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A Study With Event-Related Potentials and Functional Magnetic Resonance Imaging

Corinna Haenschel, PhD; Robert A. Bittner, MA; Fabian Haertling, MD; Anna Rotarska-Jagiela, MSc; Konrad Maurer, MD; Wolf Singer, MD; David E. J. Linden, MD, PhD

Arch Gen Psychiatry. 2007;64(11):1229-1240.

Context  Working memory (WM) deficits in patients with schizophrenia have mainly been associated with prefrontal dysfunction. However, the contribution of perceptual deficits and abnormalities in sensory areas has not been explored. The present study closes this important gap in our understanding of WM dysfunction in schizophrenia by monitoring neural activity during WM encoding and retrieval with event-related potentials (ERPs) and functional magnetic resonance imaging (fMRI).

Objective  To investigate the neurophysiological changes that contribute to WM impairment in early-onset schizophrenia at perceptual and cognitive stages using the ERP components P1, P3a, P370, and P570 and fMRI data from extrastriate visual areas.

Design  We conducted the study between June 1, 2003, and December 20, 2006. Electroencephalographic and fMRI data were acquired separately during a visual delayed discrimination task. Participants encoded up to 3 abstract shapes that were presented sequentially for 600 milliseconds each and decided after a 12-second delay whether a probe matched 1 of the sample stimuli.

Setting  Between-group study at an inpatient psychiatric hospital and outpatient psychiatric facilities.

Participants  Seventeen adolescents with early-onset schizophrenia according to DSM-IV criteria and 17 matched controls participated in the study.

Main Outcome Measures  Amplitude of the ERP components P1, P3a, P370, and P570 and the fMRI signal from extrastriate visual areas.

Results  The P1 amplitude was reduced in patients during encoding and retrieval. The P1 amplitude increased with WM load during encoding only in controls. In this group, a stronger P1 amplitude increase predicted better WM performance. The P1 reduction was mirrored by reduced activation of visual areas in patients in fMRI. The P370 amplitude during encoding and retrieval was also reduced in patients.

Conclusions  The P1 amplitude reduction indicates an early visual deficit in adolescents with schizophrenia. Our findings suggest that P1 is of particular relevance for successful WM encoding. Early visual deficits contribute to impaired WM in schizophrenia in addition to deficits in later memory-related processes.

Author Affiliations: Laboratory for Neurophysiology and Neuroimaging, Department of Psychiatry (Drs Haenschel, Maurer, and Linden, Mr Bittner, and Ms Rotarska-Jagiela), and Department of Child and Adolescent Psychiatry (Dr Haertling), Johann Wolfgang Goethe-University, and Max Planck Institute for Brain Research (Drs Haenschel and Singer and Mr Bittner), Frankfurt, Germany; and Wolfson Centre for Cognitive Neuroscience, School of Psychology, University of Wales, Bangor (Dr Linden).

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