Functional magnetic resonance imaging studies of schizophrenic patients during word production: effects of d-cycloserine Deborah A. Yurgelun-Todd a,b, * , Joseph T. Coyle b , Staci A. Gruber a,b , Perry F. Renshaw b,c , Marisa M. Silveri a,b , Edward Amico b,d , Bruce Cohen b,c,e , Donald C. Goff b,d a Cognitive Neuroimaging Laboratory, Brain Imaging Center, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA b Department of Psychiatry, Harvard Medical School, Boston, MA, USA c Brain Imaging Center, McLean Hospital, Belmont, MA, USA d Schizophrenia Research Program of the Massachusetts General Hospital, Boston, MA, USA e Psychopharmacology Research Laboratory, McLean Hospital, Belmont, MA, USA Received 10 February 2004; received in revised form 26 November 2004; accepted 27 November 2004 Abstract The objective of the present study was to examine patterns of cortical activation underlying d-cycloserine’s therapeutic efficacy in schizophrenic patients using functional magnetic resonance imaging (fMRI). We measured frontal and temporal lobe activation following a word fluency task in 12 subjects meeting DSM-IV criteria for schizophrenia at baseline and after 8 weeks of supervised treatment, using a double-blind, placebo-controlled design. Half of the patients received d-cycloserine (n=6) as a supplement to their conventional neuroleptic treatment while the other half (n =6) was augmented with placebo. Patients receiving d-cycloserine, but not placebo, demonstrated a significant increase in temporal lobe activation. This increased activation was significantly associated with a reduction in negative symptoms. These results suggest that the addition of d- cycloserine to conventional neuroleptics may improve negative symptoms through enhanced temporal lobe function. D 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Schizophrenia; d-cycloserine; fMRI; Verbal fluency; Negative symptoms 1. Introduction Studies of cerebral activation in healthy adult subjects using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) indicate that frontal and temporal cortical regions demonstrate the greatest change in metabolism during 0925-4927/$ - see front matter D 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.pscychresns.2004.11.006 * Corresponding author. Cognitive Neuroimaging Laboratory, Brain Imaging Center, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA. Tel.: +1 617 855 3238; fax: +1 617 855 3713. E-mail address: ytodd@mclean.harvard.edu (D.A. Yurgelun-Todd). Psychiatry Research: Neuroimaging 138 (2005) 23 – 31 www.elsevier.com/locate/psychresns