title: Tinnitus distress is linked to enhanced resting-state functional connectivity from the limbic system to the auditory cortex.
abstract: The phantom sound of tinnitus is believed to be triggered by aberrant neural activity in the central auditory pathway, but since this debilitating condition is often associated with emotional distress and anxiety, these comorbidities likely arise from maladaptive functional connections to limbic structures such as the amygdala and hippocampus. To test this hypothesis, resting-state functional magnetic resonance imaging (fMRI) was used to identify aberrant effective connectivity of the amygdala and hippocampus in tinnitus patients and to determine the relationship with tinnitus characteristics. Chronic tinnitus patients (n = 26) and age-, sex-, and education-matched healthy controls (n = 23) were included. Both groups were comparable for hearing level. Granger causality analysis utilizing the amygdala and hippocampus as seed regions were used to investigate the directional connectivity and the relationship with tinnitus duration or distress. Relative to healthy controls, tinnitus patients demonstrated abnormal directional connectivity of the amygdala and hippocampus, including primary and association auditory cortex, and other non-auditory areas. Importantly, scores on the Tinnitus Handicap Questionnaires were positively correlated with increased connectivity from the left amygdala to left superior temporal gyrus (r = 0.570, P = 0.005), and from the right amygdala to right superior temporal gyrus (r = 0.487, P = 0.018). Moreover, enhanced effective connectivity from the right hippocampus to left transverse temporal gyrus was correlated with tinnitus duration (r = 0.452, P = 0.030). The results showed that tinnitus distress strongly correlates with enhanced effective connectivity that is directed from the amygdala to the auditory cortex. The longer the phantom sensation, the more likely acute tinnitus becomes permanently encoded by memory traces in the hippocampus. Hum Brain Mapp 38:2384-2397, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Department of Radiology, Nanjing First Hospital, Nanjing Medical University, 210006, Nanjing, China.
authors.forename: Yu-Chen
authors.identifier: 0000-0002-8539-7224
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, 210006, Nanjing, China.
authors.forename: Wenqing
authors.initials: W
authors.lastname: Xia
authors.affiliation: Department of Radiology, Nanjing First Hospital, Nanjing Medical University, 210006, Nanjing, China.
authors.forename: Huiyou
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Radiology, Nanjing First Hospital, Nanjing Medical University, 210006, Nanjing, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Otolaryngology, Nanjing First Hospital, Nanjing Medical University, 210006, Nanjing, China.
authors.forename: Jin-Jing
authors.initials: JJ
authors.lastname: Xu
authors.affiliation: Department of Vascular and Interventional Radiology, Nanjing First Hospital, Nanjing Medical University, 210006, Nanjing, China.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Gu
authors.affiliation: Center for Hearing and Deafness, University at Buffalo, State University of New York, Buffalo, 14214, New York.
authors.forename: Richard
authors.initials: R
authors.lastname: Salvi
authors.affiliation: Department of Radiology, Nanjing First Hospital, Nanjing Medical University, 210006, Nanjing, China.
authors.forename: Xindao
authors.initials: X
authors.lastname: Yin
mesh_terms: D000328:Adult; D001303:Auditory Cortex / Q000000981:diagnostic imaging / Q000503:physiopathology*; D001306:Auditory Pathways / Q000503:physiopathology; D001931:Brain Mapping; D005260:Female; D007839:Functional Laterality; D006801:Humans; D021621:Imaging, Three-Dimensional; D008032:Limbic System / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009415:Nerve Net; D012146:Rest; D013223:Statistics as Topic; D014012:Tinnitus / Q000000981:diagnostic imaging / Q000473:pathology*
keywords: effective connectivity; functional connectivity; limbic system; resting-state fMRI; tinnitus