The Pathophysiology of Tics; An Evolving Story

Harvey    S.    Singer; Farhan       Augustine
Abstract

Background: Tics, defined as quick, rapid, sudden, recurrent, non-rhythmic motor movements or vocalizations are required components of Tourette Syndrome (TS) - a complex disorder characterized by the presence of fluctuating, chronic motor and vocal tics, and the presence of co-existing neuropsychological problems. Despite many advances, the underlying pathophysiology of tics/TS remains unknown.
Objective: To address a variety of controversies surrounding the pathophysiology of TS. More specifically: 1) the configuration of circuits likely involved; 2) the role of inhibitory influences on motor control; 3) the classification of tics as either goal-directed or habitual behaviors; 4) the potential anatomical site of origin, e.g. cortex, striatum, thalamus, cerebellum, or other(s); and 5) the role of specific neurotransmitters (dopamine, glutamate, GABA, and others) as possible mechanisms (Abstract figure).
Methods: Existing evidence from current clinical, basic science, and animal model studies are reviewed to provide: 1) an expanded understanding of individual components and the complex integration of the Cortico-Basal Ganglia-Thalamo-Cortical (CBGTC) circuit - the pathway involved with motor control; and 2) scientific data directly addressing each of the aforementioned controversies regarding pathways, inhibition, classification, anatomy, and neurotransmitters.
Conclusion: Until a definitive pathophysiological mechanism is identified, one functional approach is to consider that a disruption anywhere within CBGTC circuitry, or a brain region inputting to the motor circuit, can lead to an aberrant message arriving at the primary motor cortex and enabling a tic. Pharmacologic modulation may be therapeutically beneficial, even though it might not be directed toward the primary abnormality.
Keywords: Pathophysiology, tics, neurotransmitters, CBGTC circuits, habitual behaviors.
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Graphical Abstract

[1] 
Kurlan R, McDermott MP, Deeley C, et al. Prevalence of tics in schoolchildren and association with placement in special education. Neurology  2001; 57(8): 1383-8.
[http://dx.doi.org/10.1212/WNL.57.8.1383] [PMID: 11673576] 
[2] 
Mataix-Cols D, Isomura K, Pérez-Vigil A, et al. Familial risks of tourette syndrome and chronic tic disorders: A population-based cohort study. JAMA Psychiatry  2015; 72(8): 787-93.
[http://dx.doi.org/10.1001/jamapsychiatry.2015.0627] [PMID: 26083307] 
[3] 
Huang AY, Yu D, Davis LK, et al. Tourette Syndrome Association International Consortium for Genetics (TSAICG); Gilles de la Tourette Syndrome GWAS Replication Initiative (GGRI). Rare Copy Number Variants in NRXN1 and CNTN6 Increase Risk for Tourette Syndrome. Neuron  2017; 94(6): 1101-1111.e7.
[http://dx.doi.org/10.1016/j.neuron.2017.06.010] [PMID: 28641109] 
[4] 
Kwak C, Dat Vuong K, Jankovic J. Premonitory sensory phenomenon in Tourette’s syndrome. Mov Disord  2003; 18(12): 1530-3.
[http://dx.doi.org/10.1002/mds.10618] [PMID: 14673893] 
[5] 
Banaschewski T, Woerner W, Rothenberger A. Premonitory sensory phenomena and suppressibility of tics in Tourette syndrome: developmental aspects in children and adolescents. Dev Med Child Neurol  2003; 45(10): 700-3.
[http://dx.doi.org/10.1111/j.1469-8749.2003.tb00873.x] [PMID: 14515942] 
[6] 
Belluscio BA, Jin L, Watters V, Lee TH, Hallett M. Sensory sensitivity to external stimuli in Tourette syndrome patients. Mov Disord  2011; 26(14): 2538-43.
[http://dx.doi.org/10.1002/mds.23977] [PMID: 22038938] 
[7] 
Hirschtritt ME, Lee PC, Pauls DL, et al. Tourette Syndrome Association International Consortium for Genetics. Lifetime prevalence, age of risk, and genetic relationships of comorbid psychiatric disorders in Tourette syndrome. JAMA Psychiatry  2015; 72(4): 325-33.
[http://dx.doi.org/10.1001/jamapsychiatry.2014.2650] [PMID: 25671412] 
[8] 
Jahanshahi M, Obeso I, Rothwell JC, Obeso JA. A fronto-striato-subthalamic-pallidal network for goal-directed and habitual inhibition. Nat Rev Neurosci  2015; 16(12): 719-32.
