Accepted Manuscript

The neuropsychology of basal ganglia

Daria Riva, MD, Matilde Taddei, PhD, Bulgheroni Sara, PsyD

PII: S1090-3798(17)31833-0
DOI: 10.1016/j.ejpn.2018.01.009
Reference: YEJPN 2364

To appear in: European Journal of Paediatric Neurology

Received Date: 4 August 2017

Accepted Date: 8 January 2018

Please cite this article as: Riva D, Taddei M, Sara B, The neuropsychology of basal ganglia, European
Journal of Paediatric Neurology (2018), doi: 10.1016/j.ejpn.2018.01.009.

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.
 ACCEPTED MANUSCRIPT
The neuropsychology of basal ganglia

Daria Riva, MD, Matilde Taddei, PhD, and Bulgheroni Sara, PsyD

Developmental Neurology Division

PT
Fondazione IRCCS Istituto Neurologico C. Besta

RI
Via Celoria 11 – 20133, Milan, Italy

SC
Corresponding author

Daria Riva

Phone: +39 02 23942215

U
AN
daria.riva@istituto-besta.it
M
D
TE
C EP
AC

1
 ACCEPTED MANUSCRIPT
Abstract

Basal Ganglia are subcortical structures specialized at very early age, functionally different

according to the right or left side. They are part of complex distributed network composed by

parallel segregated loops where specific information are processed and open loops where

different information are integrated. These loops are connected to specialized cortical areas

PT
thus entering into distributed processing of higher order cognitive functions and behaviors.

RI
Lesion or malfunction of basal ganglia nuclei cause deficits in different neuropsychological

functions and neurobehavioural diseases, such Autism Spectrum Disorder, Attention

SC
Deficit/Hyperactivity Disorder, Tourette syndrome, etc., for the reciprocal connections from

and to the limbic system and the frontal system.

U
Basal ganglia have a computational functioning, working by activation and inhibition
AN
sequences, coded in time and space and regulated by inhibitory and excitatory mechanisms,
M

with such accuracy to guarantee an effective and elegant product.

D

Key words: basal ganglia; neuropsychology; movement; cognition; behaviour

TE
C EP
AC

2
 ACCEPTED MANUSCRIPT
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 regulation and

non-motor complex behaviours that need to process and integrate different types of

information. These evidences stems from the clinical experience with patients with movement

disorders that also show associated symptoms both in emotional and cognitive-

PT
neuropsychological domain, and from anatomical and functional imaging that show how BG

RI
are activated together with other cortical regions in complex non-motor tasks. There are also

BG diseases that cause only neuropsychological and neurocognitive deficits without

SC
movement disorder.1-3

The aforementioned evidences demonstrate how BG are implicated in the processing of

U
higher cognitive functions as first defined by Alexander,1, 4-5 then resumed by other authors.6-8
AN
These functions are the ultimate product of complex operations possible underlined by
M

associative connections between BG and sensorimotor cortexes. These areas are highly

specialized, work synergistically (every area is always aware of what's happening in another
D

area) thanks to a high degree of connectivity, guaranteed by complex networks widely

TE

distributed throughout the brain.9

The brain organization in large scale circuits is active very early in childhood and develops
EP

from more elementary networks, connecting only sensorimotor areas, to very complex circuits

connecting several brain regions, mainly with associative or multimodal role, able to integrate
C
AC

stimuli by different modalities. There is converging evidence suggesting that by age 7–9

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 topology, i.e. distributed networks interconnect different areas,

some of which are more specialized in processing a specific part of the function. The brain is
3
 ACCEPTED MANUSCRIPT
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 integrated information processing . In the right handers it is more

PT
represented on the left hemisphere, but with an extended distribution throughout the two

RI
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.

SC
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

U
The functional organization of the BG formulated in the 1980s was based on the concept that
AN
neuronal signals from the cortex flow to the striatum, through the Globus Pallidus and
M

Substantia Nigra pars reticulata, and project back to the cortex via the thalamus, forming

parallel cortico–basal ganglia–thalamo–cortical loops. Although the model was primarily

D

formulated to understand the pathophysiology of movement, the existence of parallel circuits

TE

subserving oculo-motor control, executive functions, and emotions was also recognized.9

