Prefrontal cortex

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 popular science memes justify researchers’ cruelties to monkeys?

gettingwell4 0-1 star Wasted resources, Anterior cingulate cortex, Cerebrum, Limbic system

This 2015 Oxford study of 38 humans and 25 macaques drew correlations of brain activities between the two species. The study title included buzzwords such as “reward” and “decision making” and the study focused on the ever-popular “frontal cortex.”

Humans and macaques are separated by 25 million years of evolutionary adaptations and developments. Studies done with macaque subjects don’t automatically have human applicability.

Was a major reason for the study’s comparisons to provide justifications for keeping macaques as study subjects? Accepting these justifications and going along with the popular memes would ease the way for whatever cruelties researchers want to inflict on our primate relatives.

http://www.pnas.org/content/112/20/E2695.full “Connectivity reveals relationship of brain areas for reward-guided learning and decision making in human and monkey frontal cortex”

Kids who have a larger and better-connected hippocampus learn math better when tutored

gettingwell4 0-1 star Wasted resources, Brain development, Cerebrum, Hippocampus, Limbic system, Memory, Thalamus ,

This 2013 Stanford study of 24 eight- and nine-year-old children found that measurements of limbic system areas predicted how well the 11 boys and 13 girls would respond to 8 weeks of one-on-one math tutoring!

“Pretutoring hippocampal volume predicted performance improvements. Furthermore, pretutoring intrinsic functional connectivity of the hippocampus with dorsolateral and ventrolateral prefrontal cortices and the basal ganglia also predicted performance improvements.

Brain regions associated with learning and memory, and not regions typically involved in arithmetic processing, are strong predictors of responsiveness to math tutoring in children. More generally, our study suggests that quantitative measures of brain structure and intrinsic brain organization can provide a more sensitive marker of skill acquisition than behavioral measures.”

None of the assessments, such as IQ and working memory tests, predicted how much benefit a child would receive from one-on-one math tutoring. The 16 children in the control group who didn’t receive one-on-one math tutoring didn’t improve their math performance over the 8-week period. Adults use different brain areas when solving math problems.

Much of the news coverage was from vested interests who dismissed the findings. A typical headline was “Your child’s brain on math: Don’t bother?”

The No Child Left Behind people were concerned that science could predict that some children were better suited to math tutoring than others. Psychiatrists and psychologists responded with general dismissals like small sample size, and the journalist let that stand without asking them how they disagreed with any of the specific P-, T- and other values found in the study’s supplementary material.

The researchers were careful to invoke a politically-correct meme of “individual differences“ 19 times, including the study’s title!

“Individual differences” isn’t a causal explanation, however. The journalist whiffed and also gave a pass to the researchers on this uninformative-but-PC meme.

It certainly would have been within the scope of this study for the researchers to inquire further into causes for the findings. It possibly could have informed us of causal factors had the children’s test battery included emotional content, as did the subjects in the Early emotional experiences change our brains: Childhood maltreatment is associated with reduced volume in the hippocampus study.

http://www.pnas.org/content/110/20/8230.full “Neural predictors of individual differences in response to math tutoring in primary-grade school children”

The prefrontal cortex develops more repressive function at puberty

gettingwell4 4-5 stars Advanced knowledge, Brain development, Cerebrum, Primal Therapy , ,

This 2014 primate study found:

“The average magnitude of functional connections measured between neurons was lower overall in the prefrontal cortex of peripubertal [age when puberty starts] monkeys compared with adults. The difference resulted because negative functional connections (indicative of inhibitory interactions) were stronger and more prevalent in peripubertal compared with adult monkeys.”

The researchers found more inhibitory functional connections at the onset of puberty than during adulthood. This repressive functionality presumably develops at puberty because that’s when it’s relatively more needed:

“The bias toward increased inhibitory connectivity we report here for young monkeys might also be an intrinsic feature of human prefrontal cortex at a comparable stage of development.”

One hypothesis of Dr. Arthur Janov’s Primal Therapy is that repression is an important function that the prefrontal cortex evolved.

http://www.pnas.org/content/111/10/3853.full “Age-dependent changes in prefrontal intrinsic connectivity”

Can a Romanian orphan give informed consent to be an experimental subject?

gettingwell4 < 0 Detracted from science, Amygdala, Brain development, Cerebrum, Cortisol, Hypothalamus, Limbic system, Neurochemicals, Stress , ,

This 2015 study used Romanian orphans as lab rats for findings of which I failed to see the value. The world didn’t really need any further research to demonstrate that foster care would be better for a child than staying in an orphanage.

