e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y 2 2 ( 2 0 1 8 ) 3 2 1 e3 2 6

Official Journal of the European Paediatric Neurology Society

Review article

The neuropsychology of basal ganglia

Daria Riva*, Matilde Taddei, Sara Bulgheroni

Developmental Neurology Division, Fondazione IRCCS Istituto Neurologico C. Besta, Via Celoria 11, 20133, Milan,
Italy

abstract

Keywords: Basal ganglia are subcortical structures specialized at very early age, functionally different
Basal ganglia according to the right or left side. They are part of complex distributed network composed
Neuropsychology by parallel segregated loops where specific information are processed and open loops
Movement where different information are integrated. These loops are connected to specialized
Cognition cortical areas thus entering into distributed processing of higher order cognitive functions
Behaviour and behaviours. Lesion or malfunction of basal ganglia nuclei cause deficits in different
neuropsychological functions and neurobehavioural diseases, such Autism Spectrum
Disorder, Attention Deficit/Hyperactivity Disorder, Tourette syndrome, etc., for the recip-
rocal connections from and to the limbic system and the frontal system. Basal ganglia have
a computational functioning, working by activation and inhibition sequences, coded in
time and space and regulated by inhibitory and excitatory mechanisms, with such accu-
racy to guarantee an effective and elegant product.
© 2018 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights
reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 322
2. Neuropsychological deficits in disorders after lesions of BG . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 323
2.1. Language . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 323
2.2. Spatial Neglect . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 323
2.3. Memory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 324
2.4. Executive functions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 324
3. Neurodevelopmental disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 324
3.1. Autism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 324
3.2. Attention Deficit/Hyperactivity Disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 324
3.3. Tourette's syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325
4. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325
Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325

* Corresponding author.
E-mail address: daria.riva@istituto-besta.it (D. Riva).
https://doi.org/10.1016/j.ejpn.2018.01.009
1090-3798/© 2018 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
322 e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y 2 2 ( 2 0 1 8 ) 3 2 1 e3 2 6
1. Introduction
Basal Ganglia (BG) are involved not only into motor
sequencing, motor skills and complex actions, but also in the
modulation of higher order cognitive functions, mood regu-
lation and non-motor complex behaviours that need to pro-
cess and integrate different types of information. These
evidences stems from the clinical experience with patients
with movement disorders that also show associated symp-
toms both in emotional and cognitive-neuropsychological
domain, and from anatomical and functional imaging that
show how BG are activated together with other cortical re-
gions in complex non-motor tasks. There are also BG diseases
that cause only neuropsychological and neurocognitive defi-
cits without movement disorder.1e3
The aforementioned evidences demonstrate how BG are
implicated in the processing of higher cognitive functions as
first defined by Alexander,1,4,5 then resumed by other
authors.6e8
These functions are the ultimate product of complex op-
erations possible underlined by associative connections be-
tween BG and sensorimotor cortexes. These areas are highly
specialized, work synergistically (every area is always aware
of what's happening in another area) thanks to a high degree
of connectivity, guaranteed by complex networks widely
distributed throughout the brain.9
The brain organization in large scale circuits is active very
early in childhood and develops from more elementary net-
works, connecting only sensorimotor areas, to very complex
circuits connecting several brain regions, mainly with asso-
ciative or multimodal role, able to integrate stimuli by
different modalities. There is converging evidence suggesting
that by age 7e9 children manifest a similar type of functional
architecture and organization as adults, at least at a whole-
brain level.10 The mathematical models derived from the
Graph Theory11 and confirmed by neuroimaging studies
describe how the brain works as a single entity thanks to its
high connectivity, but maintaining strong local specialization.
