title: Localized abnormalities in the cingulum bundle in patients with schizophrenia: a Diffusion Tensor tractography study.
abstract: The cingulum bundle (CB) connects gray matter structures of the limbic system and as such has been implicated in the etiology of schizophrenia. There is growing evidence to suggest that the CB is actually comprised of a conglomeration of discrete sub-connections. The present study aimed to use Diffusion Tensor tractography to subdivide the CB into its constituent sub-connections, and to investigate the structural integrity of these sub-connections in patients with schizophrenia and matched healthy controls. Diffusion Tensor Imaging scans were acquired from 24 patients diagnosed with chronic schizophrenia and 26 matched healthy controls. Deterministic tractography was used in conjunction with FreeSurfer-based regions-of-interest to subdivide the CB into 5 sub-connections (I1 to I5). The patients with schizophrenia exhibited subnormal levels of FA in two cingulum sub-connections, specifically the fibers connecting the rostral and caudal anterior cingulate gyrus (I1) and the fibers connecting the isthmus of the cingulate with the parahippocampal cortex (I4). Furthermore, while FA in the I1 sub-connection was correlated with the severity of patients' positive symptoms (specifically hallucinations and delusions), FA in the I4 sub-connection was correlated with the severity of patients' negative symptoms (specifically affective flattening and anhedonia/asociality). These results support the notion that the CB is a conglomeration of structurally interconnected yet functionally distinct sub-connections, of which only a subset are abnormal in patients with schizophrenia. Furthermore, while acknowledging the fact that the present study only investigated the CB, these results suggest that the positive and negative symptoms of schizophrenia may have distinct neurobiological underpinnings.
authors.affiliation: School of Psychology, University of New South Wales, Sydney, NSW, Australia ; Psychiatry Neuroimaging Laboratory, Departments of Psychiatry and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Whitford
authors.affiliation: Psychiatry Neuroimaging Laboratory, Departments of Psychiatry and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA ; Department of Psychiatry, School of Medicine, Chungnam National University, Daejeon, South Korea.
authors.forename: Sun Woo
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Psychiatry Neuroimaging Laboratory, Departments of Psychiatry and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA ; Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Jungsu S
authors.initials: JS
authors.lastname: Oh
authors.affiliation: Laboratory of Mathematics in Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA ; Laboratorio de Procesado de Imagen, Universidad de Valladolid, Spain.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: de Luis-Garcia
authors.affiliation: Psychiatry Neuroimaging Laboratory, Departments of Psychiatry and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA ; Laboratory of Mathematics in Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Savadjiev
authors.affiliation: Psychiatry Neuroimaging Laboratory, Departments of Psychiatry and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Alvarado
authors.affiliation: Laboratory of Mathematics in Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Carl-Fredrik
authors.initials: CF
authors.lastname: Westin
authors.affiliation: Clinical Neuroscience Division, Laboratory of Neuroscience, Department of Psychiatry, Boston Veterans Affairs Healthcare System, Brockton Division, Brockton, MA, USA and Harvard Medical School, Boston, MA, USA.
authors.forename: Margaret
authors.initials: M
authors.lastname: Niznikiewicz
authors.affiliation: Clinical Neuroscience Division, Laboratory of Neuroscience, Department of Psychiatry, Boston Veterans Affairs Healthcare System, Brockton Division, Brockton, MA, USA and Harvard Medical School, Boston, MA, USA ; Boston Veterans Affairs Healthcare System, Brockton Division, Brockton, MA, USA ; Department of Psychology, University of Massachusetts, Boston, MA, USA.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Nestor
authors.affiliation: Clinical Neuroscience Division, Laboratory of Neuroscience, Department of Psychiatry, Boston Veterans Affairs Healthcare System, Brockton Division, Brockton, MA, USA and Harvard Medical School, Boston, MA, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: McCarley
authors.affiliation: Psychiatry Neuroimaging Laboratory, Departments of Psychiatry and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Marek
authors.initials: M
authors.lastname: Kubicki
authors.affiliation: Psychiatry Neuroimaging Laboratory, Departments of Psychiatry and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA ; Boston Veterans Affairs Healthcare System, Brockton Division, Brockton, MA, USA.
authors.forename: Martha E
authors.initials: ME
authors.lastname: Shenton
mesh_terms: D000328:Adult; D016880:Anisotropy; D001931:Brain Mapping; D056324:Diffusion Tensor Imaging; D006179:Gyrus Cinguli / Q000503:physiopathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000503:physiopathology*
keywords: Cingulate gyrus; Cingulum bundle; DTI; Diffusion Tensor Imaging; Fractional Anisotropy; Schizophrenia