title: Voxel-based, brain-wide association study of aberrant functional connectivity in schizophrenia implicates thalamocortical circuitry.
abstract: BACKGROUND
  Wernicke's concept of 'sejunction' or aberrant associations among specialized brain regions is one of the earliest hypotheses attempting to explain the myriad of symptoms in psychotic disorders. Unbiased data mining of all possible brain-wide connections in large data sets is an essential first step in localizing these aberrant circuits.
  
  
  METHODS
  We analyzed functional connectivity using the largest resting-state neuroimaging data set reported to date in the schizophrenia literature (415 patients vs. 405 controls from UK, USA, Taiwan, and China). An exhaustive brain-wide association study at both regional and voxel-based levels enabled a continuous data-driven discovery of the key aberrant circuits in schizophrenia.
  
  
  RESULTS
  Results identify the thalamus as the key hub for altered functional networks in patients. Increased thalamus-primary somatosensory cortex connectivity was the most significant aberration in schizophrenia (P=10(-18)). Overall, a number of thalamic links with motor and sensory cortical regions showed increased connectivity in schizophrenia, whereas thalamo-frontal connectivity was weakened. Network changes were correlated with symptom severity and illness duration, and support vector machine analysis revealed discrimination accuracies of 73.53-80.92%.
  
  
  CONCLUSIONS
  Widespread alterations in resting-state thalamocortical functional connectivity is likely to be a core feature of schizophrenia that contributes to the extensive sensory, motor, cognitive, and emotional impairments in this disorder. Changes in this schizophrenia-associated network could be a reliable mechanistic index to discriminate patients from healthy controls.
authors.affiliation: Centre for Computational Systems Biology, Fudan University , Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cheng
authors.affiliation: Centre for Translational Neuroimaging, Division of Psychiatry and Applied Psychology, Institute of Mental Health, University of Nottingham , Nottingham, UK.
authors.forename: Lena
authors.initials: L
authors.lastname: Palaniyappan
authors.affiliation: The Mental Health Center and the Psychiatric Laboratory, West China Hospital, Sichuan University , Chengdu, China.
authors.forename: Mingli
authors.initials: M
authors.lastname: Li
authors.affiliation: Key Laboratory for Neuroinformation, Ministry of Education of China, School of Life Science and Technology, University of Electronic Science and Technology of China , Chengdu, China.
authors.forename: Keith M
authors.initials: KM
authors.lastname: Kendrick
authors.affiliation: Centre for Computational Systems Biology, Fudan University , Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Centre for Computational Systems Biology, Fudan University , Shanghai, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Luo
authors.affiliation: Institute of Mental Health, Second Xiangya Hospital, Central South University , Changsha, China.
authors.forename: Zening
authors.initials: Z
authors.lastname: Liu
authors.affiliation: School of Psychology and Center for Studies of Psychological Application, South China Normal University , Guangzhou, China.
authors.forename: Rongjun
authors.initials: R
authors.lastname: Yu
authors.affiliation: The Mental Health Center and the Psychiatric Laboratory, West China Hospital, Sichuan University , Chengdu, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
authors.affiliation: The Mental Health Center and the Psychiatric Laboratory, West China Hospital, Sichuan University , Chengdu, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: The Mental Health Center and the Psychiatric Laboratory, West China Hospital, Sichuan University , Chengdu, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Ma
authors.affiliation: The Mental Health Center and the Psychiatric Laboratory, West China Hospital, Sichuan University , Chengdu, China.
authors.forename: Wanjun
authors.initials: W
authors.lastname: Guo
authors.affiliation: Sir Peter Mansfield MR Centre, University of Nottingham , Nottingham, UK.
authors.forename: Susan
authors.initials: S
authors.lastname: Francis
authors.affiliation: Centre for Translational Neuroimaging, Division of Psychiatry and Applied Psychology, Institute of Mental Health, University of Nottingham , Nottingham, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Liddle
authors.affiliation: The Mind Research Network , Albuquerque, USA.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Mayer
authors.affiliation: Medical Research Council-Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, De Crespigny Park , London, UK.
authors.forename: Gunter
authors.initials: G
authors.lastname: Schumann
authors.affiliation: The Mental Health Center and the Psychiatric Laboratory, West China Hospital, Sichuan University , Chengdu, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Centre for Computational Systems Biology, Fudan University, Shanghai, China; Department of Computer Science, University of Warwick, Coventry, UK; School of Life Science and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Feng