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.

Modulatory Effects of Actual and Imagined Acupuncture on the Functional Connectivity of the Periaqueductal Gray and Ventral Tegmental Area.

OBJECTIVE: Both acupuncture and guided imagery hold promise for treating pain. The mechanisms underlying these alternative interventions remain unclear. The reported study aimed to comparatively investigate the modulation effect of actual and imagined acupuncture on the functional connectivity of descending pain modulation system and reward network. METHODS: Twenty-four healthy participants (mean [standard error], 25.21 [0.77] years of age; 66.67% female) completed a crossover study that included five sessions, a training session and four intervention sessions administered in randomized order. We investigated the modulation effect of real acupuncture, sham acupuncture, video-guided acupuncture imagery treatment (VGAIT) and VGAIT control on the resting-state functional connectivity (rsFC) of periaqueductal gray (PAG) and ventral tegmental area (VTA). These are key regions of the descending pain modulatory system and dopaminergic reward system, respectively. RESULTS: Compared with sham acupuncture, real acupuncture produced decreased PAG-precuneus (Pcu) rsFC and increased VTA-amygdala/hippocampus rsFC. Heat pain threshold changes applied on the contralateral forearm were significantly associated with the decreased PAG-Pcu (r = 0.49, p = .016) and increased VTA-hippocampus rsFC (r = -0.77, p < .001). Compared with VGAIT control, VGAIT produced decreased PAG-paracentral lobule/posterior cingulate cortex/Pcu, middle cingulate cortex (MCC), and medial prefrontal cortex rsFC, and decreased VTA-caudate and MCC rsFC. Direct comparison between real acupuncture and VGAIT showed that VGAIT decreased rsFC in PAG-paracentral lobule/MCC, VTA-caudate/anterior cingulate cortex/nucleus accumbens, and VTA-MCC. CONCLUSIONS: Results suggest that both actual and imagined acupuncture can modulate key regions in the descending pain modulatory system and reward networks, but through different pathways. Identification of different pain relief mechanisms may facilitate the development of new pain management methods.

Interfering with fear memories by eye movement desensitization and reprocessing.

OBJECTIVE: Pharmacologic and behavioral interventions that block reconsolidation of reactivated fear memory have demonstrated only limited success in modifying stronger and long-standing fear memories. Given the efficacy of Eye Movement Desensitization and Reprocessing (EMDR) in treating PTSD, pursuit eye movements are a promising and novel intervention for studies of human memory reconsolidation. Here, we examined the efficacy of pursuit eye movements in interfering with reconsolidation of conditioned fear memories. METHODS: We conducted a 3-day differential Pavlovian fear conditioning procedure in healthy adults, using videos of biologically prepared stimuli (tarantulas), partly reinforced with electrical shocks while recording skin conductance response (SCR) as a measure of autonomic conditioned responses. Fear conditioning was performed on Day 1. On Day 2, 38 participants were randomized into groups performing pursuit eye movements either immediately after fear memory reactivation, when the fear memory was stable, or 10 min later, when the fear memory was assumed to be more labile. On Day 3, fear memory strength was assessed by SCR to both reactivated and nonreactivated fear memories. RESULTS: Strong differential conditioning to the spider stimuli were observed during both fear acquisition and fear memory reactivation. Reactivated fear memory conditioned responses of participants performing pursuit eye movements after a 10-min delay were significantly smaller in the reinstatement phase (0.16 µS; 95% CI [0.02, 0.31]). CONCLUSIONS: Pursuit eye movements were effective in reducing fear-conditioned SCR in reinstatement. This result supports the theoretical proposition that EMDR can interfere with reactivated fear memory reconsolidation.

Imagined and Actual Acupuncture Effects on Chronic Low Back Pain: A Preliminary Study.

