When did Mozart Become a Mozart? Neurophysiological Insight Into Behavioral Genetics
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Brain and Mind 4: 327–339, 2003.
°
C 2003 Kluwer Academic Publishers. Printed in the Netherlands. 327
When did Mozart Become a Mozart?
Neurophysiological Insight Into Behavioral Genetics
YURI I. ARSHAVSKY
Institute for Nonlinear Science, UCSD, La Jolla, CA 92093-0402, U.S.A., e-mail: yarshavs@ucsd.edu
(Received: June 12, 2002; Final: March 20, 2003)
Abstract. The prevailing concept in modern cognitive neuroscience is that cognitive functions are performed
predominantly at the network level, whereas the role of individual neurons is unlikely to extend beyond forming
the simple basic elements of these networks. Within this conceptual framework, individuals of outstanding cog-
nitive abilities appear as a result of a favorable configuration of the microarchitecture of the cognitive-implicated
networks, whose final formation in ontogenesis may occur in a relatively random way. Here I suggest an alter-
native concept, which is based on neurological data and on data from human behavioral genetics. I hypothesize
that cognitive functions are performed mainly at the intracellular, probably at the molecular level. Central to this
hypothesis is the idea that the neurons forming the networks involved in cognitive processes are complex elements
whose functions are not limited to generating electrical potentials and releasing neurotransmitters. According to
this hypothesis, individuals of outstanding abilities are so due to a ‘lucky’ combination of specific genes that
determine the intrinsic properties of neurons involved in cognitive functions of the brain.
Key words: behavioral genetics, cognitive ability, modular organization, quantitative trait locus, specific congenital
impairments.
Dedicated to my teacher Professor Israil M. Gelfand
Preamble
This year, one of the most outstanding mathematicians of our time, Israil M. Gelfand,
celebrates his 90th birthday. I. M. Gelfand is a member of the Russian Academy of Sciences,
National Academy of Sciences (USA), American Academy of Art and Sciences (Boston),
Royal Society (United Kingdom), Academie des Sciences (France), Imperial Academie of
Sciences (Japan), Royal Society of Sweden, Academie de Lincei (Italy), and Royal Irish
Academy; an Honorary Doctor of Oxford University (England), Harvard University (USA),
Sorbonne (France), University of Lyons (France), Scuola Normale de Pisa (Italy), Kyoto
University (Japan), University of Pennsylvania (USA), Uppsala University (Sweden), and
New York University (USA); winner of the Wolf Prize (1978), Wigner Medal (1979), Kyoto
Prize (1989), and the MacArthur Award (1994).
At the end of the 1950s, I. M. Gelfand became interested in problems of neurobiology. At
the beginning of the 1960s, he organized two research groups at the Institute of Biophysics
of the Russian Academy of Sciences (after 1967, this group continued to work at the Institute
for Information Transmission Problems) and at Moscow State University. At that time, I. M.
Gelfand used to ask us, a group of relatively young electrophysiologists, whether we thoughtP1: GDP
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328 YURI I. ARSHAVSKY
that nervous cells have ‘a soul,’ or only electrical potentials. It took me about 40 years to
understand the entire wisdom hidden behind this question. This paper is my attempt to
answer Gelfand’s question.
1. Introduction
It is trivial to say that no training can make a person into a Mozart or an Einstein. To be a
Mozart it is necessary to be born a Mozart. But what does it mean to be born a Mozart? In
other words, when did Mozart become a Mozart? There are at least two possible answers
to this question:
(i) Mozart became a Mozart at the moment of the zygote formation;
(ii) Mozart became a Mozart in the process of prenatal and early postnatal development of
the nervous system.
The prevailing concept of modern cognitive neuroscience is that cognitive functions of
the brain are performed at the network level. According to this concept, these functions
cannot be explained in terms of the behavior of individual cells or cellular groups, but
only in terms of behavior of whole networks. Such networks are regarded as computational
models that learn to perform cognitive functions (for example, the production and compre-
hension of language, face recognition, etc.) on the basis of the adjustment of the connection
weights between units in a network (see, for example, Seidenberg, 1997). When authors
refer to properties of neurons, they usually mean those properties that determine network
architecture and the spreading of excitation within and between networks (anatomy of neu-
rons, their connections and electrophysiological properties, dynamics of a neurotransmitter
release, synaptic plasticity, etc.). This means that individual neurons are considered only as
simple elements of networks and their own role in performing cognitive functions is thought
to be negligible.
Within this conceptual framework, the most seemingly evident answer to the above ques-
tion is that Mozart became a Mozart in the process of development of the nervous system.
The human brain contains about 1012 neurons and the number of synaptic connections
within the brain is astronomical. Yet, the number of genes in the human genome is rather
small and does not exceed 42,000–75,000 (Hogenesch et al., 2001; Zhuo et al., 2001).
This is clearly insufficient to determine all interconnections between neurons constituting
networks involved in cognitive functions. This makes it plausible to suggest that only the
general architecture of the brain, including specific neuron-to-neuron connections, are de-
termined genetically (see Benson et al., 2001), whereas the detailed microarchitecture of the
centers implicated in cognitive functions (number of neurons, length and branching patterns
of dendrites, number and location of synapses, etc.) is formed in a relatively random way
(Crick, 1979; Edelman, 1999). Therefore, the randomness in forming a unique morpholog-
ical and functional microarchitecture of neural networks may appear to be the major factor
in determining the differences in general or specific cognitive abilities between individuals.P1: GDP
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WHEN DID MOZART BECOME A MOZART 329
Here I will discuss several experimental observations that have led me to the conclusion
that we will not be able to understand neural mechanisms of cognitive functions if we
continue to believe that they are produced by neuronal networks where individual neurons
represent no more than ‘simple’ building elements. On the basis of these observations,
I will advocate a rival hypothesis that cognitive functions are performed mostly at the
cellular (likely molecular) level by the groups of neurons specialized in performing a given
function (see also Arshavsky, 2001). The specificity of neurons implicated in different
cognitive functions is determined by the expression of different genes. According to this
view, the major factor determining differences in general and specific cognitive abilities
among individuals is the accidental variation of genes implicated in cognitive functions.
