ORIGINAL CONTRIBUTION

Internal Pallidal and Thalamic Stimulation

in Patients With Tourette Syndrome
Marie-Laure Welter, MD, PhD; Luc Mallet, MD, PhD; Jean-Luc Houeto, MD, PhD;
Carine Karachi, MD, PhD; Virginie Czernecki, PhD; Philippe Cornu, MD; Soledad Navarro, MD;
Bernard Pidoux, MD; Didier Dormont, MD, PhD; Eric Bardinet, PhD; Jérôme Yelnik, MD;
Philippe Damier, MD, PhD; Yves Agid, MD, PhD

Background: Tourette syndrome (TS) is thought to Main Outcome Measures: Effects of thalamic, palli-
result from dysfunction of the associative-limbic terri- dal, simultaneous thalamic and pallidal, and sham stimu-
tories of the basal ganglia, and patients with severe lation on neurologic, neuropsychological, and psychiat-
symptoms of TS respond poorly to medication. ric symptoms.
High-frequency stimulation has recently been applied
to patients with TS in open studies using the Results: A dramatic improvement on the Yale Global Tic
centromedian-parafascicular complex (CM-Pf ) of Severity Scale was obtained with bilateral stimulation of
the thalamus, the internal globus pallidus (GPi), or the GPi (reduction in tic severity of 65%, 96%, and 74%
the anterior limb of the internal capsule as the princi- in patients 1, 2, and 3, respectively). Bilateral stimula-
tion of the CM-Pf produced a 64%, 30%, and 40% re-
pal target.
duction in tic severity, respectively. The association of
thalamic and pallidal stimulation showed no further re-
Objective: To report the effect of high-frequency stimu-
duction in tic severity (60%, 43%, and 76%), whereas mo-
lation of the CM-Pf and/or the GPi, 2 associative-limbic tor symptoms recurred during the sham condition. No
relays of the basal ganglia, in patients with TS. neuropsychological, psychiatric, or other long-term ad-
verse effect was observed.
Design: Controlled, double-blind, randomized cross-
over study. Conclusions: High-frequency stimulation of the associa-
tive-limbic relay within the basal ganglia circuitry may be
Setting: Medical research. an effective treatment of patients with TS, thus heighten-
ing the hypothesis of a dysfunction in these structures in
Patients: Three patients with severe and medically re- the pathophysiologic mechanism of the disorder.
fractory TS.
Trial Registration: clinicaltrials.gov Identifier:
Intervention: Bilateral placement of stimulating elec- NCT00139308
trodes in the CM-Pf (associative-limbic part of the thala-
mus) and the GPi (ventromedial part). Arch Neurol. 2008;65(7):952-957

T
OURETTE SYNDROME (TS) IS lation of the centromedian-parafascicular
characterized by motor and complex (CM-Pf) of the thalamus,6 the in-
vocal tics associated with ternal part of the globus pallidus (GPi),7-9
various psychiatric manifes- and the anterior limb of the internal cap-
tations, which can cause sule10 has been tested, with a positive but
major familial and social disability.1 In pa- variable effect on tics. Recently, bilateral
tients with severe and debilitating tics, the stimulation of the CM-Pf and/or the ventro-
best available drug therapy is often inef- oralis nucleus of the thalamus was ap-
fective and has serious potential adverse ef- plied in 18 patients with TS, resulting in a
fects.2,3 Several attempts at neurosurgical 65% improvement in tics.11 However, these
creation of lesions have yielded disappoint- results were obtained at various postop-
Author Affiliations are listed at ing results and severe adverse effects.4,5 In erative delays through an open-label evalu-
the end of this article. sparse case reports, high-frequency stimu- ation. Given the proposed dysfunction of

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 Table 1. Preoperative Clinical Characteristics of 3 Patients With Tourette Syndrome

