Decreased hemispheric connectivity and decreased intra- and inter- hemisphere asymmetry of resting state functional network connectivity in schizophrenia
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Many studies have shown that schizophrenia patients have aberrant functional network connectivity (FNC) among brain regions, suggesting schizophrenia manifests with significantly diminished (in majority of the cases) connectivity. Schizophrenia is also associated with a lack of hemispheric lateralization. Hoptman et al. (2012) reported lower inter-hemispheric connectivity in schizophrenia patients compared to controls using voxel-mirrored homotopic connectivity. In this study, we merge these two points of views together using a group independent component analysis (gICA)-based approach to generate hemisphere-specific timecourses and calculate intra-hemisphere and inter-hemisphere FNC on a resting state fMRI dataset consisting of age- and gender-balanced 151 schizophrenia patients and 163 healthy controls. We analyzed the group differences between patients and healthy controls in each type of FNC measures along with age and gender effects. The results reveal that FNC in schizophrenia patients shows less hemispheric asymmetry compared to that of the healthy controls. We also found a decrease in connectivity in all FNC types such as intra-left (L_FNC), intra-right (R_FNC) and inter-hemisphere (Inter_FNC) in the schizophrenia patients relative to healthy controls, but general patterns of connectivity were preserved in patients. Analyses of age and gender effects yielded results similar to those reported in whole brain FNC studies.
KeywordsFunctional network connectivity Laterality Schizophrenia Hemisphere Lateral connectivity Heterotopic connectivity Homotopic connectivity
This work was supported in part by NIH grants P20GM103472 and R01EB020407.
Compliance with ethical standards
This study was funded in part by NIH grants P20GM103472 and R01EB020407.
Conflict of interest
Author Oktay Agcaoglu, Author Robyn Miller, Author Eswar Damaraju, Author Barnaly Rashid, Author Juan Bustillo, Author Mustafa S. Cetin, Author Theo G.M. Van Erp, Author Sarah McEwen, Author Adrian Prada, Author Judith Ford, Author Dara S. Manoach, Author Kelvin O. Lim, Author Daniel H. Mathalon, Author Steven G. Potkin and Author Vince D. Calhoun declare that they have no conflict of interest.
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975 and the applicable revisions at the time of the investigation. Informed consent was obtained from all patients for being included in the study.
- Agcaoglu, O., Miller, R., Mayer, A. R., Hugdahl, K., & Calhoun, V. D. (2015). Increased spatial granularity of left brain activation and unique age/gender signatures: A 4D frequency domain approach to cerebral lateralization at rest. Brain Imaging and Behavior. doi: 10.1007/s11682-015-9463-8.CrossRefGoogle Scholar
- Broca, Paul. (1861). Sur le principe des localisations cerebrales. Bulletin de la Societe d"Anthropologie, 2, 190-204.Google Scholar
- Cai, Q., Van der Haegen, L., & Brysbaert, M. (2013). Complementary hemispheric specialization for language production and visuospatial attention. Proceedings of the National Academy of Sciences of the United States of America, 110(4), E322–E330. doi: 10.1073/pnas.1212956110.CrossRefPubMedPubMedCentralGoogle Scholar
- Cetin, M. S., Christensen, F., Abbott, C. C., Stephen, J. M., Mayer, A. R., Canive, J. M., ... Calhoun, V. D. (2014). Thalamus and posterior temporal lobe show greater inter-network connectivity at rest and across sensory paradigms in schizophrenia. Neuroimage, 97, 117-126. Doi: DOI 10.1016/j.neuroimage.2014.04.009
