Localization of cerebral functional deficits in treatment-naive, first-episode schizophrenia using resting-state fMRI

BACKGROUND Spontaneous low-frequency fluctuations (LFF) in the blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signal have been shown to reflect cerebral spontaneous neural activity, and the present study attempts to explore the functional changes in the regional brain in patients with schizophrenia using the amplitude of the BOLD signals. METHODS A total of 66 treatment-naïve, first-episode schizophrenia (FES) patients and 66 normal age- and sex-matched controls were recruited. Resting-state fMRIs were obtained using a gradient-echo echo-planar imaging sequence. The amplitude of LFF (ALFF) was calculated using REST software. Voxel-based analysis of the ALFF maps between control and patient groups was performed with twos-sample t-tests using SPM2. RESULTS Compared to the controls, the FES group showed significantly decreased ALFF in the medial prefrontal lobe (MPFC) and significant increases in the ALFF in the left and right putamen. Significant positive correlations were observed between ALFF values in the bilateral putamen in both the patient and control groups. CONCLUSIONS Alterations of the ALFF in the MPFC and putamen in FES observed in the present study suggest that the functional abnormalities of those areas are at an early stage of the disease.

[1]  Thomas J. Whitford,et al.  Grey matter deficits and symptom profile in first episode schizophrenia , 2005, Psychiatry Research: Neuroimaging.

[2]  A. Pfefferbaum,et al.  Functional Neuroanatomy of Auditory Working Memory in Schizophrenia: Relation to Positive and Negative Symptoms , 2001, NeuroImage.

[3]  Lewis A. Opler,et al.  Reliability and validity of the positive and negative syndrome scale for schizophrenics , 1988, Psychiatry Research.

[4]  Paul Cumming,et al.  Elevated [18F]Fluorodopamine Turnover in Brain of Patients with Schizophrenia: An [18F]Fluorodopa/Positron Emission Tomography Study , 2007, The Journal of Neuroscience.

[5]  Chaozhe Zhu,et al.  Amplitude of low frequency fluctuation within visual areas revealed by resting-state functional MRI , 2007, NeuroImage.

[6]  Y. Zang,et al.  Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI , 2007, Brain and Development.

[7]  R. Coppola,et al.  Functional Magnetic Resonance Imaging Brain Mapping in Psychiatry: Methodological Issues Illustrated in a Study of Working Memory in Schizophrenia , 1998, Neuropsychopharmacology.

[8]  D. Collier,et al.  Association of cerebral deficits with clinical symptoms in antipsychotic-naive first-episode schizophrenia: an optimized voxel-based morphometry and resting state functional connectivity study. , 2009, The American journal of psychiatry.

[9]  Yuan Zhou,et al.  Widespread functional disconnectivity in schizophrenia with resting-state functional magnetic resonance imaging , 2006, Neuroreport.

[10]  Lei Wang,et al.  Structural analysis of the basal ganglia in schizophrenia , 2007, Schizophrenia Research.

[11]  Vince D. Calhoun,et al.  Functional Classification of Schizophrenia Using Feed Forward Neural Networks , 2006, 2006 International Conference of the IEEE Engineering in Medicine and Biology Society.

[12]  Koki Ito,et al.  Olanzapine and risperidone block a high dose of methamphetamine-induced schizophrenia-like behavioral abnormalities and accompanied apoptosis in the medial prefrontal cortex , 2008, Schizophrenia Research.

[13]  Katya Rubia,et al.  An fMRI study of reduced left prefrontal activation in schizophrenia during normal inhibitory function , 2001, Schizophrenia Research.

[14]  B. Biswal,et al.  Functional connectivity in the motor cortex of resting human brain using echo‐planar mri , 1995, Magnetic resonance in medicine.

[15]  R Coppola,et al.  Computed electroencephalographic activity mapping in schizophrenia. The resting state reconsidered. , 1987, Archives of general psychiatry.

[16]  Lina Shihabuddin,et al.  Internal capsule size in good-outcome and poor-outcome schizophrenia. , 2006, The Journal of neuropsychiatry and clinical neurosciences.

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

[18]  D. Barch,et al.  Working and long-term memory deficits in schizophrenia: is there a common prefrontal mechanism? , 2002, Journal of abnormal psychology.

[19]  Nobumasa Kato,et al.  Abnormal glucose metabolism in the anterior cingulate cortex in patients with schizophrenia , 2007, Psychiatry Research: Neuroimaging.

[20]  Yong He,et al.  Disrupted small-world networks in schizophrenia. , 2008, Brain : a journal of neurology.

[21]  Takashi Hanakawa,et al.  Social cognition and frontal lobe pathology in schizophrenia: A voxel-based morphometric study , 2007, NeuroImage.

[22]  Jonathan D. Brodie,et al.  Stability of resting deoxyglucose metabolic values in PET studies of schizophrenia , 1991, Psychiatry Research: Neuroimaging.

[23]  Paul C Fletcher,et al.  Does the brain have a baseline? Why we should be resisting a rest. , 2007, NeuroImage.

