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Anterior cingulate glutamate levels associate with functional activation and connectivity during sensory integration in schizophrenia: a multimodal 1H-MRS and fMRI study

Published online by Cambridge University Press:  06 July 2022

Xin-lu Cai
Neuropsychology and Applied Cognitive Neuroscience Laboratory, CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China Sino-Danish College, University of Chinese Academy of Sciences, Beijing, China Sino-Danish Centre for Education and Research, Beijing, China
Cheng-cheng Pu
Peking University Sixth Hospital, Peking University Institute of Mental Health, Beijing, China NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China
Shu-zhe Zhou
Peking University Sixth Hospital, Peking University Institute of Mental Health, Beijing, China NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China
Yi Wang
Neuropsychology and Applied Cognitive Neuroscience Laboratory, CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China Department of Psychology, University of Chinese Academy of Sciences, Beijing, China
Jia Huang
Neuropsychology and Applied Cognitive Neuroscience Laboratory, CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China Department of Psychology, University of Chinese Academy of Sciences, Beijing, China
Simon S. Y. Lui
Department of Psychiatry, School of Clinical Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China
Arne Møller
Sino-Danish College, University of Chinese Academy of Sciences, Beijing, China Sino-Danish Centre for Education and Research, Beijing, China Centre of Functionally Integrative Neuroscience, Aarhus University, Aarhus, Denmark Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark
Eric F. C. Cheung
Castle Peak Hospital, Hong Kong Special Administrative Region, China
Kristoffer H. Madsen
Sino-Danish Centre for Education and Research, Beijing, China Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Amager and Hvidovre, Denmark Department of Applied Mathematics and Computer Science, Technical University of Denmark, Kongens Lyngby, Denmark
Rong Xue
Sino-Danish College, University of Chinese Academy of Sciences, Beijing, China Sino-Danish Centre for Education and Research, Beijing, China State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China Beijing Institute for Brain Disorders, Beijing, China
Xin Yu
Peking University Sixth Hospital, Peking University Institute of Mental Health, Beijing, China NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China
Raymond C. K. Chan*
Neuropsychology and Applied Cognitive Neuroscience Laboratory, CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China Sino-Danish College, University of Chinese Academy of Sciences, Beijing, China Sino-Danish Centre for Education and Research, Beijing, China Department of Psychology, University of Chinese Academy of Sciences, Beijing, China Department of Diagnostic Radiology, the University of Hong Kong, Hong Kong Special Administrative Region, China
Author for correspondence: Raymond C. K. Chan, E-mail:



Glutamatergic dysfunction has been implicated in sensory integration deficits in schizophrenia, yet how glutamatergic function contributes to behavioural impairments and neural activities of sensory integration remains unknown.


Fifty schizophrenia patients and 43 healthy controls completed behavioural assessments for sensory integration and underwent magnetic resonance spectroscopy (MRS) for measuring the anterior cingulate cortex (ACC) glutamate levels. The correlation between glutamate levels and behavioural sensory integration deficits was examined in each group. A subsample of 20 pairs of patients and controls further completed an audiovisual sensory integration functional magnetic resonance imaging (fMRI) task. Blood Oxygenation Level Dependent (BOLD) activation and task-dependent functional connectivity (FC) were assessed based on fMRI data. Full factorial analyses were performed to examine the Group-by-Glutamate Level interaction effects on fMRI measurements (group differences in correlation between glutamate levels and fMRI measurements) and the correlation between glutamate levels and fMRI measurements within each group.


We found that schizophrenia patients exhibited impaired sensory integration which was positively correlated with ACC glutamate levels. Multimodal analyses showed significantly Group-by-Glutamate Level interaction effects on BOLD activation as well as task-dependent FC in a ‘cortico-subcortical-cortical’ network (including medial frontal gyrus, precuneus, ACC, middle cingulate gyrus, thalamus and caudate) with positive correlations in patients and negative in controls.


Our findings indicate that ACC glutamate influences neural activities in a large-scale network during sensory integration, but the effects have opposite directionality between schizophrenia patients and healthy people. This implicates the crucial role of glutamatergic system in sensory integration processing in schizophrenia.

