Control group

Running a marathon, cortisol, depression, causes, effects, and agendas

gettingwell4 < 0 Detracted from science, Cerebrum, Cortisol, Limbic system, Lower brain, Memory, Neurochemicals, Stress , ,

Let’s imagine that you decide you want to run a marathon. You haven’t run in six months, and you know you’ll have to train.

On the first day of training, as you run your first mile a friend pops out of nowhere and says, “You’re sweating! That means you’re going up to Mile 14 today! Good job, you’re on your way!”

You may appreciate the encouragement, but would a friend’s assessment have anything to do with your physical reality? Before you’ve run one mile, can an observer of your sweat say with certainty that you’ll run 14 miles on your first day of training?

Yeah. That’s how I felt when reading this 2014 UK study that found:

“Adolescent boys who have high levels of stress hormone ‘cortisol’ along with some symptoms of depression are at a 14 times higher risk of the condition than their peers.”

The researchers latched onto teenagers (12-16 years old, mean 13.7) to assess a psychiatric condition. They stated that a physical effect as common as visible sweat was a biomarker that predicted where some of the teenagers were going with their lives.

The study’s only physical measurements were cortisol from saliva samples at 8:00 a.m. on four consecutive days, then repeated a year later. For comparison, a standard lab test is to measure cortisol from saliva taken four times in one day at 9:00 a.m., 1:00 p.m., 5:00 p.m., and 9:00 p.m.

Cortisol is an effect of multiple potential causes, including stress, which itself is often an effect of multiple potential causes. One common cause of stress and its cortisol byproduct is diet, for example, when a person consumes caffeine.

“Mean time between waking and morning-cortisol collection was 50 min.”

I found it hard to believe that teenagers who:

  • woke up at 7:10 a.m.,
  • gulped down who knows what for breakfast,
  • got ready for, and then
  • went to school for an 8:00 a.m. cortisol test

wouldn’t have relatively “elevated morning cortisol” from the resultant stress.

Subjects self-reported depressive symptoms via a 33-item questionnaire initially and again every four months. They were interviewed for psychiatric diagnoses.

The largest separator used for stratification within subjects was an autobiographic memory test. Without this test, the study wouldn’t have made its main finding, so let’s look at the test’s details:

“Anxious and depressed adolescent patients report significantly elevated levels of over-general categoric memories compared with well controls. Six positive and six negative words are presented on flashcards in pseudorandom order, and participants are instructed to recall a particular memory of an event in their life after each word. Sixty seconds were allowed for each response.

Responses were categorized as specific if they referred to an event with a specific time and place, lasting no longer than 1 d[ay]. Responses were considered overgeneral if they formed a general class of repeated events.”

We can see that the autobiographical memory test only considered the subjects’ verbal expressions – within a short time period – of their recalls of emotionally triggered memories. As informed by the principles described in Agenda-driven research on emotional memories, the recall of an emotional memory is a product of the cerebrum responding to input from limbic system and lower brain areas. When someone describes their recall of an emotionally triggered memory, it’s yet another level further removed from the brain areas that store emotional memories.

We can also see that test scores of the subjects’ verbal expressions aren’t capable of providing any etiologic evidence for an effect of high cortisol. A correlation is the best that could ever be shown by an autobiographic memory test. Again, the study’s main finding hinged on this third-order observational method of trying to figure out what’s going on inside subjects’ brains.

The researchers developed a control group, and made only a token attempt to trace the control group teenagers’ histories:

“The primary caregiver was interviewed about the quality of the family environment in three epochs (0–5, 6–11, and 12–14 y of age).

Four classes were found: optimal class, aberrant parenting, discordant, and hazardous.”

Were we supposed to believe that any primary caregiver would tell the truth about anything in a teenager’s history that indicated they had damaged their child? Good luck with that.

Anyway, the researchers didn’t act as though teenagers’ histories had any significant relationships with any present or future conditions. Their ahistoric biases showed by subsequently processing the entire history of each of the control group teenagers into a 1 or a 0 for the model.

