Psychopharmacology (2004) 175:296–302 DOI 10.1007/s00213-004-1828-4 ORIGINAL INVESTIGATION Sabine M. Grüsser · Jana Wrase · Sabine Klein · Derik Hermann · Michael N. Smolka · Matthias Ruf · Wolfgang Weber-Fahr · Herta Flor · Karl Mann · Dieter F. Braus · Andreas Heinz Cue-induced activation of the striatum and medial prefrontal cortex is associated with subsequent relapse in abstinent alcoholics Received: 11 July 2003 / Accepted: 26 January 2004 / Published online: 1 May 2004  Springer-Verlag 2004 Abstract Rationale: Animal experiments have provided evidence that the striatum and medial prefrontal cortex play a predominant role in the acquisition and mainte- nance of drug-seeking behavior. Objectives: Alcohol-as- sociated stimuli that were regularly paired with alcohol intake may become conditioned cues and elicit a moti- vational response that triggers relapse in alcohol-depen- dent patients. Methods: We used functional magnetic resonance imaging and visual alcohol-associated and con- trol cues to assess brain activation in ten abstinent alco- holics and control subjects. Patients were followed for 3 months, and alcohol intake was recorded. Results: Al- cohol-related versus neutral visual stimuli activated the putamen, anterior cingulate and adjacent medial pre- frontal cortex in alcoholics compared with healthy con- trols. Cue-induced activation of these brain areas was pronounced in the five alcoholics who subsequently re- lapsed during the observation period. A multiple regres- sion analysis showed that, in alcoholics, the amount of subsequent alcohol intake was associated with the inten- sity of cue-induced brain activation but not the severity of alcohol craving, amount of previous alcohol intake or duration of abstinence before scanning. Conclusions: This pilot study showed that cue-induced activation of the anterior cingulate, medial prefrontal cortex and striatum may play a role in the attribution of incentive salience to alcohol-associated stimuli, thus increasing the motiva- tional value and attentional processing of alcohol cues. Functional brain imaging may help to identify a group of alcoholics with an otherwise undetected high risk of re- lapse. Keywords fMRI · Habit formation · Cue-induced brain activation · Relapse · Alcoholism Introduction Former neutral stimuli that were regularly paired with alcohol intake may become conditioned cues and evoke alcohol craving. Craving for alcohol, however, is subject to denial and poorly correlated with subsequent relapse risk (Tiffany and Carter 1998). It was previously shown that abstinent alcoholics may evaluate alcohol-related cues negatively and show little craving but still display a positive emotional response to the cues as assessed by startle response inhibition (Mucha et al. 2000; Grüsser et al. 2002). This suggests that continued non-conscious ac- tivation of appetitive responses to alcohol-related stimuli may be present in abstinent alcoholics and might initiate S. M. Grüsser Department of Medical Psychology, Campus CharitØ Mitte, CharitØ—University Medicine Berlin, Berlin, Germany J. Wrase · A. Heinz ( ) ) Department of Psychiatry, CharitØ Campus Mitte, CharitØ—University Medicine Berlin, Schumannstr. 20/21, 10117 Berlin, Germany e-mail: andreas.heinz@charite.de Tel.: +49-30-450517002 Fax: +49-30-450517921 S. Klein · D. Hermann · M. N. Smolka · K. Mann Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany M. Ruf Department of NMR-Research in Psychiatry, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany H. Flor Department of Neuropsychology, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany W. Weber-Fahr · D. F. Braus Neuroimage Nord, Department of Psychiatry, University of Hamburg, Hamburg, Germany