Original Article
Copyright © The Author(s), 2022. Published by Cambridge University Press

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Balu, D. T. (2016). The NMDA receptor and schizophrenia: From pathophysiology to treatment. Advances in Pharmacology, 76, 351382. doi: 10.1016/bs.apha.2016.01.006CrossRefGoogle ScholarPubMed
Baumann, O., Vromen, J., Cheung, A., McFadyen, J., Ren, Y., & Guo, C. C. (2018). Neural correlates of temporal complexity and synchrony during audiovisual correspondence detection. eNeuro, 5(1), ENEURO.0294-17.2018. doi: 10.1523/ENEURO.0294-17.2018.CrossRefGoogle ScholarPubMed
Benes, F. M., Sorensen, I., Vincent, S. L., Bird, E. D., & Sathi, M. (1992). Increased density of glutamate-immunoreactive vertical processes in superficial laminae in cingulate cortex of schizophrenic brain. Cerebral Cortex, 2(6), 503512. doi: 10.1093/cercor/2.6.503CrossRefGoogle ScholarPubMed
Binder, M. (2015). Neural correlates of audiovisual temporal processing--comparison of temporal order and simultaneity judgments. Neuroscience, 300, 432447. doi: 10.1016/j.neuroscience.2015.05.011CrossRefGoogle ScholarPubMed
Bojesen, K. B., Broberg, B. V., Fagerlund, B., Jessen, K., Thomas, M. B., Sigvard, A., … Glenthøj, B. Y. (2021). Associations between cognitive function and levels of glutamatergic metabolites and gamma-aminobutyric acid in antipsychotic- naïve patients with schizophrenia or psychosis. Biological Psychiatry, 89(3), 278287. doi: 10.1016/j.biopsych.2020.06.027CrossRefGoogle ScholarPubMed
Bombin, I., Arango, C., & Buchanan, R. W. (2005). Significance and meaning of neurological signs in schizophrenia: Two decades later. Schizophrenia Bulletin, 31(4), 962977. doi: 10.1093/schbul/sbi028CrossRefGoogle ScholarPubMed
Brandt, A. S., Unschuld, P. G., Pradhan, S., Lim, I. A., Churchill, G., Harris, A. D., … Margolis, R. L. (2016). Age-related changes in anterior cingulate cortex glutamate in schizophrenia: A (1)H MRS study at 7 tesla. Schizophrenia Research, 172(1–3), 101105. doi: 10.1016/j.schres.2016.02.017CrossRefGoogle ScholarPubMed
Cadena, E. J., White, D. M., Kraguljac, N. V., Reid, M. A., Maximo, J. O., Nelson, E. A., … Lahti, A. C. (2018). A longitudinal multimodal neuroimaging study to examine relationships between resting state glutamate and task related BOLD response in schizophrenia. Frontiers in Psychiatry, 9, 632. doi: 10.3389/fpsyt.2018.00632CrossRefGoogle ScholarPubMed
Cappe, C., Morel, A., Barone, P., & Rouiller, E. M. (2009). The thalamocortical projection systems in primate: An anatomical support for multisensory and sensorimotor interplay. Cerebral Cortex, 19(9), 20252037. doi: 10.1093/cercor/bhn228CrossRefGoogle ScholarPubMed
Carli, M., Calcagno, E., Mainolfi, P., Mainini, E., & Invernizzi, R. W. (2011). Effects of aripiprazole, olanzapine, and haloperidol in a model of cognitive deficit of schizophrenia in rats: Relationship with glutamate release in the medial prefrontal cortex. Psychopharmacology (Berl), 214(3), 639652. doi: 10.1007/s00213-010-2065-7CrossRefGoogle Scholar
Cavanna, A. E., & Trimble, M. R. (2006). The precuneus: A review of its functional anatomy and behavioural correlates. Brain: A Journal of Neurology, 129(Pt 3), 564583. doi: 10.1093/brain/awl004CrossRefGoogle ScholarPubMed
Chan, R. C., & Gottesman, I. I. (2008). Neurological soft signs as candidate endophenotypes for schizophrenia: A shooting star or a Northern star? Neuroscience and Biobehavioral Reviews, 32(5), 957971. doi: 10.1016/j.neubiorev.2008.01.005CrossRefGoogle ScholarPubMed