[http://dx.doi.org/10.1038/nrn4038] [PMID: 26530468] 
[9] 
Gage GJ, Stoetzner CR, Wiltschko AB, Berke JD. Selective activation of striatal fast-spiking interneurons during choice execution. Neuron  2010; 67(3): 466-79.
[http://dx.doi.org/10.1016/j.neuron.2010.06.034] [PMID: 20696383] 
[10] 
Hamani C, Saint-Cyr JA, Fraser J, Kaplitt M, Lozano AM. The subthalamic nucleus in the context of movement disorders. Brain  2004; 127(Pt 1): 4-20.
[http://dx.doi.org/10.1093/brain/awh029] [PMID: 14607789] 
[11] 
Meidahl AC, Orlowski D, Sørensen JCH, Bjarkam CR. The retrograde connections and anatomical segregation of the Göttingen Minipig Nucleus Accumbens Front Neuroanat 2016.  10: 117.
[http://dx.doi.org/10.3389/fnana.2016.00117] 
[12] 
Flanigan M, LeClair K. shared motivational functions of ventral striatum d1 and d2 medium spiny neurons. J Neurosci  2017; 37(26): 6177-9.
[http://dx.doi.org/10.1523/JNEUROSCI.0882-17.2017] [PMID: 28659329] 
[13] 
Natsubori A, Tsutsui-Kimura I, Nishida H, et al. ventrolateral striatal medium spiny neurons positively regulate food-incentive, goal-directed behavior independently of d1 and d2 selectivity. J Neurosci  2017; 37(10): 2723-33.
[http://dx.doi.org/10.1523/JNEUROSCI.3377-16.2017] [PMID: 28167674] 
[14] 
Wright WJ, Schlüter OM, Dong Y. A feedforward inhibitory circuit mediated by cb1-expressing fast-spiking interneurons in the nucleus accumbens. Neuropsychopharmacology  2017; 42(5): 1146-56.
[http://dx.doi.org/10.1038/npp.2016.275] [PMID: 27929113] 
[15] 
Winters BD, Krüger JM, Huang X, et al. Cannabinoid receptor 1-expressing neurons in the nucleus accumbens. Proc Natl Acad Sci USA  2012; 109(40): E2717-25.
[http://dx.doi.org/10.1073/pnas.1206303109] [PMID: 23012412] 
[16] 
Fudge JL, Kelly EA, Pal R, Bedont JL, Park L, Ho B. beyond the classic vta: extended amygdala projections to da-striatal paths in the primate. Neuropsychopharmacology  2017; 42(8): 1563-76.
[http://dx.doi.org/10.1038/npp.2017.38] [PMID: 28220796] 
[17] 
Burton AC, Nakamura K, Roesch MR. From ventral-medial to dorsal-lateral striatum: neural correlates of reward-guided decision-making. Neurobiol Learn Mem  2015; 117: 51-9.
[http://dx.doi.org/10.1016/j.nlm.2014.05.003] [PMID: 24858182] 
[18] 
Rich MT, Huang YH, Torregrossa MM. plasticity at thalamo-amygdala synapses regulates cocaine-cue memory formation and extinction. Cell Rep  2019; 26(4): 1010-1020.e5.
[http://dx.doi.org/10.1016/j.celrep.2018.12.105] [PMID: 30673597] 
[19] 
Ferrari PF, Gerbella M, Coudé G, Rozzi S. Two different mirror neuron networks: The sensorimotor (hand) and limbic (face) pathways. Neuroscience  2017; 358: 300-15.
[http://dx.doi.org/10.1016/j.neuroscience.2017.06.052] [PMID: 28687313] 
[20] 
LeDoux JE, Farb CR, Romanski LM. Overlapping projections to the amygdala and striatum from auditory processing areas of the thalamus and cortex. Neurosci Lett  1991; 134(1): 139-44.
[http://dx.doi.org/10.1016/0304-3940(91)90526-Y] [PMID: 1815147] 
[21] 
Bosch-Bouju C, Hyland BI, Parr-Brownlie LC. Motor thalamus integration of cortical, cerebellar and basal ganglia information: implications for normal and parkinsonian conditions. Front Comput Neurosci  2013; 7: 163.
[http://dx.doi.org/10.3389/fncom.2013.00163] [PMID: 24273509] 
[22] 
Hooks BM, Mao T, Gutnisky DA, Yamawaki N, Svoboda K, Shepherd GM. Organization of cortical and thalamic input to pyramidal neurons in mouse motor cortex. J Neurosci  2013; 33(2): 748-60.
