Altered frontal-mediated inhibition and white matter connectivity in pediatric chronic tic disorders

Abstract

Tics are unique from most movement disorders, in that they are partially suppressible. As part of the inhibitory motor network, the pre-supplementary motor area is engaged in motor control and may be involved in tic physiology. We used dual-site transcranial magnetic stimulation to assess inhibitory connectivity between right pre-supplementary motor area and left primary motor cortex, which has previously been demonstrated in healthy adults. We also used diffusion tensor imaging to investigate white matter connectivity in children with chronic tics. Twelve children with chronic tic disorder and fourteen typically developing controls underwent MRI with diffusion tensor imaging indices analysis followed by single and paired-pulse transcranial magnetic stimulation with conditioning pulse over the right pre-supplementary motor area followed by left motor cortex test pulse. Neurophysiologic and imaging data relationships to measures of tic severity and suppressibility were also evaluated in tic patients. Pre-supplementary motor area-mediated inhibition of left motor cortex was present in healthy control children but not in chronic tic disorder participants. Less inhibition correlated with worse tic suppressibility (ρ = − 0.73, p = 0.047). Imaging analysis showed increased fractional anisotropy in the right superior longitudinal fasciculus, corpus callosum, corona radiata and posterior limb of the internal capsule (p < 0.05) in tic participants, which correlated with lower self-reported tic suppressibility (ρ = − 0.70, p = 0.05). Physiologic data revealed impaired frontal-mediated motor cortex inhibition in chronic tic participants, and imaging analysis showed abnormalities in motor pathways. Collectively, the neurophysiologic and neuroanatomic data correlate with tic suppressibility, supporting the relevancy to tic pathophysiology.

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Availability of data and material

The data that support the findings of this study are available upon reasonable request.

References

  1. American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders: DSM-5. American Psychiatric Association, Washington, D.C.

    Google Scholar 

  2. Arai N, Muller-Dahlhaus F, Murakami T, Bliem B, Lu MK, Ugawa Y, Ziemann U (2011) State-dependent and timing-dependent bidirectional associative plasticity in the human SMA-M1 network. J Neurosci 31:15376–15383. https://doi.org/10.1523/JNEUROSCI.2271-11.2011

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  3. Arai N, Lu MK, Ugawa Y, Ziemann U (2012) Effective connectivity between human supplementary motor area and primary motor cortex: a paired-coil TMS study. Exp Brain Res 220:79–87. https://doi.org/10.1007/s00221-012-3117-5

    Article  PubMed  Google Scholar 

  4. Aron AR (2011) From reactive to proactive and selective control: developing a richer model for stopping inappropriate responses. Biol Psychiatry 69:e55-68. https://doi.org/10.1016/j.biopsych.2010.07.024

    Article  PubMed  Google Scholar 

  5. Aron AR, Poldrack RA (2006) Cortical and subcortical contributions to Stop signal response inhibition: role of the subthalamic nucleus. J Neurosci 26:2424–2433. https://doi.org/10.1523/JNEUROSCI.4682-05.2006

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  6. Banaschewski T, Woerner W, Rothenberger A (2003) Premonitory sensory phenomena and suppressibility of tics in Tourette syndrome: developmental aspects in children and adolescents. Dev Med Child Neurol 45:700–703

    Article  Google Scholar 

  7. Baumer T, Thomalla G, Kroeger J et al (2010) Interhemispheric motor networks are abnormal in patients with Gilles de la Tourette syndrome. Mov Disord 25:2828–2837. https://doi.org/10.1002/mds.23418

    Article  PubMed  Google Scholar 

  8. Behler N, Leitner B, Mezger E et al (2018) Cathodal tDCS over motor cortex does not improve Tourette syndrome: lessons learned from a case series. Front Behav Neurosci 12:194. https://doi.org/10.3389/fnbeh.2018.00194

    Article  PubMed  PubMed Central  Google Scholar 

  9. Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate—a practical and powerful approach to multiple testing. J R Stat Soc Ser B Stat Methodol 57:289–300. https://doi.org/10.1111/j.2517-6161.1995.tb02031.x

    Article  Google Scholar 

  10. Bohlhalter S, Goldfine A, Matteson S et al (2006) Neural correlates of tic generation in Tourette syndrome: an event-related functional MRI study. Brain 129:2029–2037

