Abstract
Purpose
The present study combined resting-state functional connectivity (FC) and Granger causality analysis (GCA) to explore frontostriatal network dysfunction in unilateral acute tinnitus (AT) patients with hearing loss.
Methods
The participants included 42 AT patients and 43 healthy control (HC) subjects who underwent resting-state functional magnetic resonance imaging (fMRI) scans. Based on the seed regions in the frontostriatal network, FC and GCA were conducted between the AT patients and HC subjects. Correlation analyses were used to examine correlations among altered FC values, GCA values, and clinical features in AT patients.
Results
Compared with HCs, AT patients showed a general reduction in FC between the seed regions in the frontostriatal network and nonauditory areas, including the frontal cortices, midcingulate cortex (MCC), supramarginal gyrus, and postcentral gyrus (PoCG). Using the GCA algorithm, we detected abnormal effective connectivity (EC) in the inferior occipital gyrus, MCC, Cerebelum_Crus1, and PoCG. Furthermore, correlations between disrupted FC/EC and clinical characteristics, especially tinnitus distress-related characteristics, were found in AT patients.
Conclusions
Our work demonstrated abnormal FC and EC between the frontostriatal network and several nonauditory regions in AT patients with hearing loss, suggesting that multiple large-scale network dysfunctions and interactions are involved in the perception of tinnitus. These findings not only enhance the current understanding of the frontostriatal network in tinnitus but also serve as a reminder of the importance of focusing on tinnitus at an early stage.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Availability of data and materials
The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.
Code availability
Not applicable.
References
Baguley, D., McFerran, D., & Hall, D. (2013). Tinnitus. Lancet, 382(9904), 1600–1607. https://doi.org/10.1016/s0140-6736(13)60142-7
Barry, K., Paolini, A., Robertson, D., & Mulders, W. J. N. (2015). Modulation of medial geniculate nucleus neuronal activity by electrical stimulation of the nucleus accumbens. Neuroscience, 308, 1–10. https://doi.org/10.1016/j.neuroscience.2015.09.008
Burton, H., Wineland, A., Bhattacharya, M., Nicklaus, J., Garcia, K. S., & Piccirillo, J. F. (2012). Altered networks in bothersome tinnitus: A functional connectivity study. BMC Neuroscience, 13, 3. https://doi.org/10.1186/1471-2202-13-3
Cai, Y., Huang, D., Chen, Y., Yang, H., Wang, C., Zhao, F., Liu, J., Sun, Y., Chen, G., Chen, X., Xiong, H., & Zheng, Y. J. (2018). Deviant dynamics of resting state electroencephalogram microstate in patients with subjective tinnitus. Frontiers in Behavioral Neuroscience, 12, 122. https://doi.org/10.3389/fnbeh.2018.00122
Cai, Y., Xie, M., Su, Y., Tong, Z., Wu, X., Xu, W., Li, J., Zhao, F., Dang, C., Chen, G., Lan, L., Shen, J., & Zheng, Y. (2020). Aberrant functional and causal connectivity in acute tinnitus with sensorineural hearing loss. Frontiers in Neuroscience, 14, 592. https://doi.org/10.3389/fnins.2020.00592
Cai, Y., Zhou, Q., Yang, H., Jiang, J., Zhao, F., Huang, X., Mo, H., Chen, X., Xiong, H., Chen, S., Zhang, X., & Zheng, Y. (2017). Logistic regression analysis of factors influencing the effectiveness of intensive sound masking therapy in patients with tinnitus. British Medical Journal Open, 7(11), e018050. https://doi.org/10.1136/bmjopen-2017-018050
Cauda, F., Cavanna, A., Dagata, F., Sacco, K., Duca, S., & Geminiani, G. (2011). Functional connectivity and coactivation of the nucleus accumbens: A combined functional connectivity and structure-based meta-analysis. Journal of Cognitive Neuroscience, 23(10), 2864–2877. https://doi.org/10.1162/jocn.2011.21624
