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 lowfrequency
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.