[http://dx.doi.org/10.1523/JNEUROSCI.4338-12.2013] [PMID: 23303952] 
[23] 
Alloway KD, Smith JB, Mowery TM, Watson GDR. sensory processing in the dorsolateral striatum: The contribution of thalamostriatal pathways. Front Syst Neurosci  2017; 11: 53.
[http://dx.doi.org/10.3389/fnsys.2017.00053] [PMID: 28790899] 
[24] 
Marano M, Migliore S, Squitieri F, Insola A, Scarnati E, Mazzone P. 2019.http://www.sciencedirect.com/science/article/pii/S0967586818320587
[25] 
Testini P, Min H-K, Bashir A, Lee KH. Deep brain stimulation for Tourette’s syndrome: The case for targeting the thalamic centromedian-parafascicular complex. Front Neurol  2016; 7: 193.
[http://dx.doi.org/10.3389/fneur.2016.00193] [PMID: 27891112] 
[26] 
Minamimoto T, Kimura M. Participation of the thalamic CM-Pf complex in attentional orienting. J Neurophysiol  2002; 87(6): 3090-101.
[http://dx.doi.org/10.1152/jn.2002.87.6.3090] [PMID: 12037210] 
[27] 
Bostan AC, Strick PL. The basal ganglia and the cerebellum: nodes in an integrated network. Nat Rev Neurosci  2018; 19(6): 338-50.
[http://dx.doi.org/10.1038/s41583-018-0002-7] [PMID: 29643480] 
[28] 
Caligiore D, Pezzulo G, Baldassarre G, et al. consensus paper: towards a systems-level view of cerebellar function: the interplay between cerebellum, basal ganglia, and cortex. Cerebellum  2017; 16(1): 203-29.
[http://dx.doi.org/10.1007/s12311-016-0763-3] [PMID: 26873754] 
[29] 
Tanaka H, Ishikawa T, Kakei S. Neural evidence of the cerebellum as a state predictor. Cerebellum  2019; 18(3): 349-71.
[http://dx.doi.org/10.1007/s12311-018-0996-4] [PMID: 30627965] 
[30] 
Augustine F, Singer HS. Merging the pathophysiology and pharmacotherapy of tics. Tremor Other Hyperkinet Mov (N Y)  2019; 8: 595.
[PMID: 30643668] 
[31] 
Carta I, Chen CH, Schott AL, Dorizan S, Khodakhah K. Cerebellar modulation of the reward circuitry and social behavior. Science  2019; 363(6424)eaav0581
[http://dx.doi.org/10.1126/science.aav0581] [PMID: 30655412] 
[32] 
Bostan AC, Dum RP, Strick PL. The basal ganglia communicate with the cerebellum. Proc Natl Acad Sci USA  2010; 107(18): 8452-6.
[http://dx.doi.org/10.1073/pnas.1000496107] [PMID: 20404184] 
[33] 
Pelzer EA, Hintzen A, Goldau M, von Cramon DY, Timmermann L, Tittgemeyer M. Cerebellar networks with basal ganglia: feasibility for tracking cerebello-pallidal and subthalamo-cerebellar projections in the human brain. Eur J Neurosci  2013; 38(8): 3106-14.
[http://dx.doi.org/10.1111/ejn.12314] [PMID: 23879686] 
[34] 
Albin RL, Young AB, Penney JB. The functional anatomy of basal ganglia disorders. Trends Neurosci  1989; 12(10): 366-75.
[http://dx.doi.org/10.1016/0166-2236(89)90074-X] [PMID: 2479133] 
[35] 
Bonnavion P, Fernández EP, Varin C, de Kerchove d’Exaerde A. It takes two to tango: Dorsal direct and indirect pathways orchestration of motor learning and behavioral flexibility. Neurochem Int  2019; 124: 200-14.
[http://dx.doi.org/10.1016/j.neuint.2019.01.009] [PMID: 30659871] 
[36] 
Klaus A, Martins GJ, Paixao VB, Zhou P, Paninski L, Costa RM. the spatiotemporal organization of the striatum encodes action space. Neuron  2017; 95(5): 1171-1180.e7.
[http://dx.doi.org/10.1016/j.neuron.2017.08.015] [PMID: 28858619] 
[37] 
Cazorla M, Kang UJ, Kellendonk C. Balancing the basal ganglia circuitry: a possible new role for dopamine D2 receptors in health and disease. Mov Disord  2015; 30(7): 895-903.
