Differing approaches to a life wasted on beliefs

Let’s start by observing that people structure their lives around beliefs. As time goes on, what actions would a person have taken to ward off non-confirming evidence?

One response may be that they would engage in ever-increasing efforts to develop new beliefs that justified how they spent their precious life’s time so far.

Such was my take on the embedded beliefs in https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5684598/pdf/PSYCHIATRY2017-5491812.pdf “Epigenetic and Neural Circuitry Landscape of Psychotherapeutic Interventions”:

“Animal models have shown the benefits of continued environmental enrichment (EE) on psychopathological phenotypes, which carries exciting translational value.

This paper posits that psychotherapy serves as a positive environmental input (something akin to EE).”

The author conveyed his belief that wonderful interventions were going to happen in the future, although, when scrutinized, most human studies have demonstrated null effects of psychotherapy interventions on causes. Without sound evidence that treatments affect causes, this belief seemed driven by something else.

The author saw the findings of research like A problematic study of oxytocin receptor gene methylation, childhood abuse, and psychiatric symptoms as supporting external interventions to tamp down symptoms of patients’ presenting problems. Did any of the paper’s 300+ citations concern treatments where patients instead therapeutically addressed their problems’ root causes?

For an analogous religious example, a person’s belief caused him to spend years of his life trying to convince men to act so that they could get their own planet after death, and trying to convince women to latch onto men who had this belief. A new and apparently newsworthy belief developed from his underlying causes:

“The founder and CEO of neuroscience company Kernel wants “to expand the bounds of human intelligence”. He is planning to do this with neuroprosthetics; brain augmentations that can improve mental function and treat disorders. Put simply, Kernel hopes to place a chip in your brain.

He was raised as a Mormon in Utah and it was while carrying out two years of missionary work in Ecuador that he was struck by what he describes as an “overwhelming desire to improve the lives of others.”

He suffered from chronic depression from the ages of 24 to 34, and has seen his father and stepfather face huge mental health struggles.”

https://www.theguardian.com/small-business-network/2017/dec/14/humans-20-meet-the-entrepreneur-who-wants-to-put-a-chip-in-your-brain “Humans 2.0: meet the entrepreneur who wants to put a chip in your brain”

The article stated that the subject had given up Mormonism. There was nothing to suggest, though, that he had therapeutically addressed any underlying causes for his misdirected thoughts, feelings, and behavior. So he developed other beliefs instead.

What can people do to keep their lives from being wasted on beliefs? As mentioned in What was not, is not, and will never be:

“The problem is that spending our time and efforts on these ideas, beliefs, and behaviors won’t ameliorate their motivating causes. Our efforts only push us further away from our truths, with real consequences: a wasted life.

The goal of the therapeutic approach advocated by Dr. Arthur Janov’s Primal Therapy is to remove the force of the presenting problems’ motivating causes. Success in reaching this goal is realized when patients become better able to live their own lives.


Experience-induced transgenerational programming of neuronal structure and functions

The second paper of Transgenerational epigenetic inheritance week was a 2017 German/Israeli review focused on:

“The inter- and transgenerational effects of stress experience prior to and during gestation..the concept of stress-induced (re-)programming in more detail by highlighting epigenetic mechanisms and particularly those affecting the development of monoaminergic transmitter systems, which constitute the brain’s reward system..we offer some perspectives on the development of protective and therapeutic interventions in cognitive and emotional disturbances resulting from preconception and prenatal stress.”

The reviewers noted that human studies have difficulties predicting adult responses to stress that are based on gene expression and early life experience. Clinical studies that experimentally manipulate the type, level and timing of the stressful exposure aren’t possible. Clinical studies are also predicated on the symptoms being recognized as disorders and/or diseases.

The researchers noted difficulties in human interventions and treatments. Before and during pregnancy, and perinatal periods are where stress effects are largest, but current human research hasn’t gathered sufficient findings to develop practical guidelines for early intervention programs.

I’m not persuaded by arguments that cite the difficulties of performing human research on transgenerational epigenetic inheritance. There are overwhelming numbers of people who have obvious stress symptoms: these didn’t develop in a vacuum.


  • Design human studies to test what’s known from transgenerational epigenetic inheritance animal studies that will include documenting the subjects’ detailed histories with sufficient biometric samples and data obtained from their lineage.
  • Induce the subjects to at least temporarily avoid what’s harmful for them and/or the offspring, in favor of what’s beneficial.
  • Document the subjects’ actions with history and samples.

I acknowledge that economic incentives may not be enough to get people to participate. I’m familiar with a juvenile sickle-cell study that didn’t get enough subjects despite offering free transportation and hundreds of dollars per visit. The main problem seemed to be that the additional income would be reported and threaten the caregivers’ welfare benefits.

Stop whining that your jobs are difficult, researchers. Society doesn’t owe you a job. Earn it – get yourself and the people in your organization motivated to advance science.

http://www.sciencedirect.com/science/article/pii/S014976341630731X “Experience-induced transgenerational (re-)programming of neuronal structure and functions: Impact of stress prior and during pregnancy” (not freely available)

Does living near a forest keep your amygdala healthier?

