76 The BNST is considered to be part of the extended amygdala.77

It appears to be a center for the integration of information originating from the CHIR 258 amygdala and the hippocampus (Figure 1), and is clearly involved in the modulation of the neuroendocrine stress response.78,79 Activation of the BNST, notably by corticotropin-releasing factor (CRF), may be more specific for anxiety than fear. Studies in rats with the startle reflex suggest that explicit cues such as light, tone, or touch activate the amygdala, which then activates hypothalamic and brainstem target areas involved in the expression of Inhibitors,research,lifescience,medical fear, whereas less specific (or more complex) stimuli of longer duration, such as exposure to a threatening environment or intraventricular administration of CRF, may preferentially involve the BNST.73 The PFC and the control of emotional responses The primary roles of the PFC appear to be the analysis of complex stimuli or situations and the control of emotional responses. In a revised version of his Inhibitors,research,lifescience,medical original BIS model, Gray postulated that the PFC may modulate septohippocampal activity, and Inhibitors,research,lifescience,medical that lesions to this area would impair the processing of vital information for the subicular comparator, and subsequently

affect behavioral inhibition and anticipatory anxiety.51 He also suggested that the role Inhibitors,research,lifescience,medical of cortical structures in anxiety was probably more prominent in primates, based on the increased anatomical relationship between the septohippocampal system and the prefrontal and cingulate cortices observed in monkeys. Recent studies in humans and primates have largely confirmed Gray’s hypothesis, and it is now clear that the various subdivisions of the human PFC

(dorsolateral, ventromedial, and orbital sectors) have specific roles in representing affect in the absence of immediate rewards or punishments and in controlling emotional responses.80,81 Inhibitors,research,lifescience,medical There appear to be important functional differences between the left and right sides within each of these sectors. Earlier studies on patients with unilateral brain lesions have through already emphasized the role of cerebral lateralization in emotional information processing.82 More recently, brain electrical activity measures and positron emission tomography (PET) studies have indicated that negative affect and anxiety are associated with increased activation of the right PFC; moreover, individual differences in baseline levels of asymmetric activation in the PFC may be associated with individual differences in affective styles and vulnerability to mood and anxiety disorders.81 There is also increasing evidence that the PFC plays an important role in controlling anxiety and the associated stress response in rats, and that cerebral laterality is an important feature of the PFC system.