Chan, R. C., Wang, Y., Wang, L., Chen, E. Y., Manschreck, T. C., Li, Z. J., … Gong, Q. Y. (2009). Neurological soft signs and their relationships to neurocognitive functions: A re-visit with the structural equation modeling design. PLoS One, 4(12), e8469. doi: 10.1371/journal.pone.0008469CrossRefGoogle ScholarPubMed
Chan, R. C., Xie, W., Geng, F. L., Wang, Y., Lui, S. S., Wang, C. Y., … Rosenthal, R. (2016). Clinical utility and lifespan profiling of neurological soft signs in schizophrenia spectrum disorders. Schizophrenia Bulletin, 42(3), 560570. doi: 10.1093/schbul/sbv196CrossRefGoogle ScholarPubMed
Chan, R. C., Xu, T., Heinrichs, R. W., Yu, Y., & Wang, Y. (2010). Neurological soft signs in schizophrenia: A meta-analysis. Schizophrenia Bulletin, 36(6), 10891104. doi: 10.1093/schbul/sbp011CrossRefGoogle ScholarPubMed
Chandrasekaran, C., & Ghazanfar, A. A. (2009). Different neural frequency bands integrate faces and voices differently in the superior temporal sulcus. Journal of Neurophysiology, 101(2), 773788. doi: 10.1152/jn.90843.2008CrossRefGoogle ScholarPubMed
Chen, E. Y., Shapleske, J., Luque, R., McKenna, P. J., Hodges, J. R., Calloway, S. P., … Berrios, G. E. (1995). The Cambridge Neurological Inventory: A clinical instrument for assessment of soft neurological signs in psychiatric patients. Psychiatry Research, 56(2), 183204.10.1016/0165-1781(95)02535-2CrossRefGoogle ScholarPubMed
Cloke, J. M., Nguyen, R., Chung, B. Y., Wasserman, D. I., De Lisio, S., Kim, J. C., … Winters, B. D. (2016). A novel multisensory integration task reveals robust deficits in rodent models of schizophrenia: Converging evidence for remediation via nicotinic receptor stimulation of inhibitory transmission in the prefrontal Cortex. The Journal of Neuroscience : the official journal of the Society for Neuroscience, 36(50), 1257012585. doi: 10.1523/JNEUROSCI.1628-16.2016CrossRefGoogle ScholarPubMed
Cloke, J. M., & Winters, B. D. (2015). α4β2 nicotinic receptor stimulation of the GABAergic system within the orbitofrontal cortex ameliorates the severe crossmodal object recognition impairment in ketamine-treated rats: Implications for cognitive dysfunction in schizophrenia. Neuropharmacology, 90, 4252. doi: 10.1016/j.neuropharm.2014.11.004CrossRefGoogle ScholarPubMed
Cohen, P., West, S. G., & Aiken, L. S. (2014). Applied multiple regression/correlation analysis for the behavioral sciences. New York: Psychology Press.10.4324/9781410606266CrossRefGoogle Scholar
De Gelder, B., & Bertelson, P. (2003). Multisensory integration, perception and ecological validity. Trends in Cognitive Sciences, 7(10), 460467. doi: 10.1016/j.tics.2003.08.014CrossRefGoogle ScholarPubMed
de Gelder, B., Vroomen, J., Annen, L., Masthof, E., & Hodiamont, P. (2003). Audio-visual integration in schizophrenia. Schizophrenia Research, 59(2–3), 211218. doi: 10.1016/s0920-9964(01)00344-9CrossRefGoogle ScholarPubMed
de Jong, J. J., Hodiamont, P. P., Van den Stock, J., & de Gelder, B. (2009). Audiovisual emotion recognition in schizophrenia: Reduced integration of facial and vocal affect. Schizophrenia Research, 107(2–3), 286293. doi: 10.1016/j.schres.2008.10.001CrossRefGoogle ScholarPubMed
