Creative Innovation: Possible Brain Mechanisms
Kenneth M. Heilman, Stephen E. Nadeau and David O. Beversdorf
Departments of Neurology and Clinical and Health Psychology, University of Florida College of Medicine and College
of Health Related Professions, the Center for Neuropsychological Studies, the Neurology Service, and the Geriatric Research
Education Clinical Center, Malcolm Randall Department of Veterans Affairs Medical Center, Gainesville, FL, USA
This article reviews and develops some theories about the neurobiological basis of creative innovation (CI). CI is deﬁned
as the ability to understand and express novel orderly relationships. A high level of general intelligence, domain-
speciﬁc knowledge and special skills are necessary components of creativity. Specialized knowledge is stored in
speciﬁc portions of the temporal and parietal lobes. Some anatomic studies suggest that talented people might have
alterations of speciﬁc regions of the posterior neocortical architecture, but further systematic studies are needed.
Intelligence, knowledge and special skills, however, are not sufﬁcient for CI. Developing alternative solutions or divergent
thinking has been posited to be a critical element of CI, and clinical as well as functional imaging studies suggest that the
frontal lobes are important for these activities. The frontal lobes have strong connections with the polymodal and
supramodal regions of the temporal and parietal lobes where concepts and knowledge are stored. These connections
might selectively inhibit and activate portions of posterior neocortex and thus be important for developing
alternative solutions. Although extensive knowledge and divergent thinking together are critical for creativity they alone
are insufﬁcient for allowing a person to ﬁnd the thread that unites. Finding this thread might require the binding of
different forms of knowledge, stored in separate cortical modules that have not been previously associated. Thus, CI
might require the co-activation and communication between regions of the brain that ordinarily are not strongly
connected. The observations that CI often occurs during levels of low arousal and that many people with depression are
creative suggests that alterations of neurotransmitters such as norepinephrine might be important in CI. High levels
of norepinephrine, produced by high rates of locus coeruleus ﬁring, restrict the breadth of concept representations
and increase the signal to noise ratio, but low levels of norepinephrine shift the brain toward intrinsic neuronal activation
with an increase in the size of distributed concept representations and co-activation across modular networks. In
addition to being important in divergent thinking, the frontal lobes are also the primary cortical region that controls
the locus coeruleus-norepinephrine system. Thus creative people may be endowed with brains that are capable of
storing extensive specialized knowledge in their temporoparietal cortex, be capable of frontal mediated divergent thinking
and have a special ability to modulate the frontal lobe-locus coeruleus (norepinephrine) system, such that during
creative innovation cerebral levels of norepinephrine diminish, leading to the discovery of novel orderly relationships.
This article will discuss the possible brain mechanisms under-
lying creativity. Webster’s II University Dictionary (Soukhanov,
1988) gives three deﬁnitions of creativity: having the power or
ability to create, productive, marked by originality. Writing
a list of non-words, randomly applying colors to a canvas, or
generating a random list of variables may be novel or original
but not creative. Thus, the Webster’s dictionary deﬁnition is
inadequate. According to Bronowski (1972), creativity is
ﬁnding unity in what appears to be diversity. Great art works
have a myriad of colors and forms and great musical works
have a large variety of melodies and rhythms, but in both
paintings and symphonies the artist is able to develop a thread
that unites diverse elements and displays order. Creative
scientists such as Copernicus were able to see order in what
appeared to be a disorderly solar system and Einstein was able
to see the thread that unites matter and energy. Thus, in this
paper creativity is deﬁned as the ability to understand, de-
velop and express in a systematic fashion, novel orderly
Helmholtz (1826) and Wallas (1926) suggested that crea-
tivity has four stages, preparation, incubation, illumination
and veriﬁcation. Preparation is the acquisition of the skills and
knowledge that allow a person to create. For example,
Einstein developed superb skills in physics and math before
he made his great discoveries and Picasso learned to draw
forms and mix colors before he painted his masterpieces.
2003, Vol. 9, No. 5, pp. 369–379
Swets & Zeitlinger
Correspondence to: Kenneth M. Heilman, Department of Neurology, University of Florida, Box 100236, Gainesville, FL 32610-0236, USA. Fax: þ1-352-392-6893;
Many important scientiﬁc discoveries are made when a
scientist perceives signiﬁcance in apparently accidental
occurrences. The scientists, however, who made these dis-
coveries must be prepared to understand the importance of
these accidents. Kuhn (1996) noted that many important
discoveries are initiated by the observation of an anomaly.
Although these discoveries are based on an anomaly, it is the
‘‘prepared mind’’ that enables creators to perceive the impor-
tance of the phenomenon they observed. Thus, it is highly
probable that creative people were incubating ideas about the
phenomenon prior to the observation, but the observation
altered the cognitive processes such that with the observation
they have what has been termed an ‘‘Aha!’’ experience. It is
this ‘‘Aha’’ experience or epiphany that Helmholtz (1826) and
Wallas (1926) termed illumination. Subsequently, creative
people such as scientists have to perform experiments that
attempt to disprove or support their hypothesis. This is the
process of veriﬁcation.
In this paper, the terms preparation and veriﬁcation, as
suggested by Wallas (1926), will be used. The constructs of
incubation and illumination, however, have received much
criticism. For example, Metcalfe and Wiebe (1987) demon-
strated that the subjective feeling of knowing (illumination)
did not predict performance on insight problems. Weisberg
(1986) suggested that creativity does not require great leaps
(e.g., illumination) and the processes that lead to many great
discoveries might not be subconscious incubation, but rather a
series of conscious steps. Even according to Helmholtz and
Wallas, illumination, rather than being an independent factor,
appears to be the culmination of the incubation process. Since
there is not consensus on the stages of creativity and the
staging of creativity is not the focus of this paper, instead of
discussing incubation and illumination as independent stages
the term ‘‘creative innovation’’ will be used. Although this
paper primarily discusses preparation and creative innovation,
veriﬁcation and production are critical components of the
creative process. Much, however, is already known about
these processes and thus, they will not be discussed here.
