In any great organization it is far, far safer to be wrong with the majority than to be right alone. -- John Kenneth Galbraith
If the only tool you have is a hammer, you tend to see every problem as a nail.
-- Abraham Maslow
In the land of the blind, the one-eyed man is king. How autism provides resistance to the delusional thinking of groupthink (aka drinking the Kool-Aid). When your primary competition is with other people, life is a zero sum game. When your primary competition is with reality, there are no limits. The cause(s) of Autism Spectrum Disorders (ASDs) remain unknown. The complex genetic disorder hypothesis posits ASDs are an emergent disorder of multiple genes, perhaps dozens or more. How a common disorder of so many genes could evolve has not been suggested. One hypothesis is that genes associated with ASDs did confer some advantage resulting in their selection in the past, but are now detrimental. I suggest ASDs are not disorders at all, but normal (even human defining) developmental responses, particularly to stress in utero and early childhood. This fundamental human neurodevelopmental paradigm programs the brain and behaviors mediated by that brain so as to optimize survival and reproduction depending on maternal and infant stress; invoking abilities to understand, interact with and manipulate other humans when times are good, and abilities to understand, interact with and manipulate the environment via tool production when times are hard. It is hypothesized that this trade-off between Theory of Mind (ToM) and Theory of Reality (ToR) is the quintessential trade-off along the Autism Spectrum. Implications for interaction difficulties between individuals with ASDs and Neurologically Typical individuals (NTs) are discussed. Prevention and treatment are also discussed.
Background ASDs
The Autism Spectrum Disorders (ASDs) are defined and diagnosed by difficulties in communication, social interaction and by repetitive behaviors. In ASDs, there is a high (but not absolute) concordance between monozygous twins, [1] moderate concordance between dizygous twins, [2], [3] and lesser concordance between siblings. With no generally accepted environmental cause, ASDs are thought to be primarily genetic in origin with associations of perhaps 135 genes.[4] No doubt the complex effects on brain structure and behavior observed in ASDs are not mediated via a single pathway, but calls to abandon a search for a single explanation are premature. [5]
A number of single mutations have been associated with multiple cases of autism-like symptoms. I call these "autism-like" because it is not clear if the cause and sequelae of these autism-like syndromes are identical to or even similar to the common cases of autism and ASDs (which remain unknown). A good example is Rett Syndrome which is known to be caused by a loss in the MeCP2 gene which is on the X chromosome. Females have 2 copies of the X chromosome, one of which is silenced. Active MeCP2 in some cells rescues the organisms from the fatal loss of MeCP2 which afflicts males (who have only one X chromosome). RS females develop seemingly normally until 6-18 months when they develop the characteristic RS phenotype which includes autism-like symptoms, but is also characterized by non-autistic symptoms of small head size, breathing abnormalities, vascular abnormalities, scoliosis, growth retardation and others. Because the effects of MeCP2 deletion are mediated through aberrant transcription of methylated DNA, then aberrant transcription of methylated DNA is sufficient to lead to autism-like symptoms. Perhaps the symptoms of common ASDs are also caused by DNA methylation, or perhaps via a shared final common pathway triggered by aberrant DNA methylation.
Nitric oxide is a pleiotropic signaling molecule used in thousands of metabolic pathways where it regulates, ATP supply, O2 consumption, steroid physiology, transcription, axon targeting, the cell cycle, epigenetic programming and many other aspects of physiology, development and neurodevelopment. Many of the pathways observed to be abnormal in ASDs are mediated through NO signaling.
I suggest that the final common pathway mediating autism and autism-like symptoms is low NO in utero, during neurodevelopment and as an adult. Low NO is the archetypal stress response. Virtually any type of stress ultimately results in low NO which physiology uses to trigger compensatory responses. For example, oxidative stress occurs when superoxide levels are increased. Superoxide consumes NO at near diffusion limited kinetics so a high superoxide state is necessarily a low NO state. NO inhibits cytochrome c oxidase. To release that inhibition and increase O2 consumption to maximize aerobic ATP production, the NO level must be lowered. Psychosocial stress increases oxidative stress through catecholamine oxidation, ATP stress increases oxidative stress through increased mitochondrial potential necessary to increase ATP flux, xenobiotic stress increases superoxide through the cytochrome P450 pathway, immune system stress increases superoxide through the respiratory burst. Just about any type of metabolic stress would decrease NO levels and according to the present hypothesis would tend to produce a more autistic-like phenotype. This may be the mechanism for the association of copy number variations with autism. This may also be the mechanism behind the ASD-like symptoms produced by MeCP2 deletion. Females with MeCP2 deletion are mosaic. Some of their cells do have appropriate methylation readout and some do not. Presumably this differential regulation of DNA expression causes metabolic inefficiencies and metabolic "stress" due to cells being out of "sync". In a mosaic organ with non-synchronous regulation, some cells would be working harder than others, perhaps even working at cross purposes. The final common pathway of essentially every kind of metabolic stress is decreased NO.
Virtually all ASD physical symptoms are consistent with pathways regulated by NO being skewed in a low basal NO direction. I suggest that the ASD phenotype is a stress compensatory pathway mediated by low NO.
NO/ROS Balance Programs adult physiology in utero
The physiology of virtually all adult organs is known to be programmed in utero in response to a number of fetal stressors including nutrition[6] stress and hormonal factors. [7] NO/ROS balance in utero does lead to epigenetic programming of adult blood pressure in rats. [8] Stress is a low NO
state. [9] The most characteristic physical feature of ASD children is a larger brain[10], with smaller and more numerous minicolumns. [11] Low NO is suggested to cause the characteristic minicolumn structure associated with autism[12] and the timing of stressors may be crucial to the development of the autism phenotype. [13] In guinea pigs, brief prenatal stress increases brain/body mass ratio, and changes adult behavior. [14] Prenatal stress increases learning ability in rats. [15] Prenatal stress does program hypothalamo-pituitary-adrenal function. [16] Low NO does cause neuronal hyperplasia. [17] The patterning of many neural structures is determined in part by gradients in NO mediating proliferation, differentiation, or apoptosis. [18] There are increased asymmetries in the brains of ASD individuals[19], suggesting differential regulation of neuronal growth when the sizes of those structures are formed in utero. Stress in utero causes adaptive changes in the adult physiology of multiple organs; it would be beyond surprising if it did not exert adaptive influences on the most important organ, the brain.
I suggest that low NO in utero, brought about by maternal stress leads to the ASD phenotype in affected individuals, and the genotype that leads to the ASD phenotype was adaptive under conditions where humans evolved, in the “wild”, but is perhaps now less adaptive due to environmental change(s). What possible advantages could the ASD phenotype hold?
