Does function follow form?: Methods to fuse structural and functional brain images show decreased linkage in schizophrenia

When both structural magnetic resonance imaging (sMRI) and functional MRI (fMRI) data are collected they are typically analyzed separately and the joint information is not examined. Techniques that examine joint information can help to find hidden traits in complex disorders such as schizophrenia. The brain is vastly interconnected, and local brain morphology may influence functional activity at distant regions. In this paper we introduce three methods to identify inter-correlations among sMRI and fMRI voxels within the whole brain. We apply these methods to examine sMRI gray matter data and fMRI data derived from an auditory sensorimotor task from a large study of schizophrenia. In Method 1 the sMRI-fMRI cross-correlation matrix is reduced to a histogram and results show that healthy controls (HC) have stronger correlations than do patients with schizophrenia (SZ). In Method 2 the spatial information of sMRI-fMRI correlations is retained. Structural regions in the cerebellum and frontal regions show more positive and more negative correlations, respectively, with functional regions in HC than in SZ. In Method 3 significant sMRI-fMRI inter-regional links are detected, with regions in the cerebellum showing more significant positive correlations with functional regions in HC relative to SZ. Results from all three methods indicate that the linkage between gray matter and functional activation is stronger in HC than SZ. The methods introduced can be easily extended to comprehensively correlate large data sets.

[1]  Moo K. Chung,et al.  Integrating VBM into the General Linear Model with voxelwise anatomical covariates , 2007, NeuroImage.

[2]  P. Fox,et al.  Intersubject variability of functional areas in the human visual cortex , 1998, Human brain mapping.

[3]  Karl J. Friston.  The disconnection hypothesis , 1998, Schizophrenia Research.

[4]  D. Weinberger,et al.  Physiologic dysfunction of dorsolateral prefrontal cortex in schizophrenia. I. Regional cerebral blood flow evidence. , 1986, Archives of general psychiatry.

[5]  R. Woods,et al.  Mathematical/computational challenges in creating deformable and probabilistic atlases of the human brain , 2000, Human brain mapping.

[6]  P T Fox,et al.  Structure--function spatial covariance in the human visual cortex. , 2001, Cerebral cortex.

[7]  F. Gonzalez-Lima,et al.  Structural equation modeling and its application to network analysis in functional brain imaging , 1994 .

[8]  C. Carter,et al.  Anterior cingulate cortex activity and impaired self-monitoring of performance in patients with schizophrenia: an event-related fMRI study. , 2001, The American journal of psychiatry.

[9]  V. Calhoun,et al.  Temporal lobe and “default” hemodynamic brain modes discriminate between schizophrenia and bipolar disorder , 2008, Human brain mapping.

[10]  M. Corbetta,et al.  A Common Network of Functional Areas for Attention and Eye Movements , 1998, Neuron.

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

[12]  Karl J. Friston,et al.  Dynamic causal modelling , 2003, NeuroImage.

[13]  Judith M. Ford,et al.  Delayed hemodynamic responses in schizophrenia , 2005, NeuroImage.

[14]  N. Tzourio-Mazoyer,et al.  Automated Anatomical Labeling of Activations in SPM Using a Macroscopic Anatomical Parcellation of the MNI MRI Single-Subject Brain , 2002, NeuroImage.

[15]  Alan C. Evans,et al.  Focal gray matter density changes in schizophrenia. , 2001, Archives of general psychiatry.

[16]  Michele T. Diaz,et al.  Voxel-based morphometric multisite collaborative study on schizophrenia. , 2009, Schizophrenia bulletin.

[17]  Jean-Francois Mangin,et al.  What is the best similarity measure for motion correction in fMRI time series? , 2002, IEEE Transactions on Medical Imaging.

[18]  N. Makris,et al.  Cortical abnormalities in schizophrenia identified by structural magnetic resonance imaging. , 1999, Archives of general psychiatry.

[19]  Karl J. Friston,et al.  Voxel-Based Morphometry—The Methods , 2000, NeuroImage.