[http://dx.doi.org/10.1002/mds.26282] [PMID: 26018615] 
[38] 
Jaeger D, Kita H. Functional connectivity and integrative properties of globus pallidus neurons. Neuroscience  2011; 198: 44-53.
[http://dx.doi.org/10.1016/j.neuroscience.2011.07.050] [PMID: 21835227] 
[39] 
Mallet N, Schmidt R, Leventhal D, et al. Arkypallidal cells send a stop signal to striatum. Neuron  2016; 89(2): 308-16.
[http://dx.doi.org/10.1016/j.neuron.2015.12.017] [PMID: 26777273] 
[40] 
Saunders A, Oldenburg IA, Berezovskii VK, et al. A direct GABAergic output from the basal ganglia to frontal cortex. Nature  2015; 521(7550): 85-9.
[http://dx.doi.org/10.1038/nature14179] [PMID: 25739505] 
[41] 
Hegeman DJ, Hong ES, Hernández VM, Chan CS. The external globus pallidus: progress and perspectives. Eur J Neurosci  2016; 43(10): 1239-65.
[http://dx.doi.org/10.1111/ejn.13196] [PMID: 26841063] 
[42] 
Aran A, Segel R, Kaneshige K, et al. Vesicular acetylcholine transporter defect underlies devastating congenital myasthenia syndrome. Neurology  2017; 88(11): 1021-8.
[http://dx.doi.org/10.1212/WNL.0000000000003720] [PMID: 28188302] 
[43] 
Zandbelt BB, Vink M. On the role of the striatum in response inhibition. PLoS One  2010; 5(11)e13848
[http://dx.doi.org/10.1371/journal.pone.0013848] [PMID: 21079814] 
[44] 
Milardi D, Gaeta M, Marino S, et al. Basal ganglia network by constrained spherical deconvolution: a possible cortico-pallidal pathway? Mov Disord  2015; 30(3): 342-9.
[http://dx.doi.org/10.1002/mds.25995] [PMID: 25156805] 
[45] 
Naito A, Kita H. The cortico-pallidal projection in the rat: an anterograde tracing study with biotinylated dextran amine. Brain Res  1994; 653(1-2): 251-7.
[http://dx.doi.org/10.1016/0006-8993(94)90397-2] [PMID: 7526961] 
[46] 
Channon S, Sinclair E, Waller D, Healey L, Robertson MM. Social cognition in Tourette’s syndrome: intact theory of mind and impaired inhibitory functioning. J Autism Dev Disord  2004; 34(6): 669-77.
[http://dx.doi.org/10.1007/s10803-004-5287-x] [PMID: 15679186] 
[47] 
Wylie SA, Claassen DO, Kanoff KE, Ridderinkhof KR, van den Wildenberg WP. Impaired inhibition of prepotent motor actions in patients with Tourette syndrome. J Psychiatry Neurosci  2013; 38(5): 349-56.
[http://dx.doi.org/10.1503/jpn.120138] [PMID: 23820185] 
[48] 
Roessner V, Albrecht B, Dechent P, Baudewig J, Rothenberger A. Normal response inhibition in boys with Tourette syndrome. Behav Brain Funct  2008; 4: 29.
[http://dx.doi.org/10.1186/1744-9081-4-29] [PMID: 18638368] 
[49] 
Mueller SC, Jackson GM, Dhalla R, Datsopoulos S, Hollis CP. Enhanced cognitive control in young people with Tourette’s syndrome. Curr Biol  2006; 16(6): 570-3.
[http://dx.doi.org/10.1016/j.cub.2006.01.064] [PMID: 16546080] 
[50] 
Morand-Beaulieu S, Grot S, Lavoie J, Leclerc JB, Luck D, Lavoie ME. The puzzling question of inhibitory control in Tourette syndrome: A meta-analysis. Neurosci Biobehav Rev  2017; 80: 240-62.
[http://dx.doi.org/10.1016/j.neubiorev.2017.05.006] [PMID: 28502600] 
[51] 
Brandt VC, Patalay P, Bäumer T, Brass M, Münchau A. Tics as a model of over-learned behavior-imitation and inhibition of facial tics. Mov Disord  2016; 31(8): 1155-62.
[http://dx.doi.org/10.1002/mds.26607] [PMID: 27062184] 
[52] 
Sales-Carbonell C, Taouali W, Khalki L, et al. no discrete start/stop signals in the dorsal striatum of mice performing a learned action. Curr Biol  2018; 28(19): 3044-3055.e5.
