Facial threat conveys important information about imminent environmental danger. The rapid detection of this information is critical for survival and social interaction. However, due to technical and methodological difficulties, the spatiotemporal profile for facial threat processing is unknown. By utilizing Magnetoencephalography (MEG), a brain-imaging technique with superb temporal resolution and fairly good spatial resolution, Synthetic Aperture Magnetometry (SAM), a recently developed source analysis technique, and a sliding window analysis, we identified the spatiotemporal development of facial threat processing in the gamma frequency band. We also tested the dual-route hypothesis by LeDoux who proposed, based on animal research, that there are two routes to the amygdala: a quick subcortical routeand a slower and cortical route. Direct evidence with humans supporting this model has been lacking. Moreover, it has been unclear whether the subcortical route responds specifically to fearful expressions or to threatening expressions in general. We found early event-related synchronizations (ERS) in response to fearful faces in the hypothalamus/thalamus area (10-20 ms) and then the amygdala (20-30 ms). This was even earlier than the ERS response seen to fearful faces in visual cortex (40-50 ms). These data support LeDoux's suggestion of a quick, subcortical thamaloamygdala route. Moreover, this route was specific for fear expressions; the ERS response in the amygdala to angry expressions had a late onset (150-160 ms). The ERS onset in prefrontal cortex followed that seen within the amygdala (around 160-210 ms). This is consistent with its role in higher-level emotional/cognitive processing.

The ventromedial prefrontal cortex (vmPFC) and dorsal anterior cingulate cortices (ACd) are considered important for reward-based decision making. However, work distinguishing their individual functional contributions has only begun. One aspect of decision making that has received little attention is that making the right choice often translates to making the better choice. Thus, response choice often occurs in situations where both options are desirable (e.g., choosing between mousse au chocolat or crème caramel cheesecake from a menu) or, alternatively, in situations where both options are undesirable. Moreover, response choice is easier when the reinforcements associated with the objects are far apart, rather than close together, in value. We used functional magnetic resonance imaging to delineate the functional roles of the vmPFC and ACd by investigating these two aspects of decision making: (1) decision form (i.e., choosing between two objects to gain the greater reward or the lesser punishment), and (2) between-object reinforcement distance (i.e., the difference in reinforcements associated with the two objects). Blood oxygen level-dependent (BOLD) responses within the ACd and vmPFC were both related to decision form but differentially. Whereas ACd showed greater responses when deciding between objects to gain the lesser punishment, vmPFC showed greater responses when deciding between objects to gain the greater reward. Moreover, vmPFC was sensitive to reinforcement expectations associated with both the chosen and the forgone choice. In contrast, BOLD responses within ACd, but not vmPFC, related to between-object reinforcement distance, increasing as the distance between the reinforcements of the two objects decreased. These data are interpreted with reference to models of ACd and vmPFC functioning.

Context Generalized social phobia (GSP) is characterized by fear/avoidance of social situations. Previous studies have examined the neural responses in GSP to one class of social stimuli, facial expressions. However, studies have not examined the neural response in GSP to another equally important class of social stimuli, the communication of praise or criticism. Objective To examine the neural response to receipt of praise or criticism in GSP; specifically, to determine whether patients with GSP show an increased response to the receipt of both praise and criticism and whether self-relevance modulates this relationship. Design Case-control study. Setting Government clinical research institute. Participants Unmedicated individuals with GSP (n=17) and age-, IQ-, and sex-matched healthy comparison individuals (n=17). Main Outcome Measure Blood oxygenation level–dependent signal, as measured via functional magnetic resonance imaging. During functional magnetic resonance imaging scans, individuals read positive (eg, You are beautiful), negative (eg, You are ugly), and neutral (eg, You are human) comments that could be either about the self or about somebody else (eg, He is beautiful). Results Hypothesized significant group×valence×referent interactions were observed within regions of the medial prefrontal cortex and bilateral amygdala. In these regions, the patients with GSP showed significantly increased blood oxygenation level–dependent responses, relative to comparison individuals, to negative comments (criticism) referring to themselves. However, in contrast, there were no significant group differences with respect to negative comments referring to others or neutral or positive comments referring to self or others. Conclusions These results implicate the medial prefrontal cortex, involved in the representation of the self, together with the amygdala, in the pathophysiology of GSP. Further, findings demonstrate a meaningful effect of psychological context on neural-circuitry hyperactivity in GSP.

