Neuroscience and Biobehavioral Reviews 33 (2009) 909–925

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Neuroscience and Biobehavioral Reviews

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Review

Neuroscience of learning arithmetic—Evidence from brain imaging studies

L. Zamarian a,*, A. Ischebeck b, M. Delazer a
a
Clinical Department of Neurology, Medical University Innsbruck, Anichstrasse, 35, A-6020 Innsbruck, Austria
b
Institute for Psychology, Section of Applied Neuropsychology, University of Graz, Austria

A R T I C L E I N F O A B S T R A C T

Article history: It is widely accepted that the human brain is remarkably adaptive not only in child development, but also
Received 1 December 2008 during adulthood. Aim of this work is to offer an overview and a systematic analysis of neuroimaging
Received in revised form 5 March 2009 studies on the acquisition of arithmetic expertise. In normally developing children and adults, the gain of
Accepted 11 March 2009
arithmetic competence is reflected by a shift of activation from frontal brain areas to parietal areas
relevant for arithmetic processing. A shift of activation is also observed within the parietal lobe from the
Keywords: intraparietal sulci to the left angular gyrus. Increases in angular gyrus activation with gaining of
Learning
expertise have also been documented in other cognitive domains. It appears that the left angular gyrus
Training
activation is modulated by inter-individual differences in arithmetic performance. The comparison of
Arithmetic
Brain plasticity normal individuals with exceptionally performing individuals (e.g., calculating prodigies) suggests that
Brain activation changes the experts’ arithmetic proficiency relies on a more extended activation network than the network found
Gray matter changes in non-experts. In expert individuals with long-lasting, extensive mathematical training, specific
Dyscalculia structural brain modifications are also evident.
ß 2009 Elsevier Ltd. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 909
2. Calculation in adults . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 910
3. Imaging arithmetic learning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 911
3.1. Learning simple arithmetic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 911
3.2. Learning complex arithmetic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 912
3.3. Learning effects associated with different learning methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 912
3.4. Learning effects specific to the learning content . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 912
3.5. The trajectory of learning effects. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 913
3.6. Transfer between operations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 913
3.7. Specificity of training-related brain activation changes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 914
4. The development of arithmetic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 914
5. The neural basis of expertise in arithmetic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 915
6. Inter-individual differences in arithmetic. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 916
7. Structural brain changes due to learning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 916
8. Rehabilitation of arithmetic skills in patients. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 917
9. Methodological considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 917
10. Summary and discussion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 918
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 918
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 923

1. Introduction

Recent studies using neuroimaging methods have shown that the

human brain is remarkably adaptive not only in child development,
* Corresponding author. Tel.: +43 0512 504 23661. but also later on throughout adulthood (e.g., Kelly et al., 2006;
E-mail address: laura.zamarian@uki.at (L. Zamarian). Poldrack, 2000). It is well recognised that genetic predisposition, but