General Intelligence: The creative person needs knowledge
and skills. To many psychologists intelligence is a measure of
a person’s ability to acquire the knowledge and skills that will
allow them to adapt to their environment (Sternberg, 1997).
Sternberg and O’Hara (1999) suggest that there are several
possible relationships between intelligence and creativity,
from overlapping to unrelated.
Guilford (1973), who played an important role in generat-
ing interest in creativity, thought that creativity was a subset of
intelligence. Guilford attempted to develop psychometric
tests that could measure creativity. These tests are similar
to those developed by Torrance (1974). Most of these tests
assess subjects’ ability to develop novel uses of common
objects. For example, subjects would be asked to name in a
ﬁxed time interval the different ways in which they might be
able to use a brick. Guilford found that students with low IQ
consistently performed poorly on these tests, but for the
students with high IQ, their performance on creativity tests
did not highly correlate with their IQ. After reviewing the
relationship between intelligence and creativity Torrance
(1975) suggested that IQ and creativity are only moderately
related. Finally, Barron and Harrington (1981) found a weak
relationship between the creativity of architects and their IQ.
They concluded that above an IQ of about 120, the IQ does not
predict creativity as much as it does if the IQ is below 120.
This theory suggests that there is an IQ threshold. A person
needs to be above this threshold to be intelligent enough to
learn and have sufﬁcient knowledge about the domain of their
creativity. Barron and Harrington also found that although the
threshold was 120 for architects, different IQ thresholds might
be found for other disciplines. Studies that assessed the IQ’sof
known creative people have provided converging evidence for
the postulate that after a threshold is reached there is not a
direct relationship between intelligence and creativity. For
example, Simonton (1994) and Herr et al. (1965) using this
method found that the correlation between IQ and creativity is
weak. Thus, intelligence is a necessary but not sufﬁcient
component of creativity.
Speciﬁc Knowledge and Special Talents: Studies of
patients with discrete brain lesions suggest that a person
can have speciﬁc cognitive disabilities. Developmental dis-
orders can also be associated with speciﬁc cognitive disabil-
ities. There are multiple reports of children with speciﬁc
disabilities in reading, math, drawing, music, and route ﬁnd-
ing who develop into creative geniuses. For example, there are
many great artists, such as Picasso, who did not do well in
school because of language disabilities and even mathe-
matical geniuses such as Einstein had language learning dis-
abilities. Thus, general intelligence or what Spearman (1905)
called the ‘‘g’’ factor alone can not explain speciﬁc disabilities
or speciﬁc talents and several theorists have placed more
emphasis on special factors or what Spearman called the ‘‘s’’
factor. For example, Howard Gardner (1985) suggested that
people have multiple intelligences and if creativity is related
to intelligence it would appear to be related to a speciﬁc factor
or a special form of intelligence.
Weisberg (1999) examined the relationship between knowl-
edge and creativity. The basic conclusion he drew from this
review is that domain-speciﬁc knowledge is a prerequisite for
creativity. Domain-speciﬁc knowledge in humans appears to be
stored in areas of the posterior neocortex. One of the most
important evolutionary changes in the brain of humans is the
development of the supramodal association areas of the inferior
parietal lobe, including the supramarginal and the angular gyri
(Brodmann’s areas 40 and 39) as well as the posterior portion of
the temporal lobe (Brodmann’s area 37). Lesion and functional
imaging studies have revealed that these areas are important in
mediating many higher cognitive activities such as language,
mathematics, and spatial computations.
One of Gall and Spurzheim’s (1810) postulates is that the
larger the area of brain devoted to a function the better that
370 K. M. Heilman, S. E. Nadeau and D. Beversdorf
function is performed. Gall’s postulate has already received
support from the work of Geschwind and Levitsky (1968) who
showed that the left temporal planum, which mediates lan-
guage, is larger than that on the right and anatomic asymme-
tries have been demonstrated in other areas (Geschwind and
Galaburda, 1985; Foundas et al., 1999). Spitzka (1907) noted
that several eminent mathematicians and physicists had large
parietal lobes, but little research was performed to document
this observation. One of the most creative physicists of the
modern era, Albert Einstein, was aware that one of the best
means to understand the brain mechanisms underlying crea-
tivity is to study the brains of creative individuals. Although
Einstein wished to be cremated, he also wanted his brain to be
used for research and therefore instructed that after death his
brain be used for this purpose. Einstein died on 18 April, 1955.
Thomas Harvey, the pathologist at the Princeton (New Jersey)
Hospital, removed Einstein’s brain. Rather than keeping the
brain intact, as Paul Broca had done with Leborgne’s brain,
Harvey sectioned the brain into 240 blocks and sent it to a
variety of people. Unfortunately, little was reported until 30
years later when Diamond and coworkers (1985) performed a
histological analysis of both right and left Brodmann’s area 9
(a portion of the superior frontal gyrus) and area 39 (the
angular gyrus). They found that, when compared to the brains
of control subjects, area 39 on the left side of Einstein’s brain
contained a higher glial cell to neuron ratio. These investi-
gators attempted to explain this result by suggesting that this
unusual ratio was, ‘‘... a response by glial cells to greater
neuronal metabolic need ...’’ They also suggested that this
increased metabolic need may be related to Einstein’s unusual
conceptual powers. The report of Diamond et al. (1985) was
severely criticized because with aging there is a loss of
cortical neurons and their control subjects were younger than
Einstein (Hines, 1998). Diamond and coworkers provided no
information about the control subjects’ socio-economic status,
their cause of death, or their premorbid health. Even if one
assumes that methodological errors did not account for the
results reported by Diamond et al. (1985), it is not apparent
from this report how a relative reduction of neurons could
account for Einstein’s creativity. Einstein had developmental
language disorders manifested by a delay in speaking.
