5+ stars Premium

Premium

Using citations to develop beliefs instead of evidence

gettingwell4 5+ stars Premium, Beliefs, Cerebrum

This 2009 Harvard study analyzed how citations were used as tools to establish a belief.

The researched data was gathered from 1992 to 2007 on a specific subject of Alzheimer’s research. The belief was:

“β amyloid is produced by inclusion body myositis myofibres or is uniquely present in inclusion body myositis muscle.”

The author used social network analysis to determine:

“Four primary data papers, five model papers, and one review paper constituted the 10 most authoritative papers that the claim was true.

The supportive papers received 94% of the 214 citations to these primary data, whereas the six papers containing data that weakened or refuted the claim received only 6% of these citations.

95% of all citation paths flow through four review papers by the same research group.

Amplification of a claim is instead introduced into belief systems through the citing of review papers and other papers that lack data addressing the claim.”

Some of the benefits believers received included:

  1. It became easier to build models if a researcher believed:

    “Animal and cell culture experiments are valid models of inclusion body myositis”

    although:

    “The uncited data suggest that the animal and cell culture experiments are no more models of inclusion body myositis than any other neuromuscular disease in which muscle regeneration occurs.”

  2. Believers used exaggerations in their confirming research that diverted the original claim’s meaning. As an example:

    “Three supportive citations developed into 7,848 supportive citation paths—chains of false claim in the network.”

  3. Citation biases and diversions could be used to support proposals for new funding.

Just imagine how compressed this phenomenon’s timeframe is now with our social networks! The tools available for creating memes and widespread nonfactual distortions are children’s play.

A few questions for the current year:

  1. What do we believe in that isn’t thoroughly investigated, where we haven’t found the time or inclination to search for opposing results?
  2. What causes us to believe these things?
  3. What are the positive and negative consequences of our beliefs?

http://www.bmj.com/content/339/bmj.b2680 “How citation distortions create unfounded authority: analysis of a citation network”

Hat tip to Jon in the comments section of Neuroskeptic’s blog post “The Ethics of Citation” http://blogs.discovermagazine.com/neuroskeptic/2017/03/12/the-ethics-of-citation

Beyond Belief: What we do instead of getting well

gettingwell4 5+ stars Premium, Beliefs, Cerebrum, Primal Therapy , ,

Continuing Dr. Arthur Janov’s May 2016 book Beyond Belief:

“p. 61 Heavy pains with no place to go just pressures the cortex into concocting an idea commensurate with the feeling.

The feeling itself makes no sense since the original feeling has no scene with it nor verbal capacity; it was laid down in a preverbal time without context, save for the feeling itself.

We cling to those ideas as strongly as the feelings driving us are.

Sometimes we argue with someone not realizing that we are battling a defense which is implacable. They don’t want to hear what we have to say. They want to protect their psyche.

p. 63 Suffocation at birth is registered not as an idea, but as a physiologic fact. It becomes an idea when the brain evolves enough to produce ideas. Then it can produce, ‘There is no air in here.’

A slightly stifling atmosphere in the present can set off this great pain and with it an exaggerated response. ‘I have to leave this woman because she stifles me.’

p. 64 It doesn’t matter about the facts we know if we cannot stop drinking or if we cannot maintain a relationship with someone else.

p. 68 My task is to examine why individuals adopt belief systems, whatever they are, and how certain feelings provoke specific kinds of belief systems..to demonstrate how feeling feelings can alter those beliefs without once addressing the beliefs at all.

Deprogramming is not necessary. Probing need is. Resolving feelings seems to render belief systems inoperative.

p. 71 We are a nation and a world of seekers, a people who seek refuge in all manner of beliefs.

p. 75-76 Later in life, equipped with the cortical ability to substitute ideation for feeling, the traumatized baby can call upon a god to save him from his inner pain, even when he doesn’t know where the pain originated, or even that there is pain. He just calls upon a god to watch over him, to see that he gets justice, who won’t let him down, and above all, who will help him make it into life.

p. 106 Neurosis is the only malady on the face of this earth that feels good..numbs the feeling. Numb feels good – not ‘good’ in the absolute sense, just not ‘bad.’

So we settle..we get numbed out and feel no pain and in return, life is blah blah. The person then feels she is not getting anything out of life and seeks out salvation or a guru in one form or another.”

“We are a nation and a world of seekers, a people who seek refuge in all manner of beliefs.” The patient’s story on pages 89 – 105 told of HORRIFIC damages inflicted by believers and the subsequent consequences!

Variations of his story with its adverse childhood experiences could be told by tens of millions of people in the US alone!

Why isn’t the internet flooded with 10+ million similar stories of people who have faced their realities, and effectively addressed the real causes of what’s wrong in their lives?

Said another way: Why is the internet instead flooded with stories of 10+ million people

  • NOT facing their realities,
  • Doing things to prolong their conditions, and
  • Avoiding getting well?

The many reasons why people do things that don’t truly get them well are covered in Beyond Belief and Dr. Janov’s other publications. One obstacle for people who want enduring therapeutic help is the intentional misrepresentation of Primal Therapy.

Every day I look at the results of an automated search that uses “primal therapy” as the search term. Along with the scams and irrelevancies are the “scream” results.

This misrepresentation is addressed here:

“Primal Therapy is not Primal ‘Scream’ Therapy. Primal Therapy is not just making people scream; it was never ‘screaming’ therapy. The Primal Scream was the name of the 1st book by Dr. Janov about Primal Therapy.”

People who perpetuate the “scream” meme are only a few seconds away from search results that would inform them and their readers of accurate representations of Primal Therapy.

What purpose does it serve to misdirect people away from doing something to effectively address the real causes of what’s wrong in their lives?

