Corpus callosum

Beneficial dietary erucic acid?

gettingwell4 4-5 stars Advanced knowledge, Brain development, Cerebellum, Epigenetics, Lower brain , , , ,

A 2022 review to follow up Caution on broccoli seed erucic acid content?:

“Erucic acid is found to cause cardiac lipidosis in young animals, yet direct evidence of cardiac injury does not exist for young humans. Concerns about erucic acid safety and cardiotoxicity have been published in the press which are based on scientific reports in the 1970s that erucic acid disrupted oxidative phosphorylation and lead to accumulation of lipids in rat cardiac tissue.

Spanish toxic oil syndrome was a major concern, leading to questions about erucic acid cardiotoxicity. Yet it was found that not rapeseed oil per se, rather its carcinogen anilin-dye refined derivative caused cardiotoxicity.

Later, it was understood that reduced ATP production with erucic acid treatment was due to unapt isolation of rat cardiac mitochondria and lipid accumulation that was unique to rats that inherently harbour a low β-oxidative peroxisomal activity and tissue-specific metabolism of erucic acid. Similar structural or metabolic perturbations and tissue injuries were not encountered in monkeys, humans, and pigs.

Potential mechanisms regarding antineoplastic effects of erucic acid in brain tumors:

erucic acid

In children (0 to 14 years), medulloblastomas accounted for less than 10% of brain neoplasias in China, African countries, and Ireland. The ratio was in the range 20%–29% in Brazil, Argentina, Thailand, Korea and Poland, the proportion was 30% in Ecuador, 31% in Taiwan and Jordan.

In adults, the ratio of brain neoplasias diagnosed as glioblastoma was:

  • Below 10% only in China;
  • In the range 10%–29% in India, Thailand, Malaysia, Nigeria, Algeria, Malta, Costa Rica, Ecuador, and the Russian Federation;
  • In the range 30%–49% in some South American countries, Singapore, Taiwan, Japan, Korea, Turkey, Denmark, Iceland, Italy, and Spain among others; and
  • In the range 50%–70% in North America, Puerto Rico, Martinique, Israel, Cyprus, Jordan, Kuwait, and in Oceania.

The low ratio of medulloblastomas in children and of glioblastomas in adult Chinese population cannot be easily attributed to a single genetic and nurture pattern. Very likely, many complex factors interact to explain this difference regarding the Chinese population.

Several hypotheses can be put forward to illuminate the cause of reduced ratios of high grade brain tumors in Chinese which would be of benefit for global reduction and prevention of brain tumors. Erucic acid is very highly consumed in the Chinese diet, and 8-fold higher erucic acid levels exist in Chinese women’s milk in comparison to many other countries.

We hypothesized that dietary erucic acid may be – at least among many factors – associated with reduced ratios of high grade brain tumors in Chinese. If epidemiological and animal studies would prove such an association, an effective, cheap, and relatively non-toxic dietary supplementary strategy may be employed to prevent brain tumors at erucic acid doses lower than those associated with any cardiotoxic effects.”

https://link.springer.com/article/10.1007/s11011-022-01022-4 “Could dietary erucic acid lower risk of brain tumors? An epidemiological look to Chinese population with implications for prevention and treatment” (not freely available) Thanks to Dr. Meric Altinoz for providing a copy.

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Young gut, young eyes

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I’ll highlight this 2022 rodent study findings of effects on eye health:

“We tested the hypothesis that manipulating intestinal microbiota influences development of major comorbidities associated with aging and, in particular, inflammation affecting the brain and retina. Using fecal microbiota transplantation, we exchanged intestinal microbiota of young (3 months), old (18 months), and aged (24 months) mice.

Transfer of aged donor microbiota into young mice accelerates age-associated central nervous system inflammation, retinal inflammation, and cytokine signaling. It promotes loss of key functional protein in the eye, effects which are coincident with increased intestinal barrier permeability.

