Brain Effective Connectivity Analysis Facilitates the Treatment Outcome Expectation of Sound Therapy in Patients With Tinnitus

Tinnitus is associated with abnormal functional connectivity of multiple regions of the brain. However, previous analytic methods have disregarded information on the direction of functional connectivity, leading to only a moderate efficacy of pretreatment planning. We hypothesized that the pattern of directional functional connectivity can provide key information on treatment outcomes. Sixty-four participants were enrolled in this study: eighteen patients with tinnitus were categorized into the effective group, twenty-two patients into the ineffective group, and twenty-four healthy participants into the healthy control group. We acquired resting-state functional magnetic resonance images prior to sound therapy and constructed an effective connectivity network of the three groups using an artificial bee colony algorithm and transfer entropy. The key feature of patients with tinnitus was the significantly increased signal output of the sensory network, including the auditory, visual, and somatosensory networks, and parts of the motor network. This provided critical insights into the gain theory of tinnitus development. The altered pattern of functional information orchestration, represented by a higher degree of hypervigilance-driven attention and enhanced multisensory integration, may explain poor clinical outcomes. The activated gating function of the thalamus is one of the key factors for a good prognosis in tinnitus treatment. We developed a novel method for analyzing effective connectivity, facilitating an understanding of the tinnitus mechanism and treatment outcome expectation based on the direction of information flow.