For example, most decision-making tasks do not only measure the process of decision making, but also processes related to attention, WM, reward expectation, and reward and punishment

processing. Identifying these separate components of, for example, decision making may also be achieved by including carefully selected control tasks. In addition to these issues related to task paradigms, differences in fMRI data acquisition and analysis are likely to be another major source of discrepancies across studies. As discussed previously, studies may differ with regard to scanner type, field strength, acquisition parameters, and data modeling (e.g., block vs. event-related). Inhibitors,research,lifescience,medical More generally, Inhibitors,research,lifescience,medical the BOLD fMRI technique has several limitations, such as susceptibility to signal distortion and dropout in the vicinity of bone-air transitions, such as the nasal sinuses, resulting in poor sensitivity to detect activity in, for example, medial OFC. Also, while BOLD fMRI is predicated on the assumption of increased regional perfusion being associated with greater neural activity, this neurovascular coupling may be compromised in elderly people but also following drug intake (Schwarz et al. 2007). Finally, the use of various Inhibitors,research,lifescience,medical data analysis techniques and (the massive number of) statistical

tests can also be an important source of variation. Ideally, greater weight should be given to studies in which type I error is adequately controlled for, either by using whole-brain corrections Inhibitors,research,lifescience,medical for multiple testing or the use of independently derived a priori (as opposed to post hoc) ROIs. Some of the described studies have used various types of corrections (for whole-brain analyses [Daumann et al. 2003b; Okuyemi et al. 2006; Karageorgiou et al. 2009], multiple testing [Paulus et al. 2003; Bolla et al. 2004; Hester and Garavan 2004; Ersche et al. 2005; Kubler et al. 2005; Hoffman Inhibitors,research,lifescience,medical et al. 2006; Goldstein et al. 2007b; Li et al. 2008; Hanlon et al. 2009; de Ruiter et al. 2009], or pre-defined ROI analyses [Maas et al. 1998; Due et al. 2002; Bolla et al. 2004; Jacobsen et al. 2004; Ersche et al. 2005; Okuyemi et al. 2006; Li et al. 2008; Karageorgiou et al. 2009]) to

BIO GSK-3 chemical structure reduce possible type I errors. However, only a limited number of these have controlled adequately for type next I errors (Ersche et al. 2005; Okuyemi et al. 2006; Karageorgiou et al. 2009), and results from these studies should receive greater weight. Other studies used no (Childress et al. 1999) or inadequate (Bolla et al. 2003; Daumann et al. 2003a; Goldstein et al. 2007b) corrections, or did not provide information on this issue (Garavan et al. 2000; Wexler et al. 2001; Kaufman et al. 2003; David et al. 2005; Monterosso et al. 2007; Goldstein et al. 2009b), making it difficult to exclude possible false positive findings. A final issue concerns interpretation of results, in particular with regard to behavioral and neurophysiological (BOLD) data.