Enhance Extinction Learning Research Articles

Acute and chronic cannabis vapor exposure produces immediate and delayed impacts on phases of fear learning in a sex specific manner.

Current treatment options for PTSD have unreliable efficacy, with many individuals unable to achieve complete remission. Cannabis and cannabinoids that act through the endogenous cannabinoid (endocannabinoid) system to help promote trauma recovery by means of enhanced extinction learning are potential therapeutic, pharmacological candidates. Using a preclinical model of translationally-relevant cannabis administration in rodents, we examined the impact of cannabis exposure on aversive memory. Our study investigated the effects of acute cannabis exposure prior to (1) fear conditioning and (2) fear extinction, as well as (3) chronic cannabis exposure prior to fear conditioning, on the behavioural representations of fear memory dynamics in a Pavlovian auditory conditioning paradigm. Male and female Sprague Dawley rats were acutely or chronically exposed to THC-dominant cannabis extract or vehicle vapor as described above. We then assessed both passive (freezing) and active (darting) fear behaviours during conditioning, extinction, retrieval, and spontaneous recovery. Acute cannabis exposure prior to conditioning had no immediate effects on fear acquisition, but impaired fear recall in females 24h later and prevented spontaneous recovery of conditioned fear following a two-week retrieval test in both male and female rats. Acute cannabis exposure prior to extinction training impaired extinction in females while enhancing extinction acquisition in males. Finally, chronic THC exposure prior to fear conditioning initially potentiated fear responses, predominately in females, but produced no differences in spontaneous recovery in a two-week retrieval test. Cannabis exposure has complex dynamics on fear memory, however, acute cannabis exposure prior to fear learning appears to result in destabilization of the fear memory long term, which could have potential implications for PTSD.

Transcutaneous Auricular Vagus Nerve Stimulation Does Not Accelerate Fear Extinction: A Randomized, Sham-Controlled Study.

Transcutaneous auricular vagus nerve stimulation (taVNS) has been tested as a strategy to facilitate fear extinction learning based on the hypothesis that taVNS increases central noradrenergic activity. Four studies out of six found taVNS to enhance extinction learning especially at the beginning of extinction. Facilitatory effects of taVNS were mainly observed in US expectancy, less in fear-potentiated startle (FPS), and not in the skin conductance response (SCR). Suboptimal stimulation parameters may explain the reported mixed results. Also, variability in selected fear conditioning paradigms and statistical power impedes the comparability between studies. This study sought to further test whether taVNS accelerates fear extinction learning as indexed by US expectancy, FPS, and SCR. Similar to most previous studies, we employed a differential fear conditioning paradigm. The left ear of 79 healthy participants was stimulated with either sham (earlobe) or taVNS (cymba concha) during extinction learning. To maximize the beneficial effects of taVNS, the stimulation of the left cymba concha was administered continuously at the maximum level below the pain threshold. Results of the pre-registered frequentist and exploratory Bayesian analyses indicate that taVNS did not accelerate extinction learning in any of the outcomes. The null results indicate that taVNS with commonly used stimulation parameters does not reliably optimize fear extinction learning. More research is needed to test if the stimulation protocol determines the efficacy of taVNS in optimizing fear extinction learning.

How Psychedelics Modulate Multiple Memory Mechanisms in Posttraumatic Stress Disorder.

Posttraumatic stress disorder (PTSD) is a psychiatric disorder with defining abnormalities in memory, and psychedelics may be promising candidates for the treatment of PTSD given their effects on multiple memory systems. Most PTSD and psychedelic research has investigated memory with fear conditioning and extinction. While fruitful, conditioning and extinction provide a limited model of the complexity of PTSD and phenomenology of psychedelics, thereby limiting the refinement of therapies. In this review, we discuss abnormalities in fear conditioning and extinction in PTSD and review 25 studies testing psychedelics on these forms of memory. Perhaps the most reliable effect is that the acute effects of psychedelics can enhance extinction learning, which is impaired in PTSD. However, the post-acute effects may also enhance extinction learning, and the acute effects can also enhance fear conditioning. We then discuss abnormalities in episodic and semantic memory in PTSD and review current knowledge on how psychedelics impact these memory systems. Although PTSD and psychedelics acutely impair the formation of hippocampal-dependent episodic memories, psychedelics may acutely enhance cortical-dependent learning of semantic memories that could facilitate the integration of trauma memories and disrupt maladaptive beliefs. More research is needed on the acute effects of psychedelics on episodic memory consolidation, retrieval, and reconsolidation and post-acute effects of psychedelics on all phases of episodic memory. We conclude by discussing how targeting multiple memory mechanisms could improve upon the current psychedelic therapy paradigm for PTSD, thereby necessitating a greater emphasis on assessing diverse measures of memory in translational PTSD and psychedelic research.