Inter-regional connectivity is organized in small-world to-
pology, i.e. distributed networks interconnect different areas,
some of which are more specialized in processing a specific
part of the function. The brain is organized in tightly clustered
sub-networks and combined with a high level of local and
global connectivity. This model supports: a) segregation and
super-specialization, b) extended distributed information
processing but integrated and c) economics and efficiency.12
The distributed language system is a good example of
networking which conjugates high specialization and inte-
grated information processing. In the right handers it is more
represented on the left hemisphere, but with an extended
distribution throughout the two hemispheres. A lesion at any
point in the network causes a language disorder, but the
severity of the disorder is higher when the lesion involves
super-specialized areas the so-called hubs. For example, a
lesion in the Broca area will cause a major language disorder
than possible injury in areas defined as 'minor' or
‘provincial’.13
The functional organization of the BG formulated in the
1980s was based on the concept that neuronal signals from
the cortex flow to the striatum, through the Globus Pallidus
and Substantia Nigra pars reticulata, and project back to the
cortex via the thalamus, forming parallel corticoebasal gan-
gliaethalamoecortical loops. Although the model was pri-
marily formulated to understand the pathophysiology of
movement, the existence of parallel circuits subserving oculo-
motor control, executive functions, and emotions was also
recognized.9 Growing experimental and clinical evidence
supports that the cortico-basal ganglia-thalamo-cortical loops
proceed along parallel circuits linking cortical and subcortical
regions subserving the processing of sensorimotor, associa-
tive and affective tasks.14
Thus the BG role is to participate in complex circuits that
are in strong connection with different areas of the cerebral
cortex, from which they collect information and to which after
a local processing they re-sent through the output nuclei,
Thalamus and Substantia Nigra. Highly-segregated circuits
process information from specific cortical areas before pro-
jecting back to their cortical original regions. Thus each loops
appear to be involved in distinct behavioural functions.8
There are two distinct pathways that process signals
through the BG: the direct and the indirect pathways which
have opposite effects on thalamic target structures. The
exciting indirect pathway inhibits thalamic neurons
rendering them unable to excite motor cortex neurons. The
normal BG functioning apparently involves a proper balance
between the activity of these two pathways.7 One hypothesis
is that the direct pathway selectively facilitates certain motor
or cognitive programs in the cerebral cortex that are adaptive
for the present task, whereas the indirect pathway simulta-
neously inhibits the execution of competing motor programs.
An upset of the balance between the direct and indirect
pathways results in the motor dysfunctions that characterize
the extrapyramidal syndrome. If the inhibition prevails, the
prototypic disease is the Huntington Disease, while the prev-
alence of the indirect pathway causes diseases like Parkin-
son's disease.
BG intervene in regulating the balance between inhibitory
and excitatory effects by inhibiting motor sequences that do
not serve in the reference, or that may be interfering, allowing
an elegant and effective end product. At the cortical level, the
information goes through the input structures (Caudate, Pu-
tamen and Ventral Striatum), and then arrive at the output
structures that reverberate in the thalamus to return back to
the cortex (Internal Globus Pallidus, and Substantia Nigra pars
reticulata). Transferring this mode of operation to cognitive,
relational and emotional functions permits to understand
how the main role of the BG, also in this context, is to
modulate a balance to reach an harmonious and smooth
behaviour.