According to Hoffman and Dukas (1972), in a letter Einstein
wrote in 1954 he said, ‘‘My parents were worried because I
started to talk comparatively late, and they consulted a doctor
because of it. I cannot tell how old I was at that time, but
certainly not younger than three.’’ Einstein also had devel-
opmental dyslexia (Kantha, 1992). Dejerine (1891) demon-
strated that lesions of the left angular gyrus (Brodmann’s area
39) induce acquired alexia and it is possible that people with
developmental dyslexia may also have abnormalities in this
region. Kantha (1992) suggested that the abnormalities
reported by Diamond et al. (1985) may have been related
to Einstein’s dyslexia rather than his genius. Alternatively,
as we will discuss in the next section, creativity according
to James (1890) requires ‘‘transitions from one idea to
another ...unheard of combination of elements, the subtlest
associations of analogy ...where partnerships can be joined
or loosened ...’’ and thus connectivity, including the mye-
linated subcortical connections, might be important for crea-
tivity and the high index of glial cell found in Einstein’s brain
might have indicated a high degree of connectivity.
Witelson et al. (1999) viewed the pictures of Einstein’s
brain, taken in 1955 before it was sectioned, and based on
these photographs they attempted to learn if the brain had
aberrant morphology. They found that at the end of the
Sylvian ﬁssure, rather than there being an ascending ramus
that divided the supramarginal gyrus into rostral and caudal
divisions, the Sylvian ﬁssure in Einstein’s brain ended at the
postcentral sulcus. Based on these observations, not only did
Witelson and her colleagues suspect that Einstein had an
enlarged left inferior parietal lobe but also unlike most people,
Einstein’s parietal lobe was not divided. They suggested that
this large and uninterrupted or more highly connected supra-
modal cortex allowed Einstein to have a functional advantage
in performing mathematics and spatial computations. In a
previous paper; however, Witelson and Kigar (1992) suggest
that the posterior ascending ramus is the continuation of the
main stem of the Sylvian ﬁssure and unlike gyri that are
formed by the infolding of cortex, the Sylvian ﬁssure, includ-
ing the ascending ramus, results from uneven growth of the
outer cortex relative to inner structure. That Einstein did not
have an ascending ramus, therefore, may suggest that the
growth of his inferior parietal cortex was not as great as in
those who do have such a ﬁssure. In addition, whereas creative
people such as Einstein are extremely rare, Foundas and her
coworkers (1999) note that the posterior ascending gyrus is
not present in 15 to 20% of people’s brains. Thus, an unin-
terrupted supramarginal gyrus cannot solely account for
Einstein’s exceptional creativity.
Geschwind and Galaburda (1985) suggested that the delay
in development of the left hemisphere may allow the right
hemisphere, that mediates spatial computations, to become
highly specialized. Although a person’s insight into the
mechanisms underlying their creative process is limited
(Metcalfe and Wiebe, 1987), according to Einstein his crea-
tivity was heavily dependent on spatial reasoning, and the
abnormal development of his left hemisphere may have
allowed his right hemisphere to become highly specialized
for spatial computations. Recently Miller and coworkers
(2000) described a series of patients with frontal temporal
dementia who acquired new musical or visual-artistic abil-
ities. Many of these patients had evidence of left temporal
dysfunction and the authors posited that the degeneration of
the left anterior temporal lobe may lead to facilitation of
artistic or musical skills.
Studies of patients with focal lesions and experiments using
functional magnetic imaging (fMRI) or positron emission
tomography (PET) have revealed that speciﬁc portions of
the brain are critical for storing different forms of knowledge.
Not all people who have high levels of specialized knowledge
or talent are creative, but we also know that to be creative one
often needs to have specialized knowledge. Unfortunately,
there have not been many systematic studies of talented and
creative people to learn if they have either gross structural or
histological features that are different from matched control
subjects. One of the few studies that examined this possibility
was performed on musicians with perfect pitch. Bever and
Chiarello (1974) using a dichotic listening task demonstrated
that whereas non-musicians are right hemisphere dominant
for identifying melodies, skilled musicians are left hemi-
sphere dominant. Using in vivo magnetic resonance (MRI)
morphometry of the brains of musicians and non-musicians,
Schlaug et al. (1995) demonstrated that the size of the left
planum temporale relative to the right, was greater in musi-
cians than non-musicians. The planum temporale is an area of
the cortex that contains the auditory association cortex.
Whereas composers are likely to have more creative skills
than musicians, most composers are musicians and great
musicians do not just play the written notes, they interpret,
and this interpretation is often creative. In the future, anatomic
studies of people who have creative skills and special talents
in other domains also need to be investigated. Although the
presence of speciﬁc anatomic differences in creative people
could account for a high degree of specialized knowledge,
specialized knowledge might also depend on a region’s
cellular organization and the neuro-chemicals (transmitters
and modulators) found in this region.
According to Hebb (1976), learning and memory are based
on modiﬁcations of synaptic strength among neurons that are
simultaneously active (i.e. neurons that ﬁre together, wire
together). A corollary of Hebb’s hypothesis might be that the
more neurons with which a person is endowed, the greater
their ability to learn and store knowledge. Thus, a person
with high levels of knowledge might have more neurons
in the brain region that stores these representations and this
could be reﬂected in the size of this region. Partial support for
this hypothesis came from the works of Rosenzweig (1972) as
well as Rosenzweig and Bennett (1996) who found that rodents
who were put in an enriched environment and who could learn
better, had a thicker cerebral cortex with an increase in the
number of dendritic spines that are critical for neuronal con-
nectivity and the storage of knowledge. The degree of neuronal
connectivity might be inﬂuenced by nerve growth factors. For
example, in a study of the effects of environmental enrichment
on levels of brain nerve growth factor, its receptors, and their
relationships to cognitive function, Pham and coworkers (1999)
found that animals placed in the enriched condition had sig-
niﬁcantly higher levels of nerve growth factor when compared
to the control animals housed in unenriched environments.
If, according to Hebb’s rule, learning and memory are based
on modiﬁcations of synaptic strength between neurons that are
simultaneously active, an increase in the sensitivity of synaptic
coincidence detection would also lead to better learning and
memory. The N-methyl-D-aspartate (NMDA) gated ion chan-
nel is a neural depolarization coincidence detector and the
inﬂux of calcium through this channel enables an increase in
synaptic strength. Thus, enhanced NMDA gated ion channel
activity could enhance learning and memory.