Background: Research suggests that imagined experiences can produce brain responses similar to those produced by actual experiences. Shared brain responses that support both imagination and perception may underlie the functional nature of mental imagery. In a previous study, we combined acupuncture and imagery to develop a new treatment method, video-guided acupuncture imagery treatment (VGAIT). We found that VGAIT significantly increased pain thresholds in healthy subjects. The aim of this study is to extend our previous finding by investigating whether VGAIT can relieve symptoms in patients with chronic low back pain. Methods: We first performed a single-arm study in which we administered video-guided acupuncture imagery treatment (VGAIT) on patients with chronic low back pain (cLBP) (Study 1, n = 18, 12 females). We then compared our findings to those from a recently published study in which real or sham acupuncture treatment was applied on patients with cLBP (Study 2, n = 50, 31 females) using a similar protocol. All patients in Studies 1 and 2 received 6 treatments over 4 weeks. Results: All three treatments (VGAIT, real, and sham acupuncture) significantly reduced pain severity as measured by a low back pain bothersomeness score. VGAIT produced similar effects to real acupuncture (p = 0.97) and nonsignificantly greater pain bothersomeness relief compared to sham acupuncture (p = 0.14). Additional analysis showed that there was no significant difference on the sensations evoked by different treatment modalities. Conclusion: These findings support VGAIT as a promising method for pain management.

Characterizing the analgesic effects of real and imagined acupuncture using functional and structure MRI.

Acupuncture and imagery interventions for pain management have a long history. The present study comparatively investigated whether acupuncture and video-guided acupuncture imagery treatment (VGAIT, watching a video of acupuncture on the participant's own body while imagining it being applied) could modulate brain regional connectivity to produce analgesic effects. The study also examined whether pre-intervention brain functional and structural features could be used to predict the magnitude of analgesic effects. Twenty-four healthy participants were recruited and received four different interventions (real acupuncture, sham acupuncture, VGAIT, and VGAIT control) in random order using a cross-over design. Pain thresholds and magnetic resonance imaging (MRI) data were collected before and after each intervention. We first compared the modulatory effects of real acupuncture and VGAIT on intra- and inter-regional intrinsic brain connectivity and found that real acupuncture decreased regional homogeneity (ReHo) and functional connectivity (FC) in sensorimotor areas, whereas VGAIT increased ReHo in basal ganglia (BG) (i.e., putamen) and FC between the BG subcortical network and default mode network. The altered ReHo and FC were associated with changes in pain threshold after real acupuncture and VGAIT, respectively. A multimodality fusion approach with pre-intervention ReHo and gray matter volume (GMV) as features was used to explore the brain profiles underlying individual variability of pain threshold changes by real acupuncture and VGAIT. Variability in acupuncture responses was associated with ReHo and GMV in BG, whereas VGAIT responses were associated with ReHo and GMV in the anterior insula. These results suggest that, through different pathways, both real acupuncture and VGAIT can modulate brain systems to produce analgesic effects.

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.

Analgesic Effects Evoked by Real and Imagined Acupuncture: A Neuroimaging Study.

Acupuncture can provide therapeutic analgesic benefits but is limited by its cost and scheduling difficulties. Guided imagery is a commonly used method for treating many disorders, such as chronic pain. The present study examined a novel intervention for pain relief that integrates acupuncture with imagery called video-guided acupuncture imagery treatment (VGAIT). A total of 27 healthy subjects were recruited for a crossover-design study that included 5 sessions administered in a randomized order (i.e., baseline and 4 different interventions). We investigated changes in pain threshold and fMRI signals modulated by: 1) VGAIT, watching a video of acupuncture previously administered on the participant's own body at baseline while imagining it being concurrently applied; 2) a VGAIT control condition, watching a video of a cotton swab touching the skin; 3) real acupuncture; and 4) sham acupuncture. Results demonstrated that real acupuncture and VGAIT significantly increased pain threshold compared with respective control groups. Imaging showed that real acupuncture produced greater activation of the insula compared with VGAIT. VGAIT produced greater deactivation at the rostral anterior cingulate cortex. Our findings demonstrate that VGAIT holds potential clinical value for pain management.

Heart rate reactivity to trauma-related imagery as a measure of PTSD symptom severity: Examining a new cohort of Veterans.