The organization of the BG system is based on striatal af-
ferents coming from all the cortices organized in three distinct
pathways. The premotor, motor, and somatosensory cortices
in the frontal lobe project mostly to the postcommissural
putamen where a somatotopic representation of the leg, arm,
and face occurs in the form of obliquely arranged strips. The
caudate nucleus and precommissural putamen receive pro-
jections, mostly unilateral, from association areas of the pre-
frontal, temporal, parietal, and cingulate cortices, and motor
areas in the frontal lobe that control eye movements. The
 e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y 2 2 ( 2 0 1 8 ) 3 2 1 e3 2 6
afferents from limbic cortical areas as well as from the
amygdala and the hippocampus terminate preferentially in
the ventral portion of the striatum.15
The cortical motor oculomotor, dorso-lateral prefrontal,
orbitofrontal and limbic areas, sends and receives afferences,
demonstrating how the brain works through segregated loops
that ensure specialization. Haber and colleagues studied the
organization of thalamic connections between cortex and BG,
in particular the striatum, in the Macaque monkey and
showed how connections make it possible for multiple stimuli
to coexist, i.e. the striatum is organized as small associative
areas that act as integrators of different stimuli.16e18
The integration of the information is ensured by the exis-
tence of open loops coupled with the specialized processing,
which is ensured by the specialization of the typical circuit of
that particular structure. The presence of distinct cortico-
striatal connections that are organized as multiple circuits
has been confirmed by Diffusion Tensor Imagingebased fibre
tracking studies, showing that the posterior (sensorimotor),
anterior (associative), and ventral (limbic) compartments of
the human striatum have specific connections with the cor-
tex, and particularly the frontal lobes.19
In particular, there is evidence that a strict topographic
segregation is maintained during the processing of sensori-
motor information flowing from cortical motor areas to the
sensorimotor areas of the BG. The output from the BG to the
motor thalamus, which projects back to neocortical motor
areas, is also organized into topographically segregated
channels. This high degree of topographic segregation is
demonstrated by the presence of a well-defined somatotopic
organization in the sensorimotor areas of the BG. The pres-
ence of body maps in the BG has become clinically relevant
with the increasing use of surgical procedures, such as
lesioning or deep brain stimulation, which are selectively
aimed at restricted subcortical targets in the sensorimotor
loop such as the subthalamic nucleus or the globus pallidus
pars interna.14
2. Neuropsychological deficits in disorders
after lesions of BG
We discuss the neuropsychological deficits in acquired dis-
orders caused by BG lesions and then neurodevelopmental
disorders characterized by BG dis-function. Neuropsycholog-
ical and behavioural deficit concerning movement disorders
are described in the relative chapters.
2.1. Language
Alexander,1,4 one of the earliest supporters of the BG
involvement in the processing of higher cognitive functions,
distinguishes various types of aphasia in relation to lesion
localization in BG. Lesion in the motor loop (Putamen, genu
Corpus Callosum) cause speech disorder as dysarthria or
anarthria, injuries in the motor initiation loop (fibres from the
pre-frontal cortex, cingulate lap, supplementary motor area)
result in mutism, hypokinesia and hypophonia, finally the
involvement of Broca or Wernicke areas may lead to Broca or
Wernicke aphasia characterized by impaired word retrieval or
323
language comprehension. In children subcortical aphasia
presents variable symptoms in relation to the cortex con-
nections, but there are always speech motor disorders, prob-
ably because BG participate in the motor repetition at the base
of language learning.
The case reports of subcortical aphasia are few. Aram and
colleagues20 described some patients with subcortical aphasia
identifying in all speech disorders and good recovery in short
time. Martins and Ferro21 studied subjects with Broca aphasia,
transcortical aphasia and anomic aphasia while Paquier22
collected from different series patients with Broca aphasia,
sensori aphasia, and fluent aphasia.
We have evaluated ourselves 14 children, a mean of 10
years after BG acquired stroke, we didn't find diverse clinical
aphasic pictures in relation to lesion side localization, but
persistent deficit in phonological fluency (group mean z score
-1.7) (personal data).
The authors also assessed hemiplegic children with left
unilateral congenital lesions involving or not BG, using the
dichotic listening task to evaluate hemispheric language
lateralization.23 The main result is the shift of the language
phonological coding to the right hemisphere was strong
correlated with lesion size and involvement of BG, in partic-
ular the Thalamus.
In language process, BG not only acts as a computational
part in complex circuits, but also participate in the application
of rules, such as allow the ability to combine morphems to
form complex words and declarative verbs.24e26 Teichmann
et al.27 confirmed that the left Striatum participates not only in
processing lexicon in language and arithmetic (i.e. to give the
right name to things and numbers), but also in processing
morphological and syntactic combinatorial rules. An internal
topography is also described: the ventral part of the left
striatum would process the rule-based mechanisms, while
the dorsal part would be involved in lexical procedures.
