The relationship between performance and f MRI signal during working memory in patients with schizophrenia, unaffected co-twins, and control subjects Katherine H. Karlsgodt a , David C. Glahn b , Theo G.M. van Erp a , Sebastian Therman c , Matti Huttunen c , Marko Manninen c , Jaakko Kaprio c,d , Mark S. Cohen e,f,g , Jouko Lönnqvist c,h , Tyrone D. Cannon a,e,i, ⁎ a Department of Psychology, UCLA b Department of Psychiatry and Research Imaging Center, UTHSCA, USA c Department of Mental Health and Alcohol Research, National Public Health Institute of Finland, Finland d Department of Radiology, Helsinki University Central Hospital, Finland e Department of Psychiatry and Biobehavioral Sciences, UCLA, USA f Department of Neurology, Radiology, Biomedical Physics UCLA, USA g Division of Brain Mapping, UCLA, USA h Department of Psychiatry, University of Helsinki, Finland i Department of Human Genetics, UCLA, USA Received 29 May 2006; received in revised form 9 August 2006; accepted 11 August 2006 Available online 5 October 2006 Abstract While behavioral research shows working memory impairments in schizophrenics and their relatives, functional neuroimaging studies of patients and healthy controls show conflicting findings of hypo- and hyperactivation, possibly indicating different relationships between physiological activity and performance. In a between-subjects regression analysis of f MRI activation and performance, low performance was associated with relatively lower activation in patients than controls, while higher performance was associated with higher activation in patients than controls in DLPFC and parietal cortex, but not occipital cortex, with unaffected twins of schizophrenics being intermediate between the groups. Accordingly, this supports the idea that both hyper and hypoactivation may be possible along a continuum of behavioral performance in a way consistent with a neural inefficiency model. Further, this study offers preliminary evidence that the relationship between behavior and physiology in schizophrenia may be heritable. © 2006 Elsevier B.V. All rights reserved. Keywords: Schizophrenia; Working memory; fMRI; Twin; Genetic; Inefficiency 1. Introduction Functional magnetic resonance imaging (f MRI) of working memory (WM) in schizophrenia has generated conflicting findings of hypofrontality (Barch et al., 2003; Cannon et al., 2005; Ragland et al., 1998; Stevens et al., 1998) and hyperfrontality (Callicott et al., 2000; Schizophrenia Research 89 (2007) 191 – 197 www.elsevier.com/locate/schres ⁎ Corresponding author. Department of Psychology, UCLA, 1285 Franz Hall, Los Angeles, CA 90095-1563, USA. Tel.: +1 310 206 8765; fax: +1 310 794 9740. E-mail address: cannon@psych.ucla.edu (T.D. Cannon). 0920-9964/$ - see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.schres.2006.08.016