de la Fuente-Sandoval, C., Leon-Ortiz, P., Azcarraga, M., Stephano, S., Favila, R., Diaz-Galvis, L., … Graff-Guerrero, A. (2013). Glutamate levels in the associative striatum before and after 4 weeks of antipsychotic treatment in first-episode psychosis: A longitudinal proton magnetic resonance spectroscopy study. JAMA Psychiatry, 70(10), 10571066. doi: 10.1001/jamapsychiatry.2013.289CrossRefGoogle ScholarPubMed
Erickson, L. C., Heeg, E., Rauschecker, J. P., & Turkeltaub, P. E. (2014). An ALE meta-analysis on the audiovisual integration of speech signals. Human Brain Mapping, 35(11), 55875605. doi: 10.1002/hbm.22572CrossRefGoogle ScholarPubMed
Falkenberg, L. E., Westerhausen, R., Craven, A. R., Johnsen, E., Kroken, R. A., Em, L. B., … Hugdahl, K. (2014). Impact of glutamate levels on neuronal response and cognitive abilities in schizophrenia. NeuroImage. Clinical, 4, 576584. doi: 10.1016/j.nicl.2014.03.014CrossRefGoogle ScholarPubMed
Friston, K. J., Buechel, C., Fink, G. R., Morris, J., Rolls, E., & Dolan, R. J. (1997). Psychophysiological and modulatory interactions in neuroimaging. NeuroImage, 6(3), 218229. doi: 10.1006/nimg.1997.0291CrossRefGoogle ScholarPubMed
Fusar-Poli, P., Broome, M. R., Matthiasson, P., Williams, S. C., Brammer, M., & McGuire, P. K. (2007). Effects of acute antipsychotic treatment on brain activation in first episode psychosis: An fMRI study. European Neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 17(6–7), 492500. doi: 10.1016/j.euroneuro.2007.01.003CrossRefGoogle ScholarPubMed
Gao, C., Weber, C. E., & Shinkareva, S. V. (2019). The brain basis of audiovisual affective processing: Evidence from a coordinate-based activation likelihood estimation meta-analysis. Cortex; a Journal Devoted to the Study of the Nervous System and Behavior, 120, 6677. doi: 10.1016/j.cortex.2019.05.016CrossRefGoogle ScholarPubMed
Gau, R., Bazin, P. L., Trampel, R., Turner, R., & Noppeney, U. (2020). Resolving multisensory and attentional influences across cortical depth in sensory cortices. eLife, 9, e46856. doi: 10.7554/eLife.46856CrossRefGoogle ScholarPubMed
Gottesman, I. I., & Gould, T. D. (2003). The endophenotype concept in psychiatry: Etymology and strategic intentions. American Journal of Psychiatry, 160(4), 636645. doi: 10.1176/appi.ajp.160.4.636CrossRefGoogle ScholarPubMed
Heinrichs, D. W., & Buchanan, R. W. (1988). Significance and meaning of neurological signs in schizophrenia. American journal of Psychiatry, 145(1), 1118. doi: 10.1176/ajp.145.1.11Google ScholarPubMed
Huang, J., Reinders, A., Wang, Y., Xu, T., Zeng, Y. W., Li, K., … Dazzan, P. (2018). Neural correlates of audiovisual sensory integration. Neuropsychology, 32(3), 329336. doi: 10.1037/neu0000393CrossRefGoogle ScholarPubMed
Iwata, Y., Nakajima, S., Plitman, E., Mihashi, Y., Caravaggio, F., Chung, J. K., … Graff-Guerrero, A. (2018). Neurometabolite levels in antipsychotic-naive/free patients with schizophrenia: A systematic review and meta-analysis of 1H-MRS studies. Progress in Neuro-psychopharmacology & Biological Psychiatry, 86, 340352. doi: 10.1016/j.pnpbp.2018.03.016CrossRefGoogle Scholar
Jacklin, D. L., Goel, A., Clementino, K. J., Hall, A. W., Talpos, J. C., & Winters, B. D. (2012). Severe cross-modal object recognition deficits in rats treated sub-chronically with NMDA receptor antagonists are reversed by systemic nicotine: Implications for abnormal multisensory integration in schizophrenia. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 37(10), 23222331. doi: 10.1038/npp.2012.84CrossRefGoogle ScholarPubMed
