title: Phase-specific brain change of spatial working memory processing in genetic and ultra-high risk groups of schizophrenia.
abstract: Spatial working memory (WM) processing has 3 distinct phases: encoding, maintenance, and retrieval and its dysfunction is a core feature in schizophrenia. We examined phase-specific brain activations associated with spatial WM in first-degree relatives of schizophrenia (genetic high risk, GHR), ultra-high risk (UHR) subjects, patients with schizophrenia, and healthy controls. We used an event-related functional magnetic resonance imaging in 17 GHR subjects, 21 UHR subjects, 15 clinically stable patients with schizophrenia and 16 healthy controls, while subjects were performing a spatial delayed-response task. During the encoding phase, the GHR group showed increased activation in the fronto-parietal regions, whereas the UHR and schizophrenia groups showed significantly less activation in these regions than did the healthy control group. Especially, frontal activation was strongest in GHR subjects, followed by healthy controls, and occurred to a lesser degree in the UHR group, with the least activation occurring in the schizophrenia group. During the maintenance phase, the thalamus showed a differential activation, similar to frontal activation pattern during the encoding phase. During the retrieval phase, no prominent differential activations were found. Increased activations were observed in the superior temporal gyrus during the encoding and maintenance phases in the GHR, UHR, and schizophrenia groups relative to healthy controls. Our findings suggest that functional deficits associated with spatial WM processing emerge in the UHR before the onset of schizophrenia and compensatory neural processes exist in the GHR with genetic liability to schizophrenia.
authors.affiliation: Department of Psychiatry, Seoul National University College of Medicine, 101 Daehak-no, Chongno-gu, Seoul 110-744, Korea.
authors.forename: Jung-Seok
authors.initials: JS
authors.lastname: Choi
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Park
authors.forename: Myung Hun
authors.initials: MH
authors.lastname: Jung
authors.forename: Joon Hwan
authors.initials: JH
authors.lastname: Jang
authors.forename: Do-Hyung
authors.initials: DH
authors.lastname: Kang
authors.forename: Wi Hoon
authors.initials: WH
authors.lastname: Jung
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Han
authors.forename: Chi-Hoon
authors.initials: CH
authors.lastname: Choi
authors.forename: Kyung Sue
authors.initials: KS
authors.lastname: Hong
authors.forename: Jun Soo
authors.initials: JS
authors.lastname: Kwon
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D016022:Case-Control Studies; D005190:Family / Q000523:psychology; D005260:Female; D005625:Frontal Lobe / Q000503:physiopathology; D059907:Functional Neuroimaging; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology*; D008570:Memory, Short-Term; D010296:Parietal Lobe / Q000503:physiopathology; D062706:Prodromal Symptoms; D011930:Reaction Time; D012306:Risk; D012559:Schizophrenia / Q000150:complications / Q000235:genetics* / Q000503:physiopathology*; D013702:Temporal Lobe / Q000503:physiopathology; D013788:Thalamus / Q000503:physiopathology