Early sensory contributions to contextual encoding deficits in schizophrenia.

CONTEXT The AX version of the visual continuous performance task (AX-CPT) is widely used for investigating visual working memory dysfunction in schizophrenia. Event-related potentials (ERP) provide an objective index of brain function and can be used to evaluate brain substrates underlying impaired cognition in schizophrenia. OBJECTIVE To assess the mechanisms that underlie visual working memory dysfunction in schizophrenia relative to impairment of early visual processing. DESIGN Case-control study. SETTING Inpatient and outpatient facilities associated with the Nathan Kline Institute for Psychiatric Research. PARTICIPANTS A total of 30 individuals with schizophrenia and 17 healthy comparison subjects. INTERVENTIONS Three versions of the AX-CPT, with parametric variations in the proportions of trial types, were used to test performance and underlying neural activity during differential challenge situations. Contrast sensitivity measures were obtained from most subjects. MAIN OUTCOME MEASURES Behavioral performance was assessed using d' context scores. Integrity of stimulus- and task-related cortical activation to both cue and probe stimuli was assessed using sensory (C1, P1, N1) and cognitive (N2, contingent negative variation [CNV]) ERP components. Early magnocellular/parvocellular function was assessed using contrast sensitivity. Linear regression and path analyses were used to assess relations between physiological and behavioral parameters. RESULTS Patients showed reduced amplitude of both early sensory (P1, N1) and later cognitive (N2, CNV) ERP components. Deficits in sensory (N1) and cognitive (N2) component activation to cue stimuli contributed independently to impaired behavioral performance. In addition, sensory deficits predicted impaired cognitive ERP generation. Finally, deficits in performance correlated with impairments in contrast sensitivity to low, but not high, spatial frequency stimuli. CONCLUSIONS Working memory deficits in schizophrenia have increasingly been attributed to impairments in stimulus encoding rather than to failures in memory retention. This study provides objective physiological support for encoding hypotheses. Further, deficits in sensory processing contribute significantly to impaired working memory performance, consistent with generalized neurochemical models of schizophrenia.

[1]  Jacob Cohen.  Statistical Power Analysis for the Behavioral Sciences , 1969, The SAGE Encyclopedia of Research Design.

[2]  Denis G. Pelli,et al.  The visual filter mediating letter identification , 1994, Nature.

[3]  K. Kiehl,et al.  Rostral anterior cingulate cortex dysfunction during error processing in schizophrenia. , 2003, Brain : a journal of neurology.

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

[5]  Ruben C Gur,et al.  Sensory contributions to impaired emotion processing in schizophrenia. , 2009, Schizophrenia bulletin.

[6]  John J. Foxe,et al.  The neural substrates of impaired prosodic detection in schizophrenia and its sensorial antecedents. , 2007, The American journal of psychiatry.

[7]  Michael F. Green,et al.  Cognitive impairment and functional outcome in schizophrenia and bipolar disorder. , 2006, The Journal of clinical psychiatry.

[8]  Junghee Lee,et al.  Working memory impairments in schizophrenia: a meta-analysis. , 2005, Journal of abnormal psychology.

[9]  Deanna M Barch,et al.  Context-processing deficits in schizophrenia: diagnostic specificity, 4-week course, and relationships to clinical symptoms. , 2003, Journal of abnormal psychology.

[10]  Niels G. Waller.  The Scale for the Assessment of Negative Symptoms , 1995 .

[11]  D. Javitt,et al.  Encoding vs. retention: Differential effects of cue manipulation on working memory performance in schizophrenia , 2007, Schizophrenia Research.

[12]  John J. Foxe,et al.  Subcortical visual dysfunction in schizophrenia drives secondary cortical impairments. , 2007, Brain : a journal of neurology.

[13]  Daniel C. Javitt,et al.  Changing plans: neural correlates of executive control in monkey and human frontal cortex , 2006, Experimental Brain Research.

[14]  Matthew Davidson,et al.  Context Modulates Early Stimulus Processing when Resolving Stimulus-response Conflict , 2006, Journal of Cognitive Neuroscience.

[15]  C. Carter,et al.  Event-related FMRI study of context processing in dorsolateral prefrontal cortex of patients with schizophrenia. , 2003, Journal of abnormal psychology.

[16]  R. O’Reilly,et al.  A computational approach to prefrontal cortex, cognitive control and schizophrenia: recent developments and current challenges. , 1996, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[17]  D. Javitt,et al.  Magnocellular and parvocellular contributions to backward masking dysfunction in schizophrenia , 2003, Schizophrenia Research.

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

[19]  D. Javitt,et al.  Ketamine-induced deficits in auditory and visual context-dependent processing in healthy volunteers: implications for models of cognitive deficits in schizophrenia. , 2000, Archives of general psychiatry.

[20]  Carol H. Ammons,et al.  The Quick Test (QT): Provisional Manual 1 , 2 , 1962 .

[21]  S. Woods,et al.  Chlorpromazine equivalent doses for the newer atypical antipsychotics. , 2003, The Journal of clinical psychiatry.

[22]  S. Hillyard,et al.  Cortical sources of the early components of the visual evoked potential , 2002, Human brain mapping.

[23]  D. Javitt,et al.  Panmodal processing imprecision as a basis for dysfunction of transient memory storage systems in schizophrenia. , 1999, Schizophrenia bulletin.

[24]  M. Minzenberg,et al.  Meta-analysis of 41 functional neuroimaging studies of executive function in schizophrenia. , 2009, Archives of general psychiatry.

[25]  J. Overall,et al.  The Brief Psychiatric Rating Scale , 1962 .

