Acute stress enhances general-knowledge semantic memory.

Acute psychological stress consistently impairs episodic memory, which consists of memory for events that are associated with a specific context. However, researchers have not yet established how stress influences semantic memory, which consists of general knowledge that is devoid of context. In the present study, participants either underwent stress induction or a control task prior to taking a trivia test that was designed to measure semantic memory. In contrast to the wealth of prior research on episodic memory, we found that stress enhanced semantic-memory retrieval. Supporting this finding, higher cortisol reactivity to stress was associated with better performance on the trivia test. Together with the results from previous studies of episodic memory, our findings suggest that stress differentially influences memory retrieval, depending on the degree to which the retrieval of a given memory relies on medial-temporal, neocortical, and striatal brain regions.

Retrieval practice improves item memory but not source memory in the context of stress.

Smith, Floerke, and Thomas (2016) demonstrated that learning by repeated testing, or retrieval practice, reduced stress-related memory impairment when compared to learning by repeatedly studying material. In the present experiment, we tested whether, relative to study practice, retrieval practice would improve post-stress memory by increasing access to both item and source information. Participants learned two wordlists, which were temporally segregated to facilitate distinction between the two lists. Participants returned one week later for stress induction and two memory tests. Each test featured a recognition test that was given to assess item memory accessibility, and a list-discrimination task that was given to assess source memory. Relative to study practice, successful retrieval practice during learning reduced false alarms but did not improve source memory on the post-stress test. Results are discussed as they relate to current theories surrounding stress effects and retrieval practice effects.

From Pavlov to PTSD: the extinction of conditioned fear in rodents, humans, and anxiety disorders.

Nearly 100 years ago, Ivan Pavlov demonstrated that dogs could learn to use a neutral cue to predict a biologically relevant event: after repeated predictive pairings, Pavlov's dogs were conditioned to anticipate food at the sound of a bell, which caused them to salivate. Like sustenance, danger is biologically relevant, and neutral cues can take on great salience when they predict a threat to survival. In anxiety disorders such as posttraumatic stress disorder (PTSD), this type of conditioned fear fails to extinguish, and reminders of traumatic events can cause pathological conditioned fear responses for decades after danger has passed. In this review, we use fear conditioning and extinction studies to draw a direct line from Pavlov to PTSD and other anxiety disorders. We explain how rodent studies have informed neuroimaging studies of healthy humans and humans with PTSD. We describe several genes that have been linked to both PTSD and fear conditioning and extinction and explain how abnormalities in fear conditioning or extinction may reflect a general biomarker of anxiety disorders. Finally, we explore drug and neuromodulation treatments that may enhance therapeutic extinction in anxiety disorders.

Impulsivity and the modular organization of resting-state neural networks.

Impulsivity is a complex trait associated with a range of maladaptive behaviors, including many forms of psychopathology. Previous research has implicated multiple neural circuits and neurotransmitter systems in impulsive behavior, but the relationship between impulsivity and organization of whole-brain networks has not yet been explored. Using graph theory analyses, we characterized the relationship between impulsivity and the functional segregation ("modularity") of the whole-brain network architecture derived from resting-state functional magnetic resonance imaging (fMRI) data. These analyses revealed remarkable differences in network organization across the impulsivity spectrum. Specifically, in highly impulsive individuals, regulatory structures including medial and lateral regions of the prefrontal cortex were isolated from subcortical structures associated with appetitive drive, whereas these brain areas clustered together within the same module in less impulsive individuals. Further exploration of the modular organization of whole-brain networks revealed novel shifts in the functional connectivity between visual, sensorimotor, cortical, and subcortical structures across the impulsivity spectrum. The current findings highlight the utility of graph theory analyses of resting-state fMRI data in furthering our understanding of the neurobiological architecture of complex behaviors.

Anxiety dissociates dorsal and ventral medial prefrontal cortex functional connectivity with the amygdala at rest.