The Brain is fundamentally the most Human organ
Humans evolved large and complex brains only because such brains conferred survival and reproductive benefits. Human evolution was shaped mostly by events 100k or more years ago. Humans are social animals, as are all primates. Humans are unique in their use of language with syntax and grammar to convey complex ideas. Humans are the only extant hominin that manufactures and uses tools. The first instances of manufactured stone tools date to about 2.5 to 2.7 MYA (million years ago), and was near universal by 2 MYA[20]. Manufactured tools of perishable materials perhaps were earlier. Modern humans are good at tool manufacture and tool use. Tool use has profoundly shaped human evolution and those parts of the human genome that affect brain structures important for tool creation and use. Similarly, communication and language has profoundly shaped human evolution and those parts of the genome that affect brain structures important for language acquisition and use. The major structures of the brain are formed in utero and early childhood, and are then largely fixed throughout adult life. It is only in utero and early childhood that neurons can be epigenetically programmed to form the major structures in the brain with the characteristic neuroanatomy observed in ASDs such as increased asymmetries, larger numbers of neurons[21] and larger brains.
Brain size at birth limited by female pelvis: Brain optimization requires tradeoffsThe size of the newborn brain is limited by the size of the mother's pelvis through which it can be successfully born. In the absence of medical C-section, cephalopelvic disproportion results in significant infant and maternal mortality. What ever advantages a large brain at birth provides it comes to naught if the infant or mother dies. The structure and size of the brain at birth must be an evolved trade-off between the multiple tasks that brain will be called upon to perform at birth and over the life of the individual and the substantial risk during a natural birth. The only time the most fundamental aspects of brain structure can be modified is while those structures are being formed. Much of the formation of those brain structures occurs in utero, much of it in the first trimester following closure of the neural tube (which is when teratogens such as thalidomide can cause autism). Epigenetic programming of cells occurs when those cells are dividing and undergoing differentiation. Much of the differentiation in early human development occurs in the first trimester. Patterns of methylation modify DNA expression and modify the phenotype of that differentiated cell for the lifetime of that cell. Many neurons do not divide over the lifetime of the individual. NO does modify methylation through the folate pathway and so
modifies DNA methylation in ways that are quite complex (for at least this one gene system). Presumably multiple genes are epigenetically modified in complex ways by this same mechanism.
Oxidative stress and low NO cause changes in DNA methylation. Presumably this is part of the normal mechanism by which stress (which results in oxidative stress and low NO) causes global epigenetic reprogramming of diverse genes in diverse tissue compartments under diverse circumstances. Psychological stress causes long lasting changes in neurological functioning as
for example PTSD. The details of how psychological stresses of what types cause the characteristic neurological changes that manifest as PTSD are mostly unknown. We know it happens, so there must be physiology that supports those characteristic changes.
DNA methylation mediated through NO does influence expression of genes that are involved in some autism-like syndromes, such as
Fragile-X mental retardation gene (FMR1). Aberrant readout of DNA methylation is implicated in the autism-like symptoms of Rett Syndrome (RS). Many of the symptoms of RS are characterized by physiology being skewed in the direction of low basal NO.
Fundamental brain optimization tradeoff: Theory of Mind (ToM) for Theory of Reality (ToR)
Humans are unique among animals for their abilities at communication; language making and language using and tools; tool making and tool using. These abilities are highly dependent on a large brain with substantial plasticity for self modification via learning throughout life. The relative importance of these two extremely important human behavioral characteristics is dependant upon the environment the infant is born into. The major neuroanatomy of the brain originates from structures arising during early neuron proliferation and differentiation during and after neurulation in the first trimester. These structures are then elaborated on later in utero. It would be beyond surprising if the relative aptitude of the brain for communication and/or tool making/using (including manual dexterity for manipulating objects) were not to some extent programmed in utero.
That trade-off would show up as a trade-off between abilities to understand and manipulate other humans (Theory of Mind), and abilities to understand and manipulate reality (Theory of Reality). These are the differences that are seen in people along the autism spectrum. I will discuss how a less developed ToM interferes with ASDs communicating with neurologically typical individuals (NTs) and their very well developed ToM. For the most part ASDs don't pick up the nuances of communication, particularly how it relates to motivations, beliefs and other mental states. The NT ToM forces NTs to think in anthropomorphic terms, even when it is inappropriate because they lack a robust ToR.
I spend a lot of time trying to explain this in several different ways using several different analogies. What I am trying to describe is exceedingly complex, as complex as an entire human brain. Something that complex cannot be described simply except in simplistic terms. It would be like trying to describe a library in a single paragraph.
Good times --> Need Good ToM
One hypothesis of this paper is that when times are good, and a woman's first trimester of pregnancy is characterized by low stress, then the "optimum" infant brain will be one optimized for better communication. If times are good, there will be plenty of other humans around, and the infant's primary competition for food and mates will be with other humans. Because times are good, the cultural information the adults have is working well to produce those good times. Copying that good cultural information with high fidelity is important. Good communication, a good ToM with the ability to understand and manipulate other humans is the best strategy when times are good.
Hard times --> Need Good ToR
When times are hard, a woman's first trimester will be characterized by high stress. The optimum infant brain will be skewed away from communication because during evolutionary time, hard times meant fewer humans in the territory. With fewer other humans around the need for communication is reduced. The cultural practices of the adults are not working well to produce good times. If the cultural practices are not working well, they need to be modified until they are working well. When times are hard, there won't be many other humans around because they will die in infancy. Competition will be against reality for food, shelter, and to stay alive. The adults don't know how to make good times, so that is something the infant will have to figure out for him/herself.
Theory of mind, theory of reality and theory of cognition
I will make a distinction between being able to think about something (cognition) and being able to think about that thinking process (meta-cognition) and coin a term Theory of Cognition (ToC), to denote the ability to think about and emulate different types of cognition. The term is an attempt to be analogous to ToM and ToR, which are meta-abilities to think about and compare multiple models of other minds (necessary for communication by emulating other mental states), and multiple models of potential realities. I am making this distinction because the different types of computation that humans do are not necessarily mapable onto each other.
Analogy:
Word processing ToM Theory of Mind Emulating other minds
Spread sheet software ToR Theory of Reality Emulating Reality
Operating system ToC Theory of Cognition Choosing EmulationsTrying to understand human communication with a ToR might be like trying to write a document not with word processing software but with a spread sheet. A document could be written in a spread sheet. It would be slow, cumbersome and the document wouldn't have the right formatting and wouldn't be as polished as something done in a word processor. On the other hand, a large spread sheet calculation simply can not be done using word processing software. The word processing software doesn't support the primitive functions, addition, subtraction, multiplication, etc that a spread sheet calculation requires. Some of the complex word processing functions can be emulated on a spread sheet but spell checking and grammar correction would be very cumbersome and difficult.
