#77. How the Cerebellum May Adjust the Gains of Reflexes [Neuroscience]

 

NE

Red, theory; black, fact

The cerebellum is a part of the brain involved in ensuring accuracy in the rate, range, and force of movements and is well known for its regular matrix-like structure and the many theories it has spawned.

Background about the cerebellum

The sensory inputs to the cerebellum are the mossy fibers, which drive the granule cells of the cerebellar cortex, whose axons are the parallel fibers. The spatial arrangement of the parallel fibers suggests a bundle of raw spaghetti or the bristles of a paint brush. These synapse on Purkinje cells at synapses that are probably plastic and thus capable of storing information. The Purkinje cells are the output cells of the cerebellar cortex. Thus, the synaptic inputs to these cells are a kind of watershed at which stimulus data becomes response data. The granule-cell axons are T-shaped: one arm of the T goes medial (toward the midplane of the body) and the other arm goes lateral (the opposite). Both arms are called parallel fibers. Parallel fibers are noteworthy for not being myelinated; the progress of nerve impulses through them is steady and not by jumps. The parallel fibers thus resemble a tapped delay line, and Desmond and Moore seem to have [paywall] proposed this in 1988.

The space-time graph of one granule-cell impulse entering the parallel-fiber array is thus V-shaped, and the omnibus graph is a lattice, or trellis, of intersecting Vs.

The cerebellar cortex is also innervated by climbing fibers, which are the axons of neurons in the inferior olive of the brainstem. These carry motion error signals and play a teacher role, teaching the Purkinje cells to avoid the error in future. Many error signals over time install specifications for physical performances in the cerebellar cortex. The inferior olivary neurons are all electrically connected by gap junctions, which allows rhythmic waves of excitation to roll through the entire structure. The climbing fibers only fire on the crests of these waves. Thus, the spacetime view of the cortical activity features climbing fiber impulses that cluster into diagonal bands. I am not sure what this adds up to, but what would be cute?

A space-time theory

Cute would be to have the climbing fiber diagonals parallel to half of the parallel-fiber diagonals and partly coinciding with the half with the same slope. Two distinct motor programs could therefore be stored in the same cortex depending on the direction of travel of the olivary waves. This makes sense, because each action you make has to be undone later, but not necessarily at the same speed or force. The same region of cortex might therefore store an action and it’s recovery.

The delay-line theory, revisited

As the parallel-fiber impulses roll along, they pass various Purkinje cells in order. If the response of a given Purkinje cell to the parallel-fiber action potential is either to fire or not fire one action potential, then the timing of delivery of inhibition to the deep cerebellar neurons could be controlled very precisely by the delay-line effect. (The Purkinje cells are inhibitory.) The output of the cerebellum comes from relatively small structures called the deep cerebellar nuclei, and there is a great convergence of Purkinje-cell axons on them, which are individually connected by powerful multiple synapses. If the inhibition serves to curtail a burst of action potentials triggered by a mossy-fiber collateral, then the number of action potentials in the burst could be accurately controlled. Therefore, the gain of a single-impulse reflex loop passing through the deep cerebellar nucleus could be accurately controlled. Accuracy in gains would plausibly be observed as accuracy in the rate, range, and force of movements, thus explaining how the cerebellum contributes to the control of movement. (Accuracy in the ranges of ballistic motions may depend on the accuracy of a ratio of gains in the reflexes ending in agonist vs. antagonist muscles.)

Control of the learning process

If a Purkinje cell fires too soon, the burst in the deep cerebellar nucleus neuron will be curtailed too soon, and the gain of the reflex loop will therefore be too low. The firing of the Purkinje cell will also disinhibit a spot in the inferior olive due to inhibitory feedback from the deep nucleus to the olive. I conjecture that if a movement error is subsequently detected somewhere in the brain, this results in a burst of synaptic release of some monoamine modulator into the inferior olive, which potentiates the firing of any recently-disinhibited olivary cell. On the next repetition of the faulty reflex, that olivary cell reliably fires, causing long-term depression of concurrently active parallel fiber synapses. Thus, the erroneous Purkinje cell firing is not repeated. However, if the firing of some other Purkinje cell hits the sweet spot, this success is detected somewhere in the brain and relayed via monoamine inputs to the cerebellar cortex where the signal potentiates the recently-active parallel-fiber synapse responsible, making the postsynaptic Purkinje cell more likely to fire in the same context in future. Purkinje cell firings that are too late are of lesser concern, because their effect on the deep nucleus neuron is censored by prior inhibition. Such post-optimum firings occurring early in learning will be mistaken for the optimum and thus consolidated, but these consolidations can be allowed to accumulate randomly until the optimum is hit.

Photo by Robina Weermeijer on Unsplash

#70. How Noncoding RNA May Work [chemistry]

 CH

Red, theory; black, fact.

Back, DNA; red, long noncoding RNA; green, transcription complex. I am assuming that transcription initiation involves a DNA-RNA triplex, but this is not essential to the theory. Imagine that a loop closes through an RNA running from bottom to top.

No junk DNA?

The junk-DNA concept is quite dead, killed by the finding that the noncoding sections (sections that do not specify functional proteins) have base-pair sequences that are highly conserved in evolution and are therefore doing something useful.

What does long non-coding RNA do?