For over three decades, there has been considerable research documenting increased physiological reactivity to trauma-related stimuli as a characteristic feature of posttraumatic stress disorder (PTSD). The present study explored the potential for physiological assessment to aid in defining and validating screening criteria for the presence of significant PTSD-related symptoms in a sample of OEF/OIF/OND Veterans seeking care in a VA post-deployment health clinic. Heart rate reactivity scores during the imagining phase of the script-driven imagery paradigm were compared across groups of individuals with and without probable PTSD diagnoses, as defined by PCL-IV cutoff scores ranging from 40 to 60. Significant differences were found for groups defined by PCL-IV cutoff scores of 50 and 60, with 50 producing the largest effect size. Diagnosing PTSD is made challenging by the presence of overlapping symptoms shared with other diagnoses, as well as by the necessity for patients to accurately report their symptoms. An objective physiological measure capable of accurately differentiating individuals with and without PTSD provides potential adjunctive diagnostic and treatment information to clinicians. The present findings support the validity of physiological reactivity during SDI as a NIMH RDoC measure that can be used in research and clinical applications assessing trauma-related symptom severity.

Locus Coeruleus Activity Mediates Hyperresponsiveness in Posttraumatic Stress Disorder.

BACKGROUND: Patients with posttraumatic stress disorder (PTSD) are hyperresponsive to unexpected or potentially threatening environmental stimuli. Research in lower animals and humans suggests that sensitization of the locus coeruleus-norepinephrine system may underlie behavioral and autonomic hyperresponsiveness in PTSD. However, direct evidence linking locus coeruleus system hyperactivity to PTSD hyperresponsiveness is sparse. METHODS: Psychophysiological recording and functional magnetic resonance imaging were used during passive listening to brief, 95-dB sound pressure level, white noise bursts presented intermittently to determine whether behavioral and autonomic hyperresponsiveness to sudden sounds in PTSD is associated with locus coeruleus hyperresponsiveness. RESULTS: Participants with PTSD (n = 28) showed more eye-blink reflexes and larger heart rate, skin conductance, and pupil area responses to loud sounds (multivariate p = .007) compared with trauma-exposed participants without PTSD (n = 26). PTSD participants exhibited larger responses in locus coeruleus (t = 2.60, region of interest familywise error corrected), intraparietal sulcus, caudal dorsal premotor cortex, and cerebellar lobule VI (t ≥ 4.18, whole-brain familywise error corrected). Caudal dorsal premotor cortex activity was associated with both psychophysiological response magnitude and levels of exaggerated startle responses in daily life in PTSD participants (t ≥ 4.39, whole-brain familywise error corrected). CONCLUSIONS: Behavioral and autonomic hyperresponsiveness in PTSD may arise from a hyperactive alerting/orienting system in which processes related to attention and motor preparation localized to lateral premotor cortex, intraparietal sulcus, and posterior superior cerebellar cortex are modulated by atypically high phasic noradrenergic influences originating in the locus coeruleus.

Effects of Posture and Stimulus Spectral Composition on Peripheral Physiological Responses to Loud Sounds.

In the "loud-tone" procedure, a series of brief, loud, pure-tone stimuli are presented in a task-free situation. It is an established paradigm for measuring autonomic sensitization in posttraumatic stress disorder (PTSD). Successful use of this procedure during fMRI requires elicitation of brain responses that have sufficient signal-noise ratios when recorded in a supine, rather than sitting, position. We investigated the modulating effects of posture and stimulus spectral composition on peripheral psychophysiological responses to loud sounds. Healthy subjects (N = 24) weekly engaged in a loud-tone-like procedure that presented 500 msec, 95 dB sound pressure level, pure-tone or white-noise stimuli, either while sitting or supine and while peripheral physiological responses were recorded. Heart rate, skin conductance, and eye blink electromyographic responses were larger to white-noise than pure-tone stimuli (p's < 0.001, generalized eta squared 0.073-0.076). Psychophysiological responses to the stimuli were similar in the sitting and supine position (p's ≥ 0.082). Presenting white noise, rather than pure-tone, stimuli may improve the detection sensitivity of the neural concomitants of heightened autonomic responses by generating larger responses. Recording in the supine position appears to have little or no impact on psychophysiological response magnitudes to the auditory stimuli.