Chen, Y. C., Chen, H., Bo, F., Xu, J. J., Deng, Y., Lv, H., Cai, Y., Xia, W., Yin, X., Gu, J.-P., & Lu, G. (2018a). Tinnitus distress is associated with enhanced resting-state functional connectivity within the default mode network. Neuropsychiatric Disease and Treatment, 14, 1919–1927. https://doi.org/10.2147/ndt.S164619
Chen, Y. C., Feng, Y., Xu, J. J., Mao, C. N., Xia, W., Ren, J., & Yin, X. (2016). Disrupted brain functional network architecture in chronic tinnitus patients. Front Aging Neurosci, 8, 174. https://doi.org/10.3389/fnagi.2016.00174
Chen, Y. C., Wang, F., Wang, J., Bo, F., Xia, W., Gu, J. P., & Yin, X. (2017). Resting-state brain abnormalities in chronic subjective tinnitus: A meta-analysis. Frontiers in Human Neuroscience, 11, 22. https://doi.org/10.3389/fnhum.2017.00022
Chen, Y. C., Xia, W., Feng, Y., Li, X., Zhang, J., Feng, X., Wang, C.-X., Cai, Y., Wang, J., Salvi, R., & Teng, G. J. (2015). Altered interhemispheric functional coordination in chronic tinnitus patients. BioMed Research International, 2015, 345647. https://doi.org/10.1155/2015/345647
Chen, Y. C., Yong, W., Xing, C., Feng, Y., Haidari, N. A., Xu, J. J., Gu, P. P., Yin, X., & Wu, Y. (2020). Directed functional connectivity of the hippocampus in patients with presbycusis. Brain Imaging and Behavior, 14(3), 917–926. https://doi.org/10.1007/s11682-019-00162-z
Chen, Y. C., Zhang, H., Kong, Y., Lv, H., Cai, Y., Chen, H., Feng, Y., & Yin, X. (2018b). Alterations of the default mode network and cognitive impairment in patients with unilateral chronic tinnitus. Quantitative Imaging in Medicine and Surgery, 8(10), 1020–1029. https://doi.org/10.21037/qims.2018.11.04
Chen, Y. C., Zhang, J., Li, X. W., Xia, W., Feng, X., Gao, B., Ju, S.-H., Wang, J., Salvi, R., & Teng, G. J. (2014). Aberrant spontaneous brain activity in chronic tinnitus patients revealed by resting-state functional MRI. NeuroImage Clinical, 6, 222–228. https://doi.org/10.1016/j.nicl.2014.09.011
De Ridder, D., Elgoyhen, A. B., Romo, R., & Langguth, B. (2011). Phantom percepts: Tinnitus and pain as persisting aversive memory networks. Proceedings of the National Academy of Sciences of the United States of America, 108(20), 8075–8080. https://doi.org/10.1073/pnas.1018466108
De Ridder, D., Vanneste, S., Gillett, G., Manning, P., Glue, P., & Langguth, B. (2016). Psychosurgery Reduces uncertainty and increases free will? A review. Neuromodulation, 19(3), 239–248. https://doi.org/10.1111/ner.12405
Friston, K. J., Williams, S., Howard, R., Frackowiak, R. S., & Turner, R. (1996). Movement-related effects in fMRI time-series. Magnetic Resonance in Medicine, 35(3), 346–355. https://doi.org/10.1002/mrm.1910350312
Froemke, R. C., & Martins, A. R. (2011). Spectrotemporal dynamics of auditory cortical synaptic receptive field plasticity. Hearing Research, 279(1–2), 149–161. https://doi.org/10.1016/j.heares.2011.03.005
Golm, D., Schmidt-Samoa, C., Dechent, P., & Kroner-Herwig, B. (2013). Neural correlates of tinnitus related distress: An fMRI-study. Hearing Research, 295, 87–99. https://doi.org/10.1016/j.heares.2012.03.003
Gunbey, H., Gunbey, E., Aslan, K., Bulut, T., Unal, A., & Incesu, L. (2017). Limbic-auditory interactions of tinnitus: An evaluation using diffusion tensor imaging. Clinical Neuroradiology, 27(2), 221–230. https://doi.org/10.1007/s00062-015-0473-0
Guo, W., Liu, F., Zhang, Z., Liu, J., Yu, M., Zhang, J., Xiao, C., & Zhao, J. (2015). Unidirectionally affected causal connectivity of cortico-limbic-cerebellar circuit by structural deficits in drug-naive major depressive disorder. Journal of Affective Disorders, 172, 410–416. https://doi.org/10.1016/j.jad.2014.10.019
