The emotional power of environmental sounds affects our sensory experiences

This 2015 Chinese/Australian study found:

“Human emotions systematically track changes in the acoustic environment, affecting not only how we experience those sounds but also how we perceive facial expressions in other people.

Three changes in acoustic attributes known to signal emotional states in speech and music [frequency spectrum, intensity, and rate] were imposed upon 24 environmental sounds.

Evolution promotes development in the direction toward selective advantage. Thus, it is reasonable to suggest that the capacity to track changes in the acoustic environment evolved before the development of a vocalization system for emotional communication.

Regardless of the evolutionary implications of the effect, the findings illustrate the emotional power of environmental sounds on both our experience of sounds and our evaluations of accompanying visual stimuli.”

Here are the sounds used in the study:

“Human actions (breathing, chatting, chewing, clapping, stepping, typing), animal sounds (bird, cat, cricket, horse, mosquito, rooster), machine noise (car engine, electrical drill, helicopter, jet plane, screeching tires, train), and sounds in nature (dripping water, rain, river, thunder, waves, wind)”

Does this emotional communication’s frequency spectrum, intensity, and rate affect your perception of her face? “Human emotions track changes in the acoustic environment”

Who chooses whether research is important enough to be funded?

This 2015 Chicago study of biomedical research published over a 30-year period found:

“Biomedical scientists pursue conservative research strategies exploring the local neighborhood of central, important molecules.

Although such strategies probably serve scientific careers, we show that they slow scientific advance, especially in mature fields, where more risk and less redundant experimentation would accelerate discovery of the network.”

“Importance” was determined as an objective variable in the study, then simultaneously emphasized and disavowed by the lead researcher in an interview:

“The trick is to find something really important, and not being attacked by thousands of other people around the globe.

One protein and all its connections is surely important, but what is the objective measure of importance?

You need to think about networks and interacting parts, not one protein.”

and in the study’s Discussion section:

“Efficient discovery of radically new knowledge in a mature field, including many areas of biomedicine, requires abandoning the current focus on important, nearby chemicals.”

A researcher who wasn’t involved in the study commented:

“Greater synthesis, and step-wise progress may sometimes be more important than disruptive innovation.”

Rationale that it was important for “scientific advance” to abandon studies in areas closely related to important chemicals disregarded researchers’ individual interests. It was implausible that the study’s recommendation to publish all research failures would be implemented without being forced, which would again disregard individual interests.

The researchers made recommendations as if these could be carried out by people who hypothetically acted independently of their personal histories and interests when making decisions important for “scientific advance.”

Who are these people? Just one example would suffice.

If these recommendations would be enforced by systems without people, who gets the funding to design and put such systems into place? Would scientists’ participation be voluntary, or essentially mandatory in order to work in covered areas?

There are many influences on which research proposal receives funding, of course. I didn’t see any coverage in the study or in the accompanying news articles of the influences discussed in How do we assess “importance” in our lives? An example from scientists’ research choices. That study was referenced, but only for its data distribution characteristics.

The current study assessed the importance of research choices as if each individual scientist had no motivating personal history. The researchers may have achieved actionable findings if the study’s design and methodology better incorporated the hypothesis that scientists’ career and personal choices were influenced by whether or not the work made them feel important. “Choosing experiments to accelerate collective discovery”

Mitochondria interface genetic/epigenetic responses to psychological stress

This 2015 Pennsylvania rodent study found:

Mitochondria can regulate complex whole-body physiological responses, impacting stress perception at the cellular and organismal levels.

Mitochondrial dysfunctions altered the

  1. hypothalamic–pituitary–adrenal [HPA] axis, sympathetic adrenal–medullary activation and catecholamine levels,
  2. the inflammatory cytokine IL-6,
  3. circulating metabolites, and
  4. hippocampal gene expression

responses to stress.


  1. neuroendocrine,
  2. inflammatory,
  3. metabolic, and
  4. transcriptional responses

coalesced into unique signatures that distinguish groups based on their mitochondrial genotype.”