0149-7634/$ – see front matter ß 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.neubiorev.2009.03.005
910 L. Zamarian et al. / Neuroscience and Biobehavioral Reviews 33 (2009) 909–925
also experience and learning may alter the human brain (for a
review, e.g., Ansari and Coch, 2006). Recent studies have specifically
assessed the effect of targeted training on cerebral structures and
brain activation patterns. For example, Draganski et al. (2006) used
voxel-based morphometry (VBM) to detect gray matter changes
while (and after) medical students learned for their medical exam.
Increase in gray matter during learning was found in the posterior
and inferior parietal cortex bilaterally, as well as in the posterior
hippocampus. Moreover, gray matter in the posterior hippocampus
continued to increase in the 3 months after the learning period.
Results of this study suggest that learning a great amount of highly
abstract information leads to a specific pattern of structural gray
matter modifications. Learning-induced changes of cerebral activa-
tion patterns have also been demonstrated. Recent functional
magnetic resonance imaging (fMRI) investigations have, for
example, found that specific training may influence the brain
activation patterns in individuals with dyslexia (e.g., Eden et al.,
2004; Gaab et al., 2007; Richards et al., 2007). In a study by Eden et al.
(2004), adults with developmental dyslexia underwent a phonolo-
gically targeted training programme. Behavioural effects of training
were also reflected by brain activation patterns as measured by fMRI.
Compared with dyslexics who performed no training, trained
dyslexics showed increased activation in left parietal regions
suggesting increased reliance on neuronal circuits that are used
by normal readers, as well as increased activation in the right
perisylvian cortex pointing to the engagement of compensatory
mechanisms. Functional plasticity induced by learning has also been
investigated by imaging studies in other domains, several of them
concerning the effects of musical training (e.g., Bosnyak et al., 2004;
Gaab et al., 2006, 2007; for reviews, e.g., Pantev et al., 2001, 2003;
Trainor et al., 2003). Gaab et al. (2006) compared the activation
patterns of two groups of healthy individuals, one group having had
strong learning effects in a pitch memory task, the second group
with weaker training effects. A random-effects analysis comparing
successful learners with less successful learners yielded increased
parietal activation in the left supramarginal gyrus. As suggested by
the authors, activation of the left supramarginal gyrus was due to
short-term memory of auditory material.
Few imaging investigations have been concerned with the effect
of arithmetic training, though this topic is of eminent importance.
The acquisition of arithmetic competence is a precondition for
successful participation in social and professional life as well as for
effective exercise of citizenship in a numerate society (Butther-
worth, 2005a). Individuals with deficits in numerical and arithmetic
processing face limitations in their autonomy and have poor chances
to qualify for adequate professional occupation. Given the high
incidence of dyscalculia (approximately 6% across various countries;
Shalev, 2004), better understanding of the learning processes and
possible disturbances is highly needed. Improved knowledge on the
acquisition of arithmetic skills and concepts is not only essential in
the case of disturbances, but also for efficient teaching to normally
achieving students. Cross-country comparisons have yielded sig-
nificant differences, possibly linked to the teaching style and
training methods (e.g., OECD, 2007a). Though investigating struc-
tural and functional effects of arithmetic training may contribute to
the development of targeted teaching and intervention in the future,
the primary aim of this review is not to propose direct classroom
applications (which are regarded by some as being all too often
simple and unsatisfying; Goswami, 2006), but to inform researchers
from different disciplines as well as practitioners about the
neuroscience of arithmetic learning. Aim of the present review is
to contribute to the dialogue between neuroscience and education
(for a discussion, e.g., Ansari and Coch, 2006) and to summarize our
current knowledge on the processes related to arithmetic learning.
As proposed by Ansari and Coch (2006), bridges between education
and neuroscience will enable educators and neuroscientists to gain a
new perspective and to pose and answer new and otherwise
unforeseeable questions about the learning brain.
Over the past decades, rich evidence has been accumulated on
the ontogenetic development of arithmetic abilities (for a review,
Buttherworth, 2005a), on learning disabilities and developmental
dyscalculia (e.g., Buttherworth, 2005b; Geary and Hoard, 2005;
Landerl et al., 2004; Noël et al., 2005), on the decline of arithmetic
knowledge in advanced age (e.g., Duverne and Lemaire, 2005), as
well as on the breakdown of arithmetic processing after acquired
brain damage (e.g., Grafman et al., 1989; Hecaen et al., 1961;
McCloskey et al., 1991; Sokol et al., 1991; Warrington, 1982; for
reviews, e.g., Domahs and Delazer, 2005; Zamarian et al., 2007). The
development of brain imaging techniques has allowed the specific
investigation of the cerebral networks supporting quantity proces-
sing and calculation (for a review, Ansari, 2008). So far, only a small
number of studies have been concerned with the cerebral networks
supporting arithmetic learning and the acquisition of arithmetic
expertise. In the present review, we will first summarize neurop-
sychological findings on the cognitive architecture of arithmetic
abilities and on the cerebral networks supporting calculation. Then,
we will discuss brain imaging studies on the gain of arithmetic skills
by healthy adults and on the acquisition of arithmetic abilities
during childhood. Finally, we will summarize evidence on the
relation between arithmetic expertise, cerebral activation patterns
and brain structure.
2. Calculation in adults
Cognitive neuropsychological studies with adults have pro-
vided compelling evidence that arithmetic expertise requires
the interplay of different types of knowledge and that number
processing (e.g., reading number words or writing Arabic
numerals) and calculation are subserved by a number of different
modules in the adult brain (e.g., Cappelletti et al., 2001, 2005;
Cipolotti and de Lacy Costello, 1995; Dagenbach and McCloskey,
1992; Dehaene and Cohen, 1997; Delazer et al., 2004, 2006;
Delazer and Benke, 1997; Lampl et al., 1994; McCloskey, 1992;
McCloskey et al., 1985; McNeil and Warrington, 1994; Pesenti
et al., 1994; Sokol et al., 1991; Van Harskamp and Cipolotti, 2001;
Warrington, 1982). In calculation, declarative knowledge of
simple, overlearned arithmetic facts (knowing that 2 + 2 gives 4)
can be distinguished from procedural knowledge (knowing how to
multiply 34  67) and from the recognition of arithmetic signs
(e.g., McCloskey, 1992; McCloskey et al., 1985). It has also been
shown that conceptual knowledge, which entails a basic under-
standing of operations and arithmetic principles, is an essential
and independent component of meaningful and efficient arith-
metic (e.g., Hittmair-Delazer et al., 1994, 1995). A number of
influential neuropsychological studies in the last three decades
focused on the cognitive architecture of calculation and number
processing (e.g., McCloskey, 1992). Other studies investigated the
relation between lesion localisation and affected cognitive
components (for reviews, Dehaene et al., 2003; Domahs and
Delazer, 2005). Several papers confirmed the role of the left
parietal structures in simple calculation (e.g., Delazer et al., 2006;
Lee, 2000; Van Harskamp and Cipolotti, 2001; Warrington, 1982),
although frontal areas seem also to be crucially involved in more
complex calculation processes (e.g., Lucchelli and De Renzi, 1993;
Semenza et al., 1997). Moreover, not only cortical lesions but also
sub-cortical lesions, such as those affecting the basal ganglia, have
shown to cause impairment in calculation (e.g., Corbett et al., 1986;
Dehaene and Cohen, 1997; Delazer et al., 2004; Whitaker et al.,
1985; Zamarian et al., in press).
The rapid development of brain imaging techniques in the
last 15 years has helped the precise identification of the
neuro-anatomical brain areas supporting arithmetic functions.
 L. Zamarian et al. / Neuroscience and Biobehavioral Reviews 33 (2009) 909–925
In a pioneering study, Roland and Friberg (1985) used single
photon emission tomography to measure regional changes in
cerebral blood flow induced by different cognitive tasks. The
arithmetic task (serial subtraction) specifically activated the
angular gyrus (AG), bilaterally. This AG activation was explained
to be due to the retrieval of numerical information from memory. A
number of later studies have shown that number processing and
calculation are mediated by a distributed network within the
parietal lobes (e.g., Fias et al., 2003; Gruber et al., 2001; Kong et al.,
2005; Menon et al., 2000a; Rickard et al., 2000; Venkatraman et al.,
2005). According to a highly influential model (e.g., Dehaene et al.,
2003; Dehaene and Cohen, 1997), three parietal circuits are
involved in number processing. One of these circuits (bilateral
horizontal intraparietal sulci) is thought to be domain-specific for
numerical processing; the other two (posterior parietal attention
system and left AG verbal system) are most probably shared with
other cognitive domains. The assumption that the intraparietal
sulcus (IPS) bilaterally is the crucial area for the representation of
quantities has been supported by a large number of neuroimaging
studies. Different paradigms have been used to assess the
representation of quantity, including number comparison tasks
(e.g., Chochon et al., 1999; Fias et al., 2003; Pesenti et al., 2000;
Pinel et al., 2001), discrete and analogue comparison tasks (Castelli
et al., 2006), or adaptation to quantities tasks (Cohen Kadosh et al.,
2007; Piazza et al., 2007). As regards calculation, the IPS is more
strongly activated in approximate calculation than in exact
calculation (e.g., Stanescu-Cosson et al., 2000), and more strongly
activated in subtraction than in multiplication (e.g., Chochon et al.,
1999; Kazui et al., 2000; Lee, 2000). The parietal circuit which relies
on the left AG is thought to mediate, among other functions, exact
and highly automated calculation such as the retrieval of multi-
plication facts from memory (e.g., 3  4 = ?; Chochon et al., 1999;
Duffau et al., 2002; Lee, 2000; but see Rickard et al., 2000). While
the AG is assumed to subserve skilled arithmetic fact retrieval, it
does not mediate quantity-based operations such as approxima-
tion, estimation or number comparison. The third parietal region
includes the superior parietal lobule and supports visuo-spatial
processes, attention and spatial working memory related to
numerical processing (Dehaene et al., 2003; Simon et al., 2002).
Evidence has been accumulated on the involvement of the IPS, AG
and superior parietal lobule in different aspects of numerical
processing. However, some assumptions of the triple-code model
have been controversially discussed. For example, not all authors
agree that the retrieval of arithmetic facts is mediated by verbal
processes (e.g., Zago et al., 2001). A recent topic of debate is
whether numbers or magnitudes are represented in the brain in
abstract form, i.e. independent from symbolic (Arabic numerals,
number words or other) or non-symbolic notation (e.g., dot-
patterns), as suggested by Dehaene et al. (1998). In a recent review,
Cohen Kadosh and Walsh (in press) challenge the view of abstract
numerical representations and discuss in detail evidence for non-
Fig. 1. Latency (a) and accuracy (b) of 17 young participants as a function of operation (multiplication, subtraction) and training session (days 1–5) (related functional results
are reported in Ischebeck et al., 2006). The contrast day 1 versus day 5 is significant for both operations at both latency and accuracy level, t-tests, all p < 0.0001.
911
abstract numerical representations mediated by specific neuronal
populations in the parietal lobes.
3. Imaging arithmetic learning
A crucial aspect in the acquisition of arithmetic expertise
consists in the shift from slow and effortful processing to skilled
and fast retrieval. Such a shift has been documented in several
developmental studies (e.g., Ashcraft, 1992; Barrouillet and Fayol,
1998; Fuson, 1982, 1988; Lemaire and Siegler, 1995; Siegler, 1988)
as well as in learning studies with adults (Anderson et al., 1999;
Logan, 1988; Logan and Klapp, 1991; Rickard, 2004; Wenger,
1999). Typically, developmental studies describe the acquisition of
arithmetic fact knowledge (such as 3  5 = 15), whereas studies
with adults also employ more complex paradigms. Recent
publications have documented how short-term, although inten-
sive training on arithmetic problems induces increases in accuracy
and speed that are accompanied by significant changes in brain
activation patterns (Delazer et al., 2003, 2005; Grabner et al., in
press; Ischebeck et al., 2006, 2007, 2009; Pauli et al., 1994). Fig. 1
depicts an example of improvements of response times and
accuracy over 5 days of intensive training on complex arithmetic
problems (e.g., 16  7 = ?; 45 27 = ?). As indicated by the trend
lines over the five sessions, the longer the training, the faster and
the more accurate the participants’ performance. Functionally,
acquisition of arithmetic proficiency is reflected by modifications
of cerebral activation patterns. Here below, we report the main
findings of these imaging studies on brain activation modifications
after arithmetic training.
3.1. Learning simple arithmetic
Pauli et al. (1994) focused their attention on the effects of
training on one-digit arithmetic problems and monitored the
evoked-related potentials (ERPs) responses of fourteen young
adults over four sessions of intensive practice. Results indicated a
decrease in response times with practice which was greater for
the problems with the larger operands (e.g., 8  7) than for the
problems with the smaller operands (e.g., 3  4). Changes in ERPs
were mainly characterized by reduction in fronto-central
positivity, while positivity in parietal sites remained relatively
stable over time for both problem sizes. Arithmetic processing
therefore correlated with a stable level of parietal activity all
along the training course; frontal activity diminished as a
function of increasing practice. Possibly, with repetition of the
problems, participants strengthened retrieval of the correct
solution from memory, while demands on processes such as
working memory, monitoring and attention sustained by frontal
areas diminished. To our knowledge, this was the first study
providing evidence that intensive practice of arithmetic leads to
significant modifications of brain activity.
912 L. Zamarian et al. / Neuroscience and Biobehavioral Reviews 33 (2009) 909–925
3.2. Learning complex arithmetic
Later studies used fMRI to trace training-related modifications
of brain activation (Delazer et al., 2003, 2005; Grabner et al., in
press; Ischebeck et al., 2006, 2007, 2009). In order to make sure
that the problems being trained are not known by heart, more
complex problems were used. The solution of a problem such as
23  8 is not commonly part of our declarative memory and thus
has to be calculated. This necessitates the application of sometimes
effortful, resource demanding and error-prone procedures, and
training should show marked effects at the behavioural level that
might be correlated with changes in brain activation patterns.
In the first study of this series (Delazer et al., 2003), young adults
were trained over 5 days on a set of complex multiplication
problems (e.g., 23  8 = ?). After training (day 5), participants
showed proficiency in solving the trained problems, which were
answered almost perfectly and more quickly than novel, untrained
problems of equal difficulty. Learning effects were also evident in the
imaging results. Untrained problems relative to trained problems
significantly activated the IPS, the inferior parietal lobule, and the
inferior frontal gyrus (all left lateralised). The reverse contrast
(trained versus untrained) indicated relatively stronger activation
within the left AG. These results were interpreted as suggestive of a
shift from quantity-based processing and complex procedures (e.g.,
23  8 = (20  8) + (3  8) = 160 + 24 = 184), relying on working
memory and executive control, to direct memory retrieval of the
correct solution (e.g., 23  8 = 184). Findings of this study agree with
the observation by Poldrack (2000) that learning is reflected by a
shift from general purpose processes to task-specific processes, in
this case to stronger reliance on arithmetic fact retrieval. In Fig. 2, we
propose a representation of this shift from frontal and intraparietal
areas to the left AG following intensive training and automated
retrieval of arithmetic memory associations.
3.3. Learning effects associated with different learning methods
Discussions on the effect of different learning methods have a
long tradition in educational psychology and cognitive psychology
(Brownell, 1935; Thorndike, 1922). Following a drill approach,
instructions focus on the rote memorization of computational
skills, i.e. arithmetic fact knowledge and arithmetic procedures
(Cowan, 2003). Children are taught bonds or associations between
unrelated stimuli and understanding is not necessary for the
formation of such bonds (Baroody, 2003). In this view, direct
instruction and drill are seen as efficient methods to ensure the
formation of arithmetic expertise. Other approaches put emphasis
on the understanding of basic principles and arithmetic relations,
and suggest that arithmetic fact knowledge should be acquired
gradually by procedures and strategies till the students build up a
set of memorized facts.
Fig. 2. Schematic illustration of the brain activations for the contrast untrained versus trained problems and the contrast trained versus untrained problems. Extended
activations in frontal and intraparietal areas are typically found in the contrast untrained versus trained problems. A relative activation of the left angular gyrus is found in the
contrast trained versus untrained problems.
Several studies have assessed the characteristics of fact acquisi-
tion such as processing speed, accuracy and strategy use in children
(e.g., Ashcraft, 1992; Lemaire and Siegler, 1995; Siegler, 1988),
healthy adults (e.g., Anderson et al., 1999; Logan, 1988; Logan and
Klapp, 1991; Rickard, 2004; Wenger, 1999) and dyscalculic
individuals (e.g., Domahs et al., 2003, 2008; Girelli et al., 2002;
Hittmair-Delazer et al., 1994; for a review, Domahs and Delazer,
2005). Some of these studies have also directly compared the effects
of different learning methods (e.g., Logan and Klapp, 1991; Domahs
et al., 2003). Brain imaging techniques allow the assessment of the
brain activation patterns associated with fact acquisition as well as
the comparison between the neural circuits recruited by different
learning methods. In Delazer et al.’s (2005) study, young adults were
intensively trained on two new arithmetic operations. One
operation – strategy condition – had to be learned by applying a
new algorithm (e.g., 3 § 12 = {[(12 3) + 1] + 12} = 22), the other
operation – drill condition – by memorising the operands-result
association (e.g., 4 # 15 = 24). Note that participants can only solve
new problems in the strategy condition where they are familiar with
the underlying algorithm. Hence, three conditions were compared in
the fMRI experiment, i.e. the two trained conditions (strategy and
drill) and a condition of new (strategy) problems. After training,
trained problems in both conditions were solved equally fast, and
new (strategy) problems were solved more slowly (Fig. 3). In the
fMRI results, stronger AG activation was observed for trained
strategy problems compared with new problems, replicating and
extending previous observations for training effects in multi-
plication (Delazer et al., 2003). This means that participants made
use of result retrieval in the strategy condition for the problems they
were familiar with through training. However, when both trained
conditions were compared with each other, greater left AG
activation was observed for the drill condition than for the strategy
condition, indicating that solution by result retrieval was more
dominant in the drill condition. The lesser activation of the left AG in
the strategy condition may be possibly related to the fact that
participants sometimes or simultaneously applied the algorithm
even in the case of trained problems they had learned by heart.
Results suggest that the way problems are trained makes a great
difference for the active involvement of brain areas necessary for
problem processing, although both types of training resulted in
problems being solved equally fast.
3.4. Learning effects specific to the learning content
To investigate whether training effects are comparable across
arithmetic operations, participants of a third study were provided
with the same training procedure, but had to learn two different
operations (complex multiplication: e.g., 15  7; complex sub-
traction: e.g., 43 26; Ischebeck et al., 2006). The triple-code
model (e.g., Dehaene et al., 2003; Dehaene and Cohen, 1997)
 L. Zamarian et al. / Neuroscience and Biobehavioral Reviews 33 (2009) 909–925 913