Henry, J., Roberts, L., Caspary, D., Theodoroff, S., & Salvi, R. (2014). Underlying mechanisms of tinnitus: review and clinical implications. The Journal of the American Academy of Audiology 25(1), 5–22; quiz 126. https://doi.org/10.3766/jaaa.25.1.2
Heywood, R., Gao, Q., Nyunt, M., Feng, L., Chong, M., Lim, W., Yap, P., Lee, T. S., Yap, K. B., Wee, S. L., & Ng, T. P. (2017). Hearing loss and risk of mild cognitive impairment and dementia: Findings from the singapore longitudinal ageing study. Dementia and Geriatric Cognitive Disorders, 43, 259–268. https://doi.org/10.1159/000464281
Hu, T., Wang, R., Du, Y., Guo, F., Wu, Y., Wang, Y., Wang, S., Li, X.-Y., Zhang, S.-H., & Chen, Z. (2019). Activation of the intrinsic pain inhibitory circuit from the midcingulate Cg2 to zona incerta alleviates neuropathic pain. Journal of Neuroscience., 39(46), 9130–9144. https://doi.org/10.1523/jneurosci.1683-19.2019
Hullfish, J., Abenes, I., Yoo, H. B., De Ridder, D., & Vanneste, S. (2019). Frontostriatal network dysfunction as a domain-general mechanism underlying phantom perception. Human Brain Mapping, 40(7), 2241–2251. https://doi.org/10.1002/hbm.24521
Job, A., Pons, Y., Lamalle, L., Jaillard, A., Buck, K., Segebarth, C., & Delon-Martin, C. (2012). Abnormal cortical sensorimotor activity during “Target” sound detection in subjects with acute acoustic trauma sequelae: An fMRI study. Brain and Behavior: A Cognitive Neuroscience Perspective, 2(2), 187–199. https://doi.org/10.1002/brb3.21
Koechlin, E. (2016). Prefrontal executive function and adaptive behavior in complex environments. Current Opinion in Neurobiology, 37, 1–6. https://doi.org/10.1016/j.conb.2015.11.004
Lammel, S., Lim, B., Ran, C., Huang, K., Betley, M., Tye, K., Deisseroth, K., & Malenka, R. (2012). Input-specific control of reward and aversion in the ventral tegmental area. Nature, 491(7423), 212–217. https://doi.org/10.1038/nature11527
Leaver, A. M., Renier, L., Chevillet, M. A., Morgan, S., Kim, H. J., & Rauschecker, J. P. (2011). Dysregulation of limbic and auditory networks in tinnitus. Neuron, 69(1), 33–43. https://doi.org/10.1016/j.neuron.2010.12.002
Leaver, A. M., Seydell-Greenwald, A., & Rauschecker, J. P. (2016b). Auditory-limbic interactions in chronic tinnitus: Challenges for neuroimaging research. Hearing Research, 334, 49–57. https://doi.org/10.1016/j.heares.2015.08.005
Leaver, A., Seydell-Greenwald, A., Turesky, T., Morgan, S., Kim, H., & Rauschecker, J. (2012). Cortico-limbic morphology separates tinnitus from tinnitus distress. Frontiers in Systems Neuroscience, 6, 21. https://doi.org/10.3389/fnsys.2012.00021
Leaver, A., Turesky, T., Seydell-Greenwald, A., Morgan, S., Kim, H., & Rauschecker, J. (2016a). Intrinsic network activity in tinnitus investigated using functional MRI. Human Brain Mapping, 37(8), 2717–2735. https://doi.org/10.1002/hbm.23204
Lefebvre, S., Demeulemeester, M., Leroy, A., Delmaire, C., Lopes, R., Pins, D., Thomas, P., & Jardri, R. (2016). Network dynamics during the different stages of hallucinations in schizophrenia. Human Brain Mapping, 37(7), 2571–2586. https://doi.org/10.1002/hbm.23197
Mahoney, C. J., Rohrer, J. D., Goll, J. C., Fox, N. C., Rossor, M. N., & Warren, J. D. (2011). Structural neuroanatomy of tinnitus and hyperacusis in semantic dementia. Journal of Neurology, Neurosurgery and Psychiatry, 82(11), 1274–1278. https://doi.org/10.1136/jnnp.2010.235473
Maudoux, A., Lefebvre, P., Cabay, J. E., Demertzi, A., Vanhaudenhuyse, A., Laureys, S., & Soddu, A. (2012). Auditory resting-state network connectivity in tinnitus: A functional MRI study. PLoS ONE, 7(5), e36222. https://doi.org/10.1371/journal.pone.0036222
Meng, Z., Zheng, Y., Liu, S., Wang, K., Kong, X., Tao, Y., Xu, K., & Liu, G. (2012). Reliability and validity of the chinese (mandarin) tinnitus handicap inventory. Clinical and Experimental Otorhinolaryngology, 5(1), 10–16. https://doi.org/10.3342/ceo.2012.5.1.10
