Emotionless brain research that didn’t deal with human reality

Are the tasks you do at work and home never influenced by emotional content or contexts?

Does your ability to focus on a task always have nothing to do with your emotional state?

The researchers who designed this 2015 Boston human study acted as if both of your answers to the above questions were “Yes” by stripping out any emotional content from their experiments. As a result, the study which purported to:

“Have the potential to provide additional insights into how inhibitory control may break down in a wide variety of individuals with neurological or psychiatric difficulties”

couldn’t achieve anything near this goal.

This study included fMRI scans of the subjects’ entire brains. Limbic system areas were in 3 of the 5 modules, and lower brain areas were in one.

Functional MRI signals depend on the changes in blood flow that follow changes in brain activity. Given this study’s goal, did it make sense for the researchers to design experiments that didn’t actively engage the scanned areas of the subjects’ brains?

It wasn’t all that difficult to include emotional content that could potentially contribute to the purported goal. This 1996 review described studies that developed varieties of emotional content with the same test type (Stroop) used in the current study. Presumably these approaches had made progress since 1996 incorporating emotional content in Stroop tests given to normal people, who were the subjects of this study.

http://www.pnas.org/content/112/32/10020.full “Flexible brain network reconfiguration supporting inhibitory control”

Further limits on using monkeys to understand human brains

This 2015 Columbia human/macaque study found:

“Fundamental differences in the attention-related brain areas in the two species, including the complete absence, in monkeys, of a ventral-attention network present in humans.

We did not find functional evidence of a temporoparietal junction in macaques.

The two species last shared a common ancestor 25 million years ago, and in the intervening time the brain areas underlying cognition have likely evolved along different paths.

The results of this study indicate that macaque data should be applied to human models of cognition cautiously, and demonstrate how evolution may shape cortical networks.”

The main point of this study was the same as noted in Limits of dMRI brain studies, which advised – instead of performing studies on monkeys to understand humans:

“Assess human anatomical connections directly and comprehensively.”

We can look forward to times when using macaques in studies such as:

is no longer acceptable.

http://www.pnas.org/content/112/30/9454.full “Functional evolution of new and expanded attention networks in humans”

Genetic statistics don’t necessarily predict the effects of an individual’s genes

I curated this 2015 Howard Hughes Medical Institute rodent study of DNA methylation because of the reason driving the researchers’ efforts:

“Epigenomic analyses are limited by averaging of population-wide dynamics and do not inform behavior of single cells. We observe dynamics at the single-cell level not predicted by epigenomic analysis.”

This rationale was also the driving force behind the Is what’s true for a population what’s true for an individual? study and its companion Changing an individual’s future behavior even before they’re born. The methodology of genome-wide association studies (GWAS) usually:

“Focuses on the average effect of alternative alleles averaged in a population.”

What this methodology often missed was:

“When phenotypic variation results from alleles that modify phenotypic variance rather than the mean, this link between genotype and phenotype will not be detected.”

Population-wide epigenetic statistics don’t necessarily inform us about the epigenetic activities and attributes of an individual’s genes, even down at the single-cell level.

http://www.pnas.org/content/112/31/E4216.full “The Xist RNA-PRC2 complex at 20-nm resolution reveals a low Xist stoichiometry and suggests a hit-and-run mechanism in mouse cells”

How brain neurons remain stable when constantly stimulated

This 2015 UK rodent study provided details of how neurons in the hippocampus respond to stimuli. The researchers found that hippocampal neurons:

“Remain electrically stable when confronted with chronic increases in neuronal activity.”

Changes in electrical potential changed the initial segment of the neuron’s axon.

Synapses formed along the segment, and stayed in place while this highly-plastic segment moved along the axon. The location mismatch:

“Allows the GABAergic [producing gamma-Aminobutyric acid, an inhibitory neurochemical] synapses to strongly oppose action potential generation, and thus downregulate pyramidal cell excitability.”

The researchers also used the two antioxidants endogenous to humans, superoxide dismutase and glutathione, to supplement the culture medium.

http://www.pnas.org/content/112/31/9757.full “Activity-dependent mismatch between axo-axonic synapses and the axon initial segment controls neuronal output”

Are a child’s genes the causes for their anxiety?

