Share This Article:

Potential Biomarkers of Schizophrenia from MEG Resting-State Functional Connectivity Networks: Preliminary Data

Abstract Full-Text HTML XML Download Download as PDF (Size:2794KB) PP. 1-11
DOI: 10.4236/jbbs.2015.51001    3,678 Downloads   4,479 Views   Citations


Previous studies examining coherence and connectivity deviations in schizophrenia patients relied on standard coherence measures between recording sites (at the sensor level). A coherence source imaging (CSI) methodology where coherence is assessed within imaged brain structures (at the source level) was developed recently by our group and applied successfully for detecting coherent areas in the cortical networks of patients with epilepsy. We applied this Magnetoencephalography (MEG)-CSI technique to measure normal and pathological patterns of brain oscillations (biomarkers) in normal subjects and patients diagnosed with schizophrenia. Twelve patients diagnosed with schizophrenia and twelve healthy control subjects were studied. A ten-minute resting state MEG brain scan was performed with eyes open. MEG-CSI analysis was performed to identify the cortical areas that interacted strongly within the 3 - 50 Hz frequency range. Statistically significant increased regions of coherence were detected in schizophrenia patients compared to controls in the right inferior frontal gyrus (BA 47—pars orbitalis), left superior frontal gyrus (BA9— dorsolateral prefrontal cortex), right middle frontal gyrus (BA 10—anterior prefrontal cortex & BA 46—dorsolateral prefrontal cortex), and right cingulate gyrus (BA 24—ventral anterior cingulate cortex). These areas are involved in language, memory, decision making, empathy, executive and, higher cognitive functioning. We conclude that MEG-CSI can detect imaging biomarkers from resting state brain activity in schizophrenia patients that deviates from normal control subjects in several behaviorally salient brain regions. Analysis with MEG-CSI can provide biomarkers of abnormalities in the resting-state. The findings and procedures described can be used to probe the pathophysiology of schizophrenia and possibly detect subtypes.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Bowyer, S. , Gjini, K. , Zhu, X. , Kim, L. , Moran, J. , Rizvi, S. , Gumenyuk, V. , Tepley, N. and Boutros, N. (2015) Potential Biomarkers of Schizophrenia from MEG Resting-State Functional Connectivity Networks: Preliminary Data. Journal of Behavioral and Brain Science, 5, 1-11. doi: 10.4236/jbbs.2015.51001.


[1] Kurt, H., Dikmen, M., Basaran, A., Yenilmez, C., Ozdemir, F., Degirmenci, I., Gunes, H.V., Kucuk, M.U. and Mutlu, F. (2011) Dopamine D2 Receptor Gene-141C Insertion/Deletion Polymorphism in Turkish Schizophrenic Patients. Molecular Biology Reports, 38, 1407-1411.
[2] Barrett, E.A., Sundet, K., Faerden, A., Agartz, I., Bratlien, U., Romm, K.L., Mork, E., Rosberg, J.I., Steen, N.E., Andreassen, O.A. and Melle, I. (2010) Suicidality in First Episode Psychosis Is Associated with Insight and Negative Beliefs about Psychosis. Schizophrenia Research, 123, 257-262.
[3] Jepsen, J.R., Fagerlund, B., Pagsberg, A.K., Christensen, A.M., Nordentoft, M. and Mortensen, E.L. (2010) Deficient Maturation of Aspects of Attention and Executive Functions in Early Onset Schizophrenia. European Child & Adolescent Psychiatry, 19, 773-786.
[4] Voss, M., Moore, J., Hauser, M., Gallinat, J., Heinz, A. and Haggard, P. (2010) Altered Awareness of Action in Schizophrenia: A Specific Deficit in Predicting Action Consequences. Brain, 133, 3104-3112.
[5] Keshavan, M.S., Nasrallah, H.A. and Tandon, R. (2011) Schizophrenia, “Just the Facts” 6. Moving ahead with the Schizophrenia Concept: From the Elephant to the Mouse. Schizophrenia Research, 127, 3-13.
