2-3 stars Required further work

Research needing further work

Dopamine may account for differences in cognitive performance

gettingwell4 2-3 stars Required further work, Anterior cingulate cortex, Cerebrum, Dopamine, Hippocampus, Limbic system, Memory, Neurochemicals, Thalamus ,

This 2015 German human study found:

“Dopamine may account for adult age differences in brain signal variability.”

The researchers administered amphetamine to the subjects to boost their dopamine levels, and measured their cognitive performance on several working memory tests under fMRI:

“Older adults expressed lower brain signal variability at placebo, but met or exceeded young adult..”

brain signal variability levels when on speed.

The order of the tests also influenced the results. Older adults who received amphetamine during the initial series of tests performed better on placebo during the second series of tests.

As is often done, the researchers focused on effects and not causes. I didn’t see questionnaires or investigation into possible historical or biological factors for reduced dopamine levels, leaving the researchers with age as the only correlated-but-not-causative explanation.

http://www.pnas.org/content/112/24/7593.full “Amphetamine modulates brain signal variability and working memory in younger and older adults”

Measuring the signal-to-noise ratio of a brain neuron

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

This 2015 study found that a single brain neuron’s

“Spiking history is often a more informative predictor of spiking propensity than the signal or stimulus activating the neuron.

Characterizing the reliability with which neurons represent and transmit information is an important question in computational neuroscience.”

Three of the four brain neuron areas studied were of the limbic system: a rat thalamus, a monkey hippocampus, and a human subthalamus area.

http://www.pnas.org/content/112/23/7141.full.pdf “Measuring the signal-to-noise ratio of a neuron” (pdf file is linked because the html has errors)

An inhibitory gene that affects alcohol binge behavior

gettingwell4 2-3 stars Required further work, Beliefs, Cerebrum, Dopamine, Limbic system, Lower brain, Neurochemicals, Thalamus , , ,

This 2015 La Jolla rodent study found that an inhibitory gene affected alcohol binging behavior:

“Our study reveals the behavioral impact of this cellular effect, whereby the level of GIRK3 [the gene] expression in the VTA [ventral tegmental area] tunes ethanol intake under binge-type conditions: the more GIRK3, the less ethanol drinking.”

GIRK3-silenced mice still binged, though, and got alcohol’s rewarding effects through dopamine’s other neural pathways.

High concentrations of the gene were found in the thalamus part of the limbic system of wild-type mice, the control group. Per the study’s title, this gene presumably contributes to the thalamus’ overall function of gating information from limbic system and lower brain areas to reach the cerebrum and vice versa.

And the potential causes for reduced GIRK3 expression are..?? Hopefully – someday – researchers will be focused on finding causes for abnormal gene expression rather than being content to just study effects of abnormal gene expression. Until then, the usual practice of considering only the effects led these researchers to:

“Believe that a compound selectively targeting GIRK3-containing channels may hold promise for reducing alcohol consumption in heavy binge drinkers.”

http://www.pnas.org/content/112/22/7091.full “GIRK3 gates activation of the mesolimbic dopaminergic pathway by ethanol”

RNA as a proxy signal for context-specific biological activity

gettingwell4 2-3 stars Required further work, Brain development, Cerebrum, Hippocampus, Hypothalamus, Limbic system, Thalamus , ,

This 2015 Harvard/MIT rodent study was of long (more than 200 nucleotides) noncoding (non-protein coding) RNAs (ribonucleic acids). These are of interest because:

“Within the mammalian body, the largest repertoire and diversity of lncRNA genes outside the germ line occurs in the brain, where lncRNAs exhibit regional and cell-specific localization.

The expression patterns of lncRNAs may serve as a proxy signal for important, context-specific biological activity.”

The researchers explained what they could and couldn’t determine with current techniques and technologies:

“The whole-gene ablation method used here is often a first approach to determine the functionality of a locus.

Although each of these loci contains a lncRNA, it is important to consider that any observation resulting from this strategy could reflect the loss of any regulatory element in the deleted region.

The rate of lncRNA gene discovery has significantly outpaced our ability to evaluate both the physiological significance and function of these genes. It is difficult to predict whether the loss of any particular lncRNA locus will present a phenotype, but crucial information on the spatiotemporal dynamics of expression from each locus can provide significant direction and focus to downstream mechanistic studies by highlighting those loci most likely to have a physiological impact.

