#66. Neuromodulators as Peril Specialists [Neuroscience]

NE

Red: theory; black, fact.

Solanum dulcamara, a plant with anticholinesterase activity.

“Life is Difficulty”

My PhD thesis was about a neuromodulator (acetylcholine) acting on mammalian brain. It was tough to decapitate all those rats; I never got used to it. But if you can’t stand the formaldehyde, get out of the lab.

The basic theory

I conjecture that the primordial function of any type of transmitter substance acting on the g-protein-coupled cell-surface receptors or nuclear receptors of neurons was to coordinate the whole-organism response to some class of perils.

 

Complications

Glutamate, GABA, and acetylcholine are usually considered neurotransmitters, not neuromodulators, but all three have G-protein-coupled receptors in addition to ionotropic receptors and are thus both.

In thermoregulation, hypothalamic glutamate and GABA act on the body via the serotonergic raphe pallidus nucleus. The implied connection with predation (See table) would be due to the fact that animals become torpid at extremes of temperature and thus easy prey. The larger predator would have a smaller surface to volume ratio and thus slower warming and cooling after leaving its refugium to hunt. The predator thermal advantage would have been the selection pressure for thermal sensitivity in the anti-predation system, which eventually became upstream of temperature regulation effectors generally. 

The functional assignments suggested in Table 1 would mostly pertain to a very primordial brain. The implication is that any modern biological function of the neuromodulator substance other than organizing the response to a specific type of peril was elaborated out of the primordial function over long-term evolution, which can act opportunistically to confer new functions on preexisting adaptations.

An example of such elaboration is shown for dopamine in the inferred social role. A pre-adaptation for this role split may have been breast-feeding.

Table 1.

Peril	Substance	Failure mode
Extremes of heat and cold	glutamate and GABA	?
Predator	serotonin	depression
Parasite	histamine	phobia
Rival conspecific	noradrenaline	paranoia
Social isolation

#65. Baryogenesis [physics]

PH

(Part 5, Deprecated)

#64. The Drill Sergeants of the Apocalypse [evolutionary psychology, population]

EP     PO     

Red, theory; black, fact.

Seen in a hospital ward.

Updated 10-30-2024

The trickster type may really be a penetration tester. 

The type probably emerges in contexts of unequal power (Elmer Fudd has the shotgun; Bugs Bunny doesn’t). Thus, an abiding fear is the soil out of which tricksterism grows, by the following positive feedback:

A successful trick shows up the Fudds and shows them in a feckless light, which reduces the fear level of the trickster, which reinforces trick-playing. This is a short-term high that comes at the expense of worse relations with the Fudds and thus eventually even greater fear levels for the tricksters, which they try to remedy with still more tricks.

An example of an unequal power relationship is between a foreign invader and the defenders. Invasion is such a common event in history that by now, countermeasures will have evolved. Tricksterism is likely to be a tile in the mosaic of any such adaptation.

A biological precedent for penetrations testing?

Evidence for a biological precedent may be the many retroviruses integrated into the human genome. Presumably, one of these becomes active now and then at random and kills the host cell if the anti-viral defenses of the latter have become weak due to some somatic mutation. The red team-blue team strategy seems to be too good a trick for nature to miss (TGTNM).

Evolution of the trickster

09-27-2020: Modern human populations may have two (independent?) axes of political polarization: oppressor-oppressed and trickster-control freak. The first may sub serve dispersal by generating refugee groups and the second may sub serve building. Any built thing must serve in a complex world in which many constraints must be simultaneously observed. Thus, after the initial build, a long period of tweaking must typically follow. The role of the tricksters is to powerfully motivate this tweaking before the complacency of the control-freak builders leads to disaster. <03-12-2021: This may have been how engineering was done by an archaic version of Homo sapiens.><12-02-2022: The tricksters can also make mistakes, causing damage that cannot have a silver lining in any possible world, and moving to correct this is a natural role of the builders. If you are a builder, ask this: “What is the best use of my indignation?” It is to keep to a strict harm-reduction approach.><01-08-2024: Tricksterism can intensify into sadism, in which the protagonist takes pleasure in the victim’s torment and wants to make it last. Well, boy, if you make it last, you are giving the victim plenty of time and motivation to figure out solutions, like a patient old instructor giving his pupil his lessons one at a time, as he is ready for them, and this is how the wise victim will construct the situation. Such a victim will end up with information and know-how others will pay for.>

A tangent about our evolutionary context

Our evolutionary forebears may have been champion dispersers for a long time <12-21-2020: i.e., Homo erectus*> before the ice age** forced some of them to become champion builders (initially, of shelters and warm clothing). <12-31-2020: "champion environment modifiers" may be closer to the mark than "champion builders"> It is an interesting fact that physically, humans exceed all other animals only in long-distance running, which can be read as dispersal ability. Our carelessness with preserving the local environments and our propensity for overpopulation can be read as typical r-selected disperser behavior. <12-21-2020: The r-selecting niche was probably big game hunting. H. erectus sites indicate consumption of medium and large meat animals. Overhunting would have occurred routinely, due to the slow reproduction rates of large animals and the high hunting efficiency of H. erectus due to tool use, so that dispersal of the hunters to new habitats would likewise have been routine.>

* H. erectus: lived 2 million years ago to 100,000 years ago. H. sapiens: earliest fossils, 300,000 years old. Evidence of behavioral modernity: 100,000–70,000 y ago.