This DNA is useful because the RNA transcripts made from it are useful, serving as controllers of the transcription process itself and thus, indirectly, of protein expression. (Changes in protein expression may be considered the immediate precursor of a cell's response to its environment, analogous to muscle contractions in an intact human.) Small noncoding RNAs seem to be repressors of transcription and long noncoding RNAs (lncRNA) may either repress or promote. (lncRNA molecules also control chromatin remodeling, but this may be an aspect of stem-cell differentiation during development.) Despite the accumulation of much biochemical information, summaries of what lncRNA seems to do for the cell have been vague, unfocussed, and unsatisfactory (to me).

Control of gene expression: background

The classical scheme of protein expression, due to Jacob and Monod, was discovered in bacteria, in which a signal molecule from the environment (lactose in the original discovery) acts by binding to a protein to change its conformation (folding pattern). The changed protein loses the ability to bind to DNA upstream from the sequence that specifies the lactase enzyme, where it normally acts to block transcription. The changed protein then desorbs from DNA, which triggers transcription of lactase messenger RNA, which is then translated into lactase enzyme, which confers on the bacterium the ability to digest lactose. Thus, the bacterium adapts to the availability of this food source.

Since I have a neuroscience degree, I naturally wonder if all this can be modelled in neurobiological terms. Clearly, it's a reflex, comparable to the spinal reflexes in vertebrates. An elementary sensorium goes in, and an elementary response comes out. But vertebrates also have something higher than spinal reflexes: operations by the brain. (Don't worry, I am not about to go off the deep end on you.)

My neuron-inspired theory of long non-coding RNA

I propose a coordinating role for the noncoding RNAs: rather than relying on a bunch of independently acting reflexes, eukaryotic cells can sense many promoter signals at once, as a gestalt, and respond with the expression of many proteins at once, as another gestalt. You do not need an entire brain to model this process, just one neuron. The synaptic inputs to the dendrites of the neuron can model the multiple promoter activations, and the eventual output of a nerve impulse (action potential) can represent the signal to co-express a certain set of proteins, which is hard-wired to that metaphorical neuron by axon collaterals. In real neurons, action potentials are generated by a positive feedback between membrane depolarization and activation of the voltage-gated sodium channel, which causes further depolarization, so around we go. This potential positive feedback can be translated into terms of molecular biology by supposing a cyclic, autocatalytic pattern of lncRNA transcription, in which each lncRNA transcript in the cycle activates the enhancer (which is like a promoter) of the DNA of the next lncRNA in the cycle. The neuron model suggests that the entire cycle has a low level of baseline activity (is "constitutively active" to some extent) but the inhibitory effect of the small noncoding RNAs (analogous to what is called the rheobase current in neurons) suppresses explosive activation. However, when substantially all the promoters in the cycle are activated simultaneously, such explosive transcription does occur. The messenger RNA of the proteins to be co-expressed as the coordinated response is generated as a co-product of lncRNA hyper-transcription, and the various DNA coding regions involved do not have to be on the same chromosome.

#69. Storming South [Evolution]

EV

Red, theory; black, fact.

This is a theory of the final stages of human evolution, when the large brain expansion occurred.

At least, we did.

Homo sapiens: created by ice

H. sapiens appears to have arisen from Homo erectus over the last 0.8 million years due to climate instability in the apparent origin area, namely East Africa. During this time, Europe was getting glaciated every 0.1 million years because of the astrophysical Milankovitch cycle, a rhythm in the amount of eccentricity in the Earth's orbit due to the influence of the planet Jupiter.

However, I am thinking of the poor slobs who had settled in Europe (or Asia, it doesn't matter for this argument) during the interglacial periods (remember that H. erectus was a great disperser) and when the ice began advancing again, were now facing much worse cooling and drying than in Africa, and thus much greater selection pressures. At least during the last continental glaciation, the ice cap only extended to the Baltic Sea at the maximum, but long before the ice arrives, the land is tundra, which can support only a very thin human population. In any given glaciation, the number of souls per hectare the land could support was relentlessly declining in northern Europe/Asia, and eventually the residents had to get out of Dodge City and settle on land further south, almost certainly over the dead bodies of the former owners. This would have selected Europeans or Asians for warlike tendencies and warfaring skills, which explains a lot of human history. 

Our large brains

However, our large brains seem to be great at something else besides concocting Games of Thrones: that is, environment modification. It's a no-brainer that the first thing someone living in the path of a 2-km wall of ice needs is to keep from freezing to death, and this would have been the first really good reason to modify environments. Unlike chipping a stone axe, environment modification involves fabricating something bigger than the fabricator. Even a parka has to be bigger than you or you can't get into it. This plausibly would have required a larger brain to enable a qualitatively new ability: making something you can't see all at once when it is at working distance.

Our rhythmic evolution

After parkas, early northerners might have evolved enough association cortex (maybe on the next glaciation cycle) to build something a little bigger, like a tent or a lean-to. On the next cycle, they might have been able to pull off a decent longhouse made of wattle. On the next, a jolly good castle surrounded by cultivated lands and drainage ditches. These structures would have delayed the moment of decision when you have to go and take on the Pleistocene-era Low-brows to the south. This will buy you time to build up your numbers, and I understand that winning battles is very much a numbers game. Therefore, environment modification skill would have been selected for in tandem with making like army ants.