While these observations suggest that cognitive attributes
such as specialized knowledge may be related to the size of
neuron networks, their degree of connectivity and the ability to
alter the strength of connections, specialized knowledge, like
general intelligence, is necessary but not sufﬁcient for creative
innovation. Thus, in the next section the possible neurobiolog-
ical basis of creative-innovation will be discussed.
Creativity requires the novel understanding and expression of
orderly relationships. Novelty requires that the creative
person take a different direction from the prevailing modes of
thought or expression, which is called divergent thinking. The
concept of divergent thinking was put forth by William James
(1890) who stated, ‘‘Instead of thoughts of concrete things
patiently following one another in a beaten track of habitual
suggestion, we have the most abrupt cross-cuts and transitions
from one idea to another ...unheard of combination of
elements ...we seem suddenly introduced into a seething
caldron of ideas ...where treadmill routine is unknown and
the unexpected is the only law’’ (Albert and Runco, 1999).
Oliver Zangwell (1966) suggested that frontal lobe dys-
function would disrupt divergent thinking. There might be
two components to divergent thinking, disengagement and
developing alternative solutions. In order to ﬁnd a creative
solution to a problem that has remained unsolved a person
must alter the means by which they have previously attempted
to solve this problem. Berg (1948) developed the Wisconsin
Card Sorting test in which subjects are required to sort a deck
of cards according to the various dimensions illustrated on
these cards (e.g. shape, color, number). The subjects are not
informed of the sorting principles (e.g. shape) but must
deduce this from the response of the examiner after each
sort. Throughout this test the sorting principles change (e.g.
from shape to color) and the subjects must switch her or his
strategy based on the examiner’s responses. Milner (1984)
demonstrated that patients who had frontal lobectomies for
the surgical treatment of intractable epilepsy were impaired at
this test, suggesting that the frontal lobes might be critical for
the ability to disengage and shift to new solutions. Cognitive
perseveration, the inability to switch set or change the form of
an activity, is often observed in brain-impaired individuals
who have frontal lobe injuries. Denny-Brown and Chambers
(1958) proposed that whereas the frontal lobes mediate
avoidance behaviors, the temporal-parietal lobes mediate
approach behaviors and thus with frontal injury there is
inappropriate approach. Luria (1969) demonstrated in a series
of studies that patients with frontal lobe dysfunction are
stimulus (environmentally) dependent and even on simple
motor tasks (‘‘When I put up one ﬁnger you put up two and
when I put up two you put up one.’’) they have a propensity to
produce behavior that is entrained by the stimulus (a disen-
372 K. M. Heilman, S. E. Nadeau and D. Beversdorf
James (1890) suggested that the ability to change strategies
was important in divergent thinking. Converging evidence for
the postulate that the frontal lobes are important for the ability
to disengage and shift to new strategies (divergent thinking)
comes from studies of regional blood ﬂow in normal subjects
who are performing the Wisconsin Card Sorting Test or
performing a divergent thinking tests similar to those
described by Guilford (1967) and Torrance (1988). When
normal subjects were performing the Wisconsin Card Sorting
Test (Weinberger et al., 1986) they activated their frontal
lobes. When creative subjects were providing alternative uses
of bricks, their frontal lobes showed more activation than
those who were less creative (Carlsson et al., 2000).
Studies of patients with lesions (Damasio and Anderson,
1993; Stuss and Knight, 2002) and functional imaging studies
suggest that the frontal lobes are important for disengagement
and developing alternative strategies (divergent thinking). The
means by which the frontal lobes accomplish this, however,
remains unknown. The frontal lobes have strong connections to
the polymodal and supramodal regions of the temporal and
parietal lobes (Pandya and Kuypers, 1969). Perhaps these con-
nections are important for inhibiting the activated networks that
store semantically similar information while exciting or activat-
ing the semantic conceptual networks that have been only
weakly activated or not activated at all. Activation of these
remote networks might be important in developing the alter-
native solutions so important in divergent thinking. Support for
the postulate that the frontal lobe might be important in either
activating or inhibiting semantic networks comes from a recent
study, using positron emission tomography (PET), that sug-
gested different roles for medial and lateral rostral prefrontal
cortex (Brodmann’s area 10), with the former involved in
suppressing internally-generated thought and the latter in main-
taining them (Burgess et al., 2003).
In addition to being able to perform divergent thinking,
creative people are often looking for what is new and different
and thus are noveltyseekers. Creative people, especially writers,
composer-musicians and ﬁne artists, have a very high rate of
substance abuse such as alcoholism (Post, 1994, 1996). Studies
of large cohorts of college students also found that the students
who use marijuana tend to be novelty seeking and more creative
(Eisenmen et al., 1980). The reason for the relationship between
substance abuse and creativity has not been determined. One
hypothesis is that drugs enhance creative performance, but
studies of creativity under normal versus intoxicated states do
not reveal that drugs enhance creativity (Lang et al., 1984; Lapp
et al., 1994). Another possibilityis thatcreative people are prone
to addiction. In orderto be creative one hasto produce works that
are original or novel. Cloninger and coworkers (1993) presented
a psychobiological model of personality that includes 3 tem-
peraments or character dimensions. One of these dimensions is
noveltyseeking and creative people would have to be considered
novelty seekers. Several investigators have found that novelty
seekers are at increased risk for drug abuse. There is some
evidence that exposure to novelty activates the mesolimbic
dopamine (DA) system of the brain (Bardo et al.,1996).This
is the same neural substrates that mediate the rewarding effects
of drugs of abuse, such as alcohol. The mesolimbic dopami-
nergic system projectsto the nucleus accumbensand this portion
of the ventral striatum along with its connections to the limbic
system (e.g. amygdala) have been posited to be important in
alcohol addiction. Tupala and coworkers (2001) evaluated the
densities of dopamine receptors and transporters in the nucleus
accumbens and amygdala of the brain of people who have a
history of alcohol abuse. When compared with controls, the
mean number of dopamine receptor sites in the brain of the
alcoholic subjects was lower in both the nucleus accumbens and
the amygdala than that of the control subjects. These results
indicate that dopaminergic functions in these limbic areas may
be impaired among people who abuse alcohol. These results also
suggest that people with alcohol addiction might use alcohol and
novelty as a means of stimulating DA function because they ﬁnd
this stimulation is highly rewarding.