These detrimental effects can be reversed by transfer of young donor microbiota.

young and aged fmt

We provide the first direct evidence that aged intestinal microbiota drives retinal inflammation, and regulates expression of the functional visual protein RPE65. RPE65 is vital for maintaining normal photoceptor function via trans-retinol conversion. Mutations or loss of function are associated with retinitis pigmentosa, and are implicated in age-related macular degeneration.

Our finding that age-associated decline in host retinal RPE65 expression is induced by an aged donor microbiota, and conversely is rescued by young donor microbiota transfer, suggests age-associated gut microbiota functions or products regulate visual function.”

https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-022-01243-w “Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain”

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Human agency vs. brain dysfunction

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This 2021 human study used epigenetic clock technology to assess chronic inflammation as a driver of cognitive decline through its effects on brain structure:

“An epigenetic measure of C-reactive protein (DNAm CRP) was assembled for each participant. We found that higher inflammatory burden, indexed by DNAm CRP scores, associated with poor cognitive and neuroimaging brain health outcomes.

inflammation vs cognitive ability

DNAm CRP exhibited significantly larger associations with brain structural MRI metrics (including global grey and white matter atrophy, poorer white matter microstructure, and increased white matter hyperintensity burden) than serum CRP. Given that the 7 CpGs which make up DNAm CRP score reside in inflammation and vascular-related genes, these DNAm CRP-brain MRI associations may be capturing the impact of upstream inflammatory activity above and beyond that of serum CRP levels.

Our results indicate that some cognitive domains (processing speed) may be more mediated by brain structural consequences of chronic inflammation than others (verbal memory, visuospatial ability).

Our results add to the evidence base that DNAm-based predictors of inflammation may act as a quantifiable archive of longitudinal effects of these exposures – and other unaccounted for health and genetic profiles – that serum CRP levels fail to capture. By utilising an epigenetic inflammation measure, which integrates information from multiple immune-related CpG sites, we may provide a more reliable measure of chronic inflammation and thus a more comprehensive overview of consequences of chronic inflammation on brain structure and function.”

https://n.neurology.org/content/early/2021/11/17/WNL.0000000000012997.long “DNA Methylation and Protein Markers of Chronic Inflammation and Their Associations With Brain and Cognitive Aging”

These researchers essentially negated many of their findings by acknowledging:

“Although we endeavoured to remove participants with cognition-related pathology, these were screened via self-reported diagnoses, and we may be missing undiagnosed or subclinical incident neurodegenerative pathology.”

It wasn’t sufficient to claim in the Abstract section “Participants (N = 521) were cognitively normal, around 73 years of age” then include in the Discussion section a one-sentence limitation of relying on self-reports. Everyone defends themself against current and past realities and experiences.

Hard to imagine that objective measures such as the three comprising cognitive ability weren’t better screens. But then too many 73-year-old subjects may not have been “cognitively normal” and this study wouldn’t be adequately powered?

Can humans counteract inflammation? Non-communicable diseases? Smoking? Immune system degradation? Yes. No personal-agency actions were mentioned.

Also note this study’s social norming. The above-pictured 30-year-old female was busy at work, and subsequently hoisted a cat instead of a child in later years.

Take responsibility for your own one precious life.

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The amino acid ergothioneine

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A trio of papers on ergothioneine starts with a 2019 human study. 3,236 people without cardiovascular disease and diabetes mellitus ages 57.4 ± 6.0 were measured for 112 metabolites, then followed-up after 20+ years:

“We identified that higher ergothioneine was an independent marker of lower risk of cardiometabolic disease and mortality, which potentially can be induced by a specific healthy dietary intake.

overall mortality and ergothioneine

Ergothioneine exists in many dietary sources and has especially high levels in mushrooms, tempeh, and garlic. Ergothioneine has previously been associated with a higher intake of vegetables, seafood and with a lower intake of solid fats and added sugar as well as associated with healthy food patterns.”

https://heart.bmj.com/content/106/9/691 “Ergothioneine is associated with reduced mortality and decreased risk of cardiovascular disease”

I came across this study by its citation in a 2021 review:

