Functional Dissociation of Confident and Not-Confident Errors in the Spatial Delayed Response Task Demonstrates Impairments in Working Memory Encoding and Maintenance in Schizophrenia

Even though extensively investigated, the nature of working memory (WM) deficits in patients with schizophrenia (PSZ) is not yet fully understood. In particular, the contribution of different WM sub-processes to the severe WM deficit observed in PSZ is a matter of debate. So far, most research has focused on impaired WM maintenance. By analyzing different types of errors in a spatial delayed response task (DRT), we have recently demonstrated that incorrect yet confident responses (which we labeled as false memory errors) rather than incorrect/not-confident responses reflect failures of WM encoding, which was also impaired in PSZ. In the present study, we provide further evidence for a functional dissociation between confident and not-confident errors by manipulating the demands on WM maintenance, i.e., the length over which information has to be maintained in WM. Furthermore, we investigate whether these functionally distinguishable WM processes are impaired in PSZ. Twenty-four PSZ and 24 demographically matched healthy controls (HC) performed a spatial DRT in which the length of the delay period was varied between 1, 2, 4, and 6 s. In each trial, participants also rated their level of response confidence. Across both groups, longer delays led to increased rates of incorrect/not-confident responses, while incorrect/confident responses were not affected by delay length. This functional dissociation provides additional support for our proposal that false memory errors (i.e., confident errors) reflect problems at the level of WM encoding, while not-confident errors reflect failures of WM maintenance. Schizophrenic patients showed increased numbers of both confident and not-confident errors, suggesting that both sub-processes of WM—encoding and maintenance—are impaired in schizophrenia. Combined with the delay length-dependent functional dissociation, we propose that these impairments in schizophrenic patients are functionally distinguishable.

[1]  Carly J. Leonard,et al.  Selective Attention, Working Memory, and Executive Function as Potential Independent Sources of Cognitive Dysfunction in Schizophrenia , 2018, Schizophrenia bulletin.

[2]  D. Prvulovic,et al.  Visual working memory encoding in schizophrenia and first-degree relatives: neurofunctional abnormalities and impaired consolidation , 2018, Psychological Medicine.

[3]  M. Chafee,et al.  Abnormal cortical neural synchrony during working memory in schizophrenia , 2018, Clinical Neurophysiology.

[4]  Benjamin M. Robinson,et al.  Impaired suppression of delay-period alpha and beta is associated with impaired working memory in schizophrenia. , 2017, Biological psychiatry. Cognitive neuroscience and neuroimaging.

[5]  Xiao-Jing Wang,et al.  Schizophrenia is associated with a pattern of spatial working memory deficits consistent with cortical disinhibition , 2017, Schizophrenia Research.

[6]  G. A. Miller,et al.  Deficient attention modulation of lateralized alpha power in schizophrenia. , 2016, Psychophysiology.

[7]  Rainer Goebel,et al.  The When and Where of Working Memory Dysfunction in Early-Onset Schizophrenia-A Functional Magnetic Resonance Imaging Study. , 2015, Cerebral cortex.

[8]  Sohee Park,et al.  Working memory impairment as an endophenotypic marker of a schizophrenia diathesis , 2014, Schizophrenia Research: Cognition.

[9]  Albert Compte,et al.  Serotonin regulates performance nonmonotonically in a spatial working memory network. , 2014, Cerebral cortex.

[10]  Xiao-Jing Wang,et al.  Linking microcircuit dysfunction to cognitive impairment: effects of disinhibition associated with schizophrenia in a cortical working memory model. , 2014, Cerebral cortex.

[11]  Jutta S. Mayer,et al.  Failure to benefit from target novelty during encoding contributes to working memory deficits in schizophrenia , 2014, Cognitive neuropsychiatry.

[12]  Daniel H. Mathalon,et al.  Converting positive and negative symptom scores between PANSS and SAPS/SANS , 2014, Schizophrenia Research.

[13]  Sohee Park,et al.  Visuospatial imagery and working memory in schizophrenia , 2014, Cognitive neuropsychiatry.

[14]  Carly J. Leonard,et al.  Toward the neural mechanisms of reduced working memory capacity in schizophrenia. , 2013, Cerebral cortex.