This conceptual framework suggests that Mozart became a Mozart at the moment of the
formation of the zygote, due to a ‘lucky’ combination in the variation of genes determining
musical abilities.
2. Modular Organization of Cognitive Functions
A wealth of neurological evidence indicates that cognitive functions are performed by
highly specialized brain centers. Many clinical observations have shown that local damage
to the cerebral cortex in adults can result in irreversible impairments of specific cognitive
functions. For example, many cases have been described in which brain lesions have lead to
specific disorders in different aspects of language production and comprehension, reading, or
writing, without impairments of other cognitive functions. One such example was described
by Antonio Damasio and his colleagues (Anderson et al., 1990) who examined a patient
suffering from alexia and agraphia following a lesion in the left premotor cortex. Her visual
perception, intellect, memory, oral spelling, and drawing were normal. She could read and
write numbers and perform written calculations. However, her ability to read and write
letters and words was severely impaired. Another example described by Alexander Luria
and colleagues (Luria et al., 1965) illustrates the dissociation between musical and other
cognitive abilities. The Russian composer Vissarion Shebalin, who had several thromboses
in his left hemisphere which resulted in severe aphasia, did not lose the ability to compose.
In fact, following the stroke he composed his Fifth Symphony, which Dmitri Shostakovich
considered Shebalin’s best work.
Another convincing illustration of a modular, domain-specific organization of cognitive
functions is provided by studies on individuals with congenital sensory impairments. For
example, in congenitally blind individuals, Braille reading – which is a tactile task – activates
the secondary visual areas of the cortex, which is engaged in reading perception in normal
individuals (Büchel et al., 1998). Even more striking evidence of domain specificity of
cognitive functions was obtained upon studying sign language in deaf individuals. Computer
emission positron tomography (CT) and functional magnetic resonance imaging (fMRI)
scans indicated that the areas of the left hemisphere that are normally involved in the
production (mainly Broca’s area) and comprehension (mainly Wernicke’s area) of spoken
languages are also involved in the production and comprehension of sign (visual–spatial)
languages in deaf individuals. In addition, damage to the right hemisphere, which resultsP1: GDP
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330 YURI I. ARSHAVSKY
in severe impairments in visual-spatial abilities in all patients, did not compromise the
production and comprehension of sign language in deaf patients (McGuire et al., 1997;
Bavelier et al., 1998; Hickok et al., 1998, 2001; Nishimura et al., 1999; Neville and Bavelier,
2000; Petitto et al., 2000). These findings illustrate that, regardless of the language modality,
language comprehension and production are performed by the same highly specialized brain
structures.1
A great deal of information essential to understanding the organization of cogni-
tive functions was obtained from individuals with congenital cognitive impairments
(‘developmental-specific impairments’). All such developmental impairments have two
common features. First, they usually affect only one particular cognitive function and poorly
correlate with other functions or general intellectual abilities. Second, they are poorly (if at
all) compensated over the course of a life span.
One of the best-studied developmental cognitive impairments is dyslexia, a specific dis-
order relating to reading ability, which affects up to 10% of the population (see Pennington,
1999; Habib, 2000; Fisher and DeFries, 2002). All authors who studied developmental
dyslexia emphasize that it does not correlate with general intelligence, educational opportu-
nities, sensory and neurological handicaps, or the performance of other cognitive functions,
including other linguistic abilities. Remarkably, developmental dyslexia is accompanied by
minimal evidence of neuropathology as revealed by CT and fMRI scans, or by postmortem
examinations of the brains of affected individuals.
Two other developmental cognitive impairments are face agnosia (prosopagnosia) and
amusia. Face agnosia is the specific inability to recognize human faces (Damasio et al.,
1990; McNeil and Warrington, 1993; Farah, 1996). Face agnosia is not correlated with im-
paired intellectual abilities or defective visual perception. Although prosopagnosia patients
are not able to identify familiar faces, they are able to discriminate the age, gender, and
emotional expression of faces. In my recent paper (Arshavsky, 2001), I described the case
of Russian neuroscientist Dr Ivan Pigarev, who suffers from developmental face agnosia.
All of Pigarev’s other cognitive abilities, including the recognition of other visual images,
are normal. Amusia is the complete inability to recognize and memorize music. People
suffering from amusia have no trouble recognizing and understanding speech and other
environmental sounds (Peretz, 2001; Peretz et al., 2002).
Taken together, these data indicate that different neural centers involved in human cogni-
tion have specific properties that allow them to perform their highly specialized functions.
The question is whether this specificity determined by network properties or the properties
of individual neurons forming these networks. The discussion of genetic studies of cognitive
abilities and disabilities will help in approaching this question.