It is important to stress that no single method exists that can account for all possible mechanisms of action of a noncoding locus. Within these limits, the phenotypes observed after ablation of specific lncRNA loci confirm that expression of this class of noncoding RNAs can serve as a proxy signal to identify functional genomic loci with physiological relevance to disease and development, independent of whether this activity is directly ascribed to a functional lncRNA molecule.”

http://www.pnas.org/content/112/22/6855.full “Spatiotemporal expression and transcriptional perturbations by long noncoding RNAs in the mouse brain”

Limits of dMRI brain studies

gettingwell4 2-3 stars Required further work, Cerebrum

This 2015 macaque study found:

“∼50% of the cortical surface was effectively inaccessible for long-range diffusion tracking.

Current and future high-resolution dMRI [diffusion magnetic resonance imaging] studies of the human brain will need to develop methods to overcome the challenges posed by superficial white matter systems to determine long-range anatomical connections accurately.”

The researchers stated:

“Although in many respects the macaque brain is a good approximation of the human brain, both species have undergone profound evolutionary changes since the time of their most recent common ancestor living more than 20 million years ago, particularly in regard to the massive expansion of the cerebral cortex in the human brain. Thus, it is of great value to assess human anatomical connections directly and comprehensively.”

Sound familiar? That’s also the point I made in Do popular science memes justify researchers’ cruelties to monkeys?

http://www.pnas.org/content/112/21/E2820.full “Superficial white matter fiber systems impede detection of long-range cortical connections in diffusion MR tractography”

The thalamus part of the limbic system has a critical period for connections

gettingwell4 2-3 stars Required further work, Anterior cingulate cortex, Brain development, Cerebrum, Limbic system, Lower brain, Primal Therapy, Thalamus , , ,

This highly-jargoned 2015 UK study found that connections made by the thalamus of the developing human fetus had a critical period of the last trimester of womb-life. Babies born before the 33rd week of gestation experienced thalamic disconnections compared with normal-term babies and adults. The disconnections increased with a shorter womb-life.

The thalamus of premature babies also developed stronger connections with areas of the face, lips, tongue, jaw, and throat. They presumably needed these connections for survival actions such as breathing and feeding that aren’t a part of the last trimester of womb-life.

The study confirmed that the structures of thalamic connections of normal-term babies were very similar to those of adults. The study added to the research that shows that human limbic systems and lower brains closely approximate their lifelong functionalities at the normal time of birth.

It was difficult to measure the thalamus at this stage of life with current technology, and the researchers had to discard over two-thirds of their results. The researchers recommended monitoring these premature babies for difficulties in later childhood that may be caused by their early-life experiences.

Why would this monitoring recommendation apply to just the study’s subjects? We know from other studies that a main purpose of thalamic connections is to actively control and gate information to and from the cerebrum.

Would it make sense for a medical professional to disregard any patient’s birth history if they had problems in their brain’s gating functions or connectivity?

One researcher said:

“The ability of modern science to image the connections in the brain would have been inconceivable just a few years ago, but we are now able to observe brain development in babies as they grow, and this is likely to produce remarkable benefits for medicine.”

This study’s results provided evidence for a principle of Dr. Arthur Janov’s Primal Therapy: the bases for disconnection from aspects of oneself are often set down during gestation. The “remarkable benefits for medicine” are more likely to be along the lines of what I describe in my Scientific evidence page.

http://www.pnas.org/content/112/20/6485.full “Specialization and integration of functional thalamocortical connectivity in the human infant”

Do strong emotions cause our brain hemispheres to interact more closely?

gettingwell4 2-3 stars Required further work, Brain hemispheres, Cerebrum, Limbic system, Memory, Primal Therapy , ,

This 2015 human/macaque study found:

“The functional coordination between the two hemispheres of the brain is maintained by strong and stable interactions.

These findings suggest a notable role for the corpus callosum in maintaining stable functional communication between hemispheres.”

The human subjects were asked to:

“Generate four negative autobiographical memories and create word cues that reminded them of each event. Participants then underwent a 6-min IR fMRI scan during which they were cued with the words they had created to recall the two most negative autobiographic memories generated outside the scanner.”

However, the study’s supplementary material didn’t address why the researchers used this particular technique.

Does recalling strong emotional memories that engage our limbic systems cause our brain hemispheres to interact more closely than do cerebral exercises?

This study demonstrated that including emotional content in brain studies was essential. It may have provided additional information had the researchers also used the two least-negative emotional memories.

As noted in Agenda-driven research on emotional memories, one hypothesis of Dr. Arthur Janov’s Primal Therapy is that recalling an emotional memory engages one’s brain differently than does re-experiencing an emotional memory. Asking the subjects to attempt to re-experience the two least-negative emotional memories may have provided data relevant to the study.

I didn’t understand why macaques were used as subjects. The researchers didn’t provide any tasks for the monkeys during the scans. The information this study gained only duplicated other studies.

