Sophia A. Bibb’s research while affiliated with The Ohio State University and other places

Because extinction forms the empirical foundation of exposure therapy, strategies to enhance extinction could lead to more effective interventions for post-traumatic stress disorder (PTSD). Here, we used functional MRI to compare immediate and long-term efficacy of enhanced versus standard extinction in 54 adults with (n=32) and without (n=22) PTSD. In both control and PTSD groups, counterconditioning—an enhanced form of extinction that replaces threat with positive outcomes—was more effective than standard extinction. It reduced threat-related neural activity and promoted reinstatement of safety (extinction) patterns in the ventromedial prefrontal cortex (a region involved in learning and retrieving safety associations). However, the PTSD group continued to reinstate both threat- and safety-related neural patterns in the dorsal anterior cingulate cortex (a region involved in learning and retrieving threat associations). These findings represent novel evidence that enhanced extinction outperforms standard extinction in promoting more rapid and persistent neural representations of safety in PTSD.

No prior work has directly compared the impacts of transcranial photobiomodulation (tPBM) and transcranial magnetic stimulation (TMS) on the human brain. This within-subjects pilot study compares the effects of tPBM and TMS of human somatomotor cortex on brain structural and functional connectivity. Eight healthy participants underwent four lab visits each, each visit consisting of a pre-stimulation MRI, stimulation or sham, and a post-stimulation MRI, respectively. Stimulation and sham sessions were counterbalanced across subjects. Collected measures included structural MRI data, functional MRI data from a finger-tapping task, resting state functional connectivity, and structural connectivity. Analyses indicated increased activation of the left somatomotor region during a right-hand finger-tapping task following both tPBM and TMS. Additionally, trending increases in left-lateralized functional and structural connectivity from M1 to thalamus were observed after tPBM, but not TMS. Thus, tPBM may be superior to TMS at inducing changes in connected nodes in the somatomotor cortex, although further research is warranted to explore the potential therapeutic benefits and clinical utility of tPBM.

Poor inhibitory control and exaggerated threat reactivity are two well‐established risk factors for suicide. Theory suggests that these two factors may interact to influence suicide risk, although few studies have directly tested these relationships. In the present study, we examined the unique and interactive effects of inhibitory control (IC) and threat reactivity on self‐reported suicide risk in a sample of 132 youth, ages 16–19. The stop signal task was used as a behavioral index of IC. Threat reactivity was captured using a modified version of the No‐Predictable–Unpredictable threat paradigm that includes threat of predictable (P‐) and unpredictable (U‐) mild electrical shock. Startle eyeblink potentiation was measured throughout the task as an index of aversive responding. All participants completed a battery of well‐validated self‐report measures including current suicide risk. Hierarchical linear regression analyses controlling for age and sex revealed no main effects of IC or threat reactivity. However, there was a significant IC by reactivity to uncertain threat (U‐threat) interaction. At lower levels of IC, greater startle reactivity to U‐threat was associated with greater suicide risk. At higher levels of IC, there was no association between reactivity to U‐threat and suicide risk. These results suggest that individual differences in IC and reactivity to U‐threat interact to influence suicide cognitions, shedding light on potential subgroups of individuals who might be at elevated risk.

Fear conditioning and extinction generate conflicting memory representations for a conditioned stimulus (CS). Retrieval of either memory is largely determined by the context where the CS is encountered. While fear typically generalizes to CSs encountered in new contexts, extinction is specific to the environment in which it was learned. Here we used an fMRI design (N = 30) to tag and track the extent which individual participants reinstated competing episodic mental contexts associated with threat conditioning and extinction. We examined whether reactivation of past encoding contexts influences threat expectancy behavior and neural responses to a threat-ambiguous CS encountered in a new context. Results showed that the relative balance between conditioning and extinction context reinstatement in higher-order visual cortex influenced threat expectancy and neural activity in canonical threat processing regions. The link between context reinstatement and fear-related processes was specific to an extinguished CS, as opposed to an unextinguished CS that had never been encountered in the extinction context. These effects were observed 24 hours later, but not after 3 weeks. Additionally, threat conditioning produced long-lasting changes in primary sensory cortex that persisted up to 3 weeks following extinction. These findings show that neural representations of threat can endure over long durations, even in the healthy brain. Our results indicate competition between divergent mental contexts determines feelings of danger or safety when the meaning of the CS is ambiguous, and suggest a mechanism by which the brain resolves ambiguity by reinstating the more dominant context associated with either fear or extinction.