Where is the fossil evidence for this theory?

Why do we not find fossil evidence of all this in Europe or Asia? <05-19-2022: Actually, we do: the Neanderthals and Denisovans, who have been difficult to account for in terms of previous theories of human origins.> My scenario can be defended against the inconvenient fossil evidence for a human origin in East Africa in general terms, by citing the well known incompleteness of the fossil record and its many biases, but, of course, I want details. Note, however, what else is in East Africa: the Suez, a land bridge to both Europe and Asia via the Arabian tectonic block, which was created by plate tectonics near the end of the Miocene, thus antedating both H. sapiens and H. erectus. Not only can hominins disperse through it to other continents during interglacials, but they can come back in, fiercer and brainier than before, when the ice is advancing again, to then deposit their fossil evidence in the Rift Valley region of East Africa. The Eurasian backflow event of 3000 years ago may be a relatively recent example of this. The Isthmus of Suez is low-lying and thus easily drowned by the sea, but the probability of this was minimal at times of continental glaciation, when sea levels are minimal. I assume that early hominins expanded like a gas into whatever continent they could access. Increasing glaciation/tundrafication of that continent would have recompressed the "gas" southward, causing it to retrace its path, partly back into Africa. 

Pleistocene selection pressures

To reiterate, this process would have been accompanied by great mortality and therefore, potentially, much selection. Moreover, during the period we are considering, temperatures were declining most of the time; the plot of temperature versus time has a saw-tooth pattern, with long declines alternating with short warming events, and it is the declines that would have been the times of natural selection of hominins living at high latitudes.

A limestone block in Canada showing scratches left by stones
embedded in the underside of a continental glacier.
The rock has also been ground nearly flat by the same process. Scary.

Glaciated boulder by night. Have a nice interglacial.

#68. Consciousness is Google Searches Within Your Brain [neuroscience]

NE

Red, theory; black, fact.

The Google search is one of those things that are too good a trick for Nature to miss (TGTNM) and she didn't, and it's called consciousness.

Brain mechanism of consciousness

I conjecture that the human brain launches something like a Google search each time an attentional focus develops. This is not necessarily a literal focus of activity on the cortex; it is almost certainly a sub-network activation. The sub-net activity relays through the prefrontal cortex and then back to sensory cortex, where it activates several more sub-nets; each of these, in turn, activates further sub-nets via the prefrontal relay, and so on, exponentially. At each stage, however, the degree of activation declines, thereby keeping the total cortical activation limited.

Accounting for subjective experience

The first-generation associations are likely to be high in the search rankings, and thus subjectively "close" to the triggering attentional focus and relatively strongly in consciousness, although still in the penumbra that is subjectively "around" the attentional focus. Lower-ranking search results would form a vast crowd of associations only dimly in consciousness, but would give conscious experience its richness. Occasionally, an association far out in the penumbra will be just what you are looking for, and will therefore be promoted to the next attentional focus: you get an idea.

The role of emotions

The evaluation process responsible for this may involve the mediolateral connections of the cortex, which lead back to the limbic system, where emotions are thought to be mediated, at the cingulate gyrus. Some kind of pattern recognition seems unavoidable, whereby a representation of what you desire <06-25-2021: itself a sub-network activation> elaborated by the mediolateral system is matched to retrieved associations. Your target may be only a part of the retrieved association, but will suffice to pull the association into the attentional focus.

This is a great system, because it allows a mammal to converge everything it knows on every task, rather than having to perform as a blinkered if-then machine.

Brain mechanisms and our evolutionary history

01-02-2021: Why should we have this back-and-forthing between the prefrontal cortex and the sensory association cortex? Two possibilities: 1) the backward projections serve a priming function, getting certain if-then rules closer to firing threshold in a context-sensitive manner; 2) This is a uniquely human adaptation for our ecological niche as environment modifiers. In ordinary tool use and manufacturing, dating back to Homo habilis, the built thing is smaller than the builder's body, but in environment modification, the built thing is larger than the builder's body—an important distinction. Thus, the builder can only see one part of it at a time. Viewings must therefore be interleaved with reorientations involving the eyes, neck, trunk, and feet. These reorientations, being motoric in nature, will be represented frontally, and I place these representations in the prefrontal cortex. The mental representation of the macro-built-thing therefore ends up being an interleaved collection of views and reorientations. <07-11-2021: In other words, a simulation.> The reorientations would have to be calibrated by the vestibular system to allow the various views to be assembled into a coherent whole. By this theory, consciousness is associated with environment modification.

05-24-2021: Consistent with this theory, the cortical representation of vestibular sense data is atypical. There is no "primary vestibular area." Rather, islands of vestibular-responsive neurons are scattered over the sensory cortex, distributing across the other senses. This seems analogous to a little annotation for xyz coordinates, etc., automatically inserted in a picture, as seen in computer-generated medical diagnostic images.

#66. Neuromodulators as Peril Specialists [Neuroscience]

NE

Red: theory; black, fact.

“Life is Difficulty”

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 nuclei. 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

#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." 

Stress and madness in culture and history

For an example of this from literature, recall that Shakespeare's King Lear "went mad" when his lofty status disintegrated as a result of his mishandling the succession to the throne. In the film Little Big Man, General Custer becomes delusional on the battlefield during the debacle for which he is famous, immediately before taking an arrow from an equally disturbed Pawnee character. It must be even more humiliating when an animal brings you down, as happened to Captain Ahab, who was not notably on an even keel towards the end of the story. In real life, one suspects a case of stress-induced madness in Adolf Hitler toward the end of WWII.

