Disrupted white matter integrity of corticopontine-cerebellar circuitry in schizophrenia

Evidence for white matter abnormalities in patients with schizophrenia is increasing. Decreased fractional anisotropy (FA) in interhemispheric commissural fibers as well as long-ranging fronto-parietal association fibers belongs to the most frequent findings. The present study used tract-based spatial statistics to investigate white matter integrity in 35 patients with schizophrenia and 35 healthy volunteers. We found that patients exhibited significantly decreased FA relative to healthy subjects in the corpus callosum, the cerebral peduncle, the left inferior fronto-occipital fasciculus, the anterior thalamic radiation, the right posterior corona radiata, the middle cerebellar peduncle, and the right superior longitudinal fasciculus. Increased FA was detectable in the inferior sections of the corticopontine-cerebellar circuit. Present data indicate extended cortical-subcortical alterations of white matter integrity in schizophrenia using advanced data analysis strategies. They corroborate preceding findings of white matter structural deficits in mainly long-ranging association fibers and provide first evidence for neuroplastic changes in terms of an increased directionality in more inferior fiber tracts.

[1]  Timothy Edward John Behrens,et al.  Anatomically related grey and white matter abnormalities in adolescent-onset schizophrenia. , 2007, Brain : a journal of neurology.

[2]  H. Möller,et al.  Differences in hippocampal volume between major depression and schizophrenia: a comparative neuroimaging study , 2010, European Archives of Psychiatry and Clinical Neuroscience.

[3]  D. Hubl,et al.  Hallucinations, Thought Disorders, and the Language Domain in Schizophrenia , 2008, Clinical EEG and neuroscience.

[4]  K. Fouad,et al.  Compensatory Sprouting and Impulse Rerouting after Unilateral Pyramidal Tract Lesion in Neonatal Rats , 2000, The Journal of Neuroscience.

[5]  P. C. Fletcher,et al.  Investigating principles of human brain function underlying working memory: What insights from schizophrenia? , 2006, Neuroscience.

[6]  이승구,et al.  White matter abnormalities associated with auditory hallucinations in schizophrenia: A combined study of voxel-based analyses of diffusion tensor imaging and structural magnetic resonance imaging , 2007 .

[7]  Jong H. Yoon,et al.  Association of dorsolateral prefrontal cortex dysfunction with disrupted coordinated brain activity in schizophrenia: relationship with impaired cognition, behavioral disorganization, and global function. , 2008, The American journal of psychiatry.

[8]  E. Bullmore,et al.  White matter volume changes in people who develop psychosis. , 2008, The British journal of psychiatry : the journal of mental science.

[9]  Dennis Velakoulis,et al.  Morphology of the corpus callosum at different stages of schizophrenia: cross-sectional study in first-episode and chronic illness. , 2008, The British journal of psychiatry : the journal of mental science.

[10]  Tianzi Jiang,et al.  White matter integrity of the whole brain is disrupted in first-episode schizophrenia , 2006, Neuroreport.

[11]  Gareth J. Barker,et al.  Diffusion tensor imaging in schizophrenia , 2008, European Psychiatry.

[12]  S. Woods,et al.  Chlorpromazine equivalent doses for the newer atypical antipsychotics. , 2003, The Journal of clinical psychiatry.

[13]  Theo G. M. van Erp,et al.  Diffusion Tensor Imaging of the Superior Longitudinal Fasciculus and Working Memory in Recent-Onset Schizophrenia , 2008, Biological Psychiatry.

[14]  G Price,et al.  The corpus callosum in first episode schizophrenia: a diffusion tensor imaging study , 2005, Journal of Neurology, Neurosurgery & Psychiatry.

[15]  P. Brodal,et al.  The corticopontine projection in the rhesus monkey. Origin and principles of organization. , 1978, Brain : a journal of neurology.

[16]  Jürgen R. Reichenbach,et al.  Inefficient executive cognitive control in schizophrenia is preceded by altered functional activation during information encoding: An fMRI study , 2008, Neuropsychologia.

[17]  S. Wakana,et al.  MRI Atlas of Human White Matter , 2005 .