    CAS  Article  Google Scholar 

  11. Bozkurt B, Yagmurlu K, Middlebrooks EH et al (2016) Microsurgical and tractographic anatomy of the supplementary motor area complex in humans. World Neurosurg 95:99–107. https://doi.org/10.1016/j.wneu.2016.07.072

    Article  PubMed  Google Scholar 

  12. Carvalho S, Goncalves OF, Soares JM, Sampaio A, Macedo F, Fregni F, Leite J (2015) Sustained effects of a neural-based intervention in a refractory case of Tourette syndrome. Brain Stimul 8:657–659. https://doi.org/10.1016/j.brs.2014.12.008

    Article  PubMed  Google Scholar 

  13. Chouinard PA, Paus T (2010) What have we learned from “perturbing” the human cortical motor system with transcranial magnetic stimulation? Front Hum Neurosci 4:173. https://doi.org/10.3389/fnhum.2010.00173

    Article  PubMed  PubMed Central  Google Scholar 

  14. Civardi C, Cantello R, Asselman P, Rothwell JC (2001) Transcranial magnetic stimulation can be used to test connections to primary motor areas from frontal and medial cortex in humans. Neuroimage 14:1444–1453. https://doi.org/10.1006/nimg.2001.0918

    CAS  Article  PubMed  Google Scholar 

  15. Conelea CA, Woods DW, Zinner SH et al (2011) Exploring the impact of chronic tic disorders on youth: results from the Tourette syndrome impact survey. Child Psychiatry Hum Dev 42:219–242. https://doi.org/10.1007/s10578-010-0211-4

    Article  PubMed  Google Scholar 

  16. Conforto AB, Z’Graggen WJ, Kohl AS, Rosler KM, Kaelin-Lang A (2004) Impact of coil position and electrophysiological monitoring on determination of motor thresholds to transcranial magnetic stimulation. Clin Neurophysiol 115:812–819. https://doi.org/10.1016/j.clinph.2003.11.010

    Article  PubMed  Google Scholar 

  17. Cubo E (2012) Review of prevalence studies of tic disorders: methodological caveats. Tremor Other Hyperkinet Mov (N Y) 2

  18. Cunnington R, Windischberger C, Deecke L, Moser E (2002) The preparation and execution of self-initiated and externally-triggered movement: a study of event-related fMRI. Neuroimage 15:373–385. https://doi.org/10.1006/nimg.2001.0976

    CAS  Article  PubMed  Google Scholar 

  19. Cunnington R, Windischberger C, Moser E (2005) Premovement activity of the pre-supplementary motor area and the readiness for action: studies of time-resolved event-related functional MRI. Hum Mov Sci 24:644–656. https://doi.org/10.1016/j.humov.2005.10.001

    Article  PubMed  Google Scholar 

  20. Debes N, Jeppesen S, Raghava JM, Groth C, Rostrup E, Skov L (2015) Longitudinal magnetic resonance imaging (MRI) analysis of the developmental changes of Tourette syndrome reveal reduced diffusion in the cortico-striato-thalamo-cortical pathways. J Child Neurol 30:1315–1326. https://doi.org/10.1177/0883073814560629

    Article  PubMed  Google Scholar 

  21. Draganski B, Martino D, Cavanna AE et al (2010) Multispectral brain morphometry in Tourette syndrome persisting into adulthood. Brain 133:3661–3675. https://doi.org/10.1093/brain/awq300

    Article  PubMed  PubMed Central  Google Scholar 

  22. Draper A, Stephenson MC, Jackson GM, Pepes S, Morgan PS, Morris PG, Jackson SR (2014) Increased GABA contributes to enhanced control over motor excitability in Tourette syndrome. Curr Biol 24:2343–2347. https://doi.org/10.1016/j.cub.2014.08.038

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. Dum RP, Strick PL (1991) The origin of corticospinal projections from the premotor areas in the frontal lobe. J Neurosci 11:667–689

    CAS  Article  Google Scholar 

  24. DuPaul GJ (1998) ADHD rating scale-IV: checklists, norms, and clinical interpretation. Guilford Press, New York

    Google Scholar 

  25. Eichele H, Plessen KJ (2013) Neural plasticity in functional and anatomical MRI studies of children with Tourette syndrome. Behav Neurol 27:33–45. https://doi.org/10.3233/BEN-120294

