Abstract
Background
The coexistence of tics with Parkinson's disease (PD) is rare, as they often emerge at different ages, follow different trajectories and involve contrasting pathophysiological mechanisms related to dopamine availability and function in the brain.
Cases
We present 10 individuals with primary tic disorders who later developed PD. Tic severity remained unchanged with the onset of parkinsonism or dopaminergic treatment. Peak‐dose dyskinesias in two cases did not affect tics, and deep brain stimulation of the subthalamic nucleus transiently induced tics in one individual with PD.
Conclusions
The evidence drawn from this case series does not support a linear relation between nigrostriatal dopaminergic availability and tics. It suggests that tics may instead arise from a more complex interplay between multiple neurotransmitter systems acting on several networks within the cortico‐striatal‐thalamic circuits.
Keywords: Neurotransmitters, Parkinson's disease, parkinsonism, Tics, Tourette's syndrome
Introduction
In movement disorders, the combination of specific neurological signs often informs pathophysiological enquiry and guides etiological considerations. 1 Strikingly, one rarely reported syndromic association is the coexistence of tics with neurodegenerative parkinsonism. Tics and parkinsonism are hypothesized to have contrasting pathophysiological mechanisms related to dopaminergic availability and function. 2 Considering the rarity of this association and the unique pathophysiological repercussions, we here wish to reappraise the coexistence of tics in individuals with Parkinson's disease (PD) by presenting 10 cases.
Case Series
We present 10 patients (three females) with a pre‐existing primary tic disorder (seven patients with Tourette's syndrome [TS] and three patients with chronic motor tic disorder [CMTD]) who later developed PD. In four cases PD diagnosis was further supported by a dopamine transporter SPECT (Fig. 1A). The onset and diagnosis of tic disorders occurred during childhood or early adolescence, while the median age at diagnosis of PD was 57 years (range 36–74 years) and median follow‐up period was 4.5 years (range 3 months–21 years). Tic severity and clinically relevant changes were assessed by a retrospective chart review including scrutinization of the documented clinical examination and list of medications used over time.
Figure 1.
(A) DAT SPECT of four individuals showing a reduced tracer uptake most clearly in the posterior putamen. The color scale represents z‐scores of the Striatal Binding Ratio (SBR) with respect to a standard healthy population. (B) 2D reconstructions of case 2, Medtronic 3387 leads targeting the globus pallidus internus. Left GPi: 2‐c + (most dorsal contact)/3.8 mA/60 μs/125 Hz. Right GPi: 2‐3‐c + (second most dorsal and most dorsal contact/2.8 mA/60 μs/125 Hz. (C) 3D reconstruction of case 3, Boston Scientific directional 1–3–3‐1 leads targeting the subthalamic nucleus. Red: volume of tissue activated of parameters eliciting the tic behavior. Left STN: 2–3‐4‐c + (second most ventral level)/2.3 mA/60 μs/130 Hz. Right STN: 5–6‐7‐c + (second most dorsal level)/2.0 mA/60 μs/130 Hz. Reconstructions made in Lead DBS v3.0 (Supplementary Reference S20).
Different dopaminergic agents were used for PD, including monotherapy with levodopa/carbidopa (LD/CD) and combinations with COMT inhibitors, MAO‐B inhibitors, dopamine agonists, and amantadine. One patient (case 4) received rasagiline monotherapy, while another patient (case 6) remained untreated due to mild symptoms. The LD equivalent daily dose varied between 400 and 1243 mg. In all individuals, the onset of PD or the initiation of pharmacotherapy used in its management did not affect tic symptoms. During hypodopaminergic states, one individual reported feeling anxious, and we observed a significant worsening of tics, when off medication during a levodopa challenge test (case 7). Two patients underwent deep brain stimulation (DBS) for parkinsonism, targeting the ventroposterior globus pallidus internus (GPi) (case 2) and the subthalamic nucleus (STN) (case 3). We present three illustrative cases below and include the characteristics of 10 cases in Table 1.
TABLE 1.