The study’s design was comprehensive for the subject of mitochondrial function and stress response categories. It interrelated elements that had a common cause of stress, such as:

  • Hyperglycemia
  • Increased lipids
  • Corticosterone sensitivity
  • Epigenetic changes within the brain

The study’s Figure 6E was a hierarchical “heat map” of the correlations among the 77 stress-induced changes that were measured. Figure 6G presented these variables per the five mitochondrial genotypes (a control wild-type and four genetic dysfunctions). Many of the lines forming the hierarchy needed careful reading of the study’s interpretations.

I downgraded the study’s rating because the authors inappropriately forced the “allostatic load” buzzword into the Significance statement and otherwise informative Discussion section. The term refers to a hypothetical long-term situation, but the study’s experiments lasted 2 hours at most before the subjects were killed. “Mitochondrial functions modulate neuroendocrine, metabolic, inflammatory, and transcriptional responses to acute psychological stress”

Neural pathways for forgetting bad smells

This 2015 New York fruit fly study found:

“Forgetting is regulated by multiple neural pathways that impinge upon a memory center.

Forgetting over time and the acute forgetting of conflicting memory during reversal learning rely on separable neural circuits.

Inactivating these neurons inhibits memory decay without altering learning, whereas activating them promotes forgetting. These neurons [include] a cluster of dopaminergic neurons and a pair of glutamatergic neurons.

Although activity of these neurons is required for memory decay over time, they are not required for acute forgetting during reversal learning. Our results thus not only establish the presence of multiple neural pathways for forgetting in Drosophila but also suggest the existence of diverse circuit mechanisms of forgetting in different contexts.”

Here’s a 3D view of the glutamatergic neurons: “Dissecting neural pathways for forgetting in Drosophila olfactory aversive memory”

Familiar stress opens up an epigenetic window of neural plasticity

This 2015 Italian rodent study found:

“There is a window of plasticity that allows familiar and novel experiences to alter anxiety– and depressive-like behaviors, reflected also in electrophysiological changes in the dentate gyrus (DG).

A consistent biomarker of mood-related behaviors in DG is reduced type 2 metabotropic glutamate (mGlu2), which regulates the release of glutamate. Within this window, familiar stress rapidly and epigenetically up-regulates mGlu2..and improves mood behaviors.

These hippocampal responses reveal a window of epigenetic plasticity that may be useful for treatment of disorders in which glutamatergic transmission is dysregulated.”

The current study included two of the authors of A common dietary supplement that has rapid and lasting antidepressant effects.

The supplementary material showed the:

“Light–dark test as a screening method allowed identification of clusters of animals with a different baseline anxiety profile”

for the BDNF Val66Met subjects. This research methodology better handled the individual differences that often confound studies.

The study’s press release provided further details such as:

“Here again, in experiments relevant to humans, we saw the same window of plasticity, with the same up-then-down fluctuations in mGlu2 and P300 in the hippocampus, Nasca says. This result suggests we can take advantage of these windows of plasticity through treatments, including the next generation of drugs, such as acetyl-L-carnitine, that target mGlu2—not to ‘roll back the clock’ but rather to change the trajectory of such brain plasticity toward more positive directions.”

I disagree with the authoring researchers’ extrapolation of these rodent findings to humans, which seemed to favor chemical intervention. Causes of human stress should be removed or otherwise addressed.

I hope that the study’s “familiar stress” findings won’t be use to attempt to justify potentially harmful practices such as Critical Incident Stress Debriefing, which mandatorily guides people to process recent trauma. Instead, An interview with Dr. Rachel Yehuda on biological and conscious responses to stress made a point about “windows of plasticity” that’s relevant to who we are as feeling human beings:

“What I hear from trauma survivors — what I’m always struck with is how upsetting it is when other people don’t help, or don’t acknowledge, or respond very poorly to needs or distress.” “Stress dynamically regulates behavior and glutamatergic gene expression in hippocampus by opening a window of epigenetic plasticity”

The function of the dorsal ACC is to monitor pain in survival contexts

This 2015 California human study was of the dorsal anterior cingulate cortex (dACC):

“No neural region has been associated with more conflicting accounts of its function than the dACC.

