New evidence for involvement of the entorhinal region in schizophrenia: a combined MRI volumetric and DTI study

Postmortem examinations and magnetic resonance imaging (MRI) studies suggest involvement of the entorhinal cortex (EC) in schizophrenic psychoses. However, the extent and nature of the possible pathogenetical process underlying the observed alterations of this limbic key region for processing of multimodal sensory information remains unclear. Three-dimensional high-resolution MRI volumetry and evaluation of the regional diffusional anisotropy based on diffusion tensor imaging (DTI) were performed on the EC of 15 paranoid schizophrenic patients and 15 closely matched control subjects. In schizophrenic patients, EC volumes showed a slight, but not significant, decrease. However, the anisotropy values, expressed as inter-voxel coherences (COH), were found to be significantly decreased by 17.9% (right side) and 12.5% (left side), respectively, in schizophrenics. Reduction of entorhinal diffusional anisotropy can be hypothesized to be functionally related to disturbances in the perforant path, the principal efferent EC fiber tract supplying the limbic system with neuronal input from multimodal association centers. Combinations of different MRI modalities are a promising approach for the detection and characterization of subtle brain tissue alterations.

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

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

[3]  H. Braak,et al.  The human entorhinal cortex: normal morphology and lamina-specific pathology in various diseases , 1992, Neuroscience Research.

[4]  James C. Gee,et al.  Spatial transformations of diffusion tensor magnetic resonance images , 2001, IEEE Transactions on Medical Imaging.

[5]  S. Arnold,et al.  Cellular and Molecular Neuropathology of the Parahippocampal Region in Schizophrenia , 2000, Annals of the New York Academy of Sciences.

[6]  R. Insausti,et al.  The human entorhinal cortex: A cytoarchitectonic analysis , 1995, The Journal of comparative neurology.

[7]  S. Skare,et al.  Noise considerations in the determination of diffusion tensor anisotropy. , 2000, Magnetic resonance imaging.

[8]  P. Basser,et al.  Toward a quantitative assessment of diffusion anisotropy , 1996, Magnetic resonance in medicine.

[9]  P. Kalus,et al.  Disturbances of Corticogenesis in Schizophrenia: Morphological Findings Provide New Evidence for the Maldevelopmental Hypothesis , 1999, Neuropsychobiology.

[10]  Julie Kreyenbuhl,et al.  Practice guideline for the treatment of patients with schizophrenia , 1997 .

[11]  Neda Bernasconi,et al.  Entorhinal Cortex MRI Assessment in Temporal, Extratemporal, and Idiopathic Generalized Epilepsy , 2003, Epilepsia.

[12]  Adolf Pfefferbaum,et al.  Diffusion tensor imaging in normal aging and neuropsychiatric disorders. , 2003, European journal of radiology.

[13]  H. Nasrallah,et al.  The volume of the entorhinal cortex in schizophrenia: A controlled MRI study , 1997, Progress in Neuro-psychopharmacology and Biological Psychiatry.

[14]  Dae-Shik Kim,et al.  Conventional DTI vs. slow and fast diffusion tensors in cat visual cortex , 2003, Magnetic resonance in medicine.

[15]  R. Saunders,et al.  A qualitative and quantitative analysis of the entorhinal cortex in schizophrenia. , 1997, Cerebral cortex.

[16]  Effects of method and MRI slice thickness on entorhinal cortex volumetry , 2003, Neuroreport.

[17]  M. Witter,et al.  Projections from the parahippocampal region to the prefrontal cortex in the rat: evidence of multiple pathways , 2002, The European journal of neuroscience.

[18]  G. Pearlson,et al.  Medial and superior temporal gyral volumes and cerebral asymmetry in schizophrenia versus bipolar disorder , 1997, Biological Psychiatry.

[19]  David R Roalf,et al.  Decrements in volume of anterior ventromedial temporal lobe and olfactory dysfunction in schizophrenia. , 2003, Archives of general psychiatry.

[20]  M. Akil,et al.  Cytoarchitecture of the entorhinal cortex in schizophrenia. , 1997, The American journal of psychiatry.

