Functional and anatomical connectivity abnormalities in left inferior frontal gyrus in schizophrenia

Functional studies in schizophrenia demonstrate prominent abnormalities within the left inferior frontal gyrus (IFG) and also suggest the functional connectivity abnormalities in language network including left IFG and superior temporal gyrus during semantic processing. White matter connections between regions involved in the semantic network have also been indicated in schizophrenia. However, an association between functional and anatomical connectivity disruptions within the semantic network in schizophrenia has not been established. Functional (using levels of processing paradigm) as well as diffusion tensor imaging data from 10 controls and 10 chronic schizophrenics were acquired and analyzed. First, semantic encoding specific activation was estimated, showing decreased activation within the left IFG in schizophrenia. Second, functional time series were extracted from this area, and left IFG specific functional connectivity maps were produced for each subject. In an independent analysis, tract‐based spatial statistics (TBSS) was used to compare fractional anisotropy (FA) values between groups, and to correlate these values with functional connectivity maps. Schizophrenia patients showed weaker functional connectivity within the language network that includes left IFG and left superior temporal sulcus/middle temporal gyrus. FA was reduced in several white matter regions including left inferior frontal and left internal capsule. Finally, left inferior frontal white matter FA was positively correlated with connectivity measures of the semantic network in schizophrenics, but not in controls. Our results indicate an association between anatomical and functional connectivity abnormalities within the semantic network in schizophrenia, suggesting further that the functional abnormalities observed in this disorder might be directly related to white matter disruptions. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.

[1]  August B. Hollingshead,et al.  Two Factor Index of Social Position , 1957 .

[2]  H Merskey,et al.  Coherence on Electroencephalography and Aberrant Functional Organisation of the Brain in Schizophrenic Patients During Activation Tasks , 1991, British Journal of Psychiatry.

[3]  R. Buchanan,et al.  Brain morphology and schizophrenia. A magnetic resonance imaging study of limbic, prefrontal cortex, and caudate structures. , 1992, Archives of general psychiatry.

[4]  Karl J. Friston,et al.  Functional topography: multidimensional scaling and functional connectivity in the brain. , 1996, Cerebral cortex.

[5]  S. Maier,et al.  Line scan diffusion imaging , 1996, Magnetic resonance in medicine.

[6]  P. Williamson,et al.  EEG coherence and syndromes in schizophrenia , 1997, British Journal of Psychiatry.

[7]  S. Maier,et al.  Line scan diffusion imaging: characterization in healthy subjects and stroke patients. , 1998, AJR. American journal of roentgenology.

[8]  G. Pearlson,et al.  Structural evaluation of the prefrontal cortex in schizophrenia. , 1998, The American journal of psychiatry.

[9]  M S Buchsbaum,et al.  MRI white matter diffusion anisotropy and PET metabolic rate in schizophrenia , 1998, Neuroreport.

[10]  R Kikinis,et al.  Left planum temporale volume reduction in schizophrenia. , 1999, Archives of general psychiatry.

[11]  R. McCarley,et al.  Abnormal angular gyrus asymmetry in schizophrenia. , 2000, The American journal of psychiatry.

[12]  R. Buckner,et al.  Neural correlates of verbal memory encoding during semantic and structural processing tasks , 2001, Neuroreport.

[13]  T. Goldberg,et al.  A comparison of verbal fluency tasks in schizophrenic patients and normal controls , 2001, Schizophrenia Research.

[14]  Ron Kikinis,et al.  Prefrontal cortex, negative symptoms, and schizophrenia: an MRI study , 2001, Psychiatry Research: Neuroimaging.

[15]  N. Alpert,et al.  Prefrontal regions supporting spontaneous and directed application of verbal learning strategies: evidence from PET. , 2001, Brain : a journal of neurology.

[16]  J. Ford,et al.  Reduced communication between frontal and temporal lobes during talking in schizophrenia , 2002, Biological Psychiatry.

[17]  Ingrid Agartz,et al.  Reduced grey and white matter volumes in the temporal lobe of male patients with chronic schizophrenia , 2002, European Archives of Psychiatry and Clinical Neuroscience.

[18]  J. Mazziotta,et al.  Brain Mapping: The Methods , 2002 .

[19]  Karl J. Friston,et al.  Reduced frontotemporal functional connectivity in schizophrenia associated with auditory hallucinations , 2002, Biological Psychiatry.

[20]  Thomas E. Nichols,et al.  Nonparametric permutation tests for functional neuroimaging: A primer with examples , 2002, Human brain mapping.