The researchers then modeled this binary assessment to be relevant to the study’s main subjects!

The researchers’ agenda led to predetermined findings. Was the reviewer onboard with this agenda?

  • By disregarding the main subjects’ histories, it couldn’t provide etiologic evidence for any present or future effects.
  • By measuring only early morning cortisol, are we surprised that model numbers could be processed into some correlation?
  • Comparing this sole measurement to 325 measurements taken of subjects in Assessing a mountain climber’s condition without noticing their empty backpack made me wonder about the study designers’ real intentions.

News coverage of the study jumped on its flimsy finding to demand that something must be done. What did researchers offer teenagers who needed help?

  • After citing research that:

    “Showed null effects for two active treatments [cognitive behavioral therapy (CBT) and attentional training, respectively]”

    they recommended some unspecific:

    “New models of public mental health education and intervention in the youth population.”

  • After citing research that found:

    “Current diagnostic classifications [e.g., the Diagnostic and Statistical Manual for Mental Disorders (DSM) and the International Classification of Diseases (ICD)] have proved to have low diagnostic validity for investigations on the etiology, prevention, or treatment of MD [major depression]“

    the study relied on these diagnoses anyway, and then disclaimed:

    “It may also be the case that current classifications, as used in this study, such as DSM and ICD are simply not optimally specified.”

They didn’t make their case that “elevated morning cortisol” effect was an adequate biomarker for teenagers who needed help. They did a disservice to their subjects by neither investigating nor providing any etiologic evidence for observed effects.

Who really benefited from this underlying agenda? I didn’t see that it was teenagers who may have actually needed assistance.

Did the study’s funders know that these efforts had enormous lacks? And what did:

“New models of public mental health education and intervention in the youth population”

really mean?

http://www.pnas.org/content/111/9/3638.full “Elevated morning cortisol is a stratified population-level biomarker for major depression in boys only with high depressive symptoms”

Changing an individual’s future behavior even before they’re born

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

This 2015 Harvard fruit fly research was a companion of the Is what’s true for a population what’s true for an individual? study.

The researchers began with the question:

“If we could rear genetically identical individuals from a variety of genetic backgrounds and rear them in the same environment, how much phenotypic variation between individuals of the same genotype would we see?”

They answered with:

“We show that different genotypes vary dramatically in their propensity for variability, that phenotypic variability itself, as a trait, can be heritable, and that loci affecting variability can be mapped.”

The specific problem that probably prompted this study was that 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.”

The researchers altered the environment during a critical period of fruit flies’ development in order to induce epigenetic changes in the fruit fly pupae brains:

“Disruption of Ten-a [the synaptic target recognition gene Tenascin accessory] expression in midpupa affects behavioral variance [the standard statistical dispersion parameter].

In all cases, disrupting Ten-a increased the variability [the median of the absolute deviation from each observation’s median] in turning bias with no effect on the mean.”

I fully expect researchers to demonstrate that this finding has general applicability for humans, especially during womb-life. Research such as:

are steps in this direction just for one factor in the human fetal environment – stress. The effects of stressing a human fetus should be at least as significant as the effects produced on the study’s subjects with increased temperature during pupation.

http://www.pnas.org/content/112/21/6706.full “Behavioral idiosyncrasy reveals genetic control of phenotypic variability”

A mixed bag of findings about oxytocin, its receptor, and autism

gettingwell4 0-1 star Wasted resources, Epigenetics, Neurochemicals, Oxytocin ,

This 2014 Stanford human study found:

“No empirical support for the OXT [oxytocin] deficit hypothesis of ASD [autism spectrum disorder], nor did plasma OXT concentrations differ by sex, OXTR [oxytocin receptor] SNPs [single nucleotide polymorphisms], or their interactions.”

Apparently, there was a:

“Prevalent but not well-interrogated OXT deficit hypothesis of ASD.”