[6] Qi, Z., Miller, G. and Voit, E.O. (2010) The Neuregulin Signaling Pathway and Schizophrenia: From Genes to Synapses and Neural Circuits. Pharmacopsychiatry, 43, S50-S60.
[7] Hoffman, E.J. and State, M.W. (2010) Progress in Cytogenetics: Implications for Child Psychopathology. Journal of the American Academy of Child & Adolescent Psychiatry, 49, 736-751.
[8] Murray, R.M., Lappin, J. and Di Forti, M. (2008) Schizophrenia: From Developmental Deviance to Dopamine Dysregulation. European Neuropsychopharmacology, 18, S129-S134.
[9] Javitt, D.C. (2007) Glutamate and Schizophrenia: Phencyclidine, N-Methyl-D-Aspartate Receptors, and Dopamine- Glutamate Interactions. International Review Neurobiology, 78, 69-108.
[10] Ascher-Svanum, H., Zhu, B., Faries, D.E., Salkever, D., Slade, E.P., Peng, X. and Conley, R.R. (2010) The Cost of Relapse and the Predictors of Relapse in the Treatment of Schizophrenia. BMC Psychiatry, 10, 1-7.
[11] Knyazeva, M.G., Jalili, M., Meuli, R., Hasler, M., De Foe, O. and Do, K.Q. (2008) Alpha Rhythm and Hypofrontality in Schizophrenia. Acta Psychiatrica Scandinavica, 118, 188-199.
[12] Harris, A.W., Bahramali, H., Slewa-Younan, S., Gordon, E., Williams, L. and Li, W.M. (2001) The Topography of Quantified Electroencephalography in Three Syndromes of Schizophrenia. International Journal of Neuroscience, 107, 265-278.
[13] Boutros, N.N., Arfken, C., Galderisi, S., Warrick, J., Pratt, G. and Iacono, W. (2008) The Status of EEG Abnormality as a Diagnostic Test for Schizophrenia. Schizophrenia Research, 99, 225-237.
[14] Jalili, M., Lavoie, S., Deppen, P., Meuli, R., Do, K.Q., Cuenod, M., Hasler, M., De Feo, O. and Knyazeva, M.G. (2007) Dysconnection Topography in Schizophrenia Revealed with State-Space Analysis of EEG. PLOS One, 2, e1059.
[15] Raichle, M.E., MacLeod, M.A., Snyder, A.Z., Powers, W.J., Gusnard, D.A. and Shulman, G.L. (2001) A Default Mode of Brain Function. Proceedings of the National Academy of Sciences of the USA, 98, 676-682.
[16] Laufs, H. (2008) Endogenous Brain Oscillations and Related Networks Detected by Surface EEG-Combined fMRI. Human Brain Mapping, 29, 762-769.
[17] Fransson, P. (2006) How Default Is the Default Mode of Brain Function? Further Evidence from Intrinsic BOLD Signal Fluctuations. Neuropsychologia, 44, 2839-2845.
[18] Thomason, M.E., Chang, C.E., Glover, G.H., Gabrieli, J.D., Greicius, M.D. and Gotlib, I.H. (2008) Default-Mode Function and Task-Induced Deactivation Have Overlapping Brain Substrates in Children. NeuroImage, 41, 1493-1503.
[19] Pyka, M., Beckmann, C.F., Schoning, S., Hauke, S., Heider, D., Kugel, H., Arolt, V. and Konrad, C. (2009) Impact of Working Memory Load on fMRI Resting State Pattern in Subsequent Resting Phases. PLOS One, 4, e7198.
[20] Fox, M.D., Zhang, D., Snyder, A.Z. and Raichle, M.E. (2009) The Global Signal and Observed Anticorrelated Resting State Brain Networks. Journal Neurophysiology, 101, 3270-3283.
[21] Ongür, D., Lundy, M., Greenhouse, I., Shinn, A.K., Menon, V., Cohen, B.M. and Renshaw, P.F. (2010) Default Mode Network Abnormalities in Bipolar Disorder and Schizophrenia. Psychiatry Research, 183, 59-68.
[22] Tu, P.C., Lee, Y.C., Chen, Y.S., Li, C.T. and Su, T.P. (2013) Schizophrenia and the Brain’s Control Network: Aberrant within- and between-Network Connectivity of the Frontoparietal Network in Schizophrenia. Schizophrenia Research, 147, 339-347.