Fig. 3. Latency (a) and accuracy (b) of 16 young participants at post-training (day 5) as a function of learning method (by strategy, by drill) and problems’ type (trained,
untrained) (related functional data are reported in Delazer et al., 2005). In the behavioural post-training assessment (day 5) of the strategy condition, participants were asked
to solve the trained strategy problems (e.g., 3 § 12 = ? (= 22), known algorithm {[(b a) + 1] + b}) as well as new, untrained problems (e.g., 4 § 18 = ? (= 33)). In the assessment
of the drill condition, they were presented with the trained drill problems (e.g., 4 # 15 = ? (=24), unknown algorithm), but also with new problems (e.g., 5 # 12 = ? (=19)).
Obviously, participants could solve the new strategy problems by applying the learned algorithm, whereas with new drill problems they could only guess the answer. Overall,
untrained problems were answered more slowly and less accurately than trained problems, t-tests, all p < 0.05.

assumes that simple multiplication (e.g., 3  4) and simple
subtraction (e.g., 9 4) rely on different cognitive processes
supported by partially different cortical substrates. According to
this model, multiplication relies on skilled retrieval of arithmetic
facts from verbal long-term memory, whereas subtraction is
solved directly by manipulating the numerical representations of
the operands involved. Consequently, multiplication more strongly
activates the left AG, whereas subtraction relies more strongly on
the IPS bilaterally. Differences between operations may be due to
the method how simple multiplications and subtractions are
taught at school. However, they may also be due to differences
with regard to efficiency. Procedures and back-up strategies might
be the best and most simple way for addition and subtraction,
whereas they become very effortful for multiplication. In multi-
plication, a greater reliance on memorized results might be the
most efficient strategy. It is therefore a question of interest
whether comparable training on two different operations, multi-
plication and subtraction, would lead to similar or different
training effects. In Ischebeck et al.’s (2006) study, identical and
intensive training was provided for complex multiplication and
complex subtraction problems of similar difficulty. Post-training
results demonstrated a similar learning curve for both operations
(Fig. 1). The analysis of fMRI data, however, revealed systematic
differences in brain activation patterns between the trained
operations. While the left AG was significantly activated for
trained multiplication relative to untrained multiplication, no AG
activation was evident for trained subtraction relative to untrained
subtraction (Fig. 4). These operation-specific brain activation
changes after identical training are possibly associated with
differences between operations. Well-known complex multiplica-
tion problems are possibly more efficiently solved by memory
retrieval. By contrast, fast and effortless computation may still play
a role in the solution of well-known subtraction problems.
3.5. The trajectory of learning effects
In Ischebeck et al. (2007), the development of the learning
process itself was explored. Differently from previous studies, no
training was provided prior to the fMRI session. Participants were
presented in the scanner with two sets of complex multiplication
problems: one set had high frequency of repetition (‘repeated’), the
other set had low frequency of repetition (‘novel’). With passing
time in the scanner, problems’ repetition led to decreases in
activation within fronto-parietal areas and the caudate nucleus,
while relative activation increases were observed in temporo-
parietal regions including the left AG. These effects became
significant after approximately eight repetitions of a problem and
were, as a pattern, similar to previously reported experiments
where participants had to train much more intensively (Delazer
et al., 2003, 2005; Ischebeck et al., 2006). Findings of this study
suggest that learning-related brain activation modifications
appear very early during training and do not differ in principle
from brain activation changes observed after intensive training.
3.6. Transfer between operations
Successful transfer between related arithmetic operations is a
key feature of efficient arithmetic. The investigation of transfer
effects is important because only the flexible use of acquired
knowledge enables people to efficiently answer to new problems.
Also, rehabilitation cannot be considered to be successful if a
patient learns, for example, to retrieve arithmetic facts from
memory, but is unable to adapt this knowledge to new situations
(for discussions, Delazer, 2003; Lochy et al., 2005). While transfer
between operations has been assessed in experimental psychology
(e.g., Rickard, 2004, 2005) and in neuropsychological case studies
(Cipolotti and de Lacy Costello, 1995; Delazer et al., 2004;