The researchers followed up this worthwhile finding with three weak findings. The first, as stated by one of the study’s lead researchers, was:

“It didn’t matter if you were a typically developing child, a sibling or an individual with autism: Your social ability was related to a certain extent to your oxytocin levels.”

The second weak finding was that, regarding OXTR SNPs:

“The minor allele of rs2254298 predicted global social impairments on the SRS [Social Responsiveness Scale] and diagnostic severity on the ADI-R [Autism Diagnostic Interview-Revised]. In contrast, the major allele of rs53576 predicted impaired affect recognition performance on the NEPSY [A Developmental NEuroPSYchological Assessment].”

This was at odds with other relevant research, leading the researchers to state:

“The functional significance of these two intronic variants remains unknown.”

The third weak finding irked me:

“Plasma OXT concentrations were highly heritable.”

because the researchers didn’t attempt to differentiate the contribution of the environment for the observed blood oxytocin levels, as did the similar How epigenetic DNA methylation of the oxytocin receptor gene affects the perception of anger and fear study.

I wonder what the reviewer’s feedback was about these weak findings. Did he make the researchers insert specific language into the lengthy paragraph about the study’s limitations, or did he give them a pass?

http://www.pnas.org/content/111/33/12258.full “Plasma oxytocin concentrations and OXTR polymorphisms predict social impairments in children with and without autism spectrum disorder”

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”

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”

Translating PTSD research findings from animals to humans

gettingwell4 0-1 star Wasted resources, Amygdala, Cortisol, Hippocampus, Limbic system, Neurochemicals, Stress

This 2014 rodent study stressed the animals, measured their stress responses, then killed them and sampled genes in their amygdala, hippocampus, and blood. The researchers found that glucocorticoid receptor signaling genes were the primary pathway associated with “exposure-related individual differences“ in stress responses for the amygdala and blood. This pathway also placed first for the hippocampus in female rats (glucocorticoid receptor was second in male rats and prostate cancer signaling was first).

I’ll quote one press article’s coverage to show where the researchers wanted to go with the study’s findings:

“We found that most of the genes and pathways that are different in PTSD [post-traumatic stress disorder]-like animals compared to resilient animals are related to the glucocorticoid receptor, which suggests we might have identified a therapeutic target for treatment of PTSD.”

How about this lead sentence:

“There may some day be a blood test to determine whether someone suffers from Post-Traumatic Stress Disorder or is at risk for the psychiatric condition.”

Here’s another article’s paraphrase of a different researcher:

“Those are genes that become activated in the presence of stress. Like a key fitting into a lock, the hormone corticosterone, produced naturally by the body, connects to the receptor and has a calming effect.

In some rodents, and apparently in some people, the pathway appears to be defective, and this puts them at higher risk for PTSD.”

Also, from the study’s abstract:

“Corticosterone treatment 1 h[our] after PSS [predator-scent-stress]-exposure prevented anxiety and hyperarousal 7 d[ays] later in both sexes, confirming the GR [glucocorticoid receptor] involvement in the PSS behavioral response.”

Like other researchers continue to do, they stopped this study short of finding causes for the effects:

  1. What were the causes for genes in the glucocorticoid receptor signaling pathway being differentially expressed? “Exposure-related individual differences” isn’t a causal finding.
  2. If this pathway is “defective,” what exactly happened to make it that way?
  3. Did dampening the effects of stress with a shot of cortisol one hour after the stress treat the cause such that the rats were cured? Since the readers of the study and associated articles were led to infer that this treatment was a cure, why destroy the treated animals afterwards before the proofs of long-term efficacy were thoroughly documented and tested?

When studies like this are carried forward with humans, researchers should try to find the causes for these effects. It isn’t sufficient to pretend that there aren’t early-life causes for these effects. Such a pretense leads to the follow-on pretense that later-life consequences are mysteries such as “exposure-related individual differences” and not effects.

