Our brains are shaped by our early environments

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 that remains 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?

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”

Reductionism vs. reductionism

This 2004 essay by an evolutionary biologist reviewed his field’s direction in the current century:

“Science is impelled by two main factors, technological advance and a guiding vision (overview). A properly balanced relationship between the two is key to the successful development of a science.

Without the proper technological advances the road ahead is blocked. Without a guiding vision there is no road ahead; the science becomes an engineering discipline, concerned with temporal practical problems.

Empirical reductionism is in essence methodological; it is simply a mode of analysis, the dissection of a biological entity or system into its constituent parts in order better to understand it. Empirical reductionism makes no assumptions about the fundamental nature, an ultimate understanding, of living things.

Fundamentalist reductionism (the reductionism of 19th century classical physics), on the other hand, is in essence metaphysical. It is ipso facto a statement about the nature of the world: living systems (like all else) can be completely understood in terms of the properties of their constituent parts.

This is a view that flies in the face of what classically trained biologists tended to take for granted, the notion of emergent properties. Whereas emergence seems to be required to explain numerous biological phenomena, fundamentalist reductionism flatly denies its existence: in all cases the whole is no more than the sum of its parts.”

Regarding cellular evolution:

“Modern concepts of cellular evolution are effectively petrified versions of 19th century speculations. Try to imagine a biology released from the intellectual shackles of mechanism, reductionism, and determinism.

Evolution, as a complex dynamic process, will encounter critical points in its course, junctures that result in phase transitions (drastic changes in the character of the system as a whole). Human language is a development that has set Homo sapiens worlds apart from its otherwise very close primate relatives, adding new dimensions to the phase space within which human evolution occurs. Another good critical-point candidate is the advent of (eucaryotic) multicellularity.

Nowhere in thinking about a symbiotic origin of the eucaryotic cell has consideration been given to the fact that the process as envisioned would involve radical change in the designs of the cells involved. You can’t just tear cell designs apart and willy-nilly construct a new type of design from the parts.

The organization of the mitochondrial endosymbiont is radically changed during its evolution, but that change is a degeneration to a far simpler “cell-like” design. The mitochondrial design could never evolve back to the level of complexity that its free-living [bacterial] ancestor had.

A common thread that links language and multicellularity is communication (interaction at a distance). In each case a complex, sophisticated network of interactions forms the medium within which the new level of organization (entities) comes into existence.

Our experience with variation and selection in the modern context does not begin to prepare us for understanding what happened when cellular evolution was in its very early, rough-and-tumble phase(s) of spewing forth novelty. Cellular evolution began in a highly multiplex fashion, from many initial independent ancestral starting points, not just a single one.”

https://mmbr.asm.org/content/68/2/173 “A New Biology for a New Century”

I came across this review by it being referenced in this researcher’s blog post:

Chinese Longevity Herb
I often don’t agree with him, but I subscribe to his blog because it’s interesting.


This 2018 UK review subject was colored-hearing experiences from music:

“Music-colour synaesthesia has a broad scope encompassing not only tone-colour synaesthesia elicited on hearing individual tones, but a complex and idiosyncratic mixture of phenomenological experiences often mediated by timbre, tempo, emotion and differing musical style.

The possession of synaesthesia or absolute pitch was shown to have very little effect on the actual colours chosen for each of the musical excerpts, but it might be reasonable to expect that music that elicits a strong emotional response may be more likely to induce synaesthesia than music that does not.

The examination of eight neuroimaging studies were found to be largely inconclusive in respect of confirming the perceptual nature of music-colour synaesthesia. Neither the hyperconnectivity nor the disinhibited feedback theory currently holds as a single categorical explanation for synaesthesia.

Theories promoting the notion of ‘ideaesthesia’ have highlighted the importance of the role of concept and meaning in the understanding of synaesthesia..and a replacement definition: Synaesthesia is a phenomenon in which a mental activation of a certain concept or idea is associated consistently with a certain perception-like experience.”

Much of the review was philosophizing and casting around for clues. The review cited interesting studies and reviews, including The Merit of Synesthesia for Consciousness Research.