Demographic, clinical characteristics and previous and current medications of reported cases
| Gender | Age at tic onset (years) | Current tic features | Tic features | Age at onset of PD (years) | Parkinsonian features at onset | Psychiatric comorbidities | Anti‐parkinsonian and anti‐tic(*) therapy | |
|---|---|---|---|---|---|---|---|---|
| Case 1 | M | Child‐hood | Facial grimace and mouth movements | Orofacial motor | 51 | Left‐lateralized bradykinesia, rest tremor and rigidity | OCB | Pramipexole (discontinued due to malaise) Rotigitine (discontinued due to non‐specific unsteadiness) LD 600 mg daily; LEDD: 600 mg |
| Case 2 | F | 7 | Facial grimace, mouth movements and left shoulder shrug | Orofacial and left upper limb | 56 | Moderate bradykinesia and rigidity on the right side and mild parkinsonian features on the left | OCD, ADHD, Anxiety, Depression | LD/CD 600/150 mg daily, Pramipexole 2.75 mg daily, GPi DBS, LEDD: 875 mg, Aripiprazole 2 mg (discontinued due to worsening parkinsonism and restlessness)*, Topiramate 25 mg BID (discontinued due to cognitive worsening)*, Guanfacine (discontinued due to lack of effect)* |
| Case 3 | M | Child‐hood | Facial grimace, head jerks and abdominal tensing | Face, head, trunk | 36 | Right‐lateralized bradykinesia, rest tremor and rigidity | NA | Pre‐STN DBS: Opicapone 50 mg daily, LD 575 mg daily, Amantadine 150 mg daily, Safinamide 50 mg daily, Rotigotine 6 mg daily, LEDD: 1243 mg |
| Post‐STN DBS: LD 150 mg daily | ||||||||
| Case 4 | M | Child‐hood | Facial grimace, head jerks and arms movements | Face, neck, arms | 57 | Right‐lateralized bradykinesia, rest tremor and rigidity | OCB, depression | Rasagiline 1 mg daily, LEDD: 100 mg |
| Case 5 | M | 11 | Facial grimace and coughing | Face, cough | 56 | Right‐lateralized bradykinesia, rest tremor and rigidity | OCD, Generalized anxiety disorder | Rotigitine 6 mg/day (discontinued due to ICD symptoms), LD/CD ER (Rytary) 145/36.25 mg 2 tablets TID, Amantadine ER 137 mg daily, LEDD: 659 mg, Risperidone (discontinued due to weight gain and depression)*, Aripiprazole 5 mg (discontinued due to lack of effect on tics)* |
| Case 6 | F | 12 | Right arm movements | Right arm | 64 | Right‐lateralized bradykinesia, bilateral tremor | ADHD, Depression | LEDD: 0 mg, Haloperidol (during her childhood only)*, Aripiprazole 5 mg* |
| Case 7 | M | 12 | Facial grimace, mouth movements, shoulder shrug and meaningless sounds | Orofacial, vocal and shoulders | 57 | Left–lateralized bradykinesia, rest tremor and rigidity | OCD, ADHD, Anxiety | (LD/CD/entacapone) 2 tablets 100/25/200 mg QID, LEDD: 1064 mg, Cannabinoids* |
| Case 8 | M | Child‐hood | Facial grimace, mouth movements and simple phonic tics | Orofacial motor phonic tics | 74 | Right‐lateralized bradykinesia and rigidity | OCB | LD 600 mg daily, Entacapone 200 mg TID, Pramipexole 0.5 mg TID, LEDD: 948 mg |
| Haloperidol 1 mg daily* (switched to Aripiprazole 5 mg without change in parkinsonism) | ||||||||
| Case 9 | F | Child‐hood | Facial grimace and arm movements | Face, arm | 71 | Right‐lateralized bradykinesia and tremor | ADHD, OCD, Anxiety | Rasagiline 1 mg daily, LD 300 mg daily, LEDD: 400 mg |
| Case 10 | M | Child‐hood | Facial grimace | Face | 52 | Right‐lateralized bradykinesia, rigidity and dystonia | NA | (LD/CD/entacapone) 1 tablet 150/37.5/200 mg 5 times daily, LD/CD 1 tablet 100/25 mg 5 times daily |
| LD/CD ER (Sinemet CR) 3 tablets 100/25 mg nightly, LEED: 1723 mg |
Note: Of note, dopamine agonists served to treat Parkinson's disease in all patients, rather than as an anti‐tic medication. *indicates the anti‐tic medication.
Abbreviations: ADHD, attention deficit hyperactivity disorder; BID, two times daily; CD, carbidopa; ER, extended release; GPi DBS, globus pallidus internus deep brain stimulation; ICD, impulsive compulsive disorder; LD, levodopa; NA, not applicable; OCB, obsessive compulsive behaviors; OCD, obsessive compulsive disorder; TID, three times per day; QID, four times per day; STN DBS, subthalamic nucleus deep brain stimulation.