Researchers should act like the subjects are feeling human beings who can participate in treatments of both the causes and effects. They should remember that humans are not lab rats who need to be fixed.

http://www.pnas.org/content/111/37/13529.full “Expression profiling associates blood and brain glucocorticoid receptor signaling with trauma-related individual differences in both sexes”

Do you know a stranger’s emotional motivations for smiling?

gettingwell4 < 0 Detracted from science, Beliefs, Cerebrum

The premise of this combination of two studies was:

“Emotional understanding is the central problem of human interaction.”

The researchers reanalyzed a 2008 study’s data, supplemented it with their own 2015 study, and found:

“Social-historical factors..explain cross-cultural variation in emotional expression and smile behavior.

We also report an original study of the underlying states that people believe [my emphasis] are signified by a smile.”

The researchers presented the subjects with a survey that asked them to rate 15 possible reasons for a person to smile at them on a seven-point scale of -3 to +3 for disagreeing/agreeing.

The research methodology didn’t take the additional necessary steps of establishing paired experiments that included presenting a similar survey to a control group of subjects to self-report their emotional motivations for smiling, and then processing the two surveys.

Did the study’s reviewer have anything to say about this lack of validation of the subjects’ beliefs to any factual measurements of a stranger’s corresponding “emotional expression and smile behavior?”

This combination of studies didn’t inform us about the “emotional understanding is the central problem of human interaction” premise. The researchers only provided evidence that the subjects’ cultures were one of many causal factors for the subjects’ beliefs about a hypothetical stranger’s smiling behavior.

The combined studies didn’t contain any emotional content to establish experimental conditions toward the goal of “emotional understanding.” No emotions were involved, for example, when a subject rated “strongly agree” to the “Wants you to like them” reason on a survey for a hypothetical stranger’s smiling behavior.

The studies didn’t show that the subjects rating their beliefs contributed to their real “emotional understanding.” Including emotional content, such as experimentally evoking an actual emotion in response to an actual stranger smiling, possibly could have contributed to real “emotional understanding.”

Research that strips out emotional content can’t factually provide evidence for real “emotional expression and smile behavior.” The degrees to which beliefs about and perceptions of a stranger’s smiling actually match their emotional reality remain to be shown.

http://www.pnas.org/content/112/19/E2429.full “Heterogeneity of long-history migration explains cultural differences in reports of emotional expressivity and the functions of smiles”

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 researcher 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”

The amygdala part of the limbic system doesn’t process beliefs

gettingwell4 0-1 star Wasted resources, Amygdala, Beliefs, Cerebrum, Limbic system

Does your desk light switch on or off when other people in the office switch their desk lights on or off? Something in the wiring would probably be wrong if it did.

And wouldn’t you expect that other desk lights would still operate normally if your desk light’s bulb burned out, although everyone may be plugged into the same electrical circuit?

It surprised the researchers of this 2015 CalTech/MIT study when:

“Two patients with bilateral amygdala lesions performed a belief reasoning test.

Both patients showed typical test performance and cortical activity when compared with nearly 500 healthy controls.”

The study’s overall frame of reference was expressed as:

“Humans use a so-called “theory-of-mind” to reason about the beliefs of others. Neuroimaging studies of belief reasoning suggest it activates a specific cortical network. The amygdala is interconnected with this network and plays a fundamental role in social behavior.”

The experimental test:

“Was designed to optimize functional contrast in those brain regions thought to be involved in attempts, be they successful or unsuccessful, to evaluate the veracity of another person’s belief about the world.”

A “belief reasoning test..to reason about the beliefs of others” is a cerebral exercise. The amygdala, in contrast, is an emotional center of a person’s limbic system.

The logic by which the study may be viewed is:

  1. The “belief reasoning test” had no emotional content to activate the subjects’ amygdalae.
  2. fMRI scans confirmed that limbic system areas in the 2 lesioned subjects weren’t activated during the test.
  3. Apply the logic of Occam’s razor, and we arrive at the findings of “typical test performance and cortical activity.”