This is the sense that I am trying to convey, that people with a robust ToM can do good and robust communication that is nuanced, and well understood by others with a matching and robust ToM. Their shared ToM is analogous to the word processing software, and a well formatted document is analogous to human communication between individuals with a shared ToM. The ToR is analogous to the spread sheet software and the large spread sheet analogous to a highly technical ToR. A theory of cognition (ToC) would be the selection of the proper software type to do the required computations (ToM(English), ToM(French), ToM(ASL), ToR). There are multiple ToMs, each language is different to some extent, although there are other communication modes, body language, cultural signals, gestures. There is only one ToR, the one which accurately describes reality as it actually is. Individuals may have a ToR that is highly specialized and individualistic, physics or medicine for example. But all of the different ToRs all mesh into one (or should) because they all describe a single reality.
In this analogy I am trying to illustrate that a specialized piece of computation machinery may work very well for one task (word processing) and not at all for another (spread sheet calculation). If you tried to input a spread sheet into a word processor, you would get many error codes, many misspelled words; the word processing software would reject it as badly formed. A very well formed spread sheet cannot be read on a word processor. This is analogous the problem that some NTs have with understanding people with ASDs.
Normal background "housekeeping" features can impede communication. Many types of different word-processing software have automatic spell checking. If a word is spelled wrong, the software will change the spelling to match the spelling to one of the words in its dictionary. If the word is not misspelled, but is simply not in the dictionary, the software can't recognize it and will change it anyway. This is a type 1 error, a false positive. The software falsely identifies a character string and modifies it to match its default identity. This is an inherent property of specialized pattern recognition systems. There is a trade off of type 1 errors (false positive) for type 2 errors (non detection). If you don't have access to modify the "error correction function", it may be impossible to type certain strings because the error correction keeps changing them. In certain word processing software this can be extremely annoying and make writing outside the scope of the software impossible. If the software won't let you have certain character strings in your document, you can't write about them. If your ToM won't let you have certain ideas, you can't think about them. Appreciating that your ToM doesn't have the capacity to think certain thoughts is extremely difficult.
Being unable to conceptualize ideas is not uncommon. There are people who believe in the literal truth of ancient texts and are unable to conceive that they do not accurately describe reality, irrespective of what data can be collected today. These beliefs are from a ToM, shared with others of their community. Such beliefs did not arise from observations of reality, they were told to individuals by other individuals who believed them. Those false beliefs are derived by those false beliefs being communicated to the individual and so shaping their ToM. Such beliefs are often extremely resistant to change.
Learning can be looked at as modification of the brain's neural network so the neuroanatomy can support what ever new idea it is that is being learned. Usually this takes a long time and is quite difficult. Learning physics or mathematics is difficult because the normally developing neural patterning doesn't support that type of thinking the way it supports language. I will discuss this more later.
A mother's necessity makes her child an inventor.
Maternal stress --> fetal development along autism spectrum --> Asperger phenotypeThe hypothesis of this paper is that low NO in utero causes development along the autism spectrum so as to program the brain in utero to one that supports a better ToR. Precisely the phenotype that is needed when mothers are stressed and so times are hard. What ever technology and cultural practices are being used, they are not working well enough and so new ones need to be developed.
Which individuals are most adept at tool use today? It is people with Asperger’s, people with ASDs. Many scientists and engineers have Asperger’s, and it is suggested that Einstein, Newton, and many brilliant scientists had Asperger’s.
[22] Asperger even said “It seems that for success in science or art a dash of autism is essential.” [23] The stereotypical nerd is someone with facility at math, science and with characteristically poor social skills[24]. The mirror neuron system[25] (responsible for understanding the actions of other individuals) exhibits dysfunction proportional to ASD severity. [26]
The major barrier to revolutionary scientific innovation is conventional thinking and existing paradigms. [27] What Kuhn calls “normal science”. Ideas transmitted culturally are difficult to displace even when wrong. It is nearly 150 years since Darwin’s “Origin of Species”, with overwhelming data supporting and no datum inconsistent with evolution, yet in the USA, 40% of the population believes evolution is false. [28] Some on the Nobel Committee were unable to accept relativity as valid and so Einstein received the Nobel Prize for the photoelectric effect, not relativity. [29]
Cultural notions of what is appropriate affect abilities (i.e. what people think they or anyone can do). Women exposed to a hypothesis wrongly attributing mathematical ability to genes on the Y chromosome have impaired mathematics performance. [30] A degree of social isolation from disrupted mirror neurons may insulate ASD individuals from incorrect paradigms of science, technology and the peer pressure associated with cultural practices which must be abandoned to overcome hard times. No doubt 2.8 MYA everyone “knew” stones didn’t make good tools. The first stone tools were not developed after committees of peers reviewed proposals and selected the highest scoring for implementation; they were developed by the “Einsteins” of the time working alone. Acquisition of nut cracking skill by capuchin monkeys (Cebus apella) using stones as hammer and anvil takes about 2 years and requires considerable repetitive nonproductive effort while watching proficient individuals. [31] No doubt repetitive trial and error was needed to acquire de novo skill(s) to manufacture stone tools 2 MYA, and such individuals had to ignore criticism that they were bizarre for “uselessly” banging stones together.
These culture notions are transmitted through the robust NT ToM. To avoid being adversely influenced by potentially incorrect ToMs, ASDs require a weaker ToM, a ToM that perhaps allows some communication, but one that can easily be ignored, resulting in the ability to ignore the
"Kool-Aid" which is a stronger version of
groupthink. The delusional world views that some NTs have can become extremely compelling to them,, such that they are unable to perceive that it is delusional, particularly when a charismatic leader with a strong ToM (essentially the definition of a charismatic leader) imposes it on his/her followers. More on this later in the discussion of cargo cult science.
ASD individuals developing skills unrecognized as useful by NTs must possess a compulsion to acquire those skills despite peer pressure that such skills are useless. Many ASDs acquire skills that NTs think are useless, fascination with train spotting, bird watching, collecting, virtually every savant ability is acquired to a degree that NTs do not find useful (if they did, then NTs would acquire such skills to that degree and it would not be thought of as savant). Language and communication is the "savant" skill of NTs. NTs possess a skill at communication (with other NTs) that ASDs cannot hope to master. Just as ASDs sometimes have skills that NTs cannot hope to master. Just as elite athletes have skills that non-athletes cannot hope to master. A society with the ability to use the best skills of a highly variable and diverse group would be better able to cope with adversity than a society where all individuals had the same average abilities. Not every individual in the village needs to be proficient at making stone tools, provided there are enough proficient individuals and the tools their skills produce can be traded for other things.