Anxiety is linked to compromised interactions between the amygdala and the dorsal and ventral medial prefrontal cortex (mPFC). While numerous task-based neuroimaging studies show that anxiety levels predict amygdala-mPFC connectivity and response magnitude, here we tested the hypothesis that anxiety would predict functional connectivity between these brain regions even during rest. Resting-state functional magnetic resonance imaging scans and self-reported measures of anxiety were acquired from healthy subjects. At rest, individuals with high anxiety were characterized by negatively correlated amygdala-ventral mPFC functional connectivity, while low anxious subjects showed positively correlated activity. Further, high anxious subjects showed amygdala-dorsal mPFC activity that was uncorrelated, while low anxious subjects showed negatively correlated activity. These data show that amygdala-mPFC connectivity at rest indexes normal individual differences in anxiety.

Regional response differences across the human amygdaloid complex during social conditioning.

The amygdala is consistently implicated in biologically relevant learning tasks such as Pavlovian conditioning. In humans, the ability to identify individual faces based on the social outcomes they have predicted in the past constitutes a critical form of associative learning that can be likened to "social conditioning." To capture such learning in a laboratory setting, participants learned about faces that predicted negative, positive, or neutral social outcomes. Participants reported liking or disliking the faces in accordance with their learned social value. During acquisition, we observed differential functional magnetic resonance imaging activation across the human amygdaloid complex consistent with previous lesion, electrophysiological, and functional neuroimaging data. A region of the medial ventral amygdala and a region of the dorsal amygdala/substantia innominata showed signal increases to both Negative and Positive faces, whereas a lateral ventral region displayed a linear representation of the valence of faces such that Negative > Positive > Neutral. This lateral ventral locus also differed from the dorsal and medial loci in that the magnitude of these responses was more resistant to habituation. These findings document a role for the human amygdala in social learning and reveal coarse regional dissociations in amygdala activity that are consistent with previous human and nonhuman animal data.

Using Practice Testing, Public Speaking, and Source Monitoring to Examine the Influences of Learning Strategies and Stress on Episodic Memory.

Prior research demonstrated that learning information via retrieval practice, which entails studying and taking practice tests, resulted in less memory impairment under stress than learning information via repeated studying. The present experiment combined three experimental procedures to further examine the memory mechanisms underlying the efficacy of retrieval practice in the context of stress. A list-discrimination task was implemented, in which participants learned two distinct wordlists. This was combined with a retrieval-practice manipulation, as half of the participants engaged in practice testing and half engaged in conventional studying during learning. A week later, participants underwent stress induction, using the Trier Social Stress Test. Before and after stress induction, participants completed tests of item and source memory (i.e., list discrimination). The combination of these three procedures yielded informative results: retrieval practice, in the context of stress, improved item memory but not source memory relative to conventional studying. Limitations and future directions for the use of this methodology are discussed.

Exerting cognitive control under threat: Interactive effects of physical and emotional stress.

Individuals with stressful occupations, such as law enforcement and military personnel, are required to operate in high stakes environments that can be simultaneously physically and emotionally demanding. These individuals are tasked with maintaining peak performance under stressful and often unpredictable conditions, exerting high levels of cognitive control to sustain attention and suppress task-irrelevant actions. Previous research has shown that physical and emotional stressors differentially influence such cognitive control processes. For example, physical stress impairs while emotional stress facilitates the ability to inhibit a prepotent response, yet, interactions between the two remain poorly understood. Here we examined whether emotional stress induced by threat of unpredictable electric shock mitigates the effects of physical stress on response inhibition. Participants performed an auditory Go/NoGo task under safe versus threat conditions while cycling at high intensity (84% HRmax) for 50 min. In threat conditions, participants were told they would receive mild electric shocks that were unpredictable and unrelated to task performance. Self-reported anxiety increased under threat versus safe conditions, and perceived exertion increased with exercise duration. As predicted, we observed decrements in response inhibition (increased false alarms) as exertion increased under safe conditions, but improved response inhibition as exertion increased under threat conditions. These findings are consistent with previous work showing that anxiety induced by unpredictable threat promotes adaptive survival mechanisms, such as improved vigilance, threat detection, cautious behavior, and harm avoidance. Here, we suggest that emotional stress induced by unpredictable threat can also mitigate decrements in cognitive performance experienced under physically demanding conditions. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Criterial learning is not enough: Retrieval practice is necessary for improving post-stress memory accessibility.

