Nonlinear response of the anterior cingulate and prefrontal cortex in schizophrenia as a function of variable attentional control.

Previous studies have reported abnormal prefrontal and cingulate activity during attentional control processing in schizophrenia. However, it is not clear how variation in attentional control load modulates activity within these brain regions in this brain disorder. The aim of this study in schizophrenia is to investigate the impact of increasing levels of attentional control processing on prefrontal and cingulate activity. Blood oxygen level-dependent (BOLD) responses of 16 outpatients with schizophrenia were compared with those of 21 healthy subjects while performing a task eliciting increasing levels of attentional control during event-related functional magnetic resonance imaging at 3 T. Results showed reduced behavioral performance in patients at greater attentional control levels. Imaging data indicated greater prefrontal activity at intermediate attentional control levels in patients but greater prefrontal and cingulate responses at high attentional control demands in controls. The BOLD activity profile of these regions in controls increased linearly with increasing cognitive loads, whereas in patients, it was nonlinear. Correlation analysis consistently showed differential region and load-specific relationships between brain activity and behavior in the 2 groups. These results indicate that varying attentional control load is associated in schizophrenia with load- and region-specific modification of the relationship between behavior and brain activity, possibly suggesting earlier saturation of cognitive capacity.

[1]  G. Glover,et al.  Acquiring and inhibiting prepotent responses in schizophrenia: event-related brain potentials and functional magnetic resonance imaging. , 2004, Archives of general psychiatry.

[2]  E. Crone,et al.  Dissociation of response conflict, attentional selection, and expectancy with functional magnetic resonance imaging. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[3]  Stephan Heckers,et al.  Anterior cingulate cortex activation during cognitive interference in schizophrenia. , 2004, The American journal of psychiatry.

[4]  J. Gläscher,et al.  Gene–gene interaction associated with neural reward sensitivity , 2007, Proceedings of the National Academy of Sciences.

[5]  Jonathan D. Cohen,et al.  Decreased conflict- and error-related activity in the anterior cingulate cortex in subjects with schizophrenia. , 2005, The American journal of psychiatry.

[6]  Dennis Velakoulis,et al.  Anterior cingulate activation during Stroop task performance: a PET to MRI coregistration study of individual patients with schizophrenia. , 2002, The American journal of psychiatry.

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

[8]  A. Carlsson,et al.  Neurotransmitter interactions in schizophrenia—therapeutic implications , 1999, Biological Psychiatry.

[9]  Brita Elvevåg,et al.  Differentiating allocation of resources and conflict detection within attentional control processing , 2007, The European journal of neuroscience.

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

[11]  B. Turetsky,et al.  Visual attention circuitry in schizophrenia investigated with oddball event-related functional magnetic resonance imaging. , 2007, The American journal of psychiatry.

[12]  R. Desimone,et al.  Neural mechanisms of selective visual attention. , 1995, Annual review of neuroscience.

[13]  Felix M Mottaghy,et al.  Brain activation patterns during a selective attention test—a functional MRI study in healthy volunteers and patients with schizophrenia , 2003, Psychiatry Research: Neuroimaging.

[14]  Katharine N. Thakkar,et al.  Reduced error-related activation in two anterior cingulate circuits is related to impaired performance in schizophrenia. , 2008, Brain : a journal of neurology.

[15]  J. Cohen,et al.  Selective deficits in prefrontal cortex function in medication-naive patients with schizophrenia. , 2001, Archives of general psychiatry.

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

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

[18]  Jonathan D. Cohen,et al.  Conflict monitoring and anterior cingulate cortex: an update , 2004, Trends in Cognitive Sciences.

[19]  Daniel A. Miller,et al.  Individuals with schizophrenia present hypo- and hyperactivation during implicit cueing in an inhibitory task , 2006, NeuroImage.

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

[21]  P. Goldman-Rakic.  The cortical dopamine system: role in memory and cognition. , 1998, Advances in pharmacology.

[22]  T. Goldberg,et al.  Brain regions underlying response inhibition and interference monitoring and suppression , 2006, The European journal of neuroscience.

[23]  E. Bullmore,et al.  Functional dysconnectivity in schizophrenia associated with attentional modulation of motor function. , 2005, Brain : a journal of neurology.

[24]  Jonathan D. Cohen,et al.  Conflict monitoring versus selection-for-action in anterior cingulate cortex , 1999, Nature.

[25]  J. Duncan,et al.  Common regions of the human frontal lobe recruited by diverse cognitive demands , 2000, Trends in Neurosciences.

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

[27]  Cameron S. Carter,et al.  Prefrontal functioning during context processing in schizophrenia and major depression: An event-related fMRI study , 2005, Schizophrenia Research.

[28]  M. Corbetta,et al.  Control of goal-directed and stimulus-driven attention in the brain , 2002, Nature Reviews Neuroscience.

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

[30]  M. Egan,et al.  Effect of Catechol-O-Methyltransferase val158met Genotype on Attentional Control , 2005, The Journal of Neuroscience.

[31]  Karl J. Friston,et al.  Stochastic Designs in Event-Related fMRI , 1999, NeuroImage.

[32]  D. Navon.  Forest before trees: The precedence of global features in visual perception , 1977, Cognitive Psychology.

[33]  Tommaso Scarabino,et al.  Additive Effects of Genetic Variation in Dopamine Regulating Genes on Working Memory Cortical Activity in Human Brain , 2006, The Journal of Neuroscience.

[34]  Graham V. Williams,et al.  Inverted-U dopamine D1 receptor actions on prefrontal neurons engaged in working memory , 2007, Nature Neuroscience.

[35]  Jonathan D. Cohen,et al.  Prefrontal cortex dysfunction mediates deficits in working memory and prepotent responding in schizophrenia , 2003, Biological Psychiatry.

[36]  C. Carter,et al.  Functional Magnetic Resonance Imaging Study of Cognitive Control in the Healthy Relatives of Schizophrenia Patients , 2006, Biological Psychiatry.

[37]  Peter F. Liddle,et al.  Attention orienting dysfunction during salient novel stimulus processing in schizophrenia , 2005, Schizophrenia Research.

[38]  Leonardo Fazio,et al.  Polymorphisms in human dopamine D2 receptor gene affect gene expression, splicing, and neuronal activity during working memory , 2007, Proceedings of the National Academy of Sciences.

[39]  M. Egan,et al.  Catechol O-methyltransferase val158-met genotype and individual variation in the brain response to amphetamine , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[40]  D. Manoach.  Prefrontal cortex dysfunction during working memory performance in schizophrenia: reconciling discrepant findings , 2003, Schizophrenia Research.

[41]  M. Just,et al.  From the SelectedWorks of Marcel Adam Just 1992 A capacity theory of comprehension : Individual differences in working memory , 2017 .

[42]  Jonathan D. Cohen,et al.  Specificity of prefrontal dysfunction and context processing deficits to schizophrenia in never-medicated patients with first-episode psychosis. , 2005, American Journal of Psychiatry.

[43]  M. First,et al.  Structured clinical interview for DSM-IV axis II personality disorders : SCID-II , 1997 .