Background Posttraumatic stress disorder (PTSD) is characterized as a disorder of exaggerated defensive physiological arousal. The novel aim of the present research was to investigate within PTSD a potential dose-response relationship between past trauma recurrence and current comorbidity and intensity of physiological reactions to imagery of trauma and other aversive scenarios. Methods A community sample of principal PTSD (n = 49; 22 single-trauma exposed, 27 multiple-trauma exposed) and control (n = 76; 46 never-trauma exposed, 30 trauma exposed) participants imagined threatening and neutral events while acoustic startle probes were presented and the eye-blink response (orbicularis occuli) was recorded. Changes in heart rate, skin conductance level, and facial expressivity were also indexed. Results Overall, PTSD patients exceeded control participants in startle reflex, autonomic responding, and facial expressivity during idiographic trauma imagery and, though less pronounced, showed heightened reactivity to standard anger, panic, and physical danger imagery. Concerning subgroups, control participants with and without trauma exposure showed isomorphic patterns. Within PTSD, only the single-trauma patients evinced robust startle and autonomic responses, exceeding both control participants and multiple-trauma PTSD. Despite greater reported arousal, the multiple-trauma relative to single-trauma PTSD group showed blunted defensive reactivity associated with more chronic and severe PTSD, greater mood and anxiety disorder comorbidity, and more pervasive dimensional dysphoria (e.g., depression, trait anxiety). Conclusions Whereas PTSD patients generally show marked physiological arousal during aversive imagery, concordant with self-reported distress, the most symptomatic patients with histories of severe, cumulative traumatization show discordant physiological hyporeactivity, perhaps attributable to sustained high stress and an egregious, persistent negative affectivity that ultimately compromises defensive responding.

Heightened perception of facial cues is at the core of many theories of social behavior and its disorders. In the present study, we continuously measured electrocortical dynamics in human visual cortex, as evoked by happy, neutral, fearful, and angry faces. Thirty-seven participants endorsing high versus low generalized social anxiety (upper and lower tertiles of 2,104 screened undergraduates) viewed naturalistic faces flickering at 17.5 Hz to evoke steady-state visual evoked potentials (ssVEPs), recorded from 129 scalp electrodes. Electrophysiological data were evaluated in the time-frequency domain after linear source space projection using the minimum norm method. Source estimation indicated an early visual cortical origin of the face-evoked ssVEP, which showed sustained amplitude enhancement for emotional expressions specifically in individuals with pervasive social anxiety. Participants in the low symptom group showed no such sensitivity, and a correlational analysis across the entire sample revealed a strong relationship between self-reported interpersonal anxiety/avoidance and enhanced visual cortical response amplitude for emotional, versus neutral expressions. This pattern was maintained across the 3500 ms viewing epoch, suggesting that temporally sustained, heightened perceptual bias towards affective facial cues is associated with generalized social anxiety.

Stress resilience is mediated, in part, by our ability to predict and control threats within our environment. Therefore, determining the neural mechanisms that regulate the emotional response to predictable and controllable threat may provide important new insight into the processes that mediate resilience to emotional dysfunction and guide the future development of interventions for anxiety disorders. To better understand the effect of predictability and controllability on threat-related brain activity in humans, two groups of healthy volunteers participated in a yoked Pavlovian fear conditioning study during functional magnetic resonance imaging (fMRI). Threat predictability was manipulated by presenting an aversive unconditioned stimulus (UCS) that was either preceded by a conditioned stimulus (i.e., predictable) or by presenting the UCS alone (i.e., unpredictable). Similar to animal model research that has employed yoked fear conditioning procedures, one group (Controllable Condition; CC), but not the other group (Uncontrollable Condition; UC) was able to terminate the UCS. The fMRI signal response within the dorsolateral prefrontal cortex (PFC), dorsomedial PFC, ventromedial PFC, and posterior cingulate was diminished during predictable compared to unpredictable threat (i.e., UCS). In addition, threat-related activity within the ventromedial PFC and bilateral hippocampus was diminished only to threats that were both predictable and controllable. These findings provide insight into how threat predictability and controllability affects the activity of brain regions (i.e., ventromedial PFC and hippocampus) involved in emotion regulation, and may have important implications for better understanding neural processes that mediate emotional resilience to stress.

Rather than shifts between covert vigilance and avoidance of aversive facial expressions, social anxiety appears to confer a sustained bias for one or the other. While vigilant attention reliably increases with social anxiety severity for the majority of patients, the most impaired patients show an opposing avoidance. These distinct patterns of attentional allocation could provide a powerful means of personalizing neuroscience-based interventions to modify attention bias and related impairment.

Learning the temporal relationship between a warning cue (conditioned stimulus; CS) and aversive threat (unconditioned stimulus; UCS) is an important aspect of Pavlovian conditioning. Although prior functional magnetic resonance imaging (fMRI) research has identified brain regions that support Pavlovian conditioning, it remains unclear whether these regions support time-related processes important for this type of associative learning. Elucidating the neural substrates of temporal conditioning is important for a complete understanding of the Pavlovian conditioning process. Therefore, the present study used a temporal Pavlovian conditioning procedure to investigate brain activity that mediates the formation of temporal associations. During fMRI, twenty-three healthy volunteers completed a temporal conditioning procedure and a control task that does not support conditioning. Specifically, during the temporal conditioning procedure, the UCS was presented at fixed intervals (ITI: 20 s) while in the control condition the UCS was presented at random intervals (Average ITI: 20 s, ITI Range: 6-34 s). We observed greater skin conductance responses and expectancy of the UCS during fixed (i.e., temporal conditioning) relative to random (i.e., control procedure) interval trials. These findings demonstrate fixed trials support temporal conditioning, while random trials do not. During fixed interval trials, greater conditioned fMRI signal responses were observed within dorsolateral prefrontal cortex, inferior parietal lobule, inferior and middle temporal cortex, hippocampus, and amygdala. The current findings suggest these brain regions constitute a neural circuit that encodes the temporal information necessary for Pavlovian fear conditioning.