One relevant element missed by the underlying research and the review was critical periods of human development. A cited reference in How brains mature during critical periods was Sensitive periods in human development: Evidence from musical training (not freely available) which illuminated some aspects of the research:

“In contrast to a critical period, where a function cannot be acquired outside the specific developmental window, a sensitive period denotes a time where sensory experience has a relatively greater influence on behavioral and cortical development. Sensitive periods may also be times when exposure to specific stimuli stimulates plasticity, enhancing changes at the neuronal and behavioral levels.

The developmental window for absolute pitch may be more similar to a critical than a sensitive period.

The auditory cortex appears to have an unusually long period of developmental plasticity compared with other sensory systems; changes in its cellular organization and connectivity continue into late childhood.

The effects of musical training have been shown to impact auditory processing in the brainstem as well.”

Let’s say that a researcher wanted – as one cited study did – to examine absolute pitch, a rare trait, present in a subset of synesthetes – music-color, another rare trait. The study as designed would probably be underpowered due to an insufficient number of subjects, and it would subsequently find “very little effect.”

Let’s say another researcher focused on brain areas in the cerebrum, and like the eight cited studies, ignored the nuclei in the pons part of the brainstem which are the first brain recipients of sound and equilibrium information from the inner ear via the eighth cranial nerve. Like those studies, the researcher was also biased against including limbic brain areas that would indicate “a strong emotional response.” A study design that combined leaving out important brain-area participants in the synesthesia process with a few number of synesthetes would be unlikely to find conclusive evidence.

The reviewer viewed the lack of evidence from “eight neuroimaging studies” as indicating something about the “perceptual nature of music-colour synaesthesia.” An alternative view is that the “inconclusive” evidence had more to do with study designs that:

  • Had a small number of subjects;
  • Omitted brain areas relevant to the music-color synesthesia process;
  • Didn’t investigate likely music-color synesthesia development periods; and
  • Didn’t investigate associations of music-color synesthesia with epigenetic states.

Consider the magnitude of omitting the thalamus from synesthesia studies as one “perceptual nature” example. Just the background information of Thalamus gating and control of the limbic system and cerebrum is a form of memory indicated its relevance to synesthesia:

Despite the fundamental differences between visual, auditory and somatosensory signals, the basic layouts of the thalamocortical systems for each modality are quite similar.

For a given stimulus, the output neural response will not be static, but will depend on recent stimulus and response history.

Sensory signals en route to the cortex undergo profound signal transformations in the thalamus. A key thalamic transformation is sensory adaptation in which neural output adjusts to the statistics and dynamics of past stimuli.”

One of this study’s researchers described ways that an individual’s “stimulus and response history” became unconscious memories with the thalamus. Including the thalamus in synesthesia studies may also have findings that involve reliving or re-experiencing a memory, possibly an emotional memory.

In such future research, it could be a design element to ask synesthetes before and after the experiment to identify feelings and memories accompanying synesthesia experiences.

It shouldn’t be a requirement, however, to insist that memories and emotions be consciously identified in order to be included in the findings. Human studies, for example, Unconscious stimuli have a pervasive effect on our brain function and behavior have found:

“Pain responses can be shaped by learning that takes place outside conscious awareness.

Our results support the notion that nonconscious stimuli have a pervasive effect on human brain function and behavior and may affect learning of complex cognitive processes such as psychologically mediated analgesic and hyperalgesic responses.”

Does an orangy twilight of aging sunflowers help you feel?

https://www.sciencedirect.com/science/article/pii/S1053810017305883 “Music-colour synaesthesia: Concept, context and qualia” (not freely available)

Genomic imprinting and growth

This 2018 UK paper reviewed genomic imprinting:

“Since their discovery nearly 30 years ago, imprinted genes have been a paradigm for exploring the epigenetic control of gene expression. Moreover, their roles in early life growth and placentation are undisputed.

However, it is becoming increasingly clear that imprinted gene function has a wider role in maternal physiology during reproduction – both by modulating fetal and placental endocrine products that signal to alter maternal energy homeostasis, and by altering maternal energetic set points, thus producing downstream actions on nutrient provisioning.”