Fig. 4. Contrasts between calculation conditions (training effect). The contrasts untrained versus trained multiplication/subtraction are shown in red, trained versus
untrained multiplication in green. The contrast trained versus untrained subtraction did not yield any significant activation. This illustration is part of a figure published in
Ischebeck et al. (2006), here reproduced with permission from Elsevierß.
914 L. Zamarian et al. / Neuroscience and Biobehavioral Reviews 33 (2009) 909–925
Hittmair-Delazer et al., 1994), only one study so far has
investigated this topic by brain imaging methods. Ischebeck
et al. (2009) were interested in the modifications of brain
activation patterns associated with transfer effects from newly
acquired multiplication knowledge (e.g., 46  3 = 138) to related
division problems (e.g., 138:3 = 46). Participants were trained on
complex multiplication problems and were presented in the
scanner with trained and new, untrained multiplication problems,
as well as with division problems that were either related or
unrelated to the trained multiplication problems. Replicating
previous findings (Delazer et al., 2003, 2005; Ischebeck et al., 2006,
2007), significant training effects appeared within the left AG for
multiplication. With regard to transfer, overall effects were
relatively weak, possibly due to strong inter-individual differences.
However, relatively greater activation within the left AG was
observed for related division problems than for unrelated pro-
blems. Also, there was a significant positive correlation between
activation in the left AG and the size of transfer effects in
behavioural performance at post-training. This study showed that
transfer, i.e. flexible access to stored knowledge, is reflected by
changes in brain activation patterns, but that individuals may
differ with regard to the presence or absence of transfer.
3.7. Specificity of training-related brain activation changes
Studies on short-term, intensive arithmetic training consis-
tently reported activation increases within the left AG in
association with acquisition of arithmetic knowledge (Delazer
et al., 2003, 2005; Ischebeck et al., 2006, 2007, 2009). These
activation increases were found to be more pronounced when the
type of arithmetic operation (Ischebeck et al., 2006) or the type of
training (Delazer et al., 2005) encouraged memory retrieval. It is,
however, unclear whether these effects are specific to the learning
of arithmetic facts or whether they also emerge in case of learning
of non-arithmetic facts. To address this issue, Grabner et al. (in
press) asked their participants to train on two types of problems,
complex multiplication problems (e.g., 14  7 = ?; from Ischebeck
et al., 2006) and complex figural-spatial problems (this study is
also described below because it also addressed whether compe-
tence-related activation differences may be attenuated by
intensive training). In the figural-spatial condition, drawings of
three-dimensional objects were presented and participants had to
determine the number of object faces. Similar training was
provided and identical improvements in speed and accuracy were
found for the arithmetic and figural-spatial conditions. Functional
data replicated results of previous studies for the arithmetic
condition (e.g., Delazer et al., 2003; Ischebeck et al., 2006), as the
contrast untrained versus trained multiplication problems showed
stronger activation in fronto-parietal regions including the inferior
frontal cortex and the IPS. The contrast trained versus untrained
multiplication problems indicated stronger activation within the
AG, bilaterally, with a peak of activation in the left AG. Results for
the figural-spatial condition considerably overlapped with the
network of brain activations found for multiplication. The contrast
untrained versus trained figural-spatial problems yielded bilateral
fronto-parietal activations; the contrast trained versus untrained
figural-spatial problems demonstrated an increase in activation
within the AG, bilaterally, with a peak of activation in the right AG.
This finding of similar training effects in both the arithmetic and
the non-arithmetic condition suggests that the training-related
activation increases in the AG are not specific to arithmetic fact
learning. Differently, it points to the involvement of the AG in more
general processes of fact learning. Recently, it has been proposed
(Ansari, 2008) that the AG is involved in general symbol-referent
mapping processes, such as mapping between arithmetic pro-
blems and their solutions, grapheme–phoneme mappings or
mapping between abstract numerical symbols and the magnitudes
they represent. Callan et al. (2005), for example, trained Japanese
participants on unknown phonograms and found that the
acquisition of new orthographic-phonological mappings was
related to activation increases within the left AG. Possibly, the
AG supports general fact retrieval processes and mapping
processes to stored information in memory, although its function
may slightly differ between the hemispheres (verbal: left AG;
figural: right AG; Grabner et al., in press). Damage to the left AG has
often been found in association with calculation deficits, finger
agnosia, left–right disorientation, writing or reading difficulties,
and impairment to this AG mapping function might underlie these
disturbances (Ansari, 2008).
4. The development of arithmetic
The most basic foundations of arithmetic emerge early in
childhood and preschool children can already present a remark-
able knowledge of arithmetic. This knowledge is grounded on
biological roots, experience and cultural influences. There is broad
consensus that ‘‘numbers’’ are represented as mental magnitudes
by a developmentally and evolutionarily universal system (Cantlon
et al., 2009). This assumption is based on evidence from cognitive
development, comparative cognition, cross-cultural cognition and
neurobiology (for a recent review, Cantlon et al., 2009). However, it
is under debate whether non-numerical magnitudes such as time,
size, ordinal position and brightness recruit the same neural
mechanisms as numerical magnitudes. It has been proposed that
time, space and quantity are processed by a common generalized
magnitude system (Walsh, 2003). These three dimensions would
be tightly linked since they represent critical magnitudes in the
external world that are used for action. In extension to this view,
Cantlon et al. (2009) emphasize that not only time, space and
quantity, but also other continuous dimensions, including size and
brightness, may share the same psychophysical signatures,
comparison processes and neural substrates.
Recent research converges on the view that the development
of arithmetic abilities is based on universal cerebral circuits
devoted to the processing of magnitudes or quantities (whether
domain specific or not). Remarkable capacities have been
demonstrated for young infants. It has been, for example, shown
that infants discriminate between small sets of objects that differ
in numerosity (e.g., Antell and Keating, 1983; Starkey et al., 1990;
Starkey and Cooper, 1980; Wynn et al., 2002; for a different view,
e.g., Mix et al., 2002a,b). They are able to represent and attend to
the numerosity of small sets of objects and seem able to carry out
basic mental manipulations on them. In a highly influential
study, Wynn (1992) reported that infants as young as 4–5
months have arithmetical expectations and detect manipulations
which violate arithmetic rules when a small number of items is
used (for an alternative view, e.g., Xu and Spelke, 2000). Through
education, children gradually acquire a better understanding of
numerosity and learn to understand and use counting principles
and counting sequences (Fuson, 1988, 1992; Gelman and Meck,
1983). Progressively, children acquire skills and expertise in
applying their counting skills to arithmetic (Fuson and Kwon,
1992). As in other domains, the acquisition of arithmetic
expertise is reflected by a shift from slow and effortful processing
to skilled and fast retrieval. While young children use time-
consuming step-by-step procedures (Ashcraft, 1992; Fuson,
1982, 1988), school age children show an increasing degree of
optimization (Barrouillet and Fayol, 1998; Lemaire and Siegler,
1995) and finally retrieve a set of arithmetic problems from
memory (note, however, that adults still often use strategies for
solving arithmetic problems; Campbell et al., 2004; Campbell
and Timm, 2000; Campbell and Xue, 2001; Geary et al., 1993;
 L. Zamarian et al. / Neuroscience and Biobehavioral Reviews 33 (2009) 909–925
Geary and Wiley, 1991; Kirk and Ashcraft, 2001; LeFevre et al.,
1996a,b; LeFevre and Morris, 1999).
Although rich evidence has been accumulated on the beha-
vioural characteristics of arithmetic development (e.g., Barth et al.,
2005; Canobi and Bethune, 2008; Gilmore et al., 2007; for reviews,
e.g., Bisanz et al., 2005; Buttherworth, 2005a), less is known about
the involvement of the neural structures supporting calculation in
different age groups. Developmental neuroimaging studies on
number processing in general have shown that children rely more
on prefrontal regions than adults, at least in tasks involving
numerical symbols such as digits (e.g., Kaufmann et al., 2006;
Kucian et al., 2008). With increasing age, however, distinct parietal
circuits, the bilateral IPS and the left temporo-parietal cortex, seem
to become more specialized for numerical-magnitude processing
and calculation (for a review, Ansari, 2008). Development of
numerical cognition is thus observed to be associated with
attenuation of activation in non-critical areas and more focal
activation in number-relevant areas. This is very similar to
observations of development in other domains (e.g., cognitive
control; e.g., Durston et al., 2006; Schlaggar et al., 2002; for a
discussion, e.g., Casey et al., 2005) and may indicate that
development is achieved through a fine-tuning of relevant neural
systems (for a discussion see, e.g., Durston and Casey, 2006).
To the best of our knowledge, only two studies so far have
investigated developmental changes in mental arithmetic with
fMRI (Kawashima et al., 2004; Rivera et al., 2005). The first study
assessed age-related differences in activation patterns related to
mental arithmetic in a group of seventeen participants (8–19
years; Rivera et al., 2005). Participants were asked to verify simple
addition and subtraction equations of the type ‘‘4 + 2 = 6?’’ and
‘‘7 3 = 4?’’, a task where children and adolescents performed
with high accuracy. An increase in brain activation in correlation
with age was found in the left supramarginal gyrus and anterior
IPS, as well as in the left lateral temporo-occipital cortex. A
decrease in activation was observed in frontal brain areas, in sub-
cortical structures (basal ganglia and thalamus), in the brainstem
and the left medial temporal lobe. Findings were similar to those of
young adults where trained arithmetic problems were compared
with untrained problems (Delazer et al., 2003, 2005; Grabner et al.,
in press; Ischebeck et al., 2006, 2007, 2009; see also Pauli et al.,
1994). Both lines of research show that growing expertise or age is
related to a greater involvement of specific parietal areas and to a
decrease of reliance on general-purpose (frontal) areas. Of course,
both types of studies, namely, learning studies with adults and
studies assessing developmental changes in children, are not fully
comparable although they indicate similar results. In children,
learning and brain maturation simultaneously contribute to the
activation pattern changes observed (e.g., Durston and Casey,
2006).
Results of a second fMRI study (Kawashima et al., 2004) are also
suggestive of a functional specialization within the parietal cortex
with age. Kawashima et al. (2004) compared a group of eight
children with a group of eight middle-aged adults (age range 9–14
and 40–49, respectively). Participants were instructed to mentally
solve single-digit addition, subtraction and multiplication pro-
blems while in the scanner (e.g., ‘‘3 + 5 = ?’’, ‘‘7 2 = ?’’, and
‘‘4  8 = ?’’). A pattern of bilaterally distributed activations in
frontal and intraparietal areas, as well as in temporo-occipital
areas was revealed for the adults. Children showed similar results,
although adults showed stronger activation within the IPS,
bilaterally, for most mental arithmetic tasks. Increased involve-
ment of parietal areas in mental calculation with age further
stresses the relevance of these brain areas for numerical processing
and the acquisition of calculation skills.
Beside development, language and culture might also have an
influence on the involvement of the brain areas underlying number
915
processing. Tang et al. (2006) compared native English and Chinese
speakers on a series of visual and numerical tasks, and found
significant group differences in terms of brain activation and
functional connectivity in addition and number comparison tasks
with Arabic digits. In the case of the Chinese speakers, numerical
processing seemed to rely more on visuo-motor association
networks. English speakers recruited left perisylvian areas to a
greater extent. Language and culture might have affected the
neural substrates underlying mental arithmetic and numerical-
magnitude processing. As Tang et al. (2006) proposed, however,
these results must not only have been caused by language, but also
by reading experience and cultural differences in learning
strategies and in the education system. Cultural effects on
functional brain organization are also not specific to the number
domain and have been documented for other cognitive domains as
well such as, for example, object processing (e.g., Goh et al., 2007;