In a recent study, having participants make three retrieval attempts (i.e., retrieval practice) when learning information strengthened memory against the detrimental effects of psychological stress. We aimed to determine whether learning to criterion, in which only one successful retrieval attempt is made, would similarly buffer memory against stress, or whether multiple retrieval attempts are necessary to achieve that effect. In Experiment 1, participants learned to criterion and then engaged in additional restudying (CLS) or retrieval practice (CLR). Twenty-four hours later, stress was induced and stress-related increases in cortisol were observed. However, no differences in recall performance were observed between any of the groups. Experiment 2 was similar but introduced a 1-week delay between encoding and retrieval. Recall performance was impaired for both groups under stress, but recall for those in the CLR group was still better than either pre- or post-stress performance for those in the CLS group. Thus, criterial learning may protect memory against stress in the short-term, but additional retrieval practice is more beneficial for achieving this effect in the long-term. (PsycINFO Database Record

The impact of uncertain threat on affective bias: Individual differences in response to ambiguity.

Individuals who operate under highly stressful conditions (e.g., military personnel and first responders) are often faced with the challenge of quickly interpreting ambiguous information in uncertain and threatening environments. When faced with ambiguity, it is likely adaptive to view potentially dangerous stimuli as threatening until contextual information proves otherwise. One laboratory-based paradigm that can be used to simulate uncertain threat is known as threat of shock (TOS), in which participants are told that they might receive mild but unpredictable electric shocks while performing an unrelated task. The uncertainty associated with this potential threat induces a state of emotional arousal that is not overwhelmingly stressful, but has widespread-both adaptive and maladaptive-effects on cognitive and affective function. For example, TOS is thought to enhance aversive processing and abolish positivity bias. Importantly, in certain situations (e.g., when walking home alone at night), this anxiety can promote an adaptive state of heightened vigilance and defense mobilization. In the present study, we used TOS to examine the effects of uncertain threat on valence bias, or the tendency to interpret ambiguous social cues as positive or negative. As predicted, we found that heightened emotional arousal elicited by TOS was associated with an increased tendency to interpret ambiguous cues negatively. Such negative interpretations are likely adaptive in situations in which threat detection is critical for survival and should override an individual's tendency to interpret ambiguity positively in safe contexts. (PsycINFO Database Record

Interpreting ambiguous social cues in unpredictable contexts.

Unpredictable environments can be anxiety-provoking and elicit exaggerated emotional responses to aversive stimuli. Even neutral stimuli, when presented in an unpredictable fashion, prime anxiety-like behavior and elicit heightened amygdala activity. The amygdala plays a key role in initiating responses to biologically relevant information, such as facial expressions of emotion. While some expressions clearly signal negative (anger) or positive (happy) events, other expressions (e.g. surprise) are more ambiguous in that they can predict either valence, depending on the context. Here, we sought to determine whether unpredictable presentations of ambiguous facial expressions would bias participants to interpret them more negatively. We used functional magnetic resonance imaging and facial electromyography (EMG) to characterize responses to predictable vs unpredictable presentations of surprised faces. We observed moderate but sustained increases in amygdala reactivity to predictable presentations of surprised faces, and relatively increased amygdala responses to unpredictable faces that then habituated, similar to previously observed responses to clearly negative (e.g. fearful) faces. We also observed decreased corrugator EMG responses to predictable surprised face presentations, similar to happy faces, and increased responses to unpredictable surprised face presentations, similar to angry faces. Taken together, these data suggest that unpredictability biases people to interpret ambiguous social cues negatively.

A face versus non-face context influences amygdala responses to masked fearful eye whites.