A thought-provoking post from A Paper a Day Keeps the Scientist Okay entitled “Living Near a Forest Keeps Your Amygdala Healthier” referenced a 2017 German human study which found:

“..a relationship between place of residence and brain health: those city dwellers living close to a forest were more likely to show indications of a physiologically healthy amygdala structure and were therefore presumably better able to cope with stress.”

The researchers accomplished the imperative of meeting the study’s stated objective:

“We set out to identify and characterize the geographical elements of a city that are associated with these brain structures following a suggestion by Kennedy and Adolph that studies should begin to derive recommendations for urban planning and architecture.

The results of our study may suggest that forests in and around the cities are a valuable resource that should be promoted. However future longitudinal studies are needed to investigate the causal directionality of the effect in order to disentangle whether more forest in ones habitat facilitates brain structural integrity or potentially those people with better brain structural integrity choose to live closer to forests. Moreover we need to investigate whether living close to the forest is associated with an absence of risk factors such as noise, air pollution or stress and thereby has beneficial effects or whether the forest itself constitutes a salutary factor that promotes well-being.”

A major limitation of the study’s methodology that wasn’t noted by the researchers was the intentional non-use of an available data source. Referring to Do we need to study the brain to understand the mind? posted earlier this week:

“..self-report is still the gold standard for assessing emotional experience and the contents of thought..isn’t it easier just to ask?”

The researchers put the forest before the trees, and designed a study that didn’t ask the subjects important questions such as why they lived where they lived. The researchers inferred sketchy fMRI-geography associations because they didn’t solicit relevant primary information via individual self-reports.

I imagined myself as one of the study’s subjects. I don’t live in Berlin, and I’m not part of the selected cohort, but I otherwise generally meet the study’s subject parameters.

Something in my past causes me to actively select housing that isn’t in a noisy environment. If I were asked why I lived where I lived, my answer would have included:

  • A deciding factor in why I sold my second house was the traffic noise in wintertime;
  • A deciding factor in why I bought my fourth house was its location in the center of the housing development, away from street noise; and
  • A deciding factor in why I live where I now live is the house’s orientation away from both direct and reflective traffic noise sources.

Processing my hypothetical fMRI data with my self-reported historical housing choices may or may not have found:

“..geographical features in the proximal participants’ habitat are associated with brain integrity..”

Using the better-quality information of self-reports, though, it’s unlikely that an association this study would have found to be significant – the chance fact that I live within one kilometer of a forest – would have been deemed significant.

https://www.nature.com/articles/s41598-017-12046-7 “In search of features that constitute an “enriched environment” in humans: Associations between geographical properties and brain structure”

Do we need to study the brain to understand the mind?

A coauthor of the studies referenced in:

offered an opinion piece in A Paper a Day Keeps the Scientist Okay entitled “Do We Need To Study The Brain To Understand The Mind?”:

“The emerging consensus appears to be that implementation is important. Interestingly, the inverse question is also being asked by neurobiologists—do we need consider the mind to understand the brain?—and answered largely and increasingly in the affirmative.

Is pain different from negative emotions such as sadness and anger, or are they variants on a common theme?..pain appears to be distinct from negative emotion, but commonalities suggest ways in which they may share underlying processes such as heightened attention.

One of the biggest pitfalls is the temptation to observe brain activity and make inferences about the psychological state—for example, to infer episodic memory retrieval from hippocampal activity, fear from amygdala activity, or visual processing from activity in the ‘visual cortex.’ These inferences ignore the scope of processes which may activate each of these areas and involve a fallacy in reasoning: “if memory then hippocampus” is not the same thing as “if hippocampus then memory.”

The fact that few brain areas, including the ‘visual cortex,’ are dedicated to one process means that self-report is still the gold standard for assessing emotional experience and the contents of thought. This is a serious challenge for those who would like, for example, to assess your brand preferences or your political affiliation from a brain scan. (And isn’t it easier just to ask?)”

Epigenetic effects of early life stress exposure

This 2017 Netherlands review subject was the lasting epigenetic effects of early-life stress:

“Exposure to stress during critical periods in development can have severe long-term consequences..One of the key stress response systems mediating these long-term effects of stress is the hypothalamic-pituitary-adrenal (HPA) axis..early life stress (ELS) exposure has been reported to have numerous consequences on HPA-axis function in adulthood.

ELS is able to “imprint” or “program” an organism’s neuroendocrine, neural and behavioral responses to stress..research focuses along two complementary lines.

Firstly, ELS during critical stages in brain maturation may disrupt specific developmental processes (by altered neurotransmitter exposure, gene transcription, or neuronal differentiation), leading to aberrant neural circuit function throughout life..

Secondly, ELS may induce modifications of the epigenome which lastingly affect brain function..These epigenetic modifications are inducible, stable, and yet reversible, constituting an important emerging mechanism by which transient environmental stimuli can induce persistent changes in gene expression and ultimately behavior.”

In early life, the lower brain and limbic system brain structures are more developed and dominant, whereas the cerebrum and other brain structures are less developed (use the above rodent graphic as a rough guide). Stress and pain generally have a greater impact on the fetus than the infant, and on the infant than the adult.