Kobayashi et al., 2007; Paulesu et al., 2000).
5. The neural basis of expertise in arithmetic
While psychological research aims at revealing the modifica-
tions of cognitive processes related to extensive training and
expertise (Anderson et al., 1999; Logan, 1988; Logan and Klapp,
1991; Rickard, 2004; Wenger, 1999), neuroimaging studies focus
on the cerebral correlates of expert processing such as, for
example, Braille readers (e.g., Pascual-Leone and Torres, 1993),
musicians (e.g., Elbert et al., 1995; Pantev et al., 1998), or
sommeliers (Castriota-Scanderberg et al., 2005). In a positron
emission tomography (PET) study by Pesenti et al. (2001), a
calculation expert (R. Gamm) was scanned while doing complex
mental arithmetic. Gamm had memorized arithmetic facts and
calculation algorithms for several hours per day over several years.
Using his impressive knowledge of arithmetic problems and the
episodic encoding-retrieval strategies he has developed on his
own, Gamm was, for example, able to retrieve from long-term
memory the square of two-digit numbers (e.g., 732) or to quickly
and accurately compute complex multiplication problems (e.g.,
76  82; for a description of the behavioural investigation see
Pesenti et al., 1999). The comparison of Gamm’s activation pattern
with that of non-expert controls revealed some similarities, but
also activation foci specific for the expert. In the conjunction
analysis of computation- versus memory-based problems, Gamm
and non-expert controls showed bilateral cerebral activation, with
a left-sided predominance. Activations were, for example,
observed in the supramarginal gyrus, the IPS, the inferior occipital
and middle occipital gyri, the occipito-temporal junction, as well as
in frontal areas (for details, Pesenti et al., 2001, or Appendix of the
present review). Differently from non-expert controls, activations
specific for Gamm were observed in the medial frontal gyrus, the
parahippocampal gyrus, the anterior cingulate gyrus and the
middle occipito-temporal junction (all right sided), as well as in the
left paracentral lobule. Thus, the expert’s and the non-experts’
calculation performance relied on brain areas which are typically
involved in visuo-spatial working memory, visual imagery and
numerical processing. However, Gamm seemed to also employ
brain areas associated with episodic memory processes that might
be related to his use of specific encoding-retrieval strategies during
calculation. High-level cognitive expertise in calculation appeared
thus not to be limited to the improvement of existing processing
networks, but to involve the recruitment of new processes and
cerebral areas (Pesenti et al., 2001).
A further example that calculation expertise might be bound to
the use of specific strategies relying on distinct cerebral circuits is
reported by Hanakawa et al. (2003) in an fMRI study on skilled
abacus users. Abacus experts are not only extremely efficient in
using the tool in its physical form, but also gain the ability to
916 L. Zamarian et al. / Neuroscience and Biobehavioral Reviews 33 (2009) 909–925
mentally calculate extraordinarily large numbers with unusual
speed and accuracy (Stigler, 1984). Qualified Japanese abacus
masters with the highest degree for both mental calculation and
abacus operations were compared with non-experts in a series of
mental-operation tasks requiring the manipulation of numerical,
spatial or verbal material (Hanakawa et al., 2003). In the numerical
task, experts perfectly performed one-digit and three-digit number
additions (100% accuracy), and scored with six-digit number
additions as accurately as non-experts in the one-digit number
condition. No relevant group differences were detected in spatial
or verbal tasks, whereas the numerical condition yielded
significant activation differences. Both groups showed activation
in the superior precentral sulcus, the posterior parietal cortex
including the IPS, the fusiform gyrus and the cerebellum. However,
this activation pattern was bilaterally symmetrical in the abacus
experts, while it was strongly left lateralised in the non-experts.
Additional significant activation differences included stronger
activations within the posterior superior parietal cortex/precuneus
for the experts, and stronger activations in the prefrontal cortex
and lateral parietal cortex for the non-experts. In sum, abacus
masters showed a greater involvement of brain areas mediating
visuo-spatial and visuo-motor processing, a finding that possibly
reflects their main strategy use during complex mental calculation
(Hanakawa et al., 2003). Similarly to Pesenti et al. (2001), experts’
and non-experts’ mental calculation partially relied on common
neural correlates, but the experts also showed evidence of
employing additional cerebral areas related to the specific strategy
being used. Differently from the short-term training studies that
mainly found a modulation of activation in the cerebral networks
commonly involved in mental arithmetic, the studies with high-
performing individuals and extensive training over several years
indicate activation of different areas, pointing to the recruitment of
strategies that are very different from those used by non-experts.
Type of adopted strategy and extent of training may thus play a
crucial role in the modification of brain activations.
6. Inter-individual differences in arithmetic
Inter-individual differences in brain activation have not only
been observed between non-experts and exceptional experts, but
have also been reported for less-exceptional or normal users of
arithmetic. Menon et al. (2000b) compared a group of perfect
performers (accuracy of 100%) with a group of non-perfect
performers (mean accuracy of 92%, S.D. 6.2%) on an arithmetic
verification task with simple addition and subtraction (e.g.,
‘‘4 + 2 1 = 4?’’). Perfect performers were also faster than non-
perfect performers. With regard to brain activation, proportionally
fewer activated voxels were observed within the left AG for perfect
performers compared with non-perfect performers. The authors
concluded that greater arithmetic proficiency leads to greater
functional optimization within the left AG and thus to less
activation. However, it should be noted that this result is partly
inconsistent with findings from other studies on mathematical
competence and brain activation (see below Grabner et al., 2007, in
press), as well as from learning studies that observed an increase of
activation within the left AG due to practice, rather than a decrease.
The assumption of a U-shaped curve of activation change within
the left AG has thus been so far not well supported. It is also
possible that group effects in Menon et al.’s (2000b) study mirror
the use of different solution strategies. A problem such as
‘‘4 + 2 1 = 4?’’ can be quickly and accurately answered by
applying plausibility strategies, which have been often described
in verification paradigms (e.g., Lemaire and Reder, 1999; Lochy
et al., 2000). If verification strategies were efficiently used by
perfect performers, while non-perfect performers predominantly
relied on calculation procedures and memory retrieval of
calculation sub-results, then enhanced activation within the left
AG should be found for non-perfect performers relative to perfect
performers. Differences between perfect and non-perfect perfor-
mers in Menon et al.’s (2000b) study may thus be associated, to
some extent, with differences in the participants’ reliance on
calculation and memory retrieval: the higher the reliance on these
processes, the stronger the activation within the left AG.
Similarly to Menon et al. (2000b), Grabner et al. (2007) aimed at
exploring the relationship between mathematical competence and
brain activation in normally performing individuals. In order to
ensure that results could be generalized beyond the specific
demands of the experimental tasks, the participants’ groups were
formed on the basis of performance on standardised psychometric
tests of intelligence and arithmetic competence. Groups of
participants with high and low mathematical competence differed
in both mathematical-numerical intelligence tests and experimen-
tal multiplication tasks (simple condition: one-digit times one-digit;
complex condition: two-digit times one-digit), but not with respect
to verbal and figural-spatial intelligence. Individuals with low
mathematical competence performed the experimental multi-
plication tasks less accurately and slower than individuals with
high competence. This was particularly evident in the complex
condition (e.g., 13  7 = 91) relative to the simple condition (e.g.,
4  6 = 24). For high-achieving individuals compared with low-
achieving individuals, higher activation was observed within the AG,
the middle temporal gyrus, the supplementary motor area and the
medial superior frontal gyrus (all left lateralised). The reverse
contrast (low versus high) did not reveal any significant foci of
activation. Also, activation within the left AG was positively
correlated with the individual level of mathematical competence.
In sum, performance of the mathematically more competent
individuals was supported by a network involving the left AG to a
stronger extent than the less competent individuals’.
These findings were replicated and extended in a second study
by Grabner et al. (in press), where more competent individuals and
less competent individuals intensively practiced on complex
multiplication problems following the same training procedure
as in Ischebeck et al. (2006). Behaviourally, the more competent
individuals outperformed the less competent individuals during
the entire training as well as with the untrained multiplication
problems in the fMRI test session. In the functional results, a
stronger activation within the left AG was found for the more
competent participants relative to the less competent participants
with the untrained multiplication problems. Also, this activation
significantly and positively correlated with the individual level of
mathematical competence, replicating the results of Grabner et al.
(2007). No group difference, however, emerged for the trained
multiplication problems. As the authors suggested, these findings
may reflect, on the one side, that the more competent individuals
more strongly relied on fact retrieval processes with untrained
multiplication problems and, on the other side, that gaining of
mathematical expertise led to attenuation of the competence-
related activation difference within the left AG. This attenuation
resulted from stronger increase of the left AG activation for the less
competent individuals following intensive training.
7. Structural brain changes due to learning
It has been observed that structural lesions to parietal areas may
lead to severe arithmetic deficits (e.g., Berger, 1926; Henschen, 1919,
1920; Lewandowsky and Stadelman, 1908) and that decrease in
parietal gray matter density in premature born children is associated
with lower maths performance at the age of 15 years (Isaacs et al.,
2001). While there is ample evidence that damage to the parietal
areas leads to arithmetic deficits, little is known whether training of
arithmetic processing leads to modifications of the brain structure.
 L. Zamarian et al. / Neuroscience and Biobehavioral Reviews 33 (2009) 909–925
Several morphometric studies have shown that experience can alter
the anatomical structure of the human brain, such as, for example,
the gray matter density. Broad evidence has come in particular from
sensorimotor research (e.g., Draganski et al., 2004, 2006; Münte
et al., 2002; Pantev et al., 1998; Pascual-Leone and Torres, 1993), but
recent investigations have also observed structural changes of the
human brain after cognitive training (e.g., Aydin et al., 2007; Maguire
et al., 2000, 2003; Mechelli et al., 2004). For example, learning a
second language was found to modify the gray matter density in the
left inferior parietal cortex (Mechelli et al., 2004). It was also shown
that the amount of this change is directly proportional to the
individual’s performance improvement and to the age of acquisition.
Aydin et al. (2007) addressed the issue of experience-related
structural brain changes in a group of academic mathematicians,
hypothesizing that the extensive and persistent training in
mathematical thinking the mathematicians undergo for several
years should result in specific regional changes in their brains. This
is, to our knowledge, the only study on structural brain changes after
long-lasting and extensive training in mathematics. Significantly
higher gray matter densities were observed in mathematicians than
in non-mathematicians within the inferior parietal lobule, bilat-
erally, and in the left inferior frontal gyrus. Also, the period of time
spent as a mathematician significantly correlated with relative gray
matter density increase in the right parietal lobule. Long-term and
intense practice in mathematics seems thus to lead to anatomical
changes in those brain areas that have been previously shown to be
related to numerical processing, arithmetic calculation and visuo-
spatial processing.
8. Rehabilitation of arithmetic skills in patients
A brain lesion that disrupts number processing and calculation
abilities can clearly compromise a person’s autonomy. Impair-
ments of arithmetic fact retrieval are frequently observed after left
hemispheric brain damage, often in association with aphasic
disorders (e.g., Delazer et al., 1999; Delazer and Bartha, 2001;
Domahs et al., 2008; Domahs and Delazer, 2005; Grafman et al.,
1982; McCloskey et al., 1991). Nonetheless, acquired arithmetic
deficits are often overlooked and targeted rehabilitation pro-
grammes are rare (for overviews, Girelli and Seron, 2001; Lochy
et al., 2005). Most studies on the rehabilitation of simple