Javitt, D. C., Carter, C. S., Krystal, J. H., Kantrowitz, J. T., Girgis, R. R., Kegeles, L. S., … Lieberman, J. A. (2018). Utility of imaging-based biomarkers for glutamate-targeted drug development in psychotic disorders: A randomized clinical trial. JAMA Psychiatry, 75(1), 1119. doi: 10.1001/jamapsychiatry.2017.3572CrossRefGoogle ScholarPubMed
Javitt, D. C., Zukin, S. R., Heresco-Levy, U., & Umbricht, D. (2012). Has an angel shown the way? Etiological and therapeutic implications of the PCP/NMDA model of schizophrenia. Schizophrenia Bulletin, 38(5), 958966. doi: 10.1093/schbul/sbs069CrossRefGoogle Scholar
Kaminski, J., Mascarell-Maricic, L., Fukuda, Y., Katthagen, T., Heinz, A., & Schlagenhauf, F. (2021). Glutamate in the dorsolateral prefrontal cortex in patients with schizophrenia: A meta-analysis of 1H-magnetic resonance spectroscopy studies. Biological Psychiatry, 89(3), 270277. doi: 10.1016/j.biopsych.2020.09.001CrossRefGoogle Scholar
Kegeles, L. S., Mao, X., Stanford, A. D., Girgis, R., Ojeil, N., Xu, X., … Shungu, D. C. (2012). Elevated prefrontal cortex gamma-aminobutyric acid and glutamate-glutamine levels in schizophrenia measured in vivo with proton magnetic resonance spectroscopy. Archives of General Psychiatry, 69(5), 449459. doi: 10.1001/archgenpsychiatry.2011.1519Google ScholarPubMed
Komura, Y., Tamura, R., Uwano, T., Nishijo, H., & Ono, T. (2005). Auditory thalamus integrates visual inputs into behavioral gains. Nature Neuroscience, 8(9), 12031209. doi: 10.1038/nn1528CrossRefGoogle ScholarPubMed
Kreifelts, B., Ethofer, T., Grodd, W., Erb, M., & Wildgruber, D. (2007). Audiovisual integration of emotional signals in voice and face: An event-related fMRI study. NeuroImage, 37(4), 14451456. doi: 10.1016/j.neuroimage.2007.06.020CrossRefGoogle ScholarPubMed
Leminen, A., Verwoert, M., Moisala, M., Salmela, V., Wikman, P., & Alho, K. (2020). Modulation of brain activity by selective attention to audiovisual dialogues. Frontiers in Neuroscience, 14, 436. doi: 10.3389/fnins.2020.00436CrossRefGoogle ScholarPubMed
Li, Z., Huang, J., Xu, T., Wang, Y., Li, K., Zeng, Y. W., … Chan, R. C. K. (2018). Neural mechanism and heritability of complex motor sequence and audiovisual integration: A healthy twin study. Human Brain Mapping, 39(3), 14381448. doi: 10.1002/hbm.23935CrossRefGoogle ScholarPubMed
Lin, C. H., Lane, H. Y., & Tsai, G. E. (2012). Glutamate signaling in the pathophysiology and therapy of schizophrenia. Pharmacology, Biochemistry, and Behavior, 100(4), 665677. doi: 10.1016/j.pbb.2011.03.023CrossRefGoogle ScholarPubMed
Marsman, A., van den Heuvel, M. P., Klomp, D. W., Kahn, R. S., Luijten, P. R., & Hulshoff Pol, H. E. (2013). Glutamate in schizophrenia: A focused review and meta-analysis of (1)H-MRS studies. Schizophrenia Bulletin, 39(1), 120129. doi: 10.1093/schbul/sbr069CrossRefGoogle Scholar
Mayer, A. R., Hanlon, F. M., Teshiba, T. M., Klimaj, S. D., Ling, J. M., Dodd, A. B., … Toulouse, T. (2015). An fMRI study of multimodal selective attention in schizophrenia. The British Journal of Psychiatry: The Journal of Mental Science, 207(5), 420428. doi: 10.1192/bjp.bp.114.155499CrossRefGoogle ScholarPubMed
Mayer, A. R., Ryman, S. G., Hanlon, F. M., Dodd, A. B., & Ling, J. M. (2017). Look hear! The prefrontal Cortex is stratified by modality of sensory input during multisensory cognitive control. Cerebral Cortex, 27(5), 28312840. doi: 10.1093/cercor/bhw131Google ScholarPubMed
