title: Abnormal effective connectivity and psychopathological symptoms in the psychosis high-risk state.
abstract: BACKGROUND
  Recent evidence has revealed abnormal functional connectivity between the frontal and parietal brain regions during working memory processing in patients with schizophrenia and first-episode psychosis. However, it still remains unclear whether abnormal frontoparietal connectivity during working memory processing is already evident in the psychosis high-risk state and whether the connection strengths are related to psychopathological outcomes.
  
  
  METHODS
  Healthy controls and antipsychotic-naive individuals with an at-risk mental state (ARMS) performed an n-back working memory task while undergoing functional magnetic resonance imaging. Effective connectivity between frontal and parietal brain regions during working memory processing were characterized using dynamic causal modelling.
  
  
  RESULTS
  Our study included 19 controls and 27 individuals with an ARMS. In individuals with an ARMS, we found significantly lower task performances and reduced activity in the right superior parietal lobule and middle frontal gyrus than in controls. Furthermore, the working memory-induced modulation of the connectivity from the right middle frontal gyrus to the right superior parietal lobule was significantly reduced in individuals with an ARMS, while the extent of this connectivity was negatively related to the Brief Psychiatric Rating Scale total score.
  
  
  CONCLUSIONS
  The modest sample size precludes a meaningful subgroup analysis for participants with a later transition to psychosis.
  
  
  CONCLUSIONS
  This study demonstrates that abnormal frontoparietal connectivity during working memory processing is already evident in individuals with an ARMS and is related to psychiatric symptoms. Thus, our results provide further insight into the pathophysiological mechanisms of the psychosis high-risk state by linking functional brain imaging, computational modelling and psychopathology.
authors: Department of Psychiatry (UPK), University of Basel, Petersgraben, and the Medical Image Analysis Centre, University Hospital Basel, Schanzenstrasse, Basel, Switzerland.
authors: André
authors: A
authors: Schmidt
authors: Department of Psychiatry (UPK), University of Basel, Petersgraben, and the Medical Image Analysis Centre, University Hospital Basel, Schanzenstrasse, Basel, Switzerland.
authors: Renata
authors: R
authors: Smieskova
authors: Department of Psychiatry (UPK), University of Basel, Petersgraben, Basel, Switzerland.
authors: Andor
authors: A
authors: Simon
authors: Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, United Kingdom.
authors: Paul
authors: P
authors: Allen
authors: Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, United Kingdom.
authors: Paolo
authors: P
authors: Fusar-Poli
authors: Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, United Kingdom.
authors: Philip K
authors: PK
authors: McGuire
authors: Medical Image Analysis Centre, University Hospital Basel, Schanzenstrasse, Basel, Switzerland.
authors: Kerstin
authors: K
authors: Bendfeldt
authors: Department of Psychiatry (UPK), University of Basel, Petersgraben, Basel, Switzerland.
authors: Jacqueline
authors: J
authors: Aston
authors: Department of Psychiatry (UPK), University of Basel, Petersgraben, Basel, Switzerland.
authors: Undine E
authors: UE
authors: Lang
authors: Department of Psychiatry (UPK), University of Basel, Petersgraben, Basel, Switzerland.
authors: Marc
authors: M
authors: Walter
authors: Medical Image Analysis Centre, University Hospital Basel, Schanzenstrasse, Basel, Switzerland.
authors: Ernst-Wilhelm
authors: EW
authors: Radue
authors: Department of Psychiatry (UPK), University of Basel, Petersgraben, Basel, Switzerland.
authors: Anita
authors: A
authors: Riecher-Rössler
authors: Department of Psychiatry (UPK), University of Basel, Petersgraben, the Medical Image Analysis Centre, University Hospital Basel, Schanzenstrasse, Basel, Switzerland, and the Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, United Kingdom.
authors: Stefan J
authors: SJ
authors: Borgwardt
mesh_terms: D000328:Adult; D001499:Bayes Theorem; D001931:Brain Mapping; D003198:Computer Simulation; D005260:Female; D005625:Frontal Lobe / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology*; D008959:Models, Neurological; D009434:Neural Pathways / Q000503:physiopathology; D009483:Neuropsychological Tests; D010296:Parietal Lobe / Q000503:physiopathology*; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000503:physiopathology*; D012306:Risk