** that is, the Pleistocene ice age, itself a sequence of 5 successive continental glaciations (by oxygen isotope evidence) separated by temperate periods, starting 2.6 million years ago and thought to be not over yet. Over the past 800,000 y, continental glaciation has happened rhythmically on a 100,000-y cycle due to astronomical factors (Milankovitch cycle). Selection for building skill may therefore have occurred in multiple successive episodes over the course of the Pleistocene.

#61. Stress and Schizophrenia [neuroscience]

NE

Red, theory; black, fact.

Introduction

The main positive symptoms of schizophrenia, namely hallucinations, word salad, and loosening of associations, all seem to be variations of the latter, so loosening of associations will here be taken as the primary disorder. Stress and the brain's dopaminergic system are strongly implicated in the causation of schizophrenia. In connection with stress, psychologists speak of "the affective [emotional] pathway to schizophrenia." 

Organismal responses to stress

Stress is known to increase genetic variability in bacteria, a process known as transformation. Stress is likewise known to increase the meiotic recombination rate in sexually reproducing organisms such as fruit flies. (Stress-induced recombination and the mechanism of evolvability. Zhong W, Priest NK. Behavioral ecology and sociobiology. 2011;65:493-502.) It seems that when an organism is in trouble, it begins casting about ever more widely for solutions. If evolution is the only mode of adaptation available, this casting about will take the form of an increase in the size and frequency of mutations. In conscious humans, however, this casting about in search of solutions in the face of stress may well take the form of a loosening of associations during thought. Should the person find the solution he or she needs, then presumably the stress levels go down and the thought process tightens up again, so we have a negative feedback operating that eventually renormalizes the thought process and all is well. In optimization theory, this process is called "simulated annealing."

Disorder of a cognitive stress response

But what if the person does not find the solution they need? Then, presumably the loosening of associations gets more and more pronounced ("reverse annealing") until it begins to interfere with the activities of daily living and thus begins to contribute net stress, thus making matters worse, not better. Now we have a pernicious positive feedback operating, and it rapidly worsens the state of the sufferer in what is known as a psychotic break, resulting in hospitalization. That these psychotic breaks are associated with tremendous stress is made clear by the fact that post-traumatic stress disorder is a common sequel of a psychotic episode.

 

Stress: Molecular aspects

01-06-2020: Messenger substances (i.e., hormones and neuromodulators) known to carry the stress signal are: CRF, ACTH, cortisol, noradrenaline, adrenaline, dopamine, NGF, and prolactin. The well-known phenomenon of stress sensitization, <05-31-2020: which may be part of the disease mechanism of schizophrenia,> probably inheres in long-term changes in protein expression and will not be apparent in a simple blood test for any of the above substances without a prior standardized stress challenge. (Could that be the process of getting the needle itself? In that case, you would install a catheter through the needle to permit repeated blood sampling and collect the baseline sample long after the intervention sample, not before, as is customary in research.)

Other mental illnesses

05-31-2020: Bipolar disorder may result from an analogous positive feedback affecting another problem solving adaptation of the brain, which would be modelled by the alternation of brainstorming sessions (mania) with sessions in which the brainstormed productions are soberly critiqued (depression).

Brain mechanisms

12-04-2020: How does the loosening of associations of schizophrenia arise? I conjecture that one activated sensory memory represented in the posterior cortex does not activate another directly, but indirectly via an anatomically lengthy but fast relay through the prefrontal cortex, which has a well known dopaminergic input from the ventral tegmental area of the midbrain. Imagine that a higher vertebrate has a free-will spectrum, with machine-like performance and high dopaminergic tone at one end, and at the other, a carefully considered performance verging on overthinking, with low dopaminergic tone. Persons with schizophrenia have presumably pushed past the latter end of the spectrum into dysfunction. Dopamine could orchestrate movement along the free-will spectrum by a dual action on the prefrontal cortex: inhibiting associational reflexes passing back to posterior cortex while facilitating direct outputs to the motor system. Dual actions of neuromodulators are a neuroscientific commonplace (e.g., my PhD thesis) and dopamine is a neuromodulator. It remains to be explained how the NMDA receptor, which is also strongly implicated in schizophrenia, enters the picture. <03-07-2021: It could simply be the source of excitation of the ventral tegmental area.>

Photo by Ameer Basheer on Unsplash

#60. Gender is Pecking Order [evolutionary psychology]

EP

Red, theory; black, fact.