[24]  N C Andreasen,et al.  Change in basal ganglia volume over 2 years in patients with schizophrenia: typical versus atypical neuroleptics. , 1999, The American journal of psychiatry.

[25]  Vince D Calhoun,et al.  Correlation between the amplitude of cortical activation and reaction time: a functional MRI study. , 2004, AJR. American journal of roentgenology.

[26]  Stefan Arnborg,et al.  Morphological correlates to cognitive dysfunction in schizophrenia as studied with Bayesian regression , 2006, BMC psychiatry.

[27]  Qiyong Gong,et al.  High-field MRI reveals an acute impact on brain function in survivors of the magnitude 8.0 earthquake in China , 2009, Proceedings of the National Academy of Sciences.

[28]  G. Shulman,et al.  Medial prefrontal cortex and self-referential mental activity: Relation to a default mode of brain function , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[29]  P. Goldman-Rakic,et al.  Cortical dysfunction in schizophrenia during auditory word and tone working memory demonstrated by functional magnetic resonance imaging. , 1998, Archives of general psychiatry.

[30]  S. Rauch,et al.  Neurobiology of emotion perception I: the neural basis of normal emotion perception , 2003, Biological Psychiatry.

[31]  W. Honer,et al.  An MRI study of basal ganglia volumes in first-episode schizophrenia patients treated with risperidone. , 2001, The American journal of psychiatry.

[32]  D. Schacter,et al.  The Brain's Default Network , 2008, Annals of the New York Academy of Sciences.

[33]  D. Glahn,et al.  Beyond hypofrontality: A quantitative meta‐analysis of functional neuroimaging studies of working memory in schizophrenia , 2005, Human brain mapping.

[34]  M. Raichle,et al.  Searching for a baseline: Functional imaging and the resting human brain , 2001, Nature Reviews Neuroscience.

[35]  Sterling C. Johnson,et al.  Neural correlates of self-reflection. , 2002, Brain : a journal of neurology.

[36]  Ferath Kherif,et al.  Multivariate voxel-based morphometry successfully differentiates schizophrenia patients from healthy controls , 2007, NeuroImage.

[37]  H. Holcomb,et al.  Correlations Between rCBF and Symptoms in Two Independent Cohorts of Drug-Free Patients with Schizophrenia , 2006, Neuropsychopharmacology.

[38]  Chunshui Yu,et al.  Altered resting-state functional connectivity and anatomical connectivity of hippocampus in schizophrenia , 2008, Schizophrenia Research.

[39]  Istvan Molnar-Szakacs,et al.  Watching social interactions produces dorsomedial prefrontal and medial parietal BOLD fMRI signal increases compared to a resting baseline , 2004, NeuroImage.

[40]  G L Shulman,et al.  INAUGURAL ARTICLE by a Recently Elected Academy Member:A default mode of brain function , 2001 .

[41]  Bharat Biswal,et al.  Slow vasomotor fluctuation in fMRI of anesthetized child brain , 2000, Magnetic resonance in medicine.

[42]  Tetsuya Matsuda,et al.  An fMRI study of differential neural response to affective pictures in schizophrenia , 2004, NeuroImage.

[43]  Vince D. Calhoun,et al.  A Functional Magnetic Resonance Imaging Study of Working Memory Abnormalities in Schizophrenia , 2006, Biological Psychiatry.

[44]  Veena Kumari,et al.  Frontal lobe volumes in schizophrenia: effects of stage and duration of illness. , 2006, Journal of Psychiatric Research.

[45]  S. Rauch,et al.  Schizophrenic subjects show aberrant fMRI activation of dorsolateral prefrontal cortex and basal ganglia during working memory performance , 2000, Biological Psychiatry.

[46]  A. Meyer-Lindenberg,et al.  Heritability of Brain Morphology Related to Schizophrenia: A Large-Scale Automated Magnetic Resonance Imaging Segmentation Study , 2008, Biological Psychiatry.

[47]  Vicente Molina,et al.  Prefrontal atrophy in first episodes of schizophrenia associated with limbic metabolic hyperactivity. , 2005, Journal of psychiatric research.

[48]  Yuan Zhou,et al.  Functional dysconnectivity of the dorsolateral prefrontal cortex in first-episode schizophrenia using resting-state fMRI , 2007, Neuroscience Letters.

[49]  E. Gordon,et al.  Fronto-limbic and autonomic disjunctions to negative emotion distinguish schizophrenia subtypes , 2007, Psychiatry Research: Neuroimaging.

[50]  T. Sharma,et al.  The Relationship of Structural Alterations to Cognitive Deficits in Schizophrenia: A Voxel-Based Morphometry Study , 2005, Biological Psychiatry.

[51]  G. Glover,et al.  Functional Magnetic Resonance Imaging Evidence for Disrupted Basal Ganglia Function in Schizophrenia , 2001 .

[52]  Christian Gaser,et al.  Supporting evidence for the model of cognitive dysmetria in schizophrenia — a structural magnetic resonance imaging study using deformation-based morphometry , 2000, Schizophrenia Research.