Menon, V. (2011). Large-scale brain networks and psychopathology: A unifying triple network model. Trends in Cognitive Sciences, 15(10), 483506. doi: 10.1016/j.tics.2011.08.003CrossRefGoogle ScholarPubMed
Meredith, M. A., & Stein, B. E. (1986). Visual, auditory, and somatosensory convergence on cells in superior colliculus results in multisensory integration. Journal of Neurophysiology, 56(3), 640662. doi: 10.1152/jn.1986.56.3.640CrossRefGoogle ScholarPubMed
Merritt, K., Egerton, A., Kempton, M. J., Taylor, M. J., & McGuire, P. K. (2016). Nature of glutamate alterations in schizophrenia A meta-analysis of proton magnetic resonance spectroscopy studies. JAMA Psychiatry, 73(7), 665674. doi: 10.1001/jamapsychiatry.2016.0442CrossRefGoogle ScholarPubMed
Merritt, K., McGuire, P. K., Egerton, A., Investigators, H. M. I. S., Aleman, A., Block, W., … Yamasue, H. (2021). Association of age, antipsychotic medication, and symptom severity in schizophrenia with proton magnetic resonance spectroscopy brain glutamate level: A mega-analysis of individual participant-level data. JAMA Psychiatry, 78(6), 667681. doi: 10.1001/jamapsychiatry.2021.0380CrossRefGoogle Scholar
Mihalik, A., & Noppeney, U. (2020). Causal inference in audiovisual perception. The Journal of Neuroscience: The official journal of the Society for Neuroscience, 40(34), 66006612. doi: 10.1523/JNEUROSCI.0051-20.2020CrossRefGoogle ScholarPubMed
Modinos, G., McLaughlin, A., Egerton, A., McMullen, K., Kumari, V., Barker, G. J., … Williams, S. C. (2017). Corticolimbic hyper-response to emotion and glutamatergic function in people with high schizotypy: A multimodal fMRI-MRS study. Translational Psychiatry, 7(4), e1083. doi: 10.1038/tp.2017.53.CrossRefGoogle ScholarPubMed
Moghaddam, B., Adams, B., Verma, A., & Daly, D. (1997). Activation of glutamatergic neurotransmission by ketamine: A novel step in the pathway from NMDA receptor blockade to dopaminergic and cognitive disruptions associated with the prefrontal cortex. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 17(8), 29212927.10.1523/JNEUROSCI.17-08-02921.1997CrossRefGoogle ScholarPubMed
Nagy, A., Eordegh, G., Paroczy, Z., Markus, Z., & Benedek, G. (2006). Multisensory integration in the basal ganglia. The European Journal of Neuroscience, 24(3), 917924. doi: 10.1111/j.1460-9568.2006.04942.xCrossRefGoogle ScholarPubMed
Nakahara, T., Tsugawa, S., Noda, Y., Ueno, F., Honda, S., Kinjo, M., … Nakajima, S. (2022). Glutamatergic and GABAergic metabolite levels in schizophrenia-spectrum disorders: A meta-analysis of 1H-magnetic resonance spectroscopy studies. Molecular Psychiatry, 27(1), 744757. doi: 10.1038/s41380-021-01297-6CrossRefGoogle Scholar
Overbeek, G., Gawne, T. J., Reid, M. A., Salibi, N., Kraguljac, N. V., White, D. M., & Lahti, A. C. (2019). Relationship between cortical excitation and inhibition and task-induced activation and deactivation: A combined magnetic resonance spectroscopy and functional magnetic resonance imaging study at 7 T in first-episode psychosis. Biological Psychiatry. Cognitive Neuroscience and Neuroimaging, 4(2), 121130. doi: 10.1016/j.bpsc.2018.10.002CrossRefGoogle Scholar
Peters, S. K., Dunlop, K., & Downar, J. (2016). Cortico-Striatal-Thalamic loop circuits of the salience network: A central pathway in psychiatric disease and treatment. Frontiers in Systems Neuroscience, 10, 104. doi: 10.3389/fnsys.2016.00104CrossRefGoogle ScholarPubMed
