Through a Glass Darkly: Schizophrenia and Functional Brain Imaging

Abstract:Functional neuroimaging frequently assumes anatomically and functionally specific "modules" in the brain. Schizophrenia, which is challenging in many ways, also challenges modularity. A prominent example of a modular hypothesis links working memory (WM) deficits in schizophrenia with decreased function in the prefrontal cortex, a result confirmed in several studies. Nonetheless, these studies are systematically blind to the alternative possibility that schizophrenia reflects dysfunction in broader, more distributed systems of the brain. However, to establish hypotheses about distributed cognition in health and illness requires new interpretations of functional neuroimaging. Modularity can be assessed by large-scale meta-analyses of neuroimaging studies, illustrated here through the on-line database, Brainmap (www.brainmap.org). The apparent association of WM and prefrontal cortex fades when one considers all areas engaged in WM, and all tasks associated with prefrontal cortex. In addition, several global measures of connectivity based in functional neuroimaging may provide measures of distributed dysfunction. For example, Independent Component Analysis reveals unusual oscillations in distributed networks in patients with schizophrenia.

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

[2]  P. Fransson.  Spontaneous low‐frequency BOLD signal fluctuations: An fMRI investigation of the resting‐state default mode of brain function hypothesis , 2005, Human brain mapping.

[3]  A. Beck,et al.  Cognitive approaches to schizophrenia: theory and therapy. , 2005, Annual review of clinical psychology.

[4]  M. Greicius,et al.  Default-Mode Activity during a Passive Sensory Task: Uncoupled from Deactivation but Impacting Activation , 2004, Journal of Cognitive Neuroscience.

[5]  P F Liddle,et al.  Changes in distributed neural circuitry function in patients with first-episode schizophrenia , 2004, British Journal of Psychiatry.

[6]  N. Ramsey,et al.  Working memory capacity in schizophrenia: a parametric fMRI study , 2004, Schizophrenia Research.

[7]  D. Long,et al.  Radiant Cool: A Novel Theory of Consciousness , 2004 .

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

[9]  Henrik Walter,et al.  No hypofrontality, but absence of prefrontal lateralization comparing verbal and spatial working memory in schizophrenia , 2003, Schizophrenia Research.

[10]  D. Sander,et al.  A truly simultaneous combination of functional transcranial Doppler sonography and H(2)(15)O PET adds fundamental new information on differences in cognitive activation between schizophrenics and healthy control subjects. , 2003, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[11]  J. Callicott.  An expanded role for functional neuroimaging in schizophrenia , 2003, Current Opinion in Neurobiology.

[12]  J. Binder,et al.  A Parametric Manipulation of Factors Affecting Task-induced Deactivation in Functional Neuroimaging , 2003, Journal of Cognitive Neuroscience.

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

[14]  J. Lewin.  Functional MRI: An introduction to methods , 2003 .

[15]  Vinod Menon,et al.  Functional connectivity in the resting brain: A network analysis of the default mode hypothesis , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[16]  Dan Lloyd,et al.  Functional MRI and the Study of Human Consciousness , 2002, Journal of Cognitive Neuroscience.

[17]  M. Brammer,et al.  Effects on the brain of a psychological treatment: Cognitive remediation therapy , 2002, British Journal of Psychiatry.

[18]  V D Calhoun,et al.  Independent component analysis of fMRI data in the complex domain , 2002, Magnetic resonance in medicine.

[19]  E. Bullmore,et al.  Functional brain mapping of psychopathology , 2002, Journal of neurology, neurosurgery, and psychiatry.

[20]  A. Meyer-Lindenberg,et al.  Reduced prefrontal activity predicts exaggerated striatal dopaminergic function in schizophrenia , 2002, Nature Neuroscience.

[21]  Edward T Bullmore,et al.  De-coupling of cognitive performance and cerebral functional response during working memory in schizophrenia. , 2002, Schizophrenia Research.