Case 1
A 51‐year‐old male with childhood‐onset CMTD presented with a left‐sided rest tremor and gait difficulties along with prodromal hyposmia and rapid eye movement sleep behavioral disorder. Examination identified left‐sided parkinsonism alongside pre‐existing orofacial simple motor tics, which had not changed in frequency or severity. A DAT SPECT revealed reduced tracer uptake in both striata (Fig. 1A). LD at a dosage of 600 mg/day improved his parkinsonian symptoms without any change in tic presentation or severity. Despite a progressive deterioration of parkinsonism over a four‐year follow‐up, there was neither objective nor subjective change in tic severity, irrespective of dopaminergic treatment.
Case 2
A 77‐year‐old left‐handed woman with a history of drug‐naïve TS was diagnosed with PD at age 56. Tics included clenching movements of the jaw and teeth, forced exhalation, left forearm pronation/supination movements, and tensing the abdominal and gluteal muscles. She was on LD 600 mg/day and pramipexole 2.75 mg/day for parkinsonism. Due to motor fluctuations, including bothersome peak‐dose dyskinesias, bilateral posterolateral GPi DBS was implanted 21 years after PD diagnosis (Fig. 1B). Throughout the course of PD, there were no changes noted in tics with different dopaminergic medications or following DBS implantation. Clinical assessment in different medication and stimulation states (dopaminergic medication and DBS on/off) did not reveal any objective changes in tic severity. Stimulation parameters are reported in Figure 1B. Notably, she could distinguish LD‐induced dyskinesias from tics based on the latter's preceding urge and somatotopic distribution.
Case 3
A 50‐year‐old male was diagnosed with sporadic young‐onset PD at the age of 36. Although he experienced motor and phonic tics during childhood, he did not receive any treatment, and the tics largely subsided in late adolescence. He had been treated for parkinsonism with LD/CD, rotigotine, amantadine, safinamide and opicapone. He underwent bilateral STN DBS at age 49 to manage motor fluctuations and reduce medication‐induced neuropsychiatric symptoms (compulsivity) related to rotigotine. At the post‐surgical 3‐month monopolar review, increasing stimulation amplitude above 2.0 mA at the therapeutic contact (Fig. 1C) elicited motor tics after a 30‐min lag (eye squeezing, eyebrow raising, trunk and head thrown backwards). He also exhibited inappropriately elevated affect (singing and excessive laughter) (see Video 1). Both phenomena lasted for several hours and resolved about 15 min after reducing the stimulation amplitude. A later attempt to reactivate the initial electrode configuration elicited the same behavioral response.
Video 1.
This 50‐year‐old man, with a childhood history of tics, experienced a transient re‐emergence of tics, based on specific stimulation settings, during monopolar review (3‐months post‐STN DBS). In the video, he describes the urge of the tics including eyebrow elevation, sniffing and retropulsion.
Discussion
This is the largest case series to date documenting individuals with co‐existing primary tics and PD, evoking important clinical and pathophysiological considerations. Previous research suggests that a hyperdopaminergic state of the cortico‐striatal‐thalamic circuit (CSTC) is involved in the pathophysiology of tics. 2 , 3 In contrast, a reduction of nigrostriatal dopamine in the CSTC is known to be the defining abnormality in neurodegenerative parkinsonism. 4 Therefore, one could hypothesize that a reduction in nigrostriatal dopaminergic innervation (which is the case in PD) would result in tic improvement, whereas dopaminergic medications would lead to tic worsening. However, this case series provides clear evidence contradicting this simplified model and demonstrates that neither the onset of PD nor the use of dopaminergic agents directly impacts tics.