2.2. Spatial Neglect
Spatial neglect is lateralized disorder of space processing. The
disorder is more common in patients with a right injury and is
characterized by the difficulty/inability to explore the space
contralateral to the lesion and to react to stimuli located in
this hemispace. According to the Mesulam's model,28 the
spatial attention processing is lateralized predominantly in
the right hemisphere. Little is observed but little is sought in
children: the improvement evolution after the acute phase is
very fast making difficult to detect deficits, but the evaluation
of children at distance from the injury, showed that the deficit
contralateral to the lesion emerged when both Putamen,
Pulvinar and Caudate were involved, confirming the crucial
BG role in spatial attention also in childhood.29e31 We also
studied 24 children with unilateral congenital lesion of which
14 with involvement of BG (7 right) and we found that only
children with lesion including Putamen and Pulvinar showed
attentional deficit, but not neglect, in the hemispace contra-
lateral to the lesion either left or right (personal data). Puta-
men and Pulvinar (and to a lesser extent Caudate and
Thalamus) are connected to the Superior Temporal Gyrus
entering into the coherent and distributed cortical-subcortical
network generating spatial neglect.32
324 e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y 2 2 ( 2 0 1 8 ) 3 2 1 e3 2 6
2.3. Memory
Memory is another function whose processing involves BG.
There are no systematic studies in children. The majority of
memory data result from the comparison of adult populations
mainly with Huntington and Alzheimer diseases. Memory is a
highly complex system with a macro-distinction between
short-term and long-term memory.33 Within the long-term
memory there are the implicit memories of which we have
no consciousness, and the explicit memories, which require a
conscious processing to be recalled. BG enter the circuit of
non-cognitive memories, while cognitive memories involve
the parietal lobe and temporal-mesial structures such as
hippocampal and para-hippocampal regions, entorhinal cor-
tex and part of Amigdala. Patients with Alzheimer's have
explicit memory deficits (lexicon, semantic and narrative
verbs), while Huntington Disease patients have implicit
memory impairment (motor skill learning).34e37
The BG also play a critical role in memory-guided motor
planning and movement sequencing. Menon and colleagues38
used a motor sequencing task to investigate the differential
role of BG nuclei in memory-guided movement in normal
subjects. Significant fMRI activation was observed in the
Dorso-Lateral Pre-Frontal Cortex and posterior putamen and
globus pallidus. Their results showed that, during memory-
guided movement, the posterior putamen and globus pal-
lidus play a role in maintenance of representations in working
memory and contribute to planning and temporal organiza-
tion of motor sequencing.38
2.4. Executive functions
Executive functions are a set of cognitive functions to achieve
a specific goal with simultaneous control and integration of a
set of cognitive operations to achieve the intended goal in the
most economical and efficient way possible. They are inter-
ested in emotions, motivations, strategy planning and prob-
lem solving, monitoring, rapid attention shift, necessary when
the strategy is being implemented and the execution of the
action.
It has always been thought that the prefrontal dorsolateral
cortex governs executive functions, but the discovery of
mirror neurons and associative function of the cerebellum
make the issue more complex. It has been shown that the
Nucleus Dentate of the Cerebellum projects to the Striatum
which in turn projects to the frontal lobe. The programming of
executive functions no longer seems to be top-down process,
but it would be a snapshot of all its functions (thinking and
doing would be the same, without the action there would be
no thought). Such structures would be able to anticipate and
do the same action at the same time.39,40
3. Neurodevelopmental disorders
The connections between the BG and limbic and pre-frontal
cortices are very interesting, because their malfunction is
the basis of very dramatic neuropsychiatric disorders, char-
acterized not only by motor disorders but also by severe
behavioural and neuropsychological symptoms.
