The absence of resting-state high-gamma cross-frequency coupling in patients with tinnitus.

Tinnitus is a psychoacoustic phantom perception of currently unknown neuropathology. Despite a growing number of post-stimulus tinnitus studies, uncertainty still exists regarding the neural signature of tinnitus in the resting-state brain. In the present study, we used high-gamma cross-frequency coupling and a Granger causality analysis to evaluate resting-state electroencephalographic (EEG) data in healthy participants and patients with tinnitus. Patients with tinnitus lacked robust frontal delta-phase/central high-gamma-amplitude coupling that was otherwise clearly observed in healthy participants. Since low-frequency phase and high-frequency amplitude coupling reflects inter-regional communication during cognitive processing, and given the absence of frontal modulation in patients with tinnitus, we hypothesized that tinnitus might be related to impaired prefrontal top-down inhibitory control. A Granger causality analysis consistently showed abnormally pronounced functional connectivity of low-frequency activity in patients with tinnitus, possibly reflecting a deficiency in large-scale communication during the resting state. Moreover, different causal neurodynamics were characterized across two subgroups of patients with tinnitus; the T1 group (with higher P300 amplitudes) showed abnormal frontal-to-auditory cortical information flow, whereas the T2 group (with lower P300 amplitudes) exhibited abnormal auditory-to-frontal cortical information control. This dissociation in resting-state low-frequency causal connectivity is consistent with recent post-stimulus observations. Taken together, our findings suggest that maladaptive neuroplasticity or abnormal reorganization occurs in the auditory default mode network of patients with tinnitus. Additionally, our data highlight the utility of resting-state EEG for the quantitative diagnosis of tinnitus symptoms and the further characterization of tinnitus subtypes.

Top-down and bottom-up neurodynamic evidence in patients with tinnitus.

Although a peripheral auditory (bottom-up) deficit is an essential prerequisite for the generation of tinnitus, central cognitive (top-down) impairment has also been shown to be an inherent neuropathological mechanism. Using an auditory oddball paradigm (for top-down analyses) and a passive listening paradigm (for bottom-up analyses) while recording electroencephalograms (EEGs), we investigated whether top-down or bottom-up components were more critical in the neuropathology of tinnitus, independent of peripheral hearing loss. We observed significantly reduced P300 amplitudes (reflecting fundamental cognitive processes such as attention) and evoked theta power (reflecting top-down regulation in memory systems) for target stimuli at the tinnitus frequency of patients with tinnitus but without hearing loss. The contingent negative variation (reflecting top-down expectation of a subsequent event prior to stimulation) and N100 (reflecting auditory bottom-up selective attention) were different between the healthy and patient groups. Interestingly, when tinnitus patients were divided into two subgroups based on their P300 amplitudes, their P170 and N200 components, and annoyance and distress indices to their tinnitus sound were different. EEG theta-band power and its Granger causal neurodynamic results consistently support a double dissociation of these two groups in both top-down and bottom-up tasks. Directed cortical connectivity corroborates that the tinnitus network involves the anterior cingulate and the parahippocampal areas, where higher-order top-down control is generated. Together, our observations provide neurophysiological and neurodynamic evidence revealing a differential engagement of top-down impairment along with deficits in bottom-up processing in patients with tinnitus but without hearing loss.