[20]  Karl J. Friston,et al.  Spatial registration and normalization of images , 1995 .

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

[22]  M. Mesulam,et al.  From sensation to cognition. , 1998, Brain : a journal of neurology.

[23]  Eve C. Johnstone,et al.  Increased Prefrontal Gyrification in a Large High-Risk Cohort Characterizes Those Who Develop Schizophrenia and Reflects Abnormal Prefrontal Development , 2007, Biological Psychiatry.

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

[25]  K. Kiehl,et al.  An event-related functional magnetic resonance imaging study of an auditory oddball task in schizophrenia , 2001, Schizophrenia Research.

[26]  V. Calhoun,et al.  A method to fuse fMRI tasks through spatial correlations: Applied to schizophrenia , 2009, Human brain mapping.

[27]  B. Turetsky,et al.  Reduced gray matter volume in schizophrenia. , 1999, Archives of general psychiatry.

[28]  G. Pearlson,et al.  Schizophrenia, the heteromodal association neocortex and development: potential for a neurogenetic approach , 1996, Trends in Neurosciences.

[29]  Greg J Siegle,et al.  Relationships between Amygdala Volume and Activity during Emotional Information Processing Tasks in Depressed and Never‐Depressed Individuals , 2003, Annals of the New York Academy of Sciences.

[30]  S. Petersen,et al.  Characterizing the Hemodynamic Response: Effects of Presentation Rate, Sampling Procedure, and the Possibility of Ordering Brain Activity Based on Relative Timing , 2000, NeuroImage.

[31]  T. Wassink,et al.  Defining the phenotype of schizophrenia: cognitive dysmetria and its neural mechanisms , 1999, Biological Psychiatry.

[32]  Marek Kubicki,et al.  Recent structural and functional imaging findings in schizophrenia , 2003 .

[33]  Dinesh Bhugra,et al.  The Global Prevalence of Schizophrenia , 2005, PLoS medicine.

[34]  F. Makedon,et al.  A combined structural-functional classification of schizophrenia using hippocampal volume plus fMRI activation , 2002, Proceedings of the Second Joint 24th Annual Conference and the Annual Fall Meeting of the Biomedical Engineering Society] [Engineering in Medicine and Biology.

[35]  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.

[36]  Dinggang Shen,et al.  Multivariate examination of brain abnormality using both structural and functional MRI , 2007, NeuroImage.

[37]  Vince D. Calhoun,et al.  A method to classify schizophrenia using inter-task spatial correlations of functional brain images , 2008, 2008 30th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

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

[39]  Lothar R. Schad,et al.  Motor Dysfunction and Sensorimotor Cortex Activation Changes in Schizophrenia: A Study with Functional Magnetic Resonance Imaging , 1999, NeuroImage.

[40]  Richard S. J. Frackowiak,et al.  Cortical and subcortical gray matter abnormalities in schizophrenia determined through structural magnetic resonance imaging with optimized volumetric voxel-based morphometry. , 2002, The American journal of psychiatry.

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

[42]  A W Toga,et al.  Maps of the Brain , 2001, The Anatomical record.

[43]  J. Pekar,et al.  A method for making group inferences from functional MRI data using independent component analysis , 2001, Human brain mapping.

[44]  L. Freire,et al.  Motion Correction Algorithms May Create Spurious Brain Activations in the Absence of Subject Motion , 2001, NeuroImage.

[45]  Ravi S. Menon,et al.  Spatial and temporal limits in cognitive neuroimaging with fMRI , 1999, Trends in Cognitive Sciences.

[46]  T. Crow,et al.  Regional deficits in brain volume in schizophrenia: a meta-analysis of voxel-based morphometry studies. , 2005, The American journal of psychiatry.

[47]  N. Andreasen,et al.  Anatomic and Functional Variability: The Effects of Filter Size in Group fMRI Data Analysis , 2001, NeuroImage.

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