This study aimed to investigate alterations in brain function among different subtypes of auditory hallucinations (AH) in drug-naïve first episode schizophrenia patients. We recruited 20 patients with drug-naïve first episode schizophrenia who had constant commanding and commenting auditory verbal hallucinations (CCCAVH), 15 drug-naïve first episode schizophrenia patients who had nonverbal auditory hallucinations (NVAH), and 20 healthy controls to participate in this study. We used global functional connectivity density (gFCD) and one-way analysis of covariance to characterize differences in brain function between the two patient groups. Statistical significance was set at P < 0.05. As compared to controls, schizophrenia patients with CCCAVH demonstrated increased gFCD in the right Broca’s area, bilateral superior temporal gyri, hippocampus, bilateral insula, and anterior cingulate gyri, and decreased gFCD in the left temporoparietal junction (family-wise error [FEW] correct, P < 0.05). Schizophrenia patients with NVAH demonstrated increased gFCD in the bilateral superior temporal gyri and most of the components of the default mode network (DMN), and decreased gFCD in components of the executive control network (FWE correct, P < 0.05). We found that schizophrenia patients with CCCAVH and NVAH have distinct functional brain patterns. The features observed in patients with CCCAVH are consistent with the “inner speech” hypothesis of AH. Features of patients with NVAH suggest hyperactivity of the superior temporal gyrus and DMN, and hypoactivity of the prefrontal lobe.
This is a preview of subscription content, log in to check access.
Buy single article
Instant unlimited access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Aas, I. H. M., Sonesson, O., & Torp, S. (2018). A qualitative study of clinicians experience with rating of the global assessment of functioning (GAF) scale. Community Mental Health Journal, 54(1), 107–116.
Catani, M., Craig, M. C., Forkel, S. J., Kanaan, R., Picchioni, M., Toulopoulou, T., et al. (2011). Altered integrity of perisylvian language pathways in schizophrenia: Relationship to auditory hallucinations. Biological Psychiatry, 70(12), 1143–1150.
Chang, X., Collin, G., Xi, Y., Cui, L., Scholtens, L. H., Sommer, I. E., et al. (2017). Resting-state functional connectivity in medication-naive schizophrenia patients with and without auditory verbal hallucinations: A preliminary report. Schizophrenia Research, 18875–18881.
Curcic-Blake, B., Ford, J. M., Hubl, D., Orlov, N. D., Sommer, I. E., Waters, F., et al. (2017). Interaction of language, auditory and memory brain networks in auditory verbal hallucinations. Progress in Neurobiology, 1481–1420.
de Boer, J. N., Linszen, M. M. J., de Vries, J., Schutte, M. J. L., Begemann, M. J. H., Heringa, S. M., et al. (2019). Auditory hallucinations, top-down processing and language perception: A general population study. Psychological Medicine, 1–9.
de Leede-Smith, S., & Barkus, E. (2013). A comprehensive review of auditory verbal hallucinations: Lifetime prevalence, correlates and mechanisms in healthy and clinical individuals. Frontiers in Human Neuroscience, 7367.
Gong, Q., Li, L., Du, M., Pettersson-Yeo, W., Crossley, N., Yang, X., Li, J., Huang, X., & Mechelli, A. (2014). Quantitative prediction of individual psychopathology in trauma survivors using resting-state FMRI. Neuropsychopharmacology, 39(3), 681–687.
Heckers, S. (2016). Studies of auditory verbal hallucinations. Psychophysiology, 53(3), 305–307.
Horga, G., Fernandez-Egea, E., Mane, A., Font, M., Schatz, K. C., Falcon, C., et al. (2014). Brain metabolism during hallucination-like auditory stimulation in schizophrenia. PLoS One, 9(1), e84987.
Jardri, R., Pouchet, A., Pins, D., & Thomas, P. (2011). Cortical activations during auditory verbal hallucinations in schizophrenia: A coordinate-based meta-analysis. The American Journal of Psychiatry, 168(1), 73–81.
Lang, X., Liu, H., Qin, W., Zhang, Y., Xuan, Y., & Yu, C. (2015). Brain functional connectivity density and individual fluid reasoning capacity in healthy young adults. Neuroreport, 26(1), 17–21.
