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. 2020 Aug 14;10(3):89.
doi: 10.3390/jpm10030089.

Resting-State Isolated Effective Connectivity of the Cingulate Cortex as a Neurophysiological Biomarker in Patients with Severe Treatment-Resistant Schizophrenia

Masataka Wada  1 , Shinichiro Nakajima  1 , Ryosuke Tarumi  1   2 , Fumi Masuda  1 , Takahiro Miyazaki  1 , Sakiko Tsugawa  1 , Kamiyu Ogyu  1 , Shiori Honda  3 , Karin Matsushita  4 , Yudai Kikuchi  4 , Shinya Fujii  4 , Daniel M Blumberger  5 , Zafiris J Daskalakis  5 , Masaru Mimura  1 , Yoshihiro Noda  1
Affiliations

Resting-State Isolated Effective Connectivity of the Cingulate Cortex as a Neurophysiological Biomarker in Patients with Severe Treatment-Resistant Schizophrenia

Masataka Wada et al. J Pers Med. .

Abstract

Background: The neural basis of treatment-resistant schizophrenia (TRS) remains unclear. Previous neuroimaging studies suggest that aberrant connectivity between the anterior cingulate cortex (ACC) and default mode network (DMN) may play a key role in the pathophysiology of TRS. Thus, we aimed to examine the connectivity between the ACC and posterior cingulate cortex (PCC), a hub of the DMN, computing isolated effective coherence (iCoh), which represents causal effective connectivity. Methods: Resting-state electroencephalogram with 19 channels was acquired from seventeen patients with TRS and thirty patients with non-TRS (nTRS). The iCoh values between the PCC and ACC were calculated using sLORETA software. We conducted four-way analyses of variance (ANOVAs) for iCoh values with group as a between-subject factor and frequency, directionality, and laterality as within-subject factors and post-hoc independent t-tests. Results: The ANOVA and post-hoc t-tests for the iCoh ratio of directionality from PCC to ACC showed significant findings in delta (t45 = 7.659, p = 0.008) and theta (t45 = 8.066, p = 0.007) bands in the left side (TRS < nTRS). Conclusion: Left delta and theta PCC and ACC iCoh ratio may represent a neurophysiological basis of TRS. Given the preliminary nature of this study, these results warrant further study to confirm the importance of iCoh as a clinical indicator for treatment-resistance.

Keywords: anterior cingulate cortex; causal effective connectivity; default mode network; isolated effective coherence; posterior cingulate cortex; resting-state electroencephalography; treatment-resistant schizophrenia.

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Conflict of interest statement

M.W., R.T., F.M., T.M., S.T., K.O., S.H., K.M., and Y.K. report no biomedical interests. S.N. has received fellowship grants from CIHR, Japan Research Foundation for Clinical Pharmacology, Naito Foundation, Takeda Science Foundation, Uehara Memorial Foundation, and Daiichi Sankyo Scholarship Donation Program within the past three years. S.N. has also received research supports, manuscript fees, or speaker’s honoraria from Dainippon Sumitomo Pharma, Meiji-Seika Pharma, Otsuka Pharmaceutical, Shionogi, and Yoshitomi Yakuhin within the past three years. Z.J.D. has received research and equipment in-kind support for an investigator-initiated study through Brainsway Inc and Magventure Inc. His work was supported by the Ontario Mental Health Foundation (OMHF), the Canadian Institutes of Health Research (CIHR), the National Institutes of Mental Health (NIMH), and the Temerty Family and Grant Family and through the Centre for Addiction and Mental Health (CAMH) Foundation and the Campbell Institute. M.M. has received research support from Japan Society for the Promotion of Science and grants or speaker’s honoraria from Daiichi Sankyo, Dainippon-Sumitomo Pharma, Eisai, Eli Lilly, Fuji Film RI Pharma, Janssen Pharmaceutical, Mochida Pharmaceutical, M.S.D., Nippon Chemipher, Novartis Pharma, Ono Yakuhin, Otsuka Pharmaceutical, Pfizer, Takeda Yakuhin, Tsumura, and Yoshitomi Yakuhin within the past three years. D.M.B. receives research support from the Canadian Institutes of Health Research (CIHR), National Institutes of Health—US (NIH), Weston Brain Institute, Brain Canada, and the Temerty Family through the CAMH Foundation and the Campbell Research Institute. He received research support and in-kind equipment support for an investigator-initiated study from Brainsway Ltd. and he is the site principal investigator for three sponsor-initiated studies for Brainsway Ltd. He received in-kind equipment support from Magventure for an investigator-initiated study. He received medication supplies for an investigator-initiated trial from Indivior. He has participated in an advisory board for Janssen. Y.N. has received a Grant-in-Aid for Young Scientists (KAKENHI), a research grant from Japan Agency for Medical Research and development (AMED), an investigator-initiated clinical study grant from TEIJIN PHARMA LIMITED. Y.N. also received research grants from Japan Health Foundation, Meiji Yasuda Mental Health Foundation, Mitsui Life Social Welfare Foundation, Takeda Science Foundation, SENSHIN Medical Research Foundation, Health Science Center Foundation, Mochida Memorial Foundation for Medical and Pharmaceutical Research, and Daiichi Sankyo Scholarship Donation Program. He has received research supports from Otsuka Pharmaceutical, Shionogi, and Meiji Seika Pharma. Y.N. also received equipment-in-kind supports for an investigator-initiated study from Magventure Inc., Inter Reha Co., Ltd., Rogue Resolutions Ltd., and Miyuki Giken Co., Ltd.

