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

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Red, theory; black, fact

Midplane section of human brain annotated with the Brodmann areas, which are related to different functions

People contract 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.

The Evolution of the Human Brain

In other words, the mentally ill may carry the unfavorable mutations that have to be selected out during this progress. The mutation rate in certain categories of mutation affecting human brain development may be elevated in modern humans by some sort of "adaptive" hot-spot system. "Adaptive" is in scare quotes 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. There may not be any master program doing this coordination. Rather, the human brain would comprise scores of tissue "parcels," each with its own gene to control the final size that parcel reaches in development. This 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. 

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. The crossing-over phenomenon in egg and sperm maturation may create these linked pairs of mutations, where the two mutations are identified with the two ends of the DNA segment that translocates. Since the two linked mutations are individually random, linkage per se does not eliminate asymmetry. That must be done by natural selection, as previously stated, so there is a subtlety here. Natural selection could equally well create adaptive asymmetry. The human heart and the claws of the fiddler crab are examples.

Functional Human Brain Anatomy 

Most of the evolutionary expansion of the human brain appears to be focused on association cortex, which would implement 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.

Possible Disorders of Brain Growth

Due to such tight coordination, 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, prefrontal cortex will be starved of sensory input. In the latter case, sensory association cortex will be 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 is an adaptation to compensate for weak nerve transmission with a 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 general.

In cases of genetically-determined frontal-parietal/temporal imbalance, the input-starved side would develop denervation supersensitivity, making it prone to autonomous, noise-driven nervous activity.

Differential Growth-Related Brain Disorders 

If the growth excess is in sensory association cortex, this autonomous activity will manifest as hallucinations, resulting in schizophrenia. If the growth excess is in the prefrontal cortex, however, the result of the autonomous activity will be mania or a phobia.

The non-overgrown association cortex might 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.

Picture credit: Wiki Commons

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

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Red, theory; black, fact

A schematic of a simple rate-of-increase controller mechanism

Historical 

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. Several lines of evidence point to the idea that humans 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.

Human Population is Being Controlled for Endless Trouble

The natural population curve for humans in good times may be 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. 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; not to a constant absolute density, but 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.

Neuroscience Aspects

Researchers should look first for such a controller in the hypothalamus, already known to control other variables, such as temperature, by feedback principles.

"Nature does not reinvent the wheel" [quote from my old Professor], 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.

Engineering Aspects 

The population controller may contain a conventional PID controller. To make it control rate of increase rather than absolute population density, you put a differentiator in the feedback pathway. 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. 

Back to Neuroscience 

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  inhibit the feed-forward pathway pharmacologically with sufficient specificity 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.

The political convulsions that produce dispersal would be triggered by the value on the integrator of the PID controller rising above a threshold. The amygdala of the brain may mediate this. Consistent with this, bilateral removal of the amygdala and hippocampus in monkeys is known to have a profound taming effect accompanied by hypersexuality, known as the Kluver-Bucy syndrome.

#38. Can Irreducible Complexity Evolve? [genetics, evolution]

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Red, theory; black, fact

2 x 2

The Key Insight

Sexual reproduction may allow the evolution of irreducible complexity by increasing the intrinsic complexity of the basic building block of change, the mutation.

Irreducible Complexity 

Influential biologist Richard Dawkins wrote in "The God Delusion" that a genuine case of irreducible complexity will never be found in biology. A case of irreducible complexity would be some adaptation that would require an intelligent designer because it could never evolve one mutation at a time, and Dawkins believes there is no such intelligent designer in biology.

In classic natural selection, each mutation must be individually beneficial to its possessor in order for selection to increase its prevalence in the population to the point where the next incremental, one-mutation improvement becomes statistically possible. In this way, all manner of wondrous things are supposed to evolve bit by tiny bit. You have irreducible complexity if an advantageous evolutionary innovation requires two mutations,  but neither confers any advantage in isolation and so cannot be selected up to a sufficiently high frequency that the second mutation is likely to happen in the background of the first.

However, I am seeing irreducible complexity everywhere these days. 

Possible Cases of Irreducible Complexity

For example, your upper-jaw dentition must mesh accurately with that of your lower jaw or you can't eat. Thus, the process of evolutionary foreshortening of the muzzle of the great apes to the flat human face could never have happened, assuming that a single mutation affects only the upper or lower jaw. 

Furthermore, how can any biological signaling system evolve one mutation at a time? At a minimum, you always need both the transmitter adaptation and the receiver adaptation, not to mention further mutations to connect the receiver circuit to something useful.

The evolution of altruism presents a similar problem. The lonely first altruist in the population is always at a disadvantage in competition with the more selfish non-mutants unless it also has a signaling system that lets it recognize fellow altruists (initially, close relatives) and a further mutation that places the altruistic behavior under the control of the receiver part of this system. Thus, altruists would only be altruistic to their own kind, the requirement for altruism to be selected in the presence of selfishness. Finally, the various parts of this system must be indissolubly linked in a way that the non-altruists cannot fake.

A Solution   

Consider the crossing-over events that occur during meiosis as complex mutations: two changes to the genome from a single event, each corresponding to one end of the DNA segment that translocates. In crossing over, two homologous chromosomes pair up along their length and swap a long segment of DNA, a process requiring two double-chain breaks on each end, and their corresponding repairs. A very far-reaching change to the genetic information can occur during crossing-over that is termed unequal crossing-over. This form of the process arises because of inaccuracies, sometimes major, in the initial alignment of the homologous chromosomes prior to crossing-over. When the process is finished, one chromosome has been shortened and the other has been lengthened. This is the major source of gene duplication, which, in turn, is a major source of junk DNA, the part that is classified as broken genes.

A Mechanism for the Evolution of Complexity 

Anatomical features such as jaw length and axon targets may be controlled by variations in gene dose that originate in unequal crossing-over.

In this way, a concerted change affecting multiple distinct sites becomes possible. The two ends of the recombinant segment can in principle be functionally unrelated initially. They become related if both are affected by the same complex mutation and the entire change increases fitness and is thus selected.

A single complex mutation could in principle produce a communication channel at one stroke because of the number of simultaneous changes involved. 

Statistical Issues

The probability of a combination of simultaneous local changes being beneficial to the organism is much smaller on mathematical grounds than is the probability of a given single-nucleotide change being beneficial. However, these unfavourable statistics are at least partly offset by the existence of a dedicated system for producing complex mutations in large numbers, namely meiosis, part of the process of maturation of egg and sperm cells.

The Big Picture 

Complex mutations provide a way for a species to discontinuously jump into new niches as they open up, possibly explaining how a capacity for this kind of mutation could spread and become characteristic of surviving species over time. This idea also provides another explanation for the lack of transitional forms in the fossil record.