title: The role of white matter microstructure in inhibitory deficits in patients with schizophrenia.
abstract: Inhibitory-excitatory (I-E) imbalance has increasingly been proposed as a fundamental mechanism giving rise to many schizophrenia-related pathophysiology. The integrity of I-E functions should require precise and rapid electrical signal transmission.
  
  
  
  We hypothesized that part of the I-E abnormality in schizophrenia may originate from their known abnormal white matter connectivity that may interfere the I-E functions.
  
  
  
  We test this using short-interval intracortical inhibition (SICI) vs. intracortical facilitation (ICF) which is a non-invasive measurement of I-E signaling. SICI-ICF from left motor cortex and white matter microstructure were assessed in schizophrenia patients and healthy controls.
  
  
  
  Schizophrenia patients showed significantly reduced SICI but not ICF. White matter microstructure as measured by fraction anisotropy (FA) in diffusion tensor imaging had a significant effect on SICI in patients, such that weaker SICI was associated with lower FA in several white matter tracts, most strongly with left corona radiata (r = -0.68, p = 0.0002) that contains the fibers connecting with left motor cortex. Left corticospinal tract, which carries the motor fibers to peripheral muscular output, also showed significant correlation with SICI (r = -0.54, p = 0.005). Mediation analysis revealed that much of the schizophrenia disease effect on SICI can be accounted for by mediation through left corona radiata. SICI was also significantly associated with the performance of processing speed in patients.
  
  
  
  This study demonstrated the importance of structural circuitry integrity in inhibitory signaling in schizophrenia, and encouraged modeling the I-E dysfunction in schizophrenia from a circuitry perspective.
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address: xdu@mprc.umaryland.edu.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Du
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Kochunov
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Ann
authors.initials: A
authors.lastname: Summerfelt
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Chiappelli
authors.affiliation: The Department of Computer Science and Electrical Engineering, University of Maryland Baltimore County, Baltimore, MD, USA.
authors.forename: Fow-Sen
authors.initials: FS
authors.lastname: Choa
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: L Elliot
authors.initials: LE
authors.lastname: Hong
mesh_terms: D000328:Adult; D000368:Aged; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000503:physiopathology; D056324:Diffusion Tensor Imaging / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000000981:diagnostic imaging* / Q000503:physiopathology; D009415:Nerve Net / Q000000981:diagnostic imaging* / Q000503:physiopathology; D009433:Neural Inhibition / Q000502:physiology*; D011712:Pyramidal Tracts / Q000000981:diagnostic imaging* / Q000503:physiopathology; D012559:Schizophrenia / Q000000981:diagnostic imaging* / Q000503:physiopathology; D066127:White Matter / Q000000981:diagnostic imaging* / Q000503:physiopathology; D055815:Young Adult
keywords: Corona radiata; Diffusion tensor imaging; Intracortical inhibition; Schizophrenia; Stimulation; White matter