[18]  P. Matthews,et al.  White matter abnormalities and brain activation in schizophrenia: A combined DTI and fMRI study , 2007, Schizophrenia Research.

[19]  Mark W. Woolrich,et al.  Advances in functional and structural MR image analysis and implementation as FSL , 2004, NeuroImage.

[20]  J B Poline,et al.  Evidence for abnormal cortical functional connectivity during working memory in schizophrenia. , 2001, The American journal of psychiatry.

[21]  D. Keegan,et al.  Expression of brain‐derived neurotrophic factor mRNA in rat hippocampus after treatment with antipsychotic drugs , 2003, Journal of neuroscience research.

[22]  L. Williams,et al.  Eye Movement Dysfunction as a Biological Marker of Risk for Schizophrenia , 2000 .

[23]  J. Foong,et al.  Neuropathological abnormalities of the corpus callosum in schizophrenia: a diffusion tensor imaging study , 2000, Journal of neurology, neurosurgery, and psychiatry.

[24]  Dai Zhang,et al.  A diffusion tensor imaging study of middle and superior cerebellar peduncle in male patients with schizophrenia , 2003, Neuroscience Letters.

[25]  Hidenao Fukuyama,et al.  Anterior and posterior cingulum abnormalities and their association with psychopathology in schizophrenia: A diffusion tensor imaging study , 2007, Schizophrenia Research.

[26]  Jens Haueisen,et al.  Analysis of b‐value calculations in diffusion weighted and diffusion tensor imaging , 2005 .

[27]  S. Kay,et al.  The positive and negative syndrome scale (PANSS) for schizophrenia. , 1987, Schizophrenia bulletin.

[28]  Jan G. Bjaalie,et al.  Organization of the pontine nuclei , 1992, Neuroscience Research.

[29]  Patrick R Hof,et al.  Diffusion tensor imaging findings in first-episode and chronic schizophrenia patients. , 2008, The American journal of psychiatry.

[30]  P. Falkai,et al.  [Structural and functional brain changes in schizophrenic disorders. Indications of early neuronal developmental disturbances?]. , 2008, Der Nervenarzt.

[31]  R. Kikinis,et al.  Cingulate fasciculus integrity disruption in schizophrenia: a magnetic resonance diffusion tensor imaging study , 2003, Biological Psychiatry.

[32]  S. Lawrie,et al.  Diffusion tensor imaging (DTI) and proton magnetic resonance spectroscopy (1H MRS) in schizophrenic subjects and normal controls , 2001, Psychiatry Research: Neuroimaging.

[33]  K. Koch,et al.  Temporal modeling demonstrates preserved overlearning processes in schizophrenia: An fMRI study , 2007, Neuroscience.

[34]  Xiao-Jing Wang.  Synaptic reverberation underlying mnemonic persistent activity , 2001, Trends in Neurosciences.

[35]  Christophe Habas,et al.  Anatomical parcellation of the brainstem and cerebellar white matter: a preliminary probabilistic tractography study at 3 T , 2007, Neuroradiology.

[36]  Philip K. McGuire,et al.  Diffusion Tensor Imaging in Schizophrenia , 2005, Biological Psychiatry.

[37]  S. Lawrie,et al.  Structural disconnectivity in schizophrenia: a diffusion tensor magnetic resonance imaging study , 2003, British Journal of Psychiatry.

[38]  R. Kikinis,et al.  Uncinate fasciculus findings in schizophrenia: a magnetic resonance diffusion tensor imaging study. , 2002, The American journal of psychiatry.

[39]  Daniel Rueckert,et al.  Tract-based spatial statistics: Voxelwise analysis of multi-subject diffusion data , 2006, NeuroImage.

[40]  Peter Stoeter,et al.  Altered effective connectivity during working memory performance in schizophrenia: a study with fMRI and structural equation modeling , 2003, NeuroImage.

[41]  Vincent Giampietro,et al.  White matter microstructure in schizophrenia: effects of disorder, duration and medication , 2009, British Journal of Psychiatry.

[42]  Toshihiko Kinoshita,et al.  Neural disorganization in the superior cerebellar peduncle and cognitive abnormality in patients with schizophrenia: A diffusion tensor imaging study , 2006, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[43]  Andrew J. Saykin,et al.  Age-related deficits in fronto-temporal connections in schizophrenia: A diffusion tensor imaging study , 2008, Schizophrenia Research.