“Imprinted genes in the conceptus produce products that alter maternal resource allocation by:

  1. altering the transport capacity of the placenta;
  2. increasing fetal demand for resources by their action on the intrinsic growth rate; and
  3. signalling to the mother by the production of fetal/placental hormones that modify maternal metabolism.”

Other studies/reviews I’ve curated that covered genomic imprinting are:

http://jeb.biologists.org/content/jexbio/221/Suppl_1/jeb164517.full.pdf “Genomic imprinting, growth and maternal-fetal interactions”

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.

Parental lying thwarted both their children and researchers

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 Is what’s true for a population what’s true for 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.

The subjects didn’t provide 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!

The subjects’ parents willingly misled their children about facts of their child’s important earliest development periods. Their lies and omissions were not only unethical to the children, but also, whenever they became recognized, diminished or destroyed 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 evidence greatly increased the difficulty for researchers to determine causes of epigenetic effects still present in the subjects’ lives.

The parental lying was again unethical in that it diminished or destroyed the society between the sources of information – the research subjects – and the users of the information. It adversely affected anyone who valued 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)

Genetic imprinting, sleep, and parent-offspring conflict

This 2016 Italian review subject was the interplay of genetic imprinting and sleep regulation:

“Sleep results from the synergism between at least two major processes: a homeostatic regulatory mechanism that depends on the accumulation of the sleep drive during wakefulness, and a circadian self-sustained mechanism that sets the time for sleeping and waking throughout the 24-hour daily cycle.

REM sleep apparently contravenes the restorative aspects of sleep; however, the function of this ‘paradoxical’ state remains unknown. Although REM sleep may serve important functions, a lack of REM sleep has no major consequences for survival in humans; however, severe detrimental effects have been observed in rats.

Opposite imprinting defects at chromosome 15q11–13 are responsible for opposite sleep phenotypes as well as opposite neurodevelopmental abnormalities, namely the Prader-Willi syndrome (PWS) and the Angelman syndrome (AS). Whilst the PWS is due to loss of paternal expression of alleles, the AS is due to loss of maternal expression.

Maternal additions or paternal deletions of alleles at chromosome 15q11–13 are characterized by temperature control abnormalities, excessive sleepiness, and specific sleep architecture changes, particularly REM sleep deficits. Conversely, paternal additions or maternal deletions at chromosome 15q11–13 are characterized by reductions in sleep and frequent and prolonged night wakings.

The ‘genomic imprinting hypothesis of sleep’ remains in its infancy, and several aspects require attention and further investigation.”

http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1006004 “Genomic Imprinting: A New Epigenetic Perspective of Sleep Regulation”

A commenter to the review referenced a 2014 study Troubled sleep: night waking, breastfeeding, and parent–offspring conflict that received several reactions, including one by the same commenter. Here are a few quotes from the study author’s consolidated response:

“‘Troubled sleep’ had two major purposes. The first was to draw attention to the oppositely perturbed sleep of infants with PWS and AS and explore its evolutionary implications. The involvement of imprinted genes suggests that infant sleep has been subject to antagonistic selection on genes of maternal and paternal origin with genes of maternal origin favoring less disrupted sleep.

My second major purpose was a critique of the idea that children would be happier, healthier and better-adjusted if we could only return to natural methods of child care. This way of thinking is often accompanied by a belief that modern practices put children at risk of irrevocable harm.

The truth of such claims is ultimately an empirical question, but the claims are sometimes presented as if they had the imprimatur of evolutionary biology. This appeal to scientific authority often seems to misrepresent what evolutionary theory predicts: that which evolves is not necessarily that which is healthy.

Why should pregnancy not be more efficient and more robust than other physiological systems, rather than less? Crucial checks, balances and feedback controls are lacking in the shared physiology of the maternal–fetal unit.

Infant sleep may similarly lack the exquisite organization of systems without evolutionary conflict. Postnatal development, like prenatal development, is subject to difficulties of evolutionarily credible communication between mothers and offspring.”