    Article  PubMed  PubMed Central  Google Scholar 

  26. Ferbert A, Priori A, Rothwell JC, Day BL, Colebatch JG, Marsden CD (1992) Interhemispheric inhibition of the human motor cortex. J Physiol 453:525–546. https://doi.org/10.1113/jphysiol.1992.sp019243

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  27. Filevich E, Kuhn S, Haggard P (2012) Negative motor phenomena in cortical stimulation: implications for inhibitory control of human action. Cortex 48:1251–1261. https://doi.org/10.1016/j.cortex.2012.04.014

    Article  PubMed  Google Scholar 

  28. Fiori F, Chiappini E, Soriano M, Paracampo R, Romei V, Borgomaneri S, Avenanti A (2016) Long-latency modulation of motor cortex excitability by ipsilateral posterior inferior frontal gyrus and pre-supplementary motor area. Sci Rep 6:38396. https://doi.org/10.1038/srep38396

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  29. Franzkowiak S, Pollok B, Biermann-Ruben K et al (2012) Motor-cortical interaction in Gilles de la Tourette syndrome. PLoS ONE 7:e27850. https://doi.org/10.1371/journal.pone.0027850

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  30. Govindan RM, Makki MI, Wilson BJ, Behen ME, Chugani HT (2010) Abnormal water diffusivity in corticostriatal projections in children with Tourette syndrome. Hum Brain Mapp 31:1665–1674. https://doi.org/10.1002/hbm.20970

    Article  PubMed  PubMed Central  Google Scholar 

  31. Greene DJ, Schlaggar BL, Black KJ (2015) Neuroimaging in Tourette syndrome: research highlights From 2014–2015. Curr Dev Disord Rep 2:300–308. https://doi.org/10.1007/s40474-015-0062-6

    Article  PubMed  PubMed Central  Google Scholar 

  32. Hampson M, Tokoglu F, King RA, Constable RT, Leckman JF (2009) Brain areas coactivating with motor cortex during chronic motor tics and intentional movements. Biol Psychiatry 65:594–599. https://doi.org/10.1016/j.biopsych.2008.11.012

    Article  PubMed  Google Scholar 

  33. Hua K, Zhang J, Wakana S et al (2008) Tract probability maps in stereotaxic spaces: analyses of white matter anatomy and tract-specific quantification. Neuroimage 39:336–347. https://doi.org/10.1016/j.neuroimage.2007.07.053

    Article  Google Scholar 

  34. Ikeda A, Yazawa S, Kunieda T et al (1999) Cognitive motor control in human pre-supplementary motor area studied by subdural recording of discrimination/selection-related potentials. Brain 122(Pt 5):915–931. https://doi.org/10.1093/brain/122.5.915

    Article  PubMed  Google Scholar 

  35. Jackson SR, Parkinson A, Manfredi V, Millon G, Hollis C, Jackson GM (2013) Motor excitability is reduced prior to voluntary movements in children and adolescents with Tourette syndrome. J Neuropsychol 7:29–44. https://doi.org/10.1111/j.1748-6653.2012.02033.x

    Article  PubMed  PubMed Central  Google Scholar 

  36. Kim JH, Lee JM, Jo HJ et al (2010) Defining functional SMA and pre-SMA subregions in human MFC using resting state fMRI: functional connectivity-based parcellation method. Neuroimage 49:2375–2386. https://doi.org/10.1016/j.neuroimage.2009.10.016

    Article  PubMed  Google Scholar 

  37. Kukaswadia S, Wagle-Shukla A, Morgante F, Gunraj C, Chen R (2005) Interactions between long latency afferent inhibition and interhemispheric inhibitions in the human motor cortex. J Physiol 563:915–924. https://doi.org/10.1113/jphysiol.2004.080010

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  38. Kunieda T, Ikeda A, Ohara S et al (2000) Different activation of presupplementary motor area, supplementary motor area proper, and primary sensorimotor area, depending on the movement repetition rate in humans. Exp Brain Res 135:163–172. https://doi.org/10.1007/s002210000519

    CAS  Article  PubMed  Google Scholar 

  39. Kurlan R, McDermott MP, Deeley C et al (2001) Prevalence of tics in schoolchildren and association with placement in special education. Neurology 57:1383–1388