[21]  Jens C. Pruessner,et al.  Regional Frontal Cortical Volumes Decrease Differentially in Aging: An MRI Study to Compare Volumetric Approaches and Voxel-Based Morphometry , 2002, NeuroImage.

[22]  R. Kahn,et al.  Memory impairment in schizophrenia: a meta-analysis. , 1999, The American journal of psychiatry.

[23]  B T Hyman,et al.  Some cytoarchitectural abnormalities of the entorhinal cortex in schizophrenia. , 1991, Archives of general psychiatry.

[24]  Alan C. Evans,et al.  Volumetry of temporopolar, perirhinal, entorhinal and parahippocampal cortex from high-resolution MR images: considering the variability of the collateral sulcus. , 2002, Cerebral cortex.

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

[26]  P. Roland,et al.  The human entorhinal cortex participates in associative memory , 1994, Neuroreport.

[27]  Manzar Ashtari,et al.  Caudate nuclei volumes in schizophrenic patients treated with typical antipsychotics or clozapine , 1995, The Lancet.

[28]  Alan C. Evans,et al.  Volumetry of hippocampus and amygdala with high-resolution MRI and three-dimensional analysis software: minimizing the discrepancies between laboratories. , 2000, Cerebral cortex.

[29]  Jarmo Hietala,et al.  A volumetric MRI study of the entorhinal cortex in first episode neuroleptic-naive schizophrenia , 2002, Biological Psychiatry.

[30]  H. Wiśniewski,et al.  Contribution of Structural Neuroimaging to the Early Diagnosis of Alzheimer's Disease , 1997, International Psychogeriatrics.

[31]  P. Basser,et al.  Estimation of the effective self-diffusion tensor from the NMR spin echo. , 1994, Journal of magnetic resonance. Series B.

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

[33]  L. Frank,et al.  Persistent activity and memory in the entorhinal cortex , 2003, Trends in Neurosciences.

[34]  H. Möller,et al.  Age-related cortical grey matter reductions in non-demented Down's syndrome adults determined by MRI with voxel-based morphometry. , 2004, Brain : a journal of neurology.

[35]  Thomas Dierks,et al.  Volumetry and diffusion tensor imaging of hippocampal subregions in schizophrenia , 2004, Neuroreport.

[36]  H. Beckmann,et al.  Prenatal developmental disturbances in the limbic allocortex in schizophrenics , 2005, Journal of Neural Transmission.

[37]  B. Bogerts,et al.  Limbic pathology in schizophrenia: The entorhinal region—a morphometric study , 1988, Biological Psychiatry.

[38]  M. Lepage,et al.  Is associative recognition more impaired than item recognition memory in Schizophrenia? A meta-analysis , 2003, Brain and Cognition.

[39]  Michael D. Nelson,et al.  Hippocampal volume reduction in schizophrenia as assessed by magnetic resonance imaging : A meta-analytic study , 1998 .

[40]  H. Braak,et al.  On areas of transition between entorhinal allocortex and temporal isocortex in the human brain. Normal morphology and lamina-specific pathology in Alzheimer's disease , 2004, Acta Neuropathologica.

[41]  H. Braak,et al.  Pathological Changes in the Parahippocampal Region in Select Non‐Alzheimer's Dementias , 2000, Annals of the New York Academy of Sciences.

[42]  T. Schneider-Axmann,et al.  Entorhinal cortex pre-alpha cell clusters in schizophrenia: quantitative evidence of a developmental abnormality , 2000, Biological Psychiatry.

[43]  K. Krishnan,et al.  Diffusion tensor imaging: background, potential, and utility in psychiatric research , 2003, Biological Psychiatry.

[44]  D R Fish,et al.  Methods for normalization of hippocampal volumes measured with MR. , 1995, AJNR. American journal of neuroradiology.

[45]  S. Arnold,et al.  Further Evidence of Abnormal Cytoarchitecture of the Entorhinal Cortex in Schizophrenia Using Spatial Point Pattern Analyses , 1997, Biological Psychiatry.

[46]  H. Soininen,et al.  MR volumetric analysis of the human entorhinal, perirhinal, and temporopolar cortices. , 1998, AJNR. American journal of neuroradiology.