Commentary and Citations – Disruption of Reconsolidation as an Extinction Strategy

Methods of extinction of conditioned responses

History and theoretical foundation of SDR therapy, including evidence for efficacy of disruption of reconsolidation as a mechanism of extinction

​In the late 1990s/early 2000s, Sutherland ran four pilot studies utilising precursors to SDR Therapy for a wide range of amygdala-mediated disorders: chronic pain (two studies), clinical depression in the moderate-to-severe range, and academic and behavioural performance of children deemed “at risk”. Three of these were written up, but one of the chronic pain studies had an efficacy of 100% and was discounted as an outlier and not written up. The paper on clinical depression was submitted for peer review and published in the journal Frontier Perspectives(Sutherland, 2000), a journal of Temple University, Philadelphia.

All papers demonstrated high efficacy rates for SDR Therapy intervention, in the range of 85-90% (see “limitations” at the end of this paper), although at the time, without an overarching or well-developed hypothesis to more accurately describe the mechanism, SDR was referred to “NeuroStim”, and Sutherland proposed that efficacy was due to interruption of the smooth “replay” of the stimulus-response pair.

From 2001 to 2003 the author developed a theory of chronic pain being in most cases comprised of conditioned neurological activity rather than being nociceptive in nature. Until quite recently this theory had been broadly rejected by the medical community and is still widely regarded as novel. Today it is frequently misunderstood as “distraction”, “desensitisation”, “inhibition”, “habituation” or even as “exposure therapy”, all of which are inadequate or incomplete explanations of the neurological processes involved and the outcomes obtained.

Prior to the above pilot studies Sutherland had for some time been experimentally eliminating chronic pain in clinic clients by exposing them to highly specific conditioned stimuli associated with the pain experience, including very precise and specific idiosyncratic thoughts or perceptions suspected of being associated with (or conditioned to) the pain (language, metaphor, meaning, beliefs, etc), while simultaneously introducing disruptive sensory stimulation, both literal and imaginal.

Sutherland proposed that non-malignant chronic pain without sufficient explanatory pathology was largely due to conditioned activity in the brain and nervous system generally, and that this conditioned activity could be extinguished by disrupting the reconsolidation phase of the conditioned response, as described by Soeter et al(Soeter & Kindt, 2011), and also by Phelps and Hofmann(Phelps & Hofmann, 2019), whose work will be discussed shortly.

Although excellent results with chronic pain (and other) clients seemed to be achieved, it was appropriate and necessary to put the work to the test in formal trials. After all, it is not unusual for therapists to mis-interpret temporary results in the clinic as robust outcomes which endure. Tracey et al(Tracey et al., 2014) found that therapists tend to over-estimate their expertise, and also over-estimate effect size (if any) of the treatments they provide.

Due to lack of funding and other resources, those few clinical trials were very small (under powered, ranging from 8 to 25 participants) and not randomised, controlled, or double-blind, but consisted of treatment groups where patients were taught to self-treat. Approximately 50-60% of the groups eliminated pain entirely almost immediately, and a further 25-50% were able to reduce their pain significantly (ie, reduce their pain level more than 50%). At 2-year follow-up only half of the treatment group were contactable, but in each of those cases the results had been maintained.

Since that time, thanks to the work of many other researchers, some working to investigate the mechanisms of chronic pain, and some working to investigate disruptive (rather than inhibitory) extinction methodology for conditioned responses, Sutherland has been able to develop that theory in a way that is deeply supported by the independent research of many others.

In particular we have seen the most exciting advances in extinction of conditioned responses from scientists studying memory and emotion, in particular Soeter et al(Soeter & Kindt, 2011) and Phelps and Hofmann(Phelps & Hofmann, 2019). These researchers have independently identified what they call the “reconsolidation phase” of a conditioned response, and they have shown that where the reconsolidation phase is “disrupted”, there is a failure of the response that is permanent, ie; extinction is achieved quite rapidly and permanently.

