Ideaesthesia!

This 2018 UK review subject was colored-hearing arising on hearing 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, they were 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 orangey twilight of fading sunflowers help you feel?

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

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The truth about complex traits and GWAS

This 2017 Colorado analysis, “No Evidence That Schizophrenia Candidate Genes Are More Associated With Schizophrenia Than Noncandidate Genes,” found:

“A recent analysis of 25 historical candidate gene polymorphisms for schizophrenia in the largest genome-wide association study [GWAS] conducted to date suggested that these commonly studied variants were no more associated with the disorder than would be expected by chance.

However, the same study identified other variants within those candidate genes that demonstrated genome-wide significant associations with schizophrenia. As such, it is possible that variants within historic schizophrenia candidate genes are associated with schizophrenia at levels above those expected by chance, even if the most-studied specific polymorphisms are not.

As a group, variants in the most-studied candidate genes were no more associated with schizophrenia than were variants in control sets of noncandidate genes. While a small subset of candidate genes did appear to be significantly associated with schizophrenia, these genes were not particularly noteworthy given the large number of more strongly associated noncandidate genes.

The history of schizophrenia research should serve as a cautionary tale to candidate gene investigators examining other phenotypes: our findings indicate that the most investigated candidate gene hypotheses of schizophrenia are not well supported by genome-wide association studies, and it is likely that this will be the case for other complex traits as well.”


One reason I admire scientists is that many of them are genuinely interested in advancing science. They eventually expose the storytelling and directed narratives in reviews such as:

They uncover questionable methods and moneygrubbing to fund research with a goal of confirming sponsors’ biases such as:

They impartially examine evidence supporting agendas and personal aggrandizements in studies such as:

Unbiased facts and analyses are eventually reported by these dedicated scientists. The problem is that their works aren’t on page 1 of journals and search results.

https://www.biologicalpsychiatryjournal.com/article/S0006-3223(17)31772-9/fulltext “No Evidence That Schizophrenia Candidate Genes Are More Associated With Schizophrenia Than Noncandidate Genes” (not freely available)

A flying human tethered to a monkey

Ponder this drone photo of “a flying human tethered to a monkey” ground drawing made over 1,000 years ago as reported by National Geographic and excerpted by the Daily Star:
Flying human tethered to a monkey


Aren’t the geoglyph and its description pretty good expressions of our evolved condition? Especially since it’s the interpretation of people who lived more a millennium ago?

With so many information sources freely available now, one couldn’t successfully argue that they understood the world better than we do, though. The price paid for figuring things out today is our “flying human” time and efforts, without which we’re as ignorant as our “monkey.”

A few aspects of the current comprehension of the differences between our two pictured primates are in Genetic imprinting, sleep, and parent-offspring conflict:

“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 [genetic rather than physical fitness].”

Our “flying human” can make happiness and health choices that our “monkey” can’t:

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.”

Other aspects of each of our two pictured primates’ differences are illuminated in a reference to A study of DNA methylation and age:

“Aging is not and cannot be programmed. Instead, aging is a continuation of developmental growth, driven by genetic pathways.

Genetic programs determine developmental growth and the onset of reproduction. When these programs are completed, they are not switched off.

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.”

The epigenetic clock theory of aging cited the same author, and modified his point to say:

“The proposed epigenetic clock theory of ageing views biological ageing as an unintended consequence of both developmental programmes and maintenance programmes.”

Our “flying human” can make choices that aren’t available to our “monkey” concerning the structure, direction, and duration of our one precious life:

“What are you doing to reverse epigenetic processes and realize what you want? Do you have ideas and/or behaviors that interfere with taking constructive actions to change your phenotype?”

This dietary supplement is better for depression symptoms than placebo

This 2018 Italy/UK meta-analysis subject was the use of dietary supplement acetyl-L-carnitine to treat depression symptoms:

“Deficiency of acetyl-L-carnitine (ALC) appears to play a role in the risk of developing depression, indicating dysregulation of fatty acids transport across the inner membrane of mitochondria. However, the data regarding ALC supplementation in humans are limited. We thus conducted a systematic review and meta-analysis investigating the effect of ALC on depressive symptoms across randomized controlled trials (RCTs).

Pooled data across nine RCTs (231 treated with ALC versus 216 treated with placebo and 20 no intervention) showed that ALC significantly reduced depressive symptoms.


In three RCTs comparing ALC versus antidepressants (162 for each group), ALC demonstrated similar effectiveness compared with established antidepressants [fluoxetine (Prozac), duloxetine (Cymbalta), amisulpride (Solian) respectively below] in reducing depressive symptoms. In these latter RCTs, the incidence of adverse effects was significantly lower in the ALC group [79%] than in the antidepressant group.