Gender is pecking order

Gender, social status, and testosterone are clearly interrelated, but exactly how requires clarification when the very nature of gender is in question, as now. One possibility is that the male pecking order sits directly atop the female pecking order, and there is no barrier between. Thus, a male who falls low enough in the male pecking order will undergo a reversal in gender identification from male to female (and maybe keep on going down) and a female who rises high enough in the female pecking order will likewise undergo a reversal in gender identification from female to male (and maybe keep on going up). The entire structure could be called "the" pecking order, with the statistical median of the status ranks, and possibly the ranked testosterone levels, always dividing females from males, at least in terms of gendered social signaling. This could be an example of what is called an exact theory replacing its approximate counterpart. In this case, the corresponding approximate theory would be the gender binary. ("You are either a man or a woman.") 

05-28-2024: A limitation of this “median theory” is that no causative mechanism is provided.

Recent history of trans

Since the early sixties, we have seen a trend of increasing media exposure of trans and non-binary individuals, and this was also a period of ever-increasing human population numbers. I conjecture that the latter trend caused the former. The population trend may have produced an upward trend in the average population density at which people are living, suburban expansion notwithstanding. This may have caused an increasing incidence of aggressive one-on-one interactions among humans due to the Calhoun effect, which is much discussed in these pages. (See post #37.) Aggressive, one-on-one interactions are well known to change the social status of the combatants, the winner enjoying increased status (i.e., a higher ranking in the pecking order) and the loser suffering reduced status. Overall, population density increases can thus be expected to increase the amount of traffic on the social ladder, both upward and downward, leading to increasing numbers of individuals crossing the median and becoming trans or nonbinary. The increasing numbers of trans and nonbinary individuals in society was then faithfully reflected in the content of the news stories of the day. QED.

Trans not genetically determined

Consistent with this, PLOS blogger R. Lewis, who has a PhD in genetics, found remarkably little evidence of a direct genetic causation in transgenderism. Moreover, out of 58 studies on "transgender" listed on clinicaltrials.gov, nothing worth mentioning was found about genetics. This could be an instance of the filing-drawer effect (negative results not published but left to languish in the filing cabinet).

Tangent: how pecking-order dynamics may lead to dispersal

02-29-2020: I am indebted to Jordan Peterson for turning me on to the pecking-order idea. It can explain aspects of dispersalism, as follows: If people have no emotional memory of their social wins and losses, we would expect their distribution on the social ladder to be Gaussian (aka, a bell curve). However, if a win or loss leaves you with an emotional residue of optimism or pessimism (and, of course, it does), a positive feedback can set in if conflicts are coming faster than the emotional fallout from each can dissipate, so that the more you lose, the greater your pessimism, and the more likely you are to lose in the future. Moreover, the more you win, the greater your optimism, and the more likely you are to win in the future. <08-29-2020: Following Peterson, this emotional fallout effect may be due to prolonged up- and down-regulations of serotonin concentrations in the brain. See post 66 for my opinions on neuromodulators, e.g., serotonin.> This dynamic then splits the population into a bi-modal social distribution of oppressors and oppressed, and the latter soon join some refugee stream, resulting in dispersal. The frequency of conflicts could be measuring population density, and the conflicts would not necessarily be over resources, but over proxies for these such as land or jobs. With the addition of these ideas, the splitting and separation of overcrowded rodent populations in the behavioral-sink phase of a Calhoun experiment is explained. To connect these ideas with my earlier idea of the sadness cycle, I conjecture that sadness and its attendant social signaling expresses anger colored by pessimism about winning, whereas contempt and its social signaling expresses anger colored by optimism about winning.

05-28-2024: It seems that the attack on reproduction is the field mark of the oppressor. This gets back to the beef the ancient Egyptians had with the Hebrews. It’s always, “These [fill in the blank] breed like flies.” and if you want a group to leave*, preventing them from reproducing would be very effective, as this is the most noxious intervention imaginable. In class-based oppression, the attack would often be structurally entrenched, and nobody sees the structure because they are too close to it. In this paragraph, I am conflating class-based and ethnicity-based oppression, which may or may not warrant future amendments.

A false-flag strategy?

20-08-2020: Another idea about trans is that it is a false-flag strategy used by low-status males and females to reproduce without punishment. Pair a gay woman with a trans woman and you have a potentially fertile couple able to fool the oppressors until the deed is done. Likewise a gay man and a trans man.