The best psychological description of dACC function was related to pain processing—not executive, conflict, or salience processing.

We conclude by considering that physical pain may be an instance of a broader class of survival-relevant goals monitored by the dACC, in contrast to more arbitrary temporary goals, which may be monitored by the supplementary motor area.”

A related brain area – the paracingulate sulcus (PCS) – and its impact on the study’s findings was discussed in the supplementary material:

“The PCS is present in a subset of the population and thus extends the dACC further in the dorsal direction. This possible additional sulcus is relevant because, for some individuals, the ventral portion of the SMA [supplementary motor area]/pre-SMA may actually be the PCS.

The vast majority of fMRI studies overlook most individual differences in neuroanatomy and depend on the probabilistic neuroanatomy averaged across a group of participants and then on standard atlases that typically don’t take these individual differences into account.

There are two structural forms of PCS. The “prominent” form extends through the entire dACC region; however the “present” form begins in the rostral ACC and ends near the anterior border of the dACC.

Men are significantly more likely than women to have unilateral or bilateral PCS.

Additionally, six morphology studies have indicated the existence of a PCS that is left-lateralized.”

How about that? A brain area that:

  • Assists in monitoring pain in the contexts of survival goals;
  • Size, form, and placement varies widely among individuals;
  • Is missing in some people!

Here’s a long critique of the study that included dialog with the authors:

“If you observe activation in dACC..your single best guess as to what process might be involved..should be ‘motor’ by a landslide. You could also guess ‘reward’ or ‘working memory’ with about the same probability as ‘pain.’

Of course, the more general message you should take away from this is that it’s probably a bad idea to infer any particular process on the basis of observed activity.”

And the authors’ “last comment”:

“Based on Neurosynth evidence, is more of the dACC selective for pain than for attention, autonomic, avoidance, conflict, emotion, error, executive, fear, negative affect, response inhibition, response selection, reward, and salience? Absolutely.” “The dorsal anterior cingulate cortex is selective for pain: Results from large-scale reverse inference”

A review of genetic and epigenetic approaches to autism

This 2015 Chicago review noted:

“Recent developments in the research of ASD [autistic spectrum disorder] with a focus on epigenetic pathways as a complement to current genetic screening.

Not all children with a predisposing genotype develop ASD. This suggests that additional environmental factors likely interact with the genome in producing ASD.

Increased risk of ASD is associated with mutations in genes that overlap with chromatin remodeling proteins, transcriptional regulators and synapse-associated proteins. Interestingly, these genes are also targets of environmentally induced changes in gene expression.”

Evidence was discussed for both broad and specific epigenetic ASD causes originating in the prenatal environment:

  • Maternal stress:

    “Prenatal stress exerts a profound epigenetic influence on GABAergic interneurons by altering the levels of proteins such as DNMT1 and Tet1 and decreasing the expression of various targets such as BDNF.

    Ultimately, this results in reducing the numbers of fully functional GABAergic neurons postnatally and a concomitant increased susceptibility toward hyperexcitability. The delayed migration of GABAergic interneuron progenitors results in reduced gene expression postnatally which is likely the consequence of increased amounts of DNA methylation.

    The net effect of stress during early development is to disrupt the balance of excitatory/inhibitory neuronal firing due to the loss of function associated with disrupted neuronal migration and maturation.”

  • Prenatal nutrition:

    “Exposure to a wide range of environmental toxins that impact neurodevelopment also result in global DNA hypomethylation. This model was extended to connect pathways between dietary nutrition and environmental exposures in the context of DNA hypomethylation. More recently, this hypothesis was expanded to show how dietary nutrients, environmental toxins, genome instability and neuroinflammation interact to produce changes to the DNA methylome.”

  • Maternal infections:

    “Inflammation, autoimmunity and maternal immune activation have long been suspected in the context of aberrant neurodevelopment and ASD risk.”