Cognition: Non-algorithmic calculationCognition in human brains is done by neural networks, the fundamental details of which are mostly unknown. Some cognitive abilities (such as savant calendar)
are known to be non-algorithmic because the errors are not always the same, and the time for performing the calculation is not asymmetric depending on calculation direction the way a computation performed using an algorithm would be. [32] It is likely that most if not all other types of human cognition are non-algorithmic.
I am using algorithm in the sense that an algorithm is what a Turing machine executes. An algorithm is a series of instructions that when acted upon manipulate data and perform a calculation. The computers that people are familiar with are algorithmic. Calculators use a calculating engine (the processor) to operate an algorithm (the software) to manipulate the data. In general the data does not modify the software or the processor while the computation is in process, and given the same data, the same processor running the same software will produce the same output each and every time the calculation is performed.
Neural networks are inherently non-algorithmic in the sense that there is no "algorithm" explicitly being implemented by the neural network. A neural network may be used to implement an algorithm. For example, humans and other animals have the ability to do approximate mathematical operations such as comparison. Two groups of objects can be compared and the one with the larger number can be selected even when the members of each group have not been counted. This selection can be made by individuals unable to count and even by animals. This selection is non-algorithmic. An individual able to count is also able to count the members of each group and then tell which group is larger by comparing the two values. The person, who can count, knows that the counting algorithm produces a more reliable comparison than the non-algorithmic visual comparison. The person who cannot count does not know how to implement the counting algorithm.
Human brains are not optimally configured to run algorithms. A processor that can run algorithms is in essence emulated in a human brain to run the algorithm under consideration, such as counting or multiplication. The form that the data is in may greatly limit what algorithms that data can be manipulated with. For example multiplication using Arabic numerals is easy. Multiplication using Roman numerals is exceedingly difficult. There is essentially no algorithm for multiplying Roman numerals, individuals use a look-up table. Learning algorithms takes considerable time and effort for many individuals.
Communication requires a Theory of Mind
Exactly how neural networks in the brain configure and reconfigure themselves to do the computations that certain cognitive tasks require is unknown. Presumably there is some type of feedback that modifies the network when sub-optimal results are achieved so as to configure the network to produce better results. How this occurs is unknown, but for language acquisition, some conclusions as to how this optimization works can be made which I discuss below. What I want to emphasize the compulsive aspects of language acquisition. People do not choose to acquire the language they acquire as children, their brains acquire it (or synthesize it de novo) for them.
All communication requires two parties, a sender and a receiver. The sender must have a mental concept, translate that mental concept into a communication medium, transmit that message to the receiver, who must receive and then translate that message back into a mental concept. In that sense, all communication is only the transmission of representations of internal mental states. For there to be communication, the mental concept must necessarily be mapable onto the neural structures of both individuals. If one party is not able to represent the mental concept in their brain, the concept cannot be communicated either from them or to them. In a sense, communication is the transmission of data that allows the receiver to identify and map that concept into a mental representation, in effect the receiver is doing pattern recognition on the data stream and generating a mental representation, in effect a pattern of thought either generated de novo, or a familiar pattern previously used.
In this sense, communication can only occur between individuals with a shared Theory of Mind. This is the sense that I am using ToM in this paper, the emulation of the cognition of another individual to achieve a mapping of the mental state of one individual with the mental state of another individual. The possible fidelity of that mapping determines the possible fidelity of that communication. If a mental state cannot be mapped onto another individual's ToM, then that mental state cannot be communicated to that individual.
Pattern recognition is a well recognized ability. All systems encoding pattern recognition are subject to different forms of error. There is the type 1 error, the false positive, the error in wrongly identifying a false instance as positive. There is also the type 2 error, the false negative, the error in missing the correct identification of a correct instance. In a general sense any pattern recognition system can be made more sensitive, that is with a reduced type 2 error, but then there is an increased type 1 error and there are more false positives.
A type 1 error is getting the attempted message wrong; a type 2 error is missing the attempted message. Since communication is a two-party interaction, the "fault" of miscommunication cannot be attributed to either party, the "fault" lies in their interaction.
Many human interactions engender other types of error. There is no generally accepted definition of what is a Type 3 error, but one definition is "the error committed by giving the right answer to the wrong problem". When times are hard, and the culturally transmitted traditional information isn't capable of solving the hard times, that is an example of the right answer to the wrong problem. The time of adolescence and early adulthood is often a time of rebellion against authority, against conventional wisdom, against cultural norms. Young people are testing the limits of their culturally acquired information; testing to see what works and what doesn't. This is somewhat speculative but this might be a mechanism to reduce the cultural transmission of obsolete or dysfunctional practices. In the absence of a written language, the only cultural practices that can be transmitted are those adopted by the next generation. If the older members of the tribe live long enough to transfer their wisdom to adults past their adolescent rebellion period, perhaps the wisdom is worth transferring. If not, then perhaps it isn't and the tribe should try new approaches until that happens.
Communication and language acquisitionSocial animals communicate with each other. In humans the ability to develop language is innate and the brain structures to support language and language development must be coded for genetically. Language itself must be learned or is synthesized de novo during certain periods of brain development. This point is quite important. When humans are growing up in a culture, they adopt the language of the culture, provided that the language is "well formed". If the language the adults are using is not "well formed", the children synthesize a new language that is "well formed". That is, when the children of immigrant parents grow up, they do not adopt the pigeon language their parents are speaking, they either adopt the "well formed" dominant language, or synthesize a "well formed" Creole. The various sign languages did not become "well formed" until children grew up with signing as their first language, which they modified into a "well formed" language.
The acquisition of language in this way tells us several things; that the ability to acquire language is innate, that there is a more "primitive" cognitive structure underlying language (by that I mean that the structure of "thought" has a component that is simpler than the linguistic components humans communicate with). Without a simpler and more primitive cognitive structure, the Creole could not be analyzed as it is being formed to ensure the resulting Creole has a "well formed" grammar. However, the ability to form a Creole is lost at a certain age. The immigrant parents of the Creole synthesizing children continue to speak their pigeon language. This implies that the cognitive structure that analyzes language as it is being learned and forces it to be "well formed", i.e. to conform to standard human linguistic patterns is lost (to some extent) with age. It also implies a compulsion to learn the "standard" language and a compulsion to force others to comply with the "standard".
The development of a de novo language, such as a Creole, is a collective outcome produced by a population. It is not produced by a single individual. Another way of describing it is that the population developing the language acquires a shared neural mapping of the medium of the language (sounds, gestures, etc) to neural structures producing the mental states that are the ultimate outcome of communication (that is the ideas being communicated). In this context, there is no arbitrarily correct mapping. The mapping is correct so long as it is the mapping shared by the group. In the sense of the Galbraith quote at the start what ever the majority adopts as the linguistic mapping is the correct mapping. This is a very important point. What ever the majority adopts as correct is correct; everything else is wrong.