1 The theory of the modular organization of cognitive functions is not universally accepted. The main argument
against this theory is that the performance of each cognitive task usually involves broad areas of the brain (see,
for example, Fuster, 2000). I disagree that this argument can be regarded as a valid objection against the theory
of the modular organization of cognitive functions. Clearly, the performance of complex cognitive tasks requires
the combined action of different modules, which creates the impression that there is a lack of modularity in the
cortex organization.P1: GDP
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3. Genetics of Cognitive Abilities and Disabilities
The role of genetic factors in the individual variances of general and specific cognitive
abilities was extensively studied over the past decades. The findings obtained in these
titanic studies, performed on many thousands of monozygotic and dizygotic twins as well
as adopted children, strongly indicate that genetic factors play a significant role in human
differences in general and specific cognitive abilities. Studies of general cognitive abilities
(g) in monozygotic and dizygotic twins have shown that genetic factors (heritability) explain
at least one half of the total variability in g (Plomin and DeFries, 1998; Plomin, 1999, 2001;
Plomin et al., 2001; Plomin and Craig, 2001; Plomin and Kosslyn, 2001; Posthuma et al.,
2001). Identical twins reared apart are almost as similar for g as are identical twins reared
together (McGue and Bouchard, 1998). A study of identical twins aged 80 years and older,
who had differing life experiences from one another, reported the heritability for g of about
60% (McClearn et al., 1997). As has been concluded by Plomin et al. (2001, p. 168):
“Regardless of the precise estimate of heritability, the point is that genetic influence on g is
not only statistically significant, it is also substantial.”
Similar results have been obtained in the studies of the role of genetic factors in specific
cognitive abilities and disabilities. The overall contribution of genetic factors to specific con-
genital impairments, such as spoken language disabilities, including agrammatism (Tomblin
and Buckwalter, 1998; Bishop, 2000; Stromswold, 2000, 2001), reading disability, dyslexia
(DeFries and Alarcón, 1996; Plomin and DeFries, 1998; Plomin et al., 2001), and math-
ematics disability (Alarcón et al., 1997), has been estimated to exceed 50%. Importantly,
the intensity of training causes only a little, if any, effect on an individual’s variability in
specific cognitive abilities. As emphasized by Dorothy Bishop, “. . .large variations in lan-
guage input have relatively small effects on rates of language learning, or eventual language
competence” (Bishop, 2000, p. 139). Genetic correlates of musical abilities were recently
studied on adult monozygotic and dizygotic twins (Drayna et al., 2001). The authors used
the distorted tunes test, which requires subjects to recognize notes with incorrect pitch in
simple popular melodies. The correlation of the test scores between twins was estimated
at 0.67 for monozygotic pairs and 0.44 for dizygotic pairs and only weakly correlated with
measures of peripheral hearing. The heritability for musical abilities was estimated to be
71–80%. The studies on individuals with absolute pitch have also suggested a strong role
for genetic influences on the development of this trait (Gregersen et al., 1999; Baharloo
et al., 2000). In summary, these results show that genetic factors are as or more important
in determining individual differences in both general and specific cognitive abilities as all
other factors (including special training) combined.
The findings that genetic factors play a significant role in human cognitive aptitudes
are in conflict with the concept that differences in general and specific cognitive abilities
among individuals are determined by the randomness in forming microarchitecture of neural
networks. It is more reasonable to suggest that these differences are determined by the
variations in the genes implicated in cognitive functions. The heritability of complex traits,
including g and specific cognitive abilities, is thought to be determined by a system of
multiple genes called ‘quantitative trait loci,’ or QTLs (Plomin et al., 1994, 2001; Plomin andP1: GDP
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332 YURI I. ARSHAVSKY
DeFries, 1998; Plomin, 1999, 2001; Craig et al., 2000; Plomin and Crabbe, 2000; McGuffin
et al., 2001). QTLs are inherited in the same Mendelian manner as single-gene effects.
However, since many genes affect one trait, each individual gene may make a relatively
small contribution. The traits determined by multiple genes are distributed quantitatively and
described by a bell-shaped curve (see figure 1 in Plomin and Kosslyn, 2001). Therefore,
individuals with moderate genetically determined cognitive disabilities are likely to be
the quantitative trait extremes caused by the same genetic factors that are responsible for
normal variations throughout the dimension (Plomin et al., 1994, 2001; Plomin and DeFries,
1998; Plomin, 1999, 2001; Pennington and Lefly, 2001; Plomin and Kosslyn, 2001). In
other words, developmental cognitive disabilities are the ‘lowest’ end of the continuum of
individual differences for a given ability, rather than distinct disorders. Following the same
logic, one can suggest that individuals with outstanding cognitive abilities are the opposite,
‘highest’ extremes of quantitative traits.
4. Search for the Genes: Specificity
As many as ∼20% human genes are expressed solely in the brain (Sutcliffe, 1988, 2001;
Plomin et al., 2001). At present, the understanding regarding which of these genes are impli-
cated in cognitive functions is minimal at best. The main strategy for identifying the relevant
genes is a positional localization of QTLs to a particular chromosomal region (Brzustowicz,
1998; Smith et al., 1998; Pennington, 1999; Plomin, 1999; Plomin and Crabbe, 2000; Plomin
et al., 2001). The most extensive studies were performed on individuals suffering from de-
velopmental dyslexia. Putative QTLs implicated in dyslexia have been found on different
chromosomes, including chromosomes 6 and 15 (Cardon et al., 1994; Grigorenko et al.,
1997; Smith et al., 1998; Fisher et al., 1999b; Gayan et al., 1999; Nöthen et al., 1999;
Pennington, 1999; Morris et al., 2000; Nopola-Hemmi et al., 2000; Fisher and DeFries,
2002; Kaplan et al., 2002). The effects of these genes on reading ability appear to be strictly
specific. Other cognitive abilities, including g, have not been found to be influenced by
the reading-related QTLs. Grigorenko et al. (1997), who combined behavioral and genetic
studies, concluded that loci on chromosomes 6 and 15 contribute to differing phenotypes of
reading disability. Deficits in phonological awareness were linked to loci on chromosome
6, whereas deficits in word recognition were linked to loci on chromosome 15. This means
that cognitively dissociable components of reading are linked to separate genes (see also
Nöthen et al., 1999). However, the latter conclusion that different cognitive components
of reading process are linked to separate genes is not generally accepted (see Fisher et al.,
1999b; Gayan et al., 1999; Fisher and DeFries, 2002 for an opposing view).
