Disrupted Brain Functional Network Architecture in Chronic Tinnitus Patients

Abstract

Purpose: Resting-state functional magnetic resonance imaging (fMRI) studies have demonstrated the disruptions of multiple brain networks in tinnitus patients. Nonetheless, several studies found no differences in network processing between tinnitus patients and healthy controls (HCs). Its neural bases are poorly understood. To identify aberrant brain network architecture involved in chronic tinnitus, we compared the resting-state fMRI (rs-fMRI) patterns of tinnitus patients and HCs.Materials and Methods: Chronic tinnitus patients (n = 24) with normal hearing thresholds and age-, sex-, education- and hearing threshold-matched HCs (n = 22) participated in the current study and underwent the rs-fMRI scanning. We used degree centrality (DC) to investigate functional connectivity (FC) strength of the whole-brain network and Granger causality to analyze effective connectivity in order to explore directional aspects involved in tinnitus.Results: Compared to HCs, we found significantly increased network centrality in bilateral superior frontal gyrus (SFG). Unidirectionally, the left SFG revealed increased effective connectivity to the left middle orbitofrontal cortex (OFC), left posterior lobe of cerebellum (PLC), left postcentral gyrus, and right middle occipital gyrus (MOG) while the right SFG exhibited enhanced effective connectivity to the right supplementary motor area (SMA). In addition, the effective connectivity from the bilateral SFG to the OFC and SMA showed positive correlations with tinnitus distress.Conclusions: Rs-fMRI provides a new and novel method for identifying aberrant brain network architecture. Chronic tinnitus patients have disrupted FC strength and causal connectivity mostly in non-auditory regions, especially the prefrontal cortex (PFC). The current findings will provide a new perspective for understanding the neuropathophysiological mechanisms in chronic tinnitus.

Resting-State Brain Abnormalities in Chronic Subjective Tinnitus: A Meta-Analysis

“…Rauschecker et al (2010) developed a model to demonstrate structural and functional differences in ventromedial prefrontal cortex that were associated with tinnitus subjective loudness, indicating that frontal cortex may contribute to certain perceptual features of tinnitus. Resting-state fMRI studies have pointed out that the abnormalities of the frontal cortex could act as a direct mechanism of tinnitus chronification (Burton et al, 2012; Schmidt et al, 2013; Chen et al, 2014, 2015c,d, 2016), which are confirmed by the current meta-analysis. Based on the previous fMRI studies, the SFG has been regarded as a major integrative hub of the tinnitus network architecture (Chen et al, 2016), which can receive and integrate all kinds of information from different parts of the brain from inside and outside the body.…”

“…Resting-state fMRI studies have pointed out that the abnormalities of the frontal cortex could act as a direct mechanism of tinnitus chronification (Burton et al, 2012; Schmidt et al, 2013; Chen et al, 2014, 2015c,d, 2016), which are confirmed by the current meta-analysis. Based on the previous fMRI studies, the SFG has been regarded as a major integrative hub of the tinnitus network architecture (Chen et al, 2016), which can receive and integrate all kinds of information from different parts of the brain from inside and outside the body. Besides, it can also timely organize efferent impulses to ensure the coordination of the central nervous system as a whole (Mathiak et al, 2007; Melloni et al, 2007).…”

“…Using our inclusion/exclusion criteria, we identified nine eligible neuroimaging studies utilizing different methods, including SPECT (Laureano et al, 2014; Ueyama et al, 2015), PET (Geven et al, 2014), and fMRI (Maudoux et al, 2012a; Chen et al, 2014, 2015d, 2016; Leaver et al, 2016b). Figure 1 is a flow diagram showing the steps in the identification, exclusion and inclusion of the studies.…”

“…However, these studies reported relatively inconsistent results. For instance, most researches demonstrated the increased resting-state brain activity between tinnitus patients and healthy controls (Maudoux et al, 2012a; Chen et al, 2014, 2016; Laureano et al, 2014; Yang et al, 2014; Ueyama et al, 2015), while others failed to identify any regions of increased brain activity (Geven et al, 2014; Leaver et al, 2016b). Moreover, several studies have failed to detect any differences in network processing between tinnitus patients and controls (Wineland et al, 2012; Davies et al, 2014).…”

Tinnitus distress is linked to enhanced resting‐state functional connectivity from the limbic system to the auditory cortex

“…In most cases, tinnitus was associated with an increase in effective connectivity rather than a decrease [Chen et al, 2016;Hong et al, 2016;Zobay et al, 2015]. In tinnitus patients, significant changes in effective connectivity occurred in a relatively circumscribed network emanating from and projecting to the amygdala or the hippocampus.…”