Beyond Belief: The impact of merciless beatings on beliefs

gettingwell4 5+ stars Premium, Beliefs, Cerebrum, Primal Therapy , , , ,

Continuing with Dr. Arthur Janov’s May 2016 book Beyond Belief:

“p. 17 When someone insults us, we immediately create reasons and rationales for it. We cover the pain. Now imagine a whole early childhood of insults and assaults and how that leaves a legacy that must be dealt with.

The mind of ideas and philosophies doesn’t know it is being used; doesn’t know it serves as a barricade against the danger of feeling.

It is why no one can convince the person out of her ideas. They serve a key purpose and should not be tampered with. We are tampering with a survival function.

p. 19 It seems like a miracle that something as intangible and invisible as an idea has the power to transform our biologic system. It makes us see what doesn’t exist and sometimes not see what does. What greater power exists than that? To be fooled is not only to convince someone to believe the false, but also to convince others to not believe the truth.

The unloved child who cannot bear the terrible feelings of hopelessness shuts down his own feeling centers and grows insensitive, not only to his pain, but to that of others. So he commits the same error on his child that was visited upon him, and he does so because of the way he was unloved early on. He cannot see his own hopelessness or that of his child.

p. 56 All defensive beliefs must have a kernel of hope inside of them. It is the embedded hopelessness that gives rise to its opposite – hope – and its accompanying biochemistry of inhibition or gating.

To be even more precise, it is the advent of pain surrounding hopelessness that produces the belief entwined with hope. All defensive belief serves the same function – repression, absorbing the energy of pain.

p. 57 An unloved child is a potential future believer.

p. 58 NO ONE HAS THE ANSWER TO LIFE’S QUESTIONS BUT YOU. How you should lead your life depends on you, not outside counsel.

We do not direct patients, nor dispense wisdom upon them. We have only to put them in touch with themselves; the rest is up to them.

Everything the patient has to learn already resides inside. The patient can make herself conscious. No one else can.”

“p. 29 The personal experience stories throughout the book are written by my patients and, with the exception of a few grammatical corrections, they are presented here exactly as they were given to me.”

All of the Primal Therapy patients’ stories started with HORRENDOUS childhoods that produced correspondingly strong beliefs!

I came across a public figure example today in 10 Defining Moments In The Childhood Of Martin Luther King Jr. The author included two items germane to an understanding of how beliefs may develop from adverse childhood experiences:

  • 8. King Sr. “Would beat Martin and his brother, Alfred, senseless for any infraction, usually with a belt.”
  • 6. “By the time King was 13, he’d tried to kill himself twice.”

Every reference I found tied King Jr.’s suicide attempts to his grandmother’s death. What an implausible narrative!

“A whole early childhood of insults and assaults” certainly had more to do with the causes for his preteen suicide attempts.

Consider a child’s feelings of helplessness, worthlessness, pain, and betrayal when the people who are supposed to love them are cruel to them instead. Feelings like what I expressed in Reflections on my four-year anniversary of spine surgery.

Consider the appeal of escaping from this life when “The unloved child cannot bear the terrible feelings of hopelessness.”

Granted that it’s only the patient who can put together what happened in their life so that it’s therapeutic. Beyond Belief and Dr. Janov’s other publications outline the framework.

Genetic imprinting, sleep, and parent-offspring conflict

gettingwell4 5+ stars Premium, Amygdala, Beliefs, Brain development, Cerebrum, Epigenetics, Hypothalamus, Limbic system, Memory, Neurochemicals, Oxytocin , , ,

This 2016 Italian review subject was the interplay of genetic imprinting and sleep regulation:

“Sleep results from the synergism between at least two major processes: a homeostatic regulatory mechanism that depends on the accumulation of the sleep drive during wakefulness, and a circadian self-sustained mechanism that sets the time for sleeping and waking throughout the 24-hour daily cycle.

REM sleep apparently contravenes the restorative aspects of sleep; however, the function of this ‘paradoxical’ state remains unknown. Although REM sleep may serve important functions, a lack of REM sleep has no major consequences for survival in humans; however, severe detrimental effects have been observed in rats.

Opposite imprinting defects at chromosome 15q11–13 are responsible for opposite sleep phenotypes as well as opposite neurodevelopmental abnormalities, namely the Prader-Willi syndrome (PWS) and the Angelman syndrome (AS). Whilst the PWS is due to loss of paternal expression of alleles, the AS is due to loss of maternal expression.

Maternal additions or paternal deletions of alleles at chromosome 15q11–13 are characterized by temperature control abnormalities, excessive sleepiness, and specific sleep architecture changes, particularly REM sleep deficits. Conversely, paternal additions or maternal deletions at chromosome 15q11–13 are characterized by reductions in sleep and frequent and prolonged night wakings.

The ‘genomic imprinting hypothesis of sleep’ remains in its infancy, and several aspects require attention and further investigation.”

http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1006004 “Genomic Imprinting: A New Epigenetic Perspective of Sleep Regulation”

A commenter to the review referenced a 2014 study Troubled sleep: night waking, breastfeeding, and parent–offspring conflict that received several reactions, including one by the same commenter. Here are a few quotes from the study author’s consolidated response:

“‘Troubled sleep’ had two major purposes. The first was to draw attention to the oppositely perturbed sleep of infants with PWS and AS and explore its evolutionary implications. The involvement of imprinted genes suggests that infant sleep has been subject to antagonistic selection on genes of maternal and paternal origin with genes of maternal origin favoring less disrupted sleep.

My second major purpose was a critique of the idea that children would be happier, healthier and better-adjusted if we could only return to natural methods of child care. This way of thinking is often accompanied by a belief that modern practices put children at risk of irrevocable harm.

The truth of such claims is ultimately an empirical question, but the claims are sometimes presented as if they had the imprimatur of evolutionary biology. This appeal to scientific authority often seems to misrepresent what evolutionary theory predicts: that which evolves is not necessarily that which is healthy.