For a single majority linguistic mapping to arise spontaneously there must be very powerful mechanism(s) to eliminate deviation from the mapping acquired by the majority. The majority acquire a shared Theory of Mind with respect to linguistic mapping. In other words, the differences between the shared Theory of Mind and that of any individuals in the population are reduced. The deviation is not reduced by changes to the shared theory of mind; the deviation is reduced by individuals adopting the shared ToM as their own. This is an important point. There is no "shared" ToM. There are only individual ToMs which correspond to the shared ToM more or less. The shared TOM can only be shared to the extent that all individuals have the same components and the same structural relationships between those components. The shared ToM reflects the "lowest common denominator"; the ToM that overlaps with everyone else's ToM is all that can be shared. I think this relates to the importance of "peer pressure" in the age group capable of forming a Creole language. If peer pressure were not so compelling, a single coherent language would be difficult to achieve.
The rigidity of an inflexible ToM maintains stability of communication, of information transmitted culturally to the next generation. If your ToM doesn't support an idea, you cannot transmit it, receive it, understand it, or even think it. When times are easy, transmitting the cultural information that led to those easy times is important. It is important to do so with high fidelity because it worked. When times are hard, the culturally transmitted information isn't working, and so needs to be abandoned or modified. The fidelity of transmission must be reduced so what ever is wrong and/or isn't working can be eliminated.
The ToM of NTs that allows them to communicate so easily with each other limits what they can communicate to ideas that are within the shared ToM. This is an extremely important point, but it is a point that NTs have an extremely difficult time understanding because they can only think using ideas that are within their shared ToM. If an individual's ToM is insufficiently flexible to map an idea, that idea cannot be understood unless the ToM changes. But there is tremendous peer pressure to maintain the shared ToM of the group and to not change it.
This rigidity of the NT ToM is what causes ideas to persist even when those ideas are wrong and the rejection of correct ideas even when well supported by incontrovertible data. Many religious ideas have no supporting evidence and are in fact demonstrably wrong. For example the idea that the Earth is less than 10,000 years old and was created in 6 days as described in Genesis. Similarly the idea of evolution is rejected without a single piece of data inconsistent with it.
Most ToM ideas are transmitted from other individuals, not generated de novo.
Conflicting compulsions for ToM and ToR
A specific ToM is only useful for communication in the context of the group of individuals that share it. The mapping of a data stream (i.e. speech or gestures) into ideas and mental states is arbitrary and the only correct mapping is the one that everyone else in the group shares. There must be a tremendous compulsion to modify one's ToM to conform to that of the group. It is this compulsion that forces the emergence of a single language in a group.
In contrast, a ToR is only useful in so far as it actually corresponds to reality. To eventually develop a robust ToR, the individual must have a compulsion to modify his/her own ToR until it does correspond with reality, irrespective of the ToR of others in the group.
Thus developing and maintaining a good ToR is in conflict with developing a good ToM. A ToM needs to remain static for individuals to be able to communicate with each other. A ToR needs to be dynamic and change when ever it is found to be in error or to be dysfunctional.
I think this is the source of much of the resistance to new ideas in human culture but also in the scientific community. These concepts are laid out by Thomas Kuhn in his book, The Structure of Scientific Revolutions. Most scientists do what Kuhn calls "ordinary science", where they work within the paradigm of their scientific field. It is difficult to work outside the paradigms of a scientific field. Any contradiction of an existing paradigm is considered extraordinary and so requires extraordinary evidence. Some individuals are unable to reject paradigms even when they have been shown to be wrong. In these individuals, their rigid ToM has locked them into a perpetual state of error, and they don't have a sufficiently robust ToC to appreciate that their thinking is faulty and in error. It is mechanisms similar to the mechanisms that enforce a rigid ToM during language acquisition that compel adherence to the faulty ToM in later life, peer pressure, appeal to authority, tradition.
Communication and ASDs
Communication in humans encompasses a number of modalities including speech, sign language, body language, written language, music, artistic expression and perhaps pheromones. Most of these have components that are learned, improve with practice and degrade with disuse demonstrating the involvement of neural structures which retain plasticity (positive and negative) even in adulthood.
Autism is defined by behaviors, behaviors related to social interactions where autistic individuals have what are called characteristic deficits which can be reliably measured. However what constitutes a deficit is a matter of perspective. One example is a "deficit" in the
ability to impute anthropomorphic motivation and emotion to inanimate objects as in the work of Frith. In this research, triangles were animated and made to move in three different ways, randomly, goal directed and moving interactively with implied intentions. The two sets of purposeful motions were designed to evoke anthropomorphic responses, e.g. chasing, fighting and coaxing, tricking. Individuals were scored on how closely they matched the scripts the animators of the triangles were trying to portray.
The ASD individuals scored lower than the NTs did, and this was described as a "mentalizing dysfunction". This was taken as a confirmation that people with ASDs have an impairment in attribution of mental states. However, whose "mental state" did the ASDs have an impairment in recognizing? The "mental state" of the triangles? Was this error a type 1 error (false positive), or type 2 error (false negative)? One might say the ASDs had a type 2 error, failure to recognize the "mental state" of the triangles, but one could (more correctly I think) say that the NTs had a type 1 error of falsely attributing a "mental state" to obviously inanimate triangles.
There is no intrinsically correct representation of the mental state of triangles. Triangles do not have mental states. The only way that a mental state can be attributed to triangles is via anthropomorphic projection of human-type intentions onto inanimate objects. In most circumstances this would be a Type 1 error; falsely observing anthropomorphic attributes in inanimate objects. It could also be thought of as a type 3 error, wrongly using a human based anthropomorphic model where it is inappropriate. This type of projection is not uncommon. Imputation of motivation and intentions to inanimate objects was at one time the basis for the religious belief that demons and spirits inhabit and animate virtually every object.
Inappropriate invocation of anthropomorphic feelings is a large part of the entertainment industry. Many cartoons are stylized after humans and many humans develop grossly and dangerously wrong ToR based on these erroneous ideas. In regions where bears are endemic, campers feeding bears is a serious problem. People assume that the anthropomorphic representations they have seen on TV are representative of how bears will react in real life. There have even been cases where a parent has applied peanut butter to a child's face so a bear cub would lick it off to obtain cute pictures.
This relates to the second quote, "If the only tool you have is a hammer, you tend to see every problem as a nail." If the only cognitive structures you have to think with are the cognitive structures of human emotions and communication, trying to figure out the properties of inanimate objects would consist of trying to ascribe human motivations and intentions to those inanimate objects and trying to figure out what they would do next in human terms.