Pharmacological blockade of memory reconsolidation in posttraumatic stress disorder: three negative psychophysiological studies.

Posttraumatic stress disorder (PTSD) may involve over-consolidated emotional memories of the traumatic event. Reactivation (RP) can return a memory to an unstable state, from which it must be restabilized (reconsolidated) if it is to persist. Pharmacological agents administered while the memory is unstable have been shown to impair reconsolidation. The N-methyl-d-aspartate (NMDA) partial agonist d-cycloserine (DCS) may promote memory destabilization. In the three studies reported here, we investigated whether the ß-adrenergic blocker propranolol or the glucocorticoid (GR) antagonist mifepristone, given at the time of traumatic memory reactivation, could reduce PTSD symptoms and physiological responding during subsequent traumatic imagery. Individuals with PTSD were randomized as follows: Study One: propranolol with memory reactivation (n=10) or without reactivation (n=8); Study Two: reactivation mifepristone (n=13), non-reactivation (NRP) mifepristone (n=15), or double placebo (PL) (n=15); Study Three: reactivation mifepristone plus d-cycloserine (n=16), or two placebos (n=15). Subjects underwent memory retrieval by describing their traumatic event. A week later they engaged in script-driven traumatic mental imagery, while heart rate (HR), skin conductance (SC), and facial electromyogram (EMG) responses were measured. There were no significant group differences in physiological responsivity or change in PTSD symptoms in any of the studies. These results do not support successful blockade of reconsolidation of traumatic memories in PTSD.

Single dose propranolol does not affect physiologic or emotional reactivity to smoking cues.

BACKGROUND: Smoking cue exposure reactivates salient smoking-related memories, triggering craving to smoke, a phenomenon associated with maintenance of smoking behavior and relapse after periods of abstinence. Acute ß-adrenergic blockade with propranolol reduces physiologic reactivity during subsequent recollection of traumatic events by inhibiting reconsolidation of reactivated memories in a process called memory reconsolidation blockade. OBJECTIVE: The objective of this study is to determine whether a single dose of propranolol prior to retrieval of smoking-related memories reduces subsequent physiologic reactivity to personally salient smoking imagery scripts in current smokers. METHODS: Fifty-four overnight-abstinent, adult smokers received a single-dose propranolol or placebo prior to reactivation of smoking-related memories in a randomized, double-blind, placebo-controlled trial and resumed smoking afterward. One week later, skin conductance (SC), heart rate (HR), left corrugator electromyogram (EMG), self-reported emotional state, and craving were assessed following script-driven imagery with neutral and personalized smoking-related scripts. RESULTS: Smoking scripts were associated with increased physiologic activation (SC, HR, EMG), craving, and negative emotional state compared with neutral scripts. Propranolol did not moderate the effect of script type on any outcome. CONCLUSION: Personalized smoking script-driven imagery robustly increased physiologic activation, negative emotional state, and craving, and a single dose of propranolol prior to memory reactivation did not moderate this effect.

Trauma reactivation plus propranolol is associated with durably low physiological responding during subsequent script-driven traumatic imagery.