Why should pregnancy not be more efficient and more robust than other physiological systems, rather than less? Crucial checks, balances and feedback controls are lacking in the shared physiology of the maternal–fetal unit.

Infant sleep may similarly lack the exquisite organization of systems without evolutionary conflict. Postnatal development, like prenatal development, is subject to difficulties of evolutionarily credible communication between mothers and offspring.”

The author addressed comments related to attachment theory:

“Infants are classified as having insecure-resistant attachment if they maintain close proximity to their mother after a brief separation while expressing negative emotions and exhibiting contradictory behaviors that seem to both encourage and resist interaction. By contrast, infants are classified as having insecure-avoidant attachment if they do not express negative emotion and avoid contact with their mother after reunion.

Insecure-avoidant and insecure-resistant behaviors might be considered antithetic accommodations of infants to less responsive mothers; the former associated with reduced demands on maternal attention, the latter with increased demands. A parallel pattern is seen in effects on maternal sleep. Insecure-avoidant infants wake their mothers less frequently, and insecure-resistant infants more frequently, than securely attached infants.

Parent–child interactions are transformed once children can speak. Infants with more fragmented sleep at 6 months had less language at 18 and 30 months.

Infants with AS have unconsolidated sleep and never learn to speak. The absence of language in the absence of expression of one or more MEGs [maternally expressed imprinted genes] is compatible with a hypothesis in which earlier development of language reduces infant demands on mothers.”

Regarding cultural differences:

“China, Taiwan and Hong Kong have both high rates of bed-sharing and high rates of problematic sleep compared with western countries. Within this grouping, however, more children sleep in their own room but parents report fewer sleep problems in Hong Kong than in either China or Taiwan.

Clearly, cultural differences are significant, and the causes of this variation should be investigated, but the differences cannot be summarized simply as ‘west is worst’.

The fitness [genetic rather than physical fitness] gain to mothers of an extra child and the benefits for infants of longer IBIs [interbirth intervals] are substantial. These selective forces are unlikely to be orders of magnitude weaker than the advantages of lactase persistence, yet the selective forces associated with dairying have been sufficient to result in adaptive genetic differentiation among populations.

The possibility of gene–culture coevolution should not be discounted for behaviors associated with infant-care practices.”

Regarding a mismatch between modern and ancestral environments:

“I remain skeptical of a tendency to ascribe most modern woes to incongruence between our evolved nature and western cultural practices. We did not evolve to be happy or healthy but to leave genetic descendants, and an undue emphasis on mismatch risks conflating health and fitness.

McKenna [a commenter] writes ‘It isn’t really nice nor maybe even possible to fool mother nature.’ Here I disagree. Our genetic adaptations often try to fool us into doing things that enhance fitness at costs to our happiness.

Our genes do not care about us and we should have no compunction about fooling them to deliver benefits without serving their ends. Contraception, to take one obvious example, allows those who choose childlessness to enjoy the pleasures of sexual activity without the fitness-enhancing risk of conception.

Night waking evolved in environments in which there were strong fitness costs from short IBIs and in which parents lacked artificial means of birth-spacing. If night waking evolved because it prolonged IBIs, then it may no longer serve the ends for which it evolved.

Nevertheless, optimal infant development might continue to depend on frequent night feeds as part of our ingrained evolutionary heritage.

It could also be argued that when night waking is not reinforced by feeding, and infants sleep through the night, then conflict within their genomes subsides. Infants would then gain the benefit of unfragmented sleep without the pleiotropic costs of intragenomic conflict. Plausible arguments could be presented for either hypothesis and a choice between them must await discriminating evidence.”

Commenters on the 2014 study also said:

“[Crespi] The profound implications of Haig’s insights into the roles of evolutionary conflicts in fetal, infant and maternal health are matched only by the remarkable absence of understanding, appreciation or application of such evolutionary principles among the research and clinical medical communities, or the general public.

[Wilkins] A mutation may be selected for its effect on the trait that is the basis of the conflict, but that mutation also likely affects other traits. In general, we expect that these pleiotropic effects to be deleterious: conflict over one trait can actually drive other traits to be less adapted. Natural selection does not necessarily guarantee positive health outcomes.

[McNamara] Assuming that AS/REM is differentially influenced by genes of paternal origin then both REM properties and REM-associated awakenings can be better explained by mechanisms of genomic conflict than by traditional claims that REM functions as an anti-predator ‘sentinel’ for the sleeping organism.

[Hinde] Given this context of simultaneous coordination and conflict between mother and infant, distinguishing honest signals of infant need from self-interested, care-extracting signals poses a challenge.“

Enduring epigenetic memories? Or continuous toxic stimulation?

gettingwell4 5+ stars Premium, Epigenetics, Immune system, Memory

This 2016 French review subject was bacterial infections that produce long-lasting host memories:

“Virulence factors modify the epigenomic landscape through targeting of host signaling cascades, or chromatin complexes directly. Additionally, some bacterial factors have intrinsic catalytic activity enabling them to directly modify chromatin.

Virus, fungi, and parasites also induce similar processes.

Epigenomic changes are not the only possible marks contributing to epigenetic memory. Every inducible change that is not rapidly reversed has the potential to maintain a lasting effect.

Most studies in this field have been performed in vitro with fully terminally differentiated cells such as epithelial cells. Since in such cell types cell fate is already established and a short lifespan often occurs in vivo, this raises the question of whether such memory would be relevant for these cells. The same can be applied to differentiated innate immune cells, which also have a short lifetime.