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.)

Take home 

If you are under stress and noticing a loosening of associations, see a doctor, take a valium or whatever he prescribes, and focus intently on solving that problem; you may not have a lot of time to solve it. Don't go off and paint pictures, as Van Gogh did. We all know what happened to him.

02-15-2020: Is society as a whole becoming "schizophrenic" at this time, by the mechanism of stress-induced reverse annealing? (The stress in question would be coming from overpopulation.) Food for thought.

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

#53. Advanced Human Depopulation Model [Population, Evolutionary Psychology]

Picture 1: A four-stage model of a human depopulation event. C = cycle; growth = growth phase; depop = depopulation

PO     EP     

Red, theory; black, fact

I present in Picture 1 a four-stage model of human depopulation events that is intended to account for more data. The same two emotional programs, the anger cycle and the sadness cycle (see post #41), occur in two "generations," with the second generation having greater violence and using modified signals.

• Stage 1: depopulation by emigration; accomplishes dispersal of the human species; coordinated by an exchange of anger signals;
• Stages 2-4: depopulation by mass murder: accomplishes long-term population density confinement within limits;
• Stage 2: coordinated by an asymmetric exchange of contempt and sadness signals; has similarities with cannibalism;
• Stage 3: total war program; coordinated by an exchange of anger signals with mimicry added;
• Stage 4: loss of civilization; triggered by a repudiation of the social contract by trusted elites with grudges: coordinated by increasing paralysis on the part of victims and increasing cynicism on the part of perpetrators. May be too recent an evolutionary development to have an efficient halting signal.

Nevertheless, the modes of worship of Islam are the best place to look for such a signal (06-02-2019: or other remedy) if it exists. 

In this connection, the Islamic prayer discipline has extraordinary potential to alter brain physiology, based on variations in blood flow to this organ, known to be highly sensitive to same. The variations would come about as a result of the highly regimented posture changes occurring during Islamic prayer. I have coded these postures according to the probable effect on blood pressure measured at the brain, and the result looks like this:

Picture 2. The inferred brain physiology of Islamic prayer. Source of data: YouTube, "Time to pray with Zacky," accessed 05-23-2019.

 Shown are my inferred variations in brain oxygenation during two rakat, or units of prayer. Bowing is coded the same as sitting, namely 1. Prostration is coded as 2 and standing is coded as 0. Some forms of Islam prescribe up to 19 rakat per day. Special procedures (Sujud Sahwi) exist for fixing prayers performed erroneously due to "forgetfulness" but this "forgetfulness" I find suggestive of temporary brain dysfunction due to lack of oxygen from getting up too quickly, possibly at about minute 2, above.

06-02-2019: Unprompted revision for clarity and sensitivity: The above observation is to help establish that Islamic prayer manipulates a variable that matters, always an important issue at the outset of a research project. You don't want to waste taxpayer money blindly researching variable after variable and concluding at great expense merely that none of them was relevant.

#49. The Reentrant-pathway Theory of Mental Illness [Neuroscience]

NE

Red, theory; black, fact.

This theory is a further development of post #45, “The Denervation supersensitivity Theory of Mental Illness.”

The basic idea here is that if a region of cerebral cortex is overgrown relative to a major synaptic partner, not only will it be starved of synaptic input from the partner, but it will also produce excess axons going to that partner that will have difficulty finding enough dendritic territories on which to synapse. Both difficulties can be solved at one stroke, however, if the overgrown area synapses on itself. The logic is similar to the application of valence rules in chemistry.

This mode of repair will produce cyclic signaling pathways (called “reentrant” in Neurospeak) that could support endlessly circulating neural activity. This is therefore an alternative way of getting what I have called “autonomous activity” from disregulated cortical growth, with no need to invoke the phenomenon of denervation supersensitivity. The loop circumnavigation time would have to be long enough to allow for the recovery of any refractory periods that may follow nerve-impulse firing.

The autonomous activity will give rise to hallucinations (called psychotic symptoms) if the re entrant pathway is in sensory cortex, and to manic behavior if in cortex with decidedly motoric functions, which would include planning. Since I have conjectured in these pages that an emotion is a high-level motor command, a re entrant pathway in frontal limbic cortex would produce an apparent emotion disconnected from conscious experience and if in posterior limbic cortex, a hallucinated emotion trigger.

The situation is very similar if a cortical area is normal in size but one of its main synaptic partners is reduced in size by disease. In epileptogenesis, the post-damage remodelling of the local neural networks is known to be associated with new-synapse formation and the sprouting of axon collaterals. The hyperexcitable brain tissue responsible for triggering seizures is known to lie just outside the dead core zone of the damaged region, and can therefore be called “overgrown” relative to the dead zone, which has zero functioning neurons.

All this is compatible with the formation, during the epileptogenesis latent period, of a pair of counter circulating, polysynaptic “ring roads” around the perimeter of the damaged area. This process would be determined by simple rules of valency satisfaction. Both ring roads would be capable of carrying autonomous activity that progresses to a seizure. This might only happen if inhibitory tone is also compromised. Hallucinations and seizures seem to be different grades of the same phenomenon.  Indeed, auditory hallucinations commonly occur in association with temporal-lobe seizures. The temporal lobe is the location of the auditory cortex (Brodmann areas 41 and 42).