Fear conditioning and extinction generate conflicting memory representations for a conditioned stimulus (CS). Retrieval of either memory is largely determined by the context where the CS is encountered. While fear typically generalizes to CSs encountered in new contexts, extinction is specific to the environment in which it was learned. Here we used an fMRI design (N = 30) to tag and track the extent which individual participants reinstated competing episodic mental contexts associated with threat conditioning and extinction. We examined whether reactivation of past encoding contexts influences threat expectancy behavior and neural responses to a threat-ambiguous CS encountered in a new context. Results showed that the relative balance between conditioning and extinction context reinstatement in higher-order visual cortex influenced threat expectancy and neural activity in canonical threat processing regions. The link between context reinstatement and fear-related processes was specific to an extinguished CS, as opposed to an unextinguished CS that had never been encountered in the extinction context. These effects were observed 24 hours later, but not after 3 weeks. Additionally, threat conditioning produced long-lasting changes in primary sensory cortex that persisted up to 3 weeks following extinction. These findings show that neural representations of threat can endure over long durations, even in the healthy brain. Our results indicate competition between divergent mental contexts determines feelings of danger or safety when the meaning of the CS is ambiguous, and suggest a mechanism by which the brain resolves ambiguity by reinstating the more dominant context associated with either fear or extinction.

Emotional experiences can profoundly impact our conceptual model of the world, modifying how we represent and remember a host of information even indirectly associated with that experienced in the past. Yet, how a new emotional experience infiltrates and spreads across pre-existing semantic knowledge structures (e.g., categories) is unknown. We used a modified aversive sensory preconditioning paradigm in fMRI (n = 35) to investigate whether threat memories integrate with a pre-established category to alter the representation of the entire category. We observed selective but transient changes in the representation of conceptually related items in the amygdala, medial prefrontal cortex, and occipitotemporal cortex following threat conditioning to a simple cue (geometric shape) pre-associated with a different, but related, set of category exemplars. These representational changes persisted beyond 24 h in the hippocampus and perirhinal cortex. Reactivation of the semantic category during threat conditioning, combined with activation of the hippocampus or medial prefrontal cortex, was predictive of subsequent amygdala reactivity toward novel category members at test. This provides evidence for online integration of emotional experiences into semantic categories, which then promotes threat generalization. Behaviorally, threat conditioning by proxy selectively and retroactively enhanced recognition memory and increased the perceived typicality of the semantic category indirectly associated with threat. These findings detail a complex route through which new emotional learning generalizes by modifying semantic structures built up over time and stored in memory as conceptual knowledge.

Emotional experiences can profoundly impact our conceptual model of the world, modifying how we represent and remember a host of information even indirectly associated with that experience in the past. Yet, how a new emotional experience infiltrates and spreads across pre-existing semantic categories is unknown. We used an aversive sensory preconditioning paradigm in fMRI (N=35) to investigate whether threat memories integrate with a pre-established category to alter the representation of the entire category. We observed selective but transient changes in the representation of conceptually-related items in the amygdala, medial prefrontal cortex, and occipitotemporal cortex following threat conditioning to a simple cue (geometric shape) pre-associated with a different, but related, set of category exemplars. These representational changes persisted beyond 24-hours in the hippocampus and perirhinal cortex. During threat conditioning, reactivation of the semantic category interacted with hippocampal/medial prefrontal cortex activity to predict subsequent amygdala activity toward novel category members at test, providing evidence for online integration promoting threat generalization. Behaviorally, threat conditioning by proxy selectively and retroactively enhanced recognition memory, and increased the perceived typicality of the semantic category indirectly associated with threat. These findings detail a complex route through which new emotional learning generalizes by modifying associative networks built up over time and stored in memory as conceptual knowledge.

A challenge for translating fear extinction research into clinical treatments for stress and anxiety disorders is that extinction learning tends not to generalize beyond the treatment context. This may be because the hippocampus limits the expression of extinction memories. Consequently, downregulating the hippocampus may help to promote the generalization of extinction learning. One nonpharmacological strategy to downregulate hippocampal activity in humans is motivated forgetting, in which a participant deliberately attempts to suppress the encoding and/or retrieval of episodic memories. Here, we evaluated whether this strategy could facilitate extinction generalization by augmenting extinction training with thought suppression. Participants were threat conditioned using two conditioned stimulus (CS) categories paired with an electrical shock. Subsequently, during extinction training, one CS category was accompanied by thought suppression. Participants were tested for extinction generalization 24h later with conceptual variations of the extinguished stimuli. Contrary to our prediction, we found that extinction training paired with thought suppression resulted in enhanced shock expectancy (i.e., worse generalization) relative to standard extinction. We conclude that thought suppression during memory encoding likely acts as an inhibitory cue that blocks the acquisition of extinction memories, and therefore may not be a viable tactic to promote extinction generalization in the treatment of anxiety disorders.