    CAS  Article  Google Scholar 

  40. Landeros-Weisenberger A, Mantovani A, Motlagh MG, de Alvarenga PG, Katsovich L, Leckman JF, Lisanby SH (2015) Randomized sham controlled double-blind trial of repetitive transcranial magnetic stimulation for adults with severe Tourette syndrome. Brain Stimul 8:574–581. https://doi.org/10.1016/j.brs.2014.11.015

    Article  PubMed  Google Scholar 

  41. Leckman JF, Riddle MA, Hardin MT, Ort SI, Swartz KL, Stevenson J, Cohen DJ (1989) The yale global tic severity scale: initial testing of a clinician-rated scale of tic severity. J Am Acad Child Adolesc Psychiatry 28:566–573

    CAS  Article  Google Scholar 

  42. Leckman JF, Walker DE, Cohen DJ (1993) Premonitory urges in Tourette’s syndrome. Am J Psychiatry 150:98–102

    CAS  Article  Google Scholar 

  43. Li CS, Huang C, Constable RT, Sinha R (2006) Imaging response inhibition in a stop-signal task: neural correlates independent of signal monitoring and post-response processing. J Neurosci 26:186–192. https://doi.org/10.1523/JNEUROSCI.3741-05.2006

    CAS  Article  PubMed  Google Scholar 

  44. Liu Y, Miao W, Wang J et al (2013) Structural abnormalities in early Tourette syndrome children: a combined voxel-based morphometry and tract-based spatial statistics study. PLoS ONE 8:e76105. https://doi.org/10.1371/journal.pone.0076105

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  45. Makki MI, Behen M, Bhatt A, Wilson B, Chugani HT (2008) Microstructural abnormalities of striatum and thalamus in children with Tourette syndrome. Mov Disord 23:2349–2356. https://doi.org/10.1002/mds.22264

    Article  PubMed  Google Scholar 

  46. Mars RB, Klein MC, Neubert FX, Olivier E, Buch ER, Boorman ED, Rushworth MF (2009) Short-latency influence of medial frontal cortex on primary motor cortex during action selection under conflict. J Neurosci 29:6926–6931. https://doi.org/10.1523/JNEUROSCI.1396-09.2009

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  47. Martino D, Delorme C, Pelosin E, Hartmann A, Worbe Y, Avanzino L (2017) Abnormal lateralization of fine motor actions in Tourette syndrome persists into adulthood. PLoS ONE 12:e0180812. https://doi.org/10.1371/journal.pone.0180812

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  48. Mills KR, Nithi KA (1997) Corticomotor threshold to magnetic stimulation: normal values and repeatability. Muscle Nerve 20:570–576

    CAS  Article  Google Scholar 

  49. Misirlisoy E, Brandt V, Ganos C, Tubing J, Munchau A, Haggard P (2015) The relation between attention and tic generation in Tourette syndrome. Neuropsychology 29:658–665. https://doi.org/10.1037/neu0000161

    Article  PubMed  Google Scholar 

  50. Muller-Vahl KR, Riemann L, Bokemeyer S (2014) Tourette patients’ misbelief of a tic rebound is due to overall difficulties in reliable tic rating. J Psychosom Res 76:472–476. https://doi.org/10.1016/j.jpsychores.2014.03.003

    Article  PubMed  Google Scholar 

  51. Nachev P, Kennard C, Husain M (2008) Functional role of the supplementary and pre-supplementary motor areas. Nat Rev Neurosci 9:856–869. https://doi.org/10.1038/nrn2478

    CAS  Article  PubMed  Google Scholar 

  52. Neubert FX, Mars RB, Buch ER, Olivier E, Rushworth MF (2010) Cortical and subcortical interactions during action reprogramming and their related white matter pathways. Proc Natl Acad Sci U S A 107:13240–13245. https://doi.org/10.1073/pnas.1000674107

    Article  PubMed  PubMed Central  Google Scholar 

  53. Neuner I, Kupriyanova Y, Stocker T et al (2010) White-matter abnormalities in Tourette syndrome extend beyond motor pathways. Neuroimage 51:1184–1193. https://doi.org/10.1016/j.neuroimage.2010.02.049