Radua, J., Borgwardt, S., Crescini, A., Mataix-Cols, D., Meyer-Lindenberg, A., McGuire, P. K., & Fusar-Poli, P. (2012). Multimodal meta-analysis of structural and functional brain changes in first episode psychosis and the effects of antipsychotic medication. Neuroscience and Biobehavioral Reviews, 36(10), 23252333. doi: 10.1016/j.neubiorev.2012.07.012CrossRefGoogle ScholarPubMed
Reig, R., & Silberberg, G. (2014). Multisensory integration in the mouse striatum. Neuron, 83(5), 12001212. doi: 10.1016/j.neuron.2014.07.033CrossRefGoogle ScholarPubMed
Ross, L. A., Saint-Amour, D., Leavitt, V. M., Molholm, S., Javitt, D. C., & Foxe, J. J. (2007). Impaired multisensory processing in schizophrenia: Deficits in the visual enhancement of speech comprehension under noisy environmental conditions. Schizophrenia Research, 97(1–3), 173183. doi: 10.1016/j.schres.2007.08.008CrossRefGoogle ScholarPubMed
Rothman, D. L., Behar, K. L., Hyder, F., & Shulman, R. G. (2003). In vivo NMR studies of the glutamate neurotransmitter flux and neuroenergetics: Implications for brain function. Annual Review of Physiology, 65, 401427. doi: 10.1146/annurev.physiol.65.092101.142131CrossRefGoogle ScholarPubMed
Shenhav, A., Botvinick, M. M., & Cohen, J. D. (2013). The expected value of control: An integrative theory of anterior cingulate cortex function. Neuron, 79(2), 217240. doi: 10.1016/j.neuron.2013.07.007CrossRefGoogle ScholarPubMed
Sherman, S. M. (2007). The thalamus is more than just a relay. Current Opinion in Neurobiology, 17(4), 417422. doi: 10.1016/j.conb.2007.07.003CrossRefGoogle ScholarPubMed
Steffens, M., Neumann, C., Kasparbauer, A. M., Becker, B., Weber, B., Mehta, M. A., … Ettinger, U. (2018). Effects of ketamine on brain function during response inhibition. Psychopharmacology (Berl), 235(12), 35593571. doi: 10.1007/s00213-018-5081-7CrossRefGoogle ScholarPubMed
Stevenson, R. A., Park, S., Cochran, C., McIntosh, L. G., Noel, J. P., Barense, M. D., … Wallace, M. T. (2017). The associations between multisensory temporal processing and symptoms of schizophrenia. Schizophrenia Research, 179, 97103. doi: 10.1016/j.schres.2016.09.035CrossRefGoogle ScholarPubMed
Stone, J. M., Dietrich, C., Edden, R., Mehta, M. A., De Simoni, S., Reed, L. J., … Barker, G. J. (2012). Ketamine effects on brain GABA and glutamate levels with 1H-MRS: Relationship to ketamine-induced psychopathology. Molecular Psychiatry, 17(7), 664665. doi: 10.1038/mp.2011.171CrossRefGoogle ScholarPubMed
Straube, B., Green, A., Sass, K., & Kircher, T. (2014). Superior temporal sulcus disconnectivity during processing of metaphoric gestures in schizophrenia. Schizophrenia Bulletin, 40(4), 936944. doi: 10.1093/schbul/sbt110CrossRefGoogle ScholarPubMed
Straube, B., Green, A., Sass, K., Kirner-Veselinovic, A., & Kircher, T. (2013). Neural integration of speech and gesture in schizophrenia: Evidence for differential processing of metaphoric gestures. Human Brain Mapping, 34(7), 16961712. doi: 10.1002/hbm.22015CrossRefGoogle ScholarPubMed
Strube, W., Marshall, L., Quattrocchi, G., Little, S., Cimpianu, C. L., Ulbrich, M., … Bestmann, S. (2020). Glutamatergic contribution to probabilistic reasoning and jumping to conclusions in schizophrenia: A double-blind, randomized experimental trial. Biological Psychiatry, 88(9), 687697. doi: 10.1016/j.biopsych.2020.03.018CrossRefGoogle ScholarPubMed
