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Rationale: Motivational drive and its underlying affect-related states are the core mechanisms that precede the seeking and taking of drugs in substance dependence. Objective: The present study aimed to investigate the motivational relevance of cocaine cues and whether or not an appetitive emotional system is involved employing event-related potential (ERP) measurements. Methods: Cocaine-addicted subjects and healthy controls were exposed to neutral and cocaine-related pictures whilst ERPs were recorded simultaneously over frontal, parietal and midline sites. Results: Patients exhibited ERP amplitude discrepancies between neutral and cocaine-related pictures for N300, late slow positive wave (LSPW) and sustained slow positive wave (SSPW), whilst this effect was absent in control subjects. Differences in neutral and cocaine cue-evoked ERP waves were also found at left frontal sites for LSPW and SSPW in the patient group only. No group-specific cue-evoked ERP amplitudes were observed at parietal and midline sites. Conclusion: The findings confirm the assumption that cocaine cues induce motivational relevance in cocainedependent individuals. It is possible that exposure to cocaine cues triggers an appetitive emotional system since left frontal sites are assumed to be involved in processing positive emotional-laden stimuli. The present study provides evidence that the sensitivity of ERP correlates for cocaine cues may be an indicator of motivational and emotional processes in drug-dependent individuals.

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Inhibition of prepotent responding and attentional flexibility were assessed in 58 early and continuously treated phenylketonuria (PKU) patients and 69 controls, age 7 to 14 years. A computerized task was used requiring participants to process consecutive stimuli according to various attentional sets. Analysis of error rate suggested poorer inhibition of prepotent responding in PKU patients compared with controls. No influence of concurrent plasma phenylalanine (phe) was shown, neither in the younger (age < 11 years) nor in the older participants (age > or = 11 years). Analysis of error rate provided strong evidence for poorer attentional flexibility in PKU patients compared with controls. The difference between attentional flexibility in controls and PKU patients could mainly be attributed to younger PKU patients, with concurrent phe levels higher than 360 micromol/L. Younger PKU patients with phe levels below 360 micromol/L performed at the same level as age-matched controls. Performance of PKU patients was strongly associated with phe levels in age periods during the first 10 years of life, which are characterized by a strong development of executive functioning (ages 2-7 and age 9). High phe levels during these age periods could delay development of inhibitory control and attentional flexibility. With regard to treatment, analyses with lifetime and concurrent phe levels support strict dietary control throughout the first decade of life, after which the phe-restricted diet can be relaxed. However, based on the evidence that development of specific executive functions continues until approximately age 12, it is recommended to maintain phe levels below 360 micromol/L throughout early adolescence.