    Article  PubMed  Google Scholar 

  54. Picard N, Strick PL (1996) Motor areas of the medial wall: a review of their location and functional activation. Cereb Cortex 6:342–353

    CAS  Article  Google Scholar 

  55. Picazio S, Veniero D, Ponzo V, Caltagirone C, Gross J, Thut G, Koch G (2014) Prefrontal control over motor cortex cycles at beta frequency during movement inhibition. Curr Biol 24:2940–2945. https://doi.org/10.1016/j.cub.2014.10.043

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  56. Rossi S, Hallett M, Rossini PM, Pascual-Leone A (2011) Screening questionnaire before TMS: an update. Clin Neurophysiol 122:1686. https://doi.org/10.1016/j.clinph.2010.12.037

    Article  PubMed  Google Scholar 

  57. Rushworth MF, Hadland KA, Paus T, Sipila PK (2002) Role of the human medial frontal cortex in task switching: a combined fMRI and TMS study. J Neurophysiol 87:2577–2592. https://doi.org/10.1152/jn.2002.87.5.2577

    CAS  Article  PubMed  Google Scholar 

  58. Saporta AS, Chugani HT, Juhasz C, Makki MI, Muzik O, Wilson BJ, Behen ME (2010) Multimodality neuroimaging in Tourette syndrome: alpha-[11C] methyl-l-tryptophan positron emission tomography and diffusion tensor imaging studies. J Child Neurol 25:336–342. https://doi.org/10.1177/0883073809339394

    Article  PubMed  Google Scholar 

  59. Scahill L, Riddle MA, McSwiggin-Hardin M et al (1997) Children’s Yale-Brown obsessive compulsive scale: reliability and validity. J Am Acad Child Adolesc Psychiatry 36:844–852

    CAS  Article  Google Scholar 

  60. Serrien DJ, Orth M, Evans AH, Lees AJ, Brown P (2005) Motor inhibition in patients with Gilles de la Tourette syndrome: functional activation patterns as revealed by EEG coherence. Brain 128:116–125. https://doi.org/10.1093/brain/awh318

    Article  PubMed  Google Scholar 

  61. Shirota Y, Hamada M, Terao Y, Ohminami S, Tsutsumi R, Ugawa Y, Hanajima R (2012) Increased primary motor cortical excitability by a single-pulse transcranial magnetic stimulation over the supplementary motor area. Exp Brain Res 219:339–349. https://doi.org/10.1007/s00221-012-3095-7

    CAS  Article  PubMed  Google Scholar 

  62. Sigurdsson HP, Pepes SE, Jackson GM, Draper A, Morgan PS, Jackson SR (2018) Alterations in the microstructure of white matter in children and adolescents with Tourette syndrome measured using tract-based spatial statistics and probabilistic tractography. Cortex 104:75–89. https://doi.org/10.1016/j.cortex.2018.04.004

    Article  PubMed  PubMed Central  Google Scholar 

  63. Smith SM, Nichols TE (2009) Threshold-free cluster enhancement: addressing problems of smoothing, threshold dependence and localisation in cluster inference. Neuroimage 44:83–98. https://doi.org/10.1016/j.neuroimage.2008.03.061

    Article  Google Scholar 

  64. Smith SM, Jenkinson M, Woolrich MW et al (2004) Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage 23(Suppl 1):S208-219. https://doi.org/10.1016/j.neuroimage.2004.07.051

    Article  Google Scholar 

  65. Thomalla G, Siebner HR, Jonas M et al (2009) Structural changes in the somatosensory system correlate with tic severity in Gilles de la Tourette syndrome. Brain 132:765–777. https://doi.org/10.1093/brain/awn339

    Article  PubMed  Google Scholar 

  66. Wagner J, Wessel JR, Ghahremani A, Aron AR (2018) Establishing a right frontal beta signature for stopping action in scalp EEG: implications for testing inhibitory control in other task contexts. J Cogn Neurosci 30:107–118. https://doi.org/10.1162/jocn_a_01183

    Article  PubMed  Google Scholar 

  67. Wang Z, Maia TV, Marsh R, Colibazzi T, Gerber A, Peterson BS (2011) The neural circuits that generate tics in Tourette’s syndrome. Am J Psychiatry 168:1326–1337. https://doi.org/10.1176/appi.ajp.2011.09111692