Subgroup analyses suggested that ALC was most efficacious in older adults..Future large scale trials are required to confirm/refute these findings.”

From the Study selection subsection:

“Studies were excluded if:

  1. did not include humans;
  2. did not include a control group;
  3. did not use validated scales for assessing depression;
  4. did not report data at follow-up evaluation regarding tests assessing depression;
  5. included the use of ALC with another agent vs. placebo/no intervention.”

The Discussion section was informative regarding possible mechanisms of ALC affecting depression, pain, and linked symptoms. Several citations were of a review rather than of the original studies, however.


Research needs to proceed on to investigate therapies that address ultimate causes for depression and pain. Researchers and sponsors shouldn’t stop at just symptoms and symptom relief, notwithstanding the requirement from a statistical point of view for “future large scale trials.”

Here are other acetyl-L-carnitine topics I’ve curated:

https://journals.lww.com/psychosomaticmedicine/Citation/2018/02000/Acetyl_L_Carnitine_Supplementation_and_the.4.aspx “Acetyl-L-Carnitine Supplementation and the Treatment of Depressive Symptoms: A Systematic Review and Meta-Analysis” (not freely available)


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.

Your need to feel important will run your life, and you’ll never feel satisfied

Yesterday’s team meeting at work provided one display after another of a person’s need to feel important. These eye-openers were the reason the scheduled 30-minute meeting lasted 45 minutes.

Although half of the forty or so attendees are under the age of 40, curiously, only two of them spoke during the meeting. I wasn’t among the older people who had something to say.

Not that I wasn’t tempted by the team-building exercise with its Skittles prompts:

  • Red – Tell us something you do well
  • Orange – Tell us something about your childhood
  • Purple – What could you live without?
  • Yellow – What couldn’t you live without?

Participation in the exercise was voluntary. Yes, I drew an orange Skittle.

Everyone knew there wasn’t enough time for each of us to speak and have the exercise become team-building, yet a dozen people piped up. Every one of the self-selected responses could have been prefaced with “I’m important because..”



There are many needs a person develops and tries to satisfy as substitutes for real needs that weren’t fulfilled. In this blog I’ve focused on the need to feel important.

I started with How do we assess “importance” in our lives? An example from scientists’ research choices and highlighted it on my Welcome page:

“Do you agree that an individual’s need to feel important is NOT a basic human need on the same level as nourishment, protection, and socialization? How does this need arise in our lives?”

I supported an explanation of the need to feel important with evidence and arguments on my Scientific evidence page and said:

“If the explanation is true yet someone rejected it, they at least wouldn’t have suffered from exposure to it. They’ll just remain in our world’s default mode of existence:

  1. Unaware of their own unconscious act-outs to feel important;
  2. Unaware of what’s driving such personal behavior; and
  3. Uninformed of other people’s behavioral origins as a consequence of 1 and 2.”

Other examples of substitute needs include:

What do you think? Any arguments for or against interrupting people’s default mode of existence?

An emotional center of our brains

This 2018 McGill/UC San Diego rodent study was on the dentate gyrus area of the hippocampus:

“Early life experience influences stress reactivity and mental health through effects on cognitive-emotional functions that are, in part, linked to gene expression in the dorsal and ventral hippocampus. The hippocampal dentate gyrus (DG) is a major site for experience-dependent plasticity associated with sustained transcriptional alterations, potentially mediated by epigenetic modifications.

Peripubertal environmental enrichment increases hippocampal volume and enhances dorsal DG-specific differences in gene expression..Overall, our transcriptome and DNA methylation data support a model of regional and environmental effects on the molecular profile of DG neurons.”

The study thoroughly investigated several areas. I’ll quote a few parts with the section heading.

Introduction:

“The dorsal hippocampus, corresponding to the posterior hippocampus in primates, associates closely with cognitive functions and age-related cognitive impairments. In contrast, the ventral hippocampus, (anterior region in primates) is implicated in the regulation of emotional states and vulnerability for affective disorders. This functional specialization is reflected in patterns of gene expression.”

Results subsections:

“Environmental enrichment promotes hippocampal neurogenesis – hippocampal volume is enlarged in mice raised in an enriched environment (EE) compared with standard housing (SH) in both the dorsal and ventral poles..EE also associates with >60% more newborn neurons.

Specialization of gene expression in dorsal and ventral DG – Gene expression was more affected by EE in dorsal than ventral DG, and dorsal DG has twice as many differentially-expressed genes.