The researchers placed the orphans in five separate stressful situations, and measured their cortisol and DHEA-S levels, along with their electrocardiograph and impedance cardiograph activity. The findings were:

“Children who were removed from the Romanian institutions and placed with foster parents before the age of 24 months had stress system responses similar to those of children being raised by families in the community.

The children raised in institutions showed blunted responses in the sympathetic nervous system, associated with the flight or fight response, and in the HPA axis, which regulates cortisol.”

One unsupported assertion from the researchers was:

“We provide evidence for a causal link between the early caregiving environment and stress response system reactivity in humans with effects that differ markedly from those observed in rodent models.”

The researchers stated that rodent studies have converged to find:

“Early-life adversity results in hyperreactivity of the sympathetic nervous system (SNS) and hypothalamic–pituitary–adrenal (HPA) axis.”

It’s baloney that the same results from early life adversity in rodents haven’t also been present in humans. Even the lead researcher herself said in a news article:

“More significantly, McLaughlin said, their [the orphans] stress response systems might have been initially hyperactive at earlier points in development, then adapted to high levels of stress hormones.”

The difference was that the rodents were monitored 24/7 until researchers killed and dissected them. The children’s periods of adversity likely started while in the womb, and their lives had been monitored for research purposes sporadically after their births.

Everybody knows that just because adverse events and effects in these children’s lives weren’t recorded by researchers didn’t mean these effects weren’t present at some point.

Particularly irksome was another unsupported assertion from the lead reviewer:

“The children involved in the study are now about 16 years old, and researchers next plan to investigate whether puberty has an impact on their stress responses. It could have a positive effect, McLaughlin said, since puberty might represent another sensitive period when stress response systems are particularly tuned to environmental inputs. “It’s possible that the environment during that period could reverse the impacts of early adversity on the system,” she said.”

No, this is NOT possible. We may as well expect an apple to fall upward.

The impacts of early adversity persist with enduring physiological changes as shown in experimental studies. Studies have NOT provided evidence that the subjects’ environment can cause the effects of complete reversal of all these changes, no matter the stage of life of the subjects.

This point was addressed in The effects of early-life stress are permanent alterations in the child’s brain circuitry and function rodent study:

“The current study manipulates the type and timing of a stressor and the specific task and age of testing to parallel early-life stress in humans reared in orphanages.

The results provide evidence of both early and persistent alterations in amygdala circuitry and function following early-life stress.

These effects are not reversed when the stressor is removed nor diminished with the development of prefrontal regulation regions.”

That study had the same reviewer as the current study. The current study’s lead researcher knew or should have known of this and other relevant research. She knew or should have known of the irreversibility of critical periods, during which developments either occurred or were forever missed.

Did the lead researcher make assertions not supported by the study or relevant research – assertions made counter to her scientific knowledge – show her unease about treating the orphans as lab rats? Was there was some other agenda in play?

The larger problem was the study’s informed consent with this group of Romanian orphans. If you were in contact with a damaged person, and implicitly gave them hope that you would improve their life, then who are you as a feeling human being when you don’t personally carry through? Does the legal documentation matter?

Also, I’ve noticed problems with several studies that had this particular reviewer:

Add the current study to the list.

http://www.pnas.org/content/112/18/5637.full “Causal effects of the early caregiving environment on development of stress response systems in children”

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Problematic research that ignored the hippocampus as the seat of emotional memories

gettingwell4 < 0 Detracted from science, Cerebrum, Hippocampus, Limbic system, Memory

If this 2015 human study from the San Diego Veterans Administration developed findings of any note, I didn’t see them.

Like other studies, this study ignored the hippocampus’ position as the seat of emotional memories. The experiments were designed to not contain any emotional content.

The researchers mainly wanted to fight a 60-year old battle on whether or not the hippocampus contributed to spatial processing. They ignored all the research on place cells, such as:

to name three of the hundreds of place cell studies available.

By ignoring these and other studies, the researchers declared:

“We have not found evidence that this is the case.”

The lead researcher continued with speculations that couldn’t be verified with the current experiments’ data:

“We think they can do these spatial tasks because these tasks can be managed within short-term memory functions, supported by the frontal lobe of the neocortex.

The spatial tasks that we can do with our neocortex using short-term memory must be performed by the hippocampus in rats.”

Basically, the rest of the scientific world must supply irrefutable evidence (which will be ignored) but the reader can just take the lead researcher’s words as fact for what’s going on inside human and rodent brains, although:

  • No fMRI scans were performed during the experiments,
  • No hard measurements were taken.

The findings were based on observations of six subjects:

  • With hippocampal lesions of unspecified duration,
  • Drawing pictures, and
  • Narrating what they imagined about a playground.

