2-3 stars Required further work

Research needing further work

Assessing a mountain climber’s condition without noticing their empty backpack

gettingwell4 2-3 stars Required further work, Acetylcholine, Cortisol, Neurochemicals, Stress

A metaphor: for a mountain climber, which point has the most influence on their condition during the climb?

  • The path ahead?
  • The current situation?
  • The recent past?
  • The starting point?
  • The preparations?

Hard to say? Once the climb has started and until it’s finished, though, are there any points at which the preparations have no influence?

Let’s imagine that factors beyond the climber’s control ruined their preparations, leaving them with no reserves and a limited capability to adapt to environmental changes.

Let’s imagine further that researchers take initial physical and psychological measurements of the climber’s condition at an arbitrary point of the ascent or descent. Due to the design of their measurement system, however, they don’t discover that this climber has an empty backpack.

When the researchers interpret the results, will they understand how the climber’s measurements were influenced by the ruined preparations?  end metaphor

A 2014 Israeli study primary finding was of:

“Fear of terror-induced annual increases in resting heart rate.”

The researchers took 325 measurements each “of 17,380 apparently healthy volunteers” who had “consistent exposure to terror threats.”

The study was opaque in some areas. For example, what was the content and handling of a 4-item anxiety questionnaire?

The supplementary material showed that the headlined “fear of terror” term involved three disparate factors:

  • feeling unsafe;
  • fear of crowds; and
  • anxiety about future harm.

I’d like to understand the bases of why the researchers and the reviewer felt it was appropriate that:

“The scores on these items were averaged to yield a continuous FOT [fear-of-terror] score.”

The researchers probably had sufficient measurements of the subjects’ current conditions. They didn’t have a frame of reference that incorporated the present data with contextual information from each individual’s history back to the earliest parts of their life.

Lacking the links provided by such a framework, the researchers likely misassessed measurements that were influenced by how the subjects’ backpacks were packed.

http://www.pnas.org/content/112/5/E467.full “Fear and C-reactive protein cosynergize annual pulse increases in healthy adults”

Are hippocampal place cells controlled by theta brain waves from grid cells?

gettingwell4 2-3 stars Required further work, Hippocampus, Limbic system, Memory

This 2015 Canadian rodent study tried to establish that grid cells in the medial entorhinal cortex generated brain waves in the theta frequency range that controlled place cells in the hippocampus part of the limbic system.

The researchers stated:

“Our results deviate from the prediction.”

but a commentary Do the spatial frequencies of grid cells mold the firing fields of place cells? said the researchers:

“Obtained fascinating results, largely supporting the model.”

What’s fascinating to me is the volume of studies on the hippocampus that ignore its position as the seat of emotional memories. Human experiments involving the hippocampus are usually designed to not contain any emotional content.

Two studies showed functions of hippocampal place cells:

A summary study of 118 other studies What do grid cells contribute to place cell firing? provided additional information on grid cells and hippocampal place cells, head direction cells, boundary cells, and cells that encode object locations.

The summary study related to the current study by stating that the research through early 2014 arguably found:

“Grid and place cell firing patterns are not successive stages of a processing hierarchy, but complementary and interacting representations that work in combination.”

http://www.pnas.org/content/112/13/4116.full “Place field expansion after focal MEC inactivations is consistent with loss of Fourier components and path integrator gain reduction”

Epigenetic DNA methylation of the oxytocin receptor gene affected the perception of anger and fear

gettingwell4 2-3 stars Required further work, Amygdala, Anterior cingulate cortex, Brain development, Brain hemispheres, Cerebrum, Epigenetics, Hippocampus, Limbic system, Neurochemicals, Oxytocin, Thalamus ,

This 2015 Virginia human study:

“Reveals how epigenetic variability in the endogenous oxytocin system impacts brain systems supporting social cognition and is an important step to better characterize relationships between genes, brain, and behavior.”

The researchers did a lot of things right:

  • They studied a priori selected brain areas, followed by whole brain analyses;
  • Their subjects were carefully selected

    “Because methylation levels have been shown to differ as a function of race, we restricted our sample to Caucasians of European descent”

    but they didn’t restrict subjects to the same gender;

  • They acknowledged as a limitation:

    “A lack of behavioral evidence to reveal how these epigenetic and neural markers impact the overt social phenotype.”