Also, the monkeys were anesthetized throughout the experiments. An assumption that wasn’t addressed: fMRI scan data on anesthetized macaques provided comparable evidence to fMRI scan data on normal non-anesthetized humans who were recalling emotional memories?

Did the researchers use macaques simply because they were available?

http://www.pnas.org/content/112/20/6473.full “Stable long-range interhemispheric coordination is supported by direct anatomical projections”

Do our unique visual perceptions arise from brain structural differences?

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

This 2014 UK/German human study involved fMRI scans of the subjects inferior temporal cortex while viewing images:

“Brain representational idiosyncrasies accessible to fMRI are expressed in an individual’s perceptual judgments.

We found evidence for an individually unique representation predictive of perceptual idiosyncrasies in hIT [human inferior temporal cortex] (but not in early visual areas) and for personally meaningful (but not for unfamiliar) objects.”

Citing other studies, the researchers said:

“The size of primary visual cortex varies across individuals by a factor of about 2.5.

Although other areas might vary by smaller factors, many parts of the brain, including cortical and subcortical structures, show gross anatomical variation across individuals that is predictive of cognitive and behavioral differences.”

The researchers asserted:

“Functional differences as reported here ultimately must arise from differences in the physical structure of each individual brain.”

However, no evidence was provided for this assertion.

The researchers acknowledged this lack of evidence, but in a way that required further evidence:

“Our study demonstrates individual differences in high-level semantic representations but cannot address their structural basis. Our current interpretation is that the representational idiosyncrasies might arise from the microstructural plasticity of cortex, which is driven by individual experience.”

The researchers’ assertion beyond the study’s supporting data was at best a statement of their goal. Further, their bias to focus on the inferior temporal cortex area of the cerebrum led them to not investigate other areas of the brain that may have been involved with the “personally meaningful (but not for unfamiliar) objects” finding, such as the subjects’ limbic systems.

I hope that researchers won’t think that their research is complete when they reach their goal of finding “differences in the physical structure of each individual brain.” It would be far more informative to understand the causes for these effects.

http://www.pnas.org/content/111/40/14565.full “Unique semantic space in the brain of each beholder predicts perceived similarity”

People who donated a kidney to a stranger have a larger amygdala

gettingwell4 2-3 stars Required further work, Amygdala, Brain hemispheres, Cerebrum, Epigenetics, Limbic system ,

This 2014 Georgetown study was of people who had donated a kidney to a stranger. The study found that the subjects had a larger right amygdala part of their limbic systems:

“Our results support the possibility of a neural basis for extraordinary altruism.

In sum, our findings suggest that individuals who have performed an act of extraordinary altruism can be distinguished from healthy controls by increased right amygdala volume, as well as heightened responsiveness in right amygdala to fearful facial expressions, which may support enhanced recognition of these expressions.”

The researchers stopped short of causal explanations. They stated in the study’s abstract that:

“Individual variation in altruistic tendencies may be genetically mediated”

but didn’t develop any evidence to support this statement.

It would have been within the scope of the study had the researchers continued on to examine:

  • What may have happened in the subjects’ lives to possibly cause their neurobiological and psychological attributes?
  • What were the causes for the subjects’ extreme altruistic behavior?
  • Were these the same causes for their larger, more sensitive amygdala?

An accompanying PNAS commentary from a Harvard researcher made other points. However, the author showed his biases that the cerebrum rules human behavior with an out-of-left-field question at the end of a paragraph in which he developed specious reasoning.

The commentator was completely off base when he stated:

“Could it be that extraordinary altruists such as Maupin [a study participant] and the 19 individuals studied by Marsh et al. [the researchers] are special, not only because of how they feel when they see people in distress, but because of how they think?”

I don’t imagine that the brilliant commentator’s attempt to upstage the study’s subjects and put the spotlight on himself for some brilliant idea was much appreciated by anyone involved.

The amygdala is the central hub of a person’s limbic system. The study’s findings had very little to say about the subjects’ cerebral activity – thinking.

To postulate that the researchers missed that there was something different about the subjects’ thinking was out of touch with the realities of both the researchers’ scientific bases and the subjects. It’s another example of the current research mindset/social meme of cerebral dominance.

http://www.pnas.org/content/111/42/15036.full “Neural and cognitive characteristics of extraordinary altruists”

A missed opportunity to research the oxytocin receptor gene and autism

gettingwell4 2-3 stars Required further work, Amygdala, Brain development, Epigenetics, Hypothalamus, Limbic system, Neurochemicals, Oxytocin, Vasopressin ,

This 2013 study:

“Examined whether genetic variants of the OXTR [oxytocin receptor] affect face recognition memory in families with an autistic child.