Growing experimental and clinical evidence supports that the cortico-basal ganglia-thalamo-
EP

cortical loops proceed along parallel circuits linking cortical and subcortical regions

subserving the processing of sensorimotor, associative and affective tasks.14

C
AC

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 projecting

back to their cortical original regions. Thus each loops appear to be involved in distinct

behavioural functions.8

4
 ACCEPTED MANUSCRIPT
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

PT
facilitates certain motor or cognitive programs in the cerebral cortex that are adaptive for the

RI
present task, whereas the indirect pathway simultaneously inhibits the execution of competing

motor programs. An upset of the balance between the direct and indirect pathways results in

SC
the motor dysfunctions that characterize the extrapyramidal syndrome. If the inhibition

prevails, the prototypic disease is the Huntington Disease, while the prevalence of the indirect

U
pathway causes diseases like Parkinson's disease.
AN
BG intervene in regulating the balance between inhibitory and excitatory effects by inhibiting
M

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
D

input structures (Caudate, Putamen and Ventral Striatum), and then arrive at the output
TE

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
EP

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
C
AC

behaviour.

The organization of the BG system is based on striatal afferents 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 projections, mostly unilateral, from

association areas of the prefrontal, temporal, parietal, and cingulate cortices, and motor areas
5
 ACCEPTED MANUSCRIPT
in the frontal lobe that control eye movements. The 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, orbitaofrontal and limbic areas, sends

and receives afferences, demonstrating how the brain works through segregated loops that

PT
ensure specialization. Haber and colleagues studied the organization of thalamic connections

RI
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

SC
small associative areas that act as integrators of different stimuli.16-18

The integration of the information is ensured by the existence of open loops coupled with the

U
specialized processing, which is ensured by the specialization of the typical circuit of that
AN
particular structure. The presence of distinct cortico-striatal connections that are organized as
M

multiple circuits has been confirmed by Diffusion Tensor Imaging–based fiber tracking

studies, showing that the posterior (sensorimotor), anterior (associative), and ventral (limbic)
D

compartments of the human striatum have specific connections with the cortex, and
TE

particularly the frontal lobes.19

In particular, there is evidence that a strict topographic segregation is maintained during the
EP

processing of sensorimotor 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
C
AC

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 presence 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
6
 ACCEPTED MANUSCRIPT

Neuropsychological deficits in disorders after lesions of BG

We discuss the neuropsychological deficits in acquired disorders caused by BG lesions and

then neurodevelopmental disorders characterized by GB dis-function. Neuropsychological

and behavioural deficit concerning movement disorders are described in the relative chapters.

PT
Language

Alexander,1,4 one of the earliest supporters of the BG involvement in the processing of higher

RI
cognitive functions, distinguishes various types of aphasia in relation to lesion localization in

SC
BG. Lesion in the motor loop (Putamen, genu Corpus Callosum) cause speech disorder as

dysarthria or anarthria, injuries in the motor initiation loop (fibers from the pre-frontal cortex,

U
cingulate lap, supplementary motor area) result in mutism, hypokinesia and hypophonia,
AN
finally the involvement of Broca or Wernicke areas may lead to Broca or Wernicke aphasia
M

characterized by impaired word retrieval or language comprehension. In children subcortical

aphasia presents variable symptoms in relation to the cortex connections, but there are always
D

speech motor disorders, probably because BG participate in the motor repetition at the base of
TE

language learning.

The case reports of subcortical aphasia are few. Aram and colleagues20 described some
EP

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
C

anomic aphasia while Paquier 22 collected from different series patients with Broca aphasia,
AC

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
7
 ACCEPTED MANUSCRIPT
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 particular 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.24-26

PT
Teichmann et al.27 confirmed that the left Striatum participates not only in processing lexicon

RI
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

SC
described: the ventral part of the left striatum would process the rule-based mechanisms,

while the dorsal part would be involved in lexical procedures.

U
AN
Spatial neglect is lateralized disorder of space processing. The disorder is more common in
M

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
D

Mesulam’s model,28 the spatial attention processing is lateralized predominantly in the right
TE

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
EP

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
C

spatial attention also in childhood.29-31 We also studied 24 children con unilateral congenital
AC

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 contralateral to the lesion either left or right (personal data).

