Memory reconsolidation

Clients with posttraumatic stress disorder (PTSD) represent a significant problem to the US Military and Veterans Administration. Upwards of 30 percent go on to lifelong chronicity with or without treatment (Kessler, Sonnega, Bromet, Hughes, & Nelson, 1995). Most mainline treatments are not meeting the needs of our veterans and active duty warriors. The current case study describes four individuals previously diagnosed with PTSD who volunteered for treatment in a waitlist RCT of a brief, non-traumatizing intervention, Reconsolidation of Traumatic Memories (RTM). These individuals completed five 90-min sessions of RTM. In the larger study 96% (25/26) of treated clients no longer met diagnostic criteria for PTSD at the end of treatment, with these gains maintained at 6-and 26-week posttreatment. Implications for delivery of RTM and its further investigation are discussed.

The posttraumatic stress disorder (PTSD) condition is a systemic neuroinflammatory state that emanates from a failure to recover from traumatic occurrence(s). Major complications associated with PTSD include problems with impulse control and issues related to verbal and physical outbursts of anger and rage. The Veteran's Administration (VA) projects a post-9/11 veteran population of around 3.5 million by 2019. Emotional problems are prevalent among combat service members and veterans with about half of the group suffering from various symptoms of PTSD. Three in four among them report they are reliving traumas in the form of flashbacks and nightmares. Current mental health treatments have not fully remediated the negative impact that results from PTSD. We present a case study of a novel and transformative treatment approach called Reconsolidation Enhancement by Stimulation of Emotional Triggers (RESET) Therapy. The intervention uses binaural sound to unlock the memory reconsolidation process, thereby releasing the emotional component of experienced trauma. RESET Therapy offers a compelling therapeutic adjunct to the practicing biofeedback/neurofeedback clinician, who is under constant pressure to deliver interventions that are rapid, tolerable, and cost-effective. Additionally, the treatment spares the therapist from repeated exposures to the raw limbic activity of traumatized patients, thereby minimizing the potential for vicarious traumatization.

Addicted individuals are highly susceptible to relapse when exposed to drug-associated conditioned stimuli (CSs; “drug cues”) even after extensive periods of abstinence. Until recently, these maladaptive emotional drug memories were believed to be permanent and resistant to change. The rediscovery of the phenomenon of memory reconsolidation—by which retrieval of the memory can, under certain conditions, destabilize the previously stable memory before it restabilizes in its new, updated form—has led to the hypothesis that it may be possible to disrupt the strong maladaptive drug-memories that trigger a relapse. Furthermore, recent work has suggested that extinction training “within the reconsolidation window” may lead to a long-term reduction in relapse without the requirement for pharmacological amnestic agents. However, this so-called “retrieval-extinction” effect has been inconsistently observed in the literature, leading some to speculate that rather than reflecting memory updating, it may be the product of facilitation of extinction. In this mini review article, we will focus on factors that might be responsible for the retrieval-extinction effects on preventing drug-seeking relapse and how inter-individual differences may influence this therapeutically promising effect. A better understanding of the psychological and neurobiological mechanisms underpinning the “retrieval-extinction” paradigm, and individual differences in boundary conditions, should provide insights with the potential to optimize the translation of “retrieval-extinction” to clinical populations.

Recently, it has become clear that retrieval (i.e., reactivation) of consolidated memories may return these memories into a labile state before they are restored into long-term memory ('reconsolidation'). Using behavioral manipulations, reactivated memories can be disrupted via the mechanism of novel learning. In the present study, we investigated whether changing a strong memory during reconsolidation depends on the strength of novel learning. To test this, participants (N = 144) in six groups acquired a relatively strong memory on Day 1 by viewing and recalling a series of pictures three times. On Day 8, these pictures were reactivated in three groups, and they were not reactivated in the other three groups. Then, participants viewed and recalled new pictures once (weak new learning) or three times (strong new learning), or they did not learn any new pictures. On Day 9, participants performed a recognition test in which their memory for Day 1 pictures was assessed. Two main results are noted. First, the groups that reactivated pictures from Day 1 and received weak or strong new learning did not differ in memory performance. Second, these two groups consistently performed similar to groups that controlled for new learning without reactivation. Because these results contradict what was expected based on the reconsol-idation hypothesis, we discuss possible explanations and implications.