    Article  PubMed  PubMed Central  Google Scholar 

  68. Wen H, Liu Y, Wang J et al (2016) Combining tract- and atlas-based analysis reveals microstructural abnormalities in early Tourette syndrome children. Hum Brain Mapp 37:1903–1919. https://doi.org/10.1002/hbm.23146

    Article  PubMed  PubMed Central  Google Scholar 

  69. Wolff N, Luehr I, Sender J, Ehrlich S, Schmidt-Samoa C, Dechent P, Roessner V (2016) A DTI study on the corpus callosum of treatment-naive boys with “pure” Tourette syndrome. Psychiatry Res Neuroimaging 247:1–8. https://doi.org/10.1016/j.pscychresns.2015.12.003

    Article  PubMed  Google Scholar 

  70. Woods DW, Piacentini J, Himle MB, Chang S (2005) Premonitory Urge for Tics Scale (PUTS): initial psychometric results and examination of the premonitory urge phenomenon in youths with Tic disorders. J Dev Behav Pediatr 26:397–403

    Article  Google Scholar 

  71. Wu SW, Maloney T, Gilbert DL et al (2014) Functional MRI-navigated repetitive transcranial magnetic stimulation over supplementary motor area in chronic tic disorders. Brain Stimul 7:212–218. https://doi.org/10.1016/j.brs.2013.10.005

    Article  PubMed  Google Scholar 

  72. Xu B, Sandrini M, Wang WT et al (2016) PreSMA stimulation changes task-free functional connectivity in the fronto-basal-ganglia that correlates with response inhibition efficiency. Hum Brain Mapp 37:3236–3249. https://doi.org/10.1002/hbm.23236

    Article  PubMed  PubMed Central  Google Scholar 

  73. Yazawa S, Ikeda A, Kunieda T et al (2000) Human presupplementary motor area is active before voluntary movement: subdural recording of Bereitschaftspotential from medial frontal cortex. Exp Brain Res 131:165–177. https://doi.org/10.1007/s002219900311

    CAS  Article  PubMed  Google Scholar 

  74. Zhang S, Ide JS, Li CS (2012) Resting-state functional connectivity of the medial superior frontal cortex. Cereb Cortex 22:99–111. https://doi.org/10.1093/cercor/bhr088

    Article  PubMed  Google Scholar 

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Acknowledgements

We appreciate participants and families who took time to participate in this study.

Funding

This research was supported in part by The Sage Foundation (Brighton, MI), Cincinnati Children’s Research Foundation, Tourette Association of America and National Institutes of Health.

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ABB: research project—organization and execution; statistical analysis—review and critique; manuscript preparation—writing of the first draft, review and critique. WY: research project—conception, organization, and execution; statistical analysis—design, execution, review and critique; manuscript preparation—review and critique. DLG: research project conception, and organization; statistical analysis—review and critique; manuscript preparation—review and critique. PSH: statistical analysis—design, execution, review and critique; manuscript preparation—review and critique. HSJ: research project—organization and execution. DAH: research project—organization and execution. SWW: research project—conception, organization, and execution; statistical analysis—design, execution, review and critique; manuscript preparation—writing, review and critique.

Corresponding author

Correspondence to Steve W. Wu.

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Conflict of interest

DG has received honoraria and travel support from the Tourette Association of America and has received research support from the National Institutes of Health. PH has received research support through the National Institutes of Health. SW received funding support from Cincinnati Children’s Research Foundation, has received salary support from Tourette Association of America and the National Institute of Health, and received funding for equipment used in this study from The Sage Foundation (Brighton, MI). The rest of the authors have no disclosures relevant to this study. On behalf of all authors, the corresponding author states that there is no conflict of interest.

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This study was approved by the CCHMC Institutional Review Board.

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A parent or legal guardian of pediatric participants gave written informed consent. Children also gave written assent for the study.

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Communicated by Winston D Byblow.

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Bruce, A.B., Yuan, W., Gilbert, D.L. et al. Altered frontal-mediated inhibition and white matter connectivity in pediatric chronic tic disorders. Exp Brain Res (2021). https://doi.org/10.1007/s00221-020-06017-0

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Keywords

  • Transcranial magnetic stimulation
  • Diffusion tensor imaging
  • Tourette
  • Tics
  • Pre-supplementary motor area