title: The When and Where of Working Memory Dysfunction in Early-Onset Schizophrenia-A Functional Magnetic Resonance Imaging Study.
abstract: Behavioral evidence indicates that working memory (WM) in schizophrenia is already impaired at the encoding stage. However, the neurophysiological basis of this primary deficit remains poorly understood. Using event-related fMRI, we assessed differences in brain activation and functional connectivity during the encoding, maintenance and retrieval stages of a visual WM task with 3 levels of memory load in 17 adolescents with early-onset schizophrenia (EOS) and 17 matched controls. The amount of information patients could store in WM was reduced at all memory load levels. During encoding, activation in left ventrolateral prefrontal cortex (VLPFC) and extrastriate visual cortex, which in controls positively correlated with the amount of stored information, was reduced in patients. Additionally, patients showed disturbed functional connectivity between prefrontal and visual areas. During retrieval, right inferior VLPFC hyperactivation was correlated with hypoactivation of left VLPFC in patients during encoding. Visual WM encoding is disturbed by a failure to adequately engage a visual-prefrontal network critical for the transfer of perceptual information into WM. Prefrontal hyperactivation appears to be a secondary consequence of this primary deficit. Isolating the component processes of WM can lead to more specific neurophysiological markers for translational efforts seeking to improve the treatment of cognitive dysfunction in schizophrenia.
authors.affiliation: Laboratory for Neurophysiology and Neuroimaging, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy and Brain Imaging Center, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany Department of Neurophysiology, Max-Planck-Institute for Brain Research, Frankfurt am Main, Germany Ernst Strüngmann Institute for Neuroscience (ESI) in Cooperation with Max Planck Society, Frankfurt am Main, Germany.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Bittner
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine School of Psychology, Cardiff University, Cardiff, UK.
authors.forename: David E J
authors.initials: DE
authors.lastname: Linden
authors.affiliation: Department of Neurocognition, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands.
authors.forename: Alard
authors.initials: A
authors.lastname: Roebroeck
authors.affiliation: Department of Child and Adolescent Psychiatry, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Härtling
authors.affiliation: Laboratory for Neurophysiology and Neuroimaging, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy and Brain Imaging Center, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany Department of Neurophysiology, Max-Planck-Institute for Brain Research, Frankfurt am Main, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Rotarska-Jagiela
authors.affiliation: Laboratory for Neurophysiology and Neuroimaging, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy and Brain Imaging Center, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany.
authors.forename: Konrad
authors.initials: K
authors.lastname: Maurer
authors.affiliation: Department of Neurocognition, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands.
authors.forename: Rainer
authors.initials: R
authors.lastname: Goebel
authors.affiliation: Department of Neurophysiology, Max-Planck-Institute for Brain Research, Frankfurt am Main, Germany Ernst Strüngmann Institute for Neuroscience (ESI) in Cooperation with Max Planck Society, Frankfurt am Main, Germany.
authors.forename: Wolf
authors.initials: W
authors.lastname: Singer
authors.affiliation: Laboratory for Neurophysiology and Neuroimaging, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy and Brain Imaging Center, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany School of Psychology, City University, London, UK.
authors.forename: Corinna
authors.initials: C
authors.lastname: Haenschel
mesh_terms: D000293:Adolescent; D000544:Alzheimer Disease / Q000150:complications* / Q000473:pathology*; D000704:Analysis of Variance; D002540:Cerebral Cortex / Q000098:blood supply*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000209:etiology*; D008570:Memory, Short-Term / Q000502:physiology*; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D011930:Reaction Time / Q000502:physiology; D055815:Young Adult
chemical_list: D010100:Oxygen
keywords: fMRI; functional connectivity; prefrontal cortex; schizophrenia; working memory