Lui, S., Deng, W., Huang, X., Jiang, L., Ma, X., Chen, H., Zhang, T., Li, X., Li, D., Zou, L., Tang, H., Zhou, X. J., Mechelli, A., Collier, D. A., Sweeney, J. A., Li, T., & Gong, Q. (2009). Association of cerebral deficits with clinical symptoms in antipsychotic-naive first-episode schizophrenia: An optimized voxel-based morphometry and resting state functional connectivity study. The American Journal of Psychiatry, 166(2), 196–205.
Mallikarjun, P. K., Lalousis, P. A., Dunne, T. F., Heinze, K., Reniers, R. L., Broome, M. R., et al. (2018). Aberrant salience network functional connectivity in auditory verbal hallucinations: A first episode psychosis sample. Translational Psychiatry, 8(1), 69.
McCarthy-Jones, S., Trauer, T., Mackinnon, A., Sims, E., Thomas, N., & Copolov, D. L. (2014). A new phenomenological survey of auditory hallucinations: Evidence for subtypes and implications for theory and practice. Schizophrenia Bulletin, 40(1), 231–235.
Mondino, M., Poulet, E., Suaud-Chagny, M. F., & Brunelin, J. (2016). Anodal tDCS targeting the left temporo-parietal junction disrupts verbal reality-monitoring. Neuropsychologia, 89478–89484.
Moseley, P., Fernyhough, C., & Ellison, A. (2013). Auditory verbal hallucinations as atypical inner speech monitoring, and the potential of neurostimulation as a treatment option. Neuroscience and Biobehavioral Reviews, 37(10 Pt 2), 2794–2805.
Northoff, G. (2014). Are auditory hallucinations related to the Brain's resting state activity? A 'Neurophenomenal resting state hypothesis. Clinical Psychopharmacology and Neuroscience, 12(3), 189–195.
Northoff, G., & Qin, P. (2011). How can the brain's resting state activity generate hallucinations? A 'resting state hypothesis' of auditory verbal hallucinations. Schizophrenia Research, 127(1–3), 202–214.
O'Brien, J. M., Salowe, R. J., Fertig, R., Salinas, J., Pistilli, M., Sankar, P. S., et al. (2018). Family history in the primary open-angle African American Glaucoma genetics study cohort. American Journal of Ophthalmology, 192239–192247.
Pienkos, E., Giersch, A., Hansen, M., Humpston, C., McCarthy-Jones, S., Mishara, A., et al. (2019). Hallucinations beyond voices: A conceptual review of the phenomenology of altered perception in psychosis. Schizophrenia Bulletin, 45(45 Suppl 1), S67–S77.
Qin, W., Xuan, Y., Liu, Y., Jiang, T., & Yu, C. (2015). Functional connectivity density in congenitally and late blind subjects. Cerebral Cortex, 25(9), 2507–2516.
Scheinost, D., Tokoglu, F., Hampson, M., Hoffman, R., & Constable, R. T. (2019). Data-driven analysis of functional connectivity reveals a potential auditory verbal hallucination network. Schizophrenia Bulletin, 45(2), 415–424.
Simons, C. J., Tracy, D. K., Sanghera, K. K., O'Daly, O., Gilleen, J., Dominguez, M. D., et al. (2010). Functional magnetic resonance imaging of inner speech in schizophrenia. Biological Psychiatry, 67(3), 232–237.
Sommer, I. E., Daalman, K., Rietkerk, T., Diederen, K. M., Bakker, S., Wijkstra, J., et al. (2010). Healthy individuals with auditory verbal hallucinations; who are they? Psychiatric assessments of a selected sample of 103 subjects. Schizophrenia Bulletin, 36(3), 633–641.
Steinmann, S., Leicht, G., & Mulert, C. (2019). The interhemispheric miscommunication theory of auditory verbal hallucinations in schizophrenia. International Journal of Psychophysiology.
Thomas, N., Rossell, S. L., & Waters, F. (2016). The changing face of hallucination research: The international consortium on hallucination research (ICHR) 2015 meeting report. Schizophrenia Bulletin, 42(4), 891–895.
Thompson, G. J., Riedl, V., Grimmer, T., Drzezga, A., Herman, P., & Hyder, F. (2016). The whole-brain "global" signal from resting state fMRI as a potential biomarker of quantitative state changes in glucose metabolism. Brain Connectivity, 6(6), 435–447.