[23] Salmelin, R. and Kujala, J. (2006) Neural Representation of Language: Activation versus Long-Range Connectivity. Trends in Cognitive Sciences, 10, 519-525.
[24] Hamalainen, M., Hari, R., Ilmoniemi, J., Knuutila, J. and Lounamaa, O.V. (1993) Magnetoencephalography-Theory, Instrumentation and Applications to Noninvasive Studies of the Working Human Brain. Review of Modern Physics, 65, 413-497.
[25] Morika, T., Hayashib, M. and Hori, T. (1997) Auto Power and Coherence Analysis of Delta-Theta Band EEG during Waking-Sleeping Transition Period. Electroencephalography and Clinical Neurophysiology, 103, 633-641.
[26] Georgopoulos, A.P., Karageorgiou, E., Leuthold, A.C., Lewis, S.M., Lynch, J.K., Alonso, A.A., Aslam, Z., Carpenter, A.F., Georgopoulos, A., Hemmy, L.S., Koutlas, I.G., Langheim, F.J.P., McCarten, J.R., McPherson, S.E., Pardo, J.V., Pardo, P.J., Parry, G.J., Rottunda, S.J., Segal, B.M., Sponheim, S.R., Stanwyck, J.J., Stephane, M. and Westermeyer, J.J. (2007) Synchronous Neural Interactions Assessed by Magnetoencephalography: A Functional Biomarker for Brain Disorders. Journal of Neural Engineering, 4, 349-355.
[27] Fehr, T., Kissler, J., Wienbruch, C., Moratti, S., Elbert, T., Watzl, H. and Rockstroh, B. (2003) Source Distribution of Neuromagnetic Slow-Wave Activity in Schizophrenic Patients—Effects of Activation. Schizophrenia Research, 63, 63-71.
[28] Canive, J.M., Lewine, J.D., Edgar, J.C., Davis, J.T., Miller, G.A., Torres, F. and Tuason, V.B. (1998) Spontaneous Brain Magnetic Activity in Schizophrenia Patients Treated with Aripiprazole. Psychopharmacology Bulletin, 34, 101-105.
[29] Sperling, W., Vieth, J., Martus, M., Demling, J. and Barocka, A. (1999) Spontaneous Slow and Fast MEG Activity in Male Schizophrenics Treated with Clozapine. Psychopharmacology, 142, 375-382.
[30] Belardinelli, P., Ciancetta, L., Staudt, M., Pizzella, V., Londei, A., Birbaumer, N., Romani, G.L. and Braun, C. (2007) Cerebro-Muscular and Cerebro-Cerebral Coherence in Patients with pre- and Perinatally Acquired Unilateral Brain Lesions. NeuroImage, 37, 1301-1314.
[31] Hinkley, L.B., Vinogradov, S., Guggisberg, A.G., Fisher, M., Findlay, A.M. and Nagarajan, S.S. (2011) Clinical Symptoms and Alpha Band Resting-State Functional Connectivity Imaging in Patients with Schizophrenia: Implications for Novel Approaches to Treatment. Biological Psychiatry, 70, 1134-1142.
[32] Uhlhaas, P.J. and Singer, W. (2010) Abnormal Neural Oscillations and Synchrony in Schizophrenia. Natural Reviews Neuroscience, 11, 100-113.
[33] Rutter, L., Carver, F.W., Holroyd, T., Nadar, S.R., Mitchell-Francis, J., Apud, J., Weinberger, D.R. and Coppola, R. (2009) Magnetoencephalographic Gamma Power Reduction in Patients with Schizophrenia during Resting Condition. Human Brain Mapping, 30, 3254-3264.
[34] Moran, J.E., Bowyer, S. and Tepley, N. (2005) Multi-Resolution FOCUSS: A Source Imaging Technique Applied to MEG Data. Brain Topography, 18, 1-17.
[35] Moran, J.E., Drake, C.L. and Tepley, N. (2004) ICA Methods for MEG Imaging. Neurophysiology and Clinical Neurophysiology, 72.