Patient No., Sex

1, F 2, M 3, F
Age, y
At onset of tics 7 6 13
At time of surgery 36 30 30
Tourette syndrome symptoms
Tics
Motor Eyes, mouth and arms, shoulder shrugs, Eyes, face and arms, head jerks, Eyes, face and arms, head and
touching, copropraxia shoulder shrugs, knee flexion abdominal jerks
Phonic Throat clearing, shouting, coprolalia Throat clearing, shouting, animal Coughing, throat clearing, grunting,
noises animal noises
Self-injurious behaviors Self-inflicted eye lesions, severe lip biting, Jaw biting None
hair tearing, burning
Associated behavioral Borderline personality Arithmomania (mental counting) None
disorders
Treatments
Neuroleptic, mg/d Loxapine succinate, 700; Pimozide, 6; Risperidone, 3;
Pimozide, 18 Tiapride, 300 Loxapine succinate, 25
Others, mg/d Venlafaxine hydrochloride, 300; Fluoxetine hydrochloride, 60; Venlafaxine hydrochloride, 37.5
Clonazepam, 16 Diazepam, 20
Global functioning
Familial Married, living alone, 4-year-old son placed Unmarried, living with mother Divorced, living alone with
with grandparents 3-year-old daughter
Socioprofessional Unemployed for 10 mo (secretary), Unemployed for 19 mo (waiter) Unemployed for 4 mo (checkout
hospitalized in neurologic unit for 10 mo assistant)

the associative-limbic component of the basal ganglia cir-

cuitry in TS, 12-14 we evaluated the efficacy of high-
frequency stimulation of 2 associative-limbic relays, the
CM-Pf of the thalamus and ventromedial part of the GPi,13,15
in a controlled, double-blind, randomized crossover study.16

METHODS

Three patients with severe TS were selected for bilateral implan-

tation of quadripolar electrodes (Medtronic, Minneapolis, Min-
nesota) in the ventromedial part of the GPi and the CM-Pf
(Table 1, Figure 1).16 Inclusion criteria for surgery were as
follows: (1) TS according to Diagnostic and Statistical Manual of
Mental Disorders (Fourth Edition)18 (DSM-IV) criteria, (2) age
greater than 18 years, (3) severe form of the disease adversely
affecting social integration, (4) failure of best treatment by medi-
cation or intolerance after a minimum of 6 months of treat-
ment, (5) absence of cognitive deficits or psychosis, and (6) abil-
ity to give written informed consent.19 The protocol, agreed on 1 cm
and sponsored by INSERM (RBM 00-008), was approved by the
local ethics committee.16
The 4 quadripolar electrodes were implanted stereotacti- Figure 1. Axial magnetic resonance image of the 3 patients showing the
2 targets, the ventromedial part of the internal globus pallidus (GPi) and the
cally (2 within the left and right CM-Pf and 2 within the left centromedian-parafascicular complex (CM-Pf ) of the thalamus, after adjustment
and right GPi) and connected to 2 subclavicular implanted pro- of the 3-dimensional atlas in the image of each patient and normalization in the
grammable pulse generators (Kinetra; Medtronic) with the pa- atlas space.17 The CM-Pf is medial (centromedian, green; parafascicular, gray),
tient under general anesthesia. The electrodes and their 4 in- and the ventromedial GPi target is lateral. The limbic pallidum is yellow; the as-
dividual contact locations were plotted on the postoperative sociative pallidum, violet; and the sensorimotor pallidum, green. The therapeutic
contacts are yellow (GPi: contact 0 in patient 1, contacts 0 and 1 in patients 2
magnetic resonance image by means of automatic alignment and 3 [mean coordinates: 20 mm anterior, 12 mm lateral, 3 mm ventral to the
with a 3-dimensional digital atlas of the basal ganglia (Figure 1).20 posterior commissure point]; amplitude, 1.5-3.5 V; CM-Pf: contacts 0 and 1
Patients were examined 1 month before surgery and 2 months [mean coordinates: 2.5 mm anterior, 6.0 mm lateral, 1.2 mm dorsal to the pos-
after surgery without stimulation. Two months after surgery, terior commissure point]; amplitude,1.5-1.7 V), and the other contacts are blue.
4 stimulation conditions were individually randomly assigned Inset, Three-dimensional representation of the same structures as seen from an
in a crossover design (n of 1 design study), with both patients anterior, dorsal, and lateral point of view. Colors are the same as in the main
figure. This oblique orientation and the transparent mode of representation of
and investigators blinded to the condition: (1) bilateral tha- the GPi and the CM-Pf improve the visibility of the therapeutic contact positions
lamic, (2) bilateral pallidal, (3) bilateral pallidal and thalamic, (yellow circles).
and (4) no stimulation (sham). Each stimulation condition was
maintained for 2 months, and patients were examined monthly
(Figure 2). Assessments were performed, blind to the condi- evaluation included the following: (1) tic severity assessed by
tion, every month during a 5-day hospitalization. Clinical the Yale Global Tic Severity Scale (YGTSS) (primary outcome

