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

Wood, N.; Rosasco, Maria L.; Surís, Alina; Spring, Justin D.; Marin, Marie‐France; Lasko, Natasha B.; Goetz, Jared M; Fischer, Avital; Orr, Scott P.; Pitman, Roger K.

doi:10.1016/j.psychres.2014.09.005

Cited by 160 publications

(133 citation statements)

References 33 publications

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“…Increased salience network connectivity has also been documented in a host of anxiety disorders, notably including PTSD (Peterson et al, 2014). Furthermore, propranolol-another pharmacological agent investigated as an adjunct for PTSD therapy (Brunet et al, 2008, but see Wood et al, 2015;Steenen et al, 2016)-decreases connectivity within the salience network (Hermans et al, 2011). Thus, it is worth considering whether action at the salience network might be an important component of the mechanism by which MDMA operates in MDMA-assisted psychotherapy for PTSD (Mithoefer et al, 2011;Mithoefer et al, 2012;Oehen et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Altered Insula Connectivity under MDMA

Walpola

Nest

Roseman

et al. 2017

Neuropsychopharmacol

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Recent work with noninvasive human brain imaging has started to investigate the effects of 3,4-methylenedioxymethamphetamine (MDMA) on large-scale patterns of brain activity. MDMA, a potent monoamine-releaser with particularly pronounced serotonin-releasing properties, has unique subjective effects that include: marked positive mood, pleasant/unusual bodily sensations and pro-social, empathic feelings. However, the neurobiological basis for these effects is not properly understood, and the present analysis sought to address this knowledge gap. To do this, we administered MDMA-HCl (100 mg p.o.) and, separately, placebo (ascorbic acid) in a randomized, doubleblind, repeated-measures design with twenty-five healthy volunteers undergoing fMRI scanning. We then employed a measure of global resting-state functional brain connectivity and follow-up seed-to-voxel analysis to the fMRI data we acquired. Results revealed decreased right insula/salience network functional connectivity under MDMA. Furthermore, these decreases in right insula/salience network connectivity correlated with baseline trait anxiety and acute experiences of altered bodily sensations under MDMA. The present findings highlight insular disintegration (ie, compromised salience network membership) as a neurobiological signature of the MDMA experience, and relate this brain effect to trait anxiety and acutely altered bodily sensations-both of which are known to be associated with insular functioning.

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Section: Discussionmentioning

confidence: 99%

Altered Insula Connectivity under MDMA

Walpola

Nest

Roseman

et al. 2017

Neuropsychopharmacol

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“…Drug craving (Xue et al 2012;Saladin et al 2013) and PTSD (Brunet et al 2008;Menzies 2012) are two clinical conditions, in which it has been reported that targeting their underlying maintaining mechanisms through reconsolidation can lead to some clinical improvement . However, the results of other studies indicate that the practical usefulness of blocking reconsolidation in the treatment of trauma requires further exploration Wood et al 2015). containing N-methyl-D-aspartate (NMDA) receptors are activated for the memory to go from a consolidated inactive state (IS) to a labile active state (AS) (gray curved arrow).…”

Section: Potential Clinical Implicationsmentioning

confidence: 99%

Reconsolidation and the Dynamic Nature of Memory

Nader

2015

Cold Spring Harb Perspect Biol

154

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Memory reconsolidation is the process in which reactivated long-term memory (LTM) becomes transiently sensitive to amnesic agents that are effective at consolidation. The phenomenon was first described more than 50 years ago but did not fit the dominant paradigm that posited that consolidation takes place only once per LTM item. Research on reconsolidation was revitalized only more than a decade ago with the demonstration of reconsolidation in a well-defined behavioral protocol (auditory fear conditioning in the rat) subserved by an identified brain circuit (basolateral amygdala). Since then, reconsolidation has been shown in many studies over a range of species, tasks, and amnesic agents, and cellular and molecular correlates of reconsolidation have also been identified. In this review, I will first define the evidence on which reconsolidation is based, and proceed to discuss some of the conceptual issues facing the field in determining when reconsolidation does and does not occur. Last, I will refer to the potential clinical implications of reconsolidation.

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“…Golkar, Bellander, Olsson, & Öhman, 2012; Hardwicke, Taqi, & Shanks, 2016; Kindt & Soeter, 2013; Soeter & Kindt, 2011; Wichert et al, 2011) or pharmacological manipulations (e.g. Bos, Beckers, & Kindt, 2014; Wood et al, 2015). The study of Hardwicke et al (2016) makes a particularly strong case against reconsolidation effects in humans, because it attempted to directly and conceptually replicate the results of a study that has been frequently referred to as a convincing demonstration of human reconsolidation in procedural memory (Walker, Brakefield, Hobson, & Stickgold, 2003), but was unsuccessful in seven experiments.…”

Section: Discussionmentioning

confidence: 99%

“…which may manifest itself as less intrusions in PTSD). Focusing on novel behavioural interventions is especially important, because recent studies show that frequently used pharmacological agents do not consistently affect reconsolidation in patients and healthy participants (Wood et al, 2015; for a meta-analysis see Lonergan, Olivera-Figueroa, Pitman, & Brunet, 2013). Given the potential of reconsolidation manipulations in psychological treatments, an important question is whether changing memories during reconsolidation by use of behavioural manipulations is a finding that can be replicated reliably.…”

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confidence: 99%

Modification of episodic memories by novel learning: a failed replication study

Schie

Veen

Hout

et al. 2017

European Journal of Psychotraumatology

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Background: After reactivation, memories can become unstable and sensitive to modification before they are restored into long-term memory. Using behavioural manipulations, reactivated memories may be disrupted via the mechanism of interference (i.e. novel learning). In a laboratory study, Wichert et al. (2013a) showed that new learning after reactivation changed episodic memory, while new learning alone or reactivation alone did not. Objective: Given the potential clinical application of such a procedure in trauma-focused psychological treatments, such as CBT or EMDR, the aim of this study was to replicate Wichert et al. Method: On Day 1, participants (N = 96) viewed and recalled a series of emotional and non-emotional pictures. Then, participants were randomized to one of four groups. One week later, on Day 8, Group 1 reactivated the previously learned pictures and learned new pictures. To control for specific effects of reactivation or new learning, Group 2 only reactivated the previously learned pictures, and Group 3 only learned new pictures. Group 4 received no reactivation and no new learning. On Day 9, all groups indicated for each picture out of a series whether they had seen it on Day 1. Results: The data were analysed using Bayesian hypothesis testing, which allows for quantifying the evidence in favour of the alternative and the null hypothesis. In general, results showed that Group 1 recognized fewer pictures from Day 1 compared to Groups 2 and 4 on Day 9. However, the expected difference between new learning following reactivation (i.e. Group 1) and new learning alone (i.e. Group 3) was not substantially supported by the data for any of our dependent measures. Conclusions: We replicated some of the findings by Wichert et al., but did not find substantial support for the critical difference between new learning following reactivation and new learning alone.

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

Cited by 160 publications

References 33 publications

Altered Insula Connectivity under MDMA

Altered Insula Connectivity under MDMA

Reconsolidation and the Dynamic Nature of Memory

Modification of episodic memories by novel learning: a failed replication study

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