- Damaraju, E., Allen, E., & Calhoun, V. D. (2014a). Impact of head motion on ICA-derived functional connectivity measures. MA: Biennial Conference on Resting State / Brain Connectivity Boston.Google Scholar
- Damaraju, E., Allen, E. A., Belger, A., Ford, J. M., McEwen, S., Mathalon, D. H., et al. (2014b). Dynamic functional connectivity analysis reveals transient states of dysconnectivity in schizophrenia. Neuroimage-Clinical, 5, 298–308. doi: 10.1016/j.nicl.2014.07.003.CrossRefPubMedPubMedCentralGoogle Scholar
- Gotts, S. J., Jo, H. J., Wallace, G. L., Saad, Z. S., Cox, R. W., & Martin, A. (2013). Two distinct forms of functional lateralization in the human brain. Proceedings of the National Academy of Sciences of the United States of America, 110(36), E3435–E3444. doi: 10.1073/pnas.1302581110.CrossRefPubMedPubMedCentralGoogle Scholar
- Haijma, S. V., Van Haren, N., Cahn, W., Koolschijn, P. C. M. P., Hulshoff Pol, H. E., & Kahn, R. S. (2013). Brain Volumes in Schizophrenia: A Meta-Analysis in Over 18 000 Subjects. Schizophrenia Bulletin, 39(5), 1129–1138. doi; 10.1093/schbul/sbs118
- Hoptman, M. J., Zuo, X. N., D'Angelo, D., Mauro, C. J., Butler, P. D., Milham, M. P., & Javitt, D. C. (2012). Decreased interhemispheric coordination in schizophrenia: A resting state fMRI study. Schizophrenia Research, 141(1), 1–7. doi: 10.1016/j.schres.2012.07.027.CrossRefPubMedPubMedCentralGoogle Scholar
- Liu, H., Stufflebeam, S. M., Sepulcre, J., Hedden, T., & Buckner, R. L. (2009). Evidence from intrinsic activity that asymmetry of the human brain is controlled by multiple factors. Proceedings of the National Academy of Sciences of the United States of America, 106(48), 20499–20503. doi: 10.1073/pnas.0908073106.CrossRefPubMedPubMedCentralGoogle Scholar
- Mwansisya, T. E., Wang, Z., Tao, H., Zhang, H., Hu, A., Guo, S., & Liu, Z. (2013). The diminished interhemispheric connectivity correlates with negative symptoms and cognitive impairment in first-episode schizophrenia. Schizophrenia Research, 150(1), 144–150. doi: 10.1016/j.schres.2013.07.018.CrossRefPubMedGoogle Scholar
- Nielsen, J. A., Zielinski, B. A., Ferguson, M. A., Lainhart, J. E., & Anderson, J. S. (2013). An evaluation of the left-brain vs. right-brain hypothesis with resting state functional connectivity magnetic resonance imaging. PLoS One, 8(8), e71275. doi: 10.1371/journal.pone.0071275
- Oertel-Knochel, V., Knochel, C., Matura, S., Prvulovic, D., Linden, D. E., & van de Ven, V. (2013). Reduced functional connectivity and asymmetry of the planum temporale in patients with schizophrenia and first-degree relatives. Schizophrenia Research, 147(2–3), 331–338. doi: 10.1016/j.schres.2013.04.024.CrossRefPubMedGoogle Scholar
- Richard A.A. Kanaan, Jin-Suh Kim, Walter E. Kaufmann, Godfrey D. Pearlson, Gareth J. Barker, Philip K. McGuire, Diffusion Tensor Imaging in Schizophrenia, Biological Psychiatry, Volume 58, Issue 12, 15 December 2005, Pages 921-929, ISSN 0006-3223, doi : 10.1016/j.biopsych.2005.05.015
- Stark, D. E., Margulies, D. S., Shehzad, Z. E., Reiss, P., Kelly, A. M., Uddin, L. Q., et al. (2008). Regional variation in interhemispheric coordination of intrinsic hemodynamic fluctuations. The Journal of Neuroscience, 28(51), 13754–13764. doi: 10.1523/JNEUROSCI.4544-08.2008.CrossRefPubMedPubMedCentralGoogle Scholar
- Wernicke, C. (1874). Der aphasische Symptomencomplex. In Eine psychologische Studie auf anatomischer Basis. Breslau: M. Crohn und Weigert.Google Scholar
- Zuo, X. N., Kelly, C., Di Martino, A., Mennes, M., Margulies, D. S., Bangaru, S., et al. (2010). Growing together and growing apart: Regional and sex differences in the lifespan developmental trajectories of functional homotopy. The Journal of Neuroscience, 30(45), 15034–15043. doi: 10.1523/JNEUROSCI.2612-10.2010.CrossRefPubMedPubMedCentralGoogle Scholar