[21]  T. Klingberg,et al.  Combined analysis of DTI and fMRI data reveals a joint maturation of white and grey matter in a fronto-parietal network. , 2003, Brain research. Cognitive brain research.

[22]  Karl J. Friston,et al.  A disturbance of nonlinear interdependence in scalp EEG of subjects with first episode schizophrenia , 2003, NeuroImage.

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

[24]  Thomas E. Nichols,et al.  Controlling the familywise error rate in functional neuroimaging: a comparative review , 2003, Statistical methods in medical research.

[25]  Cynthia G. Wible,et al.  An fMRI study of semantic processing in men with schizophrenia , 2003, NeuroImage.

[26]  Carlo Caltagirone,et al.  Chronic schizophrenia as a brain misconnection syndrome: a white matter voxel-based morphometry study , 2003, Schizophrenia Research.

[27]  J Baudewig,et al.  Thresholding in correlation analyses of magnetic resonance functional neuroimaging. , 2003, Magnetic resonance imaging.

[28]  Valerie A. Carr,et al.  Spatiotemporal Dynamics of Modality-Specific and Supramodal Word Processing , 2003, Neuron.

[29]  T. Crow,et al.  Disintegration of the components of language as the path to a revision of Bleuler's and Schneider's concepts of schizophrenia , 2003, British Journal of Psychiatry.

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

[31]  B. Turetsky,et al.  Event-related fMRI of frontotemporal activity during word encoding and recognition in schizophrenia. , 2004, The American journal of psychiatry.

[32]  Ron Kikinis,et al.  Comparison of single-shot echo-planar and line scan protocols for diffusion tensor imaging. , 2004, Academic radiology.

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

[34]  T. Crow,et al.  Semantic fluency is impaired but phonemic and design fluency are preserved in early-onset schizophrenia , 2004, Schizophrenia Research.

[35]  Marieke Langen,et al.  Gray and white matter volume abnormalities in monozygotic and same-gender dizygotic twins discordant for schizophrenia , 2004, Biological Psychiatry.

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

[37]  Mark Elliott,et al.  Levels-of-processing effect on frontotemporal function in schizophrenia during word encoding and recognition. , 2005, The American journal of psychiatry.

[38]  Kristen M. Haut,et al.  The Influence of Encoding Strategy on Episodic Memory and Cortical Activity in Schizophrenia , 2005, Biological Psychiatry.

[39]  Richard J. Davidson,et al.  Comparison of fMRI motion correction software tools , 2005, NeuroImage.

[40]  B. Mazoyer,et al.  Atypical hemispheric specialization for language in right-handed schizophrenia patients , 2005, Biological Psychiatry.

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

[42]  Sifis Michelogiannis,et al.  EEG coherence during hemispheric activation in schizophrenics , 2005, European Archives of Psychiatry and Clinical Neuroscience.

[43]  R. Condray,et al.  Language disorder in schizophrenia as a developmental learning disorder , 2005, Schizophrenia Research.

[44]  Nathalie Tzourio-Mazoyer,et al.  New insights into the anatomo-functional connectivity of the semantic system: a study using cortico-subcortical electrostimulations. , 2005, Brain : a journal of neurology.

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

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

[47]  Derek K. Jones,et al.  The effect of filter size on VBM analyses of DT-MRI data , 2005, NeuroImage.

[48]  A. Meyer-Lindenberg,et al.  Regionally specific disturbance of dorsolateral prefrontal-hippocampal functional connectivity in schizophrenia. , 2005, Archives of general psychiatry.

[49]  L. J. Whalley,et al.  White matter integrity and cognition in childhood and old age , 2006, Neurology.

[50]  J. Kleinman,et al.  Critical Factors in Gene Expression in Postmortem Human Brain: Focus on Studies in Schizophrenia , 2006, Biological Psychiatry.

[51]  Cheuk Y. Tang,et al.  Diffusion tensor imaging of frontal lobe white matter tracts in schizophrenia , 2006, Annals of general psychiatry.

[52]  Vincent Schmithorst,et al.  Functional MRI evidence for disparate developmental processes underlying intelligence in boys and girls , 2006, NeuroImage.

[53]  Bernard Mazoyer,et al.  Meta-analyzing left hemisphere language areas: Phonology, semantics, and sentence processing , 2006, NeuroImage.

[54]  John S. Duncan,et al.  Hemispheric asymmetries in language-related pathways: A combined functional MRI and tractography study , 2006, NeuroImage.

[55]  M. Noseworthy,et al.  Diffusion tensor imaging of white matter after cranial radiation in children for medulloblastoma: correlation with IQ. , 2006, Neuro-oncology.