Brunet et al(Brunet et al., 2018) also demonstrated that a pharmaceutical agent, in this case the beta blocker propranolol (which blocks physical symptoms of anxiety), given before recall of a traumatic memory, significantly diminished PTSD symptoms over a 6-week period of treatment sessions, with results maintained at 6 month follow up. Brunet currently runs a clinic providing what he calls “reconsolidation therapy”.

We note that although interesting and significant, the outcomes of Soeter’s and Phelps and Hofmann’s, and Brunet’s trials of disruption of reconsolidation are modest, but could be much greater. There are, in our view, major flaws in the methodology of these studies due to a lack of understanding of the nature of extinction of conditioned responses via disruption of reconsolidation, as follows:

Firstly when we talk about disruption of reconsolidation, this only has meaning if we are targeting a specific conditioned response. These authors failed to elicit a specific conditioned response and instead instructed participants to merely “think about”, or focus on, a past or current event. None were teasing out the myriad of conditioned stimuli that produced the array of symptomatology they sought to resolve. This approach is too vague to specifically and accurately trigger a single conditioned response and would be expected to result in a statistically significant but nevertheless modest outcome and that is exactly the type of outcome which has been achieved using this relatively unfocussed approach.

Secondly Soeter et al and Phelps and Hofmann utilised pharmaceutical disruption, injecting substances into the amygdala region of the brain, or having participants ingest a pharmaceutical preparation (eg before or immediately after recalling a memory). This is also a critical error because the timing of disruption is critical – we must have precision – and it is doubtful that simultaneous, accurate triggering and disruption of the reconsolidation phase of the conditioned response could take place with such an imprecise protocol. The disruptive factor must occur simultaneously with presentation of a precise conditioned stimulus in order to create disruption during the reconsolidation phase and thereby achieve full extinction of the conditioned response.

To put this as plainly as possible, we cannot disrupt a reconsolidation phase in the absence of that phase, in the same way that we cannot alter the volume of music unless it is actually playing.

Given these major flaws, the fact that outcomes were statistically and clinically significant in spite of them is indeed grounds for a high level of confidence.

In contrast to our and others’ hypotheses, it should be noted that the theory of disruption of reconsolidation does not have consensus even amongst those who study extinction mechanisms, primarily because they see the issue of extinction as being about a chemical process and are focussed on pharmaceutical solutions.

Inda et al(Inda, 2005) noted: “…. extinction was also dependent on protein synthesis, following the same temporal course as that followed during acquisition and consolidation. This last fact reinforces the idea that extinction is an active learning process rather than a passive event of forgetting”. We argue against this interpretation by noting that by blocking protein synthesis for a period of time over which a conditioned stimulus was presented, the extinction of the conditioned stimulus was achieved, so one could equally say that the interference with (read: disruption of) attempted reconsolidation caused extinction.

Auchter et al(Auchter et al., 2017) noted: “Fear extinction typically results in the formation of a new inhibitory memory that suppresses the original conditioned response” proposing that it was not so much an extinction of an existing conditioned response, as a learning of a new response which in some way “overwrote” or suppressed the old response. However the “extinction training” which they described as their method in this study would certainly disrupt the reconsolidation phase of the conditioned response and Auchter does not provide evidence of a new memory. In fact they themselves cite earlier studies by Misanin et al(Misanin et al., 1968) (who showed that an electric shock could disrupt reconsolidation and cause extinction), Nader et al(Nader et al., 2000) (who showed that blocking of protein synthesis during retrieval caused extinction), and Nader and Einarsson(Nader & Einarsson, 2010) who address “reconsolidation, where consolidated memories return to a transient unstable state following their retrieval, from which they must again stabilize in order to persist”.

The theory that “new learning” inhibits an old conditioned response is popular but not demonstrated to date. In the light of the mass of neurological studies around conditioning and extinction it is more logical to consider that the old conditioned response simply fails or no longer exists because reconsolidation was disrupted.

Although the theory of “disruption of reconsolidation” is regarded as novel, Pavlov had already inadvertently discovered it over 100 years ago. In his experiments on salivation rates in dogs, he had set up conditioned responses to electric shocks. In his notes he wrote of his investigation into how far he could stray from the shock site (site of conditioned stimulus) before there was a failure of the response. He found that once he got to the point of failure of response, not only did the response fail at that point, but it was effectively extinguished permanently.