Reconsolidation has been defined as the process of memory stabilization after retrieval involving, among others, gene expression regulation and post-translational modifications. Many of these mechanisms are shared with memory consolidation. Here, we studied hippocampal ERK participation on memory reconsolidation of an inhibitory avoidance task in CF-1 mice. We found a retrieval-induced cytosolic ERK2 activation in the hippocampus (HIP) 15min after memory reactivation, and an inhibition at 45min. PD098059, a MEK1/2 (MAPK/ERK kinase) inhibitor, administered in the HIP immediately after retrieval impaired memory in a dose-dependent fashion. However, infusions of the highest dose of PD098059 performed 40min after retrieval enhanced memory in mice trained with a weaker footshock. These results suggest for the first time that ERK2 is involved in memory reconsolidation in a biphasic fashion. Furthermore, the inhibition of ERK could either impair or enhance mice performance depending on ERK state of activation.

We propose a model of memory reconsolidation that can output new sentences with additional meaning after refining information from input sentences and integrating them with related prior experience. Our model uses available technology to first disambiguate the meanings of words and extracts information from the sentences into a structure that is an extension to semantic networks. Within our long-term memory

Early life experiences program lifelong responses to stress. In agreement, resilience and vulnerability to psychopathologies, such as posttraumatic stress disorder (PTSD), have been suggested to depend on the early background. New therapies have targeted memory reconsolidation as a strategy to modify the emotional valence of traumatic memories. Here, we used animal models to study the molecular mechanism through which early experiences may later affect aversive memory reconsolidation. Handling (H)-separation of pups from dams for 10 minor maternal separation (MS)-3-h separation-were performed from PDN1-10, using non-handled (NH) litters as controls. Adult males were trained in a contextual fear conditioning (CFC) task; 24 h later, a short reactivation session was conducted in the conditioned or in a novel context, followed by administration of midazolam 3 mg/kg i.p. (mdz), known to disturb reconsolidation, or vehicle; a test session was performed 24 h after. The immunocontent of relevant proteins was studied 15 and 60 min after memory reactivation in the dorsal hippocampus (dHc) and basolateral amygdala complex (BLA). Mdz-treated controls (NH) showed decreased freezing to the conditioned context, consistent with reconsolidation impairment, but H and MS were resistant to labilization. Additionally, MS males showed increased freezing to the novel context, suggesting fear generalization; H rats showed lower freezing than the other groups, in accordance with previous suggestions of reduced emotionality facing adversities. Increased levels of Zif268, GluN2B, β-actin and polyubiquitination found in the BLA of all groups suggest that memory reconsolidation was triggered. In the dHc, only NH showed increased Zif268 levels after memory retrieval; also, a delay in ERK1/2 activation was found in H and MS animals. We showed here that reconsolidation of a contextual fear memory is insensitive to interference by a GABAergic drug in adult male rats exposed to different neonatal experiences; surprisingly, we found Frontiers in Molecular Neuroscience | www.frontiersin.org 1 May 2019 | Volume 12 | Article 134

Objective: PTSD in female veterans and service members (SM)s is understudied, and new, effective treatments for PTSD are needed. Reconsolidation of Traumatic Memories (RTM) is a brief, manualized treatment for PTSD previously piloted in RCTs of male veterans and SMs. Here we examine RTM's effect on military women with PTSD. Methods: We report a waitlist RCT using 30 military-connected females with DSM IV-TR PTSD diagnoses, including current-month nightmares or flashbacks. Trauma types include Military Sexual Trauma (MST), other sexual traumas, combat, and other trauma types. Participants were randomized to treatment or waitlist. Of those enrolled, 97% completed treatment. Independent psychometricians, blinded to treatment condition, evaluated participants at intake, post-wait, and two weeks post. The clinician took follow-up measures at six months and one year. The primary measure was the PTSD Symptom Scale-Interview (PSS-I). The secondary measure was the PTSD Checklist (PCL). Participants received up to three 120-minute sessions of RTM. Results: RTM eliminated intrusive symptoms and significantly decreased symptom scale ratings in 90% (n = 27) of participants, versus 0% of controls (p < 0.001). Two-week treatment group PSS-I scores dropped 33.9 points versus 3.9 points for post-wait controls (g = 3.7; 95% CI [2.5, 4.8]; p < 0.001). Treatment results were stable to 1 year. Conclusions: RTM effectively treated PTSD, independent of trauma source in female SMs and veterans effectively replicating previous results in male populations. Further research is recommended. Clinical Impact Statement. This study presents The Reconsolidation of Traumatic Memories Protocol (RTM for Post Traumatic Stress Disorder and tests its effectiveness for female veterans and active duty service members. The treatment is brief, non-traumatizing, and its high rates of PTSD remission are maintained for at least one year. The PTSD-diagnosed participants included many with military sexual traumas. The results for all participants were comparable to male veterans and service members in two other trials. |