The reviewers cited 50+ studies from years 2000-2015 in the “Early Life Stress Effects in a “Matching” Stressful Adult Environment” section to argue for the match/mismatch theory:

“Encountering ELS prepares an organism for similar (“matching”) adversities during adulthood, while a mismatching environment results in an increased susceptibility to psychopathology, indicating that ELS can exert either beneficial or disadvantageous effects depending on the environmental context.

Initial evidence for HPA-axis hypo-reactivity is observed for early social deprivation, potentially reflecting the abnormal HPA-axis function as observed in post-traumatic stress disorder.

Interestingly, experiencing additional (chronic) stress in adulthood seems to normalize these alterations in HPA-axis function, supporting the match/mismatch theory.”

Evidence for this theory was contrasted with the allostatic load theory presented in, for example, How one person’s paradigms regarding stress and epigenetics impedes relevant research.

The review mainly cited evidence from rodent studies that mismatched reactions in adulthood may be consequences of early-life events. These events:

“..imprint or program an organism’s neuroendocrine, neural and behavioral responses..leading to aberrant neural circuit function throughout life..which lastingly affect brain function..”

Taking this research to a personal level:

  • Have you had feelings that you were unsafe, although your environment was objectively safe?
  • Have you felt uneasy when people are nice to you?
  • Have you felt anxious when someone pays attention to you, even after you’ve acted to gain their attention?

I assert that mismatched human feelings are one form of mismatched reactions. As such, they may be interpreted as consequences of early-life experiences, and indicators of personal truths.

If researchers can let go of their biases and Advance science by including emotion in research, they may find that human subjects’ feelings produce better evidence for what actually happened during the subjects’ early lives than do standard scientific methods of:

Incorporating this evidence may bring researchers closer to backwardly predicting the major insults to an individual that knocked their development processes out of normally robust pathways and/or induced “persistent changes in gene expression and ultimately behavior.”

https://www.frontiersin.org/articles/10.3389/fncel.2017.00087/full “Modulation of the Hypothalamic-Pituitary-Adrenal Axis by Early Life Stress Exposure”

I discovered this review as a result of it being cited in http://www.sciencedirect.com/science/article/pii/S1084952117302884 “Long-term effects of early environment on the brain: Lesson from rodent models” (not freely available)

Observing pain in others had long-lasting brain effects

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.”

Limitations included:

  • “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:

  1. 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?
  2. If there’s evidence for item 1, then why aren’t “increased responses to ‘no pain'” of affected people overtly evident in everyday life?
  3. If item 2 is often observed, then what are the neurobiological consequences for affected people’s suppression of “increased responses to ‘no pain’?”
  4. Along with the effects of item 3, what may be behavioral, emotional, and other evidence of this suppressed pain effect?
  5. 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

The current paradigm of child abuse limits pre-childhood causal research

As an adult, what would be your primary concern if you suspected that your early life had something to do with current problems? Would you be interested in effective treatments of causes of your symptoms?

Such information wasn’t available in this 2016 Miami review of the effects of child abuse. The review laid out the current paradigm mentioned in Grokking an Adverse Childhood Experiences (ACE) score, one that limits research into pre-childhood causes for later-life symptoms.

The review’s goal was to describe:

“How numerous clinical and basic studies have contributed to establish the now widely accepted idea that adverse early life experiences can elicit profound effects on the development and function of the nervous system.”

The hidden assumption of almost all of the cited references was that these distant causes can no longer be addressed. Aren’t such assumptions testable here in 2016?

As an example, the Discussion section posed the top nine “most pressing unanswered questions related to the neurobiological effects of early life trauma.” In line with the current paradigm, the reviewer assigned “Are the biological consequences of ELS [early life stress] reversible?” into the sixth position.

If the current paradigm encouraged research into treatment of causes, there would probably already be plenty of evidence to demonstrate that directly reducing the source of the damage would also reverse the damaging effects. There would have been enough studies done so that the generalized question of reversibility wouldn’t be asked.

Aren’t people interested in human treatments of originating causes so that their various symptoms don’t keep bubbling up? Why wouldn’t research paradigms be aligned accordingly?

The review also demonstrated how the current paradigm of child abuse misrepresents items like telomere length and oxytocin. Researchers on the bandwagon tend to forget about the principle Einstein expressed as:

“No amount of experimentation can ever prove me right; a single experiment can prove me wrong.”

That single experiment for telomere length arrived in 2016 with Using an epigenetic clock to distinguish cellular aging from senescence. The seven references the review cited for telomere length that had “is associated with” or “is linked to” child abuse findings should now be viewed in a different light.

The same light shone on oxytocin with Testing the null hypothesis of oxytocin’s effects in humans and Oxytocin research null findings come out of the file drawer. See their references, and decide for yourself whether or not:

“Claimed research findings may often be simply accurate measures of the prevailing bias.”

http://www.cell.com/neuron/fulltext/S0896-6273%2816%2900020-9 “Paradise Lost: The Neurobiological and Clinical Consequences of Child Abuse and Neglect”