Neural net repair leading to seizures.

#47. Body-mod Bob's [evolution, evolutionary psychology]

EV     EP     

Red, theory; black, fact.

In the previous post, "Goddesses of the Glacier," evolution appears to be operating in cooperation with a general capacity for technology. Natural selection operates on the brain pathways underlying our aesthetic preferences concerning our own appearance and that of possible reproduction partners and then a technology is automatically developed to satisfy them.

As a first example, consider the oil and brush technology previously assumed for differentiating women from men by hair smoothness. A further step in this direction is to posit that hair color may have been used to code gender. The first step would have been selection for a blond(e) hair colour in both women and men. Since this is a very light colour, it will show the effect of dyeing maximally. Concurrently with this, the aesthetic preferences of men and women would have been differentiated by selection, resulting in blonde women who experience a mild euphoria from being blonde and blond men who experience a mild dysphoria from the same cause. The men would predictably get busy inventing hair-dyeing technologies to rectify this. The necessary dyes are readily obtained from plant sources such as woad and walnut shells. The result would be an effective blonde-female/nonblond-male gender code.

This style of evolution could be very fast if the brain pathways of aesthetic preferences require few mutations for their modification compared with the number required for the equivalent direct modification of the body. Let us assume this and see where it leads.

Faster evolution is generally favored if humans are typically in competition with other species to be the first to occupy a newly possible ecological niche. Such niches will be created in abundance with every dramatic change in the environment, such as a glaciation and the following deglaciation. Possibly, these specific events just slide the same suite of niches to higher or lower latitudes, but the amount of land area in each is likely to change, leading to under-capacity in some, and thus opportunity. These opportunities will vanish much faster than evolution can follow unless a diversity of phenotypes is already present in the prospective colonizing population, which might happen as a result of genetic drift in multiple, isolated sub-populations.

If technologically assisted evolution has general advantages, then we can expect its importance to grow with increases in the reach of technology. Today, we seem to be at a threshold, with male-to-female and female-to-male gender transitions becoming well known. Demand for this service is probably being driven by disordered neural development during fetal life due to contamination of the fetus by environmental pollutants that have estrogenic properties (e.g., bisphenol A, PCBs, phthalates, etc.). The result is the birth of individuals with disordered and mutually contradictory, gendered aesthetic preferences, which is tragic. However, it is an interesting natural experiment.

With further development of cell biology in the direction of supporting body-modification technology, who knows what bizarre hankerings will see the light of day on demand from some customer? Remember that in evolution, the mutation comes first, and the mutation is random. Predictably, and sadly, most such reckless acts of self-indulgence will be punished by reduced employability and reduced reproductive success, doubtless exacerbated by prejudice on the part of the normal, normative majority.

However, the very occasional success story is also to be expected, involving the creation of fortuitously hyperfunctional individuals, and thus the technologically assisted creation of a new pre-species of human.

If the engineering details learned by the body-modification trade during this process are then translated into germ-line genetic engineering, then a true artificial humanoid species will have been created.

After the Pleistocene, the Plasticine.

Photo by Дмитрий Хрусталев-Григорьев on Unsplash

#45. The Denervation-supersensitivity Theory of Mental Illness [neuroscience, evolution, genetics]

NE     EV     GE     

Red, theory; black, fact.

People get mental illness but animals seemingly do not, or at least not outside of artificial laboratory models such as the unpredictable, mild-stress rodent model of depression. A simple theory to account for this cites the paleontological fact that the human brain has been expanding at breakneck speed over recent evolutionary time and postulates that this expansion is ongoing at the present time, and that mental illness is the price we are paying for all this brain progress.

In other words, the mentally ill carry the unfavorable mutations that have to be selected out during this progress, and the mutation rate in certain categories of mutation affecting human brain development is elevated in modern humans by some sort of "adaptive" hot-spot system. "Adaptive" is in scare quotes here to indicate that the adaptation inheres in changes in the standard deviation of traits, not the average, and is therefore not Lamarkian.

In brain evolution, the growth changes in the various parts very probably have to be coordinated somehow. I conjecture that there is no master program doing this coordination. Rather, I conceive of the human brain as comprising scores of tissue "parcels," each with its own gene to control the final size that parcel reaches in development. (This idea is consistent with the finding of about 400 genes in humans that participate in establishing body size.) All harmonious symmetry, even left-right symmetry, would have to be painstakingly created by brute-force selection, involving the early deaths of millions of asymmetrical individuals. This idea was outlined in post 10.

Assuming that left and right sides must functionally cooperate to produce a fitness improvement, mutations affecting parcel growth must occur in linked, left-right pairs to avoid irreducible-complexity paradoxes. I have previously conjectured in these pages that the crossing-over phenomenon of egg and sperm maturation serves to create these linked pairs of mutations, where the two mutations are identified with the two ends of the DNA segment that translocates. (See "Can Irreducible Complexity Evolve?")

