White matter tracts in first-episode psychosis: A DTI tractography study of the uncinate fasciculus

A model of disconnectivity involving abnormalities in the cortex and connecting white matter pathways may explain the symptoms and cognitive abnormalities of schizophrenia. Recently, diffusion imaging tractography has made it possible to study white matter pathways in detail, and we present here a study of patients with first-episode psychosis using this technique. We studied the uncinate fasciculus (UF), the largest white matter tract that connects the frontal and temporal lobes, two brain regions significantly implicated in schizophrenia. Nineteen patients with first-episode schizophrenia and 23 controls were studied using a probabilistic tractography algorithm (PICo). Fractional anisotropy (FA) and probability of connection were obtained for every voxel in the tract, and the group means and distributions of these variables were compared. The spread of the FA distribution in the upper tail, as measured by the squared coefficient of variance (SCV), was reduced in the left UF in the patient group, indicating that the number of voxels with high FA values was reduced in the core of the tract and suggesting the presence of changes in fibre alignment and tract coherence in the patient group. The SCV of FA was lower in females across both groups and there was no correlation between the SCV of FA and clinical ratings.

[1]  John S. Duncan,et al.  Noninvasive in vivo demonstration of the connections of the human parahippocampal gyrus , 2004, NeuroImage.

[2]  Ellen Frank,et al.  Magnetic resonance imaging study of corpus callosum abnormalities in patients with bipolar disorder , 2003, Biological Psychiatry.

[3]  H. Barbas.  Connections underlying the synthesis of cognition, memory, and emotion in primate prefrontal cortices , 2000, Brain Research Bulletin.

[4]  Paul J. Harrison,et al.  Interstitial white matter neurons express less reelin and are abnormally distributed in schizophrenia: towards an integration of molecular and morphologic aspects of the neurodevelopmental hypothesis , 2003, Molecular Psychiatry.

[5]  M. Mesulam,et al.  Trajectories of cholinergic pathways within the cerebral hemispheres of the human brain. , 1998, Brain : a journal of neurology.

[6]  Daniel C. Alexander,et al.  Camino: Open-Source Diffusion-MRI Reconstruction and Processing , 2006 .

[7]  Hao Huang,et al.  DTI tractography based parcellation of white matter: Application to the mid-sagittal morphology of corpus callosum , 2005, NeuroImage.

[8]  E. Tulving,et al.  Episodic memory and the self in a case of isolated retrograde amnesia. , 1998 .

[9]  P. Maclean.  Some psychiatric implications of physiological studies on frontotemporal portion of limbic system (visceral brain). , 1952, Electroencephalography and clinical neurophysiology.

[10]  N C Andreasen,et al.  Acoustic analysis: an objective measure of affective flattening. , 1981, Archives of general psychiatry.

[11]  P. Morgan,et al.  Pyramidal tract mapping by diffusion tensor magnetic resonance imaging in multiple sclerosis: improving correlations with disability , 2003, Journal of neurology, neurosurgery, and psychiatry.

[12]  Kazuya Iwamoto,et al.  Altered expression of mitochondria-related genes in postmortem brains of patients with bipolar disorder or schizophrenia, as revealed by large-scale DNA microarray analysis. , 2005, Human molecular genetics.

[13]  Timothy Edward John Behrens,et al.  Probabilistic diffusion tractography: a potential tool to assess the rate of disease progression in amyotrophic lateral sclerosis. , 2006, Brain : a journal of neurology.

[14]  R. Bronen,et al.  MR imaging of the temporal stem: anatomic dissection tractography of the uncinate fasciculus, inferior occipitofrontal fasciculus, and Meyer's loop of the optic radiation. , 2004, AJNR. American journal of neuroradiology.

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

[16]  R. Drake,et al.  Diagnosis of alcohol use disorders in schizophrenia. , 1990, Schizophrenia bulletin.

[17]  P. Basser,et al.  MR diffusion tensor spectroscopy and imaging. , 1994, Biophysical journal.

[18]  Karl J. Friston,et al.  Schizophrenia: a disconnection syndrome? , 1995, Clinical neuroscience.

[19]  Derek K. Jones,et al.  Virtual in Vivo Interactive Dissection of White Matter Fasciculi in the Human Brain , 2002, NeuroImage.

[20]  J Schröder,et al.  Corpus callosum in first-episode patients with schizophrenia – a magnetic resonance imaging study , 2003, Psychological Medicine.

[21]  Timothy Edward John Behrens,et al.  Characterization and propagation of uncertainty in diffusion‐weighted MR imaging , 2003, Magnetic resonance in medicine.

[22]  Paul J. Harrison,et al.  Asymmetry of the uncinate fasciculus: a post-mortem study of normal subjects and patients with schizophrenia. , 2002, Cerebral cortex.

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

[24]  E Frank,et al.  Corpus callosum signal intensity in patients with bipolar and unipolar disorder , 2004, Journal of Neurology, Neurosurgery & Psychiatry.