[53]  J. Lieberman,et al.  Basal ganglia volumes in first-episode schizophrenia and healthy comparison subjects , 2002, Biological Psychiatry.

[54]  Stephan Felber,et al.  Neural correlates of episodic encoding and recognition of words in unmedicated patients during an acute episode of schizophrenia: a functional MRI study. , 2003, The American journal of psychiatry.

[55]  S. Paradiso,et al.  "Cognitive dysmetria" as an integrative theory of schizophrenia: a dysfunction in cortical-subcortical-cerebellar circuitry? , 1998, Schizophrenia bulletin.

[56]  N. Logothetis,et al.  Neurophysiological investigation of the basis of the fMRI signal , 2001, Nature.

[57]  Jill Harkavy-Friedman,et al.  Resting neural activity distinguishes subgroups of schizophrenia patients , 2004, Biological Psychiatry.

[58]  Kwang-Hyuk Lee,et al.  A functional magnetic resonance imaging study of social cognition in schizophrenia during an acute episode and after recovery. , 2006, The American journal of psychiatry.

[59]  Vince D. Calhoun,et al.  A method for functional network connectivity among spatially independent resting-state components in schizophrenia , 2008, NeuroImage.

[60]  S. G. Cox,et al.  Functional MRI study of the cognitive generation of affect. , 1999, The American journal of psychiatry.

[61]  S. Sponheim,et al.  Clinical and biological concomitants of resting state EEG power abnormalities in schizophrenia , 2000, Biological Psychiatry.

[62]  Yong He,et al.  Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI. , 2007, Brain & development.

[63]  S. Sponheim,et al.  Genetic and disorder-specific aspects of resting state EEG abnormalities in schizophrenia. , 2009, Schizophrenia bulletin.

[64]  M. Egan,et al.  Complexity of prefrontal cortical dysfunction in schizophrenia: more than up or down. , 2003, The American journal of psychiatry.

[65]  Robert K Heaton,et al.  A six-factor model of cognition in schizophrenia and related psychotic disorders: relationships with clinical symptoms and functional capacity. , 2004, Schizophrenia bulletin.

[66]  Adam M. Brickman,et al.  Caudate and putamen volumes in good and poor outcome patients with schizophrenia , 2003, Schizophrenia Research.

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

[68]  Jean-Marc Constans,et al.  Relationship between performance on the Stroop test and N-acetylaspartate in the medial prefrontal cortex in deficit and nondeficit schizophrenia: preliminary results , 2004, Psychiatry Research: Neuroimaging.

[69]  Jonathan D. Cohen,et al.  Lateral and medial hypofrontality in first-episode schizophrenia: functional activity in a medication-naive state and effects of short-term atypical antipsychotic treatment. , 2005, The American journal of psychiatry.

[70]  Gabriele Ende,et al.  Antipsychotic drug effects on motor activation measured by functional magnetic resonance imaging in schizophrenic patients , 1999, Schizophrenia Research.

[71]  R. Gur,et al.  Subcortical MRI volumes in neuroleptic-naive and treated patients with schizophrenia. , 1998, The American journal of psychiatry.

[72]  S. Lui,et al.  Differential interictal activity of the precuneus/posterior cingulate cortex revealed by resting state functional MRI at 3T in generalized vs. Partial seizure , 2008, Journal of magnetic resonance imaging : JMRI.

[73]  Tianzi Jiang,et al.  Decreased regional homogeneity in schizophrenia: a resting state functional magnetic resonance imaging study , 2006, Neuroreport.

[74]  Murat Yücel,et al.  Task-induced deactivation of midline cortical regions in schizophrenia assessed with fMRI , 2007, Schizophrenia Research.

[75]  Michael I. Miller,et al.  Basal Ganglia Shape Abnormalities in the Unaffected Siblings of Schizophrenia Patients , 2008, Biological Psychiatry.

[76]  Elizabeth Thomas,et al.  Differential changes in apolipoprotein E in schizophrenia and bipolar I disorder , 2005, Biological Psychiatry.

[77]  Manuel Desco,et al.  Anatomical and functional cerebral variables associated with basal symptoms but not risperidone response in minimally treated schizophrenia , 2003, Psychiatry Research: Neuroimaging.

[78]  V. Haughton,et al.  Frequencies contributing to functional connectivity in the cerebral cortex in "resting-state" data. , 2001, AJNR. American journal of neuroradiology.

[79]  Yuan Zhou,et al.  Functional disintegration in paranoid schizophrenia using resting-state fMRI , 2007, Schizophrenia Research.

[80]  S. Kiebel,et al.  Detecting Structural Changes in Whole Brain Based on Nonlinear Deformations—Application to Schizophrenia Research , 1999, NeuroImage.

[81]  M. Bergström,et al.  Increased dopamine synthesis rate in medial prefrontal cortex and striatum in schizophrenia indicated by L-(β-11C) DOPA and PET , 1999, Biological Psychiatry.

[82]  J. Meador-Woodruff,et al.  Neurocognitive measures of prefrontal cortical dysfunction in schizophrenia , 2004, Schizophrenia Research.