Szycik, G. R., Munte, T. F., Dillo, W., Mohammadi, B., Samii, A., Emrich, H. M., & Dietrich, D. E. (2009). Audiovisual integration of speech is disturbed in schizophrenia: An fMRI study. Schizophrenia Research, 110(1–3), 111118. doi: 10.1016/j.schres.2009.03.003CrossRefGoogle ScholarPubMed
Szycik, G. R., Ye, Z., Mohammadi, B., Dillo, W., Te Wildt, B. T., Samii, A., … Munte, T. F. (2013). Maladaptive connectivity of Broca's area in schizophrenia during audiovisual speech perception: An fMRI study. Neuroscience, 253, 274282. doi: 10.1016/j.neuroscience.2013.08.041CrossRefGoogle ScholarPubMed
Tayoshi, S., Sumitani, S., Taniguchi, K., Shibuya-Tayoshi, S., Numata, S., Iga, J., … Ohmori, T. (2009). Metabolite changes and gender differences in schizophrenia using 3-Tesla proton magnetic resonance spectroscopy (1H-MRS). Schizophrenia Research, 108(1–3), 6977. doi: 10.1016/j.schres.2008.11.014CrossRefGoogle ScholarPubMed
Tseng, H. H., Bossong, M. G., Modinos, G., Chen, K. M., McGuire, P., & Allen, P. (2015). A systematic review of multisensory cognitive-affective integration in schizophrenia. Neuroscience and Biobehavioral Reviews, 55, 444452. doi: 10.1016/j.neubiorev.2015.04.019CrossRefGoogle ScholarPubMed
van Wageningen, H., Jorgensen, H. A., Specht, K., Eichele, T., & Hugdahl, K. (2009). The effects of the glutamate antagonist memantine on brain activation to an auditory perception task. Human Brain Mapping, 30(11), 36163624. doi: 10.1002/hbm.20789CrossRefGoogle Scholar
Woo, T. U., Shrestha, K., Lamb, D., Minns, M. M., & Benes, F. M. (2008). N-methyl-D-aspartate receptor and calbindin-containing neurons in the anterior cingulate cortex in schizophrenia and bipolar disorder. Biological Psychiatry, 64(9), 803809. doi: 10.1016/j.biopsych.2008.04.034CrossRefGoogle ScholarPubMed
Wroblewski, A., He, Y., & Straube, B. (2020). Dynamic causal modelling suggests impaired effective connectivity in patients with schizophrenia spectrum disorders during gesture-speech integration. Schizophrenia Research, 216, 175183. doi: 10.1016/j.schres.2019.12.005CrossRefGoogle ScholarPubMed
Xu, T., Wang, Y., Li, Z., Huang, J., Lui, S. S., Tan, S. P., … Chan, R. C. (2016). Heritability and familiality of neurological soft signs: Evidence from healthy twins, patients with schizophrenia and non-psychotic first-degree relatives. Psychological Medicine, 46(1), 117123. doi: 10.1017/S0033291715001580CrossRefGoogle ScholarPubMed
Zhou, H. Y., Cai, X. L., Weigl, M., Bang, P., Cheung, E. F. C., & Chan, R. C. K. (2018). Multisensory temporal binding window in autism spectrum disorders and schizophrenia spectrum disorders: A systematic review and meta-analysis. Neuroscience and Biobehavioral Reviews, 86, 6676. doi: 10.1016/j.neubiorev.2017.12.013CrossRefGoogle ScholarPubMed
Zhou, H. Y., Cheung, E. F. C., & Chan, R. C. K. (2020). Audiovisual temporal integration: Cognitive processing, neural mechanisms, developmental trajectory and potential interventions. Neuropsychologia, 140, 107396. doi: 10.1016/j.neuropsychologia.2020.107396CrossRefGoogle ScholarPubMed
Zvyagintsev, M., Parisi, C., & Mathiak, K. (2017). Temporal processing deficit leads to impaired multisensory binding in schizophrenia. Cognitive Neuropsychiatry, 22(5), 361372. doi: 10.1080/13546805.2017.1331160CrossRefGoogle ScholarPubMed
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