Looking at the response of undifferentiated cells such as stem cells appears much more appropriate to further explore the concept of innate immune memory.

figureFINAL

The lasting potential of chromatin marks depends not only on the kinetics of the epigenome, but also on the stimulus itself. For example, in contrast to LPS [lipopolysaccharide, the major constituent of the cell wall of Gram-negative bacteria], which is rapidly cleared from the organism, BCG and the anthrax toxin may persist in the host organism.

The lasting epigenomic effect would not be due to memory, but continuous stimulation by persistent pathogens or persistent components.”

The last point emphasized the principle that damaging sources should be addressed. Enduring epigenetic effects may be symptoms rather than causes when toxic conditions persist.

Therapies that attempt to reverse epigenetic changes may not be effective when these changes aren’t the only factors.

https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(16)30148-2 “A Lasting Impression: Epigenetic Memory of Bacterial Infections?”

Lack of oxygen’s epigenetic effects

gettingwell4 5+ stars Premium, Brain development, Epigenetics, Immune system, Stress , ,

This 2016 Finnish review subject was epigenetic effects of hypoxia:

“Ever since the Cambrian period, oxygen availability has been in the center of energy metabolism. Hypoxia stabilizes expression of hypoxia-inducible transcription factor-1α (HIF-1α), which controls expression of hundreds of survival genes related to enhanced energy metabolism and autophagy.

There are several other signals, mostly related to stresses, which can increase expression of HIF factors and thus improve cellular survival. However, a chronic activation of HIF factors can have detrimental effects, e.g. stimulate cellular senescence and tissue fibrosis commonly enhanced in age-related diseases.

Stabilization of HIF-1α increases expression of histone lysine demethylases (KDM). Hypoxia-inducible KDMs support locally the gene transcription induced by HIF-1α, although they can also control genome-wide chromatin landscape, especially KDMs which demethylate H3K9 and H3K27 sites (repressive epigenetic marks).”

Gene areas where HIF-1α is involved include:

  • “angiogenesis
  • autophagy
  • glucose uptake
  • glycolytic enzymes
  • immune responses
  • embryonic development
  • tumorigenesis
  • generation of miRNAs.”

HIF-1a signaling

Figure 1 above was instructive in that the reviewers pointed out the lack of a feedback mechanism in HIF-1α signaling. A natural lack of feedback to the HIF-1α signaling source contributed to diseases such as:

  • “age-related macular degeneration
  • cancer progression
  • chronic kidney disease
  • cardiomyopathies
  • adipose tissue fibrosis
  • inflammation
  • detrimental effects which are linked to epigenetic changes.”

The point was similar to a study referenced in The PRice “equation” for individually evolving: Which equation describes your life? that:

“Evolution may preferentially mitigate damage to a biological system than reduce the source of this damage.”

This review subject has many interdependencies and timings within a complex network. Contexts are important:

“Cross-talk between NF-κB [nuclear factor kappa B] and HIF-1α in inflammation might be organized in cell type and context-dependent manner.

It seems that ROS [reactive oxygen species] affect HIF-1α signaling in a context-dependent manner.

Hypoxia stimulated expression of KDM3A and KDM4B genes in different cellular contexts. Given that KDM3A and KDM4B are the major histone demethylases which remove repressive H3K9 sites, their role as transcriptional cofactors seems to be important in activation of HIF-1α signaling. Members of KDM4 subfamily have a crucial role in DNA repair systems, although responses seem to be enzyme-specific and appear in a context-dependent manner.

Acute hypoxia can stimulate cell-cycle arrest but does not provoke cellular senescence in all contexts.”

It wasn’t mentioned that hypoxia evokes cellular Adaptations to stress encourage mutations in a DNA area that causes diseases.

The review was tailored for the publishing journal Aging and Disease, and the subject was best summed up by:

“HIF-1α can control cellular fate in adult animals, either stimulating proliferation or triggering cellular senescence, by regulating the expression of different KDMs in a context-dependent manner.”

This review covered hypoxic conditions during human development that are clearly origins of many immediate and later-life diseases. However, cited remedies only addressed symptoms.

That these distant causes can no longer be addressed is a hidden assumption of research and treatment of effects of health problems. Aren’t such assumptions testable here in the current year?

http://www.aginganddisease.org/article/2016/2152-5250/ad-7-2-180.shtml “Hypoxia-Inducible Histone Lysine Demethylases: Impact on the Aging Process and Age-Related Diseases”

Using an epigenetic clock to distinguish cellular aging from senescence

gettingwell4 5+ stars Premium, Epigenetics, Telomeres

The 2016 UK/UCLA human study found:

“Induction of replicative senescence (RS) and oncogene-induced senescence (OIS) are accompanied by ageing of the cell. However, senescence induced by DNA damage is not, even though RS and OIS activate the cellular DNA damage response pathway, highlighting the independence of senescence from cellular ageing.

We used primary endothelial cells (ECs) that were derived from the human coronary artery of a 19 year old male.

The fact that maintenance of telomere length by telomerase did not prevent cellular ageing defines the singular role of telomeres as that of a means by which cells restrict their proliferation to a certain number; which was the function originally ascribed to it. Cellular ageing on the other hand proceeds regardless of telomere length.

Collectively, our results reveal that cellular ageing is distinct from cellular senescence and independent of DNA damage response and telomere length.”

The following was the closest the study came to a Limitations statement:

“Although the characteristics of cellular ageing are still not well known, the remarkable precision with which the epigenetic clock can measure it and correlate it to biological ageing remove any doubt of its existence, distinctiveness and importance. This inevitably raises the question of what is the nature of this cellular ageing, and what are its eventual physical consequences.

Admittedly, the observations above do not purport to provide the answer, but they have however, cleared the path to its discovery by unshackling cellular ageing from senescence, telomeres and DNA damage response, hence inviting fresh perspectives into its possible mechanism.”