Meyer, M., Neff, P., Liem, F., Kleinjung, T., Weidt, S., Langguth, B., & Schecklmann, M. (2016). Differential tinnitus-related neuroplastic alterations of cortical thickness and surface area. Hearing Research, 342, 1–12. https://doi.org/10.1016/j.heares.2016.08.016
Mirz, F., Pedersen, B., Ishizu, K., Johannsen, P., Ovesen, T., Stodkilde-Jorgensen, H., & Gjedde, A. (1999). Positron emission tomography of cortical centers of tinnitus. Hearing Research, 134(1–2), 133–144.
Møller, A. (2007). Tinnitus and pain. Progress in Brain Research, 166, 47–53. https://doi.org/10.1016/s0079-6123(07)66004-x
Navratilova, E., Xie, J., Okun, A., Qu, C., Eyde, N., Ci, S., Ossipov, H., King, T., Fields, H. L., & Porreca, F. (2012). Pain relief produces negative reinforcement through activation of mesolimbic reward-valuation circuitry. Proceedings of the National Academy of Sciences of the United States of America, 109(50), 20709–20713. https://doi.org/10.1073/pnas.1214605109
Ospina, J., Jalilianhasanpour, R., & Perez, D. (2019). The role of the anterior and midcingulate cortex in the neurobiology of functional neurologic disorder. Handbook of Clinical Neurology, 166, 267–279. https://doi.org/10.1016/b978-0-444-64196-0.00014-5
Petacchi, A., Laird, A. R., Fox, P. T., & Bower, J. M. (2005). Cerebellum and auditory function: An ALE meta-analysis of functional neuroimaging studies. Human Brain Mapping, 25(1), 118–128. https://doi.org/10.1002/hbm.20137
Rauschecker, J., Leaver, A., & Mühlau, M. J. N. (2010). Tuning out the noise: Limbic-auditory interactions in tinnitus. Neuron, 66(6), 819–826. https://doi.org/10.1016/j.neuron.2010.04.032
Rauschecker, J. P., May, E. S., Maudoux, A., & Ploner, M. (2015). Frontostriatal gating of tinnitus and chronic pain. Trends in Cognitive Sciences, 19(10), 567–578. https://doi.org/10.1016/j.tics.2015.08.002
Schmidt, S., Akrofi, K., Carpenter-Thompson, J., & Husain, F. (2013). Default mode, dorsal attention and auditory resting state networks exhibit differential functional connectivity in tinnitus and hearing loss. PLoS ONE, 8(10), e76488. https://doi.org/10.1371/journal.pone.0076488
Sommer, I., Diederen, K., Blom, J., Willems, A., Kushan, L., Slotema, K., Boks, M. P. M., Hoek, H. W., Neggers, S. F. W., Daalman, K., & Kahn, R. (2008). Auditory verbal hallucinations predominantly activate the right inferior frontal area. Brain, 131, 3169–3177. https://doi.org/10.1093/brain/awn251
Song, J., Vanneste, S., & De Ridder, D. (2015). Dysfunctional noise cancelling of the rostral anterior cingulate cortex in tinnitus patients. PLoS ONE, 10(4), e0123538. https://doi.org/10.1371/journal.pone.0123538
Takahashi, Y., Batchelor, H., Liu, B., Khanna, A., Morales, M., & Schoenbaum, G. J. N. (2017). Dopamine neurons respond to errors in the prediction of sensory features of expected rewards. Neuron, 95(6), 1395-1405.e1393. https://doi.org/10.1016/j.neuron.2017.08.025
Tsai, M., Cai, Y., Wang, C., Zheng, Y., Ou, J., & Chen, Y. (2018). Tinnitus abnormal brain region detection based on dynamic causal modeling and exponential ranking. BioMed Research International, 2018, 8656975. https://doi.org/10.1155/2018/8656975
Vanneste, S., Alsalman, O., & De Ridder, D. (2019). Top-down and bottom-up regulated auditory phantom perception. Journal of Neuroscience., 39(2), 364–378. https://doi.org/10.1523/jneurosci.0966-18.2018
Vogt, B. (2016). Midcingulate cortex: Structure, connections, homologies, functions and diseases. Journal of Chemical Neuroanatomy, 74, 28–46. https://doi.org/10.1016/j.jchemneu.2016.01.010
Weiler, E. W., Brill, K., Tachiki, K. H., & Wiegand, R. (2000). Electroencephalography correlates in tinnitus. The International Tinnitus Journal, 6(1), 21–24.
