Avoidance and approach processing Medial prefrontal and particularly OFC regions are thought to play a role in regulating or inhibiting limbic regions and behavioral responses during fear processing. Neuroimaging studies in nonclinical populations report OFC and dorsomedial PFC (specifically dorsal and rostral ACC) activation in response to emotional pictures55,133,171,193 and emotional faces55,194,195

and provide evidence these Inhibitors,research,lifescience,medical regions are important for fear learning.24,60,61,139,196,197 Animal and human studies provide some evidence of an inhibitory relationship between prefrontal regions (including OFC, dmPFC, and lateral PFC) and amygdala during fear extinction or emotional regulation.198-202 Human neuroimaging research supports implications from animal studies by showing the OFC to play a primary role in reward processing.50,203 Inhibitors,research,lifescience,medical This region (as well as dmPFC) has been shown to activate

in response to rewarding and reward-predicting stimuli, such as money, appetizing food, pleasant smells or music, attractive facial Inhibitors,research,lifescience,medical stimuli, and sexual arousal.26,64,171,204,205 PFC dysfunction has been repeatedly implicated across anxiety disorders, though the direction of dysfunction differs depending upon the paradigm and the anxiety disorder being examined. In response to symptom provocation or negative emotional stimuli, OFC and dmPFC (and occasionally lOFC and dlPFC) hyperactivation has been identified for GAD,69,70,101 SAD,72,74,206 phobia,84,85,105,144,207 and panic.79,208,209 Directional effects within the PFC have been mixed for PTSD,47,78,89,96,210-214 though the majority of studies and meta-anlyses support hypoactivation of OFC and ventromedial regions.78 Experimental

approaches involving instructed Inhibitors,research,lifescience,medical downregulation of negative emotion have identified attenuated activity within OFC, dlPFC, and dmPFC regions in anxiety disorders (SAD,201,215 PTSD216). These results have been taken as evidence that anxiety disorders are FHPI datasheet associated with decreased propensity to recruit PFC regions to regulate limbic activity and/or emotional responses. Inhibitors,research,lifescience,medical Additionally, SAD has been associated with an negative relationship between ventrolateral PFC and amygdala activation,102 and PTSD has been associated with an negative relationship between mPFC and amygdala activation96 during symptom provocation. Treatment of PTSD and phobia has been associated with increased dmPFC and/or OFC activations,100,217-219 Urease though other studies report phobia treatment to result in decreased prefrontal activation.99,104,148 Neuroimaging studies using positive emotional stimuli have, for the most part, either not reported or failed to find evidence of prefrontal dysfunction in GAD70,101,149 and SAD.72,220 However, Campbell et al221 reported SAD to be associated with delayed dlPFC and dmPFC activation in response to happy faces compared with nonanxious controls.