perception of sound in the absence of any acoustic source. The literature suggests various tinnitus mechanisms, most of which invoke changes in spontaneous firing rates of central auditory neurons resulting from modification of neural gain. Here, we present an alternative model based on evidence that tinnitus is: (1) rare in people who are congenitally deaf, (2) common in people with acquired deafness, and (3) potentially suppressed by active cochlear implants used for hearing restoration. We propose that tinnitus can only develop after fast auditory fiber activity has stimulated the synapse formation between fast-spiking parvalbumin positive (PV 1 ) interneurons and projecting neurons in the ascending auditory path and coactivated frontostriatal networks after hearing onset. Thereafter, fast auditory fiber activity promotes feedforward and feedback inhibition mediated by PV 1 interneuron activity in auditory-specific circuits. This inhibitory network enables enhanced stimulus resolution, attention-driven contrast improvement, and augmentation of auditory responses in central auditory pathways (neural gain) after damage of slow auditory fibers. When fast auditory fiber activity is lost, tonic PV 1 interneuron activity is diminished, resulting in the prolonged response latencies, sudden hyperexcitability, enhanced cortical synchrony, elevated spontaneous c oscillations, and impaired attention/stress-control that have been described in previous tinnitus models. Moreover, because fast processing is gained through sensory experience, tinnitus would not exist in congenital deafness. Electrical cochlear stimulation may have the potential to reestablish tonic inhibitory networks and thus suppress tinnitus. The proposed framework unites many ideas of tinnitus pathophysiology and may catalyze cooperative efforts to develop tinnitus therapies.

The ␤ 2-transferrin assay is a specific method to identify cerebrospinal fluid (CSF). Hitherto, this test has not been widely used for the routine screening of patients with suspected CSF leakage. The purpose of this study was to investigate the clinical relevance of the identification of ␤ 2-transferrin by comparing the test results with other diagnostic measures and intraoperative findings. Design: Case series. Patients: Retrospective analysis of 182 patients tested once or multiple times for ␤ 2-transferrin. Main Outcome Measures: Information was obtained regarding different diagnostic procedures applied to diagnose CSF leakage. The effectiveness of those diagnostic measures was compared. Results: The main indication to test for ␤ 2-transferrin was posttraumatic rhinorrhea (25%), followed by spontaneous (22%) and postsurgical (22%) rhinorrhea. In 35 of 205 cases, ␤ 2-transferrin was detected in the tested specimens. Thirteen of these required surgical intervention for treatment of the CSF fistula, and the leakage site was identified in all of them. Taking all results into consideration, the highest correlation was observed between the ␤ 2-transferrin assay, intrathecal fluorescein application, and surgical exploration. Conclusions: The ␤ 2-transferrin assay is a reliable method for confirming suspected CSF and should be used as a primary screening method in all patients with suspected CSF leakage. Although less invasive, the ␤ 2transferrin assay almost matches the high sensitivity achieved by exploratory surgery and intrathecal application of fluorescein. However, the possibility of bias should be carefully considered, and in particular, negative results should be critically compared with clinical symptoms and with results from other diagnostic procedures.

Electrical stimulation (ES) of spiral ganglion cells (SGC) via a cochlear implant is the standard treatment for profound sensor neural hearing loss. However, loss of hair cells as the morphological correlate of sensor neural hearing loss leads to deafferentation and death of SGC. Although immediate treatment with ES or glial cell line-derived neurotrophic factor (GDNF) can prevent degeneration of SGC, only few studies address the effectiveness of delayed treatment. We hypothesize that both interventions have a synergistic effect and that even delayed treatment would protect SGC. Therefore, an electrode connected to a pump was implanted into the left cochlea of guinea pigs 3 weeks after deafening. The contralateral untreated cochleae served as deafened intraindividual controls. Four groups were set up. Control animals received intracochlear infusion of artificial perilymph (AP/-). The experimental groups consisted of animals treated with AP in addition to continuous ES (AP/ES) or treated with GDNF alone (GDNF/-) or GDNF combined with continuous ES (GDNF/ES). Acoustically and electrically evoked auditory brain stem responses were recorded. All animals were killed 48 days after deafening; their cochleae were histologically evaluated. Survival of SGC increased significantly in the GDNF/- and AP/ES group compared with the AP/- group. A highly significant increase in SGC density was observed in the GDNF/ES group compared with the control group. Additionally, animals in the GDNF/ES group showed reduced EABR thresholds. Thus, delayed treatment with GDNF and ES can protect SGC from degeneration and may improve the benefits of cochlear implants.