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 Yale Global Tic Severity Scale Patient 1
Rush Video-Based Tic Rating Scale Patient 2
Patient 3
Patient 1
50
100 20

Rush Video-Based Tic Rating Scale

Yale Global Tic Severity Scale

Yale Global Tic Severity Scale

40
80 16

30
60 12

20
40 8

10
20 4

0
0 0 M–1 M1 M2 M1 M2 M1 M2 M1 M2 M1 M2
M–1 M2 M3 M4 M5 M6 M7 M8 M9 M10 M60 Before After Thalamic Pallidal Thalamic Sham
Surgery Surgery Stimulation Stimulation and Pallidal
Before After Thalamic Pallidal Sham Thalamic Thalamic Stimulation
Surgery Surgery Stimulation Stimulation and Pallidal and Pallidal
Stimulation Stimulation Without Double-blind Period with Stimulation Open
Stimulation Long-term
Follow-up
Patient 2
100 20

Rush Video-Based Tic Rating Scale

Figure 3. Effects of high-frequency stimulation of the centromedian-
Yale Global Tic Severity Scale

80 16 parafascicular complex of the thalamus and ventromedial part of the internal

globus pallidus in 3 patients with Tourette syndrome on motor and phonic tic
60 12 severity (Yale Global Tic Severity Scale). Each stimulation condition
(thalamic, pallidal, simultaneous thalamic and pallidal, and sham stimulation)
40 8
was maintained for 2 months, and patients were examined monthly.
M indicates month.

20 4

effects during 24 to 48 hours, with a pulse width of 60 micro-

0 0
M–1 M2 M3 M4 M5 M6 M7 M8 M9 M10 M33 seconds and a frequency of 130 Hz, the stimulation settings were
Before After Thalamic Pallidal Thalamic Sham Pallidal activated for the next period.
Surgery Surgery Stimulation Stimulation and Pallidal Stimulation
Stimulation An open long-term follow-up evaluation was performed on
all patients in December 2006 (60, 33, and 20 months postop-
Patient 3
100 20 eratively for the 3 patients).
Rush Video-Based Tic Rating Scale
Yale Global Tic Severity Scale

