title: Classifying individuals at high-risk for psychosis based on functional brain activity during working memory processing.
abstract: The psychosis high-risk state is accompanied by alterations in functional brain activity during working memory processing. We used binary automatic pattern-classification to discriminate between the at-risk mental state (ARMS), first episode psychosis (FEP) and healthy controls (HCs) based on n-back WM-induced brain activity. Linear support vector machines and leave-one-out-cross-validation were applied to fMRI data of matched ARMS, FEP and HC (19 subjects/group). The HC and ARMS were correctly classified, with an accuracy of 76.2% (sensitivity 89.5%, specificity 63.2%, p = 0.01) using a verbal working memory network mask. Only 50% and 47.4% of individuals were classified correctly for HC vs. FEP (p = 0.46) or ARMS vs. FEP (p = 0.62), respectively. Without mask, accuracy was 65.8% for HC vs. ARMS (p = 0.03) and 65.8% for HC vs. FEP (p = 0.0047), and 57.9% for ARMS vs. FEP (p = 0.18). Regions in the medial frontal, paracingulate, cingulate, inferior frontal and superior frontal gyri, inferior and superior parietal lobules, and precuneus were particularly important for group separation. These results suggest that FEP and HC or FEP and ARMS cannot be accurately separated in small samples under these conditions. However, ARMS can be identified with very high sensitivity in comparison to HC. This might aid classification and help to predict transition in the ARMS.
authors.affiliation: Medical Image Analysis Centre, University Hospital Basel, Mittlere Strasse 83, Basel 4031, Switzerland.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Bendfeldt
authors.affiliation: Medical Image Analysis Centre, University Hospital Basel, Mittlere Strasse 83, Basel 4031, Switzerland ; Department of Psychiatry, University of Basel, Wilhelm Klein-Strasse, 27, Basel 4056, Switzerland.
authors.forename: Renata
authors.initials: R
authors.lastname: Smieskova
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University, Nussbaumstr. 7, Munich 80336, Germany.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Koutsouleris
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center, Freiburg, Freiburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Klöppel
authors.affiliation: Medical Image Analysis Centre, University Hospital Basel, Mittlere Strasse 83, Basel 4031, Switzerland ; Department of Psychiatry, University of Basel, Wilhelm Klein-Strasse, 27, Basel 4056, Switzerland.
authors.forename: André
authors.initials: A
authors.lastname: Schmidt
authors.affiliation: Department of Psychiatry, University of Basel, Wilhelm Klein-Strasse, 27, Basel 4056, Switzerland.
authors.forename: Anna
authors.initials: A
authors.lastname: Walter
authors.affiliation: Medical Image Analysis Centre, University Hospital Basel, Mittlere Strasse 83, Basel 4031, Switzerland ; Department of Psychiatry, University of Basel, Wilhelm Klein-Strasse, 27, Basel 4056, Switzerland.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Harrisberger
authors.affiliation: Department of Psychiatry, University of Basel, Wilhelm Klein-Strasse, 27, Basel 4056, Switzerland.
authors.forename: Johannes
authors.initials: J
authors.lastname: Wrege
authors.affiliation: University Hospital of Psychiatry, University of Bern, Bern 3010, Switzerland.
authors.forename: Andor
authors.initials: A
authors.lastname: Simon
authors.affiliation: Dept. of Statistics, University of Warwick, Coventry, UK.
authors.forename: Bernd
authors.initials: B
authors.lastname: Taschler
authors.affiliation: Dept. of Statistics, University of Warwick, Coventry, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Nichols
authors.affiliation: Department of Psychiatry, University of Basel, Wilhelm Klein-Strasse, 27, Basel 4056, Switzerland.
authors.forename: Anita
authors.initials: A
authors.lastname: Riecher-Rössler
authors.affiliation: Department of Psychiatry, University of Basel, Wilhelm Klein-Strasse, 27, Basel 4056, Switzerland.
authors.forename: Undine E
authors.initials: UE
authors.lastname: Lang
authors.affiliation: Medical Image Analysis Centre, University Hospital Basel, Mittlere Strasse 83, Basel 4031, Switzerland.
authors.forename: Ernst-Wilhelm
authors.initials: EW
authors.lastname: Radue
authors.affiliation: Medical Image Analysis Centre, University Hospital Basel, Mittlere Strasse 83, Basel 4031, Switzerland ; Department of Psychiatry, University of Basel, Wilhelm Klein-Strasse, 27, Basel 4056, Switzerland ; Department of Psychosis Studies, King's College London, Institute of Psychiatry, De Crespigny Park 16, London SE58AF, UK.
authors.forename: Stefan
authors.initials: S
authors.lastname: Borgwardt
mesh_terms: D000293:Adolescent; D000704:Analysis of Variance; D001921:Brain / Q000098:blood supply / Q000503:physiopathology*; D001931:Brain Mapping; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000069550:Machine Learning; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000209:etiology*; D008570:Memory, Short-Term / Q000502:physiology*; D009483:Neuropsychological Tests; D062706:Prodromal Symptoms; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000145:classification* / Q000150:complications* / Q000175:diagnosis; D012307:Risk Factors
keywords: Classification; Machine learning; Magnetic resonance imaging; Risk factors; Schizophrenia; Working memory