There is another possible relationship between the use of
drugs and creative innovation. While drugs have been shown
to intervere with creative production, some drugs lower
arousal and as we will discuss in a subsequent section, creative
innovation is enhanced by low arousal states. In contrast,
drugs such as amphetamines might impede creative innova-
tion because they heighten arousal.
Creativity was deﬁned in the beginning of this paper as the
ability to understand, develop and express in a systematic
fashion novel orderly relationships. Since the work of Paul
Broca (1863) it has repeatedly been demonstrated using
the lesion method, laterality studies (dichotic listening and
visual half ﬁeld), electrophysiological studies and functional
imaging that the brain is organized in modular fashion. Thus,
the understanding, development and expression of orderly
relationships might require communication between these
modules. Perhaps the strongest evidence for brain modularity
is hemispheric specialization, the left hemisphere being
dominant for language, even in the majority of left-handed
people (McGlone, 1984), motor control of skilled movement
(Liepmann, 1920) and categorical processing (Kosslyn, 1998).
In contrast, the right hemisphere appears to be important in
spatial cognition (Benton et al., 1975), including spatial
imagery (Butters et al., 1970), face recognition (Benton,
1990) and coordinate coding (Kosslyn, 1998). The right
hemisphere also appear to be important in emotional com-
munication and might also be dominant for mediating many
primary emotions (Heilman et al., 2000). Whereas the right
hemisphere appears to have a global attentional perspective,
(Robertson et al., 1988; Barrett et al., 1998) the left hemi-
sphere has a more focused attentional perspective. Many other
right-left hemisphere dichotomies have been described that
cannot be fully addressed in this paper. Works of scientiﬁcor
artistic creativity often require that one use the skills and
knowledge mediated by both hemispheres. For example, the
novelist who is writing about an emotional response of a
character must use the knowledge of facial emotional expres-
sions stored in the right hemisphere together with the verbal
lexicon stored in the left hemisphere. The sculptor must
imagine the rotation of spatial images mediated by the right
hemisphere while he uses the motor skills mediated by the left
hemisphere. The astronomer must combine the spatial com-
putations mediated by the right hemisphere with arithmetic
skills mediated by the left hemisphere. Thus, interhemispheric
communication might be important for combining the
knowledge and skills that are important for creative innova-
tion. James (1890) suggested that creativity requires an
‘‘ ...unheard of combination of elements and the subtlest
associations ....’’ Spearman (1931) suggested that creative
ideas result from the combination of two or more ideas that
have been previously isolated. Because the right and left
hemispheres store different forms of knowledge and mediate
different forms of cognitive activity, different neuronal archi-
tectures probably exist within the association cortices of each
of the hemispheres. A possible method of resolving a pre-
viously unsolved problem is to see this problem ‘‘in a new
light’’ and a means of seeing a problem in a new light is to use
a different form of knowledge and a different cognitive
strategy that might be mediated by the hemisphere that is
opposite to the one previously used.
The largest structure connecting independent modular sys-
tems is the corpus callosum. Lewis (1979) administered the
Rorschach test to eight patients who had undergone a cerebral
commissurotomy and noted that disconnection of the two
cerebral hemispheres tended to destroy creativity as measured
by this test. Bogen and Bogen (1988) noted that although the
corpus callosum transfers high level information, normally this
interhemispheric communication is incomplete. Bogen and
Bogen posited that incomplete interhemispheric communica-
tion permits hemispheric independence and lateralized cogni-
tion, important in the incubation of ideas.These authors mention
Frederic Bremer, who suggested that the corpus callosum sub-
serves the highest and most elaborate activities of the brain, in a
word, creativity. They also suggest that it is the momentary
suspension of this partial independence that accounts for illu-
mination. They did not say, however, what could account for this
momentary suspension of partial independence.
The corpus callosum is primarily comprised of myelinated
axons whose cells bodies are in the pyramidal layers of the
cerebral cortex. The cerebral connectivity important for crea-
tivity might not only be inter-hemispheric, but also intra-
hemispheric. In addition to the myelinated axons that carry
information between the hemispheres, from the thalamus and
basal ganglia to the cortex, and from the cortex to the basal
ganglia, thalamus, brain stem and spinal cord, these myelin-
ated axons also carry information between cortical regions in
the same hemisphere. These intrahemispheric connections
facilitate intrahemispheric communication, which might also
be important for creative innovation because widespread
connectivity allows creative people to combine the represen-
tations of ideas that have been previously isolated.
In a prior discussion of Einstein’s brain we mentioned that
it appeared that Einstein’s parietal lobe had extremely well
developed subcortical white matter. This ﬁnding might sug-
gest that Einstein’s creativity was related to his enhanced intra-
and interhemispheric connectivity.
According to Eysenck (1995), ‘‘... genius is found only in
males ...’’ There are, however, many cultural factors that might
inhibit women’s creativity. It there are sex differences in crea-
tivity that are not related to cultural factors, these differences
might be related to structural differences in the brain. Whereas
men’s brains are larger than those of women, the cerebral cortex
of women’s brains is as thick as men’s suggesting that the size
differences between men and women might be related to men
having more white matter than women.If Eysenck’sobservation
is correct, and sex differences are not entirely related to cultural
factors, they might be related to differences in connectivity.
Support for this connectivity hypothesis comes in part from
studies of aging. With aging there is a decrease of creativity,
especially in the sciences (Abra, 1989). Using neurostereology,
quantitative anatomical studies of the aging brain in non-
demented people revealed that the difference in total number
of neurons in subjects that ranged from 20 to 90 years was less
than 10%, but the total myelinated ﬁber length showed a large
reduction as a function of age (Pakkenberg et al., 2003).
