168-170 A metaanalysis reported that approximately 70% of studies involving provocation of pleasant emotion showed activation of the basal ganglia, including the striatum.171 Animal research suggests that, while some neurons within the ventral striatum respond to both rewarding and aversive stimuli,172 NAcc neurons increase or decrease in activation to reward- and punishment-predicting stimuli, respectively173 (for review see ref 16). Potentially related to this, human neuroimaging studies have reported free copy striatal activation in response to aversive or unpleasant stimuli.164, 174-176

Decision making Animal research suggests that Inhibitors,research,lifescience,medical anatomical or pharmacologic manipulation of ventral striatal neurons influences Inhibitors,research,lifescience,medical approach-avoidance behavior during conflict,177-179 delayed-discounting,180,181 effort -based,182,183 and riskrelated

decision-making models184 (see review in ref 114). The directionality of lesion effects would suggest that this region is involved in orienting an organism towards reward. Potentially in concert with these findings, human neuroimaging studies report NAcc activation to correlate with the amount of risk involved in decisions185,186 and to signal prediction errors between expected and actual reward value187 (for review see Inhibitors,research,lifescience,medical refs 188,114). The few neuroimaging studies investigating decision making in anxiety disorders provide initial evidence of Inhibitors,research,lifescience,medical striatal dysfunction. In PTSD, attenuated nucleus accumbens activation and difficulty learning the optimal response pattern during risk-related decision making has been reported.36 Attenuated striatal activation in response

to reward was also reported for PTSD during a wheel-of-fortune type task189 and this striatal attenuation was related to level of “numbing” symptoms (eg, symptoms involving difficulty experiencing positive emotions or feeling distant from others). Although somewhat unrelated to decision making, an implicit memory task known to elicit striatal activation was used to identify striatal dysfunction in SAD190; while the Inhibitors,research,lifescience,medical same task failed to identify such dysfunction in phobia.191 In summary, this research provides evidence that the ventral striatum is involved in signaling the Entinostat rewarding value of outcomes.16,114,171,188 There is initial evidence of striatal dysfunction in PTSD and SAD,36,189,190 as well as suggestions that striatal dysfunction may be related to PTSDspecific symptoms such as numbing. However, we propose it may also be important for approach valuations in other anxiety disorders and that an imbalance between striatal and amygdala/insula signals could relate to increased conflict and dysfunctional approach-avoidance behavior. Prefrontal cortex Researchers of different specialty fields use varying terminologies when referring to regions of the PFC.