80 16 RESULTS
60 12
EFFECTS OF HIGH-FREQUENCY
40 8 STIMULATION ON TIC SEVERITY

20 4 A marked improvement in tic severity occurred within

hours (patient 1) or days (patients 2 and 3) after the op-
0 0 eration, which enabled us to interrupt dopamine antago-
M–1 M2 M3 M4 M5 M6 M7 M8 M9 M10 M20
Before After Pallidal Thalamic Sham Thalamic Thalamic nist medication in patient 116 and reduce dosage by 66%
Surgery Surgery Stimulation Stimulation and Pallidal and Pallidal
Stimulation Stimulation in patient 2. Two months after surgery and without stimu-
Without Double-blind Period with Stimulation Open lation, no significant change in tic severity was ob-
Stimulation Long-term
Follow-up served in any of the patients (YGTSS and Rush Video-
Based Tic Rating Scale) (Figure 2 and Figure 3).
Figure 2. Effects of high-frequency stimulation of the centromedian-
Thalamic and/or pallidal stimulation produced a marked
parafascicular complex of the thalamus and the ventromedial part of the improvement in tic severity in comparison with preopera-
internal globus pallidus in 3 patients with Tourette syndrome on tic severity. tive and sham assessments. Compared with preoperative
M indicates month. assessment, the best improvement in tic severity was ob-
tained with ventromedial GPi stimulation, with 65%, 96%,
measure), the motor and phonic tic subscore (corresponding and 74% reduction in the total YGTSS in patients 1, 2, and
to the YGTSS less the 50-point impairment portion), and the 3, respectively (Figure 2) and 80%, 90%, and 67% reduc-
Rush Video-Based Tic Rating Scale; (2) psychiatric symptoms, tion in motor and phonic tic subscore (Figure 3). The best
ie, depression, anxiety, impulsiveness, and obsessive- effects of CM-Pf thalamic stimulation were reductions of
compulsive behaviors; and (3) neuropsychological status (at-
tention, episodic memory, working memory, and flexibility)
64%, 30%, and 40% in global tic severity (Figure 2) and
(see Houeto et al16 for details). With a view to maintaining the 41%, 37%, and 41% in motor and phonic tic severity
double blind for each patient, stimulation settings were ad- (Figure 3). Combined thalamic and pallidal stimulation did
justed for the next period as follows: after motor, psychiatric, not improve the tic reduction (60%, 43%, and 76% in the
and cognitive assessments, bilateral thalamic and pallidal stimu- total YGTSS, and 59%, 16%, and 70% in the motor and
lation was applied with intensities below the level of adverse phonic tic subscore, respectively) (Figures 2 and 3). The

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 Table 2. Effects of Thalamic and/or Pallidal Stimulation on Cognitive Performance and Psychiatric Status a

Without Stimulation Double-blind Period With Stimulation

Before After Thalamic

Test and Patient No. Surgery Surgery Thalamic Pallidal and Pallidal Sham
Episodic memory (Verbal Learning; maximum 36)
1 14 28 30 29 31 31
2 29 30 26 30 30 30
3 30 31 32 29 30 30
Working memory (Digit Ordering Test; maximum 105)
1 67 86 85 86 89 86
2 98 100 104 102 100 100
3 98 85 100 98 102 98
Flexibility (Trail Making Test A-B) b
1 96 43 28 27 30 36
2 21 3 19 22 13 14
3 27 20 27 45 23 27
Impulsivity (BIS; maximum 100)
1 77 66 35 58 61 31
2 68 65 66 69 73 73
3 63 72 65 69 63 66
Depression (MADRS; maximum 60)
1 25 19 10 23 17 20
2 2 0 1 1 2 3
3 13 3 2 9 4 7
Anxiety (BAS; maximum 60)
1 7 15 8 10 15 7
2 2 0 5 4 2 7
3 19 4 4 3 0 8

Abbreviations: BAS, Brief Anxiety Scale; BIS, Brief Impulsivity Scale; MADRS, Montgomery and Asberg Depression Scale.
a For episodic memory, working memory, and flexibility scores, high values correspond to better performance; for impulsivity, depression, and anxiety scores,
high values correspond to worse psychiatric status.
b The Trail Making Test A-B produces a reaction time expressed in seconds; the mean normal value is 35 ± 20 seconds.