Connectionist or parallel distributed processing (PDP) mod-
els suggest that there are processing units or nodes that are
similar to the neurons found in the brain and PDP models
strongly emulate the fundamentalproperties of neuralnetworks.
Information in PDP networks is stored in the strengths of
connections between units (as in the brain) and concepts are
represented as patterns of activity involving many units
(i.e. as distributed representations) (Rumelhart et al., 1986;
Martindale, 1995). The connections between concepts are re-
lated to each other to the degree that their elaboration derives
from the same information (the same connection strengths), and
their corresponding patterns of unit activity overlap. A large
number of units linked by a set of connections deﬁnes a domain
of knowledge from which any one of a large number of concepts
can be generated. Psychological studies of priming effects on
lexical decision latency provide a particularly clear demonstra-
tion of the capacity of this type of model to account for empi-
rical results. In a lexical decision task, words are ﬂashed one at a
time on a screen and the subject has to indicate, as rapidly as
possible, if the word displayed is, or is not, a real word. In a
priming paradigm, before the target word or non-word appears
on the screen, a prime word appears. If the prime is strongly
related to the target (e.g. the prime is doctor and the target is
nurse), the response time is less than when the prime and target
are unrelated (e.g. doctor-zebra). This is because, when a related
prime appears, it generates a distributed concept representation
that involves activation of many of the units that deﬁne the
distributed representation of the target. As much of the target-
distributed representation is already activated when the target
appears, response latency to the target is reduced.
374 K. M. Heilman, S. E. Nadeau and D. Beversdorf
Mednick (1962) suggested that in generating associative
responses to a stimulus, creative individuals are characterized
by a ﬂatter associative hierarchy than are less creative indivi-
duals. Hence, creative people might have the ability to activate
more highly distributed networks. There are two means by
which connectionist architectures might account for creativity.
Entities in the environment lead to activation of selected units,
thereby leadingto thegenerationof the patternsof activation that
instantiate concepts ofthose entities. There may, however, be the
capacity for the discretionary-intentional activation of selected
units ina network,thereby producing novel patternsofactivation
corresponding to novel concepts. In this way, the network
represents an internal model of some domain of knowledge,
and the discretional ability to activate selected units corresponds
to theability to ask‘‘what if’’ questions.This capability provides
thebasis fora modest creative element. For example, using one’s
internal model of house interiors, one can readily imagine the
elements that might be put in a bedroom large enough to
accommodate a sofa and a ﬁreplace.
A greater measure of creativity might be achieved by using
networks representing knowledge in one domain to help orga-
nize a quite different domain that might nevertheless share some
attributes, a sort of creativity by metaphor. Many different
network architectures probably exist within the association
corticesof the brain. Thisraisesthe possibility that this creativity
by metaphor might involve the recruitment of networks of
substantially different architecture in order to escape the con-
straints of existing (learned) internal models represented in the
networks usually used for thinking in a particular domain. The
manipulation of concepts in a network of a completely different
architecture would allow the asking of particularly novel ‘‘what
if’’ questions. An example may help to illustrate this elusive
concept. Richard Feynman, the Nobel prize winning physicist,
often began with abstract visual representations of his ideas,
which he subsequently translated into mathematical terms.
Apparently the architecture of the networks supporting his
visual representations permitted him the manipulative freedom
to escape conventionalformulations, thereby providing the basis
for creative innovation.
Support for Mednick’s (1962) proposed theory that creative
individuals are characterized by a ﬂatter associative hierarchy
than are less creative individuals and partial support for the
postulate that creative innovation is related to the recruitment of
different networks come from electroencephalographic (EEG)
studies of normal subjects who, during creative thought, demon-
strated an increase of anatomically distributed coherence of
EEG oscillations (Petsche, 1996; Jausovec and Jausovec, 2000).
The mechanism by which the size of brain networks is
modulated and co-activated is unknown, but in the next section
several possible mechanisms will be discussed.
Thebrain networksdiscussed aboveare comprisedof neurons
and their excitatory or inhibitory connections to other neurons.
Excitatory neurons give off the neurotransmitter glutamate and
the inhibitory neurons give off gamma amino butyric acid or
GABA. The neurons in these networks, however, can also be
modulated by other neurotransmitters such as the catechol-
amines and changes in the brain levels of these catecholamines
might play an important role in creativity.
Arousal and catecholamines
One of the best means of developing a neuropsychological
or neuropharmacological hypothesis about a speciﬁc behavior
is to study groups of people who can or cannot produce this
behavior, ﬁnd out the conditions that are most likely to be
associated with this behavior and learn what common factor
or factors distinguish these groups (ﬁnding the ‘‘thread’’ that
unites). Several scientists have reported that they were able to
solve a difﬁcult scientiﬁc problem during sleep or when they
were either falling asleep or awakening from sleep. One of
the most famous examples of this phenomenon is August
Kekule, who in 1865, while attempting to learn the structure
of benzene, went to sleep and dreamed of a snake chasing its
tail. This dream provided Kekule with the idea that benzene is
in a ring-like structure. Recently, Kekule’s recounting of this
episode has undergone careful scrutiny with strong arguments
that he never had such a dream (Strunz, 1993). Dehaene
(1997), however, in his book The Number Sense states, ‘‘They
[mathematical geniuses] say that in their most creative
moments, which some describe as ‘illuminations’, they do
not reason voluntarily, nor think in words, nor perform long
formal calculations. Mathematical truth descends on them,
sometimes even during sleep, as in Ramanujan’s case.’’