The epigenetic clock method was the same used by:

http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=7383&path[]=21162 “Epigenetic clock analyses of cellular senescence and ageing”

Empathy, value, pain, control: Psychological functions of the human striatum

gettingwell4 5+ stars Premium, Anterior cingulate cortex, Brain hemispheres, Cerebrum, Dopamine, Limbic system, Memory, Neurochemicals, Thalamus , ,

This 2016 US human study found:

“A link between existing data on the anatomical and physiological characteristics of striatal regions and psychological functions.

Because we did not limit our metaanalysis to studies that specifically targeted striatal function, our results extend previous knowledge of the involvement of the striatum in reward-related decision-making tasks, and provide a detailed functional map of regional specialization for diverse psychological functions, some of which are sometimes thought of as being the exclusive domain of the PFC [prefrontal cortex].”

The analysis led to dividing the striatum into five segments:

Ventral striatum (VS):

  • Stimulus Value
  • Terms such as “reward,” “losses,” and “craving”
  • The most representative study reported that monetary and social rewards activate overlapping regions within the VS.
  • Together with the above finding of a reliable coactivation with OFC [orbitofrontal cortex] and ventromedial PFC, this finding suggests a broad involvement of this area in representing stimulus value and related stimulus-driven motivational states.

Anterior caudate (Ca) Nucleus:

  • Incentive Behavior
  • Terms such as “grasping,” “reaching,” and “reinforcement”
  • The most representative study reported a stronger blood-oxygen level-dependent (BOLD) response in this region during trials in which participants had a chance of winning or losing money in a card guessing game, in comparison to trials where participants merely received feedback about the accuracy of their guess.
  • This result suggests a role in evaluating the value of different actions, contrasting with the above role of the VS in evaluating the value of stimuli.

Posterior putamen (Pp):

  • Sensorimotor Processes
  • Terms such as “foot,” “noxious,” and “taste”
  • The most representative study reported activation of this region in response to painful stimulation at the back of the left hand and foot of participants. Anatomically, the most reliable and specific coactivation is with sensorimotor cortices, and the posterior and midinsula and operculum (secondary somatosensory cortex SII) in particular, some parts of which are specifically associated with pain.
  • Together, these findings suggest a broad involvement of this area in sensorimotor functions, including aspects of their affective qualities.

Anterior putamen (Pa):

  • Social- and Language-Related Functions
  • Terms such as “read,” “vocal,” and “empathic”
  • The most representative study partially supports a role of this area in social- and language-related functions; it reported a stronger activation of the Pa in experienced singers, but not when novices were singing.
  • It is coactivated with frontal areas anterior to the ones coactivated with the Pp, demonstrating topography in frontostriatal associations. These anterior regions have been implicated in language processes.

Posterior caudate (Cp) Nucleus:

  • Executive Functions
  • Terms such as “causality,” “rehearsal,” and “arithmetic”
  • The representative study reported this region to be part of a network that included dorsolateral PFC and ACC, which supported inhibitory control and task set-shifting.
  • These results suggest a broad, and previously underappreciated, role for the Cp in cognitive control.

The authors presented comparisons of the above striatal segments with other analyses of striatal zones.

One of the coauthors was the lead researcher of the 2015 Advance science by including emotion in research. The current study similarly used a coactivation view rather than a connectivity paradigm of:

“Inferring striatal function indirectly via psychological functions of connected cortical regions.”

Another of the coauthors was a developer of the system used by the current study and by The function of the dorsal ACC is to monitor pain in survival contexts, and he provided feedback to those authors regarding proper use of the system.

The researchers’ “unbiased, data-driven approach” had to work around the cortical biases evident in many of the 5,809 human imaging studies analyzed. The authors referred to the biases in statements such as:

“The majority of studies investigating these psychological functions report activity preferentially in cortical areas, except for studies investigating reward-related and motor functions.”

The methods and results of research with cortical biases influenced the study’s use of:

“Word frequencies of psychological terms in the full text of studies, rather than a detailed analysis of psychological tasks and statistical contrasts.”

http://www.pnas.org/content/113/7/1907.full “Regional specialization within the human striatum for diverse psychological functions”

Early-life epigenetic regulation of the oxytocin receptor gene

gettingwell4 5+ stars Premium, Amygdala, Brain development, Cerebellum, Cortisol, Epigenetics, Hippocampus, Hypothalamus, Limbic system, Lower brain, Neurochemicals, Oxytocin, Stress , ,

This 2015 US/Canadian rodent study investigated the effects of natural variation in maternal care:

“The effects of early life rearing experience via natural variation in maternal licking and grooming during the first week of life on behavior, physiology, gene expression, and epigenetic regulation of Oxtr [oxytocin receptor gene] across blood and brain tissues (mononucleocytes, hippocampus, striatum, and hypothalamus).

Rats reared by high licking-grooming (HL) and low licking-grooming (LL) rat dams exhibited differences across study outcomes:

  • LL offspring were more active in behavioral arenas,
  • Exhibited lower body mass in adulthood, and
  • Showed reduced corticosterone responsivity to a stressor.

Oxtr DNA methylation was significantly lower at multiple CpGs in the blood of LL versus HL males, but no differences were found in the brain. Across groups, Oxtr transcript levels in the hypothalamus were associated with reduced corticosterone secretion in response to stress, congruent with the role of oxytocin signaling in this region.

Methylation of specific CpGs at a high or low level was consistent across tissues, especially within the brain. However, individual variation in DNA methylation relative to these global patterns was not consistent across tissues.

These results suggest that:

  • Blood Oxtr DNA methylation may reflect early experience of maternal care, and
  • Oxtr methylation across tissues is highly concordant for specific CpGs, but
  • Inferences across tissues are not supported for individual variation in Oxtr methylation.

nonsignificance

Individual DNA methylation values were not correlated across brain tissues, despite tissue concordance at the group level.