Most of the evolutionary expansion of the human brain appears to be focused on association cortex, which I conjecture implements if-then rules, like those making up the knowledge bases familiar from the field of artificial intelligence. The "if" part of the rule would be evaluated in post-Rolandic cortex, i.e., in temporal and parietal association cortices, and the "then" part of the rule would be created by the pre-Rolandic association cortex, i.e., the prefrontal cortex. The white matter tracts running forward in the brain would connect the "if" part with the "then" part, and the backward running white-matter tracts would carry priming signals to get other rules ready to "fire" if they are commonly used after the rule in question.

Due to such tight coordination, I would expect that the ideal brain will have a fixed ratio of prefrontal cortex to post-Rolandic association cortex. However, the random nature of the growth-gene bi-mutations (perhaps at mutational hot-spots) permitting human brain evolution will routinely violate this ideal ratio, leading to the creation of individuals having either too much prefrontal cortex or too much temporal/parietal cortex. In the former case, you will have prefrontal cortex starved of sensory input. In the latter case, you will have sensory association cortex starved of priming signals feeding back from motoric areas.

Denervation supersensitivity occurs when the normal nerve supply to a muscle is interrupted, resulting in a rapid overexpression of acetylcholine receptors on the muscle. This can be seen as an attempt to compensate for weak nerve transmission with a tremendous re-amplification of the signal by the muscle. Analogous effects have been found in areas of the cerebral cortex deprived of their normal supply of sensory signals, so the effect seems to be quite general.

In cases of genetically-determined frontal-parietal/temporal imbalance, I conjecture that the input-starved side develops something like denervation supersensitivity, making it prone to autonomous, noise-driven nervous activity.

If the growth excess is in sensory association cortex, this autonomous activity will manifest as hallucinations, resulting in a person with schizophrenia. If the growth excess is in the prefrontal cortex, however, the result of the autonomous activity will be mania or a phobia. Depression may originally have been an adaptation to the presence of a man-eating predator in the neighborhood, but in civilized contexts, it can get activated by the unpredictable (to the sufferer) punishments resulting from manic activity. If the mania is sufficiently mild to co-exist with depression, as in type II bipolar disorder, then the overall effect of the depressive component may be like a band-aid on the mania.

The non-overgrown association cortex might even secondarily develop the opposite of denervation supersensitivity as the result of continual bombardment with autonomous activity from the other side of the Rolandic fissure. This could account for the common observation of hypoprefrontality in cases of schizophrenia.

#44. Sunshine in Covey's Gap [evolutionary psychology, neuroscience]

EP     NE     

Red, theory; black, fact.

Who has not felt frustration at the difficulty and seeming impossibility of making a disagreeable emotion go away before we weaken and act it out, to our detriment? Techniques of true emotional control, i.e., making the bad feelings disappear rather than white-knuckle, open-ended resistance to acting them out, are not impossible, just non obvious. You just have to persuade yourself that this bad is good and believe it.

For the modern person, that second part, the believing, is difficult to achieve robustly if one is using religious solutions to the problem, the domain of soteriology (being "saved"), easier with psychoanalytical solutions, and, I am here to say, easiest of all with scientific solutions. "Believing," for me, means being prepared to bet your life on the truth of a proposition.

Steven Covey writes in "The Seven Habits of Highly Effective People" that between stimulus and [emotional] response, humans have, somewhat metaphorically, a "gap" in the causal chain and animals do not. In the gap, you find such things as imagination, self-awareness, conscience, and self will. He correctly lays tremendous emphasis on this point. George Santayana seems to have grasped this truth when he wrote: "Our dignity is not in what we do but in what we understand. The whole world is doing things." [source, Wiki quotes, accessed 11-06-2018]

Neuroscientist Joseph LeDoux has even elucidated what could be the neural pathways that make Covey's gap possible. A direct pathway from the thalamus to the amygdala mediates the basic fear response but an indirect pathway that leads from thalamus to cerebral cortex to amygdala provides a more nuanced, intelligent amendment to the first response. Full cancellation of the direct pathway by the indirect would account for Covey's gap, and in principle, this could be done by a cortical relay through the inhibitory interstitial neurons of the amygdala that terminate on the amygdalar projection cells.

The doctrines of classical religion probably lead to such cancellation of emotions such as hate and fear by activating the same circuits that are used by a parent to reassure a needlessly fearful infant.

Apparently, classical religion is all about getting people to do the right things for the wrong reasons. When the discipline of evolutionary psychology is sufficiently developed, we can look forward to the age when people do the right things for the right reasons.

#42. Corporate Sin [evolutionary psychology]

EP

Red, theory; black, fact.

7-25-2018: A moment's reflection reveals that not all of humanly willed unhappiness is due to two persons interacting, either in a sadness cycle or an anger cycle. Wars of depopulation and wars of dispersal represent these interactions promoted to the level of entire societies. This promotion theory assumes that the same hard-wired wetware is being used for both levels, but with the addition of a few more bits of code to support the social level.

Theologians such as Bishop Baycroft, writing in "The Anglican Way," are well aware of this extra dimension of human misery, referring to it as "corporate sin," and admit that it is a more difficult problem than individual sin. The advice I give in "Signaletics for Salvation" (https://nightbull.blogspot.com) will not help you efficiently if your unhappiness has its roots in corporate sin (for example, if you are caught up in a military draft or are a slave), but it may be better than nothing. But let's see what we can surmise about those extra bits of code.