Task performance and beliefs about task responses are solely cerebral exercises had a similar methodology and result in that those subjects’ limbic systems were monitored during fMRI scans and subsequent reporting, but the subjects’ limbic system areas weren’t activated during any of the experiments.

The researchers stated the results:

“Suggest a reevaluation of the role of the amygdala and its cortical interactions in human social cognition.”

But per the beginning analogy – if your desk light’s bulb burned out, would you be surprised that it didn’t affect the normal operations of desk lights in other offices, although they all may be plugged into the same circuit?

This study informed us that the amygdala isn’t slaved to the cerebrum. It’s hard to change the current research mindset/social meme of cerebral dominance, though, so maybe this information will be overlooked.

http://www.pnas.org/content/112/15/4827.full “Amygdala lesions do not compromise the cortical network for false-belief reasoning”

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”

Why do we cut short our decision-making process?

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This 2014 Zurich study found that people adapt their goal-directed decision-making processes in certain ways.

First, the researchers found that the subjects usually acted as though the computational cost of evaluating all outcomes became too high once the process expanded to three or more levels. Their approach to a goal involved developing subgoals. For example, for a three-level goal:

“Level 3 was most frequently decomposed into a tree of depth 2 followed by a depth-1 tree.”

A level 3 tree had 24 potential outcomes (24 outcomes = 3*2x2x2) whereas a level 2 tree followed by a level 1 tree had 10 potential outcomes (10 outcomes = 2*2×2 + 1*2).

Second, the subjects memorized and reused subgoals after their initial formation. The researchers found that this practice didn’t produce results significantly different than the optimal solutions, but that could have been due to the study’s particular design. The design also ensured that the subjects’ use of subgoals wasn’t influenced by rewards.

Further:

“It is known that nonhuman primate choices, for instance, depend substantially on their own past choices, above and beyond the rewards associated with the decisions. Similar arguments have been made for human choices in a variety of tasks and settings and have been argued to be under dopaminergic and serotonergic control.”

Third, ALL 37 subjects were unwilling to evaluate decisions that had initial large losses, even if they could see that the path to reach the optimal solution went through this loss outcome! The researchers termed this behavior “pruning” and stated:

“Pruning is a Pavlovian and reflexive response to aversive outcomes.”

The lead author relied on a previous study he coauthored to elaborate on the third finding. One statement in the previous study was:

“This theory predicts excessive pruning to occur in subjects at risk for depression, and reduced pruning to occur during a depressive episode.”

The current study’s subjects were screened out for depressive conditions, though. They were somewhat conditioned by the study design, but not to the extent where their behavior could be characterized as Pavlovian responses.

Fourth, the subjects’ use of larger subgoals wasn’t correlated to their verbal IQ.

So, what can we make of this research?

  1. Are shortcuts to our decision processes strictly a cerebral exercise per the first and second findings?
  2. Do we recycle our decision shortcuts like our primate relatives, uninfluenced by current rewards?
  3. Or is it rewarding to just not fully evaluate all of our alternatives?
  4. Do all of us always back away from decisions involving an initial painful loss, even when we may see the possibility of gaining a better outcome by persevering through the loss?
  5. Is it true that we excessively cut decision processes too short – such that many of our decisions are suboptimal – when we’re on our way to becoming depressed?
  6. Are we overwhelmed when depressed such that we don’t summon up the effort to cut short or otherwise evaluate decisional input?

Let me know your point of view.

http://www.pnas.org/content/112/10/3098.full “Interplay of approximate planning strategies”

Pulling on the chain of causes and effects with insulin resistance

gettingwell4 0-1 star Wasted resources, Cortisol, Dopamine, Neurochemicals, Stress , , ,

This 2015 Harvard rodent study found multiple undesirable symptoms and attributed the cause to insulin resistance, which is itself a symptom.

Humans most often develop the symptom of insulin resistance due to causes other than genetics, such as a result of abnormal eating behaviors, which are symptoms of other causes.