I wonder what the reviewers saw in this study that factually advanced science. Did the statement:

“These results support the traditional view that the human hippocampus is primarily important for memory.”

convey something new? Make a contribution to science?

Studies like this one not only detract from science. They are also a waste of resources that supposedly the Veterans Administration have in short supply.

The design and data of such studies are not able to reach levels where they can provide evidence of causes and effects of anything within their scope. That’s a good indication of some other agenda in play.

http://www.pnas.org/content/112/15/4767.full “Memory, scene construction, and the human hippocampus”

A common dietary supplement that has rapid and lasting antidepressant effects

gettingwell4 4-5 stars Advanced knowledge, Cerebrum, Epigenetics, Glutamate, Hippocampus, Limbic system, Neurochemicals, Stress , , ,

This 2012 Italian rodent study found that a common dietary supplement had rapid and lasting antidepressant effects:

“Remarkably, L-acetylcarnitine displayed a clear-cut antidepressant effect already after 3 and 7 d[ays] of daily dosing. No tolerance was developed to the action of L-acetylcarnitine. The drug was even more effective after 21 d[ays], and the effect persisted for at least 2 w[ee]k[s] after drug withdrawal.”

The researchers studied stressed mice and rats to determine that:

  1. An effect of the stress was to epigenetically change the hippocampus to produce less of an important molecule – type 2 metabotropic glutamate (mGlu2).
  2. A reduction of the mGlu2 molecule decreased the hippocampus’ regulation of the glutamate neurotransmitter.
  3. Under-regulation of glutamate, in turn, caused symptoms of depression.

L-acetylcarnitine reversed the immediate causes of stress-induced symptoms by acetylating histone proteins. These control the transcription of the brain-derived neurotrophic factor (BDNF) and mGlu2 receptors in the hippocampus and prefrontal cortex.

LAC putative action

A commentary on this research, Next generation antidepressants, had the above graphic that showed possible mechanisms for the effects of L-acetylcarnitine. Epigenetic histone modifications seem to be more easily reversible than epigenetic DNA methylation.

“Currently, depression is diagnosed only by its symptoms,” Nasca says. “But these results put us on track to discover molecular signatures in humans that may have the potential to serve as markers for certain types of depression.”

It’s tempting to extrapolate this study to humans and test whether depression symptoms could be effectively treated with some multiple of a normal acetyl-L-carnitine dietary supplement dose of 500 mg at $.25 a day. This dietary supplement is better for depression symptoms than placebo analyzed randomized control trials that tested and demonstrated its efficacy.

To cure stress-induced illnesses in humans, though, ultimate causes of stress should be removed or otherwise addressed.

http://www.pnas.org/content/110/12/4804.full “L-acetylcarnitine causes rapid antidepressant effects through the epigenetic induction of mGlu2 receptors”

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”

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”

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”

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”

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”

Can psychologists exclude the limbic system and adequately study awareness and social cognition?

gettingwell4 < 0 Detracted from science, Amygdala, Cerebrum, Limbic system, Lower brain, Memory , , , ,

This 2014 Princeton human study was proof that cognitive researchers are stuck in the cerebrum. That and gadgets.

The researchers didn’t measure limbic system or lower brain areas, yet from their use of cartoon faces and magnetically zapping their subjects’ brains they proclaimed:

“The findings suggest a fundamental connection between private awareness and social cognition.”

For just one example of the gross omissions of the study’s design, look at the limbic system’s part in “social cognition” for The amygdala is where we integrate our perception of human facial emotion.

And it’s a very limited scope of “private awareness” that excludes conscious awareness of what’s in our own feeling, instinctual, and impulsive levels of consciousness.

http://www.pnas.org/content/111/13/5012.full “Attributing awareness to oneself and to others”

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Can a study exclude the limbic system and adequately find how we process value?

gettingwell4 < 0 Detracted from science, Beliefs, Cerebrum, Limbic system, Lower brain ,

This 2014 human study was notable for defining away the limbic system and lower brain from consideration in processing positive and negative stimuli for value.

However, the researchers didn’t fully reveal their biases until the last paragraph of the supplementary material, where they were obligated to comment on a previous study that included the limbic system. Good for the reviewer if that was how the researchers became obligated to deal with the previous study.

It isn’t difficult to include the limbic system in studies of value. For example, the Teenagers value rewards more and are more sensitive to punishments than are adults study found:

  • Cerebral areas increased activity when the expected value of the reward increased.
  • Limbic system areas increased activity when the expected value of the reward decreased.

http://www.pnas.org/content/111/13/5000.full “Disentangling neural representations of value and salience in the human brain”