The role of dopamine in tic disorders is undisputed. 3 This is clearly evidenced by the efficacy of antidopaminergic agents in treating tic disorders (Supplementary Reference S1). However, the exact relation between nigrostriatal dopaminergic availability and tics remains unclear. Previous literature (Table 2) documents six cases of primary tics and PD (Supplementary References S2–S4). Interestingly, in four of them, there was no change in tics at the onset of the parkinsonism or after the initiation of dopaminergic therapy (Supplementary Reference S2). This finding aligns with the cases reported here, arguing against dopaminergic hyperactivity as the sole driver underlying the pathophysiology of chronic tic disorders (Supplementary References S5–S7). Further evidence comes from studies that examined the effects of dopaminergic substances on tics, which showed diverse results (Supplementary References S8–S12), even including improvement of tics following dopaminergic supplementation. Additionally, a growing body of evidence supports the emerging role of other neurotransmitter abnormalities in chronic tic disorders, particularly involving striatal cholinergic interneuron function, as well as glutamate, GABA, serotonin and acetylcholine (Supplementary Reference S13). 5 However, there may be an indirect influence of dopaminergic therapy on tics that could, for example, involve affective processes, considering the well‐known exacerbating impact of anxiety on tic severity. Indeed, in one patient (case 7), hypodopaminergic states provoked anxiety and caused worsening of his tics. 6
TABLE 2.
Previous reports of patients presenting with chronic tic disorders and parkinsonism
| Number of cases and sex Diagnosis | Age at tic onset (years) | Age at onset of parkinsonism (years) | Age at last follow‐up (years) | Anti‐parkinsonian treatment | Clinical observations | |
|---|---|---|---|---|---|---|
| Kumar et al. (Supplementary Reference S2) | 4 M Parkinson's disease | Childhood | 49 | 51 | LD 300 mg daily | No change in tic severity after PD onset or during progression. No worsening of tics with LD for three patients (one untreated). |
| 7 | 70 | 75 | LD 300 mg daily; Selegiline 10 mg daily | |||
| 10 | 55 | 68 | LD 2400 mg daily; Pergolide 3 mg daily | |||
| Teens | 60 | 64 | None | |||
| Shale et al. (Supplementary Reference S3) | 1 M Parkinson's disease | 6 | 46 | NR | LD/CD 2000/200 mg daily | Reduction of tic severity at PD onset and upon progression. Tic worsening 1 year after the initiation of LD/CD. |
| Zhang et al. (Supplementary Reference S4) | 1 M Parkinson's disease | 10 | 61 | 2y after GPi DBS | LD/CD 400/100 mg daily; Ropinirole 24 mg daily; Amantadine 300 mg daily; Bilateral GPi‐DBS | Worsening of tics noted on a combination of rotigotine and LD/CD. Improvement of both Parkinsonism and tics after GPi‐DBS. |
| Patel et al. (Supplementary Reference S17) | 1F Drug‐induced parkinsonism | Childhood | 21 | 15 months after Gpi‐DBS | None | Improvement of both DIP and tics after GPi‐DBS. |
| Spitz et al. (Supplementary Reference S7) | 2 M Neuro‐acanthocytosis | 36 | 41 | 46 | LD 1000 mg daily | LD did not affect parkinsonism. Coincident improvement in tics. |
| 36 | 40 | 40 | ||||
| Yamamoto et al (Supplementary Reference S5) | 1 M | 41 | +/− 41 | NR | Case 1: LD (dose not specified) | Case 1: LD did not affect tics or parkinsonian symptoms. |
| 1F Neuro‐acanthocytosis | 34 | +/− 34 | NR | Case 2: none | Case 2: no treatment reported. | |
| Nagy et al. (Supplementary Reference S6) | 1F Neuro‐acanthocytosis | 25 | 36 | NR | LD 275 mg daily | LD did not affect tics or parkinsonian symptoms. |
Abbreviations: CD: carbidopa; DIP: Drug‐induced parkinsonism; GPi DBS: globus pallidus internus deep brain stimulation; LD: levodopa; NR: not reported; PD: Parkinson's disease.
DBS is a treatment for people with advanced PD and in those with refractory TS. 7 Interestingly, some of the anatomical structures targeted with DBS for treating PD and TS differ (eg, posteroventral GPi in PD and anteromedial GPi in TS), while others may overlap (eg, dorsal STN [Supplementary Reference S14] but also more posterior targeting of the GPi) suggesting variations in the structural and functional network abnormalities implicated in these two disorders (Supplementary Reference S15). Primary tic disorders involve dysfunction of sensorimotor, limbic, and associative CSTC resulting in tic generation, while parkinsonian motor symptoms arise from the dysfunction of the motor CSTC (Supplementary Reference S16). 8 , 9 There is limited literature discussing the effects of GPi DBS in managing coexisting TS and parkinsonism. One report described an improvement in both parkinsonian motor symptoms and tics following GPi DBS (subtarget not specified) (Supplementary Reference S4). Additionally, a patient with TS who developed drug‐induced parkinsonism due to chronic treatment with neuroleptics experienced a simultaneous benefit in both the tic disorder and parkinsonism with DBS implantation targeting the GPi (subtarget not specified) (Supplementary Reference S17). When targeting the GPi, the anteromedial location has a slightly better likelihood of success in improving tics than the posteroventral, 10 and this could potentially explain why case 2 in our series (GPi DBS targeted posteroventral), experienced improvement of parkinsonism but no change in tic severity. Interestingly, symptoms of both disorders can also be treated with DBS targeting the STN, although most likely acting via distinct functional cortical connectivity networks (Supplementary Reference S18). This is illustrated by case 3, where neither the onset of PD nor dopaminergic treatments had any effect on his “long dormant” tic behaviors, but specific STN‐DBS settings to improve parkinsonian symptoms also caused tics to resurface and elicited changes in affect.