Use of insulin-resistant-due-to-genetics mice may have misdirected the researchers to lose focus that their ultimate task was to find ways that their research can help humans. If helping humans was the researchers’ focus, it may have occurred to them to develop evidence for how “something” caused symptoms such as abnormal eating behaviors, that in turn caused a symptom of insulin resistance.

The study’s unexamined causes included why genetically insulin-resistant mice developed symptoms of anxiety and depressive-like behaviors between early adulthood and late middle age. Examples of undesirable symptoms described in the supplementary material included:

  • Higher body weight in late middle age, especially in females;
  • Depressive-like behavior in both sexes by late middle age;
  • Higher corticosterone levels in both sexes by late middle age, even when unstressed; and
  • Higher corticosterone levels in late middle age when stressed, especially in males.

It’s remarkable how researchers consistently get caught in a loop of studying only symptoms, paying little attention to studying causes, then suggesting various medications and treatments to suppress the studied symptoms.

It’s not surprising then that there’s no explanation of why and how symptoms develop. The study designs seldom include trying to show causes for the effects in the first place!

http://www.pnas.org/content/112/11/3463.full “Insulin resistance in brain alters dopamine turnover and causes behavioral disorders”

How to make a child less capable even before they are born: stress the pregnant mother-to-be

gettingwell4 4-5 stars Advanced knowledge, Brain development, Cortisol, Epigenetics, Hypothalamus, Limbic system, Neurochemicals, Primal Therapy, Stress, Testosterone , ,

This 2014 rodent study showed how to make a less-capable pup by stressing the mother early in gestation. The study centered on a placental enzyme (OGT) that translates a mother’s stress into neuroprogramming of her developing fetus.

One finding was that this enzyme was less plentiful when the fetus was male compared with female.

Another finding was that the enzyme was less plentiful when the mother was stressed early in gestation, compared with unstressed mothers.

Informed by the first two findings, the researchers studied the placentae of male pups where the mother was stressed early in gestation. They found that these placentae had lower levels of an enzyme (Hsd17b3) that converts the precursor androstenedione into testosterone.

The resultant finding was that the male pups of stressed mothers had lower levels of testosterone than the control group of male pups.

A fourth finding was that offspring of both sexes born with a placenta where the OGT enzyme was less plentiful had 10-20% less body weight, a condition that developed after weaning. The researchers attributed this finding to reduced mitochondrial function in the hypothalamus compared with normal mice.

http://www.pnas.org/content/111/26/9639.full “Targeted placental deletion of OGT recapitulates the prenatal stress phenotype including hypothalamic mitochondrial dysfunction”

The amygdala is where we integrate our perception of human facial emotion

gettingwell4 4-5 stars Advanced knowledge, Amygdala, Hippocampus, Limbic system ,

We all have specialized brain circuits for recognizing faces.

Each person has their own historical judgment of the emotion in a human face, which may or may not be the emotion objectively displayed by the face.

The amygdala, not the hippocampus, was found to be where we integrate our perception of human facial emotion.

The facial information conveyed by the eyes, not the mouth, was primarily how the amygdala perceived emotion.

This 2014 study was performed on seven neurology patients who had deep-brain electrodes implanted for other purposes of diagnosis or treatment, including epilepsy and autism, and six healthy control subjects. With the electrodes, the researchers were able to measure individual neurons instead of functional MRI aggregate results.

This increased measuring capability enabled the researchers to develop other findings, such as:

“Neuronal selectivity for fear faces in the amygdala comes mainly from a suppression of activity in happy-face trials, whereas selectivity for happy faces is mainly due to an increase in activity for happy-face trials.”

Also:

“The long latency of the amygdala responses we observed already argues for considerable synthesis, consistent with the integration of face input from temporal cortex with signals from other brain regions, as well as substantial processing internal to the amygdala.”

http://www.pnas.org/content/111/30/E3110.full “Neurons in the human amygdala selective for perceived emotion”