  • Exposure to pollutants, medications, alcohol

This was a current review with many 2015 and 2014 references. However, one word in the reviewers’ vernacular that’s leftover from previous centuries was “idiopathic,” as in:

“Idiopathic (nonsyndromic) ASD, for which an underlying cause has not been identified, represent the majority of cases.”

It wasn’t sufficiently explanatory to use categorization terminology from thousands of years ago.

Science has progressed enough with measured evidence from the referenced studies that the reviewers could have discarded the “idiopathic” category and expressed probabilistic understanding of causes. They could have generalized conditional origins of a disease, and not reverted to “an underlying cause has not been identified.”

Another word the reviewers used was “pharmacotherapeutic,” as in:

“The goal for the foreseeable future is to provide a better understanding of how specific genes function to disrupt specific biological pathways and whether these pathways are amenable to pharmacotherapeutic interventions.”

Taking “idiopathic” and “pharmacotherapeutic” together – causes for the disease weren’t specifically identified, but the goal of research should be to find specific drug treatments?

Of course reviewers from the Department of Psychiatry, The Psychiatric Institute, University of Illinois at Chicago are biased to believe that “the design of better pharmacotherapeutic treatments” will fulfill peoples’ needs.

Are their beliefs supported by evidence? Without using drugs, are humans largely incapable of therapeutic actions such as:

  • Preventing epigenetic diseases from beginning in the prenatal environment?
  • Treating epigenetic causes for and alleviating symptoms of their own disease? “Merging data from genetic and epigenetic approaches to better understand autistic spectrum disorder”

An interview with Dr. Rachel Yehuda on biological and conscious responses to stress

How Trauma and Resilience Cross Generations

“The purpose of epigenetic changes, I think, is simply to increase the repertoire of possible responses.

So let’s say, for some reason, your parents transmitted to you biologic changes that are very appropriate to starvation, but you don’t live in a culture where food is not plentiful.

You’re just not optimized, but I think that if we develop an awareness of what the biologic changes from stress and trauma are meant to do, then I think we can develop a better way of explaining to ourselves what our true capabilities and potentials are.

What I hear from trauma survivors — what I’m always struck with is how upsetting it is when other people don’t help, or don’t acknowledge, or respond very poorly to needs or distress.

Feel it instead of running to someone to give you a sleeping pill.”


Telomere dynamics, stress, and aging across generations

This 2015 Pennsylvania/North Dakota animal and human review noted:

“The mechanisms linking stress exposure to disease progression and ageing either within individuals or across generations are still unclear, but recent work suggests that telomere dynamics (length and loss rate) may play an important role.

Parental stress may directly influence the parental germline telomeres pre-fertilization, affecting the telomere length inherited by offspring. Alternatively, parental stress may affect telomere dynamics indirectly either pre- or post-natally. The physiological mechanisms by which stress elicits changes in telomere length are also diverse.

We need more information about how these effects vary between developmental stages, among individuals, and within tissues of mitigate the effects of early life adversity on human health.”

I was disappointed that the reviewers chose Problematic research with telomere length as a reference. Then again, maybe their statement:

“how these traits are related to one another clearly deserves more study”

is a polite way of saying that study’s methodology was flawed?

Regarding evolutionary biology:

“While most evidence suggests that the effect of parental stress exposure on offspring telomeres is negative, it is important to remember that this is just one trait that can contribute to parental and offspring fitness.

Investment in traits that increase fitness is expected to be favoured, even if they come at a cost to traits associated with longevity, such as telomere length.”

A similar point was made in a reference of A study of DNA methylation and age that:

“Aging has no purpose (neither for individuals nor for group), no intention. Nature does not select for quasi-programs. It selects for robust developmental growth.” “Telomere dynamics may link stress exposure and ageing across generations”

Psychological therapy and DNA methylation

This 2015 worldwide human study was:

“The largest study to date investigating the role of HPA [hypothalamic–pituitary–adrenal] axis related genes in response to a psychological therapy. Furthermore, this is the first study to demonstrate that DNA methylation changes may be associated with response to psychological therapies in a genotype-dependent manner.