[26]  John J. Foxe,et al.  Impaired visual object processing across an occipital-frontal-hippocampal brain network in schizophrenia: an integrated neuroimaging study. , 2010, Archives of general psychiatry.

[27]  Daniel C Javitt,et al.  Glutamate and schizophrenia: phencyclidine, N-methyl-D-aspartate receptors, and dopamine-glutamate interactions. , 2007, International review of neurobiology.

[28]  Jong H. Yoon,et al.  Association of dorsolateral prefrontal cortex dysfunction with disrupted coordinated brain activity in schizophrenia: relationship with impaired cognition, behavioral disorganization, and global function. , 2008, The American journal of psychiatry.

[29]  D. Javitt,et al.  Early-stage visual processing and cortical amplification deficits in schizophrenia. , 2005, Archives of general psychiatry.

[30]  John H. R. Maunsell,et al.  How parallel are the primate visual pathways? , 1993, Annual review of neuroscience.

[31]  Steve Williams,et al.  Ketamine and fMRI BOLD signal: Distinguishing between effects mediated by change in blood flow versus change in cognitive state , 2003, Human brain mapping.

[32]  John J. Foxe,et al.  Changing plans: a high density electrical mapping study of cortical control. , 2003, Cerebral cortex.

[33]  Angus W MacDonald,et al.  Building a clinically relevant cognitive task: case study of the AX paradigm. , 2007, Schizophrenia bulletin.

[34]  J. Cohen,et al.  Schizophrenic deficits in the processing of context. A test of a theoretical model. , 1996, Archives of general psychiatry.

[35]  D. Barch,et al.  Imaging genetic liability to schizophrenia: systematic review of FMRI studies of patients' nonpsychotic relatives. , 2009, Schizophrenia bulletin.

[36]  J. Coyle,et al.  Glutamate and Schizophrenia: Beyond the Dopamine Hypothesis , 2006, Cellular and Molecular Neurobiology.

[37]  J. Cohen,et al.  Context, cortex, and dopamine: a connectionist approach to behavior and biology in schizophrenia. , 1992, Psychological review.

[38]  John J. Foxe,et al.  Sensory deficits and distributed hierarchical dysfunction in schizophrenia. , 2010, The American journal of psychiatry.

[39]  John J. Foxe,et al.  Visual white matter integrity in schizophrenia. , 2006, The American journal of psychiatry.

[40]  J. Cohen,et al.  Context-processing deficits in schizophrenia: converging evidence from three theoretically motivated cognitive tasks. , 1999, Journal of abnormal psychology.

[41]  John A. Swets,et al.  Invariance of signal detectability over stages of practice and levels of motivation , 1963 .

[42]  R Kikinis,et al.  A functional magnetic resonance imaging study of auditory mismatch in schizophrenia. , 2001, The American journal of psychiatry.

[43]  Michael F. Green,et al.  Functional neuroanatomy of visual masking deficits in schizophrenia. , 2009, Archives of general psychiatry.

[44]  H E ROSVOLD,et al.  A continuous performance test of brain damage. , 1956, Journal of consulting psychology.

[45]  Michael F. Green,et al.  Identifying Cognitive Mechanisms Targeted for Treatment Development in Schizophrenia: An Overview of the First Meeting of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia Initiative , 2008, Biological Psychiatry.

[46]  Peter Praamstra.  Electrophysiological markers of foreperiod effects , 2010 .

[47]  W. Singer,et al.  Contribution of impaired early-stage visual processing to working memory dysfunction in adolescents with schizophrenia: a study with event-related potentials and functional magnetic resonance imaging. , 2007, Archives of general psychiatry.

[48]  K. Kiehl,et al.  An event-related potential investigation of response inhibition in schizophrenia and psychopathy , 2000, Biological Psychiatry.

[49]  C. Schroeder,et al.  Dysfunction of early-stage visual processing in schizophrenia. , 2001, The American journal of psychiatry.

[50]  Cameron S Carter,et al.  Cognitive deficits in unaffected first-degree relatives of schizophrenia patients: a meta-analytic review of putative endophenotypes. , 2005, Schizophrenia bulletin.

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

[52]  J. Ford,et al.  Error detection failures in schizophrenia: ERPs and FMRI. , 2009, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[53]  Pejman Sehatpour,et al.  Early visual sensory deficits as endophenotypes for schizophrenia: high-density electrical mapping in clinically unaffected first-degree relatives. , 2006, Archives of general psychiatry.

[54]  David A Lewis,et al.  Cognitive dysfunction in schizophrenia: convergence of gamma-aminobutyric acid and glutamate alterations. , 2006, Archives of neurology.

[55]  Valerie M. Beck,et al.  Reduced capacity but spared precision and maintenance of working memory representations in schizophrenia. , 2010, Archives of general psychiatry.

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

[57]  Antígona Martínez,et al.  Magnocellular Pathway Impairment in Schizophrenia: Evidence from Functional Magnetic Resonance Imaging , 2008, The Journal of Neuroscience.

[58]  W. Walter,et al.  Contingent Negative Variation : An Electric Sign of Sensori-Motor Association and Expectancy in the Human Brain , 1964, Nature.

[59]  J Leon Kenemans,et al.  Source analysis of the N2 in a cued Go/NoGo task. , 2005, Brain research. Cognitive brain research.

[60]  A. B. Hollingshead,et al.  Four factor index of social status , 1975 .

[61]  J. Lieberman,et al.  Deficits in auditory and visual context-dependent processing in schizophrenia: defining the pattern. , 2000, Archives of general psychiatry.

[62]  D. Pelli,et al.  The role of spatial frequency channels in letter identification , 2002, Vision Research.