Conflict Dynamics of Post-Retrieval Extinction: A Comparative Analysis of Unconditional and Conditional Reminders Using Skin Conductance Responses and EEG.

The post-retrieval extinction paradigm, rooted in reconsolidation theory, holds promise for enhancing extinction learning and addressing anxiety and trauma-related disorders. This study investigates the impact of two reminder types, mild US-reminder (US-R) and CS-reminder (CS-R), along with a no-reminder extinction, on fear recovery prevention in a categorical fear conditioning paradigm. Scalp EEG recordings during reminder and extinction processes were conducted in a three-day design. Results show that the US-R group exhibits a distinctive extinction learning pattern, characterized by a slowed-down yet successful process and pronounced theta-alpha desynchronization (source-located in the prefrontal cortex) during CS processing, followed by enhanced synchronization (source-located in the anterior cingulate) after shock cancellation in extinction trials. These neural dynamics correlate with the subtle advantage of US-R in the Day 3 recovery test, presenting faster spontaneous recovery fading and generally lower fear reinstatement responses. Conversely, the CS reminder elicits CS-specific effects in later episodic tests. The unique neural features of the US-R group suggest a larger prediction error and subsequent effortful conflict learning processes, warranting further exploration.

Vagus Nerve Stimulation (VNS) Modulates Synaptic Plasticity in the Infralimbic Cortex via Trk-B Receptor Activation to Reduce Drug-Seeking in Male Rats.

Drugs of abuse cause changes in the prefrontal cortex (PFC) and associated regions that impair inhibitory control over drug-seeking. Breaking the contingencies between drug-associated cues and the delivery of the reward during extinction learning reduces relapse. Vagus nerve stimulation (VNS) has previously been shown to enhance extinction learning and reduce drug-seeking. Here we determined the effects of VNS-mediated release of brain-derived neurotrophic factor (BDNF) on extinction and cue-induced reinstatement in male rats trained to self-administer cocaine. Pairing 10 d of extinction training with VNS facilitated extinction and reduced drug-seeking behavior during reinstatement. Rats that received a single extinction session with VNS showed elevated BDNF levels in the medial PFC as determined via an enzyme-linked immunosorbent assay. Systemic blockade of tropomyosin receptor kinase B (TrkB) receptors during extinction, via the TrkB antagonist ANA-12, decreased the effects of VNS on extinction and reinstatement. Whole-cell recordings in brain slices showed that cocaine self-administration induced alterations in the ratio of AMPA and NMDA receptor-mediated currents in Layer 5 pyramidal neurons of the infralimbic cortex (IL). Pairing extinction with VNS reversed cocaine-induced changes in glutamatergic transmission by enhancing AMPAR currents, and this effect was blocked by ANA-12. Our study suggests that VNS consolidates the extinction of drug-seeking behavior by reversing drug-induced changes in synaptic AMPA receptors in the IL, and this effect is abolished by blocking TrkB receptors during extinction, highlighting a potential mechanism for the therapeutic effects of VNS in addiction.