[25]  W H Wong,et al.  Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[26]  Derek K. Jones,et al.  Age effects on diffusion tensor magnetic resonance imaging tractography measures of frontal cortex connections in schizophrenia , 2006, Human brain mapping.

[27]  Stephen M. Smith,et al.  A global optimisation method for robust affine registration of brain images , 2001, Medical Image Anal..

[28]  Paul J. Harrison,et al.  Synaptophysin protein and mRNA expression in the human hippocampal formation from birth to old age , 2006, Hippocampus.

[29]  G J Barker,et al.  Neuropathological abnormalities in schizophrenia: evidence from magnetization transfer imaging. , 2001, Brain : a journal of neurology.

[30]  D Castle,et al.  Psychotic Disorders in Urban Areas: An Overview of the Study on Low Prevalence Disorders , 2000, The Australian and New Zealand journal of psychiatry.

[31]  Danny Sullivan,et al.  The neuropsychiatry of Niemann-Pick type C disease in adulthood. , 2006, The Journal of neuropsychiatry and clinical neurosciences.

[32]  Daniel C. Alexander,et al.  Probabilistic Monte Carlo Based Mapping of Cerebral Connections Utilising Whole-Brain Crossing Fibre Information , 2003, IPMI.

[33]  Manzar Ashtari,et al.  White matter abnormalities in first-episode schizophrenia or schizoaffective disorder: a diffusion tensor imaging study. , 2005, The American journal of psychiatry.

[34]  Gareth J Barker,et al.  Gray and white matter brain abnormalities in first-episode schizophrenia inferred from magnetization transfer imaging. , 2003, Archives of general psychiatry.

[35]  M. Kubicki,et al.  Neuropsychological correlates of diffusion tensor imaging in schizophrenia. , 2004, Neuropsychology.

[36]  Geoff J. M. Parker,et al.  Characterizing function–structure relationships in the human visual system with functional MRI and diffusion tensor imaging , 2004, NeuroImage.

[37]  Jeffrey A. Lieberman,et al.  Characterizing and dating the onset of symptoms in psychotic illness: the Symptom Onset in Schizophrenia (SOS) inventory , 2000, Schizophrenia Research.

[38]  Paul J. Harrison,et al.  Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence , 2005, Molecular Psychiatry.

[39]  M. Mesulam.  A cortical network for directed attention and unilateral neglect , 1981, Annals of neurology.

[40]  S. Lawrie,et al.  Brain abnormality in schizophrenia , 1998, British Journal of Psychiatry.

[41]  M. Catani,et al.  The rises and falls of disconnection syndromes. , 2005, Brain : a journal of neurology.

[42]  Carlo Pierpaoli,et al.  A diffusion tensor magnetic resonance imaging study of frontal cortex connections in very-late-onset schizophrenia-like psychosis. , 2005, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

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

[44]  F. Benes,et al.  Emerging principles of altered neural circuitry in schizophrenia , 2000, Brain Research Reviews.

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

[46]  P. Allison.  Measures of Inequality , 1978 .

[47]  Sukhwinder S. Shergill,et al.  Tract-specific anisotropy measurements in diffusion tensor imaging , 2006, Psychiatry Research: Neuroimaging.

[48]  Peter B. Jones,et al.  Oligodendrocyte dysfunction in schizophrenia and bipolar disorder , 2003, The Lancet.

[49]  E. Tulving,et al.  Episodic memory and the self in a case of isolated retrograde amnesia. , 1998, Brain : a journal of neurology.

[50]  S. Arridge,et al.  Detection and modeling of non‐Gaussian apparent diffusion coefficient profiles in human brain data , 2002, Magnetic resonance in medicine.

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

[52]  M. Raichle,et al.  Tracking neuronal fiber pathways in the living human brain. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[53]  Carl-Fredrik Westin,et al.  Spatial normalization of diffusion tensor MRI using multiple channels , 2003, NeuroImage.

[54]  M. Annett.  A classification of hand preference by association analysis. , 1970, British journal of psychology.

[55]  R. McCarley,et al.  A review of MRI findings in schizophrenia , 2001, Schizophrenia Research.

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

[57]  Daniel C Alexander,et al.  Probabilistic anatomical connectivity derived from the microscopic persistent angular structure of cerebral tissue , 2005, Philosophical Transactions of the Royal Society B: Biological Sciences.

[58]  W. Honer,et al.  Abnormalities of myelination in schizophrenia detected in vivo with MRI, and post-mortem with analysis of oligodendrocyte proteins , 2003, Molecular Psychiatry.

[59]  Scott K Holland,et al.  Evidence of white matter pathology in bipolar disorder adolescents experiencing their first episode of mania: a diffusion tensor imaging study. , 2006, The American journal of psychiatry.

[60]  Gareth J. Barker,et al.  Abnormal brain connectivity in first-episode psychosis: A diffusion MRI tractography study of the corpus callosum , 2007, NeuroImage.