The basic design seems to be to transform a tiff between two individuals into a tiff between two leaders, then copy the emotions of the leaders into the heads of all the followers on both sides. Thus, a political leader is a kind of emotional conductor. This is why we have leaders.

By this theory, World War II was a tiff between Adolf Hitler and Winston Churchill, both famous for their speeches in which they inspired passions in their followers.

How do you get to be leader? The simplest answer seems to be that you just get famous and you are also someone who doesn't see a way to end his pain without involving the whole world. <07-21-22: As for how I ended my own pain, minding my own business and reaching out to family at times of need seems to have sufficed. I also had a talk with my federal MP at one point.>

An attractive theory about fame, in turn, is that all fame is 90% being-famous-for-being-famous, and 10% (or less) is being famous for something else, call it the predisposing factor. Human inter group interactions have the form we observe because these predisposing factors are not random but are due to natural selection. Furthermore, they are conditional upon prevailing conditions, such as the price of bread relative to wages. Finally, they already exist at the individual level. The process of garnering the absurd 90% of fame is the by-now familiar phenomenon of going viral, and its earlier historical equivalents. 

I imagine that this process is a positive feedback loop in the brain that involves the attentional system and Hebbian plasticity, the latter well known among students of neuroscience for having a built-in positive feedback. We also know that emotions are contagious (See: Hatfield E, Cacioppo JT, Rapson RL. Emotional Contagion. New York: Cambridge University Press, 1994).

The final bit of code we need to produce leaders and thus corporate sin is a tendency of this contagiousness to be potentiated by the famousness of the emoter one is observing. This mechanism of social control is distinctly different from the snowball effect that I likened to a black hole in an earlier post. It will take more thinking to decide which is more accurate.

#41. The Sadness Cycle [evolutionary psychology, neuroscience]

EP     NE     

Red, theory; black, fact.

7-20-2018: This post builds on "Signaletics for Salvation," a post in the companion blog, "Experimentalist's Progress, " at https://nightbull.blogspot.com. The theory part of that post is reprinted below with slight modification for the convenience of the reader.

The anger cycle and the sadness cycle reach their full flower in wars of dispersal and wars of depopulation, respectively. These were discussed in the post "Two Kinds of War" in this blog.

Wars of depopulation serve to prevent Malthusian disasters such as general famine. The sadness cycle is a form of altruism that facilitates this depopulation by making a portion of the population sad and suicidal and the remainder contemptuous and entitled. The contemptuous ones take everything the sad ones have, ultimately their lives, and the sad ones let them.

If the sacrificial lambs were fighting what is essentially a form of cannibalism tooth and nail, the transfer of property would leave the heritors with many injuries, which would defeat the purpose of the whole process, which is to leave the residual population stronger and healthier than before under conditions of restricted food supply. However, always bear in mind that the sad ones and the contemptuous ones are playing two roles within the same adaptation; if you can play one role, you can play the other. However, if you unfortunately carry some unfavorable mutation, you will be predisposed to the sad role. This is another way the adaptation leaves the population more robust than before.

Since no altruism can evolve in the presence of selfishness unless the altruists are only altruistic to other altruists, a signaling cycle is required to lock the altruists together to the exclusion of non-altruists. Thus, sadness induces contempt and contempt induces sadness, and so on in a vicious cycle leading to the complete destruction of the sad ones and the transfer of all their property specifically to the contemptuous ones. This dynamic could be the origin of elder abuse and clinical depression.

Macchiavelli wrote, "He is made contemptible who is held to be changeable, light, effeminate, pusillanimous, irresolute, and from these the Prince must guard himself as from a reef." The traits listed appear to be the symptoms of unacknowledged sadness, and were no doubt quite lethal in Macchiavelli's time. Due to the present skyrocketing of the world population with the concomitant "Calhoun effect" from crowding stress, we are no doubt due for a remacchiavellianization of daily life. For example, should I even be sharing these insights with you instead of keeping them to myself to my own advantage or at least posting them on a commercialized blog? Does my slowness to commercialize indicate suicidally self-giving tendencies that will one day prove fatal?

6-29-2018: The Anger Cycle (reprinted)

Much of human unhappiness comes from destructive, escalating signaling cycles, usually between two persons. Examples: arguments, feuds, schools of thought, gang wars, revolutions. The signals exchanged are initially personal expressions of anger. Importantly, these expressions are multi modal, and therefore highly redundant. (e.g., threatening utterances, tones of voice, facial expressions, gait, crashing and banging things, spying, following, etc.) Your anger comes out of you "through every pore."

These signals are too many and varied for conscious control, which is why most people remain enslaved by their signals and cycles. The anger cycle is presumed to escalate until one of the parties must leave the country. When people are threatened, they seek allies, so all of society eventually gets drawn in and polarized as the escalation proceeds apace, like a black hole. Therefore, it is a group that must eventually leave, not a single individual, which is the basis of the refugee phenomenon. 

In ecological terms, the refugee phenomenon is clearly sub serving the function of dispersal. However, dispersal-producing behavior is fundamentally altruistic in a backhanded way. The benefit to the supposed loser, the group that eventually gets driven out, is that occasionally they find a newly-emptied vacant habitat in which to settle and therefore can reproduce without competition. This is a tremendous benefit in evolutionary terms and may once have been great enough to redeem all the waste and suffering of human-style dispersal. 