This 2015 Wisconsin macaque study was another attempt to justify the school’s continuing captivity of thousands of monkeys. The researchers performed a study that – if its experimental design was truly informative for helping humans – could have been done with humans.

A problem I saw in the news coverage was that the finding of:

“35 percent of variation in anxiety-like tendencies is explained by family history”

was attributed to genetics, with headlines such as “Anxious Brains Are Inherited, Study Finds.” The lead researcher encouraged this misinterpretation with statements such as:

“Over-activity of these three brain regions are inherited brain alterations that are directly linked to the later life risk to develop anxiety and depression.”

However, the researchers produced this finding by running numbers on family trees, not by studying genetic samples to assess the contributions of genetic and epigenetic factors!

The study’s “family history” correlation was different than finding an inherited genetic causation that wasn’t influenced by the subjects’ caged environments!

The study found:

“Metabolism within a tripartite prefrontal-limbic-midbrain circuit mediates some of the inborn risk for developing anxiety and depression.

The brain circuit that was genetically correlated with individual differences in early-life anxiety involved three survival-related brain regions. These regions were located in the brain stem, the most primitive part of the brain; the amygdala, the limbic brain fear center; and the prefrontal cortex, which is responsible for higher-level reasoning and is fully developed only in humans and their primate cousins.”

The 592 subjects were the human-equivalent ages of 3 to 12 years old. Primate brainstems and limbic systems are fully-developed BEFORE these ages.

The researchers skipped over potential evidence for the important contributions of epigenetic factors to “the later life risk to develop anxiety and depression” that change the studied brain areas during womb-life, infancy, and early childhood. Studies such as:


  1. A developing fetus adapts to being constantly stressed by an anxious mother.
  2. When these adaptations persist after birth, they may present as physiological and behavioral maladaptations of the infant and young child to a non-stressful environment.
  3. Later in life, these enduring changes may be among the causes of symptoms such as the anxious overreactions the current study found.

http://www.pnas.org/content/112/29/9118.full “Intergenerational neural mediators of early-life anxious temperament”

Over 500 million people affected but no news coverage

Sometimes I wonder how research becomes newsworthy. I couldn’t find any news coverage of this 2015 Chinese rodent study which provided details of the effects of a gene for which:

“Over 500 million people worldwide carry a specific polymorphism.

Is a risk factor for liver cancer.”

1 out of every 15 people alive today has this condition, and can expect:

“Increased sensitivity to acute or chronic alcohol-induced toxicity

Higher risk for gastrointestinal cancers

Enzyme deficiency in the liver, leading to inefficient detoxification of aldehydes and accumulation of cancer-causing mutations.”

Was the lack of news coverage because 40% of East Asians are affected? Would this study become newsworthy if 40% of some other group was affected?

http://www.pnas.org/content/112/29/9088.full “ALDH2(E487K) mutation increases protein turnover and promotes murine hepatocarcinogenesis”

Perpetuating the meme that rodent PTSD experiments necessarily apply to humans

This 2015 Texas A&M rodent study found:

“Propranolol administration dampened the stress-induced impairment in extinction observed when extinction training is delivered shortly after fear conditioning.”

The researchers were way off base in extrapolating this study to humans:

“Propranolol may be a helpful adjunct to behavioral therapy for PTSD, particularly in patients who have recently experienced trauma.”

Would National Institutes of Health Grant R01MH065961 money have been available without perpetuating the meme that rodent PTSD experiments necessarily apply to humans? Or are a priori findings necessary in order to get research funded?

In rodent studies such as this one, the origins of both the disease and the “cure” are all exerted externally. But humans aren’t lab rats. We can perform effective therapy that doesn’t involve some outside action being done to us.

Studies such as Fear extinction is the learned inhibition of retrieval of previously acquired responses make clear that extinction is equivalent to suppression. “Behavioral therapy for PTSD” that suppresses symptoms can’t be a “cure” for humans since the original causes for the symptoms aren’t treated.

Even if this study’s recommendation to administer a drug applied to humans, neither drugs nor “behavioral therapy for PTSD” address the underlying causes.

http://www.pnas.org/content/112/28/E3729.full “Noradrenergic blockade stabilizes prefrontal activity and enables fear extinction under stress”

What could cause humans to have a unique sense of smell?

