Altered functional and anatomical connectivity in schizophrenia.

BACKGROUND Schizophrenia is characterized by a lack of integration between thought, emotion, and behavior. A disruption in the connectivity between brain processes may underlie this schism. Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) were used to evaluate functional and anatomical brain connectivity in schizophrenia. METHODS In all, 29 chronic schizophrenia patients (11 females, age: mean=41.3, SD=9.28) and 29 controls (11 females, age: mean=41.1, SD=10.6) were recruited. Schizophrenia patients were assessed for severity of negative and positive symptoms and general cognitive abilities of attention/concentration and memory. Participants underwent a resting-fMRI scan and a DTI scan. For fMRI data, a hybrid independent components analysis was used to extract the group default mode network (DMN) and accompanying time-courses. Voxel-wise whole-brain multiple regressions with corresponding DMN time-courses was conducted for each subject. A t-test was conducted on resulting DMN correlation maps to look between-group differences. For DTI data, voxel-wise statistical analysis of the fractional anisotropy data was carried out to look for between-group differences. Voxel-wise correlations were conducted to investigate the relationship between brain connectivity and behavioral measures. RESULTS Results revealed altered functional and anatomical connectivity in medial frontal and anterior cingulate gyri of schizophrenia patients. In addition, frontal connectivity in schizophrenia patients was positively associated with symptoms as well as with general cognitive ability measures. DISCUSSION The present study shows convergent fMRI and DTI findings that are consistent with the disconnection hypothesis in schizophrenia, particularly in medial frontal regions, while adding some insight of the relationship between brain disconnectivity and behavior.

[1]  A. B. Hollingshead,et al.  Social Class and Mental Illness , 1964 .

[2]  R. G. Hunt,et al.  Social Class and Mental Illness , 1959 .

[3]  N C Andreasen,et al.  Negative v positive schizophrenia. Definition and validation. , 1982, Archives of general psychiatry.

[4]  J. Carroll.  Human Cognitive Abilities-a sur-vey of factor-analytic studies , 1993 .

[5]  Karl J. Friston,et al.  Schizophrenia: a disconnection syndrome? , 1995, Clinical neuroscience.

[6]  M. Corbetta,et al.  Common Blood Flow Changes across Visual Tasks: II. Decreases in Cerebral Cortex , 1997, Journal of Cognitive Neuroscience.

[7]  Thomas E. Nichols,et al.  Anterior cingulate gyrus dysfunction and selective attention deficits in schizophrenia: [15O]H2O PET study during single-trial Stroop task performance. , 1997, The American journal of psychiatry.

[8]  R. Heinrichs,et al.  Neurocognitive deficit in schizophrenia: a quantitative review of the evidence. , 1998, Neuropsychology.

[9]  Daniel Rueckert,et al.  Nonrigid registration using free-form deformations: application to breast MR images , 1999, IEEE Transactions on Medical Imaging.

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

[11]  M. Botvinick,et al.  Parsing executive processes: strategic vs. evaluative functions of the anterior cingulate cortex. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[12]  M. McKeown.  Detection of Consistently Task-Related Activations in fMRI Data with Hybrid Independent Component Analysis , 2000, NeuroImage.

[13]  J. Cohen,et al.  Dissociating the role of the dorsolateral prefrontal and anterior cingulate cortex in cognitive control. , 2000, Science.

[14]  M. Posner,et al.  Cognitive and emotional influences in anterior cingulate cortex , 2000, Trends in Cognitive Sciences.

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

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

[17]  A. Dale,et al.  Dorsal anterior cingulate cortex: A role in reward-based decision making , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[18]  T. Paus.  Primate anterior cingulate cortex: Where motor control, drive and cognition interface , 2001, Nature Reviews Neuroscience.

[19]  Stephen M Smith,et al.  Fast robust automated brain extraction , 2002, Human brain mapping.

[20]  Thomas E. Nichols,et al.  Nonparametric permutation tests for functional neuroimaging: A primer with examples , 2002, Human brain mapping.

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

[22]  Yoshio Hirayasu,et al.  Disruption of neural systems of visual attention in schizophrenia. , 2002, Archives of general psychiatry.

[23]  J. Breeze,et al.  Abnormal anterior cingulum in patients with schizophrenia: a diffusion tensor imaging study , 2003, Neuroreport.

[24]  R. Kikinis,et al.  Cingulate fasciculus integrity disruption in schizophrenia: a magnetic resonance diffusion tensor imaging study , 2003, Biological Psychiatry.

[25]  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.

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

[27]  Philip D. Harvey,et al.  White matter changes in schizophrenia: evidence for myelin-related dysfunction. , 2003, Archives of general psychiatry.

[28]  Timothy Edward John Behrens,et al.  Characterization and propagation of uncertainty in diffusion‐weighted MR imaging , 2003, Magnetic resonance in medicine.

[29]  V. Wedeen,et al.  Reduction of eddy‐current‐induced distortion in diffusion MRI using a twice‐refocused spin echo , 2003, Magnetic resonance in medicine.

[30]  D. Javitt,et al.  MRI study of white matter diffusion anisotropy in schizophrenia , 2003, Neuroreport.

[31]  T. Kinoshita,et al.  Diffusion Tensor Magnetic Resonance Imaging of Disruption of Regional White Matter in Schizophrenia , 2003, Neuropsychobiology.