Timing of vagus nerve stimulation during fear extinction determines efficacy in a rat model of PTSD

Studies have indicated that vagus nerve stimulation (VNS) enhances extinction learning in rodent models. Here, we investigated if pairing VNS with the conditioned stimulus is required for the enhancing effects of VNS. Adult Sprague–Dawley rats were exposed to intense stress followed by fear conditioning training to produce resistant fear. Rats were then implanted with a cuff electrode around the left vagus. After recovery, rats underwent extinction training paired with VNS (0.5 s, 0.8 mA, 100 µs, and 30 Hz) or with Sham VNS (0 mA). VNS rats were randomized into the following subgroups: During VNS (delivered during presentations of the conditioned stimulus, CS), Between VNS (delivered between CS presentations), Continuous VNS (delivered during the entire extinction session), and Dispersed VNS (delivered at longer inter-stimulation intervals across the extinction session). Sham VNS rats failed to extinguish the conditioned fear response over 5 days of repeated exposure to the CS. Rats that received Between or Dispersed VNS showed modest improvement in conditioned fear at the retention test. During and Continuous VNS groups displayed the greatest reduction in conditioned fear. These findings indicate that delivering VNS paired precisely with CS presentations or continuously throughout extinction promotes the maximum enhancement in extinction learning.

Targeted Memory Reactivation During REM Sleep in Patients With Social Anxiety Disorder.

BackgroundSocial anxiety disorder (SAD) is characterized by a significant amount of fear when confronted to social situations. Exposure therapy, which is based on fear extinction, does not often lead to full remission. Here, based on evidence showing that rapid eye movement (REM) sleep promotes the consolidation of extinction memory, we used targeted memory reactivation (TMR) during REM sleep to enhance extinction learning in SAD.MethodsForty-eight subjects with SAD were randomly assigned to two groups: control or TMR group. All patients had two successive exposure therapy sessions in a virtual reality (VR) environment, where they were asked to give a public talk in front of a virtual jury. At the end of each session, and only in the TMR group (N = 24), a sound was paired to the positive feedback phase of therapy (i.e., approval of their performance), which represented the memory to be strengthened during REM sleep. All participants slept at home with a wearable headband device which automatically identified sleep stages and administered the sound during REM sleep. Participants' anxiety level was assessed using measures of parasympathetic (root mean square of successive differences between normal heartbeats, RMSSD) and sympathetic (non-specific skin conductance responses, ns-SCRs) activity, and subjective measures (Subjective Units of Distress Scale, SUDS), during the preparation phase of their talks before (T1) and after (T2) one full-night's sleep and after 1 week at home (T3). Participants also filled in a dream diary.ResultsWe observed an effect of time on subjective measures of anxiety (SUDS). We did not find any difference in the anxiety levels of the two groups after 1 week of TMR at home. Importantly, the longer the total duration of REM sleep and the more stimulations the TMR group had at home, the less anxious (increased RMSSD) these participants were. Finally, fear in dreams correlated positively with ns-SCRs and SUDS at T3 in the TMR group.ConclusionTMR during REM sleep did not significantly modulate the beneficial effect of therapy on subjective anxiety. Yet, our results support that REM sleep can contribute to extinction processes and substantiate strong links between emotions in dreams and waking stress levels in these patients.

Verbalisation of attention regulation strategies and background music enhance extinction learning and retention

Relapse and return of fear are common following exposure-based treatments which aim to decrease anxiety by reducing danger expectancies and negative stimulus evaluations. Using Pavlovian conditioning and extinction procedures, recent studies found that verbalising catchphrases to prompt attention to, and memory of, stimulus contingencies during extinction prevented US expectancy generalisation to safe stimuli and reduced anxiety ratings. Verbalizations did not improve negative evaluations of conditional stimuli. Given that negative evaluations predict return of fear, the current study examined whether verbalisation strategies combined with listening to liked, non-lyrical background music enhanced expectancy learning and positively changed stimulus evaluations. A differential Pavlovian conditioning procedure was used involving fear acquisition, extinction, and extinction retest phases. Participants were assigned to a verbalisation condition (N = 21), a verbalisation plus liked, non-lyrical music condition (N = 21) or a control condition (N = 21) during extinction. The verbalisation strategies, with and without music, prevented the generalisation of US expectancies to safe stimuli at retest. Verbalisation strategies plus music increased positive evaluations of conditional stimuli during extinction and retest. Further research on the role of verbalising attention regulation strategies and liked, non-lyrical background music during extinction is warranted with clinical samples.

