Arcuate Fasciculus Abnormalities and Their Relationship with Psychotic Symptoms in Schizophrenia

Disruption of fronto-temporal connections involving the arcuate fasciculus (AF) may underlie language processing anomalies and psychotic features such as auditory hallucinations in schizophrenia. No study to date has specifically investigated abnormalities of white matter integrity at particular loci along the AF as well as its regional lateralization in schizophrenia. We examined white matter changes (fractional anisotropy (FA), axial diffusivity (AD), asymmetry indices) along the whole extent of the AF and their relationship with psychotic symptoms in 32 males with schizophrenia and 44 healthy males. Large deformation diffeomorphic metric mapping and Fiber Assignment Continuous Tracking were employed to characterize FA and AD along the geometric curve of the AF. Our results showed that patients with schizophrenia had lower FA in the frontal aspects of the left AF compared with healthy controls. Greater left FA and AD lateralization in the temporal segment of AF were associated with more severe positive psychotic symptoms such as delusions and hallucinations in patients with schizophrenia. Disruption of white matter integrity of the left frontal AF and accentuation of normal left greater than right asymmetry of FA/AD in the temporal AF further support the notion of aberrant fronto-temporal connectivity in schizophrenia. AF pathology can affect corollary discharge of neural signals from frontal speech/motor initiation areas to suppress activity of auditory cortex that may influence psychotic phenomena such as auditory hallucinations and facilitate elaboration of delusional content.

[1]  Randy L. Gollub,et al.  Reproducibility of quantitative tractography methods applied to cerebral white matter , 2007, NeuroImage.

[2]  D. Pandya,et al.  Segmentation of subcomponents within the superior longitudinal fascicle in humans: a quantitative, in vivo, DT-MRI study. , 2005, Cerebral cortex.

[3]  T. Crow,et al.  Asymmetry loss is local rather than global in adolescent onset schizophrenia , 2010, Schizophrenia Research.

[4]  H. Pincus,et al.  DSM-IV in progress. Changes in substance-related, schizophrenic, and other primarily adult disorders. , 1994, Hospital & community psychiatry.

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

[6]  Fei Wang,et al.  Asymmetry analysis of cingulum based on scale‐invariant parameterization by diffusion tensor imaging , 2005, Human brain mapping.

[7]  Matthew F Glasser,et al.  DTI tractography of the human brain's language pathways. , 2008, Cerebral cortex.

[8]  M. Catani,et al.  A diffusion tensor imaging tractography atlas for virtual in vivo dissections , 2008, Cortex.

[9]  K Ugurbil,et al.  Functional magnetic resonance imaging of Broca's area during internal speech. , 1993, Neuroreport.

[10]  R. Kahn,et al.  Language lateralization in schizophrenia, an fMRI study , 2001, Schizophrenia Research.

[11]  Michael I. Miller,et al.  Cortical Hemisphere Registration Via Large Deformation Diffeomorphic Metric Curve Mapping , 2007, MICCAI.

[12]  Y. Kawasaki,et al.  Perigenual cingulate gyrus volume in patients with schizophrenia: a magnetic resonance imaging study , 2003, Biological Psychiatry.

[13]  Judith M Ford,et al.  Relationship of imprecise corollary discharge in schizophrenia to auditory hallucinations. , 2007, Archives of general psychiatry.

[14]  Lutz Jäncke,et al.  A voxel-based approach to gray matter asymmetries , 2004, NeuroImage.

[15]  Derek K. Jones,et al.  A diffusion tensor imaging study of fasciculi in schizophrenia. , 2007, The American journal of psychiatry.

[16]  Lin He,et al.  A family-based association study of the MOG gene with schizophrenia in the Chinese population , 2005, Schizophrenia Research.

[17]  Marek Kubicki,et al.  Evidence for white matter abnormalities in schizophrenia , 2005, Current opinion in psychiatry.

