Schizophrenia is a complex mental disorder characterized by a wide range of neurocognitive, affective and neurodevelopmental abnormalities. Neurological soft signs (NSS) have been considered to be one of the promising endophenotypes for schizophrenia. Dr. Raymond CHAN’s team from the Neuropsychology and Applied Cognitive Neuroscience (NACN) Laboratory, CAS Key Laboratory of Mental Health, Institute of Psychology, has provided substantial evidence to show NSS are sensitive, reliable and specific to schizophrenia. However, it is not clear the association of NSS and brain network abnormalities in patients with schizophrenia.
In a recent study, Dr. Chan and his postdoctoral candidate, Dr. KONG, Li working with international collaborator have specifically examined the underlying brain structural network in a group of 101 patients with first-episode schizophrenia using graph theory approach. Specifically, structural network analysis based on grey matter morphometry and their associations with NSS was conducted. They classified patients into high and low levels of NSS and examined their regional and global brain network. Their findings showed that the two groups of patients did not differ in global network properties. Subsequent regional network analysis found that NSS were correlated with betweenness centrality involving the inferior orbital frontal cortex, the middle temporal cortex, the hippocampus, the supramarginal cortex, the amygdala and the cerebellum. Findings from global network analysis further showed that NSS were correlated with the distribution of hubs involving the superior medial frontal cortex, the superior and middle temporal cortices, the postcentral cortex, the amygdala and the cerebellum. These regions are all corresponding to the cortical-subcortical-cerebellum circuit that has been considered to be the main source responsible for the clinical and behavioural manifestations observed in patients with schizophrenia.
Dr. CHAN’s team and his collaborators are now taking further steps to combine the behavioural measures of NSS and trajectory-based neuroimaging measures to examine how variations in NSS manifest as structural and functional imaging abnormalities in patients with schizophrenia. These all may allow us to gain a better understanding of the pathogenesis of schizophrenia.
This study was supported by grants from the grant from the National Key Research and Development Programme, the Beijing Training Project for the Leading Talents in Science and Technology, the CAS Key Laboratory of Mental Health, Institute of Psychology, and the National Natural Science Foundation of China.
The paper is now available online from Schizophrenia Bulletin
Kong, L., Herold, C. J., Cheung, E. F. C., Chan, R. C. K.*, Johannes Schroder. (2019). Neurological soft signs and brain network abnormalities in schizophrenia. Schizophrenia Bulletin.
Related papers of NSS include
Chan, R. C. K.*, Rao, H. Y., Chen, E. Y. H., Ye, B. B., & Zhang, C. (2006). The neural basis of motor coordination soft signs: an fMRI study of healthy subjects. Neuroscience Letters, 398, 189-194.
Rao, H.*, Di, X., Chan, R. C. K*., Ding, Y., Ye, B., Gao, D. (2008). A regulation role of the prefrontal cortex in the fist-edge-palm task: Evidence from functional connectivity analysis. NeuroImage, 41, 1345-1351.
Chan, R. C. K.*, Gottesman, I. I., Ge, X., Sam, P. C. (2010). Strategies for the study of neuropsychiatric disorders using endophenotypes in developing countries: a potential databank from China. Frontiers in Human Neuroscience, 4, 207, doi: 10.3389/fnhum.2010.00207
Chan, R. C. K.* (2011). Consortium for the Human Information and Neurocognitive Endophenotype (CHINE) in mainland China: An example from neurological soft signs for neuropsychiatric disorders. Chinese Science Bulletin, 56(32), 3409-3415.
Chan, RCK*, Huang, J, Zhao, Q, Wang, Y, Lai, YY, Hong, N., Shum, DHK, Cheung, EFC, Yu, X, Dazzan P. (2015). Prefrontal cortex connectivity dysfunction in performing the Fist-Edge-Palm task in patients with first-episode schizophrenia and non-psychotic first-degree relatives. NeuroImage: Clinical. 9, 411–417
Zhao, Q., Li, Z., Huang, J., Yan, C., Dazzan, P., Pantelis, C., Cheung, E. F. C., Lui, S. S. Y., Chan, R. C. K.*. (2014). Neurological soft signs are not “soft” in brain structure and functional networks: Evidence from ALE meta-analysis. Schizophrenia Bulletin, 40(3): 626-641.
Chan, R. C. K.*, Dai, S., Lui, S. S. Y., Ho, K K. Y., Hung, K. S. Y., Wang, Y., Geng, F. L., Li., Z., Cheung, E. F. C. (2015). Re-visiting the nature and relationships between neurological signs and neurocognitive functions in first-episode schizophrenia: An invariance model across time. Scientific Reports, 5: 11859.
Chan, R. C. K*, Geng, F. L., Lui, S. S. Y., Wang, Y., Ho, K K. Y., Hung, K. S. Y., Gur, R. E., Gur, R. C., Cheung, E. F. C. (2015). Course of neurological soft signs in first-episode schizophrenia: Relationship with negative symptoms and cognitive performances. Scientific Reports, 5:11053
Xu, T., Wang, Y., Li, Z., Huang, J., Lui, S. S. Y., Tan, S. P., Yu, X., Cheung, E. F. C., He, M.G., Ott, J., Gur, R. E., Gur, R. C., Chan, R. C. K.*. (2016). Heritability and familiality of neurological soft signs: Evidence from healthy twins, patients with schizophrenia and non-psychotic first-degree relatives. Psychological Medicine, doi:10.1017/S0033291715001580
Chan, R. C. K*., Xie, W., Geng, F. L., Wang, Y., Lui, S. S. Y., Wang, C. Y., Yu, X., Cheung, E. F. C., Rosenthal, R. (2016). Clinical utility and lifespan profiling of neurological soft signs in schizophrenia spectrum disorders, Schizophrenia Bulletin, 42(3), 560-570.
Li, Z.#, Huang#, J., Xu, T.#, Wang, Y., Li, K., Zeng, Y. W., Lui, S. S. Y., Cheung, E. F. C., Jin, Z., Dazzan, P., Glahn, D. C., 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), 143-1448. DOI: 10.1002/hbm.23935
Institute of Psychology