[44]  R. Henry,et al.  Diffusion Tensor MR Imaging and Fiber Tractography: Technical Considerations , 2008, American Journal of Neuroradiology.

[45]  Edward E. Smith,et al.  Neuroimaging studies of working memory: , 2003, Cognitive, affective & behavioral neuroscience.

[46]  Francesco Carletti,et al.  Reduced fractional anisotropy of corpus callosum in first-contact, antipsychotic drug-naive patients with schizophrenia , 2009, Schizophrenia Research.

[47]  T. Kinoshita,et al.  Diffusion tensor imaging study of the middle cerebellar peduncles in patients with schizophrenia , 2008, The Cerebellum.

[48]  H. Möller,et al.  White matter alterations in schizophrenic patients with pronounced negative symptomatology and with positive family history for schizophrenia , 2008, European Archives of Psychiatry and Clinical Neuroscience.

[49]  C. Pantelis,et al.  Diseases of white matter and schizophrenia-like psychosis. , 2005, The Australian and New Zealand journal of psychiatry.

[50]  R. Kikinis,et al.  A review of diffusion tensor imaging studies in schizophrenia. , 2007, Journal of psychiatric research.

[51]  Nancy C. Andreasen,et al.  Linking Mind and Brain in the Study of Mental Illnesses: A Project for a Scientific Psychopathology , 1997, Science.

[52]  S. Muñoz Maniega,et al.  A diffusion tensor MRI study of white matter integrity in subjects at high genetic risk of schizophrenia , 2008, Schizophrenia Research.

[53]  K. R. Ridderinkhof,et al.  Function and Structure of the Right Inferior Frontal Cortex Predict Individual Differences in Response Inhibition: A Model-Based Approach , 2008, The Journal of Neuroscience.

[54]  V. Wedeen,et al.  Reduction of eddy‐current‐induced distortion in diffusion MRI using a twice‐refocused spin echo , 2003, Magnetic resonance in medicine.

[55]  A. Heinz,et al.  Strukturelle und funktionelle Hirnveränderungen bei schizophrenen Psychosen , 2008, Der Nervenarzt.

[56]  Anna Rotarska-Jagiela,et al.  The corpus callosum in schizophrenia-volume and connectivity changes affect specific regions , 2008, NeuroImage.

[57]  Monte S. Buchsbaum,et al.  White matter fractional anisotropy and outcome in schizophrenia , 2006, Schizophrenia Research.

[58]  Gareth J. Barker,et al.  White matter tracts in first-episode psychosis: A DTI tractography study of the uncinate fasciculus , 2008, NeuroImage.

[59]  D. Gounot,et al.  Functional integration in schizophrenia: too little or too much? Preliminary results on fMRI data , 2005, NeuroImage.

[60]  Stephen M. Smith,et al.  Threshold-free cluster enhancement: Addressing problems of smoothing, threshold dependence and localisation in cluster inference , 2009, NeuroImage.

[61]  R. Kahn,et al.  Psychosis and brain volume changes during the first five years of schizophrenia , 2009, European Neuropsychopharmacology.

[62]  A. Burgess,et al.  Chlorpromazine equivalents: a consensus of opinion for both clinical and research applications , 1997 .

[63]  Carl-Fredrik Westin,et al.  DTI and MTR abnormalities in schizophrenia: Analysis of white matter integrity , 2005, NeuroImage.

[64]  Robin M. Murray,et al.  Neurological soft signs in first-episode psychosis: A systematic review , 2002, British Journal of Psychiatry.

[65]  D. Hubl,et al.  Pathways that make voices: white matter changes in auditory hallucinations. , 2004, Archives of general psychiatry.

[66]  T. Kinoshita,et al.  Olanzapine Increases Grey and White Matter Volumes in the Caudate Nucleus of Patients with Schizophrenia , 2007, Neuropsychobiology.

[67]  J. Ballenger,et al.  A diffusion tensor imaging study of structural dysconnectivity in never-medicated, first-episode schizophrenia , 2009 .