Before and after sleep, however, people are often in a state
of relaxed wakefulness. Creative people who are actively
working on a problem describe moments of insight when
they were able to solve previously insoluble problems. Often
these moments of insight come at a time when the person is
relaxed and at rest. In 1897, Ramo
n y Cajal (1999) wrote a
book entitled Advice for a Young Investigator, where he
suggested, ‘‘If a solution fails to appear after all of this,
and yet we feel success is just around the corner, try resting
for a while. Several weeks of relaxation and quiet in the
countryside bring calmness and clarity of the mind. Like the
early morning frost, this intellectual refreshment withers
the parasitic and nasty vegetation that smothers the good
seed. Bursting forth at last is the ﬂower of truth, whose calyx
usually opens after a long and profound sleep at dawn, in
those placid hours of the morning that Goethe and so
many others consider especially favorable for discovery.’’
Easterbrook (1959) and Eysenck (1995) suggested that high
cortical arousal induced by stress is often associated with
conscious attempts at problem solving, but this high arousal
might suppress the emergence of remote associations, and a
lower degree of cortical arousal might allow unusual associa-
tions to become manifest. Stress is associated with high levels
of norepinephrine and relaxation with low levels.
Many mental diseases have been associated with altera-
tions of neurotransmitters and especially the catecholamines.
Many investigators have noted a relationship between psy-
chopathology and creativity; however, many of these reports
are anecdotal and while these reports might provide us with
hypotheses about creativity one must be cautious about
drawing conclusions. Kraepelin in 1921 was perhaps the ﬁrst
to note that manic-depressive psychosis was often associated
with enhanced creativity (Weisberg, 1994). Several investi-
gators have reported that many of our most creative writers,
composers, painters and scientists have suffered with depres-
sion, either bipolar or monopolar (Poldinger, 1986; Andreasen
and Glick, 1988; Richards et al., 1988; Slaby, 1992; Post,
1996). One thread that unites dreaming, resting or relaxing
and depression is changes in neurotransmitter systems. In all
these states there appears to be a reduction of catecholamines
including norepinephrine (McCarley, 1982).
Support for the postulate that catecholamines modulate the
size of neuronal networks comes from several studies. Kischka
and coworkers (1996) used a lexical priming task similar to the
one describedearlier. Whenthey administered L-dopa to normal
subjects and tested priming they found that direct semantic
priming (e.g. doctor-nurse)was only marginally inﬂuenced. The
administration of L-dopa, however, signiﬁcantly reduced the ef-
fects of indirect priming (doctor-thermometer). Based on these
results, Kischka et al. (1996) suggested that dopamine increases
the signal to noise ratio in semantic networks by reducing the
spread of semantic activation. Although Kischka et al. (1996)
attributed this effect to the dopaminergic system, L-dopa is a
precursor to both dopamine and norepinephrine and the admin-
istration of L-dopa to these subjects may have also increased the
level of norepinephrine. In the Remote Associates Test, subjects
are presented with a series of trials in which they are given three
words and are requested to ﬁnd a word that is associated with all
three words. Like the priming task discussed earlier, this test
might assessthe size of lexical-semantic networks. Manypeople
who are creative have high trait anxiety (Carlsson et al., 2000),
but during stress (state anxiety), performance on this test
deteriorates (Martindale and Greenough, 1973). One of the
reasons why stress may reduce performance on this task is that
stress increases activity of the noradrenergic system. Further
support for this noradrenergic postulate comes from the results
of a study in which students with test anxiety dramatically
improved their scores on the Scholastic Aptitude Test (SAT)
when they took the beta adrenergic blocker propranolol
(Faigel, 1991). Propranolol is a centrally acting beta blocker
that reduces the inﬂuence of noradrenaline on neurons. The
SAT assesses both crystallized knowledge and ﬂuid reasoning.
Perhaps beta blockade improves performance on this test
because it reduces the inﬂuence of norepinephrine on the
neuronal networks, allowing increased cognitive ﬂexibility.
To directly test the hypothesis that norepinephrine modulates
cognitive ﬂexibility, Beversdorf and coworkers (1999) tested
normal subjects’ ability to solve problems when treated with
ephedrine, or propranolol. They found the anagram test that
relies heavily on cognitive ﬂexibility was performed better after
subjects took popranolol than after they took ephedrine. Pro-
pranolol is both a central and peripheral acting beta-adrenergic
antagonist. To learn if the increase in cognitive ﬂexibility
induced by propranolol was produced by central or peripheral
nervous system blockade, Broome et al. (2000) tested another
group of normal subjects with an anagram task and compared
the effects of propranolol, which enters the central nervous
system, and nadolol, a purely peripheral beta-blocker. Subjects’
solution times on the anagram test were more rapid with pro-
pranolol than with nadolol, suggesting that only central beta-
adrenergic blockade increases cognitive ﬂexibility.
Norepinephrine, which is increased during stress, changes the
signal-to-noise ratio by suppressing intrinsic excitatory synap-
tic potentials relative to the potentials elicited by direct afferent
input (Hasselmoet al., 1997). The bias toward external inputthat
occurs with high norepinephrine states might be important for
‘‘ﬂight or ﬁght’’ activities, but may prevent asking ‘‘What if’’
questions of the networks that store cognitive representations. In
addition, connectionist modeling has suggested that a moderate
amount of noise allows networks to settle into optimal solu-
tions. Suppressing intrinsic excitatory potentials may prevent
many association neurons that do not receive direct afferent
input from achieving ﬁring threshold. The reduced activity of
association neurons may lead to the activation of relatively
sparse and constricted associative networks, but as discussed
above creativity depends on the activation of highly distributed
representations that allow one to perform inference and general-
ization. Further support for this norepinephrine postulate comes
from a study of the role of the locus coeruleus in the regulation
of cognitive functions. Investigators have concluded that high
levels of tonic locus coeruleus activity, which increases the
levels of norepinephrine in the cortex, favors ‘‘bottom-up’’
processing, important for monitoring and attending to external
stimuli and increasing behavioral responsiveness to unex-
pected or novel stimuli (Aston-Jones et al., 1991). In contrast,
low levels of locus coerulus activity might be important in ‘‘top
down’’ processing, that is critical for the innovation stage of
Further support for the catecholamine-creative-innovation
hypothesis comes from EEG studies. Martindale and Hasenfus
(1978) performed a series of experiments to investigate the
relationship between arousal and creativity. To measure arousal
these investigators used the electroencephalogram. Since the
work of Berger (Jasper and Carmichael,1935) it hasbeen known
that with high levels of arousal there is desynchronization of the
EEG,butwith relaxedwakefulness there is welldeveloped alpha
activity. These investigators found that during an analogue of
creative innovation there was better developed alpha than dur-
ing an analogue of elaboration. Based on their ability to write
creative stories the authors placed subjects into either the
creative or uncreative groups. In the resting state there were
no differences in the EEGs of these two groups but during the
time they were developing their stories (‘‘innovation stage’’)the
creative subjects demonstrated better developed alpha activity
than did the uncreative subjects, suggesting that the creative
subjects were operating at a lower level of arousal. Foote and
coworkers (1991) reviewed the evidence that increased activa-
tion of the locus coeruleus, by way of its massively divergent
efferent noradrenergic projections to the cerebral cortex, parti-
cipates in arousal and can convert the EEG from non-alert to
alert or aroused states.