Putative QTLs implicated in developmental agrammatism and other language disorders
have been localized on chromosome 7 (Fisher et al., 1998; Lai et al., 2000). Yet, the identity
of genes responsible for these disorders remains controversial. Recently, the specific gene
FOXP2, involved in speech production, has been identified on chromosome 7 (Lai et al.,
2001). This gene encodes the FOXP2 protein, a member of a large family of transcription
factors. A mutation of FOXP2 was found to lead to severe speech and language disorders.
However, the finding that a mutation of this single gene results in the specific languageP1: GDP
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impairment was not confirmed in a later study, which genotyped 270 language-impaired
children in whom no such mutation of FOXP2 was found (Meaburn et al., 2002).
In the studies described above, QTLs implicated in specific linguistic abilities have been
localized in individuals with developmental language impairments. In contrast, the local-
ization of QTLs implicated in g was conducted with children of the highest abilities. One
of the putative QTLs has been identified on chromosome 4 (Fisher et al., 1999a; Plomin
and Craig, 2001).
Different localization of QTLs implicated in different cognitive functions indicates a high
specialization of the genes located in these QTLs. This is consistent with the observations
that developmental cognitive impairments are usually very specific and do not correlate
with one another (see Section 2). The specificity of the genes controlling different cognitive
functions suggests that these genes are unlikely to determine such nonspecific, network-
related aspects of brain organization as the density of synapses, intensity of the arbori-
zation of axons and dendrites, synthesis of neurotransmitters and receptors, synaptic
plasticity, etc.
5. What Characteristics of Neural Networks
Are Determined by Genetic Factors?
In the latest edition of their book, ‘Behavioral Genetics,’ Robert Plomin and his colleagues
wrote “The questions whether and how much genetic factors affect psychological dimen-
sions and disorders represent important first steps in understanding the origin of individual
differences . . . . The next steps involve question how, the mechanism by which genes have
their effects” (Plomin et al., 2001, p. 320). Although the answer to the latter question is
within the sphere of neurophysiology, the findings that emerge from these genetic studies
are rarely discussed by neurophysiologists. Yet, these findings appear to be extremely im-
portant for understanding the neural mechanisms of cognitive functions. Genetic studies
essentially deny the idea that individual variations in cognitive abilities are determined by
the randomness in forming a unique microarchitecture of neural networks. However, it is
unclear what particular aspects of the organization of the nervous centers relevant to cog-
nitive functions are determined by the QTLs discussed in the previous section. The answer
to this question is a cornerstone of the understanding of neural mechanisms of cognition.
Two possible answers can be offered:
(i) These QTLs determine certain aspects of neural networks’ organization, enabling these
networks to perform a given cognitive function;
(ii) These QTLs determine specific intrinsic properties of neurons constituting neural
networks.
I will now outline neurological and genetic data that appear to favor the second hypothesis.
As discussed in Section 2, the damages of the cerebral cortex in adults result in irreversible
impairments of cognitive functions. In contrast, the cognitive impairments resulting from
lesions in the corresponding brain areas in children can be almost completely compensated.P1: GDP
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334 YURI I. ARSHAVSKY
The most exciting examples came from the studies on children with extensive lesions of the
left hemisphere containing the main linguistic centers, including the classical Broca’s and
Wernicke’s areas. If acquired during the infancy before certain critical age, these lesions
result in only transient linguistic deficits and the children are able to relearn to speak mostly
fluently (Dronkers et al., 2000; Bates and Roe, 2001; Huttenlocher, 2002). Many authors
suggest that this difference in the ability to recover cognitive functions after cortical lesions
in children and adults is explained by a higher plasticity of the nervous system in chil-
dren. However, the results obtained in the studies of individuals with congenital cognitive
impairments show that plasticity alone is not sufficient to account for this recovery. As
discussed above, genetically determined developmental linguistic impairments are never
compensated, in spite of the fact that they are accompanied by minimal evidence of neu-
ropathology. This paradoxical discrepancy between developmental cognitive deficits and
those acquired during infancy is emphasized by many authors (Tempe, 1997; Bishop, 2000;
Stromswold, 2000). A good example is provided by Karin Stromswold: “The essentially
intact linguistic abilities in children with extensive left hemisphere lesions are particularly
remarkable when compared with the markedly impaired linguistic abilities of specific lan-
guage impairment children who have minimal evidence of neuropathology on CT and MRI
scans” (Stromswoold, 2000, p. 925).
It is plausible to speculate that acquired language impairments in children are com-
pensated because the neurons of other brain areas start expressing genes from the QTLs
implicated in linguistic functions. As a result, other brain centers, having adequate input
and output connections, but obviously different detailed architecture, can substitute the
functions of the destroyed centers. In contrast, developmental impairments of linguistic
functions cannot be compensated in principle because of the mutations in genes determin-
ing the ability of neurons to become engaged in performing specific cognitive functions.
An interesting aspect of developing cognitive abilities in ontogenesis is that they cannot
be acquired after attaining a critical age. For example, children deprived of any language
input, spoken or signed, before the age of puberty are unable to learn language later in life
(Curtiss, 1977; Newport, 1990; Mayberry et al., 2002; Newman et al., 2002). Similarly, it
has been found that the development of musical abilities requires environmental exposure to
music during childhood (Gregersen et al., 1999, 2001). Therefore, we do not know whether
Mozart’s gift would be fully manifested if his father were not a musician and Mozart had
not listened to music from his infancy. Some authors explain the existence of the critical
period for language acquisition as the result of decreasing brain plasticity (Newman et al.,
2002). However, I question the idea that brain plasticity decreases at puberty. After the
onset of puberty, adolescents acquire a vast body of knowledge, and are still able to learn
additional languages. Therefore, the existence of critical periods for learning language or
music cannot be explained by nonspecific factors, such as a general decrease in the brain
plasticity.