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

[19]  W. Eric L. Grimson,et al.  A unified framework for clustering and quantitative analysis of white matter fiber tracts , 2008, Medical Image Anal..

[20]  Georg Winterer,et al.  Disturbed structural connectivity in schizophrenia primary factor in pathology or epiphenomenon? , 2007, Schizophrenia bulletin.

[21]  V. van de Ven,et al.  Reduced Laterality as a Trait Marker ofSchizophrenia—Evidence from Structural and Functional Neuroimaging , 2010, The Journal of Neuroscience.

[22]  D. Weinberger,et al.  Normal Asymmetry of the Planum Temporale in Patients with Schizophrenia , 1995, British Journal of Psychiatry.

[23]  Dominique Hasboun,et al.  Anatomically constrained region deformation for the automated segmentation of the hippocampus and the amygdala: Method and validation on controls and patients with Alzheimer’s disease , 2007, NeuroImage.

[24]  Liberty S. Hamilton,et al.  Fiber tractography reveals disruption of temporal lobe white matter tracts in schizophrenia , 2009, Schizophrenia Research.

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

[26]  Michael I. Miller,et al.  Large Deformation Diffeomorphic Metric Curve Mapping , 2008, International Journal of Computer Vision.

[27]  Robert J Zatorre,et al.  Asymmetries of the planum temporale and Heschl's gyrus: relationship to language lateralization. , 2006, Brain : a journal of neurology.

[28]  K. Jellinger,et al.  The neuropathology of schizophrenia. , 1999, Journal of neuropathology and experimental neurology.

[29]  C. Levitan,et al.  Superior temporal gyral volumes and laterality correlates of auditory hallucinations in schizophrenia , 1999, Biological Psychiatry.

[30]  Suzanne E. Welcome,et al.  Mapping cortical change across the human life span , 2003, Nature Neuroscience.

[31]  M. Startup,et al.  Immediate source-monitoring, self-focused attention and the positive symptoms of schizophrenia. , 2008, Behaviour research and therapy.

[32]  W. Singer,et al.  Activation of Heschl’s Gyrus during Auditory Hallucinations , 1999, Neuron.

[33]  A. Toga,et al.  Mapping cortical asymmetry and complexity patterns in normal children , 2001, Psychiatry Research: Neuroimaging.

[34]  R. Murray,et al.  Functional anatomy of auditory verbal imagery in schizophrenic patients with auditory hallucinations. , 2000, The American journal of psychiatry.

[35]  C. Beaulieu,et al.  The basis of anisotropic water diffusion in the nervous system – a technical review , 2002, NMR in biomedicine.

[36]  T. Hendler,et al.  Reduced language lateralization in first-episode schizophrenia: An fMRI index of functional asymmetry , 2009, Psychiatry Research: Neuroimaging.

[37]  Arthur W. Toga,et al.  Stereotaxic white matter atlas based on diffusion tensor imaging in an ICBM template , 2008, NeuroImage.

[38]  Michael I. Miller,et al.  Multi-contrast large deformation diffeomorphic metric mapping for diffusion tensor imaging , 2009, NeuroImage.

[39]  Alan C. Evans,et al.  Structural maturation of neural pathways in children and adolescents: in vivo study. , 1999, Science.

[40]  Edward T Bullmore,et al.  Morphometric brain abnormalities in schizophrenia in a population-based sample: relationship to duration of illness. , 2010, Schizophrenia bulletin.

[41]  Carl-Fredrik Westin,et al.  White matter hemisphere asymmetries in healthy subjects and in schizophrenia: a diffusion tensor MRI study , 2004, NeuroImage.

[42]  Koushi Harada,et al.  Differentiation between dysmyelination and demyelination using magnetic resonance diffusional anisotropy , 1995, Brain Research.

[43]  H. Yost,et al.  The Left-Right Coordinator: The Role of Vg1 in Organizing Left-Right Axis Formation , 1998, Cell.