effects of both thalamic and pallidal stimulation remained reappeared during the sham stimulation condition. De-
stable or increased during the 2-month period in patients pressive mood, emotional hypersensitivity, moderate anxi-
1 and 3. In patient 2, the best result was obtained after 1 ety, and impulsiveness tended to decrease with thalamic
month with stimulation, but the improvement decreased or simultaneous thalamic and pallidal stimulation but not
or disappeared after 2 months. In the sham condition, pa- with pallidal stimulation alone (Table 2). Patient 2 had
tients 1 and 2 experienced a recurrence of motor symp- no psychiatric disorder either before or after surgery
toms, with a severity similar to that observed before sur- (Table 2). Mild anxiety-free mental counting was present
gery. In patient 3, tic severity decreased by 32% in the sham before surgery; it disappeared under both thalamic and/or
condition (Figure 2). pallidal stimulation but reappeared during the sham pro-
cedure. Patient 3 had a moderate generalized anxiety dis-
ADVERSE EFFECTS order, which was controlled at the time of surgery with
venlafaxine hydrochloride therapy (37.5 mg/d). No re-
With therapeutic stimulation settings, transient cheiro-oral surgence of anxiety occurred after surgery despite discon-
or arm paresthesias (lasting a few minutes) or lethargy (3-4 tinuation of venlafaxine therapy (Table 2). None of the 3
days) were induced under thalamic or pallidal stimulation, patients showed obsessive-compulsive symptoms either
respectively. With increasing intensity of pallidal stimula- before or after surgery (not shown).
tion, 2 patients reported sensations of nausea and vertigo Neuropsychological status, which was normal before
and1patientreportedanxiety.Alibidodecreasewasreported surgery, remained stable in all patients (Table 2).
by patient 3 under thalamic stimulation.
LONG-TERM FOLLOW-UP
EFFECTS OF STIMULATION ON PSYCHIATRIC,
NEUROPSYCHOLOGICAL, AND SOCIAL STATUS In patient 1, 60 months after surgery, simultaneous tha-
lamic and pallidal stimulation induced an 82% decrease
Before surgery, patient 1 had a major depressive disorder in tic severity and a dramatic reduction in self-injurious
with severe self-injurious behaviors and impulsiveness, ful- behaviors and impulsiveness (Figure 2). Two years af-
filling the DSM-IV criteria for borderline personality dis- ter surgery, she went back to full-time work and began
order.16 Self-injurious behaviors were dramatically re- interpersonal psychotherapy, which enabled an improve-
duced by pallidal and/or thalamic stimulation, but they ment in interpersonal relationships. Four years after sur-