During the past two decades, it has been shown that synaptic inputs can regulate the
expression of neural genes by modulating the activity of transcriptional activators and re-
pressors (Kandel, 2001; West et al., 2002). One may suggest that specific environmental
inputs (linguistic, musical, etc.) activate the expression of domain-specific genes whoseP1: GDP
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products govern the intrinsic properties of neurons implicated in cognitive functions. Acti-
vation of these genes appears to be age-dependent. This means that they are most sensitive
for activation during a certain critical period of postnatal brain development. As these genes
become activated, the amount of subsequent training has little impact on the individual cog-
nitive abilities. For example, large variations in language training have only small effects on
both the rate of language learning and the eventual language competence (Bishop, 2000).
To the contrary, the lack of gene activation before the end of the critical period could not
be compensated by any amount of subsequent training.
Additional indirect evidence that genes implicated in cognitive functions control the
intrinsic properties of neurons, rather than interactions between neurons within networks,
has been obtained in genetic studies. Plomin and colleagues investigated more than 100 DNA
markers in or near the genes relevant to the functioning of the nervous system, including the
genes relevant to neurotransmission, in children of the highest general cognitive abilities
(Plomin et al., 1995; Petrill et al., 1997; Ball et al., 1998). They found no replicated
associations of the studied markers with a high value of g. In particular, no association was
found between the high g and the markers for the dopaminergic system that is postulated
to play an important role in human intelligence (Previc, 1999).
6. Hypothesis
On the basis of the findings discussed above, I suggest the following hypothesis:
1. Cognitive functions are mainly carried out by groups of highly specialized neurons that
form modules responsible for different cognitive functions (see also Arshavsky, 2001);
2. These neurons express specific genes located within the corresponding QTL(s);
3. Expression of these genes is activated by a specific environmental input;
4. The expression of these genes is age-dependent, i.e., they are most sensitive for activation
during a certain critical period of ontogenesis;
5. The products of these genes are specifically involved in performing cognitive functions;
6. Individual differences in human general and specific cognitive abilities are determined
by variations of genes located within the corresponding QTL(s);
7. Mutations of the cognition-specific genes cannot be compensated by the expression of
other genes or by the activity of other neurons.
In summary, this hypothesis suggests that cognitive functions are performed mainly not
at the network level, but at the intracellular, likely molecular level.2 In this context, Mozart
became a Mozart at the moment of formation of his zygote due to a ‘lucky’ combination of
incidental variations of genes located within the QTL(s) implicated in musical abilities.
2 At present, the only demonstration that a complex function of the nervous system is performed at the intracellular,
molecular level was obtained in the studies of neural mechanisms of the circadian rhythm. It has been found that
the generation of the circadian rhythm is determined by molecular processes that occur within specialized neurons
(Reppert and Weaver, 2001; Panda et al., 2002).P1: GDP
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336 YURI I. ARSHAVSKY
Evidently, this hypothesis does not dismiss the role of neuronal networks in cognitive
functions. Interneural interactions within and between networks are crucial in forming
coordinated dynamic ensembles of neurons involved in performing cognitive functions
(Tononi and Edelman, 2000; Varela et al., 2001). As a result of the network activity, different
aspects of cognition (including long-term declarative memory) are ‘bound’ into a unitary
whole. However, I believe that functions of individual neurons in networks extend far beyond
generating electrical potentials and releasing neurotransmitters.
7. Conclusion
As any other hypothesis on the neural mechanisms of the human mind, the hypothesis
suggested in this paper is extremely speculative and will remain so until the identification
of cognition-specific genes and understanding of their functions. As noted in the editorial
comment of Nature Neuroscience “The explanatory gap between mutation and phenotype
is wider in cognitive genetics than in any other area of biology, and bridging will be a major
challenge” (Nature Neuroscience, 2001, p. 1049). Evidently, I do not pretend to solve this
problem. My principal goals is to emphasize that (i) the widely accepted network concept
underestimates the role of individual neurons in performing cognitive functions and, as
such, cannot explain the whole bulk of experimental data, especially those coming from
cognitive genetics; and (ii) the rival, cellular-oriented hypotheses may be productive for the
further progress in the field of cognitive neuroscience. In other words, the goal of this paper
is to motivate new approaches to studying neural mechanisms of cognitive functions.
To conclude, I would like to quote the comment by Pennington (1997) in regards to the
discovery that chromosome loci are implicated in dyslexia: “. . .the tools of genetics may
indeed prove helpful in discussion of human cognition. But no one should be surprised if
that dissection challenges our current theories of brain and mind in ways perhaps not even
dreamed now.”
References
Alarcón, M., DeFries, J. C., Light, J. G. and Pennington, B. F., 1997: A twin study of mathematics disability, J.
Learn. Disabil. 30, 617–623.
Anderson, S. W., Damasio, A. R. and Damasio, H., 1990: Troubled letters but not numbers. Domain specific
cognitive impairments following focal damage in frontal cortex, Brain 113, 749–766.
Arshavsky, Y. I., 2001: Role of individual neurons and neural networks in cognitive functioning of the brain: A
new insight, Brain Cogn. 46, 414–428.
Baharloo, S., Service, S. K., Risch, N., Gitschier, J. and Freimer, N. B., 2000: Familial aggregation of absolute
pitch, Am. J. Hum. Genet. 67, 755–758.