The anatomy and connections of the BG indicate that
these structures are important links between parts of the
brain that have classically been considered to be related to
emotional functioning and brain regions previously consid-
ered to have largely motor functions. The BG have a role in
the development and integration of motor functions, mem-
ory and attention, and reward processes. Also in processing
complex behaviours the cortexes project first to the striatum,
then to the Pallidus and return to the cortex through the
thalamus. The projections are specific: the Cingulatus Gyrus
participates to the process of motivational mechanisms and
sustained attention, projecting to specific regions of the
striatum; the orbital frontal cortex participates to the process
of empathy, social relationships, and the ability to under-
stand a context and infer others' behaviour (theory of mind);
the dorsolateral prefrontal cortex that participates in the
executive functions (as well as the Cingulum that manages
the motivation), i.e. the ability to achieve a goal by imple-
menting mechanisms that must necessarily be controlled
synchronously, project to the striatum and back to the cor-
texes of origin.
Disturbed BG function may result in abnormal activation of
the frontal lobes and thalamus, via dorsal lateral prefrontal
and orbitofrontal circuits, leading to their overlapping clinical
characteristics.
3.1. Autism
Autism is a neurodevelopmental disorder characterized by
impaired social interaction, verbal and non-verbal commu-
nication, and restricted and repetitive behaviour. The ritu-
alistic and repetitive mechanisms, encompasses a broad
range of symptoms including motor mannerisms, unusual
preoccupations and interests and extreme rigidity. This
behaviour involves the BG. The size of the nuclei can be
decreased41 or increased as demonstrated by Rojas et al.42
who found that the severity of repetitive and stereotyped
behaviour was associated with a significant increase (8%) of
caudate nucleus.
3.2. Attention Deficit/Hyperactivity Disorder
Attention Deficit/Hyperactivity Disorder (ADHD), is a chronic
condition marked by persistent inattention, hyperactivity,
and sometimes impulsivity. Convergent data from neuro-
imaging, neuropsychology, genetics and neurochemical
studies consistently point to the involvement of the frontos-
triatal network as a likely contributor to the pathophysiology
of ADHD. This network involves the lateral prefrontal cortex,
the dorsal anterior cingulate cortex, the caudate nucleus and
putamen.43
In ADHD children there is an atypical activation of the
frontal lobe and the thalamus.44,45 Volumetric studies have
demonstrated an alteration of hyper or hypo-density of the
structures involved.43,46,47
Along with prefrontal regions, the caudate nucleus and its
associated circuits have long been implicated in ADHD.48 Re-
searchers have shown both volumetric and asymmetry dif-
ferences in the caudate between ADHD and control groups,
even if these findings have not been consistent across
 e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y 2 2 ( 2 0 1 8 ) 3 2 1 e3 2 6
studies.47 Moreover, findings suggest that regional brain vol-
umes are associated with greater ADHD symptom severity.
For example Castellanos and collaborators49 found frontal and
temporal grey, caudate, and cerebellar volumes to be signifi-
cantly correlated with global clinician ratings and parent rat-
ings of child attention problems.
3.3. Tourette's syndrome
Tourette's syndrome is another very complex disorder with
onset in childhood,50 characterized by multiple motor tics
and at least one vocal (phonic) tic. Among the most severe
cases, attention deficit hyperactivity disorder and obsessive
compulsive disorder are present at higher rates. These co-
occurring diagnoses often cause more impairment to the
individual than the tics. While the exact cause is unknown, it
is believed to involve a combination of genetic and envi-
ronmental factors. The malfunctioning of fronto-striatal
circuit is a consistent finding;2,51 specifically, volumetric
studies showed decreased Caudate Nucleus volumes across
adults and children, whereas the volumes of the putamen
and the globus pallidus are decreased primarily in adults.52
Although the BG connections are widely distributed in the
two hemispheres, BG seem to be functionally different ac-
cording to the involvement of the right or left side.53e55 In our
clinical practise we observed a child with a pilocytic astrocy-
toma of the right BG who showed a perfect language, but a
cognitive behavioural phenotype characterized by disruptive
hyperactivity, a major disturbance of attention with
obsessive-compulsive behaviours and coprolalia, and deficit
in all non-verbal visual-spatial tests. This asymmetry between
verbal and non-verbal performance has already emerged in
the Wechsler Scales' profile with good Verbal versus poor
Performance IQ. Furthermore we observed a child with a
stroke in the left caudate nucleus, who showed in the acute
phase a transcortical aphasia which improved rapidly, but
with persistent deficits in semantic and phonemic fluency
over time.