We investigated whether common polymorphisms in the genes encoding the oxytocin and vasopressin 1a receptors influence social memory for faces.”

I feel that the researchers missed an opportunity to improve their assessment of the autism-related genetic contribution to the study’s findings by separating the degree of environmental influence on the oxytocin receptor gene expression, as did the How epigenetic DNA methylation of the oxytocin receptor gene affects the perception of anger and fear study.

An assessment of epigenetic DNA methylation of the oxytocin receptor gene may have been even more compelling because the researchers genetically sampled one non-autistic sibling in each of the autistic children’s families. I hope the study’s samples are still available, because they may offer the possibility of evaluating the contribution of the autistic children’s historical environment with potential confirmation from their siblings.

Both studies gave their subjects similar facial emotion recognition tests, with the current one deriving from findings about autism, and the second from findings about the amygdala. The studies also had common references, such as a 2010 study, A common allele in the oxytocin receptor gene (OXTR) impacts prosocial temperament and human hypothalamic-limbic structure and function.

http://www.pnas.org/content/111/5/1987.full “Common polymorphism in the oxytocin receptor gene (OXTR) is associated with human social recognition skills”

Emotion inclusion in basic research drives discovery

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

What happens when a meme influences science? It would seem that researchers’ perceptions start to wheel around its axis.

A meme was the driver of this short 2015 commentary that stated:

“Most preclinical biomedical research, however, has been conducted with inadequate consideration of sex.”

If researchers discovered that gender hadn’t been adequately considered in research, maybe other “evolutionarily fundamental” factors had “inadequate consideration” as well.

Maybe one day soon, researchers will stop the current widespread exclusion of emotional content in studies, especially when the studies already included areas of the brain that are the biological bases of emotions.

To imagine a potentially beneficial future meme, I substituted the word “emotion” for “sex” in the title and part of two paragraphs of this commentary. How well does this fit?

“[Emotion] inclusion in basic research drives discovery”

“Why is [emotion] so important?

Although many factors can influence an outcome, [emotion] is evolutionarily fundamental and affects the whole of the population

Across diverse disciplines, researchers risk drawing erroneous conclusions when they extrapolate outcome data from [emotional to non-emotional and vice versa].”

See A missed opportunity to study odor-evoked emotional memories for one deliberate exclusion of emotional content, although including emotions may have been appropriate, informative, and contributed to advancing science.

Click the hippocampus category to see a sample of human studies that may have included the biological seat of emotional memories, but only a scarce few of which included emotional content.

http://www.pnas.org/content/112/17/5257.full “Opinion: Sex inclusion in basic research drives discovery”

Genetic programming of hypothalamic neurons regulates food intake and body weight

gettingwell4 2-3 stars Required further work, Brain development, Hypothalamus, Limbic system ,

These 2015 Michigan/Argentinian fish and rodent studies were of the genetic programming of specific neurons in the hypothalamus. The study linked below found:

“Food intake and body weight regulation depend on proper expression of the gene” in these neurons.

In a second study released at the same time from the same researchers:

“The researchers found that the two enhancers act in ways that complement one another, both encouraging the expression of the Pomc gene at key times. One of the two is found in the same form among all mammals, the other among all placental mammals – suggesting that they’ve been kept intact throughout the evolutionary process.”

Genetic programming of these neurons begins during early brain development. One of the researchers said:

“This work represents the first example of a neuron-specific gene in vertebrates where we have found both the enhancers and a shared transcription factor that control gene expression in the developing brain and then throughout the life span of the adult.”

The first study showed that if the genetic expression of these hypothalamic neurons was disrupted, the individual lost control of their eating (hyperphagia) and the usual result was severe obesity:

“We don’t know, but we think it likely, that it [regulation of these specific hypothalamic neurons in humans] may be similar to the mouse model, where its role is like a dial, with a linear relationship between the amount of Pomc [the gene] expression and the degree of obesity.”

I hope that when extending this research to humans, the researchers don’t exclude emotional content like most studies involving areas of the limbic system have done. Everyone has feelings intermixed with eating and foods. It’s a great disservice to have publicly funded studies not include aspects of emotion that could potentially help people.

http://www.pnas.org/content/112/15/E1861.full “Islet 1 specifies the identity of hypothalamic melanocortin neurons and is critical for normal food intake and adiposity in adulthood”

Is IQ an adequate measure of the quality of a young man’s life?

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

This 2015 Virginia study used Swedish data to find:

“Adoption into improved socioeconomic circumstances is associated with a significant advantage in IQ.”