[36] Elisevich, K., Shukla, N., Moran, J.E., Smith, B., Schultz, L., Mason, K., Barkley, G.L., Tepley, N., Gumenyuk, V. and Bowyer, S.M. (2011) An Assessment of MEG Coherence Imaging in the Study of Temporal Lobe Epilepsy. Epilepsia, 52, 1110-1119.
[37] de Pasquale, F., Penna, S.D., Snyder, A.Z., Lewis, C., Mantini, D., Marzetti, L., Belardinelli, P., Ciancetta, L., Pizzella, V. and Romani, G.L. (2010) Temporal Dynamics of Spontaneous MEG Activity in Brian Networks. Proceedings of the National Academy of Sciences of the United States of America, 107, 6040-6045.
[38] Bowyer, S.M., Mason, K., Tepley, N., Smith, B. and Barkley, G.L. (2003) Magnetoencephalographic Validation Parameters for Clinical Evaluation of Interictal Epileptic Activity. Journal of Clinical Neurophysiology, 20, 87-93.
[39] Moran, J. (2004) MEG Tools Software Program.
[40] Kim, J.S., Shin, K.S., Jung, W.H., Kim, S.N., Kwon, J.S. and Chung, C.K. (2014) Power Spectral Aspects of the Default Mode Network in Schizophrenia: An MEG Study. BMC Neuroscience, 15, 104.
[41] Menon, V. and Levitin, D. (2005) The Rewards of Music Listening: Response and Physiological Connectivity of the Mesolimbic System. NeuroImage, 28, 175-184.
[42] Ongür, D., Ferry, A.T. and Price, J.L. (2003) Architectonic Subdivision of the Human Orbital and Medial Prefrontal Cortex. Journal of Comparative Neurology, 460, 425-449.
[43] Ramnani, N. and Owen, A.M. (2004) Anterior Prefrontal Cortex: Insights into Function from Anatomy and Neuroimaging. Nature Reviews Neuroscience, 5, 184-194.
[44] Medford, N. and Critchley, H.D. (2010) Conjoint Activity of Anterior Insular and Anterior Cingulate Cortex: Awareness and Response. Brain Structure and Function, 214, 535-549.
[45] Raine, A. and Yang, Y. (2006) Neural Foundations to Moral Reasoning and Antisocial Behavior. Social Cognitive & Affective Neurosci, 1, 203-213.
[46] Peters, J. and Büchel, C. (2010) Neural Representations of Subjective Reward Value. Behavioural Brain Research, 213, 135-141.
[47] Shoeunbaum, G. and Esber, G.R. (2010) How Do You (Estimate You Will) Like Them Apples? Integration as Defining Trait of Orbitofrontal Function. Current Opinion in Neurobiology, 20, 205-211.
[48] Rosen, H.R. and Rich, B.A. (2010) Neurocognitive Correlates of Emotional Stimulus Processing in Pediatric Bipolar Disorder: A Review. Postgraduate Medicine, 122, 94-104.
[49] Sperling, W., Martus, P., Kober, H., Bleich, S. and Kornhuber, J. (2002) Spontaneous, Slow and Fast Magnetoencephalographic Activity in Patients with Schizophrenia. Schizophrenia Research, 58, 189-199.
[50] Mannell, M.V., Franco, A.R., Calhoun, V.D., Canive, J.M., Thoma, R.J. and Mayer, A.R. (2010) Resting State and Task-Induced Deactivation: A Methodological Comparison in Patients with Schizophrenia and Healthy Controls. Human Brain Mapping, 31, 424-437.
[51] Flor-Henry, P. (1990) Influence of Gender in Schizophrenia as Related to Other Psychopathological Syndromes. Schizophrenia Bulletin, 16, 211-227.
[52] Slewa-Younan, S., Gordon, E., Harris, A.W., Haig, A.R., Brown, K.J., Flor-Henry, P. and Williams, L.M. (2004) Sex Differences in Functional Connectivity in First-Episode and Chronic Schizophrenia Patients. American Journal of Psychiatry, 161, 1595-1602.

comments powered by Disqus

Copyright © 2018 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.