Chronic exposure to antipsychotics—the mainstay of pharmacological tic treatments—raises the risk of drug‐induced parkinsonism, which can mimic PD. However, in some of the cases previously exposed to antipsychotics a DAT‐SPECT was performed, showing reduced putaminal tracer uptake (Fig. 1A). This together with the progressive course and response to dopaminergic therapy confirmed the clinical diagnosis of PD. For patients with comorbid PD and tics pharmacological treatment is challenging, with no established guidelines. If behavioral interventions fail, aripiprazole may be used at the lowest dose with careful monitoring when alternatives like topiramate and guanfacine prove ineffective. Other medications, such as Ecopipam may also be useful in the future (Supplementary Reference S19). Of note, tic disorders and PD are often complicated by neuropsychiatric comorbidities, making them crucial to address. For instance, anxiety can be a non‐motor symptom of PD and may worsen tics.
Our cohort lacks objective longitudinal measures of tic severity, but we found no relevant changes reported by patients or captured by their physicians during the entire follow‐up period. Moreover, we do note that the effects of nigrostriatal degeneration and dopaminergic supplementation on tics may differ in younger individuals.
In summary, this case series demonstrates that there is no linear relation between nigrostriatal dopaminergic availability and tics. Instead, it suggests a more complex interplay between several neurotransmitter systems acting on various networks of CSTC that may lie at the core of tic pathophysiology.
Author Role
(1) Research Project: A. Conception, B. Organization, C. Execution; (2) Manuscript Preparation: A. Writing of the First Draft, B. Review and Critique.
T.A.1B, 1C, 2A, 2B
A.B.1B, 1C, 2B
T.G.1C, 2B
D.I.1C, 2B
I.M.1C, 2B
R.M.1C, 2B
K.B.1C, 2B
L.H.1C, 2B
A.F.1C, 2B
S.K.1C, 2B
A.L.1C, 2B
C.G.1A, 1B, 1C, 2A, 2B
Disclosures
Ethical Compliance Statement: University Health Network ethics committee approved the study (Research Ethics Board (REB) reference: 24–5646). An informed written consent was obtained from all the patients included in this study. We confirm that all the authors have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.
Funding Sources and Conflict of Interest: No specific funding was received for this work. The authors declare that there are no conflicts of interest relevant to this work.
Financial Disclosures for the previous 12 months: TA reports no disclosures. AB reports receiving honoraria from American Academy of Neurology and Abbvie, consultancy fees from Abbvie, Abbott and Boston Scientific, and research grant from Fernand Lazard Foundation. All disclosures are not relevant to the paper. TG reports no disclosures. DI reports receiving research grant funding from the National Institute of Neurological Disorders and Stroke (K23NS131592) and Teva Neuroscience. All disclosures are not relevant to the paper. IM has participated in research funded by AbbVie, Emalex, Neuroderm, Praxis, Revance, and SAGE. She has received consulting fees from AbbVie. She has received travel compensation or honoraria from Medscape, and royalties from Robert Rose publishers. RM reports no relevant disclosures. KB reports no relevant disclosures. LH reports no relevant disclosures. AF reports the following: consultancies from Abbvie, Ceregate, Medtronic, Boston Scientific, Iota, Inbrain, Inbrain Pharma; honoraria from Abbvie, Medtronic, Boston Scientific, Sunovion, Chiesi farmaceutici, UCB, Ipsen; grants from University of Toronto, Weston foundation, Abbvie, Medtronic, Boston Scientific, CIHR. SK has received honoraria or consulting fees or research support from Abbott, Boston Scientific and Medtronic and consulting fees from Novonordisk and Bluerock. Grant support from The Michael J. Fox Foundation, Parkinson Canada, CIHR and Weston Foundation. AL served as an advisor for AbbVie, Amylyx, Aprinoia, Biogen, BioAdvance, Biohaven, BioVie, BlueRock, BMS, Denali, Janssen, Lilly, Janssen, Pharma 2B, Sun Pharma, and UCB; received honoraria from Sun Pharma, AbbVie, and Sunovion; received grants from Brain Canada, the Canadian Institutes of Health Research, the Edmond J. Safra Philanthropic Foundation, The Michael J. Fox Foundation, the Ontario Brain Institute, Parkinson's Foundation, Parkinson Canada, and the W. Garfield Weston Foundation; is serving as an expert witness in litigation related to paraquat and Parkinson's disease; and received publishing royalties from Elsevier, Saunders, Wiley‐Blackwell, Johns Hopkins Press, and Cambridge University Press. CG holds the Wolf Chair for Neurodevelopmental Psychiatry, a joint Hospital‐University Named Chair between the University of Toronto, UHN, and the UHN Foundation. He received honoraria from the Movement Disorder Society for educational activities and academic research support from the VolkswagenStiftung (Freigeist Fellowship).