The study’s all-male subjects were in 436 sibling relationships:

“..in which at least one member was reared by one or more biological parents and the other by adoptive parents. IQ was measured at age 18–20 as part of the Swedish military service conscription examination.”

One researchers said:

“Environmental effects have to be inferred, as in the rare event when pairs of siblings are raised by different parents in different socioeconomic circumstances. Swedish population data allowed us to find that homes led by better educated parents produce real gains in cognitive abilities of children they raise.”

The biological families’ situations had to be hellishly tragic in order to separate siblings and put one of them up for adoption. I didn’t find at what age separations typically took place, but can you imagine what the adopted child felt?

Let’s approach this study from the adopted boys’ perspectives:

  • Children are very sensitive to caregivers’ words, body language, facial expressions, physical touches – to all the things that show them they are loved.
  • A child learns at an early age from both implicit and overt expressions whether or not they are accepted for who they are.

It’s extremely traumatic for a child to be rejected for who they are. Consider this passage from Dr. Arthur Janov’s book The Primal Scream:

“Parental need becomes the child’s implicit command.

The child is born into his parents’ needs and begins struggling to fulfill them almost from the moment he is alive.

He may be pushed to smile (to appear happy), to coo, to wave bye-bye, later to sit up and walk, still later to push himself so that his parents can have an advanced child.

As the child develops, requirements upon him become more complex:

  • He will have to get A’s;
  • Be helpful and do his chores;
  • Be quiet and undemanding;
  • Not talk too much;
  • Say bright things; and
  • Be athletic.

What he will not do is be himself.”

All of the above can happen within a stable family.

Can you imagine what a child in an unstable family felt as they learned they weren’t accepted, and how they tried to adapt?

Everything these adopted children did to be accepted by their original caregivers failed. They were rejected by and ejected from the people who were supposed to love them!

Can you imagine how desperate these adopted children would have been in their new environment?

What wouldn’t they have done to be accepted?

The researchers made a point of cognitive development. But of all of the things that were important to the adopted child, that described his quality of life, does the finding of a higher IQ give even the slightest hint of his reality?

http://www.pnas.org/content/112/15/4612.full “Family environment and the malleability of cognitive ability: A Swedish national home-reared and adopted-away cosibling control study”

Epigenetic production of new brain neurons in the hippocampus

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

This 2015 La Jolla rodent study provided further details on the production of new neurons in the adult hippocampus:

“We propose that SOX2 sets a permissive epigenetic state in neural progenitor cells, thus enabling proper activation of the neuronal differentiation program under neurogenic cue.”

The researchers stated that the functions of these new brain neurons were:

“Newborn granule neurons generated from neural progenitor cells in the adult hippocampus play a key role in spatial learning and pattern separation.”

http://www.pnas.org/content/112/15/E1936.full “SOX2 primes the epigenetic landscape in neural precursors enabling proper gene activation during hippocampal neurogenesis“

How well can catastrophes be predicted?

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

This 2015 study found a way of modeling catastrophic shifts that smoothed the processes with selectively introduced randomness:

“Most computer models created for the purpose of predicting catastrophes are based on deterministic math—that is, they assume a perfect world where nothing is random. That approach cannot work in the real world of course, because real catastrophes quite often have several contributing factors that are random in nature.

In real life, such events exhibit another common trait of catastrophes, a group of rapid transitions that come about due to a small change in a system.”

If this study’s findings were correct, it would seem that researchers who put together models that used deterministic algorithms to predict catastrophes may have been just expressing their beliefs instead of assessing reality.

There apparently are many researchers whose models incorporate catastrophes. A search on PNAS.org for “catastrophic” shows over 100 studies published since the beginning of last year.

In a related question: Does everything happen for a reason?

  • If randomness is included as a reason, maybe things do.
  • If randomness is excluded, then we’re back to beliefs instead of reality.

In perhaps an unrelated question: Can catastrophes be predictably avoided in our personal lives?

  • Maybe most of them can, if we can eliminate sources of potential harm.
  • Probably not entirely avoided, though, because of the randomness factor.

It’s difficult to have a balanced degree of concern about future harm. Here’s a view from Dr. Arthur Janov in his Primal Healing book p. 70:

“Worrying is not a problem, it is the symptom of something that is occurring physiologically within the brain. What causes the worrying is the problem.

Constant worry is anticipating catastrophe. But what we don’t realize is that the catastrophe already has happened; we simply have no access to it.

We are actually worried about the past, not the future.”

http://www.pnas.org/content/112/15/E1828.full “Eluding catastrophic shifts”

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.