A randomized, double-blind, placebo-controlled trial of hydrocortisone augmentation of Prolonged Exposure for PTSD in U.S. combat veterans

ObjectiveCognitive behavioral therapies such as Prolonged Exposure (PE) are considered first line treatments for posttraumatic stress disorder (PTSD). Nonetheless, many continue to experience significant symptoms following treatment and there is interest in enhancing treatment effectiveness. Glucocorticoid alterations in PTSD are well documented, and these steroids have been shown to enhance extinction learning. MethodsAugmentation of PE with the synthetic glucocorticoid hydrocortisone (HCORT) was tested in a randomized, double-blind, placebo-controlled trial in 60 veterans of wars in Iraq or Afghanistan with PTSD (NCT01525680). Participants ingested 30 mg oral HCORT or placebo 30 min prior to exposure sessions. Primary outcome measure: PTSD severity assessed by the CAPS; secondary outcome measures: self reported PTSD symptoms assessed by the PDS and depression assessed by the BDI; all administered at pretreatment, posttreatment, and 3-month follow up. ResultsAcross conditions, there was a robust effect of PE over time. An intent-to-treat analysis showed that HCORT did not measurably improve PTSD symptoms or secondary outcomes. However, exploratory analyses indicated that veterans with mild TBI exposure and current postconcussive symptoms showed a greater reduction in hyperarousal symptoms following PE treatment with HCORT augmentation. Additionally, veterans with higher baseline glucocorticoid sensitivity showed a greater reduction in avoidance symptoms with HCORT augmentation. ConclusionsTreatment matching based on cognitive or biological vulnerabilities might lead to greater efficacy of PE with glucocorticoid augmentation.

Vagus nerve stimulation enhances fear extinction as an inverted-U function of stimulation intensity

Studies in rodents indicate that pairing vagus nerve stimulation (VNS) with extinction training enhances fear extinction. However, the role of stimulation parameters on the effects of VNS remains largely unknown. Identifying the optimal stimulation intensity is a critical step in clinical translation of neuromodulation-based therapies. Here, we sought to investigate the role of stimulation intensity in rats receiving VNS paired with extinction training in a rat model for Posttraumatic Stress Disorder (PTSD). Male Sprague-Dawley rats underwent single prolonged stress followed by a severe fear conditioning training and were implanted with a VNS device. After recovery, independent groups of rats were exposed to extinction training paired with sham (0 mA) or VNS at different intensities (0.4, 0.8, or 1.6 mA). VNS intensities of 0.4 mA or 0.8 mA decreased conditioned fear during extinction training compared to sham stimulation. Pairing extinction training with moderate VNS intensity of 0.8 mA produced significant reduction in conditioned fear during extinction retention when rats were tested a week after VNS-paired extinction. High intensity VNS at 1.6 mA failed to enhance extinction. These findings indicate that a narrow range of VNS intensities enhances extinction learning, and suggest that the 0.8 mA VNS intensity used in earlier rodent and human stroke studies may also be the optimal in using VNS as an adjuvant in exposure therapies for PTSD.

Presynaptic GABAB receptor inhibition sex dependently enhances fear extinction and attenuates fear renewal.