However, altruistic behavior cannot evolve in the presence of non-altruists unless a signaling system is established to ensure that altruists are only altruistic to other altruists. That is why I lay so much emphasis on signaling here. The reason why the signals are so multi modal is that the altruism program probably breaks down occasionally because of the short-term advantages of being a non-altruist. This has probably happened many times in the past and the broken algorithm was repaired each time by natural selection with the addition of yet another signal component. 

Multi modality implies the existence of a neuronal OR-element somewhere on the sensory side, and the amygdalae could be these OR-elements. More precisely, the amygdalae could be specialized for providing OR-elements generally to the brain by virtue of a characteristic, unique amygdalar cytoarchitecture.

7-20-2018: The various signal cycles may reinforce each other. The four signal cycles that seem to form the framework of human life seem to have such an interdependence. These are: mother-child bonding, which could potentiate man-woman bonding, which could potentiate the anger cycle (via jealousy), which could potentiate the sadness cycle. These insights come from introspection and my own biographical data.

#40. The 1950 Ramp [population, genetics, evolutionary psychology, engineering, neuroscience]

PO     EN     EP     NE     GE     

Red, theory; black, fact.

6-01-2018; Since about 1950, the world population has been increasing along a remarkably steady ramp function with no slackening in the rate of increase yet apparent, although one cycle of oscillation in the slope occurred during the Sixties. Malthusian reasoning predicts an exponential increase, which this is not. From several lines of evidence, I keep coming back to the idea that humans must have a subconscious population controller in their heads, and yet such a controller would have leveled out the increase by now. Until now, no theory has sufficed to explain the facts.

I here propose that the natural population curve for humans in good times is a saw-tooth waveform, with population ramps alternating with political convulsions that result in a large group being expelled permanently, resulting in the precipitous but limited drop in local population density that ends the saw-tooth cycle. This cycle accomplishes the ecological dispersal function to which I allude many times in these pages. The population must ramp up for a time to sustainably create the numbers needed for the expulsions. The WHO population curve shows only a ramp because it is a worldwide figure and therefore population losses in expelling regions are balanced by population increases in welcoming regions. This also implies that human population has been increasing in a way unrestrained by food or resource availability or any other external constraint since 1950, to now.

Clearly, human population is being controlled by instinctive factors, but not to a constant absolute density, but rather to a constant rate of increase. Population density would go up along the much faster, steeper, and more disastrous exponential curve of Malthus if there were actually no controller.

My formal training in engineering and neuroscience justifies a bit of speculation as to mechanisms at this point. Look first for such a controller in the hypothalamus, already known to control other variables, such as temperature, by feedback principles.

In school, I was taught that nature does not reinvent the wheel, which I understand to mean that once a brain structure evolves to serve a particular computational function, it will be tapped for all future needs for such a calculation. This process may make it grow larger or develop sub-nuclei, but additional, independent nuclei for the same computation will never evolve.

I will continue to assume that the controller is a conventional PID controller, as in previous posts. To make it control rate of increase rather than absolute population density, you put a differentiator in the feedback pathway. Look first in the amygdala for such a differentiator. If you are of the opinion that human population control is urgent, then you must knock out this differentiator and replace it with a simple feed-through connection. Fortunately, one common way for evolution to implement differentiation in mammals is to begin with such a feed-through connection and supplement it with an inhibitory, slow, parallel feed-forward connection. If this is the case here, then you just inhibit the feed-forward pathway pharmacologically as specifically as may be, and the job is done. Subjectively, the effect of such a drug would be to take away people's ability to get used to higher population density in deciding how many children to have. An increased propensity to riot should not occur.

I assumed in the last post that the political convulsions that produce dispersal are triggered by the value on the integrator of the PID controller rising above a threshold. However, in the above design solution, the convulsion would be triggered by the raw, undifferentiated population-density signal rising above some threshold. Look in the amygdala for this signal as well. Consistent with this, bilateral removal of the amygdalae and hippocampi in monkeys is known to have a profound taming effect accompanied by hypersexuality, known as the Kluver-Bucy syndrome.

6-17-2018: To be consistent, I would have to say that the differentiator for the population signal is more likely to be in the hippocampal formation by the argument of nature not reinventing the wheel, because in an earlier post, I interpreted the hippocampus as the site of four successive differentiations that carry out a Fourier transform by mapping sinusiodal waves back onto themselves at a particular best frequency, in the presence of a map of such best frequencies.

However, this setup would require the creation of two neuron-to-neuron connections for its evolution; a first connection to send the amygdalar raw population signal to the hippocampus, and a second to send the differentiated result back for further processing. At best, this would require two simultaneous mutations. Either change by itself would be at best useless and could never be selected. This appears to be another example of irreducible complexity requiring the bi-mutation mechanism described in the previous post. 

The mechanisms usually offered to explain cases of apparent irreducible complexity, such as spandrelling, exaptation, and scaffolding, all appear to lack time efficiency and processiveness. I previously said that in evolution there are no (absolute)  deadlines, but relative deadlines can easily be created by an interaction of processes. In the presence of relative deadlines, such as adaptive footraces to be the first clade to exploit a newly-habitable area or a new niche, time is of the essence and selection for speed and evolvability can be expected. Such selection will create mechanisms such as crossing over that enhance evolvability.