Pathways that make voices: white matter changes in auditory hallucinations.

BACKGROUND The origin of auditory hallucinations, which are one of the core symptoms of schizophrenia, is still a matter of debate. It has been hypothesized that alterations in connectivity between frontal and parietotemporal speech-related areas might contribute to the pathogenesis of auditory hallucinations. These networks are assumed to become dysfunctional during the generation and monitoring of inner speech. Magnetic resonance diffusion tensor imaging is a relatively new in vivo method to investigate the directionality of cortical white matter tracts. OBJECTIVE To investigate, using diffusion tensor imaging, whether previously described abnormal activation patterns observed during auditory hallucinations relate to changes in structural interconnections between the frontal and parietotemporal speech-related areas. METHODS A 1.5 T magnetic resonance scanner was used to acquire twelve 5-mm slices covering the Sylvian fissure. Fractional anisotropy was assessed in 13 patients prone to auditory hallucinations, in 13 patients without auditory hallucinations, and in 13 healthy control subjects. Structural magnetic resonance imaging was conducted in the same session. Based on an analysis of variance, areas with significantly different fractional anisotropy values between groups were selected for a confirmatory region of interest analysis. Additionally, descriptive voxel-based t tests between the groups were computed. RESULTS In patients with hallucinations, we found significantly higher white matter directionality in the lateral parts of the temporoparietal section of the arcuate fasciculus and in parts of the anterior corpus callosum compared with control subjects and patients without hallucinations. Comparing patients with hallucinations with patients without hallucinations, we found significant differences most pronounced in the left hemispheric fiber tracts, including the cingulate bundle. CONCLUSION Our findings suggest that during inner speech, the alterations of white matter fiber tracts in patients with frequent hallucinations lead to abnormal coactivation in regions related to the acoustical processing of external stimuli. This abnormal activation may account for the patients' inability to distinguish self-generated thoughts from external stimulation.

[1]  É. Esquirol.  Des maladies mentales : considérées sous les rapports médical, hygiénique et médico-légal. [Volume 1] / par E. Esquirol,... , 1838 .

[2]  C. Wernicke,et al.  Grundriss der Psychiatrie in klinischen Vorlesungen , 1894 .

[3]  E. Southard.  A STUDY OF THE DEMENTIA PRÆCOX GROUP IN THE LIGHT OF CERTAIN CASES SHOWING ANOMALIES OR SCLEROSES IN PARTICULAR BRAIN-REGIONS , 1910 .

[4]  A Study of the Dementia Precox Group in the Light of Certain Cases Showing Anomalies or Scleroses in Particular Brain Regions , 1910 .

[5]  E. B. Southard,et al.  ON THE TOPOGRAPHICAL DISTRIBUTION OF CORTEX LESIONS AND ANOMALIES IN DEMENTIA PRÆCOX, WITH SOME ACCOUNT OF THEIR FUNCTIONAL SIGNIFICANCE , 1914 .

[6]  Henry Rice,et al.  Fundamentals of Human Neuropsychology , 1985, The Yale Journal of Biology and Medicine.

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

[8]  Brämer Gr.  International statistical classification of diseases and related health problems. Tenth revision. , 1988, World health statistics quarterly. Rapport trimestriel de statistiques sanitaires mondiales.

[9]  J. Talairach,et al.  Co-Planar Stereotaxic Atlas of the Human Brain: 3-Dimensional Proportional System: An Approach to Cerebral Imaging , 1988 .

[10]  Richard P. Bentall,et al.  Sensory Deception: A Scientific Analysis Of Hallucination , 1988 .

[11]  G D Pearlson,et al.  Auditory hallucinations and smaller superior temporal gyral volume in schizophrenia. , 1990, The American journal of psychiatry.

[12]  C Nahmias,et al.  Regional Brain Metabolism During Auditory Hallucinations in Chronic Schizophrenia , 1990, British Journal of Psychiatry.

[13]  A. Tien,et al.  Distributions of hallucinations in the population. , 1991, Social psychiatry and psychiatric epidemiology.

[14]  A. David.  Callosal transfer in schizophrenia: too much or too little? , 1993, Journal of abnormal psychology.

[15]  R. Murray,et al.  Increased blood flow in Broca's area during auditory hallucinations in schizophrenia , 1993, The Lancet.

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

[17]  N. Andreasen,et al.  Symptom dimensions and brain morphology in schizophrenia and related psychotic disorders. , 1995, Journal of psychiatric research.

[18]  Karl J. Friston,et al.  Regional Brain Activity in Chronic Schizophrenic Patients during the Performance of a Verbal Fluency Task , 1995, British Journal of Psychiatry.

[19]  C. D. Frith,et al.  Abnormal monitoring of inner speech: a physiological basis for auditory hallucinations , 1995, The Lancet.