OBJECTIVE: In a previous, double-blind, placebo-controlled study, patients with posttraumatic stress disorder (PTSD) showed lower physiological response during script-driven traumatic imagery 1 week after receiving a single dose of propranolol given after the retrieval of a traumatic memory. We hypothesized that this effect would extend beyond 1 week using a modified treatment approach. METHOD: Twenty-eight participants with PTSD read an account of their traumatic event once weekly for 6 consecutive weeks under the influence of open-label propranolol. One week and 4-months later, skin conductance, heart rate, and left corrugator electromyogram responses were measured while participants engaged in script-driven mental imagery of their traumatic event. Results from the 22 study participants were compared with results from treated and untreated participants in a previously published trial. RESULTS: Most participants in our study were classified as non-PTSD cases at posttreatment and follow-up according to a psychophysiological discriminant function analysis. Posttreatment skin conductance and heart rate responses of the current (propranolol-treated) participants were lower than those of placebo participants from the previous study. No difference was observed between physiological responding measured posttreatment and at follow-up. CONCLUSIONS: Low physiological responding during script-driven traumatic imagery after treatment extends up to 4 months, demonstrating the durability of the treatment effect's. Limitations include the absence of a placebo-controlled group and lack of physiological baseline measures. Despite these limitations, results point to the need for future trials examining the clinical efficacy of trauma reactivation plus propranolol, as it has the potential to become a novel, cost- and time-effective treatment for PTSD.

Cortical and cerebellar modulation of autonomic responses to loud sounds.

Detecting unexpected environmental change causes modulation of autonomic activity essential for survival. Understanding the neural mechanisms associated with responses to loud sounds may provide insights into the pathophysiology of posttraumatic stress disorder (PTSD), since individuals with PTSD exhibit heightened autonomic responses to unexpected loud sounds. We combined fMRI with autonomic psychophysiological assessment to investigate central and peripheral reactivity to loud tones in 20 healthy participants. Activity in anterior insula, pregenual anterior cingulate cortex, anterior midcingulate cortex, supplementary motor area, supramarginal gyrus, and cerebellar lobules VIII-IX was associated with both tones and concomitant skin conductance responses. Since regions signaling unexpected external events modulate autonomic activity, heightened loud tone autonomic responses in PTSD may reflect sensitization of this "salience" network.

Psychophysiologic reactivity, subjective distress, and their associations with PTSD diagnosis.

Intense subjective distress and physiologic reactivity upon exposure to reminders of the traumatic event are each diagnostic features of posttraumatic stress disorder (PTSD). However, subjective reports and psychophysiological data often suggest different conclusions. For the present study, we combined data from five previous studies to assess the contributions of these two types of measures in predicting PTSD diagnosis. One hundred fifty trauma-exposed participants who were classified into PTSD or non-PTSD groups based on structured diagnostic interviews completed the same script-driven imagery procedure, which quantified measures of psychophysiologic reactivity and self-reported emotional responses. We derived four discriminant functions (DiscFxs) that each maximally separated the PTSD from the non-PTSD group using (1) psychophysiologic measures recorded during personal mental imagery of the traumatic event; (2) self-report ratings in response to the trauma imagery; (3) psychophysiologic measures recorded during personal mental imagery of another highly stressful experience unrelated to the index traumatic event; and (4) self-report ratings in response to this other stressor. When PTSD status was simultaneously regressed on all four DiscFxs, trauma-related psychophysiological reactivity was a significant predictor, but physiological reactivity resulting from the highly stressful, but not traumatic script, was not. Self-reported distress to the traumatic experience and the other stressful event were both predictive of PTSD diagnosis. Trauma-related psychophysiologic reactivity was the best predictor of PTSD diagnosis, but self-reported distress contributed additional variance. These results are discussed in relation to the Research Domain Criteria framework.

Psychophysiological assessment of PTSD: a potential research domain criteria construct.

Most research on posttraumatic stress disorder (PTSD) relies on clinician-administered interview and self-report measures to establish the presence/absence and severity of the disorder. Accurate diagnosis of PTSD is made challenging by the presence of symptoms shared with other psychopathologies and the subjective nature of patients' descriptions of their symptoms. A physiological assessment capable of reliably "diagnosing" PTSD could provide adjunctive information that might mitigate these diagnostic limitations. In the present study, we examined the construct validity of a potential psychophysiological measure of PTSD, that is, psychophysiological reactivity to script-driven imagery (SDI-PR), as measured against the current diagnostic "gold-standard" for PTSD, the Clinician-Administered PTSD Scale (CAPS). Convergent and predictive validity and stability were examined. Thirty-six individuals completed an SDI-PR procedure, the CAPS, and self-report measures of mental and physical health at their initial visit and approximately 6 months later. SDI-PR and the CAPS demonstrated excellent stability across measurement occasions. SDI-PR showed moderately strong convergent validity with the CAPS. After adjusting for self-reported depression, predictive validity for the CAPS, with regard to health sequelae, was reduced, whereas it remained mostly unchanged for SDI-PR. Findings support SDI-PR as a valid and stable measure of PTSD that captures a pathophysiologic process in individuals with PTSD. Results are discussed with regard to the research domain criteria framework.