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 gery, failure of the pallidal neurostimulator led to a re- This cannot be totally excluded, but the fact that in 2 pa-
appearance of tics and self-injury, dramatically decreasing tients the effects of stimulation were maximal after 2
a few hours after replacement. months of stimulation for each structure does not favor
Patient 2 required monthly adjustment of the stimu- this hypothesis (Figure 3).
lation settings, with an increase in the intensity of stimu- This controlled, double-blind, randomized cross-
lation and pulse width because of the resurgence of tics. over study confirms previous results obtained in open-
A stable reduction in tic severity was obtained 27 months label studies in patients with TS using high-frequency
after surgery under noncontinuous (20 hours on fol- stimulation of the CM-Pf of the thalamus,6,11 but it shows
lowed by 4 hours off) pallidal stimulation. Because of mild that stimulation of the ventromedial GPi produced a simi-
and intermittent improvement in tic severity during the lar or greater improvement in TS symptoms (Figure 2).
17 months after the end of the protocol, patient 2 did not This result is in line with the proposal of corticostriato-
recover his professional activity. pallidocortical pathway dysfunction.19 In nonhuman pri-
In patient 3, 20 months after surgery, tic severity was mates, complex stereotyped movements resembling tics
reduced by 74% without medication under pallidal and have been produced by selective modulation of the lim-
thalamic stimulation. Four months after the end of the bic (ventromedial) external part of the globus pallidus
protocol, patient 3 began a professional educational re- by means of microinjection of the ␥-aminobutyric acid
training program. antagonist bicuculline,13 and consequently of the ven-
tromedial part of the GPi.21 In our patients, stimulation
of the ventromedial part of the GPi seems to be more ef-
COMMENT
ficient than stimulation of the CM-Pf of the thalamus.
This difference could be explained by the different ana-
An improvement in tic severity with no cognitive or psy- tomic and functional positions of these structures within
chiatric adverse effects was seen with high-frequency stimu- the basal ganglia circuitry. Indeed, the ventromedial part
lation of the CM-Pf or ventromedial part of the GPi, which of the GPi is a key structure as the output nucleus of the
form part of the basal ganglia associative-limbic circuits. main direct pathway.17 Conversely, the CM-Pf is part of
In all patients, double-blind GPi stimulation induced the an internal loop of the basal ganglia circuitry receiving
greatest reduction in tic severity, with no improvement from its input from the output nuclei and projecting back to
simultaneous thalamic and pallidal stimulation (Figure 2). the striatum.17 It is therefore plausible that stimulation
Nevertheless, during long-term follow-up, an overall im- applied to the main loop, ie, the GPi, would be more ef-
provement in tic severity, as well as in impulsivity and anxi- ficient than that applied within an indirect internal loop,
ety, was confirmed in 2 patients with simultaneous tha- ie, the CM-Pf of the thalamus.
lamic and pallidal stimulation without adverse effects. In This study suggests that high-frequency stimulation
1 patient, the reduction of motor symptoms was ob- of the ventromedial part of the GPi can produce a marked
tained with intermittent pallidal stimulation. reduction in tic severity in patients with TS, which is in
The results obtained in our 3 patients are robust, for the process of being tested in a large patient population
the following reasons. (1) This was a double-blind ran- (STIC [Traitement de la maladie de Gilles de la Tourette
domized protocol including a sham period during which par stimulation bilatérale à haute fréquence de la partie
patients experienced a reappearance of symptoms. (2) The antérieure du Globus Pallidus interne] French multi-
stimulating electrodes were accurately positioned within center study).
the CM-Pf and the GPi, and the active contacts used for
continuous stimulation were identically localized in the Accepted for Publication: December 21, 2007.
structures (Figure 1). (3) The therapeutic benefit per- Author Affiliations: National Institute of Health and Medi-
sisted for a long period (20, 33, and 60 months after sur- cal Research (INSERM), Unit 679, Pierre et Marie Curie
gery), enabling a marked concomitant reduction of drug University-Paris 6, Clinical Investigation Centre, Fed-
treatment. In the pallidum, in patient 2, this improve- eration of Nervous System Diseases (Drs Welter, Karachi,
ment was obtained after intermittent adjustment of the Czernecki, Yelnik, and Agid), Department of Neurosur-
stimulation settings. We do not have any explanation for gery (Drs Karachi, Cornu, and Navarro), Federation of
this patient’s recurrences despite repeated attempts at ad- Clinical Neurophysiology (Dr Pidoux), Department of
justment and exclusion of neurostimulator malfunc- Neuroradiology (Drs Dormont and Bardinet), and Na-
tion. Similar difficulties in adjustment of stimulation set- tional Centre of Research and Health, UPR640 (Drs
tings have been reported in most patients with TS recently Dormont and Bardinet), Assistance Publique-Hôpitaux
treated by CM-Pf and/or ventro-oralis stimulation.11 This de Paris, Pitié-Salpêtrière Hospital; and INSERM, Equipe
could result from neuronal plasticity with a decrease of AVENIR Group IFR-70 (Dr Mallet), Paris, France; De-
the effects of electrical high-frequency stimulation on lo- partment of Neurology, Centre Hopitalier Universitaire
cal neuronal activity. Poitiers, Poitiers, France (Dr Houeto); and Clinical In-
Some limitations could affect these results. (1) The vestigation Centre, Department of Neurology, Laennec
number of patients is small; however, because of ethical Hospital, Centre Hopitalier Universitaire Nantes, Nantes,
issues, this investigation was a pilot study, and the cross- France (Dr Damier).
over design enabled us to evaluate the differential effect Correspondence: Marie-Laure Welter, MD, PhD, Cen-
of each stimulated structure, CM-Pf of the thalamus vs tre d’Investigation Clinique, Hôpital de la Salpêtrière, 47
ventromedial part of the GPi. (2) The duration of the bvd de l’Hôpital, 75013 Paris, France (marie-laure.welter
stimulation effects could have led to a carryover effect. @psl.aphp.fr).