calculation skills have used a drill-based approach, i.e. extensive
repetition of problems accompanied by immediate feedback (for a
discussion, e.g., Lochy et al., 2005), but conceptual approaches have
been described as well (Domahs et al., 2003; Girelli et al., 2002). So
far, only one study explored how the remediation of simple
arithmetic skills through rehabilitation may change brain activa-
tion patterns. Zaunmüller et al. (in press) scanned a patient with a
left-hemispheric brain lesion using fMRI before and after
rehabilitation. Rehabilitation consisted of training on multiplica-
tion facts. At post-training, the contrast trained versus untrained
problems evidenced an increase in activation within the right AG,
that means in the hemisphere contralateral to the lesion and
contralateral to the typical activation reported for healthy
individuals (e.g., Delazer et al., 2003). A homologue area in the
right hemisphere, contralateral to the lesion, was thus increasingly
recruited in arithmetic fact retrieval after rehabilitation. This
interesting finding can only be interpreted with caution. Results of
single-case fMRI studies may be difficult to replicate because of the
large variability between single patients with regard to a number
of variables, such as lesion location, lesion extension, aetiology,
associated deficits, spontaneous recovery and neuro-functional
reorganization. Furthermore, there is considerable inter-individual
variability in the healthy adults’ arithmetic performance (e.g.,
Grabner et al., 2007; Menon et al., 2000b), and differences in
performance as well as in the level of education or of general
917
intelligence (e.g., Kelly et al., 2006) may have an influence on the
effects of practice on the brain.
9. Methodological considerations
We would like to briefly address some methodological aspects
of functional brain imaging results that may be particularly
important for the interpretation of arithmetic learning studies. One
problem with fMRI results is their sensitivity to task difficulty.
Stronger fronto-parietal activation in more difficult arithmetic
conditions might be related to general difficulty effects rather than
to specific demands on the brain areas essential for numerical
processing. In general, more difficult tasks activate fronto-parietal
areas more strongly than easier tasks, which are associated with
faster response times and higher accuracy. This is important for the
interpretation of results of learning studies, as trained problems or
tasks are usually solved faster and more accurately than untrained
and unfamiliar problems or tasks. A specific interpretation of
stronger fronto-parietal activation with regard to numerical
processing has therefore to be motivated by concurring evidence
or by direct contrasts with other non-numerical tasks. In
neuroimaging research and from patient studies, much indepen-
dent evidence has been accumulated in recent years for a specific
role of the IPS in numerical and arithmetic processing. Contrasts
between numerical and non-numerical tasks also support this
interpretation (e.g., Eger et al., 2003), but in most experiments a
suitable non-numerical control condition cannot be constructed,
due to either a lack of comparability or to time limitations.
A second problem with fMRI research is the absence of an
absolute baseline. In general, activation foci shown and reported in
fMRI studies always have to originate from comparisons between
conditions. These are, for example, two active conditions of
interest that differ with regard to their demands on cognitive
resources, or an active and a resting condition (baseline). The
problem in the result interpretation is that there is usually no
direct information about the activation pattern of each single
condition. It should be noted that a comparison to baseline does
not solve this problem, as the resting brain is not well understood.
There are brain areas that are more active during the resting state
than in conditions where the participants have to perform a
demanding task (e.g., McKiernan et al., 2003; Raichle and Snyder,
2007; Stark and Squire, 2001; Tomasi et al., 2006). It has been
argued that, as the participants are idle during resting, the
activations observed in the precuneus and in left hemisphere
regions are due to conceptual as well as semantic and linguistic
processing (Binder et al., 1999). During easier tasks, the individuals
might have more time to indulge in these baseline activities than in
more difficult tasks (Poldrack, 2000).
When two active conditions are compared, it is usually
assumed that the activations resulting from this subtraction are
positive relative to a resting baseline. However, due to the baseline
problem outlined above, stronger activations observed for a low
difficulty task relative to a high difficulty task might also reflect a
lesser degree of deactivation for the easier task. This consideration
is important in the case of arithmetic learning studies, where the
appearance of a new activation within the left AG is usually
interpreted as evidence for a new cognitive process and for
functional reorganization (Kelly et al., 2006; Poldrack, 2000). As
the AG is one of the regions within the brain that are often observed
to be deactivated during task performance, the observed activation
could be unspecifically related to a decrease of task difficulty due to
learning. A specific interpretation of this activation difference with
regard to arithmetic processing has therefore to be additionally
motivated, either by showing that this area is more active during
arithmetic processing than during baseline, or by demonstrating a
specific task-related modulation of the activation difference. In the
918 L. Zamarian et al. / Neuroscience and Biobehavioral Reviews 33 (2009) 909–925
training studies on arithmetic, such a specificity has been observed
even when controlling for task difficulty. For example, the
activation within the left AG was stronger the more the type of
task (Ischebeck et al., 2006) or the type of training (Delazer et al.,
2005) encouraged fact retrieval from long-term memory.
10. Summary and discussion
The present paper reviewed evidence on the functional and
structural changes in the human brain that have been found in
relation to experience and practice with arithmetic processing. One
of the key findings is that, in children and in adults, the gain of
arithmetic expertise is characterized by a shift in activation from
fronto-parietal networks to specific parietal areas. This shift
indicates a change in the cognitive processes involved in task
performance following practice, although in the case of children
some of the changes observed might also be due to brain maturation.
Practice leads to a decrease in activation in frontal brain areas. These
areas sustain general-purpose processes such as working memory
and attention control, and are likely to be involved in non-
automatised and complex calculation. Practice also leads to a
relative increase in activation within the left AG. The AG is thought to
mediate, among other functions, memory retrieval of fact knowl-
edge, possibly unspecific with regard to content or knowledge
domain. Activation changes within the left AG seem to appear
already very early in the course of practice. A further finding is that
people with average calculation skills build expertise upon a pre-
existing cerebral network involved in arithmetic processing, as
inter-individual arithmetic performance differences are observed to
modulate activation within this network such as, for example, in the
left AG. The proficiency of expert individuals is, however, a different
matter. Calculation prodigies and abacus masters seem to recruit
other cognitive processes and cerebral areas. Although only few such
individuals have been investigated on a case-by-case basis, the
differences observed might be related to the very specific strategies
used by the experts.
Most of the studies reviewed here show a consistent pattern of
brain areas that are employed in mental calculation. These areas
are the IPS, bilaterally, for manipulation of quantity representa-
tions, the left AG for the retrieval of memorized facts from long-
term memory, and frontal brain areas for the demands on
performance monitoring and working memory, especially in
complex calculation. Findings of the developmental and training
studies fit well with this interpretation, as development and
training modify activation in these brain areas consistently with
their assumed specific function in calculation. As calculation
becomes more automatic in children, monitoring and working
memory demands decrease, which is reflected in a decrease of
activation within frontal brain areas. Similarly, in the training
studies with healthy young adults, the activation decrease within
fronto-intraparietal areas and the relative activation increase
within the left AG reflect a shift from calculation to result retrieval
from memory. Also, studies investigating inter-individual differ-
ences observe that in particular activation within the left AG
correlates positively with mathematical competence and not with
general intelligence. These studies all contribute to provide a
consistent picture of the brain areas involved in learning
arithmetic in people with average calculation skills.
The neuroimaging studies reviewed here offer first insights into
the functional and structural brain correlates of the acquisition of
arithmetic skills, and further issues remain to be addressed.
Training studies may, for example, investigate through morpho-
metric analysis whether intensive, but short-term practice results
in specific structural modifications of the brain areas involved in
numeric processing as was found for expert individuals with
extensive mathematical experience over several years (Aydin et al.,
2007). Also, it has not been investigated yet whether changes in
brain activation patterns following arithmetic training are stable
over time and whether they are modulated by the frequency of
practice. The issue as to whether arithmetic training effects on the
human brain are similar or different across the lifespan may be
explored, for example, by comparing individuals from different age
ranges (e.g., children vs. young adults vs. old adults) in brain
activation patterns that are found to be related to the solution of
trained and untrained problems. Investigating thoroughly how, for
example, the level of competence, the use of specific strategies or
the type of learning method specifically affects brain activation
patterns may help highlighting ways for improving teaching and
training programmes, as well as rehabilitation.
Over the past decade, the progress of neuroimaging methods
has greatly increased our knowledge about the functional and
structural changes in the learning brain. This has led to a significant
increase in the public interest in neuroscience (OECD, 2007b) as it
has raised hopes for significant improvements in the current
education systems and teaching methods. Teachers are highly
interested in exploiting the insights of neuroscience for the benefit
of their students. However, high expectations and lack of under-
standing have also led to neuroimaging findings to be overly
simplified and misunderstood (Goswami, 2006). As Goswami
(2006) points out, most advertised brain-based programmes are
even unlikely to work in the long term so that many may naturally
fall out of use. At present, researchers agree that simple one-to-one
applications of neuroscience findings to the class room cannot
work. Neuroscience has only entered the first stage of research and
is yet far from yielding solid evidence on how education can be
made more efficient.
Neuroscience research uses paradigms, concepts and constructs
which have been developed in cognitive psychology, neuropsy-
chology, or developmental and educational psychology, adding
new information by directly investigating changes in the brain due
to learning. With this, neuroscience is firmly grounded in the solid
theoretical and empirical basis created over decades of research in
the behavioural sciences. For example, the transition from
calculation strategies to arithmetic fact retrieval has been
investigated intensively in developmental psychology (Ashcraft,
1992; Barrouillet and Fayol, 1998; Lemaire and Siegler, 1995;
Siegler, 1988) and in cognitive psychology (Anderson et al., 1999;
Logan, 1988; Logan and Klapp, 1991; Rickard, 2004; Wenger,
1999). For centuries (e.g., Thorndike, 1922), there has been a
debate whether more emphasis should be put on learning by drill
or on learning by strategies in the acquisition of new arithmetic
facts. Neuroscience may contribute to the debate by showing that
different neural circuits are involved in the retrieval of arithmetic
facts as a result of the previous training strategy. Neuroscience also
shows that additional brain areas may be recruited depending on
expertise and strategy choice.
Neuroscience research alone, however, cannot develop pro-
grammes for successful teaching and cannot create learning
environments to students. Only as one part of an inter-disciplinary
work-force can neuroscience play an important role (Stern, 2005).
In the present review, we have highlighted how neuroscience
enhances our understanding of the learning brain. With other
researchers (Ansari and Coch, 2006; Goswami, 2006), we agree that
a close collaboration of neuroscience and education may lead in the
future to improved teaching and intervention.
Acknowledgements
The first author has been supported by Austrian Science Fund
(FWF) Grant P18896-B05 and by Medizinische Forschungsförder-
ung Innsbruck (MFI) Grant PDO-Nr. 12880 (2007-419). The authors
thank Ž. Stević for providing the figures and illustrations.
 L. Zamarian et al. / Neuroscience and Biobehavioral Reviews 33 (2009) 909–925 919