“The body has evolved to rely on highly abundant low molecular weight thiols such as glutathione to maintain redox homeostasis but also play other important roles including xenobiotic detoxification and signalling. Some of these thiols may also be derived from diet, such as the trimethyl-betaine derivative of histidine, ergothioneine (ET).

image description

ET can be found in most (if not all) tissues, with differential rates of accumulation, owing to differing expression of the transporter. High expression of the transporter, and hence high levels of ET, is observed in certain cells (e.g. blood cells, bone marrow, ocular tissues, brain) that are likely predisposed to oxidative stress, although other tissues can accumulate high levels of ET with sustained administration. This has been suggested to be an adaptive physiological response to elevate ET in the damaged tissue and thereby limit further injury.”

https://www.sciencedirect.com/science/article/pii/S2213231721000161 “Ergothioneine, recent developments”

The coauthors of this review were also coauthors of a 2018 review:

“Ergothioneine is avidly taken up from the diet by humans and other animals through a transporter, OCTN1. Ergothioneine is not rapidly metabolised, or excreted in urine, and has powerful antioxidant and cytoprotective properties.

ergothioneine in foods

Effects of dietary ET supplementation on oxidative damage in young healthy adults found a trend to a decrease in oxidative damage, as detected in plasma and urine using several established biomarkers of oxidative damage, but no major decreases. This could arguably be a useful property of ET: not interfering with important roles of ROS/RNS in healthy tissues, but coming into play when oxidative damage becomes excessive due to tissue injury, toxin exposure or disease, and ET is then accumulated.”

https://febs.onlinelibrary.wiley.com/doi/full/10.1002/1873-3468.13123 “Ergothioneine – a diet-derived antioxidant with therapeutic potential”

I’m upping a half-pound of mushrooms every day to 3/4 lb. (340 g). Don’t think I could eat more garlic than the current six cloves.

PXL_20210606_095517049

I came across this subject in today’s video:

Our brains are shaped by our early environments

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This 2019 McGill paper reviewed human and animal studies on brain-shaping influences from the fetal period through childhood:

“In neonates, regions of the methylome that are highly variable across individuals are explained by the genotype alone in 25 percent of cases. The best explanation for 75 percent of variably methylated regions is the interaction of genotype with different in utero environments.

A meta-analysis including 45,821 individuals with attention-deficit/hyperactivity disorder and 9,207,363 controls suggests that conditions such as preeclampsia, Apgar score lower than 7 at 5 minutes, breech/transverse presentations, and prolapsed/nuchal cord – all of which involve some sort of poor oxygenation during delivery – are significantly associated with attention-deficit/hyperactivity disorder. The dopaminergic system seems to be one of the brain systems most affected by perinatal hypoxia-ischemia.

Exposure to childhood trauma activates the stress response systems and dysregulates serotonin transmission that can adversely impact brain development. Smaller cerebral, cerebellar, prefrontal cortex, and corpus callosum volumes were reported in maltreated young people as well as reduced hippocampal activity.

Environmental enrichment has a series of beneficial effects associated with neuroplasticity mechanisms, increasing hippocampal volume, and enhancing dorsal dentate gyrus-specific differences in gene expression. Environmental enrichment after prenatal stress decreases depressive-like behaviors and fear, and improves cognitive deficits.”

The reviewers presented strong evidence until the Possible Factors for Reversibility section, which ended with the assertion:

“All these positive environmental experiences mentioned in this section could counterbalance the detrimental effects of early life adversities, making individuals resilient to brain alterations and development of later psychopathology.”

The review’s penultimate sentence recognized that research is seldom done on direct treatments of causes:

“The cross-sectional nature of most epigenetic studies and the tissue specificity of the epigenetic changes are still challenges.”

Cross-sectional studies won’t provide definitive data on cause-and-effect relationships.

The question yet to be examined is: How can humans best address these early-life causes to ameliorate their lifelong effects?

https://onlinelibrary.wiley.com/doi/full/10.1111/dmcn.14182 “Early environmental influences on the development of children’s brain structure and function” (not freely available)

Epigenetic causes of sexual orientation and handedness?