Ball, D., Hill, L., Eley, T. C., Chorney, M. J., Chorney, K., Thompson, L. A., Detterman, D. K., Benbow, C.,
Lubinski, D., Owen, M., McGuffin, P. and Plomin, R., 1998: Dopamine markers and general cognitive ability,
Neuroreport 26, 347–349.
Bates, E. and Roe, K., 2001: Language development in children with unilateral brain injury, in C. A. Nelson
and M. Luciana (eds.), Handbook of Developmental Cognitive Neuroscience, MIT Press, Cambridge, MA, pp.
281–307.
Bavelier, D., Corina, D. P. and Neville, H. J., 1998: Brain and language: A perspective from sign language, Neuron
21, 275–278.P1: GDP
PP1002-474111-03 BRAM.cls October 27, 2003 20:15
WHEN DID MOZART BECOME A MOZART 337
Benson, D. L., Colman, D. R. and Huntley, G. W., 2001: Molecules, maps and synapse specificity, Nat. Rev.
Neurosci. 2, 899–909.
Bishop, D. V., 2000: How does the brain learn language? Insights from the study of children with and without
language impairment, Dev. Med. Child Neurol. 42, 133–142.
Brzustowicz, L. M., 1998: Molecular genetic approaches to the study of language, Hum. Biol., 70, 325–345.
Büchel, C., Price, C. and Friston, K., 1998: A multimodal language region in the ventral visual pathway, Nature
394, 274–277.
Cardon, L. R., DeFries, J. C., Fulker, D. W., Kimberling, W. J., Pennington, B. F. and Smith, S. D., 1994:
Quantitative trait locus for reading disability on chromosome 6, Science 265, 276–279.
Craig, I. W., McClay, J., Plomin, R. and Freeman, B., 2000: Chasing behaviour genes into the next millennium,
Trends Biotechnol. 18, 22–26.
Crick, F., 1979: Thinking about the brain, Sci. Am. 241, 219–232.
Curtiss, S., 1977: Genie: A Psycholinguistic Study of a Modern-Day “Wild Child,” Academic Press, New York.
Damasio, A. R., Tranel, D. and Damasio, H., 1990: Face agnosia and the neural substrates of memory, Annu. Rev.
Neurosci. 13, 89–109.
DeFries, J. C. and Alarcón, M., 1996: Genetic of specific reading disability, Ment. Retard. Dev. Disabil. 2, 39–47.
Drayna, D., Manichaikul, A., de Lange, M., Snieder, H. and Spector, T., 2001: Genetic correlates of musical pitch
recognition in humans, Science 291, 1969–1972.
Dronkers, N. F., Pinker, S. and Damasio, A., 2000: Language and the aphasias, in E. R. Kandel, J. H. Schwartz
and T. M. Jessel (eds.), Principles of Neural Science, McGraw-Hill, New York, pp. 1169–1187.
Edelman, G. M., 1999: Building a picture of the brain, Ann. N. Y. Acad. Sci. 882, 68–89.
Farah, M. J., 1996: Is face recognition ‘special’? Evidence from neuropsychology, Behav. Brain Res. 76, 181–
189.
Fisher, P. J., Turic, D., Williams, N. M., McGuffin, P., Asherson, P., Ball, D., Craig, I., Eley, T., Hill, L., Chorney,
K., Chorney, M. J., Benbow, C. P., Lubinski, D., Plomin, R. and Owen, M. J., 1999a: DNA pooling indentifies
QTLs on chromosome 4 for general cognitive ability in children, Hum. Mol. Genet. 8, 915–922.
Fisher, S. E. and DeFries, J. C., 2002: Developmental dyslexia: Genetic dissection of a complex cognitive trait,
Nat. Rev. Neurosci. 3, 767–780.
Fisher, S. E., Marlow, A. J., Lamb, J., Maestrini, E., Williams, D. F., Richardson, A. J., Weeks, D. E., Stein,
J. F. and Monaco, A. P., 1999b: A quantitative-trait locus on chromosome 6p influences different aspects of
developmental dyslexia, Am. J. Hum. Genet. 64, 146–156.
Fisher, S. E., Vargha-Khadem, F., Watkins, K. E., Monaco, A. P. and Pembrey, M. E., 1998: Localisation of a gene
implicated in a severe speech and language disorder, Nat. Genet. 18, 168–170.
Fuster, J. M., 2000: The module: Crisis of paradigm, Neuron 26, 51–53.
Gayan, J., Smith, S. D., Cherny, S. S., Cardon, L. R., Fulker, D. W., Brower, A. M., Olson, R. K., Pennington, B.
F. and DeFries, J. C., 1999: Quantitative-trait locus for specific language and reading deficits on chromosome
6p, Am. J. Hum. Genet. 64, 157–164.
Gregersen, P. K., Kowalsky, E., Kohn, N. and Marvin, E. W., 1999: Absolute pitch: Prevalence, ethnic variation,
and estimation of the genetic component, Am. J. Hum. Genet. 65, 911–913.
Gregersen, P. K., Kowalsky, E., Kohn, N. and Marvin, E. W., 2001: Early childhood music education and predis-
position to absolute pitch: Teasing apart genes and environment, Am. J. Med. Genet. 98, 280–282.
Grigorenko, E. L., Wood, F. B., Meyer, M. S., Hart, L. A., Speed, W. C., Shuster, A. and Pauls, D. L., 1997:
Susceptibility loci for distinct components of developmental dyslexia on chromosomes 6 and 15, Am. J. Hum.
Genet. 60, 27–39.
Habib, M., 2000: The neurological basis of developmental dyslexia: An overview and working hypothesis, Brain
123, 2373–2399.
