Cocaine craving is associated with electrophysiological brain responses to cocaine-related stimuli Ingmar H. A. Franken 1 , Roeland C. Dietvorst 1 , Mirjam Hesselmans 1 , Ernst J. Franzek 2 , Ben J. M. van de Wetering 2 & Jan W. Van Strien 1 Erasmus University Rotterdam, the Netherlands 1 and Bouman GGZ, Rotterdam, the Netherlands 2 ABSTRACT Several studies show that substance dependence disorders are characterized by an enhanced processing of substance- related stimuli. The present study was designed to examine the association between craving levels and selective processing of drug cues in cocaine-dependent patients using event-related brain potentials (ERPs). In abstinent cocaine-dependent patients and a healthy control group, we studied the late positive potential (LPP) amplitudes elicited by neutral and cocaine-related stimuli. The results show that cocaine-dependent patients have an enhanced electro- physiological response in the late LPP time window to cocaine-related stimuli as compared to controls, suggesting an enhanced processing of these stimuli. Most importantly, a robust association was observed between cocaine craving and LPP amplitude. High craving levels were associated with larger LPP amplitudes at central electrode sites in the right hemisphere. These findings are in line with theories linking motivational aspects and appetitive stimulus processing. Furthermore, it is demonstrated that ERPs are a useful index to assess motivational properties of stimuli in cocaine- dependent patients.These findings suggest that electrophysiological measures may have clinical relevance in substance use disorders. Keywords cocaine, craving, ERP, LPP, motivation, slow waves. Correspondence to: Ingmar Franken, Institute of Psychology, Erasmus University Rotterdam, PO Box 1738, 3000 DR Rotterdam, the Netherlands. E-mail: franken@fsw.eur.nl INTRODUCTION The past decade saw a huge increase in research ef- forts addressing the psychophysiological underpinnings of drug and alcohol-related craving. In typical cue-reactivity paradigms, detoxified drug or alcohol- dependent patients were exposed to drug or alcohol- related stimuli while peripheral psychophysiological measures such as skin conductance and heart rate are simultaneously assessed. In general, these studies show that there is a change in psychophysiological parameters as result of the exposure to these drug-related stimuli. However, from review studies it has become clear that peripheral psychophysiological measures such as heart rate and skin conductance are poorly related to self- reported craving (Tiffany 1990). Accordingly, it was concluded that there is a need for laboratory-based inves- tigations into the nature of alcohol craving utilizing assessments that are more sensitive to the detection of alcohol craving (Tiffany, Carter & Singleton 2000). Recently, there have been new efforts to examine psy- chophysiological indexes of drug and alcohol reactivity. In this study, we will focus on an electrophysiological index of cue reactivity: event-related brain potentials (ERPs). Several studies have shown that alcohol- and drug-addicted patients have augmented P3 and P3- related waves, such as the late positive potentials (LPPs), on the visual presentation of addiction-related stimuli. The functional significance of both the P3 and LPP are very similar. In most studies addressing the visual pro- cessing of emotional stimuli the P3 and LPP gradually blend into each other and are difficult to discern. Until more evidence is present it can be hypothesized that the major difference between the P3 and LPP in these passive viewing paradigms of emotional visual information is that the P3 emerges more early in the ERP and reflects more initial processing while the LPP reflects more sus- tained processing. To the best of our knowledge, Genkina & Shostakovich (1987) were the first to study late ERP waves within a CLINICAL STUDY doi:10.1111/j.1369-1600.2008.00100.x © 2008 The Authors. Journal compilation © 2008 Society for the Study of Addiction Addiction Biology, 13, 386–392 Addiction Biology