4. Conclusions
BG are subcortical structures specialized at very early age,
functionally different according to the right or left side. The
network may be viewed as multiple parallel loops and re-
entering circuits whereby motor, associative, and limbic ter-
ritories are engaged mainly in the control of movement,
behaviour, and emotions. These loops have reciprocal con-
nections with specialized cortical areas and thus entering into
distributed and segregated networks underlying specific
complex functions and behaviours. There are internal spe-
cializations and internal integration areas between different
loops.
Their lesion o malfunction cause deficits in different
functions, such as language (aphasia), implicit memory,
spatial attention and executive functions.
Alexander and colleagues1,4,5 suggest that the BG have a
computational role where each component is part of complex
and widely distributed neural segregated and open circuits.
They work through activation and inhibition sequences,
325
coded in time and space and regulated by inhibitory and
excitatory transmitter mechanisms, with such precision to
ensure an effective and harmonious final product.
Conflict of interest
The authors declare that there are no known conflicts of in-
terest associated with this publication and there has been no
significant financial support for this work that could have
influenced its outcome.
references
1. Alexander GE, DeLong MR, Strick PL. Parallel organization of
functionally segregated circuits linking basal ganglia and
cortex. Annu Rev Neurosci 1986;9:357e81.
2. Leisman G, Melillo R. The basal ganglia: motor and cognitive
relationships in a clinical neurobehavioral context. Rev
Neurosci 2013;24:9e25.
3. Leisman G, Melillo R, Carrick FR. Clinical motor and cognitive
neurobehavioral relationships in the basal ganglia. In:
Barrios FA, Bauer C, editors. Basal ganglia-an integrative view.
InTech; 2013.
4. Alexander GE. Basal ganglia-thalamocortical circuits: their
role in control of movements. J Clin Neurophysiol
1994;11:420e31.
5. Alexander GE, Crutcher MD. Functional architecture of basal
ganglia circuits: neural substrates of parallel processing.
Trends Neurosci 1990;13:266e71.
ger J. Updating the functional model of the basal ganglia.
6. Fe
Trends Neurosci 1997;20:152e3.
7. Middleton FA, Strick PL. Basal ganglia and cerebellar loops:
motor and cognitive circuits. Brain Res Rev 2000;31:236e50.
8. Middleton FA, Strick PL. Anatomical evidence for cerebellar
and basal ganglia involvement in higher cognitive function.
Science 1994;266:458e61.
9. Lanciego JL, Luquin N, Obeso JA. Functional neuroanatomy of
the basal ganglia. Cold Spring Harb Perspectives Med 2012;2,
a009621.
10. Uddin LQ, Supekar K, Menon V. Typical and atypical
development of functional human brain networks: insights
from resting-state FMRI. Front Syst Neurosci 2010;4.
11. Bondy A, Murty MR. Graph theory. London: Springer-Verlag;
2008.
12. Gerloff C, Hallett M. Big news from small world networks
after stroke. Brain 2010;133:952e5.
13. Bernal B, Ardila A. The role of the arcuate fasciculus in
conduction aphasia. Brain 2009;132:2309e16.
14. Romanelli P, Esposito V, Schaal DW, Heit G. Somatotopy in
the basal ganglia: experimental and clinical evidence for
segregated sensorimotor channels. Brain Res Rev
2005;48:112e28.
15. Charara A, Sidibe  M, Smith Y. Basal ganglia circuitry and
synaptic connectivity. In: Tarsy D, Vitek JL, Lozano AM,
editors. Surgical treatment of Parkinson's disease and other
movement disorders. New York: Humana Press; 2003.
p. 19e39.
