Microstructural alterations of the arcuate fasciculus in schizophrenia patients with frequent auditory verbal hallucinations

Auditory verbal hallucinations (AVH) is a common and stressful symptom of schizophrenia. Disrupted connectivity between frontal and temporo-parietal language areas, giving rise to the misattribution of inner speech, is speculated to underlie this phenomenon. Disrupted connectivity should be reflected in the microstructure of the arcuate fasciculi (AF); the main connection between frontal and temporo-parietal language areas. In this study we compared microstructural properties of the AF and three other fiber tracts (cortical spinal tract, cingulum and uncinate fasciculus), between 44 schizophrenia patients with chronic severe hallucinations and 42 control subjects using diffusion tensor imaging (DTI) and magnetic transfer imaging (MTI). The DTI scans were used to compute fractional anisotropy (FA) and to reconstruct the fiber bundles of interest, while the MTI scans were used to compute magnetic transfer ratio (MTR) values. The patient group showed a general decrease in FA for all bundles. In the arcuate fasciculus this decreased FA was coupled to a significant increase in MTR values. A correlation was found between mean MTR values in both arcuate fasciculi and the severity of positive symptoms. The combination of decreased FA and increased MTR values observed in the arcuate fasciculi in patients suggests increased free water concentrations, probably caused by degraded integrity of the axons or the supportive glia cells. This suggests that disintegrated fiber integrity in the connection between frontal and temporo-parietal language areas in the schizophrenia patients is associated with their liability for auditory verbal hallucinations.

[1]  R I Grossman,et al.  Magnetization transfer histogram methodology: its clinical and neuropsychological correlates. , 1999, Neurology.

[2]  Carl-Fredrik Westin,et al.  Increased diffusivity in superior temporal gyrus in patients with schizophrenia: A Diffusion Tensor Imaging study , 2009, Schizophrenia Research.

[3]  Stefan Skare,et al.  How to correct susceptibility distortions in spin-echo echo-planar images: application to diffusion tensor imaging , 2003, NeuroImage.

[4]  R. C. Oldfield The assessment and analysis of handedness: the Edinburgh inventory. , 1971, Neuropsychologia.

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

[6]  P. Lauterbur,et al.  Apparent diffusion tensor measurements in myelin‐deficient rat spinal cords , 2001, Magnetic resonance in medicine.

[7]  R S Balaban,et al.  Magnetization transfer imaging: practical aspects and clinical applications. , 1994, Radiology.

[8]  L. de Haan,et al.  Diffusion tensor imaging in the early phase of schizophrenia: what have we learned? , 2010, Journal of psychiatric research.

[9]  R Fog,et al.  A Progress Report , 2015 .

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

[11]  S. Wakana,et al.  Fiber tract-based atlas of human white matter anatomy. , 2004, Radiology.

[12]  Renaud Jardri,et al.  Cortical activations during auditory verbal hallucinations in schizophrenia: a coordinate-based meta-analysis. , 2011, The American journal of psychiatry.

[13]  A. Anderson,et al.  Probing the pathophysiology of auditory/verbal hallucinations by combining functional magnetic resonance imaging and transcranial magnetic stimulation. , 2007, Cerebral cortex.

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

[15]  Barkovich Aj Concepts of Myelin and Myelination in Neuroradiology , 2000 .

[16]  R. Kahn,et al.  Can fMRI-guidance improve the efficacy of rTMS treatment for auditory verbal hallucinations? , 2007, Schizophrenia Research.

[17]  A. Barkovich Concepts of myelin and myelination in neuroradiology. , 2000, AJNR. American journal of neuroradiology.

[18]  N. Tarrier,et al.  Scales to measure dimensions of hallucinations and delusions: the psychotic symptom rating scales (PSYRATS) , 1999, Psychological Medicine.

[19]  Derek K. Jones,et al.  RESTORE: Robust estimation of tensors by outlier rejection , 2005, Magnetic resonance in medicine.

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

[21]  P. Basser,et al.  Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI. , 1996, Journal of magnetic resonance. Series B.

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

[23]  P. McGuire,et al.  Superior temporal gray and white matter changes in schizophrenia or antipsychotic related effects? , 2009, Schizophrenia Research.

[24]  Rutger Goekoop,et al.  Deactivation of the parahippocampal gyrus preceding auditory hallucinations in schizophrenia. , 2010, The American journal of psychiatry.

[25]  Stefan Skare,et al.  A Model-Based Method for Retrospective Correction of Geometric Distortions in Diffusion-Weighted EPI , 2002, NeuroImage.

[26]  J. Ford,et al.  Electrophysiological and diffusion tensor imaging evidence of delayed corollary discharges in patients with schizophrenia , 2010, Psychological Medicine.

[27]  R. Henkelman,et al.  Magnetization transfer in MRI: a review , 2001, NMR in biomedicine.

[28]  Sukhwinder S Shergill,et al.  Auditory hallucinations: a review of psychological treatments , 1998, Schizophrenia Research.

[29]  Sophia Frangou,et al.  Recent diffusion tensor imaging findings in early stages of schizophrenia , 2009, Current opinion in psychiatry.

[30]  R. Morris,et al.  Imaging age‐related cognitive decline: A comparison of diffusion tensor and magnetization transfer MRI , 2009, Journal of magnetic resonance imaging : JMRI.

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

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

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

[34]  R. Kahn,et al.  Language lateralization in female patients with schizophrenia: an fMRI study , 2003, Schizophrenia Research.

[35]  A. Benton,et al.  On Aphasia , 1874, British medical journal.

[36]  R. Murray,et al.  Mapping auditory hallucinations in schizophrenia using functional magnetic resonance imaging. , 2000, Archives of general psychiatry.

[37]  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.

[38]  Sean Marrett,et al.  Imaging Motor-to-Sensory Discharges in the Human Brain: An Experimental Tool for the Assessment of Functional Connectivity , 1996, NeuroImage.

[39]  R. Kahn,et al.  Auditory verbal hallucinations predominantly activate the right inferior frontal area. , 2008, Brain : a journal of neurology.

[40]  Jae-Jin Kim,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, Psychiatry Research: Neuroimaging.

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

[42]  N C Andreasen,et al.  The Comprehensive Assessment of Symptoms and History (CASH). An instrument for assessing diagnosis and psychopathology. , 1992, Archives of general 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]  Karl J. Friston,et al.  Unified segmentation , 2005, NeuroImage.

[45]  R. Kahn,et al.  Tract-based analysis of magnetization transfer ratio and diffusion tensor imaging of the frontal and frontotemporal connections in schizophrenia. , 2010, Schizophrenia bulletin.

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

[47]  K. Diederen,et al.  Healthy individuals with auditory verbal hallucinations; who are they? Psychiatric assessments of a selected sample of 103 subjects. , 2010, Schizophrenia bulletin.

[48]  Judith M Ford,et al.  Synch before you speak: auditory hallucinations in schizophrenia. , 2007, The American journal of psychiatry.