Anxiety and trauma-related disorders are highly prevalent worldwide, andare associated with altered associative fear learning. Despite the effectiveness of exposure therapy, which aims to reduce associative fear responses, relapse rates remain high. This is due, in part, to the context specificity of exposure therapy, which is a form of extinction. Many studies show that fear relapses when mice are tested outside the extinction context, and this is known as fear renewal. Using Pavlovian fear conditioning and extinction, we can study the mechanisms underlying extinction and renewal. The aim of the current experiment was to identify the role of presynaptic GABAB receptors in these two processes. Previous work from our lab showed that genetic deletion or pharmacological inhibition of GABAB(1a) receptors that provide presynaptic inhibition on glutamatergic terminals reduces context specificity and leads to generalization. We therefore hypothesized that inactivation of these presynaptic GABAB receptors could be used to reduce the context specificity associated with fear extinction training and suppress renewal when mice are tested outside of the extinction context. Using CGP 36216, an antagonist specific for presynaptic GABAB receptors, we blocked presynaptic GABAB receptors using intracerebroventricular injections during various time points of extinction learning in male and female mice. Results showed that blocking these receptors pre- and post-extinction training led to enhanced extinction learning in male mice only. We also found that post-extinction infusions of CGP reduced renewal rates in male mice when they were tested outside of the extinction context. In an attempt to localize the function of presynaptic GABAB receptors within regions of the extinction circuit, we infused CGP locally within the basolateral amygdala or dorsal hippocampus. We failed to reduce renewal when CGP was infused directly within these regions, suggesting that presynaptic inhibition within these regions per se may not be necessary for driving context specificity during extinction learning. Together, these results show an important sex-dependent role of presynaptic GABAB receptors in extinction and renewal processes and identify a novel receptor target that may be used to design pharmacotherapies to enhance the effectiveness of exposure therapy.

Generalization of extinction with a generalization stimulus is determined by learnt threat beliefs

Expectancy violation refers to the mismatch between an expected and the actual outcome. Maximizing expectancy violation is crucial for exposure-based treatment. Since the original stimulus of fear acquisition (CS+) is rarely available, stimuli that resemble the CS+ (generalization stimuli; GSs) are presented during treatment. A given GS may evoke either strong or weak generalized fear depending on an individual's threat beliefs. Presenting this GS in extinction would then evoke different levels of expectancy violation, which determines the strength of the subsequent generalization of extinction to other stimuli, including the CS+. After differential fear conditioning, participants exhibited discrete generalization gradients depending on their inferred relational rules (Linear vs Similarity). Crucially, the Linear group showed strong generalized fear to the GS used in extinction. This strong expectancy violation led to enhanced extinction learning and subsequently to strong generalization of extinction as characterized by a flat generalization gradient, and reduced conditioned fear to the CS+. In contrast, the Similarity group showed weak generalized fear to the same GS in extinction, and limited generalization of extinction. These results corroborate the importance of expectancy violation in exposure-based treatment, and suggest that exposure sessions designed to evoke strong threat beliefs may lead to better treatment outcome.

Testing the efficacy of a brief exercise intervention for enhancing exposure therapy outcomes

Recently, it has been hypothesized that a brief bout of exercise could cognitively enhance extinction learning processes theorized to underlie exposure therapy for pathological anxiety. The present study tested the exercise enhancement hypothesis in a sample of speech-anxious undergraduates (n = 84). During the first laboratory session, participants engaged in either 30 min of moderate-intensity exercise on a cycling ergometer (n = 37) or seated rest (n = 47) immediately following a brief speech exposure trial. They returned approximately one week later to give a follow-up speech. Contrary to expectation, there were no significant between-group differences in memory of a brief word list across four recall trials, which served as a manipulation check. Further, all main effects and interactions involving condition were nonsignificant. Post hoc tests revealed that participants who reported higher average perceived exertion during exercise demonstrated increases in an average anxiety composite across speeches relative to those who reported lower average perceived exertion, indicating that trying hard during the intervention predicted worse exposure trial outcomes. The implications of these findings, as well as future directions for this line of research, are explored.

Inhaled Lavandula angustifolia essential oil enhances extinction learning and inhibits memory updating in mice submitted to the contextual fear conditioning