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 Author Contributions: Drs Welter and Mallet contrib- 7. Ackermans L, Temel Y, Cath D, et al. Deep brain stimulation in Tourette’s syn-
drome: two targets? Mov Disord. 2006;21(5):709-713.
uted equally to this work. Study concept and design: Welter,
8. Diederich NJ, Kalteis K, Stamenkovic M, et al. Efficient internal pallidal stimula-
Mallet, Houeto, Karachi, Cornu, Dormont, Damier, and tion in Gilles de la Tourette syndrome: a case report. Mov Disord. 2005;20
Agid. Acquisition of data: Welter, Mallet, Houeto, Karachi, (11):1496-1499.
Czernecki, Navarro, Pidoux, Dormont, and Bardinet. 9. Shahed J, Poysky J, Kenney C, Simpson R, Jankovic J. GPi deep brain stimula-
Analysis and interpretation of data: Welter, Mallet, Houeto, tion for Tourette syndrome improves tics and psychiatric comorbidities. Neurology.
Yelnik, and Agid. Drafting of the manuscript: Welter, Mallet, 2007;68(2):159-160.
Houeto, Karachi, Cornu, Navarro, Yelnik, and Agid. Criti- 10. Flaherty AW, Williams ZM, Amirnovin R, et al. Deep brain stimulation of the an-
terior internal capsule for the treatment of Tourette syndrome: technical case report.
cal revision of the manuscript for important intellectual con- Neurosurgery. 2005;57(4)(suppl):E403.
tent: Welter, Mallet, Houeto, Czernecki, Pidoux, Dormont, 11. Servello D, Porta M, Sassi M, Brambilla A, Robertson MM. Deep brain stimula-
Bardinet, Damier, and Agid. Statistical analysis: Welter tion in 18 patients with severe Gilles de la Tourette syndrome refractory to treat-
and Mallet. Obtained funding: Houeto, Damier, and Agid. ment: the surgery and stimulation. J Neurol Neurosurg Psychiatry. 2008;79
Administrative, technical, and material support: Welter, (2):136-142.
12. Graybiel AM, Canales JJ. The neurobiology of repetitive behaviors: clues to the
Houeto, Yelnik, and Agid. Study supervision: Welter,
neurobiology of Tourette syndrome. Adv Neurol. 2001;85:123-131.
Mallet, Houeto, and Agid. 13. Grabli D, McCairn K, Hirsch EC, et al. Behavioural disorders induced by external
Financial Disclosure: None reported. globus pallidus dysfunction in primates, I: behavioural study. Brain. 2004;127
Funding/Support: This study was supported by INSERM, (pt 9):2039-2054.
the University of Pierre and Marie Curie (Paris VI), and 14. Mink JW. Neurobiology of basal ganglia circuits in Tourette syndrome: faulty in-
the Assistance-Publique-Hôpitaux de Paris. hibition of unwanted motor patterns? Adv Neurol. 2001;85:113-122.
15. Karachi C, Yelnik J, Tande D, et al. The pallidosubthalamic projection: an ana-
Additional Contributions: We thank the nurses of the
tomical substrate for nonmotor functions of the subthalamic nucleus in primates.
Centre d’Investigation Clinique for providing patient care. Mov Disord. 2005;20(2):172-180.
16. Houeto JL, Karachi C, Mallet L, et al. Tourette’s syndrome and deep brain stimulation.
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tion E-Mail Alert when new articles on specific topics
are published. Go to http://archneur.ama-assn.org
/collections to see these collections of articles.

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