[15]  Jutta S. Mayer,et al.  Impaired Contingent Attentional Capture Predicts Reduced Working Memory Capacity in Schizophrenia , 2012, PloS one.

[16]  Jung-Seok Choi,et al.  Phase-specific brain change of spatial working memory processing in genetic and ultra-high risk groups of schizophrenia. , 2012, Schizophrenia bulletin.

[17]  O. Krastoshevsky,et al.  The effects of perceptual encoding on the magnitude of object working memory impairment in schizophrenia , 2012, Schizophrenia Research.

[18]  Jutta S. Mayer,et al.  Working memory encoding and false memory in schizophrenia and bipolar disorder in a spatial delayed response task. , 2012, Journal of abnormal psychology.

[19]  Katharine N. Thakkar,et al.  Impaired passive maintenance and spared manipulation of internal representations in patients with schizophrenia. , 2012, Schizophrenia bulletin.

[20]  J. Lisman Excitation, inhibition, local oscillations, or large-scale loops: what causes the symptoms of schizophrenia? , 2012, Current Opinion in Neurobiology.

[21]  Patricia A. Heale Placenta Accreta: A New Take on an Old Problem , 2012 .

[22]  A. Compte,et al.  A Computational Model for Spatial Working Memory Deficits in Schizophrenia , 2012, Pharmacopsychiatry.

[23]  Sohee Park,et al.  Enhancing visual working memory encoding: The role of target novelty , 2011, Visual cognition.

[24]  Daniel C Javitt,et al.  Early sensory contributions to contextual encoding deficits in schizophrenia. , 2011, Archives of general psychiatry.

[25]  D. Linden,et al.  Exploring intermediate phenotypes with EEG: Working memory dysfunction in schizophrenia , 2011, Behavioural Brain Research.

[26]  Valerie M. Beck,et al.  Failure of Schizophrenia Patients to Overcome Salient Distractors During Working Memory Encoding , 2010, Biological Psychiatry.

[27]  W. Singer,et al.  Alpha Phase Locking Predicts Residual Working Memory Performance in Schizophrenia , 2010, Biological Psychiatry.

[28]  N. Andreasen,et al.  Antipsychotic Dose Equivalents and Dose-Years: A Standardized Method for Comparing Exposure to Different Drugs , 2010, Biological Psychiatry.

[29]  W. Singer,et al.  Abnormal neural oscillations and synchrony in schizophrenia , 2010, Nature Reviews Neuroscience.

[30]  W. Singer,et al.  Cortical Oscillatory Activity Is Critical for Working Memory as Revealed by Deficits in Early-Onset Schizophrenia , 2009, The Journal of Neuroscience.

[31]  Philip D. Harvey,et al.  Systemic hypotheses for generalized cognitive deficits in schizophrenia: a new take on an old problem. , 2009, Schizophrenia bulletin.

[32]  P. Goldman-Rakic,et al.  Impairment of Working Memory Maintenance and Response in Schizophrenia: Functional Magnetic Resonance Imaging Evidence , 2008, Biological Psychiatry.

[33]  J. Gore,et al.  Origins of Spatial Working Memory Deficits in Schizophrenia: An Event-Related fMRI and Near-Infrared Spectroscopy Study , 2008, PloS one.

[34]  D. Badcock,et al.  Examining encoding imprecision in spatial working memory in schizophrenia , 2008, Schizophrenia Research.

[35]  Philip D. Harvey,et al.  Predicting Schizophrenia Patients’ Real-World Behavior with Specific Neuropsychological and Functional Capacity Measures , 2008, Biological Psychiatry.

[36]  F. Schmidt Meta-Analysis , 2008 .

[37]  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.

[38]  J. Callicott,et al.  Dysfunctional and compensatory prefrontal cortical systems, genes and the pathogenesis of schizophrenia. , 2007, Cerebral cortex.

[39]  S. Kumra,et al.  Neurocognitive deficits in adolescents with schizophrenia: longitudinal stability and predictive utility for short-term functional outcome. , 2007, Journal of the American Academy of Child and Adolescent Psychiatry.

