Reduced plastic brain responses in schizophrenia: a transcranial magnetic stimulation study $ Paul B. Fitzgerald a, * , Timothy L. Brown a , Natasha A.U. Marston a , Tom Oxley a , Anthony de Castella a , Z. Jeff Daskalakis b , J. Kulkarni a a Department of Psychological Medicine, Alfred Psychiatry Research Centre, The Alfred and Monash University Department of Psychological Medicine, Commercial Rd. Melbourne, Victoria 3004, Australia b Centre for Addiction and Mental Health, Clarke Division, Toronto, Ontario, Canada Received 9 December 2003; accepted 21 January 2004 Available online 16 March 2004 Abstract Background: Abnormalities in brain plasticity, possibly related to abnormal cortical inhibition (CI), have been proposed to underlie the pathophysiology of schizophrenia. Transcranial magnetic stimulation (TMS) provides a dynamic method for non- invasive study of plastic processes in the human brain. We aimed to determine whether patients with schizophrenia would exhibit an abnormal response to repetitive TMS (rTMS) applied to the motor cortex and whether this would relate to deficient cortical inhibition. Methods: Measures of motor cortical excitability and cortical inhibition were made before and after a single 15-min train of 1-Hz rTMS applied to the motor cortex in medicated and unmedicated patients with schizophrenia as well as healthy controls. Results: All three groups had equal motor cortical excitability prior to rTMS, although both patient groups had a shorter cortical silent period (CSP) and less cortical inhibition than the control group. Cortical excitability, as assessed by motor threshold levels, did not reduce in both medicated and unmedicated patients in response to rTMS as was seen in the control group. Significant differences were also seen between the groups in response to the rTMS for motor-evoked potential (MEP) size and cortical silent period duration. Conclusions: Both medicated and medication free patients with schizophrenia demonstrated reduced brain responses to rTMS and deficits in cortical inhibition. D 2004 Elsevier B.V. All rights reserved. Keywords: Repetitive transcranial magnetic stimulation; Cortical plasticity; Psychosis; Cortical inhibition; Schizophrenia; TMS 1. Introduction It has been suggested that abnormalities of neural plasticity may underlie important neuropsychiatric disorders such as schizophrenia (Haracz, 1985). Neural and brain plasticity refer to the brain’s ability to change structure and function in response to experience (Kolb and Whishaw, 1998). The mecha- nisms involved in these plastic responses include 0920-9964/$ - see front matter D 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.schres.2004.01.018 $ This study was presented at the meeting of the Society for Biological Psychiatry, San Francisco, May 2003 (abstract Biological Psychiatry, 53, S107). * Corresponding author. Alfred Psychiatry Research Centre, Level 1, Old Baker Building, The Alfred, Commercial Rd. Melbourne, Victoria 3004, Australia. Tel.: +61-3-9276-6552; fax: +61-3-9276-6556. E-mail address: paul.fitzgerald@med.monash.edu.au (P.B. Fitzgerald). www.elsevier.com/locate/schres Schizophrenia Research 71 (2004) 17 – 26