Savant cognitive abilities
A striking feature of some people on the autism spectrum is that in some instances they have narrow and highly superior cognitive abilities. Human mental abilities have distributions in the population, with "normal" abilities being distributed "normally". Usually people with autism are somewhat lower on intelligence tests such as WISC, but with somewhat higher scores in block design. When intelligence tests without a communication component such as Raven's Progressive Matricies are used,
some autistic individuals score much higher, in some cases as much as 70 percentile points higher (n=7). [33] That is 70 percentile points higher. Such a lack of congruence between tests is sufficient to show they are not measuring the same thing and we shouldn't use the same label to denote what the different tests are measuring even if there is good correlation among NTs. That correlation can only be spurious.
The distribution of intellectual abilities is "normalized", that is differences are measured and then scaled to fit on a distribution. That scale is arbitrary, and does not reflect any sort of absolute scale of difficulty.
As social animals, humans live in societies, larger communities of humans where there can be specialization and division of labor. It is this specialization and division of labor that has allowed humans to collectively master many technologies. Presumably different mental tasks are optimized by different neural structures. Dispersion in mental abilities requires dispersion in neural structures.
Savant abilities are not rare among people on the autism spectrum, and sometimes occur in individuals with profound disruptions in other cognitive abilities. This shows that to some extent, some cognitive abilities are independent of each other. Presumably superior performance in some cognitive tasks and inferior performance in others represents a trade-off of abilities along multiple spectra. The brain is limited in size, its computation capacity is limited, relative cognitive abilities of individuals will depend on the myriad details of the neurodevelopmental path that individual took.
Communication is "savant" ability of NTs
Many ASDs have savant abilities, which demonstrate that what ever part of the brain is providing those cognitive abilities has superior performance to the corresponding part of NT brains with lesser performance. The one area where NTs are universally better than ASDs is in communication. I suggest that communication is the savant ability of NTs, and that NTs have traded reduced abilities on ToR and ToC for enhanced ability in ToM.
The difficulty in relations between ASDs and NTs is that NTs don't appreciate that the ToM they are using for communication is a savant ability that ASDs don't share, and shouldn't be expected to be able to emulate. An ASD can't emulate the NT savant ability to communicate any more than an NT can emulate an ASD savant ability at mathematics. If you don't have the brain structures that can do the computations, you can't emulate the behavior. You might be able to fake how it sounds, but because the fundamental neural structures are not present, it is just an act and can't have the actual content.
Trying to think about Reality with a ToM is like doing Cargo Cult Science
Richard Feynman coined a term,
Cargo Cult Science, to describe the practices of people who may be doing what they call experiments, but they are missing the fundamental intellectual honesty to be actually doing science. The term comes from the observation that tribes in the South Pacific would observe westerners arrive and set up landing strips which would bring aircraft laden with cargo, all sorts of goods that seemed to appear like magic. Along the lines of Arthur C. Clarke's observation that "any sufficiently advanced technology is indistinguishable from magic". They tried to understand the source of this cargo and how to get cargo for themselves using their understanding of reality. They generated a
Cargo Cult, and proceeded to adopt rituals to try and cause cargo to appear.
This is really an excellent metaphor for trying to think about a subject with the wrong approach. Their thinking was that such good cargo had to come from the Ancestors, but the Ancestors would only bring such good cargo if they were communicated with in the right way, which the westerners knew how to do, so copy them and the cargo would appear. They built landing strips, control towers and populated them with radio control operators, but to no avail.
Explaining that their approach was wrong would fall on deaf ears. They don't have the background to understand where the cargo actually came from. They had anthropomorphized their observations and reduced them to the human terms they could understand using their ToM. They didn't come to their beliefs via facts and logic, facts and logic won't dissuade them from their beliefs.
Obviously there are multiple individuals involved, a leader and followers and the leader may achieve lots of things even if no cargo shows up. Presumably it is the charismatic persuasion of the leader using the leader's ToM that causes the followers to believe the leader. Simply by leading the effort to obtain cargo the leader achieves status over the others. Even when doing something completely useless and wrong, the society holds together if all of the members share the same ToM. Individuals not sharing the conceptualization of obtaining cargo by building airstrips would not fit in.
To people who have savant mathematical ability, those without it who are trying to emulate mathematical abilities can be seen as trying to do cargo cult mathematics. They can go through the motions, but don't have the ability to generate the content. Similarly, ASDs who try to communicate with NTs are doing cargo cult communication. They can go through the motions, but there is a lot of stuff that is being missed.
Neurological structures required to support an idea
The only ideas that an individual can think about are ideas that can be mapped into that individual's neural network. To learn a new idea, either the neural structure present is sufficiently flexible that the new idea can be mapped into it, or the neural structure must be modified until the new idea can be mapped onto it.
The process of learning a new idea must include as the first steps, the process of modifying the neural networks of the brain such that they can support the new idea being learned. Often the first step is "unlearning" ideas that are wrong. I think that this modification of the brain to support new ideas is why learning takes such a long time. New neural structures need to be made.
All mental representations require some level of neuronal "overhead" to be sustained. The details of how the brain does that are not understood. While the capacities of the brain are large, they are not infinite, and at some point trade-offs must be made.
Socially isolated individuals develop on an autism-like pathway.All important physiological systems are under feedback control (that would be all physiological systems). Presumably an organ as important as the brain is also under feedback control, and this is reflected in the improved efficiency obtained through practice at certain mental tasks.
Presumably if there is a trade-off of ToM vs. ToR, then isolated individuals with no need for a ToM would develop a more robust ToR. This does appear to be the case in multiple organisms including humans, monkeys and rodents.
The classic work on socially isolated monkeys was done by Harlow in the 1960's, [34] and present animal welfare regulations would make such experiments problematic. Some monkeys were raised with no social contact at all, even with their mothers. Such monkeys were profoundly affected and exhibited rocking behaviors, self-injurious behaviors and profound disruption in abilities to interact with other monkeys. They were termed autistic by the experimenters.
Surprisingly, some of these socially isolated monkeys exhibited superior cognitive abilities. What is especially interesting is that these superior abilities were termed "deficits" by the experimenters. [35] Socially reared monkeys were conditioned with a tone and a startle stimulus. A redundant lamp was then paired with the tone. Socially isolated monkeys conditioned to the redundant light, the socially reared monkeys did not. The experimenters characterized the non-conditioning of the socialized monkeys to the redundant signal of the light as "blocking" the isolated monkeys then exhibited what was termed a "deficit" in blocking. Why the experimenters chose to use the term "deficit" to refer to a superior ability tells us something about the experimenters and their expectations about the socially deprived monkeys, not the monkeys.
