1. ¹Department of Psychiatry, University of Cambridge School of Clinical Medicine, Cambridge, UK
2. ²Department of Experimental Psychology, University of Cambridge, Cambridge, UK
3. ³Department of Neurology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK
4. ⁴MRC Cognition and Brain Sciences Unit, Cambridge, UK
5. ⁵Institute of Psychiatry, University of London, London, UK

Correspondence: Professor BJ Sahakian, Department of Psychiatry, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK. Tel: +44 1233 331209; Fax: +44 1223 336968

Received 13 January 2005; Revised 17 June 2005; Accepted 20 July 2005; Published online 7 September 2005.

Abstract

The frontal variant of frontotemporal dementia is a significant neurological condition worldwide. There exist few treatments available for the cognitive and behavioural sequelae of fvFTD. Previous research has shown that these patients display risky decision-making, and numerous studies have now demonstrated pathology affecting the orbitofrontal cortex. The present study uses a within-subjects, double-blind, placebo-controlled procedure to investigate the effects of a single dose of methylphenidate (40 mg) upon a range of different cognitive processes including those assessing prefrontal cortex integrity. Methylphenidate was effective in 'normalizing' the decision-making behavior of patients, such that they became less risk taking on medication, although there were no significant effects on other aspects of cognitive function, including working memory, attentional set shifting, and reversal learning. Moreover, there was an absence of the normal subjective and autonomic responses to methylphenidate seen in elderly subjects. The results are discussed in terms of the 'somatic marker' hypothesis of impaired decision-making following orbitofrontal dysfunction.