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This 2018 Austrian human study subject was various associations of prenatal testosterone levels to fetal development:

“The available evidence suggests, albeit not conclusively, that prenatal testosterone levels may be one cause for the association of sexual orientation with handedness. Associations among women were consistent with predictions of the Geschwind–Galaburda theory (GGT), whereas those among men were consistent with predictions of the callosal hypothesis. However, research on the associations between sexual orientation and handedness appears to be compromised by various methodological and interpretational problems which need to be overcome to arrive at a clearer picture.

The GGT posits that high prenatal testosterone levels cause a delay in the fetal development of the left cerebral hemisphere which results in a right-hemisphere dominance and hence in a tendency for left-handedness. According to the GGT, high prenatal testosterone levels entail not only a masculinization of the female fetus, but also a feminization of the male fetus (contrary to neurohormonal theory). Overall, the male fetus is subjected to higher levels of intrauterine testosterone than the female fetus. The GGT is thus consistent with the higher prevalence of left-handedness among men than among women.

The callosal hypothesis applies to men only and assumes, in line with neurohormonal theory, that low prenatal testosterone levels are associated with later homosexuality. According to the CH, high prenatal testosterone enhances processes of cerebral lateralization through mechanisms of axonal pruning, thereby resulting in stronger left-hemisphere dominance and a smaller corpus callosum. Consistent with this, women have a larger corpus callosum than men.”

The study’s Limitations section included the following:

  1. “Limitations of the current study pertain to the self-report nature of our data. Behavioral data may provide differing results from those obtained here.
  2. Assessment of sexual orientation relied on a single-item measure. Utilization of rating scales (e.g., the Kinsey Sexual Orientation Scale) or of multi-item scales, and assessing different components of sexual orientation, would have allowed for a more fine-grained analysis and for a cross-validation of sexual orientation ratings with sexual attraction.
  3. Albeit both our samples were large, the proportions of bisexual and homosexual individuals were, expectedly, only small, as were effects of lateral preferences. Thus, in analysis we could not differentiate bisexual from homosexual individuals. Bisexual and homosexual individuals may differ with regard to the distribution of lateral preferences.
  4. Some effect tests in this study have been underpowered. Independent replications with even larger samples are still needed.”

The largest unstated limitation was no fetal measurements. When a fetus’ epigenetic responses and adaptations aren’t considered, not only can the two competing hypotheses not be adequately compared, but causes for the studied phenotypic programming and other later-life effects will also be missed.

https://link.springer.com/article/10.1007/s10508-018-1346-9 “Associations of Bisexuality and Homosexuality with Handedness and Footedness: A Latent Variable Analysis Approach”

Are there epigenetic causes for sexual orientation and gender identity?

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This US 2018 review lead author was a gynecologic oncologist in private practice:

“Sexual orientation is biologically conferred in the first trimester of pregnancy. Gender identity is biologically conferred during the middle trimester of pregnancy.

Since the genitals differentiate in the first trimester, and the brain becomes imprinted in the latter half of gestation, it is possible for the fetal brain to be imprinted differently than the genitals. As children mature, this innate imprinting expresses as genital anatomy, gender identity, sexual orientation and other physiologic capabilities and natural preferences along a continuum, between masculine and feminine.

The evidence shows that both orientation and identity are biologic features that co-vary with a very large number of other biologic sexually dimorphic traits.”

1. A fetus’ development is influenced by survival reactions to their environment. Although fetal and placental responses to environmental stressors are relevant to sexual orientation and gender identity, the reviewers didn’t explore the subject.

2. Epigenetic adaptations to the prenatal environment involving microRNA were mentioned in a small subsection. But the reviewers didn’t cite relevant studies involving DNA methylation, chromatin and histone modifications for epigenetic causes of and effects on sexual orientation and gender identity.

3. The reviewers included a half-dozen anecdotal quotations from personal correspondence that promoted their narrative. These impressed as appeals to authority rather than evidence for scientific understanding of the subject.