Rhesus monkeys raised in social isolation have superior learning performance to those raised in social environments. [36]
Involvement of nitric oxide in social interactions and communication
The archetypal social interaction in mammals is the bonding of the mother to her infant. All mammals exhibit this behavior and have exhibited it for as long as mammals have suckled their young. The first social interaction all mammals have is with their mother. Even mammals thought of as primarily non-social do have this social interaction.
NO is involved in the development of the bonding and smell recognition that occurs in ewes within 2 hour of giving birth.
Inhibition of nNOS blocks formation of that olfactory memory, and this blockage can be reversed by infusion of NO into the olfactory bulb. [37] Oxytocin is essential in the formation of normal social attachment in mice. [38] Reduction in oxytocin release following epidural anesthesia in heifers preceded a reduction in maternal bonding type behaviors[39]. Activation of the oxytocin receptor causes activation of nitric oxide synthase. [40] The connections that mediate maternal bonding can occur in the space of a few hours[41], limiting the distance over which axons must migrate to form these new connections.
Why NO is the signaling molecule that mediated the neural remodeling to cause maternal bonding makes evolutionary sense. Lactation is extremely energy intensive. If a mother does not have the metabolic resources to generate sufficient milk of sufficient nutritional quality to sustain her infant until it is weaned, she (and her infant) is better off not bonding to her infant and abandoning it. Spending metabolic resources on a reproductive attempt that will fail will reduce the success of potential future reproductive attempts. A failed reproductive attempt has no advantage either to the mother, or to the infant. An infant's best reproductive strategy in those circumstances is to do what ever increases the likelihood that the infant's mother will have a successful reproductive event later, so that the non-surviving infant may have a surviving sibling.
I discuss this at length in my blog on infanticide. Using NO as the positive signaling molecule to mediate maternal bonding directly couples maternal bonding to energy status. The low NO of metabolic stress directly reduces the degree and fidelity of maternal bonding. In extreme metabolic stress (the most important states for maternal bonding to be blocked) the maternal instinct turns from nurturing to infanticide. It needs to be appreciated that infanticide under conditions of extreme metabolic stress is as much a "maternal" instinct as is nurturing when times are better. I see infanticide as the brutally hard state that desperate metabolic stress induces in postpartum women.
Social isolation reduces NO generating neurons in the brainWhen rodents are raised in a socially deprived setting, the numbers of NO producing neurons in some parts of their brains are reduced. [42] A reduction in basal NO in the brain due to development under socially isolated circumstances makes sense. Many social interactions are mediated via NO mediated pathways, including bonding and other pathways mediated through oxytocin. If the environment one is growing into is non-social, social neural pathways have little or no survival benefit. Better to develop the neural structures that will be useful.
Socially isolated individuals retain sufficient neural plasticity to partially recoverSocial isolation at birth produced monkeys with profoundly disrupted social abilities. Experiments demonstrated that some of the disrupted social abilities could be restored. This
involved the use of "therapist" monkeys, usually socially raised normal monkeys that were substantially younger than the isolated monkeys. [43] In females, a socially isolated female could recover somewhat and be an improved mother following pregnancy and raising an infant however many times the first born infants did not do very well but
mothering did improve with subsequence births[44] demonstrating plasticity in neural networks mediating mothering behaviors during pregnancy and/or mothering activities. Since maternal bonding is the archetypal communication pathway for mammals, this suggests that other fundamental communication pathways have plasticity also.
With NO being involved in bonding, improved bonding and mothering interactions with subsequent births is consistent with increased neurogenic nitric oxide as a causal mechanism. If a non-social environment becomes social, reconfiguring neural structures to cope with social interactions would be advantageous.
Potential for treatment
I suggest an analogous treatment for ASD individuals may be to incorporate them into play groups with significantly younger NT children that are at similar developmental stages, but with sufficient adult supervision that nothing untoward can happen.
Doing this in the context of increasing NO levels via the techniques I am working on my have important therapeutic effects.
References:
1 Kates WR, Burnette CP, Eliez S, Strunge LA, Kaplan D, Landa R, Reiss AL, Pearlson GD. Neuroanatomic Variation in Monozygotic Twin Pairs Discordant for the Narrow Phenotype for Autism. Am J Psychiatry. 2004 Mar;161(3):539-46.
2 Greenberg DA, Hodge SE, Sowinski J, Nicoll D. Excess of twins among affected sibling pairs with autism: implications for the etiology of autism. Am J Hum Genet. 2001 Nov;69(5):1062-7.
3 Visscher PM. Increased Rate of Twins among Affected Sib Pairs. Am J Hum Genet. 2002 Oct;71(4):995-6; author reply 996-9.
4 Herbert MR, Russo JP, Yang S, Roohi J, Blaxill M, Kahler SG, Cremer L, Hatchwell E. Autism and environmental genomics. Neurotoxicology 2006 Sep;27(5):671-84.
5 Happe F, Ronald A, Plomin R. Time to give up on a single explanation for autism. Nat Neurosci. 2006 Oct;9(10):1218-20.
6 Godfrey KM, Barker DJ. Fetal nutrition and adult disease. Am J Clin Nutr. 2000 May;71(5 Suppl):1344S-52S. Review.
7 Fowden AL, Giussani DA, Forhead AJ. Intrauterine programming of physiological systems: causes and consequences. Physiology (Bethesda). 2006 Feb;21:29-37. Review.
8 http://ajprenal.physiology.org/cgi/content/full/288/4/F626#BIBL
9 Esch T, Stefano GB, Fricchione GL, Benson H. Stress-related diseases – a potential role for nitric oxide. Med Sci Monit. 2002 Jun;8(6):RA103-18.
10. Herbert MR. Large Brains in Autism: The Challenge of Pervasive Abnormality. Neuroscientist. 2005 Oct;11(5):417-40.
11. Casanova MF, Buxhoeveden DP, Switala AE, Roy E. Minicolumnar pathology in autism. Neurology. 2002 Feb 12;58(3):428-32.
12. Gustafsson L. Comment on "Disruption in the inhibitory architecture of the cell minicolumn: implications for autism". Neuroscientist. 2004 Jun;10(3):189-91.
[1]3. Beversdorf DQ, Manning SE, Hillier A, Anderson SL, Nordgren RE, Walters SE, Nagaraja HN, Cooley WC, Gaelic SE, Bauman ML. Timing of prenatal stressors and autism. J Autism Dev Disord. 2005 Aug;35(4):471-8.
14. Kapoor A, Matthews SG. Short periods of prenatal stress affect growth, behaviour and hypothalamo–pituitary–adrenal axis activity in male guinea pig offspring. J Physiol. 2005 Aug 1;566(Pt 3):967-77.