[http://dx.doi.org/10.1016/j.cub.2018.07.038] [PMID: 30270180] 
[53] 
Balleine BW, Dickinson A. Goal-directed instrumental action: contingency and incentive learning and their cortical substrates. Neuropharmacology  1998; 37(4-5): 407-19.
[http://dx.doi.org/10.1016/S0028-3908(98)00033-1] [PMID: 9704982] 
[54] 
Graybiel AM. Habits, rituals, and the evaluative brain. Annu Rev Neurosci  2008; 31: 359-87.
[http://dx.doi.org/10.1146/annurev.neuro.29.051605.112851] [PMID: 18558860] 
[55] 
Colwill RM, Rescorla RA. Effect of reinforcer devaluation on discriminative control of instrumental behavior. J Exp Psychol Anim Behav Process  1990; 16(1): 40-7.
[http://dx.doi.org/10.1037/0097-7403.16.1.40] [PMID: 2303793] 
[56] 
Delorme C, Salvador A, Valabrègue R, et al. Enhanced habit formation in Gilles de la Tourette syndrome. Brain  2016; 139(Pt 2): 605-15.
[http://dx.doi.org/10.1093/brain/awv307] [PMID: 26490329] 
[57] 
Shibasaki H, Hallett M. What is the Bereitschaftspotential? Clin Neurophysiol  2006; 117(11): 2341-56.
[http://dx.doi.org/10.1016/j.clinph.2006.04.025] [PMID: 16876476] 
[58] 
van der Salm SM, Tijssen MA, Koelman JH, van Rootselaar AF. The bereitschaftspotential in jerky movement disorders. J Neurol Neurosurg Psychiatry  2012; 83(12): 1162-7.
[http://dx.doi.org/10.1136/jnnp-2012-303081] [PMID: 22952323] 
[59] 
Obeso JA, Rothwell JC, Marsden CD. Simple tics in Gilles de la Tourette’s syndrome are not prefaced by a normal premovement EEG potential. J Neurol Neurosurg Psychiatry  1981; 44(8): 735-8.
[http://dx.doi.org/10.1136/jnnp.44.8.735] [PMID: 6946193] 
[60] 
Hallett M. Physiology of psychogenic movement disorders. J Clin Neurosci  2010; 17(8): 959-65.
[http://dx.doi.org/10.1016/j.jocn.2009.11.021] [PMID: 20493708] 
[61] 
Rudorf S, Hare TA. Interactions between dorsolateral and ventromedial prefrontal cortex underlie context-dependent stimulus valuation in goal-directed choice. J Neurosci  2014; 34(48): 15988-96.
[http://dx.doi.org/10.1523/JNEUROSCI.3192-14.2014] [PMID: 25429140] 
[62] 
O’Doherty JP, Cockburn J, Pauli WM. Learning, Reward, and Decision Making. Annu Rev Psychol  2017; 68: 73-100.
[http://dx.doi.org/10.1146/annurev-psych-010416-044216] [PMID: 27687119] 
[63] 
Funahashi S. Prefrontal contribution to decision-making under free-choice conditions. Front Neurosci  2017; 11: 431.
[http://dx.doi.org/10.3389/fnins.2017.00431] [PMID: 28798662] 
[64] 
Tanaka SC, Balleine BW, O’Doherty JP. Calculating consequences: brain systems that encode the causal effects of actions. J Neurosci  2008; 28(26): 6750-5.
[http://dx.doi.org/10.1523/JNEUROSCI.1808-08.2008] [PMID: 18579749] 
[65] 
Tricomi E, Balleine BW, O’Doherty JP. A specific role for posterior dorsolateral striatum in human habit learning. Eur J Neurosci  2009; 29(11): 2225-32.
[http://dx.doi.org/10.1111/j.1460-9568.2009.06796.x] [PMID: 19490086] 
[66] 
de Wit S, Watson P, Harsay HA, Cohen MX, van de Vijver I, Ridderinkhof KR. Corticostriatal connectivity underlies individual differences in the balance between habitual and goal-directed action control. J Neurosci  2012; 32(35): 12066-75.
[http://dx.doi.org/10.1523/JNEUROSCI.1088-12.2012] [PMID: 22933790] 
[67] 
Lehéricy S, Ducros M, Krainik A, et al. 3-D diffusion tensor axonal tracking shows distinct SMA and pre-SMA projections to the human striatum. Cereb Cortex  2004; 14(12): 1302-9.
[http://dx.doi.org/10.1093/cercor/bhh091] [PMID: 15166103] 
[68] 
Draganski B, Kherif F, Klöppel S, et al. Evidence for segregated and integrative connectivity patterns in the human Basal Ganglia. J Neurosci  2008; 28(28): 7143-52.