It was insufficient for the review to note “a continuum between masculine and feminine” without also exploring evidence for an individual’s placement on the continuum. The question of possible epigenetic causes for sexual orientation and gender identity remains.

https://www.sciencedirect.com/science/article/pii/S009082581731510X “Biological origins of sexual orientation and gender identity: Impact on health” (not freely available)

Parental lying thwarted both their children and researchers

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This 2017 German human study explored the relationship between birth stress and handedness. The authors summarized previous research which, among other points, estimated epigenetic contributions to handedness as great as 75%.

The research hypothesis itself was worthwhile based on the prior studies cited and elsewhere such as Group statistics don’t necessarily describe an individual. But the study hit a snag in its reliance on the sixty participants (average age 24) completing, with the assistance of their parents and medical records, a 24-item questionnaire of maternal health problems during pregnancy, substance use during pregnancy, and birth complications.

It’s extremely unlikely that the sixty subjects provided accurate information. For example:

  • Only one of the subjects reported maternal alcohol use during pregnancy. An expected number would have been twenty-six!
  • None of the subjects reported maternal mental illness during pregnancy. An expected number would have been at least seven!

I’d guess that the subjects’ parents willingly misled their children about facts of their child’s important earliest development periods. It’s my view that parental lies and omissions are not only unethical to the children, but also, whenever the lies and omissions became recognized, they potentially diminish or destroy the society among family members.

As mentioned on the Welcome page, lies and omissions ruin the standard scientific methodology of surveying parents and caregivers. The absence of reliable evidence made it impossible for the current study’s researchers to determine causes of epigenetic effects still present in the subjects’ lives.

Parental lies and omissions also diminish or destroy the society between the sources of information – the research subjects – and the users of the information. Such lies and omissions adversely affect anyone who values evidence-based research.

http://www.tandfonline.com/doi/full/10.1080/1357650X.2017.1377726 “DNA methylation in candidate genes for handedness predicts handedness direction” (not freely available)

Epigenetic stress effects in preterm infants

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This 2017 Italian review selected 9 human studies on the epigenetic effects of:

“One of the major adverse events in human development. Preterm infants are hospitalized in the Neonatal Intensive Care Unit where they are exposed to life-saving yet pain-inducing procedures and to protective care.”

Highlights of the referenced studies included:

  • “Early exposure to adverse events during the third trimester of pregnancy is capable to alter the epigenetic status of imprinted and placenta-related genes which have relevant implications for fetal development and preterm infants’ HPA [hypothalamic–pituitary–adrenal] stress reactivity during infancy.”
  • “There was an association between DNAm [DNA methylation] and white matter tract tissue integrity and shape inferred from dMRI [diffusion MRI], suggesting that epigenetic variation may contribute to the cerebral phenotype of preterm birth.”

Limitations of the referenced studies included:

  • “A multiple sampling design that includes parental samples, placental tissue, cord blood and extends across the life-course would be required to investigate the relative contributions of in utero and postnatal exposures to changes in DNAm, and the extent to which preterm birth leaves a legacy on the methylome.”
  • Saliva, blood, and other tissues’ DNA methylation may not produce valid links to brain tissue DNA methylation of the same gene, which may hamper conclusive inferences about behavior, etc.

http://www.sciencedirect.com/science/article/pii/S0149763417302117 “Preterm Behavioral Epigenetics: A systematic review” (not freely available)

http://www.nature.com/tp/journal/v6/n1/full/tp2015210a.html “Epigenomic profiling of preterm infants reveals DNA methylation differences at sites associated with neural function” (one of the studies selected, quoted above)

The effects of imposing helplessness

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This 2016 New York rodent study found:

“By using unbiased and whole-brain imaging techniques, we uncover a number of cortical and subcortical brain structures that have lower activity in the animals showing helplessness than in those showing resilience following the LH [learned helplessness] procedure. We also identified the LC [locus coeruleus] as the sole subcortical area that had enhanced activity in helpless animals compared with resilient ones.