<06-13-2024: That said, trans is not fundamentally political, but hedonistic. That said, “the heart [unconditioned stimuli] has its reasons that reason knoweth not.” The reason is natural selection, but we still say that trans is not genetically determined because what is selected is only the potential for it, which everyone has. Triggers from the environment  are still required for expression of this adaptation, which I think of as a long-lasting state, so the idea of an unconditioned stimulus admits some nuance: the state-gated unconditioned stimulus. An example of a trigger from the environment would be your dad losing his temper in front of you to the point where you think you are about to die. The frustration behind this would be due to his experience of oppression. The outburst therefore amounts to an involuntary report to the child on conditions prevailing outside the family home.>

07-14-2024: I suppose you are thinking, “This false-flag strategy is unnecessary because, for example, no foreman would whack a couple of  workers over the head with a pipewrench if he found them kissing in the lunch room, and they appeared to be a binary couple!” Yes, he would, if he were in evolutionary throwback mode, a terribly real mode people shift into whenever the price of bread rises relative to wages, in which behaviour follows the non-human laws of Homo erectus.

*Means: have been selected in evolution to act as if you wanted them to leave.

Photo by Jonny Gios on Unsplash

# 59. Disaster Biology [evolution, evolutionary psychology]

EV     EP     

Red, theory; black, fact.

• The habitat is a unit of selection, leading to group selection.
• Much of evolution proceeds by an accumulation of founder effects, especially altruism in sexually reproducing species.
• Opportunities for colonization of recently-emptied habitats are ephemeral.
• Under disaster-prone conditions, this leads to selection pressure for migrant production and evolvability (i.e., a high rate of evolution, especially founder-effect evolution).
• Language diversification in humans is an evolvability adaptation.
• It works by preserving genetic founder effects from dilution by late-coming migrants, whose reproduction is held back by the difficulties of learning a new language. 
• Xenophobia and persistent ethnicity markers (PEMs) can be explained in the same way.
• The spread of linguistic and  PEM novelties in a population is predicted to be especially fast in newly colonized, previously empty habitats. <09-17-2020: Alternatively, the linguistic novelties may start as a thick patois developed by an oppressed group in the home habitat prior to becoming refugees, as a way to make plans under the noses of the oppressing group.>
•  Refugee-producing adaptations sub serving dispersal can be called "tough altruism."
• Populations producing more refugees are more likely to colonize further empty habitats, a selective advantage.
• Disaster biology may be what is conceptually missing from theories of the origin of life (abiogenesis). 01-02-2020: i.e., the forerunners of the first cells may have been spores.>
• Photo by Purnomo Capunk on Unsplash

#58. The Rising Tide of Refugees [evolutionary psychology]

EP

Red, theory; black, fact.

Paradigm: dispersal

Population pressure and dispersal

Currently, we are seeing a troubling increase in refugee numbers globally. I link this to ever-rising human population numbers, which will be loosely correlated with rising population densities. (Loosely, because population density also depends on area.) Population density, in turn, will be the governing psychological factor, because it can be appraised on the basis of local sensory signals (probably multimodal) whereas absolute global numbers cannot. The basis of this hypothesis is the results of Calhoun's rodent experiments on overpopulation that he carried out in the fifties and sixties, which I am here extrapolating to humans, probably as Calhoun himself intended. I postulate that refugeehood sub serves in humans the ecological function of dispersal. The underlying mechanism would be what was called "instinct" back in the day, a term that I think may still be useful in getting into one's argument quickly.

Do we have an instinct to disperse?

"Instinct-" governed behaviors are understood to owe nothing to learning and to be solely determined by the genes, and thus by evolution. In humans, of course, this position lacks credibility, so I am here speaking of that portion of the causation of our behavior that is due to evolution and can be assumed to play a biasing role rather than a determining one.

In refugee stories, there always seems to be a dichotomy between the nasty, evil bad buys and the hapless, innocent displaced persons, but, of course, this is naive. The most likely situation is that the refugee-producing adaptation has an aggressor subroutine and a victim subroutine, both in the same genetically determined program, and we all have a copy of both hard wired into our brains. Essentially by chance, one is activated in some people, and the other in others, when population density rises, and the ancient drama begins anew.

Now here's my plan

Because therapy can be expected to be more easily delivered to the victims than to the aggressors, I suggest that we start with them in seeking solutions. Their part of the dispersal program is likely to make them overly reactive to harassment and overly apt to conclude that they have no option but to flee, when this is simply not true. A related phenomenon that I have observed could be called "defensive overreaction," in which the person jumps to the false conclusion that an elaborate, expensive solution to their problem is required. A reasonable person, however, will try all the simple solutions first, one by one, evaluate the effectiveness of each, and proceed to the next more complex solution only if the less complex solution fails. I suggest that persons considering flight should be counseled and supported in this strategy, in the hopes of stemming the global tide of refugees.

Photo by Saad Chaudhry on Unsplash