[http://dx.doi.org/10.1523/JNEUROSCI.1486-08.2008] [PMID: 18614684] 
[69] 
Jackson GM, Draper A, Dyke K, Pépés SE, Jackson SR. Inhibition, disinhibition, and the control of action in Tourette syndrome. Trends Cogn Sci  2015; 19(11): 655-65.
[http://dx.doi.org/10.1016/j.tics.2015.08.006] [PMID: 26440120] 
[70] 
Gasbarri A, Pompili A, Packard MG, Tomaz C. Habit learning and memory in mammals: behavioral and neural characteristics. Neurobiol Learn Mem  2014; 114: 198-208.
[http://dx.doi.org/10.1016/j.nlm.2014.06.010] [PMID: 24981854] 
[71] 
Nishizawa K, Fukabori R, Okada K, et al. Striatal indirect pathway contributes to selection accuracy of learned motor actions. J Neurosci  2012; 32(39): 13421-32.
[http://dx.doi.org/10.1523/JNEUROSCI.1969-12.2012] [PMID: 23015433] 
[72] 
Burton AC, Bissonette GB, Lichtenberg NT, Kashtelyan V, Roesch MR. Ventral striatum lesions enhance stimulus and response encoding in dorsal striatum. Biol Psychiatry  2014; 75(2): 132-9.
[73] 
Jedynak JP, Uslaner JM, Esteban JA, Robinson TE. Methamphetamine-induced structural plasticity in the dorsal striatum. Eur J Neurosci  2007; 25(3): 847-53.
[http://dx.doi.org/10.1111/j.1460-9568.2007.05316.x] [PMID: 17328779] 
[74] 
Nelson A, Killcross S. Amphetamine exposure enhances habit formation. J Neurosci  2006; 26(14): 3805-12.
[http://dx.doi.org/10.1523/JNEUROSCI.4305-05.2006] [PMID: 16597734] 
[75] 
Nelson AJ, Killcross S. Accelerated habit formation following amphetamine exposure is reversed by D1, but enhanced by D2, receptor antagonists. Front Neurosci  2013; 7: 76.
[http://dx.doi.org/10.3389/fnins.2013.00076] [PMID: 23720609] 
[76] 
Faure A, Haberland U, Condé F, El Massioui N. Lesion to the nigrostriatal dopamine system disrupts stimulus-response habit formation. J Neurosci  2005; 25(11): 2771-80.
[http://dx.doi.org/10.1523/JNEUROSCI.3894-04.2005] [PMID: 15772337] 
[77] 
Faure A, Leblanc-Veyrac P, El Massioui N. Dopamine agonists increase perseverative instrumental responses but do not restore habit formation in a rat model of Parkinsonism. Neuroscience  2010; 168(2): 477-86.
[http://dx.doi.org/10.1016/j.neuroscience.2010.03.047] [PMID: 20362642] 
[78] 
Leckman JF, Walker DE, Cohen DJ. Premonitory urges in Tourette’s syndrome. Am J Psychiatry  1993; 150(1): 98-102.
[http://dx.doi.org/10.1176/ajp.150.1.98] [PMID: 8417589] 
[79] 
Harris EL, Schuerholz LJ, Singer HS, et al. Executive function in children with Tourette syndrome and/or attention deficit hyperactivity disorder. J Int Neuropsychol Soc  1995; 1(6): 511-6.
[http://dx.doi.org/10.1017/S1355617700000631] [PMID: 9375237] 
[80] 
Schuerholz LJ, Singer HS, Denckla MB. Gender study of neuropsychological and neuromotor function in children with Tourette syndrome with and without attention-deficit hyperactivity disorder. J Child Neurol  1998; 13(6): 277-82.
[http://dx.doi.org/10.1177/088307389801300607] [PMID: 9660511] 
[81] 
Stern ER, Blair C, Peterson BS. Inhibitory deficits in Tourette’s syndrome. Dev Psychobiol  2008; 50(1): 9-18.
[http://dx.doi.org/10.1002/dev.20266] [PMID: 18085554] 
[82] 
Minzer K, Lee O, Hong JJ, Singer HS. Increased prefrontal D2 protein in Tourette syndrome: a postmortem analysis of frontal cortex and striatum. J Neurol Sci  2004; 219(1-2): 55-61.