Yamasaki, H., LaBar, K. S., & McCarthy, G. (2002). Dissociable prefrontal brain systems for attention and emotion. Proceedings of the National Academy of Sciences of the United States of America, 99(17), 11447–11451. https://doi.org/10.1073/pnas.182176499
Yang, H., Cai, Y., Guo, H., Xiong, H., Sun, Y., Huang, X., & Zheng, Y. (2018). Prevalence and factors associated with tinnitus: Data from adult residents in Guangdong province, South of China. International Journal of Audiology, 57(12), 892–899. https://doi.org/10.1080/14992027.2018.1506169
Yu, E., Liao, Z., Mao, D., Zhang, Q., Ji, G., Li, Y., & Ding, Z. (2017). Directed functional connectivity of posterior cingulate cortex and whole brain in Alzheimer’s disease and mild cognitive impairment. Current Alzheimer Research, 14(6), 628–635. https://doi.org/10.2174/1567205013666161201201000
Zhou, G. P., Shi, X. Y., Wei, H. L., Qu, L. J., Yu, Y. S., Zhou, Q. Q., Yin, X., Zhang, H., & Tao, Y. J. (2019). Disrupted intraregional brain activity and functional connectivity in unilateral acute tinnitus patients with hearing loss. Frontiers in Neuroscience, 13, 1010. https://doi.org/10.3389/fnins.2019.01010
Zung, W. W. (1971). A rating instrument for anxiety disorders. Psychosomatics, 12(6), 371–379. https://doi.org/10.1016/s0033-3182(71)71479-0
Zung, W. W. K. (1986). Zung self-rating depression scale and depression status inventory. In N. Sartorius & T. A. Ban (Eds.), Assessment of depression (pp. 221–231). Springer.
Acknowledgements
None.
Funding
This work was supported by the Youth Medical Talents of Jiangsu Province (No. QNRC2016062), 14th “Six Talent Peaks” Project of Jiangsu Province (No. YY-079), Nanjing Outstanding Youth Fund (No. JQX17006), 333 High-level Talents Training Project of Jiangsu Province (No. BRA2019122), and Medical Science and Technology Development Foundation of Nanjing Department of Health (No. ZKX20037).
Author information
Authors and Affiliations
Contributions
Gang-Ping Zhou and Yu-Chen Chen designed the experiment, collected the data, performed the analysis, and wrote the manuscript. Wang-Wei Li, Heng-Le Wei, Yu-Sheng Yu, and Qing-Qing Zhou helped collect the data. Xindao Yin helped perform the analysis. Hong Zhang and Yue-Jin Tao contributed to the discussion and manuscript revision. All authors have read and approved the manuscript.
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare no conflict of interest.
Ethical approval
The present study was approved by the Research Ethics Committee of Nanjing Medical University.
Consent to participate
All subjects provided written informed consent prior to participation in the study.
Consent for publication
Written informed consent for publication was obtained from all participants.
Additional information
Publisher's note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Zhou, GP., Chen, YC., Li, WW. et al. Aberrant functional and effective connectivity of the frontostriatal network in unilateral acute tinnitus patients with hearing loss. Brain Imaging and Behavior 16, 151–160 (2022). https://doi.org/10.1007/s11682-021-00486-9
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11682-021-00486-9