Pavlov had inadvertently discovered that if he sufficiently disrupted the conditioned stimulus, he could achieve instant and permanent extinction. Unfortunately, rather than realising the enormity of his discovery, he wrote it up simply as a failure of the response, thus delaying an important advance for over 100 years.

Another well-accepted theory is the Rescorla-Wagner model(Miller et al., 1995; Siegel & Allan, 1996) of conditioning. Part of this model states that there is a specific quantity of conditioned activity that can simultaneously apply to a single conditioned stimulus. If the stimulus is “overloaded” it may collapse, and the response be extinguished. This also fits with the theory of disruption of reconsolidation of conditioned responses.

Crossely et al(Crossley et al., 2018) refers to “cognitive loading” as a method to “unlearn” conditioned neurological processes, but similarly to Soeter et al(Soeter & Kindt, 2011) and other researchers has not extrapolated from this in order to disrupt very specific stimulus-response pairs. Sutherland claims that weak, imprecise, or limited disruption of general sets of conditioned responses at play cannot provide optimal outcomes.

Similarly Bouton(Bouton, 1993, 2004) proposed that when a conditioned stimulus is repeatedly paired with stimuli unconnected with the conditioned response, extinction could be achieved. In fact this is a further clear example of disruption of reconsolidation being a highly effective extinction strategy.

On the basis of in-clinic observation, her own previous trials, and in the light of well-accepted findings of other researchers, Sutherland makes four claims around a theory of non-malignant chronic pain without explanatory pathology, including a mechanism for the elimination of pain:

  1. Non-malignant chronic pain without sufficient explanatory pathology (not acute pain or pain adequately explained by pathology) is almost always non-nociceptive and instead is generated by conditioned activity in the brain/nervous system
  2. To permanently extinguish that conditioned activity, we need to identify precise conditioned stimuli, and disrupt the reconsolidation phase of each specific, active stimulus-response pair by simultaneously and accurately presenting the stimulus for the unwanted response with other equally (or more) intense stimuli
  3. By extending the reconsolidation phase (in order to enable access to it) and simultaneously disrupting that reconsolidation via sensory stimulation, whether external/mechanical or internal/imaginal, we achieve extinction of the pain response
  4. The hyper-sensitivity of the nervous system should be similarly treated, with attention also given to resolution of issues which create or maintain an aroused state, whether negative (such as stress) or positive (such as excitement) so that the system can be given time to return to homeostasis. This includes attending to issues of comorbidity, as well as critical lifestyle issues such as sleep dysfunction, environmental stress, nutrition/hydration, activity levels, etc.

SDR (Sensory Disruption of Reconsolidation of conditioned responses) Therapy is the name given to specific techniques which have in common an action of rapidly and permanently extinguishing conditioned brain/nervous system activity by accurately disrupting the reconsolidation phase of a conditioned response. Since non-malignant chronic pain without adequate explanatory pathology is almost always entirely driven by conditioned brain activity, when we extinguish or “switch off” this activity, the pain ceases along with the activity. Sutherland claims that it can be a highly effective, very rapid and permanent way to eliminate or dramatically reduce chronic pain levels for most people.

To clarify and emphasise, the claim is that true chronic pain (ie; pain which is without sufficient explanatory pathology) almost always consists of conditioned responses of the brain and central nervous system, and that these conditioned responses can be extinguished very rapidly and permanently using sensory disruption strategies.

Conflict of interest: The author has spent the last 27 years investigating and refining SDR Therapy and currently teaches and supports psychologists wishing to implement SDR Therapy into their practices, specifically for non-malignant chronic pain without clear explanatory pathology, and generally for amygdala-mediated disorders and issues of all kinds, including depression, anxiety, phobias, addiction, trauma/PTSD, OCD, and many others.

