title: Altered prefrontal cortex activity during working memory task in Bipolar Disorder: A functional Magnetic Resonance Imaging study in euthymic bipolar I and II patients.
abstract: BACKGROUND
  Working memory (WM) deficits are among the most frequently impaired cognitive domains in patients with Bipolar Disorder (BD), being considered promising cognitive endophenotype of the disorder. However, the related neurobiological correlates still deserve further investigation. The present study was aimed to explore whether dorsolateral prefrontal cortex (DLPFC) activity during WM processing was abnormal in euthymic bipolar patients and may represent a potential trait-related phenotype associated with the disorder.
  
  
  METHODS
  Using 3 Tesla functional Magnetic Resonance Imaging (3T fMRI), we studied 28 euthymic bipolar patients (15 BDI and 13 BDII), and 27 healthy controls (HCs), matched for a series of socio-demographic variables, while performing the N-back task for WM assessment.
  
  
  RESULTS
  We found that euthymic bipolar patients showed increased right middle frontal gyrus engagement compared with HCs (FWE-corrected p = 1 × 10(-3)), regardless of WM load, and in spite of similar WM behavioral performance between groups. In particular, BDI patients had greater BOLD signal change compared to HCs (post-hoc Tukey HSD, p = 1 × 10(-3)), while BDII patients expressed an intermediate pattern of activation between BDI patients and HCs. No other significant effects were detected in the corrected whole-brain analysis.
  
  
  CONCLUSIONS
  Sample size, cross-sectional assessment and potential influence of some clinical variables.
  
  
  CONCLUSIONS
  Results provide direct evidence of a primary physiological abnormality in DLPFC function in BDI and II, even in the absence of behavioral differences with HCs. Such exaggerated fMRI response suggests inefficient WM processing in prefrontal circuitry, and further studies are warranted to investigate whether the dysfunction is related to the genetic risk for the disorder.
authors.affiliation: Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Dipartimento di Salute Mentale, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milano, Italy; Bipolar Disorders Clinic, Stanford Medical School, Stanford University, CA, United States. Electronic address: bernardo.dellosso@unimi.it.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Dell'Osso
authors.affiliation: U.O. Neuroradiologia, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milano, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Cinnante
authors.affiliation: Servizio di Consulenza Psichiatrica, IRCCS "Casa Sollievo della Sofferenza", Viale Cappuccini 1, 71013 San Giovanni Rotondo, Italy.
authors.forename: Annabella
authors.initials: A
authors.lastname: Di Giorgio
authors.affiliation: Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Dipartimento di Salute Mentale, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milano, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Cremaschi
authors.affiliation: Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Dipartimento di Salute Mentale, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milano, Italy.
authors.forename: M Carlotta
authors.initials: MC
authors.lastname: Palazzo
authors.affiliation: U.O. Neuroradiologia, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milano, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Cristoffanini
authors.affiliation: Group of Psychiatric Neuroscience, Department of Basic Medical Science, Neuroscience and Sense Organs, "Aldo Moro" University, Piazza Giulio Cesare 11, 70124 Bari, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Fazio
authors.affiliation: Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Dipartimento di Salute Mentale, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milano, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Dobrea
authors.affiliation: U.O. Neuroradiologia, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milano, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Avignone
authors.affiliation: U.O. Neuroradiologia, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milano, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Triulzi
authors.affiliation: Group of Psychiatric Neuroscience, Department of Basic Medical Science, Neuroscience and Sense Organs, "Aldo Moro" University, Piazza Giulio Cesare 11, 70124 Bari, Italy; pRED, NORD DTA, F. Hoffman-La Roche Ltd., Basel, Switzerland.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bertolino
authors.affiliation: Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Dipartimento di Salute Mentale, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milano, Italy.
authors.forename: A Carlo
authors.initials: AC
authors.lastname: Altamura
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000503:physiopathology* / Q000523:psychology; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D058068:Endophenotypes; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology*; D017397:Prefrontal Cortex / Q000503:physiopathology*; D055815:Young Adult
keywords: Bipolar Disorder (BD); Dorsolateral prefrontal cortex (DLPFC); Working memory (WM); functional Magnetic Resonance Imaging (fMRI)