Putamen 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

8
 ACCEPTED MANUSCRIPT

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-

PT
term memory.33 Within the long-term memory there are the implicit memories of which we

RI
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

SC
the parietal lobe and temporal-mesial structures such as hippocampal and para-hippocampal

regions, entorhinal cortex and part of Amigdala. Patients with Alzheimer's have explicit

U
memory deficits (lexicon , semantic and narrative verbs), while Huntington Disease patients
AN
have implicit memory impairment (motor skill learning).34-37
M

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
D

differential role of BG nuclei in memory-guided movement in normal subjects. Significant

TE

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
EP

posterior putamen and globus pallidus play a role in maintenance of representations in

working memory and contribute to planning and temporal organization of motor

C

sequencing.38
AC

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 interested in emotions,

motivations, strategy planning and problem solving, monitoring, rapid attention shift,

necessary when the strategy is being implemented and the execution of the action.
9
 ACCEPTED MANUSCRIPT
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

PT
(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

RI
SC
Neurodevelopmental disorders

The connections between the BG and limbic and pre-frontal cortices are very interesting,

U
because their malfunction is the basis of very dramatic neuropsychiatric disorders,
AN
characterized not only by motor disorders but also by severe behavioural and
M

neuropsychological symptoms.

The anatomy and connections of the BG indicate that these structures are important links
D

between parts of the brain that have classically been considered to be related to emotional
TE

functioning and brain regions previously considered to have largely motor functions. The BG

have a role in the development and integration of motor functions, memory and attention, and
EP

reward processes.

Also in processing complex behaviours the cortexes project first to the striatum , then to the
C
AC

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 understand 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

10
 ACCEPTED MANUSCRIPT
to achieve a goal by implementing mechanisms that must necessarily be controlled

synchronously, project to the striatum and back to the cortexes 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.

PT
Autism is a neurodevelopmental disorder characterized by impaired social interaction, verbal

RI
and non-verbal communication, and restricted and repetitive behaviour. The ritualistic and

repetitive mechanisms, encompasses a broad range of symptoms including motor

SC
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

U
Rojas et al. 42 who found that the severity of repetitive and stereotyped behaviour was
AN
associated with a significant increase (8%) of caudate nucleus.
M

Attention Deficit/Hyperactivity Disorer (ADHD), is a chronic condition marked by

persistent inattention, hyperactivity, and sometimes impulsivity. Convergent data from

D

neuroimaging, neuropsychology, genetics and neurochemical studies consistently point to the

TE

involvement of the frontostriatal network as a likely contributor to the pathophysiology of

ADHD. This network involves the lateral prefrontal cortex, the dorsal anterior cingulate
EP

cortex, the caudate nucleus and putamen.43

In ADHD children there is an atypical activation of the frontal lobe and the and Thalamus.44-
C

45
AC

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 Researchers have shown both volumetric and asymmetry differences

in the caudate between ADHD and control groups, even if these findings have not been

consistent across studies.47 Moreover, findings suggest that regional brain volumes are

associated with greater ADHD symptom severity. For example Castellanos et al.49 found
11
 ACCEPTED MANUSCRIPT
frontal and temporal gray, caudate, and cerebellar volumes to be significantly correlated with

global clinician ratings and parent ratings of child attention problems.

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

PT
present at higher rates. These co-occurring diagnoses often cause more impairment to the

RI
individual than the tics. While the exact cause is unknown, it is believed to involve a

combination of genetic and environmental factors. The malfunctioning of fronto-striatal

SC
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

U
globs pallidus are decreased primarily in adults. 52
AN
M

Although the BG connections are widely distributed in the two hemispheres, BG seem to be

functionally different according to the involvement of the right or left side.53-55 In our clinical
D

practice we observed a child with a pilocytic astrocytoma of the right BG who showed a
TE

perfect language, but a cognitive\behavioural phenotype characterized by disruptive

hyperactivity, a major disturbance of attention with obsessive-compulsive behaviours and

EP

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
C
AC

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.

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
12
 ACCEPTED MANUSCRIPT
circuits whereby motor, associative, and limbic territories are engaged mainly in the control

of movement, behaviour, and emotions. These loops have reciprocal connections with

specialized cortical areas and thus entering into distributed and segregated networks

underlying specific complex functions and behaviours. There are internal specializations and

internal integration areas between different loops.

PT
Their lesion o malfunction cause deficits in different functions, such as language (aphasia),

RI
implicit memory, spatial attention and executive functions.

Alexander and colleagues1,4-5 suggest that the BG have a computational role where each

SC
component is part of complex and widely distributed neural segregated and open circuits.