Supporting information
Data S1 Supplementary References. Supplementary references, ranging from S1 to S20, are included. Please refer to the attached Supplementary file for details.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
References
- 1. Shetty AS, Bhatia KP, Lang AE. Dystonia and Parkinson's disease: what is the relationship? Neurobiol Dis 2019;132:104462. 10.1016/j.nbd.2019.05.001. [DOI] [PubMed] [Google Scholar]
- 2. Ganos C, Neumann WJ, Müller‐Vahl KR, Bhatia KP, Hallett M, Haggard P, Rothwell J. The phenomenon of exquisite motor control in tic disorders and its pathophysiological implications. Mov Disord 2021;36(6):1308–1315. 10.1002/mds.28557. [DOI] [PubMed] [Google Scholar]
- 3. Maia TV, Conceição VA. Dopaminergic disturbances in Tourette syndrome: an integrative account. Biol Psychiatry 2018;84(5):332–344. 10.1016/j.biopsych.2018.02.1172. [DOI] [PubMed] [Google Scholar]
- 4. Kalia LV, Lang AE. Parkinson's disease. The Lancet 2015;386(9996):896–912. 10.1016/S0140-6736(14)61393-3. [DOI] [PubMed] [Google Scholar]
- 5. Robertson MM, Eapen V, Singer HS, et al. Gilles de la Tourette syndrome. Nat Rev Dis Primers 2017;3:16097. 10.1038/nrdp.2016.97. [DOI] [PubMed] [Google Scholar]
- 6. Coffey BJ, Biederman J, Smoller JW, Geller DA, Sarin P, Schwartz S, Kim GS. Anxiety disorders and tic severity in juveniles with Tourette's disorder. J Am Acad Child Adolesc Psychiatry 2000;39(5):562–568. 10.1097/00004583-200005000-00009. [DOI] [PubMed] [Google Scholar]
- 7. Martino D, Malaty I, Müller‐Vahl K, et al. Treatment failure in persistent tic disorders: an expert clinicians' consensus‐based definition. Eur Child Adolesc Psychiatry 2023;32(5):859–872. 10.1007/s00787-021-01920-5. [DOI] [PubMed] [Google Scholar]
- 8. Müller‐Vahl K, Grosskreutz J, Prell T, Kaufmann J, Bodammer N, Peschel T. Tics are caused by alterations in prefrontal areas, thalamus and putamen, while changes in the cingulate gyrus reflect secondary compensatory mechanisms. BMC Neurosci 2014;15(6):1–10. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. Yael D, Vinner E, Bar‐Gad I. Pathophysiology of tic disorders. Mov Disord 2015;30(9):1171–1178. 10.1002/mds.26304. [DOI] [PubMed] [Google Scholar]
- 10. Wehmeyer L, Schüller T, Kiess J, Heiden P, Visser‐Vandewalle V, Baldermann JC, Andrade P. Target‐specific effects of deep brain stimulation for Tourette syndrome: a systematic review and meta‐analysis. Front Neurol 2021;12:769275. 10.3389/fneur.2021.769275. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data S1 Supplementary References. Supplementary references, ranging from S1 to S20, are included. Please refer to the attached Supplementary file for details.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.