[44]  Matthew A. Lambon Ralph,et al.  Lateralization of ventral and dorsal auditory-language pathways in the human brain , 2005, NeuroImage.

[45]  Paul A. Yushkevich,et al.  Structure-specific statistical mapping of white matter tracts , 2007, NeuroImage.

[46]  Carlo Pierpaoli,et al.  PASTA: Pointwise assessment of streamline tractography attributes , 2005, Magnetic resonance in medicine.

[47]  D. Pandya,et al.  Association fiber pathways to the frontal cortex from the superior temporal region in the rhesus monkey , 1988, The Journal of comparative neurology.

[48]  Patrick R. Hof,et al.  Molecular and Cellular Evidence for an Oligodendrocyte Abnormality in Schizophrenia , 2002, Neurochemical Research.

[49]  Karl J. Friston,et al.  Hearing and saying. The functional neuro-anatomy of auditory word processing. , 1996, Brain : a journal of neurology.

[50]  T. Crow,et al.  Dichotic listening impairments in early onset schizophrenia are associated with reduced left temporal lobe volume , 2009, Schizophrenia Research.

[51]  S. H. A. Chen,et al.  Cerebellar transcranial magnetic stimulation impairs verbal working memory , 2005, Annals of neurology.

[52]  A. David,et al.  The planum temporale: a systematic, quantitative review of its structural, functional and clinical significance , 1999, Brain Research Reviews.

[53]  Kenneth Hugdahl,et al.  "Hearing voices": auditory hallucinations as failure of top-down control of bottom-up perceptual processes. , 2009, Scandinavian journal of psychology.

[54]  Derek K. Jones,et al.  Perisylvian language networks of the human brain , 2005, Annals of neurology.

[55]  G D Pearlson,et al.  Reversal of asymmetry of the planum temporale in schizophrenia. , 1995, The American journal of psychiatry.

[56]  Steven A. Chance,et al.  Macroscopic brain asymmetry is changed along the antero–posterior axis in schizophrenia , 2005, Schizophrenia Research.

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

[58]  Alessandro Rossi,et al.  Planum temporale asymmetry and thought disorder in schizophrenia , 1994, Schizophrenia Research.

[59]  Alan C. Evans,et al.  Modulation of cerebral blood-flow in the human auditory cortex during speech: role of motor-to-sensory discharges , 1996, NeuroImage.

[60]  Elia Formisano,et al.  Anatomical brain connectivity and positive symptoms of schizophrenia: A diffusion tensor imaging study , 2009, Psychiatry Research: Neuroimaging.

[61]  R. Kahn,et al.  Volume changes in gray matter in patients with schizophrenia. , 2002, The American journal of psychiatry.

[62]  F. Aboitiz,et al.  The evolutionary origin of the language areas in the human brain. A neuroanatomical perspective , 1997, Brain Research Reviews.

[63]  Byron Bernal,et al.  The connectivity of the superior longitudinal fasciculus: a tractography DTI study. , 2010, Magnetic resonance imaging.

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

[65]  Paul J. Harrison.  The neuropathology of schizophrenia , 2008 .

[66]  M. Albert,et al.  Surface-Based Analysis on Shape and Fractional Anisotropy of White Matter Tracts in Alzheimer's Disease , 2010, PloS one.

[67]  K. Hugdahl,et al.  MR MORPHOMETRY ANALYSIS OF GREY MATTER VOLUME REDUCTION IN SCHIZOPHRENIA: ASSOCIATION WITH HALLUCINATIONS , 2006, The International journal of neuroscience.

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

[69]  B. Anderson,et al.  Anatomic asymmetries of the posterior superior temporal lobes: a postmortem study. , 1999, Neuropsychiatry, neuropsychology, and behavioral neurology.

[70]  P. V. van Zijl,et al.  Three‐dimensional tracking of axonal projections in the brain by magnetic resonance imaging , 1999, Annals of neurology.