41 Panic disorder has been associated with intact IGT performance,42 but with increased sensitivity to errors during a two-choice prediction task.43 Obviously these findings are mixed, making it difficult

to draw any firm conclusions regarding the extent or specificity of decision-making dysfunction across anxiety disorders. Further behavioral and neuromaging Inhibitors,research,lifescience,medical research is warranted in order to elucidate potential decision-making dysfunction that may contribute to approach-avoidance conflict difficulties and the underlying mechanisms of anxiety disorders. Neuroanatomy of approach, avoidance, and decision making Neural substrates underlying approach, avoidance, and decision making are integrated here with a particular Inhibitors,research,lifescience,medical focus on anxiety disorders. Neuroanatomical research in animals and human neuroimaging research on fear processing have implicated a cortico-limbic circuitry including the amygdala, insula, and prefrontal cortex (PFC)44-46 – regions that have also been shown to exhibit dysfunction in anxiety disorders. Reward-processing and decision-making research has focused primarily on a corticostriatal circuitry involving ventral striatum/nucleus accumbens (NAcc) and frontal cortical regions – including the orbitofrontal cortex as well as more Inhibitors,research,lifescience,medical dorsal and lateral regions.4,26,47-49 It should be recognized that regions outside of these corticolimbic and

toward cortocostriatal loops are also implicated in these processes, including hypothalamus, Inhibitors,research,lifescience,medical thalamus, hippocampus, midbrain, parietal, and brain stem regions (for review of reward-processing and decision-making networks see refs 16,31,50; for review of fear-processing networks see refs 45,46,51). For this Inhibitors,research,lifescience,medical review, we will focus on a few regions that: (i) have been shown to play vital roles in determining the value of stimuli or choices during decision making; and (ii) we believe are likely to underlie approach-avoidance

dysfunction in anxiety disorders. These regions include the amygdala, ventral striatum, insula, and PFC. Brefeldin_A Amygdala Avoidance and approach processing The amygdala has been a primary focus of animal and human research related to fear processing, conditioning, and extinction.52-54 Human neuroimaging studies implicate the amygdala in signaling fear- or anxiety-producing stimuli characteristics, including pictures, odors, and faces55-57 as well as in signaling changes in reinforcing properties of stimuli, such as occurs during fear conditioning58-60 or instructional and observational learning.61,62 However, human neuroimaging studies have also shown the amygdala to respond to positive, rewarding stimuli and during appetitive conditioning,16,26,27,63-68 suggesting this region may be involved in processing salience (eg, the emotional significance of stimuli), rather than simply negative valence per se.