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To test this hypothesis, resting\u2010state 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                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200926) and age\u2010, sex\u2010, and education\u2010matched healthy controls (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200923) 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\u2010auditory areas. Importantly, scores on the Tinnitus Handicap Questionnaires were positively correlated with increased connectivity from the left amygdala to left superior temporal gyrus (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20090.570,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.005), and from the right amygdala to right superior temporal gyrus (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20090.487,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.018). Moreover, enhanced effective connectivity from the right hippocampus to left transverse temporal gyrus was correlated with tinnitus duration (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20090.452,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.030). 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.\n                    <jats:italic>Hum Brain Mapp 38:2384\u20132397, 2017<\/jats:italic>\n                    . \u00a9\n                    <jats:bold>2017 Wiley Periodicals, Inc.<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1002\/hbm.23525","type":"journal-article","created":{"date-parts":[[2017,1,23]],"date-time":"2017-01-23T07:56:58Z","timestamp":1485158218000},"page":"2384-2397","source":"Crossref","is-referenced-by-count":139,"title":["Tinnitus distress is linked to enhanced resting\u2010state functional connectivity from the limbic system to the auditory cortex"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8539-7224","authenticated-orcid":false,"given":"Yu\u2010Chen","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Radiology Nanjing First Hospital, Nanjing Medical University 210006 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