Experiential feeling therapy addressing the pain of the lack of love.
This 2016 German review was of the memory characteristics of immune cells:
“Innate immune memory has likely evolved as an ancient mechanism to protect against pathogens. However, dysregulated processes of immunological imprinting mediated by trained innate immunity may also be detrimental under certain conditions.
Evidence is rapidly accumulating that innate immune cells can adopt a persistent pro-inflammatory phenotype after brief exposure to a variety of stimuli, a phenomenon that has been termed ‘trained innate immunity.’ The epigenome of myeloid (progenitor) cells is presumably modified for prolonged periods of time, which, in turn, could evoke a condition of continuous immune cell over-activation.”
The reviewers focused on the particular example of atherosclerosis, although other examples were discussed of epigenetic remodeling to acquire immune memory:
“In the last ten years, several novel non-traditional risk factors for atherosclerosis have been identified that are all associated with activation of the immune system. These include chronic inflammatory diseases such as:
- rheumatoid arthritis,
- psoriatic arthritis, and
- ankylosing spondylitis,
as well as infections with bacteria or viruses.”
The reviewers also discussed diet, mainly of various diets’ negative effects. On the positive side, I was interested to see a study referenced that used a common dietary supplement:
“Pathway analysis of the promoters that were potentiated by β-glucan identified several innate immune and signaling pathways upregulated in trained cells that are responsible for the induction of trained immunity.”
Other research into the epigenetic remodeling of immune system memory includes:
- Chronic pain causes epigenetic changes in the brain and immune system
- Epigenetic regulation of natural killer cells
- Assessing epigenetic origins of allergies and asthma
http://www.sciencedirect.com/science/article/pii/S1044532316300185 “Long-term activation of the innate immune system in atherosclerosis”
This 2016 Israeli human study used whole-head magnetoencephalography (MEG) to study pain perception in military veterans:
“Our findings demonstrate alterations in pain perception following extreme pain exposure, chart the sequence from automatic to evaluative pain processing, and emphasize the importance of considering past experiences in studying the neural response to others’ states.
Differences in brain activation to ‘pain’ and ‘no pain’ in the PCC [posterior cingulate cortex] emerged only among controls. This suggests that prior exposure to extreme pain alters the typical brain response to pain by blurring the distinction between painful and otherwise identical but nonpainful stimuli, and that this blurring of the ‘pain effect’ stems from increased responses to ‘no pain’ rather than from attenuated response to pain.”
- “The pain-exposed participants showed posttraumatic symptoms, which may also be related to the observed alterations in the brain response to pain.
- We did not include pain threshold measurements. However, the participants’ sensitivity to experienced pain may have had an effect on the processing of observed pain.
- The regions of interest for the examination of pain processing in the pain-exposed group were defined on the basis of the results identified in the control group.
- We did not detect pain-related activations in additional regions typically associated with pain perception, such as the anterior insula and ACC. This may be related to differences between the MEG and fMRI neuroimaging approaches.”
The subjects self-administered oxytocin or placebo per the study’s design. However:
“We chose to focus on the placebo condition and to test group differences at baseline only, in light of the recent criticism on underpowered oxytocin administration studies, and thus all following analyses are reported for the placebo condition.”
A few questions:
- If observing others’ pain caused “increased responses to ‘no pain’,” wouldn’t the same effect or more be expected from experiencing one’s own pain?
- If there’s evidence for item 1, then why aren’t “increased responses to ‘no pain'” of affected people overtly evident in everyday life?
- If item 2 is often observed, then what are the neurobiological consequences for affected people’s suppression of “increased responses to ‘no pain’?”
- Along with the effects of item 3, what may be behavioral, emotional, and other evidence of this suppressed pain effect?
- What would it take for affected people to regain a normal processing of others’ “‘pain’ and ‘no pain’?”
https://www.researchgate.net/publication/299546838_Prior_exposure_to_extreme_pain_alters_neural_response_to_pain_in_others “Prior exposure to extreme pain alters neural response to pain in others” Thanks to one of the authors, Ruth Feldman, for providing the full study
This 2016 Swiss review of enduring memories demonstrated what happens when scientists’ reputations and paychecks interfered with them recognizing new research and evidence in their area but outside their paradigm: “A framework containing the basic assumptions, ways of thinking, and methodology that are commonly accepted by members of a scientific community.”
