Modulation of naturalistic maladaptive memories using behavioural and pharmacological reconsolidation-interfering strategies: A systematic review and meta-analysis of clinical and ‘sub-clinical’ studies.

Katie H Walsh a, Ravi K Das a, Michael E Saladinb , Sunjeev K Kamboja*


Consolidated memories can undergo enduring modification through retrieval-dependent treatments that modulate reconsolidation. This has been suggested to represent a potentially transformative clinical strategy for weakening or overwriting the maladaptive memories that underlie substance use and anxiety/trauma-related disorders. However, the ability to modulate naturalistic maladaptive memories may be limited by ‘boundary conditions’ imposed on reconsolidation by the nature of these memories. As such, the true potential of ‘reconsolidation therapy’ is currently unknown. Here, we report a meta-analyses of behavioural and pharmacological studies examining retrieval-dependent modulation of reward and threat memories in (sub)clinical substance use and anxiety/trauma respectively.
Of 4936 publications assessed for eligibility, 7 studies of substance use, and 9 of anxiety (phobia) and trauma-related symptoms were included in the meta-analyses. Overall, the findings were in the predicted direction, with the majority of effect sizes favouring the ‘Retrieval + Treatment’ condition. However, the magnitude of effects depended upon the nature of the treatment type, with pharmacological interventions (relative to behavioural strategies) showing a clearer beneficial effect in studies of phobia/trauma and post-retrieval behavioural strategies, a (significantly) larger effect in substance use studies. However, high levels of heterogeneity and small sample sizes limit the strength of conclusions that can be drawn at this stage of inquiry. We hope this review will provide an impetus to address these issues in future research.

Behavioral Disruption of Memory Reconsolidation: From Bench to Bedside and Back Again

Drexler 2018

Shira Meir Drexler and Oliver T. Wolf

During the postretrieval reconsolidation “window”, memories can be disrupted, strengthened, or updated using various pharmacological and behavioral manipulations. Behavioral manipulations are more ecologically valid, thus allowing better understating of memory modification under natural conditions, but they can also be less potent compared to pharmacological interventions. In this review we present the current human and animal literature, aiming to understand the modulatory factors (i.e., task relevance, complexity, intensity) that promote reconsolidation disruption in purely behavioral means. The reviewed studies have suggested that both very simple tasks and more complex learning paradigms can be used to disrupt or update memory reconsolidation, even of stronger emotional memories. Stress exposure is a possible interference task, yet the conflicting results leave many open questions regarding its required timing and intensity. Going from bench to bedside and back again, we point to the need for more research in clinical populations to establish the therapeutic potential of reconsolidation-based treatments. Several findings from outside the laboratory offer promising leads for future research.

Om Reconsolidation:EMDR Therapy Mechanisms Explained by the Theory of Neural Cognition

EMDR/Mekanisme/Reconsolidation/ 2017 a

Stephanie Khalfa and Touzet CF

Eye Movement Desensitization and Reprocessing (EMDR) is a therapy of choice for post-traumatic stress disorder (PTSD). The mechanism of EMDR therapy is still unknown but it is hypothesized to favor memory reconsolidation. A new learning occurs relieved from the emotional load. Based on the Theory of neural Cognition (TnC), we propose an explanation of this phenomenon that implicates hebbian synaptic plasticity, i.e., long-term potentiation (LTP) and long-term depression (LTD). The new learning is mediated by the bilateral alternating stimulations (BAS) that are essential to the EMDR therapy. These repeated BAS modify the neural traces of a traumatic memory through the incorporation of newly activated cortical columns. These activated columns form a sparse coding representation of the situation called the global state of activation (GSA). Some of these added cortical activities will eventually crystallize in a column’s activation that is able to join the current GSA, making a new GSA, i.e., a stable network of activity. This process (trauma recall and BAS) is repeated several times, and each time, the activity of new columns is being added to the current GSA, until a GSAn totally cleared of its emotional content is obtained. Each GSA is a stable network of activity which gets reinforced thanks to LTP. Each time, a lessened traumatic memory is experienced. These modifications end up with a shift from the amygdalae’s involvement in the traumatic memory towards a more cognitive representation of the traumatic event, exempt from the previously associated strong negative feeling.