Month: June 2018

Extinction during reconsolidation of threat memory diminishes prefrontal cortex involvement

Mappe: Authors/D.Schiller/ 2013 a

Daniela Schiller a,1 , Jonathan W. Kanen b , Joseph E. LeDoux c,d,1 , Marie-H. Monfils e , and Elizabeth A. Phelps

Controlling learned defensive responses through extinction does not alter the threat memory itself, but rather regulates its expression via inhibitory influence of the prefrontal cortex (PFC) over amygdala. Individual differences in amygdala–PFC circuitry function have been linked to trait anxiety and posttraumatic stress disorder. This finding suggests that exposure-based techniques may actually be least effective in those who suffer from anxiety disorders. A theoretical advantage of techniques influencing reconsolidation of threat memories is that the threat representation is altered, potentially diminishing reliance on this PFC circuitry, resulting in a more persistent reduction of defensive reactions. We hypothesized that timing extinction to coincide with threat memory reconsolidation would prevent the return of defensive reactions and diminish PFC involvement. Two conditioned stimuli (CS) were paired with shock and the third was not. A day later, one stimulus (reminded CS+) but not the other (nonreminded CS+) was presented 10 min before extinction to reactivate the threat memory, followed by extinction training for all CSs. The recovery of the threat memory was tested 24 h later. Extinction of the non-reminded CS+ (i.e., standard extinction) engaged the PFC, as previously shown, but extinction of the reminded CS+ (i.e., extinction during reconsolidation) did not. Moreover, only the nonreminded CS+ memory recovered on day 3. These results suggest that extinction during reconsolidation prevents the return of defensive reactions and diminishes PFC involvement. Reducing the necessity of the PFC–amygdala circuitry to control defensive reactions may help overcome a primary obstacle in the long-term efficacy of current treatments for anxiety disorders.

 

Nonconventional interventions for chronic post-traumatic stress disorder: Ketamine, repetitive trans-cranial magnetic stimulation (rTMS), and alternative approaches

Mappe: Terapier-pr/TIMBER/Basant/2017 a

Basant Pradhan, Jessica Kluewer D’Amico, Ramkrishna Makani & Tapan Parikh

It is alarming that only 59% of those who have post-traumatic stress disorder (PTSD) respond to selective serotonin reuptake inhibitors. Many existing treatments, both pharmacological and nonpharmacological, do not directly target trauma memories that lay at the core of the PTSD pathogenesis. Notable exceptions are medications like ketamine and propranolol and trauma-focused psychotherapies like eye-movement desensitization and reprocessing therapy (developed by Shapiro) and Trauma Interventions using Mindfulness Based Extinction and Reconsolidation (TIMBER) for trauma memories (developed by Pradhan). Although the antidepressant effects of ketamine are no longer news, ketamine’s effects on treatment refractory PTSD (TR-PTSD) is a recent concept. As TR-PTSD has a marked public health burden and significant limitations in terms of treatment interventions, a thorough assessment of current strategies is required. Research to bring clarity to the underlying pathophysiology and neurobiology of TR-PTSD delineating the chemical, structural, and circuitry abnormalities will take time. In the interim, in the absence of a 1-size-fits-all therapeutic approach, pragmatically parallel lines of research can be pursued using the pharmacological and nonpharmacological treatments that have a strong theoretical rationale for efficacy. This article aims to review the current literature on interventions for PTSD, most notably ketamine, trans-cranial magnetic stimulation treatment, yoga and mindfulness interventions, and TIMBER. We present an outline for their future use, alone as well as in combination, with a hope of providing additional insights as well as advocating for developing more effective therapeutic intervention for this treatment-resistant and debilitating condition.

 

 

 

Memory Reconsolidation Interference as an Emerging Treatment for Emotional Disorders: Strengths, Limitations, Challenges, and Opportunities

 

Mappe: Boundaries 2017 a + Merenl Kindt

Tom Beckers and Merel Kindt

Experimental research on emotional memory reconsolidation interference, or the induction of amnesia for previously established emotional memory, has a long tradition, but the potential of that research for the development of novel interventions to treat psychological disorders has been recognized only recently. Here we provide an overview of basic research and clinical studies

on emotional memory reconsolidation interference. We point out specific advantages of interventions based on memory reconsolidation interference over traditional treatment for emotional disorders. We also explain how findings from basic research suggest limitations and challenges to clinical translation that may help to understand why clinical trials have met with mixed success so far and how their success can be increased. In closing, we preview new intervention approaches beyond the induction of amnesia that the phenomenon of memory reconsolidation may afford for alleviating the burden imposed by emotional memories and comment on theoretical controversies regarding the nature of memory reconsolidation.

Extinction during memory reconsolidation blocks recovery of fear in adolescents

 

Mappe: anden Rec/2015 a

D. C. Johnson & B. J. Casey

Adolescence is a time of intensified emotional experiences, during which anxiety and stress-related disorders peak. The most effective behavioral therapies for treating these disorders share exposure-based techniques as a core component. Exposure-based therapies build on the principles of fear extinction learning and involve desensitizing the individual to cues that trigger anxiety. Yet, recent evidence shows an adolescent-specific diminished capacity to extinguish fear responses, suggesting that adolescents may respond less well to exposure-based therapies than other age groups. Here we demonstrate an alternative method for blocking the recall of fear memories in adolescents, building on principles of memory reconsolidation in adults. During memory reconsolidation, a memory that is recalled becomes labile during which time it can be updated. Prior research has shown that extinction training during memory reconsolidation attenuates the recovery of fear memory in human adults and in rodents. Using this method, we show attenuation of fear memory in adolescent humans. These findings have significant implications for treating one of the most vulnerable populations to anxiety and stress related disorders – adolescents – by optimizing exposure therapy based on principles of memory reconsolidation.