Status hierarchies constitute a fundamental organizing principle of human society. However, little is known about the neural systems that process nonverbal cues that indicate status. Preliminary neuropsychological work has suggested a role for the ventrolateral and ventromedial prefrontal cortex (VLPFC/VMPFC) and the superior temporal cortex (STC). We used functional magnetic resonance imaging to delineate the nature of these roles. Analyses revealed signal changes in the right VLPFC in connection with two primary functions attributed to status cues. Status cues moderate behavior and the right VLPFC showed increased signal for high-status relative to neutral and low-status cues. The VLPFC also showed increased signal for high-status cues displayed by individuals of the opposite gender to the perceiver; this may be relevant to the role status cues play in moderating mate choice behavior. Connectivity results indicated significant positive connectivity between the VLPFC and both the VMPFC and the STC. We suggest that the VLPFC retrieves information from these regions when processing hierarchy cues to facilitate socially adaptive behavior.

These findings document that hyper-responsiveness to threat but not to positive stimuli is specific for patients with PTSD.

Top-down attentional control is necessary to ensure successful task performance in the presence of distracters. Lateral prefrontal cortex, parietal cortex and anterior cingulate cortex have been previously implicated in top-down attentional control. However, it is unclear whether these regions are engaged independent of distracter type or whether, as has been suggested for anterior cingulate cortex, different regions provide attentional control over emotional versus other forms of salient distracter. In the current task, subjects viewed targets that were preceded by distracters that varied in both emotionality and visibility. We found that behaviorally, the presence of preceding distracters significantly interfered with target judgment. At the neural level, increases in the emotional and visual saliency of distracters were both associated with increased activity in proximal regions of prefrontal, parietal and cingulate cortex. Moreover, a conjunction analysis indicated considerable overlap in the regions of prefrontal, parietal cortex and anterior cingulate cortex responding to distracters of increased emotionality and visibility.

Background-Generalized Social Phobia (GSP) involves the fear/avoidance of social situations while Generalized Anxiety Disorder (GAD) involves an intrusive worry about everyday life circumstances. It remains unclear whether these, highly comorbid, conditions represent distinct disorders or alternative presentations of a single underlying pathology. In this study, we examined stimulus-reinforcement based decision-making in GSP and GAD.

Operant extinction, which features modification of instrumental responses to stimuli following a change in associated reinforcement, is an important form of learning for organisms in dynamic environments. Animal studies have highlighted orbital and medial prefrontal cortex and amygdala as mediators of operant extinction. Yet little is known about the neural mediators of operant extinction learning in humans. Using a novel fMRI paradigm, we report dissociable functional responses in distinct regions of medial orbitofrontal cortex (mOFC) during successful appetitive and aversive based operant extinction. During successful operant extinction, increased activity was observed in frontopolar OFC, while decreased activity was observed in caudal mOFC and rostral anterior cingulate cortex (rACC) relative to both (i) successful control trials where the reinforcement associated with the stimulus does not change; and (ii) successful acquisition trials during initial learning of the stimulus- reinforcement associations. Functional connectivity analysis demonstrated inverse connectivity between frontopolar OFC and both rACC and the amygdala. These data support animal models suggesting the importance of mOFC - amygdala interaction during operant extinction and expand our knowledge of the neural systems in humans. These findings suggest that in humans, frontopolar OFC modulates activity in caudal mOFC, rACC and amygdala during successful operant extinction learning.