Mindfulness training and exercise differentially impact fear extinction neurocircuitry.

BACKGROUND: The ability to extinguish a maladaptive conditioned fear response is crucial for healthy emotional processing and resiliency to aversive experiences. Therefore, enhancing fear extinction learning has immense potential emotional and health benefits. Mindfulness training enhances both fear conditioning and recall of extinguished fear; however, its effects on fear extinction learning are unknown. Here we investigated the impact of mindfulness training on brain mechanisms associated with fear-extinction learning, compared to an exercise-based program. METHODS: We investigated BOLD activations in response to a previously learned fear-inducing cue during an extinction paradigm, before and after an 8-week mindfulness-based stress reduction program (MBSR, n = 49) or exercise-based stress management education program (n = 27). RESULTS: The groups exhibited similar reductions in stress, but the MBSR group was uniquely associated with enhanced activation of salience network nodes and increased hippocampal engagement. CONCLUSIONS: Our results suggest that mindfulness training increases attention to anticipatory aversive stimuli, which in turn facilitates decreased aversive subjective responses and enhanced reappraisal of the memory.

Hippocampal circuits underlie improvements in self-reported anxiety following mindfulness training.

INTRODUCTION: Mindfulness meditation has successfully been applied to cultivate skills in self-regulation of emotion, as it employs the unbiased present moment awareness of experience. This heightened attention to and awareness of sensory experience has been postulated to create an optimal therapeutic exposure condition and thereby improve extinction learning. We recently demonstrated increased connectivity in hippocampal circuits during the contextual retrieval of extinction memory following mindfulness training. METHODS: Here, we examine the role of structural changes in hippocampal subfields following mindfulness training in a randomized controlled longitudinal study using a two-day fear-conditioning and extinction protocol. RESULTS: We demonstrate an association between mindfulness training-related increases in subiculum and decreased hippocampal connectivity to lateral occipital regions during contextual retrieval of extinguished fear. Further, we demonstrate an association between decreased connectivity and decreases in self-reported anxiety following mindfulness training. CONCLUSIONS: The results highlight the role of the subiculum in gating interactions with contextual stimuli during memory retrieval and, also, the mechanisms through which mindfulness training may foster resilience.

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

BACKGROUND: The 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. METHODS: We 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). RESULTS: We 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. CONCLUSIONS: These 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.

Mindfulness-Based Stress Reduction, Fear Conditioning, and The Uncinate Fasciculus: A Pilot Study.

Mindfulness has been suggested to impact emotional learning, but research on these processes is scarce. The classical fear conditioning/extinction/extinction retention paradigm is a well-known method for assessing emotional learning. The present study tested the impact of mindfulness training on fear conditioning and extinction memory and further investigated whether changes in white matter fiber tracts might support such changes. The uncinate fasciculus (UNC) was of particular interest in the context of emotional learning. In this pilot study, 46 healthy participants were quasi-randomized to a Mindfulness-Based Stress Reduction (MBSR, N = 23) or waitlist control (N = 23) group and underwent a two-day fear conditioning, extinction learning, and extinction memory protocol before and after the course or control period. Skin conductance response (SCR) data served to measure the physiological response during conditioning and extinction memory phases. Diffusion tensor imaging (DTI) data were analyzed with probabilistic tractography and analyzed for changes of fractional anisotropy in the UNC. During conditioning, participants were able to maintain a differential response to conditioned vs. not conditioned stimuli following the MBSR course (i.e., higher sensitivity to the conditioned stimuli), while controls dropped the response. Extinction memory results were not interpretable due to baseline differences. MBSR participants showed a significant increase in fractional anisotropy in the UNC, while controls did not (group by time interaction missed significance). Pre-post changes in UNC were correlated with changes in the response to the conditioned stimuli. The findings suggest effects of mindfulness practice on the maintenance of sensitivity of emotional responses and suggest underlying neural plasticity. (ClinicalTrials.gov, Identifier NCT01320969, https://clinicaltrials.gov/ct2/show/NCT01320969).

Device-based brain stimulation to augment fear extinction: implications for PTSD treatment and beyond.

Conditioned fear acquisition and extinction paradigms have been widely used both in animals and humans to examine the neurobiology of emotional memory. Studies have also shown that patients suffering from posttraumatic stress disorder (PTSD) exhibit deficient extinction recall along with dysfunctional activation of the fear extinction network, including the ventromedial prefrontal cortex, amygdala, and hippocampus. A great deal of overlap exists between this fear extinction network and brain regions associated with symptom severity in PTSD. This suggests that the neural nodes of fear extinction could be targeted to reduce behavioral deficits that may subsequently translate into symptom improvement. In this article, we discuss potential applications of brain stimulation and neuromodulation methods, which, combined with a mechanistic understanding of the neurobiology of fear extinction, could be used to further our understanding of the pathophysiology of anxiety disorders and develop novel therapeutic tools. To this end, we discuss the following stimulation approaches: deep-brain stimulation, vagus nerve stimulation, transcranial direct current stimulation, and transcranial magnetic stimulation. We propose new translational research avenues that, from a systems neuroscience perspective, aim to expand our understanding of circuit dynamics and fear processing toward the practical development of clinical tools, to be used alone or in combination with behavioral therapies.