Some of the brain areas identified in this study – such as areas in the mPFC [medial prefrontal cortex], hippocampus, and amygdala – have been previously implicated in clinical depression or depression-like behavior in animal models. We also identified novel brain regions previously not associated with helplessness. For example, the OT [olfactory tubercle], an area involved in odor processing as well as high cognitive functions including reward processing, and the Edinger–Westphal nucleus containing centrally projecting neurons implicated in stress adaptation.

The brains of helpless animals are locked in a highly stereotypic pathological state.”

Concerning the study’s young adult male subjects:

“To achieve a subsequent detection of neuronal activity related to distinct behavioral responses, we used the c-fosGFP transgenic mice expressing c-FosGFP under the control of a c-fos promoter. The expression of the c-fosGFP transgene has been previously validated to faithfully represent endogenous c-fos expression.

Similar to wild-type mice, approximately 22% (32 of 144) of the c-fosGFP mice showed helplessness.”

The final sentence of the Introduction section:

“Our study..supports the view that defining neuronal circuits underlying stress-induced depression-like behavior in animal models can help identify new targets for the treatment of depression.”

Helplessness is both a learned behavior and a cumulative set of experiences during every human’s early life. Therapeutic approaches to detrimental effects of helplessness can be different with humans than with rodents in that we can address causes.

The researchers categorized activity in brain circuits as causal in the Discussion section:

“Future studies aimed at manipulating these identified neural changes are required for determining whether they are causally related to the expression of helplessness or resilience.”

Studying whether or not activity in brain circuits induces helplessness in rodents may not inform us about causes of helplessness in humans. Our experiences are often the ultimate causes of helplessness effects. Many of our experiential “neural changes” are only effects, as demonstrated by this and other studies’ induced phenotypes such as “Learned Helplessness” and “Prenatally Restraint Stressed.”

Weren’t the researchers satisfied that the study confirmed what was known and made new findings? Why attempt to extend animal models that only treat effects to humans, as implied in the Introduction above and in the final sentence of the Discussion section:

“Future studies aimed at elucidating the specific roles of these regions in the pathophysiology of depression as well as serve as neural circuit-based targets for the development of novel therapeutics.”

http://journal.frontiersin.org/article/10.3389/fncir.2016.00003/full “Whole-Brain Mapping of Neuronal Activity in the Learned Helplessness Model of Depression” (Thanks to A Paper a Day Keeps the Scientist Okay)

Where do our beliefs about our children come from? An autism example

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A 2015 case study by Ohio physicians highlighted:

“Although only a small minority of patients with autism have a mitochondrial disease, many patients with mitochondrial myopathies have autism spectrum disorder symptoms.

These symptoms may be the presenting symptoms, which presents a diagnostic challenge for clinicians.

The case of a 15-year-old boy with a history of autism spectrum disorder and neurocardiogenic syncope, admitted to the inpatient unit for self-injury, whose young mother, age 35, was discovered to suffer from mitochondrial myopathy, dysautonomia, neurocardiogenic syncope, Ehler-Danlos syndrome, and other uncommon multisystem pathologies likely related to mitochondrial dysfunction.”

I was somewhat taken aback by the Abstract and Introduction statements:

“All autism spectrum disorders are known to be heritable, via genetic and/or epigenetic mechanisms, but specific modes of inheritance are not well characterized.

This form of ASD is known to be heritable, as are all forms of ASD, despite the previous belief to the contrary, though the mechanisms of inheritance, both genetic and epigenetic, are not well characterized.”

The definition of heritable as used was “able to be passed from parent to child before birth.” The reference provided was a 2014 French review Gene × Environment Interactions in Autism Spectrum Disorders: Role of Epigenetic Mechanisms.

I didn’t see the “known to be heritable” phrase mentioned in the referenced review. However, I also didn’t see anything stated in the review or cited from its 217 references that disproved this phrase.

I shouldn’t have been surprised by “despite the previous belief to the contrary” in the above quotation. I’d guess that the physicians frequently encountered parents who needed such beliefs when faced with their child’s condition.