Ethnopharmacological relevanceLavender (Lavandula angustifolia) essential oil (EO) has a long history of use in emotional illness, including anxiety disorders. Cognitive mechanisms of learning and memory play a pivotal role in the etiology and maintenance of anxiety since exposure to cues related to aversive situations induces high arousal and anticipatory anxiety. Memory become labile after its reactivation and can be modulated by reconsolidation or extinction. Inhibition of memory reconsolidation or facilitation of memory extinction may be effective in preventing or minimizing the effect of contextual cues on anticipatory anxiety. Aim of the studyWe investigated the effect of Lavandula angustifolia EO in the memory updating of conditioned contextual fear. Materials and methodsAdult male C57Bl6 mice were submitted to fear conditioning. Two days after conditioning the mice underwent a reactivation session in a hybrid context and were then immediately exposed to vaporized water or essential oil at concentrations of 1%, 2.5% or 5% for 3 h. Two days later, the mice were tested in the original or an altered context and their freezing behavior was measured. In addition, mice were subjected to a fear memory recovery protocol followed by a reinstatement session. ResultsIn the contextual fear test, 1% essential oil, but not 2.5% or 5%, reduced the freezing behavior response, whereas after a reinstatement session, exposure to 1% essential oil increased the freezing behavior response. ConclusionsThese results suggest that Lavandula angustifolia essential oil enhances memory extinction and, consequently, inhibits memory updating.

Efficient parameters of vagus nerve stimulation to enhance extinction learning in an extinction-resistant rat model of PTSD

Vagus nerve stimulation (VNS) has shown promise as an adjuvant treatment for posttraumatic stress disorder (PTSD), as it enhances fear extinction and reduces anxiety symptoms in multiple rat models of this condition. Yet, identification of the optimal stimulation paradigm is needed to facilitate clinical translation of this potential therapy. Using an extinction-resistant rat model of PTSD, we tested whether varying VNS intensity and duration could maximize extinction learning while minimizing the total amount of stimulation. We confirmed that sham rats failed to extinguish after a week of extinction training. Delivery of the standard LONG VNS trains (30 s) at 0.4 mA enhanced extinction and reduced anxiety but did not prevent fear return. Increasing the intensity of LONG VNS trains to 0.8 mA prevented fear return and attenuated anxiety symptoms. Interestingly, delivering 1, 4 or 16 SHORT VNS bursts (0.5 s) at 0.8 mA during each cue presentation in extinction training also enhanced extinction. LONG VNS trains or multiple SHORT VNS bursts at 0.8 mA attenuated fear renewal and reinstatement, promoted extinction generalization and reduced generalized anxiety. Delivering 16 SHORT VNS bursts also facilitated extinction in fewer trials. This study provides the first evidence that brief bursts of VNS can enhance extinction training, reduce relapse and support symptom remission using much less VNS than previous protocols. These findings suggest that VNS parameters can be adjusted in order to minimize total charge delivery and maximize therapeutic effectiveness.

Oestradiol, threat conditioning and extinction, post-traumatic stress disorder, and prolonged exposure therapy: A common link.

The accumulating evidence regarding the impact of estradiol on learning and memory synergized studies to examine its influence on enhancing animal's ability to quell fear and anxiety. In this review, we first provide a foundational platform regarding the impact of oestradiol on cellular mechanisms of learning and memory and we review recent advances from rodent and human data showing that oestrogen enhances extinction learning across species. We then propose clinical application to these data. We discuss the potential role of oestradiol variance on the aetiology, maintenance and treatment for post-traumatic stress disorder. Specifically, we argue that the use of oestradiol as an adjunct to prolonged exposure (PE) therapy for PTSD may provide a new treatment approach for enhancing the efficacy of PE in women with PTSD. This could advance our understanding of the mechanisms of PTSD and help tailor sex-specific treatments for this disorder.

Augmenting extinction learning with D-cycloserine reduces return of fear: a randomized, placebo-controlled fMRI study.