DNA methylation differences between dorsal and ventral DG – Each of the three forms of methylation [CpG, non-CpG, and hmC (hydroxymethylation)] exhibited a distinct genomic distribution in dorsal and ventral DG..A key advantage of whole-genome DNA methylation profiling is the ability to identify differentially methylated regions (DMRs), often far from any gene body, that mark tissue-specific gene regulatory elements..This strong bias, with ~40-fold more hypomethylated regions in the dorsal DG, contrasts with the balanced number of differentially expressed genes in dorsal and ventral DG, suggesting an asymmetric role for DNA methylation in region-specific gene regulation. Despite their small number, ventral hypomethylated DMRs marked key developmental patterning transcription factors..which are linked to the proliferation, maintenance and survival of neural stem cells.

DNA methylation correlates with repression at some genes – CG and non-CG DNA methylation are associated with reduced gene expression, while hmC associates with increased expression..dorsal DMRs were also enriched at genes that were up- and down-regulated in EE, although over half of dorsal up-regulated genes, and >98.5% of ventral up-regulated genes, contained no DMRs that could explain their region-specific differential expression.”

Discussion:

  • “a The cell stages occurring within the subgranular zone of the dentate gyrus are shown together with a schematic illustration of possible relative proportions consistent with our data. RGL Radial glia-like progenitor, NSC Neural stem cell.
  • b Key genes associated with the RGL stage are up-regulated in ventral DG relative to dorsal DG.
  • c We propose that mCH [non-CpG methylation] accumulates mainly in mature neurons.”

Why do human brain studies that include the hippocampus overwhelmingly ignore its role in our emotions? For example, the researchers of Advance science by including emotion in research could find only 397 suitable studies performed over 22 years from 1990 to 2011. There were tens or hundreds of times more human brain studies done during the same period that intentionally excluded emotional content!

The current study provided physiological bases for dialing back the bias of human brain research focusing exclusively on cognitive functions without also investigating attributes of emotional processing. I look forward to seeing 2018 human studies that are designed to correct this recurring research deficiency.

https://www.nature.com/articles/s41467-017-02748-x “Environmental enrichment increases transcriptional and epigenetic differentiation between mouse dorsal and ventral dentate gyrus”

How to cure the ultimate causes of migraines?

Most of the spam I get on this blog comes in as ersatz comments on The hypothalamus couples with the brainstem to cause migraines. I don’t know what it is about the post that attracts internet bots.

The unwanted attention is too bad because the post represents a good personal illustration of “changes in the neural response to painful stimuli.” Last year I experienced three three-day migraines in one month as did the study’s subject. This led to me cycling through a half-dozen medications in an effort to address the migraine causes.

None of the medications proved to be effective at treating the causes. I found one that interrupted the progress of migraines – sumatriptan, a serotonin receptor agonist. I’ve used it when symptoms start, and the medication has kept me from having a full-blown migraine episode in the past year.

1. It may be argued that migraine headache tendencies are genetically inherited. Supporting personal evidence is that both my mother and younger sister have migraine problems. My father, older sister, and younger brother didn’t have migraine problems. Familial genetic inheritance usually isn’t the whole story of diseases, though.

2. Migraine headaches may be an example of diseases that are results of how humans have evolved. From Genetic imprinting, sleep, and parent-offspring conflict:

“..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.

Both migraine causes and effects may be traced back to natural lacks of feedback loops. These lacks demonstrate that such physiological feedback wasn’t evolutionarily necessary in order for humans to survive and reproduce.

3. Examples of other processes occurring during prenatal development that also lack feedback loops, and their subsequent diseases, are:

A. Hypoxic conditions per Lack of oxygen’s epigenetic effects are causes of the fetus later developing:

  • “age-related macular degeneration
  • cancer progression
  • chronic kidney disease
  • cardiomyopathies
  • adipose tissue fibrosis
  • inflammation
  • detrimental effects which are linked to epigenetic changes.”

B. Stressing pregnant dams per Treating prenatal stress-related disorders with an oxytocin receptor agonist caused fetuses to develop a:

  • “defect in glutamate release,
  • anxiety- and depressive-like behavior,

and abnormalities:

  • in social behavior,
  • in the HPA response to stress, and
  • in the expression of stress-related genes in the hippocampus and amygdala.”

1. What would be a treatment that could cure genetic causes for migraines?

I don’t know of any gene therapies.

2. What treatments could cure migraines caused by an evolved lack of feedback mechanisms?

We humans are who we have become, unless and until we can change original causes. Can we deal with “changes in the neural response to painful stimuli” without developing hopes for therapies or technologies per Differing approaches to a life wasted on beliefs?

3. What treatments could cure prenatal epigenetic causes for migraines?

The only effective solution I know of that’s been studied in humans is to prevent adverse conditions like hypoxia from taking place during pregnancy. The critical periods of our physical development are over once we’re adults, and we can’t unbake a cake.

Maybe science will offer other possibilities. Maybe it will be necessary for scientists to do more than their funding sponsors expect?

BTW, comments are turned off for the above-mentioned post. Readers can comment on this post instead.