They work through activation and inhibition sequences, coded in time and space and

U
regulated by inhibitory and excitatory transmitter mechanisms, with such precision to ensure
AN
an effective and harmonious final product.
M
D
TE
C EP
AC

13
 ACCEPTED MANUSCRIPT
References

1. Alexander GE, DeLong MR, Strick PL. Parallel organization of functionally segregated

circuits linking basal ganglia and cortex. Annu Rev Neurosci 1986; 9: 357-381.

2. Leisman G, Melillo R. The basal ganglia: motor and cognitive relationships in a clinical

neurobehavioral context. Rev Neurosci 2013; 24: 9-25.

PT
3. Leisman G, Melillo R, Carrick FR. Clinical motor and cognitive neurobehavioral

RI
relationships in the basal ganglia. In: Barrios FA, Bauer C (ed) Basal Ganglia-An

Integrative View. InTech, 2013.

SC
4. Alexander GE. Basal ganglia-thalamocortical circuits: their role in control of

movements. J Cl Neurophysiol 1994; 11: 420-431.

5.
U
Alexander GE, Crutcher MD. Functional architecture of basal ganglia circuits: neural
AN
substrates of parallel processing. Trends Neurosci 1990; 13: 266-271.
M

6. Féger J. Updating the functional model of the basal ganglia. Trends Neurosc 1997; 20:

152-153
D

7. Middleton FA, Strick PL. Basal ganglia and cerebellar loops: Motor and cognitive
TE

circuits. Brain Res Rev 2000; 31: 236–250.

8. Middleton FA, Strick PL. Anatomical evidence for cerebellar and basal ganglia
EP

involvement in higher cognitive function. Science 1994; 266: 458-461.

9. Lanciego JL, Luquin N, Obeso JA. Functional neuroanatomy of the basal ganglia. Cold
C
AC

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:

952-955.

14
 ACCEPTED MANUSCRIPT
13. Bernal B, Ardila A. The role of the arcuate fasciculus in conduction aphasia. Brain

2009; 132: 2309-2316.

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: 112-128.

PT
15. Charara A, Sidibé M, Smith Y. Basal ganglia circuitry and synaptic connectivity.

RI
In: Tarsy D, Vitek JL, Lozano AM (eds.) Surgical Treatment of Parkinson’s Disease and

Other Movement Disorders. New York: Humana Press, 2003: 19-39.

SC
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: 3798-3813.

U
17. Haber SN, Fudge JL, McFarland NR. Striatonigrostriatal pathways in primates form an
AN
ascending spiral from the shell to the dorsolateral striatum. J Neurosci 2000; 20: 2369-
M

2382.

18. McFarland NR, Haber SN. Thalamic relay nuclei of the basal ganglia form both
D

reciprocal and nonreciprocal cortical connections, linking multiple frontal cortical

TE

areas. J Neurosci 2002; 22: 8117-8132.

19. Lehéricy S, Ducros M, De Moortele V et al. Diffusion tensor fiber tracking shows
EP

distinct corticostriatal circuits in humans. Ann Neurol 2004; 55: 522-529.

20. Aram DM, Rose DF, Rekate HL, Whitaker HA. Acquired capsular/striatal aphasia in
C
AC

childhood. Arch Neurol 1983; 40: 614-617.

21. Martins IP, Ferro JM. Acquired childhood aphasia: a clinicoradiological study of 11

stroke patients. Aphasiology 1993; 7: 489-495.

22. Paquier PF. Aphasia in children with basal ganglia lesions. In: Riva D, Njiokiktjien C

(eds) Brain Lesion Localization and Developmental Functions: Basal Ganglia,

Connecting Systems, Cerebellum, Mirror Neurons. John Libbey Eurotext 2010: 17-24.

15
 ACCEPTED MANUSCRIPT
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: 748-755.

24. Ullman MT. The declarative/procedural model of lexicon and grammar. J

Psycholinguistic Res 2001; 30: 37-69.

PT
25. Ullman MT. Contributions of memory circuits to language: The declarative/procedural

RI
model. Cognition 2004; 92: 231-270.

26. Pinker S, Ullman MT. The past and future of the past tense. Trends Cogn Sci 2002; 6:

SC
456-463.

27. Teichmann M, Gaura V, Démonet JF et al. Language processing within the striatum:

U
evidence from a PET correlation study in Huntington's disease. Brain 2008; 131: 1046-
AN
1056.
M

28. Mesulam MM. Spatial attention and neglect: parietal, frontal and cingulate contributions

to the mental representation and attentional targeting of salient extrapersonal

D

events. Philos Trans R Soc Lond B Biol Sci 1999; 354: 1325-1346.
TE

29. Ferro JM, Martins IP, Távora L. Neglect in children. Ann Neurol 1984; 15: 281-284.

30. Billingsley RL, Lang FF, Slopis JM, Schrimsher GW, Ater JL, Moore III BD. Visual–
EP

spatial neglect in a child following sub-cortical tumor resection. Dev Med Child Neurol

2002; 44: 191-200.