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

[23]  J. Cohen,et al.  Relation of prefrontal cortex dysfunction to working memory and symptoms in schizophrenia. , 2001, The American journal of psychiatry.

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

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

[26]  R. Coppola,et al.  Physiological dysfunction of the dorsolateral prefrontal cortex in schizophrenia revisited. , 2000, Cerebral cortex.

[27]  Stephan Heckers,et al.  Schizophrenia and cognitive function , 2000, Current Opinion in Neurobiology.

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

[29]  K. Nuechterlein,et al.  Should schizophrenia be treated as a neurocognitive disorder? , 1999, European Neuropsychopharmacology.

[30]  Jonathan D. Cohen,et al.  Cognition and control in schizophrenia: a computational model of dopamine and prefrontal function , 1999, Biological Psychiatry.

[31]  Norman Ringel,et al.  Social functioning and neurocognitive deficits in outpatients with schizophrenia: a 2-year follow-up 1 This work was presented in part at the Winter Workshop on Schizophrenia, Davos, Switzerland, 7–13 February 1998. 1 , 1999, Schizophrenia Research.

[32]  Karl J. Friston.  Schizophrenia and the disconnection hypothesis , 1999, Acta psychiatrica Scandinavica. Supplementum.

[33]  A. Malla,et al.  Symptoms and cognition as predictors of community functioning: a prospective analysis. , 1999, The American journal of psychiatry.

[34]  J. Cohen,et al.  Functional hypofrontality and working memory dysfunction in schizophrenia. , 1998, The American journal of psychiatry.

[35]  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.

[36]  Karl J. Friston,et al.  Cognitive Conjunction: A New Approach to Brain Activation Experiments , 1997, NeuroImage.

[37]  Karl J. Friston,et al.  The Trouble with Cognitive Subtraction , 1996, NeuroImage.

[38]  Michael F. Green,et al.  What are the functional consequences of neurocognitive deficits in schizophrenia? , 1996, The American journal of psychiatry.

[39]  P. Smolensky.  On the proper treatment of connectionism , 1988, Behavioral and Brain Sciences.

[40]  P. Liddle.  The Symptoms of Chronic Schizophrenia , 1987, British Journal of Psychiatry.

[41]  T. Crow,et al.  Molecular pathology of schizophrenia: more than one disease process? , 1980, British medical journal.

[42]  W. Wimsatt.  Reductive Explanation: A Functional Account , 1974, PSA: Proceedings of the Biennial Meeting of the Philosophy of Science Association.

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

[44]  D. Spurrett,et al.  Distributed Cognition and the Will: Individual Volition and Social Context , 2007 .

[45]  D. Barch.  The cognitive neuroscience of schizophrenia. , 2005, Annual review of clinical psychology.

[46]  D. Barch,et al.  The Cognitive Neuroscience of Schizophrenia , 2005 .

[47]  Dan Lloyd,et al.  Radiant cool : a novel theory of consciousness , 2003 .

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

[49]  Stephen M. Smith,et al.  Functional MRI : an introduction to methods , 2002 .

[50]  R. Coppola,et al.  Physiological characteristics of capacity constraints in working memory as revealed by functional MRI. , 1999, Cerebral cortex.

[51]  J. Addington,et al.  Neurocognitive and social functioning in schizophrenia. , 1999, Schizophrenia bulletin.

[52]  Michael F. Green,et al.  Should Schizophrenia Be Treated as a Neurocognitive Disorder , 1999 .

[53]  J. McGrath,et al.  The cognitive neuropsychology of schizophrenia. , 1997 .

[54]  James L. McClelland.  Explorations In Parallel Distributed Processing , 1988 .

[55]  J. Fodor.  The Modularity of mind. An essay on faculty psychology , 1986 .

[56]  S Makeig,et al.  Analysis of fMRI data by blind separation into independent spatial components , 1998, Human brain mapping.