Hickok, G., Bellugi, U. and Klima, E. S., 1998: The neural organization of language: Evidence from sign language
aphasia, Trends Cogn. Sci. 2, 129–136
Hickok, G., Bellugi, U. and Klima, E. S., 2001: Sign language in the brain, Sci. Am. 284, 58–65.
Hogenesch, J. B., Ching, K. A., Batalov, S., Su, A. I., Walker, J. R., Zhou, Y., Kay, S. A., Schultz, P. G. and Cooke,
M. P., 2001: A comparison of the Celera and Ensembl predicted gene sets reveals little overlap in novel genes,
Cell 106, 413–415.
Huttenlocher, P. R., 2002: Neural Plasticity, Harvard University Press, Cambridge, MA.
Kandel, E. R., 2001: The molecular biology of memory storage: A dialogue between genes and synapses, Science
294, 1030–1038.P1: GDP
PP1002-474111-03 BRAM.cls October 27, 2003 20:15
338 YURI I. ARSHAVSKY
Kaplan, D. E., Gayan, J., Ahn, J., Won, T. W., Pauls, D., Olson, R. K., DeFries, J. C., Wood, F., Pennington, B. F.,
Page, G. P., Smith, S. D. and Gruen, J. R., 2002: Evidence for linkage and association with reading disability
on 6p21.3–22, Am. J. Hum. Genet. 70, 1287–1298.
Lai, C. S., Fisher, S. E., Hurst, J. A., Levy, E. R., Hodgson, S., Fox, M., Jeremiah, S., Povey, S., Jamison, D. C. and
Green, E. D., 2000: The SPCH1 region on human 7q31: Genomic characterization of the critical interval and
localization of translocations associated with speech and language disorder, Am. J. Hum. Genet. 67, 357–368.
Lai, C. S., Fisher, S. E., Hurst, J. A., Vargha-Khadem, F. and Monaco, A. P., 2001: A forkhead-domain gene is
mutated in a severe speech and language disorder, Nature 413, 519–523.
Luria, A., Tsvetkova, L. and Futer, J., 1965: Aphasia in a composer, J. Neurol. Sci. 2, 288–292.
Mayberry, R. I., Lock, E. and Kazmi, H., 2002: Linguistic ability and early language exposure, Nature 417, 38.
McClearn, G. E., Johansson, B., Berg, S., Pedersen, N. L., Ahern, F. S., Petrill, A. and Plomin, R., 1997: Substantial
genetic influence on cognitive abilities in twins 80 and more years old, Science 276, 1560–1563.
McGue, M. and Bouchard, T. J., 1998: Genetic and environmental influences on human behavioral differences,
Annu. Rev. Neurosci. 21, 1–24.
McGuffin, P., Riley, B. and Plomin, R., 2001: Toward behavioral genomics, Science 291, 1232–1249.
McGuire, P. K., Robertson, D., Thacker, A., David, A. S., Kitson, N., Frackowiak, R. S. and Frith, C. D., 1997:
Neural correlates of thinking in sign language, Neuroreport 10, 695–698.
McNeil, E. K. and Warrington, J. E., 1993: Prosopagnosia: A face-specific disorder, Q. J. Exp. Psychol. A 46,
1–10.
Meaburn, E., Dale, P., Craig, I. W. and Plomin, R., 2002: Language-impaired children: No sign of the FOXP2
mutation, Neuroreport 13, 1075–1077.
Morris, D. W., Robinson, L., Turic, D., Duke, M., Webb, V., Milham, C., Hopkin, E., Pound, K., Fernando, S.,
Easton, M., Hamshere, M., Williams, N., McGuffin, P., Stevenson, J., Krawczak, M., Owen, M. J., O’Donovan,
M. C. and Williams, J., 2000: Family-based association mapping provides evidence for a gene for reading
disability on chromosome 15q, Hum. Mol. Genet. 9, 843–848.
Neville, H. J. and Bavelier, D., 2000: Specificity and plasticity in neurocognitive development in humans, in M.
S. Gazzaniga (ed.), The New Cognitive Neurosciences, MIT Press, Cambridge, MA, pp. 83–98.
Newman, A. J., Bavelier, D., Corina, D., Jezzard, P. and Neville, H. J., 2002: A critical period for right hemisphere
recruitment in American sign language processing, Nat. Neurosci. 5, 76–80.
Newport, E. L., 1990: Maturational constraints on language learning, Cogn. Sci. 14, 11–28.
Nishimura, H., Hashikawa, K., Doi, K., Iwaki, T., Watanabe, Y., Kusuoka, H., Nishimura, T. and Kubo, T., 1999:
Sign language ‘heard’ in the auditory cortex, Nature 397, 116.
Nopola-Hemmi, J., Taipale, M., Haltia, T., Lehesjoki, A. E., Voutilainen, A. and Kere, J., 2000: Two translocations
of chromosome 15q associated with dyslexia, J. Med. Genet. 37, 771–775.
Nöthen, M. M., Schulte-Korne, G., Grimm, T., Cichon, S., Vogt, I. R., Muller-Myhsok, B., Propping, P. and
Remschmidt, H., 1999: Genetic linkage analysis with dyslexia: Evidence for linkage of spelling disability to
chromosome 15, Eur. Child Adolesc. Psychiatry 8(Suppl. 3), 56–59.
Panda, S., Hogenesch, J. B. and Kay, S. A., 2002: Circadian rhythms from flies to human, Nature 417, 329–335.
Pennington, B. F., 1997: Using genetics to dissect cognition, Am. J. Hum. Genet. 60, 13–16.
Pennington, B. F., 1999: Toward an integrated understanding of dyslexia: Genetic, neurological, and cognitive
mechanisms, Dev. Psychopathol. 11, 629–654.