For each CpG, we computed the Pearson correlation coefficient r between methylation values for matched samples in pairs of brain regions (bars). Dark and light shaded regions represent 95% and 99% thresholds, respectively, of distributions of possible correlation coefficients determined from 10,000 permutations of the measured values among the individuals. These distributions represent the null hypothesis that an individual DNA methylation value in one brain region does not help to predict the value in another region in the same animal.

(A) Correlations based on pyrosequencing data for matched samples passing validation in both hippocampus (HC) and hypothalamus (Hypo). Correlations for individuals at each CpG were either weak (.2 < r < .3) or absent (r < .2), and none were significant, even prior to correction for multiple comparisons.

(B) Correlations for matched samples passing validation in both hippocampus and striatum (Str). Two correlations (CpG 1 and 11) were individually significant prior to but not following correction, and this result could be expected by chance.

Correlations between hippocampus and blood (described in the text) yielded similar results, and no particular CpG yielded consistently high correlation across multiple tissues.”

The study focused on whether or not an individual’s experience-dependent oxytocin receptor gene DNA methylation in one of the four studied tissues could be used to infer a significant effect in the three other tissues. The main finding was NO, it couldn’t!

The researchers’ other findings may have been strengthened had they also examined causes for the observed effects. The “natural variation in maternal licking and grooming” developed from somewhere, didn’t it?

The subjects’ mothers were presumably available for the same tests as the subjects, but nothing was done with them. Investigating at least one earlier generation may have enabled etiologic associations of “the effects of early life rearing experience” and “individual variation in DNA methylation.”

https://www.sciencedirect.com/science/article/abs/pii/S0018506X1500118X “Natural variation in maternal care and cross-tissue patterns of oxytocin receptor gene methylation in rats” (not freely available)

Advance science by including emotion in research

gettingwell4 5+ stars Premium, Amygdala, Anterior cingulate cortex, Beliefs, Brain hemispheres, Brainstem, Cerebellum, Cerebrum, Dopamine, Hippocampus, Hypothalamus, Limbic system, Lower brain, Memory, Neurochemicals, Thalamus , ,

This 2015 analysis of emotion studies found:

“Emotion categories [fear, anger, disgust, sadness, and happiness] are not contained within any one region or system, but are represented as configurations across multiple brain networks.

For example, among other systems, information diagnostic of emotion category was found in both large, multi-functional cortical networks and in the thalamus, a small region composed of functionally dedicated sub-nuclei.

The dataset consists of activation foci from 397 fMRI and PET [positron emission tomography] studies of emotion published between 1990 and 2011.”

From the fascinating Limitations section:

“Our analyses reflect the composition of the studies available in the literature, and are subject to testing and reporting biases on the part of authors. This is particularly true for the amygdala (e.g., the activation intensity for negative emotions may be over-represented in the amygdala given the theoretical focus on fear and related negative states). Other interesting distinctions were encoded in the thalamus and cerebellum, which have not received the theoretical attention that the amygdala has and are likely to be bias-free.

Some regions—particularly the brainstem—are likely to be much more important for understanding and diagnosing emotion than is apparent in our findings, because neuroimaging methods are only now beginning to focus on the brainstem with sufficient spatial resolution and artifact-suppression techniques.

We should not be too quick to dismiss findings in ‘sensory processing’ areas, etc., as methodological artifacts. Emotional responses may be inherently linked to changes in sensory and motor cortical processes that contribute to the emotional response.

The results we present here provide a co-activation based view of emotion representation. Much of the information processing in the brain that creates co-activation may not relate to direct neural connectivity at all, but rather to diffuse modulatory actions (e.g., dopamine and neuropeptide release, much of which is extrasynaptic and results in volume transmission). Thus, the present results do not imply direct neural connectivity, and may be related to diffuse neuromodulatory actions as well as direct neural communication.”

Why did the researchers use only 397 fMRI and PET studies? Why weren’t there tens or hundreds of times more candidate studies from which to select?

The relative paucity of candidate emotion studies demonstrated the prevalence of other researchers’ biases for cortical brain areas. The lead researcher of the current study was a coauthor of the 2016 Empathy, value, pain, control: Psychological functions of the human striatum, whose researchers mentioned that even their analyses of 5,809 human imaging studies was hampered by other imaging-studies researchers’ cortical biases.

Functional MRI signals depend on the changes in blood flow that follow changes in brain activity. Study designers intentionally limit their findings when they scan brain areas and circuits that are possibly activated by human emotions, yet exclude emotional content that may activate these areas and circuits.

Here are a few examples of limited designs that led to limited findings when there was the potential for so much more:

It’s well past time to change these practices now in the current year.

This study provided many methodological tests that should be helpful for research that includes emotion. It showed that there aren’t impenetrable barriers – other than popular memes, beliefs, and ingrained dogmas – to including emotional content in studies.

Including emotional content may often be appropriate and informative, with the resultant findings advancing science. Here are a few recent studies that did so:

http://journals.plos.org/ploscompbiol/article?id=10.1371%2Fjournal.pcbi.1004066 “A Bayesian Model of Category-Specific Emotional Brain Responses”

Chronic pain causes epigenetic changes in the brain and immune system

gettingwell4 5+ stars Premium, Cerebrum, Cortisol, Dopamine, Epigenetics, Glutamate, Immune system, Neurochemicals, Primal Therapy, Serotonin ,

This 2015 Canadian rodent study by McGill researchers found:

“The critical involvement of DNA methylation in chronic pain. We show that in the PFC [prefrontal cortex], a brain region strongly implicated in chronic pain, a stunning number of promoters [control gene expression] are differentially methylated 9 months after injury. These changes are distant both in time and space from the original injury.

The changes in DNA methylation are highly organized in functional pathways that have been implicated in pain such as dysregulation of dopaminergic, glutamatergic, opioid and serotoninergic systems and important signaling and inflammatory pathways.