[http://dx.doi.org/10.1016/j.jns.2003.12.006] [PMID: 15050438] 
[83] 
Yoon DY, Gause CD, Leckman JF, Singer HS. Frontal dopaminergic abnormality in Tourette syndrome: a postmortem analysis. J Neurol Sci  2007; 255(1-2): 50-6.
[http://dx.doi.org/10.1016/j.jns.2007.01.069] [PMID: 17337006] 
[84] 
Peterson BS, Staib L, Scahill L, et al. Regional brain and ventricular volumes in Tourette syndrome. Arch Gen Psychiatry  2001; 58(5): 427-40.
[http://dx.doi.org/10.1001/archpsyc.58.5.427] [PMID: 11343521] 
[85] 
Müller-Vahl KR, Kaufmann J, Grosskreutz J, Dengler R, Emrich HM, Peschel T. Prefrontal and anterior cingulate cortex abnormalities in Tourette Syndrome: evidence from voxel-based morphometry and magnetization transfer imaging. BMC Neurosci  2009; 10: 47.
[http://dx.doi.org/10.1186/1471-2202-10-47] [PMID: 19435502] 
[86] 
Sowell ER, Kan E, Yoshii J, et al. Thinning of sensorimotor cortices in children with Tourette syndrome. Nat Neurosci  2008; 11(6): 637-9.
[http://dx.doi.org/10.1038/nn.2121] [PMID: 18488025] 
[87] 
Worbe Y, Gerardin E, Hartmann A, et al. Distinct structural changes underpin clinical phenotypes in patients with Gilles de la Tourette syndrome. Brain  2010; 133(Pt 12): 3649-60.
[http://dx.doi.org/10.1093/brain/awq293] [PMID: 20959309] 
[88] 
Fahim C, Yoon U, Das S, et al. Somatosensory-motor bodily representation cortical thinning in Tourette: effects of tic severity, age and gender. Cortex  2010; 46(6): 750-60.
[http://dx.doi.org/10.1016/j.cortex.2009.06.008] [PMID: 19733347] 
[89] 
Cheng B, Braass H, Ganos C, et al. Altered intrahemispheric structural connectivity in Gilles de la Tourette syndrome. Neuroimage Clin  2013; 4: 174-81.
[http://dx.doi.org/10.1016/j.nicl.2013.11.011] [PMID: 24371800] 
[90] 
Draganski B, Martino D, Cavanna AE, et al. Multispectral brain morphometry in Tourette syndrome persisting into adulthood. Brain  2010; 133(Pt 12): 3661-75.
[http://dx.doi.org/10.1093/brain/awq300] [PMID: 21071387] 
[91] 
Muellner J, Delmaire C, Valabrégue R, et al. Altered structure of cortical sulci in gilles de la Tourette syndrome: Further support for abnormal brain development. Mov Disord  2015; 30(5): 655-61.
[http://dx.doi.org/10.1002/mds.26207] [PMID: 25820811] 
[92] 
Fredericksen KA, Cutting LE, Kates WR, et al. Disproportionate increases of white matter in right frontal lobe in Tourette syndrome. Neurology  2002; 58(1): 85-9.
[http://dx.doi.org/10.1212/WNL.58.1.85] [PMID: 11781410] 
[93] 
Kates WR, Frederikse M, Mostofsky SH, et al. MRI parcellation of the frontal lobe in boys with attention deficit hyperactivity disorder or Tourette syndrome. Psychiatry Res  2002; 116(1-2): 63-81.
[http://dx.doi.org/10.1016/S0925-4927(02)00066-5] [PMID: 12426035] 
[94] 
Greene DJ, Williams Iii AC, Koller JM, Schlaggar BL, Black KJ. The Tourette Association of America Neuroimaging Consortium. Brain structure in pediatric Tourette syndrome. Mol Psychiatry  2017; 22(7): 972-80.
[http://dx.doi.org/10.1038/mp.2016.194] [PMID: 27777415] 
[95] 
Debes N, Jeppesen S, Raghava JM, Groth C, Rostrup E, Skov L. 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  2015; 30(10): 1315-26.
[http://dx.doi.org/10.1177/0883073814560629] [PMID: 25535056] 
[96] 
Baumgardner TL, Singer HS, Denckla MB, et al. Corpus callosum morphology in children with Tourette syndrome and attention deficit hyperactivity disorder. Neurology  1996; 47(2): 477-82.
[http://dx.doi.org/10.1212/WNL.47.2.477] [PMID: 8757024] 
[97] 
Mostofsky SH, Wendlandt J, Cutting L, Denckla MB, Singer HS. Corpus callosum measurements in girls with Tourette syndrome. Neurology  1999; 53(6): 1345-7.