C
AC

31. Laurent-Vannier A, Pradat-Diehl P, Chevignard M, Abada G, De Agostini M. Spatial and

motor neglect in children. Neurology 2003; 60: 202-207.

32. Halligan PW, Fink GR, Marshall JC, Vallar G. Spatial cognition: evidence from visual

neglect. Trends Cogn Sci 2003; 7: 125-133.

33. Squire LR. The organization and neural substrates of human memory. Int J Neurol

1987; 21: 218-222.

16
 ACCEPTED MANUSCRIPT
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: 582-587.

35. Deweer B, Ergis AM, Fossati P et al. Explicit memory, procedural learning and lexical

priming in Alzheimer's disease. Cortex 1994; 30: 113-126.

PT
36. Knopman D, Nissen MJ. Procedural learning is impaired in Huntington's disease:

RI
Evidence from the serial reaction time task. Neuropsychologia 1991; 29: 245-254.

37. Peavy G, Jacobs D, Salmon DP et al. Verbal memory performance of patients with

SC
human immunodeficiency virus infection: Evidence of subcortical dysfunction. J Clin

Exp Neuropsychol 1994; 16: 508-523.

U
38. Menon V, Anagnoson RT, Glover GH, Pfefferbaum A. Basal ganglia involvement in
AN
memory‐guided movement sequencing. Neuroreport 2000; 11: 3641-3645.
M

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

D

reliability. Neuroimage 2005; 25: 1146-1160.

TE

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
EP

Neuroradiol 2008; 35: 42-50.

41. Estes A, Shaw DW, Sparks BF et al. Basal ganglia morphometry and repetitive behavior
C
AC

in young children with autism spectrum disorder. Autism Res 2011; 4: 212-220.

42. Rojas DC, Peterson E, Winterrowd E et al. Regional gray matter volumetric changes in

autism associated with social and repetitive behavior symptoms. BMC Psychiatry 2006;

6: 56.

43. Emond V, Joyal C, Poissant H. Structural and functional neuroanatomy of attention-

deficit hyperactivity disorder (ADHD). L'encéphale 2009; 35: 107-114.

17
 ACCEPTED MANUSCRIPT
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

Psychiatry 2006; 47: 1051-1062.

45. Christakou A, Murphy CM, Chantiluke K et al. Disorder-specific functional

abnormalities during sustained attention in youth with attention deficit hyperactivity

PT
disorder (ADHD) and with autism. Mol Psychiatry 2013; 18: 236-244.

RI
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. Cereb Cortex

SC
2006; 17: 1364-1375.

47. Krain AL, Castellanos FX. Brain development and ADHD. Clin Psychol rev 2006; 26:

433-444.
U
AN
48. Pontius AA. Dysfunction patterns analogous to frontal lobe system and caudate nucleus
M

syndromes in some groups of minimal brain dysfunction. J Am Med Womens Assoc 1973;

28: 285-292.
D

49. Castellanos FX, Lee PP, Sharp W, et al. Developmental trajectories of brain volume
TE

abnormalities in children and adolescents with attention-deficit/hyperactivity disorder.

JAMA 2002; 288: 1740-1748.

EP

50. Jankovic J. Movement Disorders, An Issue of Neurologic Clinics, E-Book (Vol. 33, No.

1). Philadelphia: Elsevier, 2014.

C
AC

51. Weeks RA, Turjanski N., Brooks DJ. Tourette’s syndrome: a disorder of cingulate and

orbitofrontal function ? QJM 1996; 89: 401–408.

52. Peterson BS, Thomas P, Kane MJ et al. Basal ganglia volumes in patients with Gilles de

la Tourette syndrome. Arch Gen Psychiatry 2003; 60: 415-424.

53. Speedie LJ, Wertman E, Ta'ir J, Heilman KM. Disruption of automatic speech following

a right basal ganglia lesion. Neurology 1993; 43: 1768-1768.

18
 ACCEPTED MANUSCRIPT
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: 136-144.

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: 204-215.

PT
RI
U SC
AN
M
D
TE
C EP
AC

19