The author addressed comments related to attachment theory:

“Infants are classified as having insecure-resistant attachment if they maintain close proximity to their mother after a brief separation while expressing negative emotions and exhibiting contradictory behaviors that seem to both encourage and resist interaction. By contrast, infants are classified as having insecure-avoidant attachment if they do not express negative emotion and avoid contact with their mother after reunion.

Insecure-avoidant and insecure-resistant behaviors might be considered antithetic accommodations of infants to less responsive mothers; the former associated with reduced demands on maternal attention, the latter with increased demands. A parallel pattern is seen in effects on maternal sleep. Insecure-avoidant infants wake their mothers less frequently, and insecure-resistant infants more frequently, than securely attached infants.

Parent–child interactions are transformed once children can speak. Infants with more fragmented sleep at 6 months had less language at 18 and 30 months.

Infants with AS have unconsolidated sleep and never learn to speak. The absence of language in the absence of expression of one or more MEGs [maternally expressed imprinted genes] is compatible with a hypothesis in which earlier development of language reduces infant demands on mothers.”

Regarding cultural differences:

“China, Taiwan and Hong Kong have both high rates of bed-sharing and high rates of problematic sleep compared with western countries. Within this grouping, however, more children sleep in their own room but parents report fewer sleep problems in Hong Kong than in either China or Taiwan.

Clearly, cultural differences are significant, and the causes of this variation should be investigated, but the differences cannot be summarized simply as ‘west is worst’.

The fitness [genetic rather than physical fitness] gain to mothers of an extra child and the benefits for infants of longer IBIs [interbirth intervals] are substantial. These selective forces are unlikely to be orders of magnitude weaker than the advantages of lactase persistence, yet the selective forces associated with dairying have been sufficient to result in adaptive genetic differentiation among populations.

The possibility of gene–culture coevolution should not be discounted for behaviors associated with infant-care practices.”

Regarding a mismatch between modern and ancestral environments:

“I remain skeptical of a tendency to ascribe most modern woes to incongruence between our evolved nature and western cultural practices. We did not evolve to be happy or healthy but to leave genetic descendants, and an undue emphasis on mismatch risks conflating health and fitness.

McKenna [a commenter] writes ‘It isn’t really nice nor maybe even possible to fool mother nature.’ Here I disagree. Our genetic adaptations often try to fool us into doing things that enhance fitness at costs to our happiness.

Our genes do not care about us and we should have no compunction about fooling them to deliver benefits without serving their ends. Contraception, to take one obvious example, allows those who choose childlessness to enjoy the pleasures of sexual activity without the fitness-enhancing risk of conception.

Night waking evolved in environments in which there were strong fitness costs from short IBIs and in which parents lacked artificial means of birth-spacing. If night waking evolved because it prolonged IBIs, then it may no longer serve the ends for which it evolved.

Nevertheless, optimal infant development might continue to depend on frequent night feeds as part of our ingrained evolutionary heritage.

It could also be argued that when night waking is not reinforced by feeding, and infants sleep through the night, then conflict within their genomes subsides. Infants would then gain the benefit of unfragmented sleep without the pleiotropic costs of intragenomic conflict. Plausible arguments could be presented for either hypothesis and a choice between them must await discriminating evidence.”

Commenters on the 2014 study also said:

[Crespi] The profound implications of Haig’s insights into the roles of evolutionary conflicts in fetal, infant and maternal health are matched only by the remarkable absence of understanding, appreciation or application of such evolutionary principles among the research and clinical medical communities, or the general public.

[Wilkins] A mutation may be selected for its effect on the trait that is the basis of the conflict, but that mutation also likely affects other traits. In general, we expect that these pleiotropic effects to be deleterious: conflict over one trait can actually drive other traits to be less adapted. Natural selection does not necessarily guarantee positive health outcomes.

[McNamara] Assuming that AS/REM is differentially influenced by genes of paternal origin then both REM properties and REM-associated awakenings can be better explained by mechanisms of genomic conflict than by traditional claims that REM functions as an anti-predator ‘sentinel’ for the sleeping organism.

[Hinde] Given this context of simultaneous coordination and conflict between mother and infant, distinguishing honest signals of infant need from self-interested, care-extracting signals poses a challenge.