Genome-wide DNA methylation modifications of T cells [circulating white blood cells that control immune response] are also associated with nerve injury.

Most of the promoters (72%) identified as differentially methylated in T cells after nerve injury were also affected in the brain. While the methylation profiles in some of these modules were affected in the same direction in the brain and the T cells, others went in opposite direction. This is consistent with the idea that the brain and the immune system play different roles in chronic pain.

These data suggest that:

  • Persistent pain is associated with broad and highly organized organism-wide changes in DNA methylation, including two critical biological systems: the central nervous and immune systems.
  • This work also provides a possible mechanistic explanation for commonly observed comorbidities observed in chronic pain (i.e anxiety, depression).
  • Finally, the sheer magnitude of the impact of chronic pain, particularly in the prefrontal cortex, illustrates the profound impact that living with chronic pain exerts on an individual.”

http://www.nature.com/articles/srep19615 “Overlapping signatures of chronic pain in the DNA methylation landscape of prefrontal cortex and peripheral T cells”

The news coverage focused on how the study’s findings may lead to non-invasive DNA methylation measurements of chronic pain as well as treatments of the effects. I’d argue that the researchers’ concluding statement of the Discussion section deserved the most focus:

“Beyond the example of chronic pain, the robust and highly organized DNA methylation changes seen here in response to nerve injury provides some of the strongest evidence to date that experience effects DNA methylation landscapes at large distances in time and space.”

The study provided “some of the strongest evidence to date” that experiences caused widespread, long-lasting epigenetic changes. Given experiences’ etiologic functions, research with working hypotheses that experiences may also reverse epigenetic changes should be green-lighted.

“DNA methylation landscapes at large distances in time and space” warrant systematic examination of how experiential epigenetic changes during early life may be reversed by experiential therapies later in life. In the current year, there’s sufficient evidence for modifying research goals to primarily address causes, not just effects.

Outward expressions of inner truth

gettingwell4 5+ stars Premium, Memory, Primal Therapy , , , ,

“Truth needs no defense except when that truth is more than the system can integrate; then it requires defenses.

Our merciful brain has found back-up ways to protect us. It keeps the truth from us even when we go on searching for the truth.

After patients have deep feelings they come up with many truths about their lives. It is buried and defended along with the pain. Thus no one has to give anyone insights; they are already there just waiting for the exit.”

In the blog post’s Comments section:

“When repression is not effective, the imprint rises for connection. But it is transformed into an act-out before it becomes conscious.

I had to get out each morning to feel free and shake my malaise. I never ever knew the origins of needing to get out. And the act out would never stop until I felt the origins and relived them.

The memory is continuously pushing and forces all kinds of act-out behaviors. The behavior has to be close to the original imprint to make act outs effective.

The brain knows, even when we don’t. And offers up all kinds of reasons for our behavior except the right one.”

http://cigognenews.blogspot.com/2016/01/the-act-out-and-more_29.html “The Act-out and More”

Confusion may be misinterpreted as altruism and prosocial behavior

gettingwell4 5+ stars Premium, Beliefs, Cerebrum ,

This 2015 Oxford human study of altruism found:

“Division of people into distinct social types relies on the assumption that an individual’s decisions in public-goods games can be used to accurately measure their social preferences. Specifically, that greater contributions to the cooperative project in the game reflect a greater valuing of the welfare of others, termed “prosociality.”

Individuals behave in the same way, irrespective of whether they are playing computers or humans, even when controlling for beliefs. Therefore, the previously observed differences in human behavior do not need to be explained by variation in the extent to which individuals care about fairness or the welfare of others.

Conditional cooperators, who approximately match the contributions of their groupmates, misunderstand the game. Answering the standard control questions correctly does not guarantee understanding.

We find no evidence that there is a subpopulation of players that understand the game and have prosocial motives toward human players.

These results cast doubt on certain experimental methods and demonstrate that a common assumption in behavioral economics experiments, that choices reveal motivations, will not necessarily hold.

When attempting to measure social behaviors, it is not sufficient to merely record decisions with behavioral consequences and then infer social preferences. One also needs to manipulate these consequences to test whether this affects the behavior.”

The researchers are evolutionary biologists who had made similar points in previous studies. They addressed possible confounders in the study and supporting information, and provided complete details in the appendix. For example, regarding reciprocity:

“Communication was forbidden, and we provided no feedback on earnings or the behavior of groupmates. This design prevents signaling, reciprocity, and learning and therefore minimizes any order effects.

It might also be argued that people playing with computers cannot help behaving as if they were playing with humans. Such ingraining of behavior would suggest a major problem for the way in which economic games have been used to measure social preferences. In particular, behavior would reflect everyday expectations from the real world, such as reputation concerns or the possibility of reciprocity, rather than the setup of the game and the true consequences of choices.”

Some of the news coverage missed the lead point of how:

“Economic experiments are often used to study if humans altruistically value the welfare of others.

These results cast doubt on certain experimental methods and demonstrate that a common assumption in behavioral economics experiments, that choices reveal motivations, will not necessarily hold.”

Here are several expressions of beliefs in one news coverage article where the author attempted to flip the discussion to cast doubt on the study. It was along the lines of “There’s something wrong with this study (that I haven’t thoroughly read) because [insert aspersion about sample size, etc.]” What motivates such reflexive behavior?

This study should inform social behavior studies that draw conclusions from flawed experimental designs. For example, both:

based their findings on a video game of popping balloons. Neither study properly interpreted their subjects’ decisions per the current study’s recommendation:

“When attempting to measure social behaviors, it is not sufficient to merely record decisions with behavioral consequences and then infer social preferences. One also needs to manipulate these consequences to test whether this affects the behavior.”

http://www.pnas.org/content/113/5/1291.full “Conditional cooperation and confusion in public-goods experiments”

This post has somehow become a target for spammers, and I’ve disabled comments. Readers can comment on other posts and indicate that they want their comment to apply here, and I’ll re-enable comments.