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

[57]  Friedemann Pulvermüller,et al.  Early MEG Activation Dynamics in the Left Temporal and Inferior Frontal Cortex Reflect Semantic Context Integration , 2007, Journal of Cognitive Neuroscience.

[58]  D. Barch,et al.  Levels-of-Processing Effects in First-Degree Relatives of Individuals with Schizophrenia , 2007, Biological Psychiatry.

[59]  T. Crow,et al.  Schneider's first rank symptoms and continuous performance disturbance as indices of dysconnectivity of left- and right-hemispheric components of language in schizophrenia , 2007, Schizophrenia Research.

[60]  E. Torrey,et al.  Schizophrenia and the inferior parietal lobule , 2007, Schizophrenia Research.

[61]  Bruce Fischl,et al.  Reduced microstructural integrity of the white matter underlying anterior cingulate cortex is associated with increased saccadic latency in schizophrenia , 2007, NeuroImage.

[62]  P Sham,et al.  A diffusion tensor imaging study of structural dysconnectivity in never-medicated, first-episode schizophrenia , 2007, Psychological Medicine.

[63]  Thomas E. Nichols,et al.  Acquisition and voxelwise analysis of multi-subject diffusion data with Tract-Based Spatial Statistics , 2007, Nature Protocols.

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

[65]  H. Duffau,et al.  Does the left inferior longitudinal fasciculus play a role in language? A brain stimulation study. , 2007, Brain : a journal of neurology.

[66]  Marek Kubicki,et al.  Attentional networks and cingulum bundle in chronic schizophrenia , 2007, Schizophrenia Research.

[67]  D. Goff,et al.  Increased temporal and prefrontal activity in response to semantic associations in schizophrenia. , 2007, Archives of general psychiatry.

[68]  Karl J. Friston,et al.  Functional Connectivity: Eigenimages and multivariate analyses , 2003 .

[69]  Michael Erb,et al.  Neural correlates of metaphor processing in schizophrenia , 2007, NeuroImage.

[70]  R. Thatcher,et al.  Intelligence and EEG current density using low‐resolution electromagnetic tomography (LORETA) , 2007, Human brain mapping.

[71]  J. Ragland,et al.  Alterations of fronto-temporal connectivity during word encoding in schizophrenia , 2007, Psychiatry Research: Neuroimaging.

[72]  Cynthia G. Wible,et al.  Functional neuroimaging of word priming in males with chronic schizophrenia , 2007, NeuroImage.

[73]  C Barbui,et al.  Cortical white-matter microstructure in schizophrenia. Diffusion imaging study. , 2007, The British journal of psychiatry : the journal of mental science.

[74]  Sven Haller,et al.  Spatial and temporal analysis of fMRI data on word and sentence reading , 2007, The European journal of neuroscience.

[75]  Andrew T. Smith,et al.  A comment on the severity of the effects of non-white noise in fMRI time-series , 2007, NeuroImage.

[76]  Noah A. Shamosh,et al.  Multiple Bases of Human Intelligence Revealed by Cortical Thickness and Neural Activation , 2008, The Journal of Neuroscience.

[77]  Peter A. Calabresi,et al.  Tract probability maps in stereotaxic spaces: Analyses of white matter anatomy and tract-specific quantification , 2008, NeuroImage.

[78]  Manzar Ashtari,et al.  Clinical and Neuropsychological Correlates of White Matter Abnormalities in Recent Onset Schizophrenia , 2008, Neuropsychopharmacology.

[79]  Jens Frahm,et al.  A novel group analysis for functional MRI of the human brain based on a two-threshold correlation (TTC) method , 2008, Journal of Neuroscience Methods.

[80]  D. Dietrich,et al.  The myelin-pathogenesis puzzle in schizophrenia: a literature review , 2008, Molecular Psychiatry.

[81]  S. Kumra.  DISRUPTION OF WHITE MATTER INTEGRITY IN THE INFERIOR LONGITUDINAL FASCICULUS IN ADOLESCENTS WITH SCHIZOPHRENIA AS REVEALED BY FIBER TRACTOGRAPHY , 2008, Schizophrenia Research.

[82]  M. Just,et al.  fMRI investigation of working memory for faces in autism: visual coding and underconnectivity with frontal areas. , 2008, Cerebral cortex.

[83]  M. Keshavan,et al.  Automated MRI parcellation study of regional volume and thickness of prefrontal cortex (PFC) in antipsychotic‐naïve schizophrenia , 2008, Acta psychiatrica Scandinavica.

[84]  Gregory G. Brown,et al.  Brain response abnormalities during verbal learning among patients with schizophrenia , 2008, Psychiatry Research: Neuroimaging.

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