16. McFarland NR, Haber SN. Convergent inputs from thalamic
motor nuclei and frontal cortical areas to the dorsal striatum
in the primate. J Neurosci 2000;20:3798e813.
17. Haber SN, Fudge JL, McFarland NR. Striatonigrostriatal
pathways in primates form an ascending spiral from the shell
to the dorsolateral striatum. J Neurosci 2000;20:2369e82.
326 e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y 2 2 ( 2 0 1 8 ) 3 2 1 e3 2 6
18. McFarland NR, Haber SN. Thalamic relay nuclei of the basal
ganglia form both reciprocal and nonreciprocal cortical
connections, linking multiple frontal cortical areas. J Neurosci
2002;22:8117e32.
19. Lehe ricy S, Ducros M, De Moortele V, et al. Diffusion tensor
fiber tracking shows distinct corticostriatal circuits in
humans. Ann Neurol 2004;55:522e9.
20. Aram DM, Rose DF, Rekate HL, Whitaker HA. Acquired
capsular/striatal aphasia in childhood. Arch Neurol
1983;40:614e7.
21. Martins IP, Ferro JM. Acquired childhood aphasia: a
clinicoradiological study of 11 stroke patients. Aphasiology
1993;7:489e95.
22. Paquier PF. Aphasia in children with basal ganglia lesions. In:
Riva D, Njiokiktjien C, editors. Brain lesion localization and
developmental functions: basal ganglia, connecting systems,
cerebellum, mirror neurons. John Libbey Eurotext; 2010.
p. 17e24.
23. Bulgheroni S, Nichelli F, Erbetta A, Bagnasco I, Riva D. Verbal
dichotic listening and manual performance in children with
congenital unilateral brain lesions. Neuropsychology
2004;18:748e55.
24. Ullman MT. The declarative/procedural model of lexicon and
grammar. J Psycholinguist Res 2001;30:37e69.
25. Ullman MT. Contributions of memory circuits to language:
the declarative/procedural model. Cognition 2004;92:231e70.
26. Pinker S, Ullman MT. The past and future of the past tense.
Trends Cogn Sci 2002;6:456e63.
27. Teichmann M, Gaura V, De monet JF, et al. Language
processing within the striatum: evidence from a PET
correlation study in Huntington's disease. Brain
2008;131:1046e56.
28. Mesulam MM. Spatial attention and neglect: parietal, frontal
and cingulate contributions to the mental representation and
attentional targeting of salient extrapersonal events. Philos
Trans R Soc Lond B Biol Sci 1999;354:1325e46.
29. Ferro JM, Martins IP, Ta vora L. Neglect in children. Ann Neurol
1984;15:281e4.
30. Billingsley RL, Lang FF, Slopis JM, Schrimsher GW, Ater JL,
Moore III BD. Visualespatial neglect in a child following sub-
cortical tumor resection. Dev Med Child Neurol
2002;44:191e200.
31. Laurent-Vannier A, Pradat-Diehl P, Chevignard M, Abada G,
De Agostini M. Spatial and motor neglect in children.
Neurology 2003;60:202e7.
32. Halligan PW, Fink GR, Marshall JC, Vallar G. Spatial cognition:
evidence from visual neglect. Trends Cogn Sci 2003;7:125e33.
33. Squire LR. The organization and neural substrates of human
memory. Int J Neurol 1987;21:218e22.
34. Heindel WC, Salmon DP, Shults CW, Walicke PA, Butters N.
Neuropsychological evidence for multiple implicit memory
systems: a comparison of Alzheimer's, Huntington's, and
Parkinson's disease patients. J Neurosci 1989;9:582e7.
35. Deweer B, Ergis AM, Fossati P, et al. Explicit memory,
procedural learning and lexical priming in Alzheimer's
disease. Cortex 1994;30:113e26.