[40]  Trevor R. Norman,et al.  Behavioural studies of spatial working memory dysfunction in schizophrenia: A quantitative literature review , 2007, Psychiatry Research.

[41]  J. Sweeney,et al.  Adverse effects of risperidone on spatial working memory in first-episode schizophrenia. , 2006, Archives of general psychiatry.

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

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

[44]  Tyrone D. Cannon,et al.  Dorsolateral prefrontal cortex activity during maintenance and manipulation of information in working memory in patients with schizophrenia. , 2005, Archives of general psychiatry.

[45]  D. Lewis,et al.  Cortical inhibitory neurons and schizophrenia , 2005, Nature Reviews Neuroscience.

[46]  Patricia S. Goldman-Rakic,et al.  Targeting the dopamine D1 receptor in schizophrenia: insights for cognitive dysfunction , 2004, Psychopharmacology.

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

[48]  J. Lieberman,et al.  Impairments in perceptual competency and maintenance on a visual delayed match-to-sample test in first-episode schizophrenia. , 2003, Archives of general psychiatry.

[49]  M. Hartman,et al.  Working memory and schizophrenia: evidence for slowed encoding , 2003, Schizophrenia Research.

[50]  P. Goldman-Rakic,et al.  Sustained Mnemonic Response in the Human Middle Frontal Gyrus during On-Line Storage of Spatial Memoranda , 2002, Journal of Cognitive Neuroscience.

[51]  R. McMahon,et al.  Visual perceptual and working memory impairments in schizophrenia. , 2002, Archives of general psychiatry.

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

[53]  P. Goldman-Rakic,et al.  Synaptic mechanisms and network dynamics underlying spatial working memory in a cortical network model. , 2000, Cerebral cortex.

[54]  D. Hell,et al.  Spatial working memory deficits and clinical symptoms in schizophrenia: a 4-month follow-up study , 1999, Biological Psychiatry.

[55]  N. Cowan,et al.  Impaired precision, but normal retention, of auditory sensory ("echoic") memory information in schizophrenia. , 1997, Journal of abnormal psychology.

[56]  J. Rabe-Jabłońska,et al.  [Affective disorders in the fourth edition of the classification of mental disorders prepared by the American Psychiatric Association -- diagnostic and statistical manual of mental disorders]. , 1993, Psychiatria polska.

[57]  Sohee Park,et al.  Schizophrenics show spatial working memory deficits. , 1992, Archives of general psychiatry.

[58]  Neil A. Macmillan,et al.  Detection Theory: A User's Guide , 1991 .

[59]  G. Reynolds,et al.  Beyond the Dopamine Hypothesis , 1989, British Journal of Psychiatry.

[60]  N A Macmillan,et al.  Detection theory analysis of group data: estimating sensitivity from average hit and false-alarm rates. , 1985, Psychological bulletin.

[61]  D. Barch,et al.  Working memory encoding and maintenance deficits in schizophrenia: neural evidence for activation and deactivation abnormalities. , 2013, Schizophrenia bulletin.

[62]  Benjamin M. Robinson,et al.  Impaired visual working memory consolidation in schizophrenia. , 2009, Neuropsychology.

[63]  Calmet Meteorological Model A User's Guide for the , 1999 .

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

[65]  H. Wittchen,et al.  SKID. Strukturiertes Klinisches Interview für DSM-IV. Achse I und II. Handanweisung , 1997 .

[66]  D H Brainard,et al.  The Psychophysics Toolbox. , 1997, Spatial vision.

[67]  P. Goldman-Rakic Working memory dysfunction in schizophrenia. , 1994, The Journal of neuropsychiatry and clinical neurosciences.

[68]  A. Raine The SPQ: a scale for the assessment of schizotypal personality based on DSM-III-R criteria. , 1991, Schizophrenia bulletin.

[69]  P. Goldman-Rakic Cellular and circuit basis of working memory in prefrontal cortex of nonhuman primates. , 1990, Progress in brain research.

[70]  S. Kay,et al.  The positive and negative syndrome scale (PANSS) for schizophrenia. , 1987, Schizophrenia bulletin.