[1]5. Cannizzaro C, Plescia F, Martire M, Gagliano M, Cannizzaro G, Mantia G, Cannizzaro E. Single, intense prenatal stress decreases emotionality and enhances learning performance in the adolescent rat offspring: interaction with a brief, daily maternal separation. Behav Brain Res. 2006 Apr 25;169(1):128-36.
[1]6. Kapoor A, Dunn E, Kostaki A, Andrews MH, Matthews SG. Fetal programming of hypothalamo-pituitary-adrenal function: prenatal stress and glucocorticoids.J Physiol. 2006 Apr 1;572(Pt 1):31-44.
[1]7. Peunova N, Scheinker V, Cline H, Enikolopov G. Nitric oxide is an essential negative regulator of cell proliferation in Xenopus brain. J Neurosci. 2001 Nov 15;21(22):8809-18.
[1]8. Contestabile A, Ciani E. R Role of nitric oxide in the regulation of neuronal proliferation, survival and differentiation. Neurochem Int. 2004 Nov;45(6):903-14..
[1]9. Herbert MR, Ziegler DA, Deutsch CK, O'Brien LM, Kennedy DN, Filipek PA, Bakardjiev AI, Hodgson J, Takeoka M, Makris N, Caviness VS Jr. Brain asymmetries in autism and developmental language disorder: a nested whole-brain analysis. Brain. 2005 Jan;128(Pt 1):213-26.
20. Susman RL. Fossil Evidence for Early Hominid Tool Use. Science. 1994 Sep 9;265(5178):1570-3.
2[1]. Courchesne E, Karns CM, Davis HR, Ziccardi R, Carper RA, Tigue ZD, Chisum HJ, Moses P, Pierce K, Lord C, Lincoln AJ, Pizzo S, Schreibman L, Haas RH, Akshoomoff NA, Courchesne RY. Unusual brain growth patterns in early life in patients with autistic disorder: an MRI study. Neurology. 2001 Jul 24;57(2):245-54.
22. James I Singular scientists. J R Soc Med. 2003 Jan;96(1):36-9.
23 quoted in 22
24. Al Yankovic. White & Nerdy. Music video by "Weird Al" Yankovic from the album "Straight Outta Lynwood" Volcano records.
http://www.youtube.com/watch?v=-xEzGIuY7kw (accessed 12/25/2006)
25. Rizzolatti G, Craighero L. The mirror-neuron system. Annu Rev Neurosci. 2004;27:169-92.
26. Dapretto M, Davies MS, Pfeifer JH, Scott AA, Sigman M, Bookheimer SY, Iacoboni M. Understanding emotions in others: mirror neuron dysfunction in children with autism spectrum disorders. Nat Neurosci. 2006 Jan;9(1):28-30.
27. Thomas S. Kuhn. The Structure of Scientific Revolutions. 3d edition. University of Chicago Press, 1996.
28. Miller JD, Scott EC, Okamoto S. Public Acceptance of Evolution. Science. 2006 Aug 11;313(5788):765-6.
29. Friedman RM. Einstein and the Nobel Committee: Authority vs. Expertise. europhysics news July/August 2005 129-133.
30. Dar-Nimrod I, Heine SJ. Exposure to Scientific Theories Affects Women’s Math Performance. Science. 2006 Oct 20;314(5798):435.
3[1]. Ottoni EB, de Resende BD, Izar P. Watching the best nutcrackers: what capuchin monkeys (Cebus apella) know about others' tool-using skills. Anim Cogn. 2005 Oct;8(4):215-9.
32. Mottron L, Lemmens K, Gagnon L, Seron X. Non-algorithmic access to calendar information in a calendar calculator with autism. J Autism Dev Disord. 2006 Feb;36(2):239-47.
33. Dawson M, Soulières I, Gernsbacher MA, Mottron L. The level and nature of autistic intelligence. Psychol Sci. 2007 Aug;18(8):657-62.
34. HARLOW HF, DODSWORTH RO, AND HARLOW MK. TOTAL SOCIAL ISOLATION IN MONKEYS PNAS VOL. 54, 1965 90-97.
35. BEAUCHAMP AJ, GLUCK JP, FOUTY EH, LEWIS MH. Associative Processes in Differentially Reared Rhesus Monkeys (Macaca mulatta) : Blocking. Developmental Psychobioiogy 24(3): 175-189 (1991).
36. YEATON SP, O'CONNELL MF, STROBEL DA. Malnutrition and social isolation: learning in the developing rhesus monkey. PHYSIOL. BEHAV. 20(2) 125-128, 1978.
37. Kendrick KM, Guevara-Guzman R, Zorrilla J, Hinton MR, Broad KD, Mimmack M, Ohkura S. Formation of olfactory memories mediated by nitric oxide. Nature. 1997 Aug 14;388(6643):670-4.
38. Jennifer N. Ferguson, J. Matthew Aldag, Thomas R. Insel, and Larry J. Young. Oxytocin in the medial amygdale is essential for social recognition in the mouse. Journal Neuroscience, October 15, 2001, 21 (20):8278-8285.
39. G. L. Williams, O. S. Gazal, L. S. Leshin, R. L. Stanko, and L. L. Anderson. Physiological regulation of maternal behavior in heifers: Roles of genital stimulation, intracerebral oxytocin release and ovarian steroids. Biology of Reproduction 65, 295-300 (2001).
40. Gerald Gimpl and Falk Fahrenholz. The oxytocin receptor system: structure, function, and regulation. Physiological reviews vol. 81, No. 2, 629-683, April 2001.
41. Okere CO, Kaba H. Increased expression of neuronal nitric oxide synthase mRNA in the accessory olfactory bulb during the formation of olfactory recognition memory in mice. Eur J Neurosci. 2000 Dec;12(12):4552-6.
42. POEGGEL G, HAASE C, GULYAEVA N, BRAUN K. QUANTITATIVE CHANGES IN REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE-DIAPHORASE-REACTIVE NEURONS IN THE BRAIN OF OCTODON DEGUS AFTER PERIODIC MATERNAL SEPARATION AND EARLY SOCIAL ISOLATION. Neuroscience Vol. 99, No. 2, pp. 381–387, 2000.
43. Harlow HF, Suomi SJ. Social recovery by isolation-reared monkeys. Proc Natl Acad Sci U S A. 1971 Jul;68(7):1534-8.
44. Ruppenthal GC, Arling GL, Harlow HF, Sackett GP, Suomi SJ. A 10-year perspective of motherless-mother monkey behavior. J Abnorm Psychol. 1976 Aug;85(4):341-9.