Appendix A

Main results of the revised papers with regard to brain activation/structural changes in relation to number processing are listed here below
(for more details, see the original paper works). Abbreviations: AG = angular gyrus; IFG = inferior frontal gyrus; IPS = intraparietal sulcus;
IOG = inferior occipital gyrus; IPG = inferior parietal gyrus; ITG = inferior temporal gyrus; MFG = middle frontal gyrus; MOG = middle occipital
gyrus; MTG = middle temporal gyrus; SFG = superior frontal gyrus; SMA = supplemental motor area; SMG = supramarginal gyrus;
SOG = superior occipital gyrus; SPG = superior parietal gyrus; STG = superior temporal gyrus.
Region Left hemisphere Right hemisphere

x y z k x y z k

Aydin et al. (2007) (VBM) (p < 0.0001 uncorrected; extent of cluster size I100)
Mathematicians vs. controls (increase in gray matter)
IFG S42 S34 12
Inferior parietal lobule S38 S50 57
Inferior parietal lobule 32 S46 60
Inferior parietal lobule 54 S58 38
Inferior parietal lobule 57 S60 34

Correlation between gray matter density and time spent as a mathematician (r = 0.84, p < 0.01)
Inferior parietal lobule 57 S60 34

Delazer et al. (2003) (fMRI) (block-related analysis; random effect analysis; one-sample t-test; p < 0.001 uncorrected; extent of cluster size >15)
Contrast complex multiplication untrained vs. trained
IFG S50 6 20 32
Inferior parietal lobule S64 S24 24 21
Sylvian fissure S62 S36 20 32
IPS S20 S56 56 43
Lingual gyrus S8 S84 0 35

Contrast complex multiplication trained vs. untrained

ITG S46 S12 S32 20
Paracentral lobule S24 S20 48 17 14 S12 44 81
Cingulate gyrus S12 S44 24 39
Cingulate gyrus S22 S44 32 43
Cerebellum S22 S58 S32 111 14 S52 S36 26
AG S46 S60 24 47

Delazer et al. (2005) (fMRI) (event-related analysis; fixed effect analysis; p < 0.001 uncorrected) (coordinates transformed in Talairach and Tournoux (1988) space)a
Contrast strategy untrained vs. trained
IFG S32 19 S5 377
MFG S28 6 48 110
MFG, IFG 40 2 37 957
Parietal lobe, IPS (bilateral) 24 S64 40 727
Cerebellum S4 S79 S22 91 44 S52 S23 68

Contrast strategy trained vs. untrained

Medial aspect of frontal lobe (bilateral) 12 54 S6 144
Hippocampal gyrus 24 S9 S18 34
MTG 59 S12 S10 53
STG extending to AG S51 S15 8 184
Precuneus 8 S49 25 104
AG extending to STG 59 S50 17 75

Contrast strategy vs. drill

IFG 36 35 S9 54
Cingulate gyrus (bilateral) S12 35 6 127
Precuneus extending to cuneus (bilateral) 4 S65 18 425

Contrast drill vs. strategy

SFG, medial aspect of frontal lobe (bilateral) S16 56 27 853
IFG S55 32 13 78
Precuneus extending laterally to left AG (bilateral) S8 S68 40 593

Grabner et al. (2007) (fMRI) (block design; random effect analysis)

Contrast multi-digit vs. single digit (whole participant group) (p < 0.01 corrected)
IFG S48 36 28 27
Insula S28 26 S4 494 30 30 S2 437
Middle cingulate gyrus S10 16 44 114 10 26 36 116
IFG, Precentral gyrus S46 8 30 183
MFG S26 S2 54 161
Thalamus S10 S22 12 37 24 S28 6 92
IPG S36 S42 44 727 38 S46 42 85
Cerebellum S42 S66 S30 154 36 S68 S26 280
Calcarine cortex 0 S70 10 69
Vermis, left cerebellum 0 S74 S24 394

Contrast single-digit vs. multi-digit (whole participant group) (p < 0.01 corrected)
AG S58 S64 32 24
920 L. Zamarian et al. / Neuroscience and Biobehavioral Reviews 33 (2009) 909–925

Appendix A (Continued )
Region Left hemisphere Right hemisphere

x y z k x y z k

Contrast higher vs. lower mathematical competence (p < 0.00001 uncorrected)

Medial SFG S6 54 34 27
SMA S10 18 56 24
MTG S50 S54 16 56
AG S52 S64 28 45

Contrast lower vs. higher mathematical competence (p < 0.00001 uncorrected)

n.s.