376 K. M. Heilman, S. E. Nadeau and D. Beversdorf
Studies of physiological arousal in depression, as determined
by EEG power analysis, have revealed that depressed patients
have reduced arousal that is altered with treatment (Nieber and
Schlegel, 1992; Knott et al., 2000). If lower levels of physio-
logical arousal allow one to increase the extent of concept
representations, promote divergent thinking and increase cog-
nitive ﬂexibility, then it would follow that people with depres-
sion might have a propensity to be creative.
Although the neurons that provide the cerebral cortex with
catecholamines such as dopamine and norepinephrine are
located in the midbrain (e.g. ventral tegmental area) and pons
(locus coeruleus) the activity of the catecholaminergic sys-
tems are modulated by the frontal lobes. The frontal lobe is the
only cortical area to project to the locus coeruleus (Arnsten
and Goldman-Rakic, 1984) which contains the noradrenergic
neurons that project to the cerebral cortex, and the frontal lobes
appear to be able to exert an inhibitory inﬂuence on the locus
coerulus (Sara and Herve-Minvielle, 1995). Increased locus
coerulus activity is associated with increased levels of cortical
norepinephrine and this induces EEG desynchronization.
Neurophysiological studies have revealed that stimulation
of only certain parts of the cerebral cortex induce desynchro-
nization of the EEG (physiological arousal) and these include
the frontal cortex and the anterior cingulate gyrus (Segundo
et al., 1955) that are strongly interconnected. Functional
imaging studies of patients with depression have shown
reduced cerebral blood ﬂow (i.e. reduced synaptic activity)
in the dorsolateral prefrontal cortex (Liotti and Mayberg,
2001). The observed reductions in dorsolateral prefrontal
blood ﬂow might be related to the relative failure of depressed
patients to be attentive and to develop thoughts or plans about
future activities (pathological disengagement). Instead they
are engaged in internally deﬁned plans (e.g. introspection,
rumination). The reduced activity in dorsolateral prefrontal
cortex and anterior cingulate cortex that occurs in depressed
patients left to their own devices might be important for
creative innovation because the frontal lobes are the primary
cortical area that controls the locus coeruleus. Reduced
activity in these frontal and cingulate regions, by virtue of
reduced input to locus coeruleus, could provide the basis for
reductions of cortical norepinephrine, associated reductions in
signal-to-noise ratio and the recruitment of widely distributed
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Received on 14 April, 2003; resubmitted on 21 May, 2003;
accepted on 20 June, 2003
Creative innovation: Possible brain
K. M. Heilman, S. E. Nadeau
and D. Beversdorf
This article reviews and develops some theories about the neurobiological basis of
creative innovation (CI). CI is deﬁned as the abilityto understand and express novel
orderly relationships. A high level of general intelligence, domain-speciﬁc knowl-
edge and special skills are necessary components of creativity. Specialized knowl-
edge is stored in speciﬁc portionsof the temporal and parietal lobes. Someanatomic
studies suggest that talented people might have alterations of speciﬁc regions of the
posterior neocortical architecture, but further systematic studies are needed. Intelli-
gence, knowledge and special skills, however, are not sufﬁcient for CI. Developing
alternativesolutionsordivergentthinkinghasbeen positedtobe acritical elementof
important for these activities. The frontal lobes have strong connections with the
polymodal and supramodal regions of the temporal and parietal lobes where
concepts and knowledge are stored. These connections might selectively inhibit
and activate portions of posterior neocortex and thus be important for developing
alternative solutions. Although extensive knowledge and divergent thinking
together are critical for creativity they alone are insufﬁcient for allowing a person
toﬁnd the thread thatunites. Finding this threadmight requirethe binding of different
forms of knowledge, stored in separate cortical modules that have not been
previouslyassociated. Thus, CI might requirethe co-activationand communication
between regions of the brain that ordinarily are not strongly connected. The
observations that CI often occurs during levels of low arousal and that many people
with depression are creative suggests that alterations of neurotransmitters such as
norepinephrine might be important in CI. High levels of norepinephrine, produced
byhighrates oflocuscoeruleus ﬁring,restrictthe breadthof conceptrepresentations
andincrease thesignal tonoise ratio, but low levels of norepinephrine shift the brain
representations and co-activation across modular networks. In addition to being
important indivergentthinking,thefrontal lobes arealsothe primarycorticalregion
that controls the locus coeruleus-norepinephrine system. Thus creative people may
be endowedwithbrainsthatare capable of storing extensivespecialized knowledge
in their temporoparietal cortex, be capable of frontal-mediated divergent thinking
and have a special ability to modulate the frontal lobe-locus coeruleus (norepi-
nephrine) system, such that during creative innovation cerebral levels of norepi-
nephrine diminish, leading to the discovery of novel orderly relationships.
Neurocase 2003; 9: 369–379
Neurocase Reference Number:
Primary diagnosis of interest
Author’s designation of case
Key theoretical issue
Key words: creativity; innovation; illumination; divergent think; genius
Scan, EEG and related measures