This 2015 Israeli human study found:

“Each person expresses a nearly unique set of different olfactory receptor genes, and therefore may have unique olfactory perception.”

From news coverage of the study, the researchers thought that their findings may be of use for:

“Smell-based social networks

A diagnostic tool for diseases that affect the sense of smell, such as Parkinson’s

A security biometric.”

The researchers attempted to link the subjects’ olfactory components to components of their immune systems. Since studies such as:

provided details on how our immune systems become unique, it would follow that this study’s subjects’ immune systems may have been the underlying cause for the findings.

However, in the study’s limitations paragraph, the researchers stated that this study didn’t demonstrate such causes:

“We did not directly measure genetic makeup.

Given that HLA [human leukocyte antigen genes that regulate our immune systems] captures self and olfactory fingerprints capture self, then there will be a link between HLA and olfactory fingerprints even if they are not the result of linked genes.”

Perhaps the causes for our “unique olfactory perception” will be researched in future studies.

http://www.pnas.org/content/112/28/8750.full “Individual olfactory perception reveals meaningful nonolfactory genetic information”

What’s an appropriate control group for a schizophrenia study?

The researchers who did the Our long-term memory usually selects what we pay closer visual attention to study were back zapping subjects’ brains again in this 2015 human study.

From news coverage of the study, prior to zapping the subjects’ brains:

“In healthy individuals, these theta waves were steady and synchronized, but in people with schizophrenia, the waves were weak and disorganized, suggesting that they were having a harder time processing the mistake. And the subjects’ behavior bore that out—the healthy subjects slowed down by a few milliseconds when they made mistakes and did better in the next round, while the subjects with schizophrenia did not.”

The processing of an appropriate control group wasn’t clear to me from reading the supplementary material. The subject patients were diagnosed with schizophrenia and took psychoactive medication which the researchers equated to chlorpromazine (Thorazine) dosages. The control group subjects had neither the condition nor were prescribed the medications.

How did the researchers differentiate the influences of psychoactive medications on the experimental results from the influences of the subject patients’ conditions?

Were there numerical calculations not shown in the supplementary material that somehow nullified the effects of psychoactive medications?

To be sure that the zapping was effective for the subject patients’ conditions, wouldn’t the control group subjects need to take the same medications so that the experimental data reflected only the differences attributable to schizophrenia?

The researchers also asserted:

“Causal changes in the low-frequency oscillations improved behavioral responses to errors and long-range connectivity at the single-trial level.”

However, brain waves can’t be termed as base causes of human behavior. Studies such as:

clearly established that brain waves are effects of base causes.

Was there something that stopped the researchers of this study from investigating the generating sources of brain waves? Was it that they work in the same Vanderbilt University department as the researchers of A study of visual perception that didn’t inform us about human conscious awareness, and were similarly biased against brain research that may lead to finding evolutionary biological causes for human behavior?

http://www.pnas.org/content/112/30/9448.full “Synchronizing theta oscillations with direct-current stimulation strengthens adaptive control in the human brain”

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Using epigenetic DNA methylation markers to estimate biological age

I curated this 2015 Georgia human study only for its use of two methods of estimating biological age. The researchers misguidedly used these techniques to help paint a scientific patina on an agenda.

One of the methods was originated by a coauthor of The degree of epigenetic DNA methylation may be used as a proxy to measure biological age study. He compared his epigenetic clock technique with the other technique here:

  • His technique used the same 353 DNA regions (CpGs, cytosine and guanine separated by only one phosphate link) across different tissues to compare tissue/organ ages;
  • “The DNA methylation levels of 193 of these markers increase with age but the remaining 160 markers show the opposite behavior.”

  • His technique had a Pearson correlation coefficient of r=0.96 with chronological age in this 2013 study;
  • The other technique:

    “Works poorly for blood samples from subjects who are younger than 20.”

That such methods were available calls into question why the researchers of A study of biological aging in young adults with limited findings didn’t avail themselves of these techniques. They used techniques that were less informative such as telomere length. As an example of how that study’s methods were known to be limited, this 2009 study found that the correlation between chronological age and telomere length was r = −0.51 in women and r = −0.55 in men.

http://www.pnas.org/content/112/33/10325.full “Self-control forecasts better psychosocial outcomes but faster epigenetic aging in low-SES youth”