Correlation between activation and mathematical–numerical intelligence (r = 0.63, p < 0.001)

AG S50 S64 28 82

Grabner et al. (in press) (fMRI) (block design; random effect analysis; p < 0.05 corrected)
Contrast complex multiplication untrained vs. trained
MFG 45 33 21 80
SMA S6 12 48 165
IFG S45 6 27 207 51 9 27 94
SFG 30 3 63 47
Insula S27 24 3 89 30 24 3 139
Pons, left thalamus 9 S21 S18 74
SPG, SMG, IPG 27 S69 54 219
SPG, IPG S27 S57 48 292
ITG S54 S60 S12 62
Cerebellum S27 S57 S36 30
Cerebellum S36 S69 S27 32
Cerebellum (bilateral) S6 S75 S30 249
MOG S21 S87 12 32

Contrast complex multiplication trained vs. untrained

Middle cingulum S3 S42 36 36
AG S60 S48 39 126 57 S57 24 75

Contrast complex figural-spatial untrained vs. trained

IFG, precentral gyrus S51 30 27 319
IFG 48 33 30 189
Insula S27 21 6 41 30 21 3 84
SMA S9 12 48 72
Precentral gyrus 51 6 27 168
MFG, precentral gyrus S27 0 57 109
SFG 24 S3 54 137
Right SMG, right SPG, left SPG, left IPG 42 S36 42 4100

Contrast complex figural-spatial trained vs. untrained

Precuneus S3 S63 24 129
AG S54 S66 33 64 54 S57 24 99

Hanakawa et al. (2003) (fMRI) (conjunction analysis; p < 0.05 corrected)

Contrast numerical mental-operation task vs. visual fixation task (abacus experts)
Frontal operculum S48 6 28 73 50 10 36 13
Superior precentral sulcus S32 S6 52 34 24 S6 54 103
IPS 42 S52 56 363
Fusiform gyrus S52 S62 S16 8
Precuneus extending to the IPS S18 S66 60 1311
Precuneus 14 S66 64 60
Cerebellar hemisphere S36 S74 S28 14 40 S74 S24 10
Cerebellar vermis 6 S76 S30 11

Contrast numerical mental-operation task vs. visual fixation task (non-experts)

Prefrontal cortex S52 34 16 97
Anterior cingulate cortex extending to medial frontal gyrus 4 14 45 191
Superior precentral sulcus extending to BA 44 S32 0 54 704
Superior precentral sulcus 34 0 54 86
Fusiform gyrus S48 S58 S12 19
Precuneus extending to lateral parietal area and IPS S24 S62 56 810
Cerebellar hemisphere S38 S62 S30 211 30 S63 S32 677

Contrast experts vs. non-experts in the numerical mental-operation task

Posterior superior parietal cortex S22 S62 58 12

Number-size effect for abacus experts

Frontal operculum S48 6 28
Superior precentral sulcus S28 S4 46 24 S4 50
IPS S34 S52 56 40 S58 56
Fusiform gyrus S46 S62 S18
Posterior superior parietal cortex/precuneus S18 S66 60 14 S66 64

Ischebeck et al. (2006) (fMRI) (event-related analysis; random effect analysis; initial threshold: p < 0.001 uncorrected, p < 0.05 corrected on cluster level)
Contrast multiplication untrained vs. trained
 L. Zamarian et al. / Neuroscience and Biobehavioral Reviews 33 (2009) 909–925 921

Appendix A (Continued )
Region Left hemisphere Right hemisphere

x y z k x y z k

SMA S3 9 51 79
Precentral gyrus, IFG S51 6 S27 164
Thalamus, Caudate S18 S21 15 39
IPS, AG 42 S45 45 104
IPS S33 S66 39 72

Contrast multiplication trained vs. untrained

AG S48 S66 39 51

Contrast subtraction untrained vs. trained

Insula, IFG S33 21 S3 183
Precentral gyrus, IFG 48 6 33 83
IPS S42 S39 39 154
IPS, AG 24 S63 51 35

Contrast subtraction trained vs. untrained

n.s.

Contrast multiplication trained vs. subtraction trained

n.s.
Contrast subtraction trained vs. multiplication trained
IOG, Fusiform gyrus 42 S69 S12 27
Precuneus, SOG 12 S69 45 96
Calcarine gyrus, Cuneus S12 S75 15 31

Contrast multiplication untrained vs. subtraction untrained

n.s.

Contrast subtraction untrained vs. multiplication untrained

MOG, SOG S33 S78 24 127
Lingual gyrus, SOG, Calcarine gyrus S18 S81 S9 287

Ischebeck et al. (2007) (fMRI) (event-related analysis; random effect analysis; initial threshold: p < 0.001 uncorrected, p < 0.05 corrected on cluster level)
Contrast novel vs. repeated (1st third of the experiment)
Anterior cingulate, SMA S6 15 39 60
Caudate 15 6 12 57

Contrast repeated vs. novel (1st third of the experiment)

n.s.
Contrast novel vs. repeated (2nd third of the experiment)
Precentral gyrus, IFG S48 3 30 65
MOG 30 S87 15 80

Contrast repeated vs. novel (2nd third of the experiment)

SMG, AG 51 S45 33 34
AG S39 S66 45 62

Contrast novel vs. repeated (3rd third of the experiment)

IFG, Precentral gyrus S45 9 24 82
Putamen S18 6 0 76

Contrast repeated vs. novel (3rd third of the experiment)

Postcentral gyrus 21 S39 63 48
SMG, STG, AG 63 S48 30 36
AG S45 S60 33 142

Ischebeck et al. (2009) (fMRI) (block-related analysis; random effect analysis; initial threshold: p < 0.001 uncorrected, p < 0.05 corrected on cluster level)
Contrast multiplication untrained vs. trained
Insula S24 18 3 1615b 30 30 6 163
IFG S42 9 24 1615
MFG S30 6 57 1615 45 39 15 58
MFG, SFG 30 9 57 110
b
SMA S6 S15 51 1615
b
Caudate S18 S3 18 110 18 3 21 110
Thalamus 24 S30 6 42
Postcentral gyrus, Inferior parietal lobule 48 S33 51 60
Superior parietal lobule, Inferior parietal lobule S24 S57 51 2557
Superior parietal lobule, SOG 24 S63 63 671
Superior parietal lobule 18 S69 51 671b
b
IOG S33 S69 S6 2557
b
MOG S30 S69 30 2557
MOG S21 S87 3 2557b

Contrast multiplication trained vs. untrained

Posterior cingulate gyrus, Precuneus S9 S48 33 274
AG S45 S69 45 120

Contrast division unrelated vs. related

n.s.
922 L. Zamarian et al. / Neuroscience and Biobehavioral Reviews 33 (2009) 909–925

Appendix A (Continued )
Region Left hemisphere Right hemisphere

x y z k x y z k

Contrast division related vs. unrelated

n.s.

Correlation between activation and the behavioral transfer index for trained multiplication (r = 0.60, p < 0.05) and related division (5 = 0.50, p < 0.05)
AG S45 S69 45

Kawashima et al. (2004) (fMRI) (block design; random effect analysis; p < 0.001 uncorrected; p < 0.05 corrected)
Adult group: addition vs. fixation point
Middle frontal S38 6 26 54 10 42
Inferior frontal S38 0 S2
Supplementary motor 4 S2 66
Premotor S22 S6 52
Inferior temporal S42 S62 S22 40 S54 S26
Intraparietal S32 S60 52
Lateral occipital S20 S94 0 28 S94 0

Adult group: subtraction vs. fixation point

Middle frontal S42 6 28
Supplementary motor S6 S4 72
Intraparietal S30 S58 48 34 S46 40
Inferior temporal S40 S78 S8 46 S62 S12
Lateral occipital S34 S92 2 30 S90 S4

Adult group: multiplication vs. fixation point

Middle frontal 52 44 12
Middle frontal S54 16 24 48 8 30
Inferior frontal S22 22 S2
Intraparietal S32 S50 44 22 S64 50
Inferior temporal S46 S76 S10 36 S58 S24
Lateral occipital S18 S92 S8 32 S86 S4

Children group: addition vs. fixation point

Middle frontal S42 16 22
Supplementary motor 0 12 46
Inferior temporal S48 S60 S18 46 S54 S36
Lateral occipital S20 S102 8 24 S100 6

Children group: subtraction vs. fixation point

Middle frontal S46 12 30
Inferior temporal S52 S52 S12 36 S50 34
Intraparietal 38 S56 52
Lateral occipital S18 S102 6 24 S94 6

Children group: multiplication vs. fixation point

Inferior frontal S36 32 4
Middle frontal S50 8 32
Inferior temporal S38 S86 8 46 S58 S24
Lateral occipital S34 S88 8 24 S98 4

Menon et al. (2000b) (short communication; no coordinates are reported)

Pesenti et al. (2001) (PET) (conjunction analysis; p = 0.001 uncorrected)

Contrast calculation vs. memory retrieval (in both prodigy and non-experts)
Inferior frontal sulcus S46 30 22 42 36 26
MFG S32 8 54
Precentral sulcus, Inferior frontal sulcus S38 2 26
SMG S52 S40 46 42 S40 50
Inferior occipito-temporal junction S52 S52 S24
IOG, MOG S50 S60 S14 54 S60 S10
IPS S22 S68 48 22 S70 54
IPS, intraoccipital sulcus S28 S84 22

Contrast calculation vs. memory retrieval (prodigy vs. non-experts)

Anterior cingulate gyrus 4 46 30
MFG 14 26 56
Parahippocampal gyrus 18 8 S44
Paracentral lobule S12 S34 68
Middle occipito-temporal junction 60 S52 S4

Rivera et al. (2005) (fMRI) (block design; random effect analysis; p < 0.01 uncorrected; p < 0.05 corrected)
Positive correlation between activation
and age
SMG, IPS S51 S37 46 292
Lateral occipital-temporal cortex, including S53 S68 7 431
IOG and MOG, ITG and MTG
 L. Zamarian et al. / Neuroscience and Biobehavioral Reviews 33 (2009) 909–925
Appendix A (Continued )
Region Left hemisphere
x y
Negative correlation between activation and age
SFG and MFG (bilateral), left IFG, left SMA, S16
left anterior cingulate cortex
Insula, frontal operculum S32
Basal ganglia including thalamus S10
(bilateral)
Brainstem (bilateral) S10
Medial temporal lobe including hippocampus, S32
parahippocampal gyrus, fusiform gyrus
k = cluster size (voxel); n.s. = not significant
a
Brett et al. (2001).
b
Activation is part of a bigger cluster.
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