The structure of the mask stimulus is crucial in backward masking studies and we recently demonstrated such an effect when masking faces. Specifically, we showed that activity of the amygdala is increased to fearful facial expressions masked with neutral faces and decreased to fearful expressions masked with a pattern mask-but critically both masked conditions discriminated fearful expressions from happy expressions. Given this finding, we sought to test whether masked fearful eye whites would produce a similar profile of amygdala response in a face vs non-face context. During functional magnetic resonance imaging scanning sessions, 30 participants viewed fearful or happy eye whites masked with either neutral faces or pattern images. Results indicated amygdala activity was increased to fearful vs happy eye whites in the face mask condition, but decreased to fearful vs happy eye whites in the pattern mask condition-effectively replicating and expanding our previous report. Our data support the idea that the amygdala is responsive to fearful eye whites, but that the nature of this activity observed in a backward masking design depends on the mask stimulus.

Botulinum toxin-induced facial muscle paralysis affects amygdala responses to the perception of emotional expressions: preliminary findings from an A-B-A design.

BACKGROUND: It has long been suggested that feedback signals from facial muscles influence emotional experience. The recent surge in use of botulinum toxin (BTX) to induce temporary muscle paralysis offers a unique opportunity to directly test this "facial feedback hypothesis." Previous research shows that the lack of facial muscle feedback due to BTX-induced paralysis influences subjective reports of emotional experience, as well as brain activity associated with the imitation of emotional facial expressions. However, it remains to be seen whether facial muscle paralysis affects brain activity, especially the amygdala, which is known to be responsive to the perception of emotion in others. Further, it is unknown whether these neural changes are permanent or whether they revert to their original state after the effects of BTX have subsided. The present study sought to address these questions by using functional magnetic resonance imaging to measure neural responses to angry and happy facial expressions in the presence or absence of facial paralysis. RESULTS: Consistent with previous research, amygdala activity was greater in response to angry compared to happy faces before BTX treatment. As predicted, amygdala activity in response to angry faces was attenuated when the corrugator/procerus muscles were paralyzed via BTX injection but then returned to its original state after the effects of BTX subsided. This preliminary study comprises a small sample size and no placebo condition; however, the A-B-A design affords the present sample to serve as its own control. CONCLUSIONS: The current demonstration that amygdala responses to facial expressions were influenced by facial muscle paralysis offers direct neural support for the facial feedback hypothesis. Specifically, the present findings offer preliminary causal evidence that amygdala activity is sensitive to facial feedback during the perception of the facial expressions of others. More broadly, these data confirm the utility of using BTX to address the effect of facial feedback on neural responses associated with the perception, in addition to the experience or expression of emotion.

Neuroimaging predictors of treatment response in anxiety disorders.

Although several psychological and pharmacological treatment options are available for anxiety disorders, not all patients respond well to each option. Furthermore, given the relatively long duration of adequate treatment trials, finding a good treatment fit can take many months or longer. Thus, both clinicians and patients would benefit from the identification of objective pre-treatment measures that predict which patients will best respond to a given treatment. Recent studies have begun to use biological measures to help predict symptomatic change after treatment in anxiety disorders. In this review, we summarize studies that have used structural and functional neuroimaging measures to predict treatment response in obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), and social anxiety disorder (SAD). We note the limitations of the current studies and offer suggestions for future research. Although the literature is currently small, we conclude that pre-treatment neuroimaging measures do appear to predict treatment response in anxiety disorders, and future research will be needed to determine the relative predictive power of neuroimaging measures as compared to clinical and demographic measures.

Diminished rostral anterior cingulate cortex activation during trauma-unrelated emotional interference in PTSD.