36. Knopman D, Nissen MJ. Procedural learning is impaired in
Huntington's disease: evidence from the serial reaction time
task. Neuropsychologia 1991;29:245e54.
37. Peavy G, Jacobs D, Salmon DP, et al. Verbal memory
performance of patients with human immunodeficiency
virus infection: evidence of subcortical dysfunction. J Clin Exp
Neuropsychol 1994;16:508e23.
38. Menon V, Anagnoson RT, Glover GH, Pfefferbaum A. Basal
ganglia involvement in memory-guided movement
sequencing. Neuroreport 2000;11:3641e5.
39. Makris N, Schlerf JE, Hodge SM, et al. MRI-based surface-
assisted parcellation of human cerebellar cortex: an
anatomically specified method with estimate of reliability.
Neuroimage 2005;25:1146e60.
40. Jissendi P, Baudry S, Baleriaux D. Diffusion tensor imaging
(DTI) and tractography of the cerebellar projections to
prefrontal and posterior parietal cortices: a study at 3T. J
Neuroradiol 2008;35:42e50.
41. Estes A, Shaw DW, Sparks BF, et al. Basal ganglia
morphometry and repetitive behavior in young children with
autism spectrum disorder. Autism Res 2011;4:212e20.
42. Rojas DC, Peterson E, Winterrowd E, et al. Regional gray
matter volumetric changes in autism associated with social
and repetitive behavior symptoms. BMC Psychiatr 2006;6:56.
43. Emond V, Joyal C, Poissant H. Structural and functional
neuroanatomy of attention-deficit hyperactivity disorder
(ADHD). L'encephale 2009;35:107e14.
44. Dickstein SG, Bannon K, Xavier Castellanos F, Milham MP.
The neural correlates of attention deficit hyperactivity
disorder: an ALE meta-analysis. J Child Psychol Psychiatr
2006;47:1051e62.
45. Christakou A, Murphy CM, Chantiluke K, et al. Disorder-
specific functional abnormalities during sustained attention
in youth with attention deficit hyperactivity disorder (ADHD)
and with autism. Mol Psychiatr 2013;18:236e44.
46. Makris N, Biederman J, Valera EM, et al. Cortical thinning of
the attention and executive function networks in adults with
attention-deficit/hyperactivity disorder. Cerebr Cortex
2006;17:1364e75.
47. Krain AL, Castellanos FX. Brain development and ADHD. Clin
Psychol Rev 2006;26:433e44.
48. Pontius AA. Dysfunction patterns analogous to frontal lobe
system and caudate nucleus syndromes in some groups of
minimal brain dysfunction. J Am Med Womens Assoc
1973;28:285e92.
49. Castellanos FX, Lee PP, Sharp W, et al. Developmental
trajectories of brain volume abnormalities in children and
adolescents with attention-deficit/hyperactivity disorder.
JAMA 2002;288:1740e8.
50. Jankovic J. Movement disorders, an issue of neurologic clinics, e-
book (vol. 33, No. 1). Philadelphia: Elsevier; 2014.
51. Weeks RA, Turjanski N, Brooks DJ. Tourette's syndrome: a
disorder of cingulate and orbitofrontal function? QJM
1996;89:401e8.
52. Peterson BS, Thomas P, Kane MJ, et al. Basal ganglia volumes
in patients with Gilles de la Tourette syndrome. Arch Gen
Psychiatr 2003;60:415e24.
53. Speedie LJ, Wertman E, Ta'ir J, Heilman KM. Disruption of
automatic speech following a right basal ganglia lesion.
Neurology 1993;43. 1768e1768.
54. Booth JR, Wood L, Lu D, Houk JC, Bitan T. The role of the basal
ganglia and cerebellum in language processing. Brain Res
2007;1133:136e44.
55. Scholz VH, Flaherty AW, Kraft E, et al. Laterality, somatotopy
and reproducibility of the basal ganglia and motor cortex
during motor tasks. Brain Res 2000;879:204e15.