1. Most of the cited references were from decades ago that established these paradigms of enduring memories. Fine, but the research these paradigms precluded was also significant.
2. All of the newer references were continuations of established paradigms. For example, a 2014 study led by one of the reviewers found:
“Successful reconsolidation-updating paradigms for recent memories fail to attenuate remote (i.e., month-old) ones.
Recalling remote memories fails to induce histone acetylation-mediated plasticity.”
The researchers elected to pursue a workaround of the memory reconsolidation paradigm when the need for a new paradigm of enduring memories confronted them directly.
3. None of the reviewers’ calls for further investigations challenged existing paradigms. For example, when the reviewers suggested research into epigenetic regulation of enduring memories, they somehow found it best to return to 1984, a time when dedicated epigenetics research had barely begun:
“Whether memories might indeed be ‘coded in particular stretches of chromosomal DNA’ as originally proposed by Crick [in 1984] and if so what the enzymatic machinery behind such changes might be remain unclear. In this regard, cell population-specific studies are highly warranted.”
As an example of relevant research the review failed to consider, the 2015 Northwestern University study I curated in A study that provided evidence for basic principles of Primal Therapy went outside existing paradigms to research state-dependent memories:
“If a traumatic event occurs when these extra-synaptic GABA receptors are activated, the memory of this event cannot be accessed unless these receptors are activated once again.
It’s an entirely different system even at the genetic and molecular level than the one that encodes normal memories.”
What impressed me about the study was the obvious nature of its straightforward experimental methods. Why hadn’t other researchers used the same methods decades ago? Doing so could have resulted in dozens of informative follow-on study variations by now, which is my point in item 1 above.
The 2015 French What can cause memories that are accessible only when returning to the original brain state? was another relevant but ignored study that supported state-dependent memories:
“Posttraining/postreactivation treatments induce an internal state, which becomes encoded with the memory, and should be present at the time of testing to ensure a successful retrieval.”
The review also showed the extent to which historical memory paradigms depended on the subjects’ emotional memories. When it comes to human studies, though, designs almost always avoid studying emotional memories.
It’s clearly past time to Advance science by including emotion in research.
http://www.hindawi.com/journals/np/2016/3425908/ “Structural, Synaptic, and Epigenetic Dynamics of Enduring Memories”
A friend of mine sent a link to this TED talk yesterday. The speaker inspired my friend to change their life along the speaker’s guidelines:
“The very act of doing the thing that scared me undid the fear.
That feeling, you can’t help but strive for greatness at any cost.
The more I work to be successful, the more I need to work.”
I wasn’t similarly inspired. Evidence doesn’t support that a fear memory is undone by behavior that covers it over and tamps it down. What I saw expressed in the TED talk was an exhausting pursuit of substitutes for feeling loved.
This February 18 blog post by Dr Arthur Janov framed the TED talk in the context that I understood the speaker:
“Most of us thought that once we choose a profession and follow it and succeed at it, becoming an expert and well known, that would be fulfilling. We would feel like a success.
Success is not a feeling, loved is.
Fame is other people’s idea of success; it is in a way their feeling…admiration, humbling, important, etc.
And why does the person, even most accomplished, never feel satisfied nor fulfilled?”
What do you feel is the appropriate context of the TED talk? What do you think are likely outcomes of a person following the speaker’s guidelines?
- How do our brains internally represent the external world?
- How did we learn what we know?
- How do we forget or disregard what we’ve learned?
- What keeps us from acquiring and learning newer or better information?
- What affects how we pay attention to our environments?
- How do our various biochemical states affect our perceptions, learning, experiences, and behavior?
- How do these factors in turn affect our biology?
- Why do we do what we do?
- How is our behavior affected by our experiences?
- How did we become attracted and motivated toward what we like?
- How do we develop expectations?
- Why do we avoid certain situations?
Not to lose sight of:
- How do the contexts affect all of the above?
- What happens over time to affect all of the above?