One thing on which I disagree with the researchers is their assessment of what needs to be done next. Their news release stated:

“When imagining the future possibilities and implications this DNA methylation and oxytocin receptor research may have, the investigators think a blood test could be developed in order to predict how an individual may behave in social situations.”

Nice idea, but the next step should be to complete the research. The next step is to develop evidence for how the oxytocin receptor gene became methylated.

The subjects had a wide range of DNA methylation at the studied gene site – from 33% to 72% methylated!

Why?

At the same gene site:

“There was a significant effect of sex such that females have a higher level of methylation than males.”

Why?

Given these significant effects, why was there no research into likely causes?

Aren’t early periods in people’s lives the most likely times when the “Epigenetic modification of the oxytocin receptor gene” that “influences the perception of anger and fear in the human brain” takes place?

Wouldn’t findings from research on the subjects’ histories potentially help other people?

http://www.pnas.org/content/112/11/3308.full “Epigenetic modification of the oxytocin receptor gene influences the perception of anger and fear in the human brain”

Differing characteristics of languages shape people’s brains differently

gettingwell4 2-3 stars Required further work, Brain development, Brain hemispheres, Cerebrum

This 2015 Chinese study found that the differing characteristics of the Chinese and English languages shape people’s brains differently:

“Our results revealed that, although speech processing is largely carried out in the common left hemisphere classical language areas (Broca’s and Wernicke’s areas) and anterior temporal cortex, speech comprehension across different language groups depends on how these brain regions interact with each other.”

For an informed discussion of the study and related issues, visit http://languagelog.ldc.upenn.edu/nll/?p=17949 and comments.

We can infer from the Would you deprive your infant in order to be in a researcher’s control group? study that this shaping process begins during womb life.

http://www.pnas.org/content/112/10/2972.full “Cross-language differences in the brain network subserving intelligible speech”

Would you deprive your infant in order to be in a researcher’s control group?

gettingwell4 2-3 stars Required further work, Brain development, Cerebrum, Epigenetics , , , ,

This 2015 Harvard study found that exposing extremely premature babies to sounds of their mothers enlarged their auditory cortex.

The lead researcher stated:

“Our findings do not prove that the brains of these babies are necessarily better, and we cannot conclude that they will end up with no developmental disabilities.

We don’t know the advantages of having a bigger auditory cortex.”

It’s too bad that studies like this one have to take deprived infants and further deprive them for use as a control group. I suppose it’s possible that the control group members’ development could just be shifted, similar to the Maternal depression and antidepressants epigenetically change infant language development study.

However, given the findings of the Our early experiences are maintained and unconsciously influence us for years, if not indefinitely study, it’s also possible that the last trimester of womb life is a critical period for a child’s auditory cortex. If timely development doesn’t take place within the environment provided by the mother, there may not be another period to fully catch up on growth and learning, even given the effects of neural plasticity.

http://www.pnas.org/content/112/10/3152.full “Mother’s voice and heartbeat sounds elicit auditory plasticity in the human brain before full gestation”

If you had a disease, would you agree to treatment where you became a lab rat?

gettingwell4 2-3 stars Required further work, Amygdala, Limbic system, Thalamus ,

This 2015 Czech research studied individual neurons in an area of the limbic system of Parkinson’s disease patients. The findings corroborated several findings of previous research, such as:

“We confirm the importance of the subthalamic nucleus as a hub within the limbic circuitry involved in both emotional valence and arousal processing as in two functionally and spatially segregated systems.”

This statement summed up the study for me:

“Several factors could affect our results and reduce the inferences that can be drawn with regards to the physiology of emotional processing and the role of the subthalamic nucleus in the limbic circuits.

One such factor is that the study was conducted with Parkinson’s disease patients, who are known to have a widespread central nervous system pathology and to experience problems in emotional processing.”

The current study referenced The amygdala is where we integrate our perception of human facial emotion study, which similarly used the opportunity of patients with electrodes implanted for deep-brain stimulation to study individual neurons in the amygdala. However, a design difference was that the amygdala study had healthy control subjects in addition to patients, which led to fewer potential limitations on their findings.