In this study, we tested the association between polymorphisms of FKBP5 [a gene that produces a protein that dampens glucocorticoid receptor sensitivity primarily in areas of the limbic system such as the hippocampus and amygdala] and GR [glucocorticoid receptor gene] and response to CBT [cognitive behavior therapy] in children with anxiety disorders (N = 1,152), and examined change in DNA methylation at specific regions of these genes during the course of CBT in a subset of the sample (n = 98).

No significant association was found between GR methylation and response. Allele-specific change in FKBP5 methylation was associated with treatment response.”

Regarding “treatment response:”

“Subjects aged 5–18 (mean: 9.8 years) met DSM-IV criteria for primary diagnosis of an anxiety disorder.

Clinical severity ratings (CSRs) were usually based on composite parent and child reports, and were assigned on a scale of 0–8. [36] [linked below]

Treatment response was defined as the change in primary anxiety disorder severity from pretreatment to follow-up. A diagnosis was made when the child met diagnostic criteria and received a CSR of 4 or more. Remission was regarded as the absence of the primary anxiety according to diagnostic criteria, as determined by the clinicians at the follow-up interview.”

Scenarios where nine-year-olds and their parents may have benefited from skewing their “composite parent and child reports” either way:

  1. Parents benefited from an anxious-child report (financial support provided, social services provided, avoided undesirable activities like going to work, continued psychological dependence, provided victim celebrity, enabled their own problems)
  2. Parents benefited from a well-child report (freed up time to pursue desirable activities, financial relief, relief from court-ordered or social-services-required activities, covered up their own contributions to the child’s problems)
  3. Nine-year-olds benefited from an anxious report (relief from undesirable activities like school attendance, continued psychological dependence, provided victim celebrity, activities structured around their condition, enabled the parents’ problems)
  4. Nine-year-olds benefited from a well report (symptom reduction, met parental expectations, freed up time to pursue desirable activities, covered up the parents’ contributions to the child’s problems).

I wonder what “treatment response” criteria were available other than self-serving reports and “diagnostic criteria, as determined by the clinicians.” Every day medical personnel hear patients self-report conditions where biological measurements may confirm or indicate something different. Did the “diagnostic criteria, as determined by the clinicians” include comparisons to relevant biological measurements?

The related study linked below points out:

“Although CBT has been established as an efficacious treatment, roughly 40% of children retain their disorder after treatment.”

Its focus was also on predictors (other than genetic) of CBT outcomes.

Neither study provided evidence of attempts to find originating causes for the children’s conditions. Were the international CBT approaches only interested in treating symptoms? “HPA AXIS RELATED GENES AND RESPONSE TO PSYCHOLOGICAL THERAPIES: GENETICS AND EPIGENETICS”

Related 2015 study: “Clinical Predictors of Response to Cognitive-Behavioral Therapy in Pediatric Anxiety Disorders: The Genes for Treatment (GxT) Study”

A review of epigenetic transgenerational inheritance of reproductive disease

This 2015 Washington review of epigenetic transgenerational inheritance of reproductive disease defined transgenerational effects as follows:

“In considering transgenerational phenomena it is important to distinguish between direct exposure effects versus germline (sperm or egg) mediated transgenerational events.

When a gestating F0 generation female is exposed the F0 generation female, the F1 generation fetus and the germ cell (sperm or egg) that is inside the fetus and that will produce the F2 generation are all directly exposed. Any effects in the F0, F1 and F2 generations may be due to direct exposure toxicity or to environmentally induced epigenetic changes in the directly exposed cells. Examination of the F3 generation (great grand-offspring) is needed to determine if a transgenerational phenomenon has occurred, since the F3 generation has had no direct exposure effects.

In contrast, in the event an adult male or non-pregnant female is exposed, the F0 generation adult and the germ cells that will generate the F1 generation are directly exposed, such that examination of the F2 generation (grand-offspring) is required to demonstrate a transgenerational phenomenon.”