Tibber, M. S., Kirkbride, J. B., Joyce, E. M., Mutsatsa, S., Harrison, I., Barnes, T. R. E., et al. (2018). The component structure of the scales for the assessment of positive and negative symptoms in first-episode psychosis and its dependence on variations in analytic methods. Psychiatry Research, 270869–270879.
Tomasi, D., & Volkow, N. D. (2010). Functional connectivity density mapping. Proceedings of the National Academy of Sciences of the United States of America, 107(21), 9885–9890.
Upthegrove, R., Broome, M. R., Caldwell, K., Ives, J., Oyebode, F., & Wood, S. J. (2016). Understanding auditory verbal hallucinations: A systematic review of current evidence. Acta Psychiatrica Scandinavica, 133(5), 352–367.
Wahab, S., Zakaria, M. N., Sidek, D., Abdul Rahman, A. H., Shah, S. A., & Abdul Wahab, N. A. (2015). Evaluation of auditory hallucinations in patients with schizophrenia: A validation study of the Malay version of psychotic symptom rating scales (PSYRATS). Psychiatry Research, 228(3), 462–467.
Waters, F., Aleman, A., Fernyhough, C., & Allen, P. (2012). Report on the inaugural meeting of the international consortium on hallucination research: A clinical and research update and 16 consensus-set goals for future research. Schizophrenia Bulletin, 38(2), 258–262.
Waters, F., Woods, A., & Fernyhough, C. (2014). Report on the 2nd international consortium on hallucination research: Evolving directions and top-10 "hot spots" in hallucination research. Schizophrenia Bulletin, 40(1), 24–27.
Zhang, J., Wang, J., Wu, Q., Kuang, W., Huang, X., He, Y., & Gong, Q. (2011). Disrupted brain connectivity networks in drug-naive, first-episode major depressive disorder. Biological Psychiatry, 70(4), 334–342.
Zhang, B., Li, M., Qin, W., Demenescu, L. R., Metzger, C. D., Bogerts, B., et al. (2016). Altered functional connectivity density in major depressive disorder at rest. European Archives of Psychiatry and Clinical Neuroscience, 266(3), 239–248.
Zhao, Z., Li, X., Feng, G., Shen, Z., Li, S., Xu, Y., et al. (2018). Altered effective connectivity in the default network of the brains of first-episode, drug-naive schizophrenia patients with auditory verbal hallucinations. Frontiers in Human Neuroscience, 12456.
Zhuo, C., Zhu, J., Qin, W., Qu, H., Ma, X., Tian, H., et al. (2014). Functional connectivity density alterations in schizophrenia. Frontiers in Behavioral Neuroscience, 8404.
Zhuo, C., Zhu, J., Wang, C., Qu, H., Ma, X., & Qin, W. (2017). Different spatial patterns of brain atrophy and global functional connectivity impairments in major depressive disorder. Brain Imaging and Behavior, 11(6), 1678–1689.
This work was supported by grants from the National Natural Science Foundation of China (81871052 to C.Z., 81801679 and 81571319 to Y.X.), the Key Projects of the Natural Science Foundation of Tianjin, China (17JCZDJC35700 to C.Z.), the Tianjin Health Bureau Foundation (2014KR02 to C.Z.), the National Key Research and Development Program of China (2016YFC1307004 to Y.X.), the Shanxi Science and Technology Innovation Training Team’s Multidisciplinary Team for Cognitive Impairment (201705D131027 to Y.X.), Zhejiang Public Welfare Fund Project (LGF18H090002 to D.J), Tianjin Anding Hospital Outstanding Award rewarding 300000¥ to C.Z., and the key project of Wenzhou Science and Technology Bureau (ZS2017011 to X.L).
The authors declare that they have no conflicts of interest.
This study was approved by the Ethics Committee of Wenzhou Seventh People’s Hospital (No. ZS2017011), Tianjin Anding Hospital (No. TJMH-Cohort Study-004) and Jining Medical University (No. JM-Senior Professor Project-001). All procedures were in accordance with the ethics standards of the institutional and national research committee and the 1964 Helsinki Declaration and its later amendments or comparable ethics standards.
Written informed consent was obtained from all participants or their legal guardians included in the study.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Zhuo, C., Li, G., Ji, F. et al. Differences in functional connectivity density among subtypes of schizophrenic auditory hallucination. Brain Imaging and Behavior (2020) doi:10.1007/s11682-019-00210-8
- Auditory verbal hallucination
- Inner speech hypothesis
- Unstable DMN hypothesis