Also referenced was a summary study entitled Exploring emotions using invasive methods: review of 60 years of human intracranial electrophysiology. Despite excluding studies of decision making, reward processing, learning, mood disorders, and pain experiences, it didn’t demonstrate that 60 years of experiments using implanted electrodes in the brains of people with epilepsy had substantially advanced science, other than confirming what fMRI and animal research had shown.

I’m not sure how I would feel if I had a disease where the physicians treated my symptoms in such a way that I became a lab rat for research that wasn’t groundbreaking. Do people with epilepsy and Parkinson’s disease have treatments available that factually resolve the underlying causes?

http://www.pnas.org/content/112/10/3116.full “Distinct populations of neurons respond to emotional valence and arousal in the human subthalamic nucleus”

Neural plasticity trumps genetics in the hippocampus part of the limbic system

gettingwell4 2-3 stars Required further work, Brain development, Epigenetics, Hippocampus, Limbic system, Memory , ,

This 2015 rodent study used a genetic strain of mice that was bred to not express a gene that enabled long-term memory in the hippocampus. The mice were not memory-impaired, however, due to their brains’ neural plasticity.

The researchers found:

“Deletion of genes in organisms does not always give rise to phenotypes because of the existence of compensation.

The current work provides an example of how a complex brain system may adjust to the effects of gene deletion to recover function.”

The Early human brain development can be greatly modified by environmental factors study showed even greater plasticity in another part of the human brain where the people faced much larger obstacles than gene deletion.

I view this finding as a cautionary tale to reference any time a study comes out stating that A and B genes are found to cause X and Y symptoms or behavior. Researchers don’t have enough evidence in 2015 to unequivocally describe what rodent brains are capable of, much less human brains.

The researchers implied how they kept faith in their work with the phrase:

“The compensatory mechanism is imperfect and does not fully restore cGKII-dependent function.”

Is perfection the standard to which their research is also held?

http://www.pnas.org/content/112/10/3122.full “Network compensation of cyclic GMP-dependent protein kinase II knockout in the hippocampus by Ca2+-permeable AMPA receptors”

Research that identified the source of generating gamma brain waves

gettingwell4 2-3 stars Required further work, Acetylcholine, Cerebrum, Neurochemicals , , ,

This 2015 Harvard rodent study found that specific brain neurons trigger cortical band oscillations in the gamma wave length. The cell type:

“Has increased activity during waking and is involved in activating the cerebral cortex and generating gamma oscillations, enabling active cortical processing.

Cortical gamma band oscillations are correlated with conscious awareness.”

1. News coverage of the study misreported the research’s consciousness findings by regurgitating the Harvard press release word-for-word. Several speculations thrown in by the PR staff weren’t supported by the findings regarding:

  • “Awareness of consciousness;
  • Aware of the lower levels of consciousness and their contents.”

2. The researchers used optogenetic stimulation of neurons, similar to the Activation of brainstem neurons induces REM sleep study. The current study took the extra step of lesioning cholinergic neurons to ensure the activity studied was due to the target neurons.

3. The neurons generated gamma waves by simultaneously turning off all receptor neurons, then simultaneously switching them all back on. The researchers said:

“Our results are surprising and novel in indicating that this presumptively inhibitory”

neuron type acted this way.

http://www.pnas.org/content/112/11/3535.full “Cortically projecting basal forebrain parvalbumin neurons regulate cortical gamma band oscillations”

How do we assess “importance” in our lives? An example from scientists’ research choices

gettingwell4 2-3 stars Required further work, Beliefs, Cerebrum, Primal Therapy , ,

This 2015 Virginia study found that scientists preferred research projects that had the potential to make:

“Deeper vs. broader contributions.

The scientists surveyed considered a hypothetical broader study, compared with an otherwise-comparable deeper study, to be riskier, a less-significant opportunity, and of lower potential importance.”

What were underlying motivations for subject scientists to become the Big Frogs in tiny puddles?