Lifelong effects of stress

gettingwell4 5+ stars Premium, Beliefs, Brain development, Cerebrum, Cortisol, Epigenetics, Immune system, Limbic system, Lower brain, Memory, Neurochemicals, Stress , , , ,

A 2016 commentary A trilogy of glucocorticoid receptor actions that included two 2015 French rodent studies started out:

“Glucocorticoids (GCs) belong to a class of endogenous, stress-stimulated steroid hormones. They have wide ranging physiologic effects capable of impacting metabolism, immunity, development, stress, cognition, and arousal.

GCs exert their cellular effects by binding to the GC receptor (GR), one of a 48-member (in humans) nuclear receptor superfamily of ligand-activated transcription factors.”

The French studies were exceedingly technical. The first GR SUMOylation and formation of an SUMO-SMRT/NCoR1-HDAC3 repressing complex is mandatory for GC-induced IR nGRE-mediated transrepression:

“GCs acting through binding to the GR are peripheral effectors of circadian and stress-related homeostatic functions fundamental for survival.

Unveils, at the molecular level, the mechanisms that underlie the GC-induced GR direct transrepression function mediated by the evolutionary conserved inverted repeated negative response element. This knowledge paves the way to the elucidation of the functions of the GR at the submolecular levels and to the future educated design and screening of drugs, which could be devoid of undesirable debilitating effects on prolonged GC therapy.”

The companion study Glucocorticoid-induced tethered transrepression requires SUMOylation of GR and formation of a SUMO-SMRT/NCoR1-HDAC3 repressing complex stated:

“GCs have been widely used to combat inflammatory and allergic disorders. However, multiple severe undesirable side effects associated with long-term GC treatments, as well as induction of glucocorticoid resistance associated with such treatments, limit their therapeutic usefulness.”

Even when researchers study causes, they often justify their efforts in terms of outcomes that address effects. Is an etiologic advancement in science somehow unsatisfactory in and of itself?

Once in a while I get a series of personal revelations while reading scientific publications. Paradoxically, understanding aspects of myself has seldom been sufficient to address historical problems.

Thoughts are only where some of the effects of problems show up, and clarifying my understanding can – at most – tamp down these effects. The causes are elsewhere, and addressing them at the source is what ultimately needs to happen.

A few glucocorticoid-related items to ponder:

  • How has stress impacted my life? When and where did it start?
  • Why do I feel wonderful after taking prednisone or other anti-inflammatories? What may be the originating causes of such effects?
  • Why have prolonged periods of my life been characterized by muted responses to stress? How did I get that way?
  • Have I really understood why I’ve reflexively put myself into stressful situations? What will break me out of that habit?
  • Why do the feelings I experience while under stressful situations feel familiar? Does my unconsciousness of their origins have something to do with “homeostatic functions fundamental for survival?”
  • Why haven’t I noticed that symptoms of stress keep showing up in my life? There are “physiologic effects capable of impacting metabolism, immunity,” etc. but I don’t do something about it?
  • How else may stress impact my biology? Brain functioning? Ideas and beliefs? Behavior?

State-dependent brain functions and adrenaline

gettingwell4 5+ stars Premium, Brainstem, Locus coeruleus, Lower brain, Memory, Neurochemicals

This 2015 German/Italian rodent study investigated:

“How a specific neuromodulatory input may influence the information content and the readout of cortical information representations of sensory stimuli.

The locus coeruleus (LC) is a brainstem neuromodulatory nucleus that likely plays a prominent role in shaping cortical states via a highly distributed noradrenaline release in the forebrain. In particular, the LC:

  • Contributes to regulation of arousal and sleep;
  • Is involved in cognitive functions such as vigilance, attention, and selective sensory processing; and
  • Modulates cortical sensory responses and cortical excitability.

An important addition of our work to previous models of state dependence was the inclusion of the contribution of an important neuromodulator – the noradrenergic system. Our results support the hypothesis that the temporal structure of LC firing causally influences cortical dynamics.

Our work highlights the importance of timing of LC burst: suitably timed LC burst (for example, triggered by an alerting stimulus) can very rapidly trigger transitions into excitable cortical states, which in turn decrease the threshold for cortical responses and thus dynamically facilitate the processing of salient or attended events.

State dependence may either:

  • Force neurons to transmit information only using codes that are robust to state fluctuations (e.g., relative firing rates), or may
  • Force downstream neurons to gain information about the state of the networks sending the sensory messages and then to use the knowledge of state to properly interpret neural responses.

Our results suggest that the latter information transmission scheme is feasible, because detecting state by either monitoring the dynamics of cortical ongoing activity alone or by also monitoring the dynamics of noradrenergic modulation substantially increased the amount of information about sensory stimuli in the late response components relevant for behavior.”

The study added to the evidence that state dependencies can’t be overlooked in explanations of brain function and resultant physical and mental activity. Locus coeruleus neural activity “can very rapidly trigger transitions into excitable cortical states..and thus dynamically facilitate the processing of salient or attended events.”

Adrenaline from the locus coeruleus produced a state of arousal in multiple brain and body areas tied into the subjects’ sympathetic nervous systems. Such internal state changes may be accompanied by state-dependent memories, following the findings of What can cause memories that are accessible only when returning to the original brain state?

The study highlighted the capability of a lower brain structure to influence other brain areas. Its findings should inform researchers in attention and behavior studies, especially when investigating causes of attention and behavior difficulties.

http://www.pnas.org/content/112/41/12834.full “Modeling the effect of locus coeruleus firing on cortical state dynamics and single-trial sensory processing”