A relevant hypothesis of Dr. Arthur Janov’s Primal Therapy is: a major function that our cerebrums have evolutionarily adapted is to use ideas and beliefs to repress pain and make us more comfortable.

I value this inference as an empathetic method of interpreting people’s behaviors and expressions of thoughts and feelings.

When a “known to be heritable” phrase can unleash pain, it likely won’t be understood in its appropriate context. Among the physicians’ challenges was a barrier that kept the parent’s pain from being felt – the belief.

http://innovationscns.com/autism-in-the-son-of-a-woman-with-mitochondrial-myopathy-and-dysautonomia-a-case-report/ “Autism in the Son of a Woman with Mitochondrial Myopathy and Dysautonomia: A Case Report”

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

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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”

What causes disconnection between the limbic system and the cerebrum?

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This 2014 Swedish human study with 339 subjects aged 25-80 years old found that as the subjects’ age increased, their hippocampus became less connected to their cerebrums:

“Age-related cortico–hippocampal functional connectivity disruption leads to a more functionally isolated hippocampus at rest, which translates into aberrant hippocampal decoupling and deficits in active mnemonic processing.”

The lead researcher said:

“What we can now show is that memory problems that come with increased age are most likely due to a process where the interaction among different regions of the hippocampus increases in response to less inhibitory cortical input. This in turn means that the hippocampus risks being more isolated from other important networks in the brain which impacts our ability to actively engage the hippocampus, for example to remember different events.”

Like other researchers commonly do, they excluded emotional content from the study. See another Swedish study Emotional memories and out-of-body–induced hippocampal amnesia as an example of why emotional memories are necessary in order to properly study the hippocampus.

1) As a result of excluding emotional content and other aspects of the study’ design such as using 25 as the beginning age of the subjects, all the researchers could muster as a explanatory factor was age. However, they had to couch their findings as “age-related” because age in and of itself wasn’t a causal explanation for the observed effects.

2) The findings weren’t even truly “age-related”  because, for example, the study didn’t necessarily apply to people below the age of 25. Had the study included 10-18 year old subjects, the researchers may have found that “less inhibitory cortical input” may also be present before puberty, as The prefrontal cortex develops more repressive function at puberty study indicated.

3) Had the study design included neurochemicals, the researchers may have found that “cortico–hippocampal functional connectivity disruption” was due to factors that influenced dopamine and glutamate levels, as A mechanistic study of neurotransmitters in the hippocampus indicated.

4) A finding that “cortico–hippocampal functional connectivity disruption” was influenced by other factors may also have been made had the study design included the subjects’ histories. Per my Welcome page, the findings of much of the recent research I’ve curated on this blog, and the references in those studies show that when basic needs aren’t met, especially early in people’s lives, and the painful conditions persist, enduring physiological changes may occur.

5) What the researchers noted in the study’s limitation paragraph were references to fMRI scans rather than limitations such as those mentioned above regarding the study design. The study provided unconvincing evidence for causes of “cortico–hippocampal functional connectivity disruption” and it wasn’t because of fMRI limitations.

http://www.pnas.org/content/111/49/17654.full “Elevated hippocampal resting-state connectivity underlies deficient neurocognitive function in aging”

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.

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

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

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

The researchers found:

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

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

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

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

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

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

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

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

Early human brain development can be greatly modified by environmental factors

gettingwell4 4-5 stars Advanced knowledge, Brain development, Brain hemispheres, Epigenetics , , ,

This 2014 Brazilian human study found that the brains of people born without the corpus callosum, the major connection between brain hemispheres, adapted to this loss:

“The authors believe that the development of alternative pathways results from the brain’s ability for long-distance plasticity and occurs in the utero during embryo development, which indicates that connections formed in the human brain early in development can be greatly modified, and most likely by environmental or genetic factors.”

BRAVO! MORE STUDIES LIKE THIS ONE!

People have limited capability to adapt later in life to corpus callosum injuries or to brain hemisphere disconnection.

http://www.pnas.org/content/111/21/7843.full “Structural and functional brain rewiring clarifies preserved interhemispheric transfer in humans born without the corpus callosum”