Pennington, B. F. and Lefly, D. L., 2001: Early reading development in children at family risk for dyslexia, Child
Dev. 72, 816–833.
Peretz, I., 2001: Brain specialization for music. New evidence from congenital amusia, Ann. N. Y. Acad. Sci. 930,
153–165.
Peretz, I., Ayotte, J., Zatorre, R. J., Mehler, J., Ahad, P., Penhune, V. B. and Jutras, B., 2002: Congenital amusia.
A disorder of fine-grained pitch discrimination, Neuron 33, 185–191.
Petitto, L. A., Zatorre, R. J., Gauna, K., Nikelski, E. J., Dostie, D. and Evans, A. C., 2000: From the cover: Speech-
like cerebral activity in profoundly deaf people processing signed languages: Implications for the neural basis
of human language, Proc. Natl. Acad. Sci. U.S.A. 97, 13961–13966.
Petrill, S. A., Plomin, R., McClearn, G. E., Smith, D. L., Vignetti, S., Chorney, M. J., Chorney, K., Thompson, L.
A., Detterman, D. K., Benbow, C., Lubinski, D., Daniels, J., Owen, M. and McGuffin, P., 1997: No association
between general cognitive ability and the A1 allele of the D2 dopamine receptor gene, Behav. Genet. 27, 29–31.
Plomin, R., 1999: Genetics and general cognitive abilities, Nature 402, C25–C29.P1: GDP
PP1002-474111-03 BRAM.cls October 27, 2003 20:15
WHEN DID MOZART BECOME A MOZART 339
Plomin, R., 2001: Genetic factors contributing to learning and language delays and disabilities, Child Adolesc.
Psychiatr. Clin. N. Am. 10, 259–277.
Plomin, R. and Crabbe, J., 2000: DNA, Psychol. Bull. 126, 806–828.
Plomin, R. and Craig, I., 2001: Genetics, environment and cognitive abilities: Review and work in progress towards
a genome scan for quantitative trait locus associations using DNA pooling, Br. J. Psychiatry (Suppl. 40) 178,
s41–s48.
Plomin, R. and DeFries, J. C., 1998: The genetics of cognitive abilities and disabilities, Sci. Am. 278, 62–69.
Plomin, R., DeFries, J. C., McClearn, G. E. and McGuffin, P., 2001: Behavioral Genetics, Worth, New York.
Plomin, R. and Kosslyn, S. M., 2001: Genes, brain and cognition, Nat. Neurosci. 4, 1153–1155.
Plomin, R., McClearn, G. E., Smith, D. L., Skuder, P., Vignetti, S., Chorney, M. J., Chorney, K., Kasarda, S.,
Thompson, L. A., Detterman, D. K., Petrill, S. A., Daniels, J., Owen, M. J. and McGuffin, P., 1995: Allelic
associations between 100 DNA markers and high versus low IQ, Intelligence 21, 31–48.
Plomin, R., Qwen, M. J. and McGuffin, P., 1994: The genetic basis of complex human behaviors, Science 264,
1733–1739.
Posthuma, D., de Geus, E. J. G. and Boomsma, D. I., 2001: Perceptual speed and IQ are associated through
common genetic factors, Behav. Genet. 31, 593–602.
Previc, F. H., 1999: Dopamine and the origins of human intelligence, Brain Cogn. 41, 299–350.
Reppert, S. M. and Weaver, D. R., 2001: Molecular analysis of mammalian circadian rhythms, Annu. Rev. Physiol.
63, 647–676.
Seidenberg, M. S., 1997: Language acquisition and use: Learning and applying probabilistic constrains, Science
275, 1599–1603.
Smith, S. D., Kelley, P. M. and Brower, A. M., 1998: Molecular approaches to the genetic analysis of specific
reading disability, Hum. Biol. 70, 239–256.
Stromswold, K., 2000: The cognitive neuroscience of language acquision, in M.S. Gazzaniga (ed.), The New
Cognitive Neurosciences, MIT Press, Cambridge, MA, pp. 909–932.
Stromswold, K., 2001: The heritability of language: A review and metaanalysis of twin, adoption, and linkage
studies, Language 77, 647–723.
Sutcliffe, J. G., 1988: mRNA in the mammalian central nervous system, Annu. Rev. Neurosci. 11, 157–198.
Sutcliffe, J. G., 2001: Open-system approaches to gene expression in the CNS, J. Neurosci. 21, 8306–8309.
Temple, C. M., 1997: Cognitive neuropsychology and its application to children, J. Child Psychol. Psychiatry 38,
27–52.
Tomblin, J. B. and Buckwalter, P. R., 1998: Heritability of poor language achievment among twins, J. Speech
Lang. Res. 41, 188–199.
Tononi, G. and Edelman, G. M., 2000: Schizophrenia and the mechanisms of conscious integration, Brain Res.
Rev. 31, 391–400.
Varela, F., Lachaux, J. P., Rodriguez, E. and Martinerie, J., 2001: The brainweb: Phase synchronization and
large-scale integration, Nat. Rev. Neurosci. 2, 229–239.
West, A. E., Griffith, E. C. and Greenberg, M. E., 2002: Regulation of transcription factors by neuronal activity.
Nat. Rev. Neurosci. 3, 921–931.
Zhuo, D., Zhao, W. D., Wright, F. A., Yang, H. Y., Wang, J. P., Sears, R., Baer, T., Kwon, D. H., Gordon, D., Gibbs,
S., Dai, D., Yang, Q., Spitzner, J., Krahe, R., Stredney, D., Stutz, A. and Yuan, B., 2001: Assembly, annotation,
and integration of UNIGENE clusters into the human genome draft, Genet. Res. 11, 904–918.You can also read