BACKGROUND: Previous research suggests that individuals with posttraumatic stress disorder (PTSD) preferentially attend to trauma-related emotional stimuli and have difficulty completing unrelated concurrent tasks. Compared to trauma-exposed control groups, individuals with PTSD also exhibit lower rostral anterior cingulate cortex (rACC) activation during tasks involving interference from trauma-related stimuli. However, it is not clear whether relatively diminished rACC activation in PTSD also occurs during interference tasks involving trauma-unrelated emotional stimuli. The present study employed functional magnetic resonance imaging (fMRI) and an interference task that involves emotional facial expressions and elicits rACC activation in healthy participants. FINDINGS: While performing a trauma-unrelated emotional interference task, participants with PTSD (n=17) showed less rACC activation than trauma-exposed non-PTSD (TENP; n=18) participants. In the PTSD group, rACC activation was negatively correlated with the severity of re-experiencing symptoms. The two groups did not significantly differ on behavioral measures (i.e., response times and error rates). CONCLUSIONS: These findings suggest that relatively diminished rACC activation in PTSD can be observed in interference tasks involving trauma-unrelated emotional stimuli, indicating a more general functional brain abnormality in this disorder. Future neuroimaging studies need not employ trauma-related stimuli in order to detect rACC abnormalities in PTSD.

Valence resolution of ambiguous facial expressions using an emotional oddball task.

Previous research suggests that neural and behavioral responses to surprised faces are modulated by explicit contexts (e.g., "He just found $500"). Here, we examined the effect of implicit contexts (i.e., valence of other frequently presented faces) on both valence ratings and ability to detect surprised faces (i.e., the infrequent target). In Experiment 1, we demonstrate that participants interpret surprised faces more positively when they are presented within a context of happy faces, as compared to a context of angry faces. In Experiments 2 and 3, we used the oddball paradigm to evaluate the effects of clearly valenced facial expressions (i.e., happy and angry) on default valence interpretations of surprised faces. We offer evidence that the default interpretation of surprise is negative, as participants were faster to detect surprised faces when presented within a happy context (Exp. 2). Finally, we kept the valence of the contexts constant (i.e., surprised faces) and showed that participants were faster to detect happy than angry faces (Exp. 3). Together, these experiments demonstrate the utility of the oddball paradigm to explore the default valence interpretation of presented facial expressions, particularly the ambiguously valenced facial expression of surprise.

A tale of two negatives: differential memory modulation by threat-related facial expressions.

Facial expressions serve as cues that encourage viewers to learn about their immediate environment. In studies assessing the influence of emotional cues on behavior, fearful and angry faces are often combined into one category, such as "threat-related," because they share similar emotional valence and arousal properties. However, these expressions convey different information to the viewer. Fearful faces indicate the increased probability of a threat, whereas angry expressions embody a certain and direct threat. This conceptualization predicts that a fearful face should facilitate processing of the environment to gather information to disambiguate the threat. Here, we tested whether fearful faces facilitated processing of neutral information presented in close temporal proximity to the faces. In Experiment 1, we demonstrated that, compared with neutral faces, fearful faces enhanced memory for neutral words presented in the experimental context, whereas angry faces did not. In Experiment 2, we directly compared the effects of fearful and angry faces on subsequent memory for emotional faces versus neutral words. We replicated the findings of Experiment 1 and extended them by showing that participants remembered more faces from the angry face condition relative to the fear condition, consistent with the notion that anger differs from fear in that it directs attention toward the angry individual. Because these effects cannot be attributed to differences in arousal or valence processing, we suggest they are best understood in terms of differences in the predictive information conveyed by fearful and angry facial expressions.

Behind the mask: the influence of mask-type on amygdala response to fearful faces.

In this study, we compared the effects of using neutral face masks vs non-face pattern masks on amygdala activity to masked fearful faces. Twenty-seven subjects viewed 18 s blocks of either fearful or happy faces masked with either neutral faces or patterns, while their brain activity was measured using functional magnetic resonance imaging. Results replicated increased amygdala activation to face-masked fearful vs happy faces. In the pattern mask condition, the amygdala discriminated between masked fearful and happy faces, but this effect manifested as a decrease in activation to fearful faces compared to happy faces. This interactive effect between facial expression and mask stimulus shows that amygdala responses to masked fearful faces are influenced by the fearful stimuli per se as well as their interaction with the mask stimulus.

Human amygdala responsivity to masked fearful eye whites.

The amygdala was more responsive to fearful (larger) eye whites than to happy (smaller) eye whites presented in a masking paradigm that mitigated subjects' awareness of their presence and aberrant nature. These data demonstrate that the amygdala is responsive to elements of.