This 2015 UCLA paper reviewed the above questions from the perspective of Pavlovian conditioning:
“The common definition of Pavlovian conditioning, that via repeated pairings of a neutral stimulus with a stimulus that elicits a reflex the neutral stimulus acquires the ability to elicit that the reflex, is neither accurate nor reflective of the richness of Pavlovian conditioning. Rather, Pavlovian conditioning is the way we learn about dependent relationships between stimuli.
Pavlovian conditioning is one of the few areas in biology in which there is direct experimental evidence of biological fitness.”
The most important question unanswered by the review is:
- How can its information be used to help humans?
How does Pavlov conditioning answer:
- What can a human do about the thoughts, feelings, behavior, epigenetic effects – the person – that they’ve been shaped into?
One relevant hypothesis of Dr. Arthur Janov’s Primal Therapy is that a person will continue to be their conditioned self until they address the sources of their pain. A corollary is that addressing symptoms will seldom address causes.
How could it be otherwise? A problem isn’t cured by ameliorating its effects.
As an example, the review pointed out in a section about fear extinction that it doesn’t involve unlearning. Fear extinction instead inhibits the symptoms of fear response. The fear memory is still intact, awaiting some other context to be reactivated and expressed.
How can that information be used to help humans?
- Is inhibiting the symptoms and leaving the fear memory in place costless with humans?
- Or does this practice have both potential and realized adverse effects?
- Where’s the human research on methods that may directly address a painful emotional memory?
http://cshperspectives.cshlp.org/content/8/1/a021717.full “The Origins and Organization of Vertebrate Pavlovian Conditioning”
This 2016 New York rodent study found:
“By using unbiased and whole-brain imaging techniques, we uncover a number of cortical and subcortical brain structures that have lower activity in the animals showing helplessness than in those showing resilience following the LH [learned helplessness] procedure. We also identified the LC [locus coeruleus] as the sole subcortical area that had enhanced activity in helpless animals compared with resilient ones.
Some of the brain areas identified in this study – such as areas in the mPFC [medial prefrontal cortex], hippocampus, and amygdala – have been previously implicated in clinical depression or depression-like behavior in animal models. We also identified novel brain regions previously not associated with helplessness. For example, the OT [olfactory tubercle], an area involved in odor processing as well as high cognitive functions including reward processing, and the Edinger–Westphal nucleus containing centrally projecting neurons implicated in stress adaptation.
The brains of helpless animals are locked in a highly stereotypic pathological state.”
Concerning the study’s young adult male subjects:
“To achieve a subsequent detection of neuronal activity related to distinct behavioral responses, we used the c-fosGFP transgenic mice expressing c-FosGFP under the control of a c-fos promoter. The expression of the c-fosGFP transgene has been previously validated to faithfully represent endogenous c-fos expression.
Similar to wild-type mice, approximately 22% (32 of 144) of the c-fosGFP mice showed helplessness.”
The final sentence of the Introduction section:
“Our study..supports the view that defining neuronal circuits underlying stress-induced depression-like behavior in animal models can help identify new targets for the treatment of depression.”
Helplessness is both a learned behavior and a cumulative set of experiences during every human’s early life. Therapeutic approaches to detrimental effects of helplessness can be different with humans than with rodents in that we can address causes.
The researchers categorized activity in brain circuits as causal in the Discussion section:
“Future studies aimed at manipulating these identified neural changes are required for determining whether they are causally related to the expression of helplessness or resilience.”
Studying whether or not activity in brain circuits induces helplessness in rodents may not inform us about causes of helplessness in humans. Our experiences are often the ultimate causes of helplessness effects. Many of our experiential “neural changes” are only effects, as demonstrated by this and other studies’ induced phenotypes such as “Learned Helplessness” and “Prenatally Restraint Stressed.”
Weren’t the researchers satisfied that the study confirmed what was known and made new findings? Why attempt to extend animal models that only treat effects to humans, as implied in the Introduction above and in the final sentence of the Discussion section:
“Future studies aimed at elucidating the specific roles of these regions in the pathophysiology of depression as well as serve as neural circuit-based targets for the development of novel therapeutics.”
http://journal.frontiersin.org/article/10.3389/fncir.2016.00003/full “Whole-Brain Mapping of Neuronal Activity in the Learned Helplessness Model of Depression” (Thanks to A Paper a Day Keeps the Scientist Okay)