Figures

Figure 1
Figure 1
Schematics of the causal effective connectivity between the posterior cingulate cortex (PCC) and anterior cingulate cortex (ACC). In patients with treatment-resistant schizophrenia (TRS), the isolated effective coherence (iCoh) ratios [(PCC to ACC) − (ACC to PCC)]/[(PCC to ACC) + (ACC to PCC)] in delta and theta bands over the left side were significantly decreased compared with patients with non-TRS (nTRS).
Figure 2
Figure 2
The relationship between the iCho ratio for the left delta PCC–ACC connectivity and positive and negative syndrome scale (PANSS) total score. In patients with TRS, there is trend toward a relationship (r = 0.38, p = 0.069), but not for the nTRS group (r = −0.18, p = 0.17).
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References

    1. Hasan A., Falkai P., Wobrock T., Lieberman J., Glenthoj B., Gattaz W.F., Thibaut F., Möller H.-J. World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Schizophrenia, Part 1: Update 2012 on the acute treatment of schizophrenia and the management of treatment resistance. World J. Biol. Psychiatry. 2012;13:318–378. doi: 10.3109/15622975.2012.696143. - DOI - PubMed
    1. Samara M.T., Dold M., Gianatsi M., Nikolakopoulou A., Helfer B., Salanti G., Leucht S. Efficacy, Acceptability, and Tolerability of Antipsychotics in Treatment-Resistant Schizophrenia: A network meta-analysis. JAMA Psychiatry. 2016;73:199. doi: 10.1001/jamapsychiatry.2015.2955. - DOI - PubMed
    1. Nakajima S., Takeuchi H., Plitman E., Fervaha G., Gerretsen P., Caravaggio F., Chung J.K., Iwata Y., Remington G., Graff-Guerrero A. Neuroimaging findings in treatment-resistant schizophrenia: A systematic review: Lack of neuroimaging correlates of treatment-resistant schizophrenia. Schizophr. Res. 2015;164:164–175. doi: 10.1016/j.schres.2015.01.043. - DOI - PMC - PubMed
    1. Carter C.S., Macdonald A., Ross L.L., Stenger V.A. Anterior Cingulate Cortex Activity and Impaired Self-Monitoring of Performance in Patients with Schizophrenia: An Event-Related fMRI Study. Am. J. Psychiatry. 2001;158:1423–1428. doi: 10.1176/appi.ajp.158.9.1423. - DOI - PubMed
    1. Walter H., Ciaramidaro A., Adenzato M., Vasic N., Ardito R.B., Erk S., Bara B.G. Dysfunction of the social brain in schizophrenia is modulated by intention type: An fMRI study. Soc. Cogn. Affect. Neurosci. 2009;4:166–176. doi: 10.1093/scan/nsn047. - DOI - PMC - PubMed

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