Effect of acute posttrauma propranolol on PTSD outcome and physiological responses during script-driven imagery.

INTRODUCTION: Animal and human research suggests that the development of posttraumatic stress disorder (PTSD) may involve the overconsolidation of memories of a traumatic experience. Previous studies have attempted to use pharmaceutical agents, especially the ß-adrenergic blocker propranolol, to reduce this overconsolidation. AIMS: In this randomized, placebo-controlled study of the efficacy of propranolol in reducing the development of PTSD, we optimized dosages and conducted both psychophysiological and clinical assessments 1 and 3 months after the traumatic event. Forty-one emergency department patients who had experienced a qualifying acute psychological trauma were randomized to receive up to 240 mg/day of propranolol or placebo for 19 days. At 4 and 12 weeks post-trauma, PTSD symptoms were assessed. One week later, participants engaged in script-driven imagery of their traumatic event while psychophysiological responses were measured. RESULTS: Physiological reactivity during script-driven traumatic imagery, severity of PTSD symptoms, and the rate of the PTSD diagnostic outcome were not significantly different between the two groups. However, post hoc subgroup analyses showed that in participants with high drug adherence, at the 5-week posttrauma assessment, physiological reactivity was significantly lower during script-driven imagery in the propranolol than in the placebo subjects. CONCLUSIONS: The physiological results provide some limited support for a model of PTSD in which a traumatic conditioned response is reduced by posttrauma propranolol. However, the clinical results from this study do not support the preventive use of propranolol in the acute aftermath of a traumatic event.

Event-related potentials to auditory stimuli in monozygotic twins discordant for combat: association with PTSD.

Studies have demonstrated ERP abnormalities related to concentration difficulties in post-traumatic stress disorder (PTSD). We used an identical-twin, case-control design to investigate whether these abnormalities reflect pre-trauma vulnerability or the acquired consequence of PTSD. Vietnam combat veterans and their non-combat-exposed, identical twins completed a three-tone oddball task. Veterans with PTSD had delayed target N2 latencies compared to veterans without PTSD. In a small nonmedicated, nonsmoking subsample, veterans with PTSD also had significantly diminished target P3b amplitudes. A mixed-model, random-effects analysis on the nonmedicated, nonsmoking subsample that included the combat-unexposed co-twins showed a significant Diagnosis x Combat Exposure interaction for target P3b amplitude. Results replicate increased N2 latency and diminished P3b amplitude in PTSD and suggest that diminished P3b amplitude is an acquired condition in PTSD.

Effect of post-retrieval propranolol on psychophysiologic responding during subsequent script-driven traumatic imagery in post-traumatic stress disorder.

The beta-adrenergic blocker propranolol given within hours of a psychologically traumatic event reduces physiologic responses during subsequent mental imagery of the event. Here we tested the effect of propranolol given after the retrieval of memories of past traumatic events. Subjects with chronic post-traumatic stress disorder described their traumatic event during a script preparation session and then received a one-day dose of propranolol (n=9) or placebo (n=10), randomized and double-blind. A week later, they engaged in script-driven mental imagery of their traumatic event while heart rate, skin conductance, and left corrugator electromyogram were measured. Physiologic responses were significantly smaller in the subjects who had received post-reactivation propranolol a week earlier. Propranolol given after reactivation of the memory of a past traumatic event reduces physiologic responding during subsequent mental imagery of the event in a similar manner to propranolol given shortly after the occurrence of a traumatic event.