For example, if scientists recognized that there was an opportunity to positively influence a great number of human lives with a “broader” study, such as the hunger research proposed in Do the impacts of early experiences of hunger affect our behavior, thoughts, and feelings today? why would they prefer a “deeper” study such as starving fruit flies?

These researchers said that “scientists’ personal dispositions” accounted for this finding. I agree, but not for any of the specific reasons they stated.

Subjects’ “lower potential importance” judgments were key, and bear closer examination. The study’s supplementary material showed this consideration was made on a sliding scale in response to a question:

“Would you describe Project A (B) as potentially very important?”

The “lower potential importance” finding was an accumulation of each scientist’s personal judgment of a project described as:

“A broad project that spans several topical domains, including at least one that coincides with your area(s) of expertise and interest.

compared with:

“A focused and specialized project that fits your particular interests and leverages your deep expertise in a specific area.”

Weren’t personal judgments of the hypothetical project’s “potentially very important” aspect how each scientist predicted the project would make them feel important?

Given vague project descriptions in above quotations, I assert that their judgments’ contexts were “important to me” rather than “important to science” or “important to society” or important to some other context.

A relevant hypothesis of Dr. Arthur Janov’s Primal Therapy that applies to the “lower potential importance” finding is: the need to feel important is a defense against feeling unimportant due to early experiences of neglect.

Using principles referenced in the hunger post, the need to feel important is:

  1. A derivative need;
  2. A substitute for an unfulfilled need; and
  3. Caused by the impact of an early unmet need.

A corollary is that if an infant didn’t have early experiences of neglect, and their early needs were met, they likely wouldn’t develop derivative needs such as the need to feel important as they progressed through childhood, adolescence, and adulthood.

Are people motivated to act like the scientists who were subjects of this study? Do we make career and personal choices based on whether or not our work and other people make us feel important?

See my Welcome page and Scientific evidence page for further elaborations of this topic.

http://www.pnas.org/content/112/12/3653.full “Different personal propensities among scientists relate to deeper vs. broader knowledge contributions”

New role discovered for a speech area of the human prefrontal cortex

gettingwell4 2-3 stars Required further work, Brain hemispheres, Cerebrum

This 2015 human study found that an area in the left hemisphere of the prefrontal cortex involved with speech has characteristics not previously known:

“Broca’s area coordinates the transformation of information across large-scale cortical networks involved in spoken word production.”

The study found that this area:

“Disengages when we actually start to utter word sequences.”

It was previously thought that the Broca’s area was active during speech.

I looked throughout the study, footnotes and references, and couldn’t find the list of words that were used. The study would have shown more promise if the researchers had made an effort to include words with emotional content. For example, it’s possible that the Broca’s area may have different activation patterns when speaking with emotional content, or that it may account for part of the slowdown that normally occurs when we speak with feeling.

http://www.pnas.org/content/112/9/2871.full “Redefining the role of Broca’s area in speech”

One possible way that epigenetic DNA changes can pass from one generation to the next generation

gettingwell4 2-3 stars Required further work, Epigenetics

This 2015 roundworm study showed one possible way that epigenetic DNA changes could pass from one generation to the next generation:

  • The researchers caused nerve cells to transmit double-stranded RNA to germline cells.
  • The RNA changed the germline cells, and
  • The changes were passed down to the next 25 generations.

This was a new direction that had several known limitations ahead. The researchers didn’t show that this transmission mechanism worked in nature. Also, more complex species don’t retain most epigenetic changes between generations.

However:

http://www.pnas.org/content/112/7/2133.full “Double-stranded RNA made in C. elegans neurons can enter the germline and cause transgenerational gene silencing”

Research on brain areas involved when we imagine people, places, and pleasantness

gettingwell4 2-3 stars Required further work, Amygdala, Beliefs, Brain hemispheres, Cerebrum, Hippocampus, Limbic system, Thalamus ,

This highly jargoned 2014 Harvard study was on how people imagine that they’ll feel in the future.

One of the researchers was an author of:

I was surprised that this study also didn’t ignore the limbic system to the point to where the researchers wouldn’t even bother to measure important areas.