This review was an example of a government agency commissioning science that narrowly supported their view. NIEHS funded this review, and the authors interpreted “environment” in “Environmentally Induced Epigenetic Transgenerational Inheritance of Reproductive Disease” to fit this conduit of public funds.

The problem was that this interpretation of “environment” limited the subject to the categories pictured in this Venn diagram. The authors’ tailoring of “environmentally induced” to the government agency’s interests should have similarly restricted the title.

F3 sperm epimutations

Other interpretations of “environment” were in studies such as:

and their references. Such studies demonstrated both that:

  1. Environmental factors like stress and nutrition – especially in early life – cause diseases in later life; and
  2. These diseases may be inherited by the subjects’ descendants.

The authors elsewhere referred generally and specifically (nutrition) to studies of other environmental factors.

Have you ever heard that our children and then their children could possibly inherit our diseases caused by stressful environments? Wouldn’t that research be of equal to or greater importance in our lives than pesticides’ harmful effects? “Environmentally Induced Epigenetic Transgenerational Inheritance of Reproductive Disease”

Fetal exposure to sex hormones and female anxiety

This 2015 Swedish rodent study found:

“Women with polycystic ovary syndrome (PCOS) display high circulating androgen levels that may affect the fetus and increase the risk of mood disorders in offspring.

Although clinical data are inconsistent, there are indications that androgens play a crucial role in behavior and mood regulation in females.

Studies on the link between testosterone and anxiety behavior in males have generated inconsistent results.

Higher circulating testosterone has previously been reported in female rat PNA [prenatal androgen] offspring. This discrepancy may be a result of the higher doses of maternal testosterone (5 mg) used in the previous study compared with the present study (0.5 mg).

Although the anxiety-like behavior observed in the female PNA offspring in the present study cannot be directly explained by high circulating androgens, the reduced AR [androgen receptor] expression in the amygdala suggests a compensatory response to the high prenatal testosterone exposure, a result implicating the amygdala as the CNS site underlying the changes in anxiety in the PNA offspring. This idea is further strengthened by our experiment showing that subchronic testosterone exposure into amygdala is sufficient to produce anxiety-like behavior in adult females.

Maternal testosterone exposure causes anxiety-like behavior in female, and to a lesser extent male offspring, an effect that seems to occur during fetal life and to be mediated via AR in the amygdala, together with changes in ER [estrogen receptor] and in the serotonergic and GABAergic pathways in the amygdala and hippocampus of female PNA rats.”

The news coverage – too much testosterone caused anxiety-like symptoms in females whether they are adults or fetuses – was NOT what the study found. The headlines disregarded its caveat:

“The anxiety-like behavior observed in the female PNA offspring in the present study cannot be directly explained by high circulating androgens.”

I look forward to research on floor levels of testosterone, below which there are also adverse effects on females. There is such evidence, but would it play well with popular memes?

See Sex hormone exposure to the developing female fetus causes infertility in adulthood for another study that used the PCOS phenotype. “Maternal testosterone exposure increases anxiety-like behavior and impacts the limbic system in the offspring”

A study of methylation’s mechanical effects on DNA molecules

This 2015 Italian study investigated effects of DNA methylation on mechanical properties of single DNA molecules:

As a consequence of cytosine methylation, the binding of proteins that are implicated in transcription to gene promoters is severely hindered, which results in gene regulation and, eventually, gene silencing. To date, the mechanisms by which methylation biases the binding affinities of proteins to DNA are not fully understood; however, it has been proposed that changes in double-strand conformations, such as stretching, bending, and over-twisting, as well as local variations in DNA stiffness/flexibility may play a role.

We observe that methylation induces no relevant variations in DNA contour lengths, but produces measurable incremental changes in persistence lengths [stiffness/flexibility].

The results reported herein support the claim that the biological consequences of the methylation process, specifically difficulties in protein-DNA binding, are at least partially due to DNA conformation modifications.” “Effects of cytosine methylation on DNA morphology: An atomic force microscopy study”