[32]  Andrew Webb,et al.  Behavioral conflict, anterior cingulate cortex, and experiment duration: Implications of diverging data , 2004, Human brain mapping.

[33]  Mark W. Woolrich,et al.  Advances in functional and structural MR image analysis and implementation as FSL , 2004, NeuroImage.

[34]  I. Nimmo-Smith,et al.  Hypofrontality in schizophrenia: a meta‐analysis of functional imaging studies , 2004, Acta psychiatrica Scandinavica.

[35]  Zhiguo Sun,et al.  Anterior cingulum abnormalities in male patients with schizophrenia determined through diffusion tensor imaging. , 2004, The American journal of psychiatry.

[36]  Jonathan D. Cohen,et al.  Anterior Cingulate Conflict Monitoring and Adjustments in Control , 2004, Science.

[37]  Stephen M. Smith,et al.  Probabilistic independent component analysis for functional magnetic resonance imaging , 2004, IEEE Transactions on Medical Imaging.

[38]  Carmen Birchmeier,et al.  Axonal Neuregulin-1 Regulates Myelin Sheath Thickness , 2004, Science.

[39]  P. Skudlarski,et al.  Brain Connectivity Related to Working Memory Performance , 2006, The Journal of Neuroscience.

[40]  D. Javitt,et al.  Voxelwise correlational analyses of white matter integrity in multiple cognitive domains in schizophrenia. , 2006, The American journal of psychiatry.

[41]  Stephen M. Smith,et al.  fMRI resting state networks define distinct modes of long-distance interactions in the human brain , 2006, NeuroImage.

[42]  Benjamin M. Robinson,et al.  Impaired Control of Visual Attention in Schizophrenia , 2005 .

[43]  Daniel Rueckert,et al.  Tract-based spatial statistics: Voxelwise analysis of multi-subject diffusion data , 2006, NeuroImage.

[44]  Jazmin Camchong,et al.  An effect of context on saccade-related behavior and brain activity , 2007, NeuroImage.

[45]  Hidenao Fukuyama,et al.  Anterior and posterior cingulum abnormalities and their association with psychopathology in schizophrenia: A diffusion tensor imaging study , 2007, Schizophrenia Research.

[46]  Abraham Z. Snyder,et al.  A default mode of brain function: A brief history of an evolving idea , 2007, NeuroImage.

[47]  Bruce Fischl,et al.  Reduced microstructural integrity of the white matter underlying anterior cingulate cortex is associated with increased saccadic latency in schizophrenia , 2007, NeuroImage.

[48]  Marek Kubicki,et al.  Attentional networks and cingulum bundle in chronic schizophrenia , 2007, Schizophrenia Research.

[49]  Daniel S. Margulies,et al.  Mapping the functional connectivity of anterior cingulate cortex , 2007, NeuroImage.

[50]  V. Calhoun,et al.  Aberrant "default mode" functional connectivity in schizophrenia. , 2007, The American journal of psychiatry.

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

[52]  Scott T. Grafton,et al.  Wandering Minds: The Default Network and Stimulus-Independent Thought , 2007, Science.

[53]  R. Bluhm,et al.  Spontaneous low-frequency fluctuations in the BOLD signal in schizophrenic patients: anomalies in the default network. , 2007, Schizophrenia bulletin.

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

[55]  Daniel H. Mathalon,et al.  Diffusion tensor imaging in schizophrenia: Relationship to symptoms , 2008, Schizophrenia Research.

[56]  Babak A. Ardekani,et al.  A DTI study of white matter microstructure in individuals at high genetic risk for schizophrenia , 2008, Schizophrenia Research.

[57]  Osamu Abe,et al.  Disrupted integrity of the fornix is associated with impaired memory organization in schizophrenia , 2008, Schizophrenia Research.

[58]  Liang Wang,et al.  Default mode network as revealed with multiple methods for resting-state functional MRI analysis , 2008, Journal of Neuroscience Methods.

[59]  Vince D. Calhoun,et al.  Measuring brain connectivity: Diffusion tensor imaging validates resting state temporal correlations , 2008, NeuroImage.

[60]  J. Gabrieli,et al.  Hyperactivity and hyperconnectivity of the default network in schizophrenia and in first-degree relatives of persons with schizophrenia , 2009, Proceedings of the National Academy of Sciences.

[61]  M. Greicius,et al.  Resting-state functional connectivity reflects structural connectivity in the default mode network. , 2009, Cerebral cortex.

[62]  Wesley K. Thompson,et al.  MATLAB toolbox for functional connectivity , 2009, NeuroImage.

[63]  Yong He,et al.  Functional and Structural Connectivity Between the Perigenual Anterior Cingulate and Amygdala in Bipolar Disorder , 2009, Biological Psychiatry.

[64]  M. Kubicki,et al.  Functional and anatomical connectivity abnormalities in left inferior frontal gyrus in schizophrenia , 2009, Human brain mapping.

[65]  E. Bleuler.  [Dementia praecox or the group of schizophrenias]. , 1968, Vertex.

[66]  J. Callicott,et al.  Age-related alterations in default mode network: Impact on working memory performance , 2010, Neurobiology of Aging.

[67]  Martijn P. van den Heuvel,et al.  FUNCTIONAL CONNECTIVITY IN SCHIZOPHRENIA , 2010, Schizophrenia Research.