Limbic system areas that process people were different than those that process places. For example, the data in Table S4 showed that the subjects’ left amygdala and hippocampus were more activated when simulating future familiar people, whereas their right hippocampus was more activated when simulating future familiar places.

The researchers may have improved the study’s findings if they were informed by studies such as the Hippocampus replays memories and preplays to extend memories into future scenarios, which found that “place” cells in the CA1 segment of the hippocampus preplay events that imagine future scenarios of:

“Novel spatial experiences of similar distinctiveness and complexity.”

Such information may have helped to disambiguate one of the study’s findings in Table S5, that both sides of the subjects’ hippocampus were more activated than other brain regions when simulating both familiar people and places.

The researchers got a little carried away in broadly attributing most of the study’s findings to the ventromedial prefrontal cortex. For example, the data in Table S6 showed that the thalamus was more activated when the subjects anticipated positive pleasantness, but not when negative effects were anticipated.

We know from Thalamus gating and control of the limbic system and cerebrum is a form of memory that this is normally how the thalamus part of the limbic system actively controls and gates information to and from the cerebrum. Their data showed thalamic gating in operation:

  • Active when passing along pleasantness to cerebral areas, and
  • Passive when blocking unpleasantness from cerebral areas.

Also, I didn’t see how the researchers differentiated some of their findings from a placebo effect. For example, Using expectations of oxytocin to induce positive placebo effects of touching is a cerebral exercise found:

“Pain reduction dampened sensory processing in the brain, whereas increased touch pleasantness increased sensory processing.”

This was very similar to the above finding involving the thalamus.

http://www.pnas.org/content/111/46/16550.full “Ventromedial prefrontal cortex supports affective future simulation by integrating distributed knowledge”

Those of us who use painkillers rarely contemplate what pain it is that we’re targeting

gettingwell4 2-3 stars Required further work, Primal Therapy , ,

Those of us who use painkillers rarely contemplate what pain it is that we’re targeting. For example, alcohol is a painkiller, but when we drink, do we focus on pain?

Detox centers work on the symptoms but seldom address the causes of the patient’s pain. Psychiatrists have no problem dispensing psychoactive medication for symptoms, but do have a problem dealing with the causes of the patient’s pain.

Patients address causes of their pain in Primal Therapy, as explained in the two short videos What is Primal Therapy by Dr. Arthur Janov and Dr. Arthur Janov Book Expo America 2008 Interview.

Painkillers can also kill us. This 2013 rodent study investigated “a potential therapeutic target for treatment of oxidative-stress related liver diseases” especially acetaminophen overdose.

Per one of this study’s references:

“Currently, the only clinically available treatment for acetaminophen overdose is N-acetyl-cysteine, a glutathione precursor, which has to be administered within 15–16 hours after acetaminophen ingestion to be effective.”

http://www.pnas.org/content/111/8/3176.full “TRPM2 channels mediate acetaminophen-induced liver damage”

Our cerebrums use ideas and beliefs to repress pain and make us more comfortable

gettingwell4 2-3 stars Required further work, Beliefs, Cerebrum, Primal Therapy

One hypothesis of Primal Therapy is that a major function our cerebrums have evolutionarily adapted is to use ideas and beliefs to repress pain and make us more comfortable.

Is it any wonder why this 2014 study found:

“Beliefs are more prevalent among societies that inhabit poorer environments and are more prone to ecological duress.”

http://www.pnas.org/content/111/47/16784.full “The ecology of religious beliefs”

More from the researchers that found people had the same personalities at age 26 that they had at age 3

gettingwell4 2-3 stars Required further work, Brain development, Cerebrum, Limbic system, Lower brain ,

This 2014 research came from the Dunedin Study in New Zealand that has studied a group of over 1,000 people for 40+ years now. They first came to worldwide fame by finding that the study’s participants at age 26 largely had the same personality that each did at age 3.

The current study linked the participants’ childhood cognitive abilities and self-control to their current cardiac age.

Would a US doctor have the knowledge and foresight to understand that significant factors in a middle-aged patient’s cardiac health came from their early childhood, infancy, or womb life experiences?

http://www.pnas.org/content/111/48/17087.full “Credit scores, cardiovascular disease risk, and human capital”