[20]  Guy.  Clinical Global Impressions 1976 , 1995 .

[21]  C. Stefanis,et al.  Clinical characteristics of auditory hallucinations , 1995, Acta psychiatrica Scandinavica.

[22]  Richard S. J. Frackowiak,et al.  A functional neuroanatomy of hallucinations in schizophrenia , 1995, Nature.

[23]  A. David,et al.  The auditory hallucination: a phenomenological survey , 1996, Psychological Medicine.

[24]  P. Liddle.  Functional imaging--schizophrenia. , 1996, British medical bulletin.

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

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

[27]  A. David.  Auditory hallucinations: phenomenology, neuropsychology and neuroimaging update , 1999, Acta psychiatrica Scandinavica. Supplementum.

[28]  M. I. Smith,et al.  A study of rotationally invariant and symmetric indices of diffusion anisotropy. , 1999, Magnetic resonance imaging.

[29]  A. D. de Crespigny,et al.  Compromised white matter tract integrity in schizophrenia inferred from diffusion tensor imaging. , 1999, Archives of general psychiatry.

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

[31]  Peter B. Jones,et al.  Spatial and temporal mapping of neural activity associated with auditory hallucinations , 1999, The Lancet.

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

[33]  Stephan Heckers,et al.  Neuroimaging of hallucinations: a review of the literature , 1999, Psychiatry Research: Neuroimaging.

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

[35]  Peter G. Morris,et al.  The functional anatomy of auditory hallucinations in schizophrenia , 2000, Psychiatry Research: Neuroimaging.

[36]  H. Holcomb,et al.  The limbic cortex in schizophrenia: focus on the anterior cingulate , 2000, Brain Research Reviews.

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

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

[39]  N. Andreasen.  Schizophrenia: the fundamental questions , 2000, Brain Research Reviews.

[40]  Ann M Graybiel,et al.  Toward a Neurobiology of Obsessive-Compulsive Disorder , 2000, Neuron.

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

[42]  A. Simmons,et al.  Corpus callosum area and functioning in schizophrenic patients with auditory–verbal hallucinations , 2001, Schizophrenia Research.

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

[44]  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.

[45]  A. Simmons,et al.  Are auditory hallucinations the consequence of abnormal cerebral lateralization? A morphometric MRI study of the sylvian fissure and planum temporale , 2001, Biological Psychiatry.

[46]  S. Skare,et al.  Abnormal brain white matter in schizophrenia: a diffusion tensor imaging study , 2001, Neuroreport.

[47]  Rainer Goebel,et al.  An Efficient Algorithm for Topologically Correct Segmentation of the Cortical Sheet in Anatomical MR Volumes , 2001, NeuroImage.

[48]  P. Halligan,et al.  Cognitive neuropsychiatry: towards a scientific psychopathology , 2001, Nature Reviews Neuroscience.

[49]  A L Brody,et al.  Prefrontal-subcortical and limbic circuit mediation of major depressive disorder. , 2001, Seminars in clinical neuropsychiatry.

[50]  J. Allman,et al.  The Anterior Cingulate Cortex , 2001, Annals of the New York Academy of Sciences.

[51]  D. Le Bihan,et al.  Diffusion tensor imaging: Concepts and applications , 2001, Journal of magnetic resonance imaging : JMRI.

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

[53]  G. Barker,et al.  Investigating regional white matter in schizophrenia using diffusion tensor imaging , 2002, Neuroreport.

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

[55]  Carl-Fredrik Westin,et al.  High-resolution line scan diffusion tensor MR imaging of white matter fiber tract anatomy. , 2002, AJNR. American journal of neuroradiology.

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

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

[58]  J. Helpern,et al.  Neuropsychiatric applications of DTI – a review , 2002, NMR in biomedicine.

[59]  G. Egan,et al.  Cortical activation associated with the experience of auditory hallucinations and perception of human speech in schizophrenia: a PET correlation study , 2003, Psychiatry Research: Neuroimaging.

[60]  G M Innocenti,et al.  Schizophrenia, neurodevelopment and corpus callosum , 2003, Molecular Psychiatry.

[61]  Michael Sanfilipo,et al.  Inferior frontal white matter anisotropy and negative symptoms of schizophrenia: a diffusion tensor imaging study. , 2003, The American journal of psychiatry.

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

[63]  C. Habel,et al.  Language , 1931, NeuroImage.

[64]  A. Tien.  Distribution of hallucinations in the population , 1991, Social Psychiatry and Psychiatric Epidemiology.

[65]  Thomas L Chenevert,et al.  Clinical applications of diffusion tensor imaging , 2004, Journal of magnetic resonance imaging : JMRI.

[66]  S. Katzenelbogen,et al.  Dementia praecox , 1942, The Psychiatric Quarterly.