Keywords: persistent pain, non-malignant chronic pain, chronic pain, nociception, amygdala, fMRI, mechanism of action, extinction, SDR Therapy, classical conditioning, associative and non-associative learning, disruption of reconsolidation

Recommendations for Further Research

The next research project should be a much larger examination of the impact of SDR Therapy on non-malignant chronic pain without sufficient explanatory pathology.

Following this, more extensive, randomised, controlled trials of the complete SDR program should be conducted in order to assess the final outcomes of treatment over the 16 sessions that are recommended in a staged process over 8 months. Thoroughness is essential as we know that when extinction is incomplete, there is always likelihood that recovery of the unwanted conditioned response/s can occur. Rosas et al(Rosas & Bouton, 1996) provide an excellent rationale for recovery post extinction.

However these trials should seek to avoid confounding elements which have so far plagued studies on a range of other treatment strategies and this should include testing against appropriate controls, which given the current interest in multi-disciplinary programs, should be comprehensive chronic pain treatment strategies in hospitals and pain clinics, which at least have higher efficacy rates than “treatment as usual” as seen very clearly in the Deloitte report(Painaustralia, 2019) and others(CADTH, 2011).

 

References

Auchter, A., Cormack, L. K., Niv, Y., Gonzalez-Lima, F., & Monfils, M. H. (2017). Reconsolidation-Extinction Interactions in Fear Memory Attenuation: The Role of Inter-Trial Interval Variability. Frontiers in Behavioral Neuroscience. https://doi.org/10.3389/fnbeh.2017.00002

Bouton, M. E. (1993). Context, time, and memory retrieval in the interference paradigms of pavlovian learning. Psychological Bulletin. https://doi.org/10.1037/0033-2909.114.1.80

Bouton, M. E. (2004). Context and behavioral processes in extinction. In Learning and Memory. https://doi.org/10.1101/lm.78804

Brunet, A., Saumier, D., Liu, A., Streiner, D. L., Tremblay, J., & Pitman, R. K. (2018). Reduction of PTSD symptoms with Pre-reactivation propranolol therapy: A randomized controlled trial. American Journal of Psychiatry. https://doi.org/10.1176/appi.ajp.2017.17050481

CADTH. (2011). Multidisciplinary Treatment Programs for Patients with Non-Malignant Pain: A Review of the Clinical Evidence, Cost-Effectiveness, and Guidelines. In Rapid Response Report: Summary with Critical Appraisal.

Crossley, M. J., Maddox, W. T., & Ashby, F. G. (2018). Increased cognitive load enables unlearning in procedural category learning. Journal of Experimental Psychology: Learning Memory and Cognition. https://doi.org/10.1037/xlm0000554

Inda, M. C. (2005). Acquisition, Consolidation, Reconsolidation, and Extinction of Eyelid Conditioning Responses Require De Novo Protein Synthesis. Journal of Neuroscience. https://doi.org/10.1523/jneurosci.4163-04.2005

Miller, R. R., Barnet, R. C., & Grahame, N. J. (1995). Assessment of the Rescorla-Wagner model. Psychological Bulletin. https://doi.org/10.1037/0033-2909.117.3.363

Misanin, J. R., Miller, R. R., & Lewis, D. J. (1968). Retrograde amnesia produced by electroconvulsive shock after reactivation of a consolidated memory trace. Science. https://doi.org/10.1126/science.160.3827.554

Nader, K., & Einarsson, E. Ö. (2010). Memory reconsolidation: An update. In Annals of the New York Academy of Sciences. https://doi.org/10.1111/j.1749-6632.2010.05443.x

Nader, K., Schafe, G. E., & Le Doux, J. E. (2000). Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval. Nature. https://doi.org/10.1038/35021052

Painaustralia. (2019). The Cost of Pain in Australia. March, 121.

Phelps, E. A., & Hofmann, S. G. (2019). Memory editing from science fiction to clinical practice. In Nature. https://doi.org/10.1038/s41586-019-1433-7

Rosas, J. M., & Bouton, M. E. (1996). Spontaneous recovery after extinction of a conditioned taste aversion. Animal Learning & Behavior. https://doi.org/10.3758/BF03198982

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