D-cycloserine (DCS), a partial NMDA-receptor agonist, seems to be a promising enhancer for exposure therapy in anxiety disorders. It has been tested successfully in animal models of fear extinction, where DCS enhanced extinction learning. Applied in clinical studies, results of DCS-augmented exposure therapy remain ambiguous, calling for a deeper understanding of the underlying mechanisms of DCS and its exact effect on extinction learning and return of fear (ROF) in humans. In the present study, we investigated the effect of DCS-augmented extinction learning on behavioral, psychophysiological, and neural indices of ROF during a 24-h delayed recall test. Thirty-seven participants entered a randomized, placebo-controlled, double-blind, 3-day fear conditioning and delayed extinction fMRI design. One hour before extinction training, participants received an oral dose of 50 mg ofDCS or a placebo. Behavioral arousal ratings revealed a generalized ROF during extinction recall in the placebo but not DCS group. Furthermore, participants receiving DCS compared to placebo showed attenuated differential BOLD responses in left posterior hippocampus and amygdala from extinction learning to extinction recall, due to increased hippocampal recruitment in placebo and trendwise decreased amygdala responding in DCS subjects. Our finding that DCS reduces ROF in arousal ratings and neural structures subserving defensive reactions support a role for NMDA receptors in extinction memory consolidation and encourage further translational research.

From Extinction Learning to Anxiety Treatment: Mind the Gap.

Laboratory models of extinction learning in animals and humans have the potential to illuminate methods for improving clinical treatment of fear-based clinical disorders. However, such translational research often neglects important differences between threat responses in animals and fear learning in humans, particularly as it relates to the treatment of clinical disorders. Specifically, the conscious experience of fear and anxiety, along with the capacity to deliberately engage top-down cognitive processes to modulate that experience, involves distinct brain circuitry and is measured and manipulated using different methods than typically used in laboratory research. This paper will identify how translational research that investigates methods of enhancing extinction learning can more effectively model such elements of human fear learning, and how doing so will enhance the relevance of this research to the treatment of fear-based psychological disorders.

Strengthened Hippocampal Circuits Underlie Enhanced Retrieval of Extinguished Fear Memories Following Mindfulness Training

BackgroundThe role of hippocampus in context-dependent recall of extinction is well recognized. However, little is known about how intervention-induced changes in hippocampal networks relate to improvements in extinction learning. In this study, we hypothesized that mindfulness training creates an optimal exposure condition by heightening attention and awareness of present moment sensory experience, leading to enhanced extinction learning, improved emotion regulation, and reduced anxiety symptoms. MethodsWe tested this hypothesis in a randomized controlled longitudinal study design using a 2-day fear conditioning and extinction protocol. The mindfulness training group included 42 participants (28 women) and the control group included 25 participants (15 women). ResultsWe show that mindfulness training is associated with differential engagement of the right supramarginal gyrus as well as hippocampal-cortical reorganization. We also report enhanced hippocampal connectivity to the primary sensory cortex during retrieval of extinguished stimuli following mindfulness training. ConclusionsThese findings suggest hippocampal-dependent changes in contextual retrieval as one plausible neural mechanism through which mindfulness-based interventions enhance fear extinction and foster stress resilience.

Attention narrowing followed by broadening enhances threat reactivity and generalisation during extinction but reduces physiological arousal at retest: A preliminary examination

Anxiety disorders are common and impairing, however, approximately 40% of affected individuals do not respond in the short or long term to gold-standard, exposure-based treatments. The current preliminary study examined whether goal-directed attention during extinction (the experimental analogue of exposure therapy) enhances extinction learning and retention. Thirty-six participants completed a differential Pavlovian conditioning and extinction task. Goal-directed attention (GDA) participants (N = 18) received instructions to narrow attention on the most threat salient feature of the CS + for the first half of extinction trials and then broaden attention over the CS + and surrounding context during the last half of extinction trials. Controls (CON) (N = 18) received instructions to continue to focus on the screen. Trial-by-trial US expectancies and CS evaluations, skin conductance responses (SCRs), and between-phase anxiety, CS valence and arousal ratings were assessed. No significant group differences were found during the attention narrowing phase. During the attention broadening phase, GDA, but not CON participants, exhibited increasingly larger SCRs to the CS + and elimination of differential US expectancies that was due, in part, to increasing US expectancies to the CS-. However, GDA participants exhibited reduced physiological arousal when subsequently re-exposed to the CSs at retest compared to CON participants. There were no significant differences on between-phase CS evaluations and subjective anxiety ratings. This initial study of attention strategies during extinction suggest that attention narrowing followed by broadening may enhance threat reactivity and generalisation during extinction but reduce physiological arousal at retest.