[http://dx.doi.org/10.1212/WNL.53.6.1345] [PMID: 10522898] 
[98] 
Plessen KJ, Wentzel-Larsen T, Hugdahl K, et al. Altered interhemispheric connectivity in individuals with Tourette’s disorder. Am J Psychiatry  2004; 161(11): 2028-37.
[http://dx.doi.org/10.1176/appi.ajp.161.11.2028] [PMID: 15514403] 
[99] 
Cavanna AE, Stecco A, Rickards H, et al. Corpus callosum abnormalities in Tourette syndrome: an MRI-DTI study of monozygotic twins. J Neurol Neurosurg Psychiatry  2010; 81(5): 533-5.
[http://dx.doi.org/10.1136/jnnp.2009.173666] [PMID: 20176604] 
[100] 
Roessner V, Overlack S, Schmidt-Samoa C, et al. Increased putamen and callosal motor subregion in treatment-naïve boys with Tourette syndrome indicates changes in the bihemispheric motor network. J Child Psychol Psychiatry  2011; 52(3): 306-14.
[http://dx.doi.org/10.1111/j.1469-7610.2010.02324.x] [PMID: 20883521] 
[101] 
Jackson SR, Parkinson A, Jung J, et al. Compensatory neural reorganization in Tourette syndrome. Curr Biol  2011; 21(7): 580-5.
[http://dx.doi.org/10.1016/j.cub.2011.02.047] [PMID: 21439830] 
[102] 
Plessen KJ, Lundervold A, Grüner R, et al. Functional brain asymmetry, attentional modulation, and interhemispheric transfer in boys with Tourette syndrome. Neuropsychologia  2007; 45(4): 767-74.
[http://dx.doi.org/10.1016/j.neuropsychologia.2006.08.006] [PMID: 17045315] 
[103] 
Worbe Y, Marrakchi-Kacem L, Lecomte S, et al. Altered structural connectivity of cortico-striato-pallido-thalamic networks in Gilles de la Tourette syndrome. Brain  2015; 138(Pt 2): 472-82.
[http://dx.doi.org/10.1093/brain/awu311] [PMID: 25392196] 
[104] 
Church JA, Wenger KK, Dosenbach NU, Miezin FM, Petersen SE, Schlaggar BL. Task control signals in pediatric tourette syndrome show evidence of immature and anomalous functional activity. Front Hum Neurosci  2009; 3: 38.
[http://dx.doi.org/10.3389/neuro.09.038.2009] [PMID: 19949483] 
[105] 
Govindan RM, Makki MI, Wilson BJ, Behen ME, Chugani HT. Abnormal water diffusivity in corticostriatal projections in children with Tourette syndrome. Hum Brain Mapp  2010; 31(11): 1665-74.
[http://dx.doi.org/10.1002/hbm.20970] [PMID: 20162597] 
[106] 
Liao W, Yu Y, Miao HH, Feng YX, Ji GJ, Feng JH. Inter-hemispheric intrinsic connectivity as a neuromarker for the diagnosis of boys with Tourette syndrome. Mol Neurobiol  2017; 54(4): 2781-9.
[http://dx.doi.org/10.1007/s12035-016-9863-9] [PMID: 27011382] 
[107] 
Neuner I, Werner CJ, Arrubla J, et al. Imaging the where and when of tic generation and resting state networks in adult Tourette patients. Front Hum Neurosci  2014; 8: 362.
[http://dx.doi.org/10.3389/fnhum.2014.00362] [PMID: 24904391] 
[108] 
Bohlhalter S, Goldfine A, Matteson S, et al. Neural correlates of tic generation in Tourette syndrome: an event-related functional MRI study. Brain  2006; 129(Pt 8): 2029-37.
[http://dx.doi.org/10.1093/brain/awl050] [PMID: 16520330] 
[109] 
Zapparoli L, Tettamanti M, Porta M, et al. A tug of war: antagonistic effective connectivity patterns over the motor cortex and the severity of motor symptoms in Gilles de la Tourette syndrome. Eur J Neurosci  2017; 46(6): 2203-13.
[http://dx.doi.org/10.1111/ejn.13658] [PMID: 28833746] 
[110] 
Conceição VA, Dias Â, Farinha AC, Maia TV. Premonitory urges and tics in Tourette syndrome: computational mechanisms and neural correlates. Curr Opin Neurobiol  2017; 46: 187-99.
[http://dx.doi.org/10.1016/j.conb.2017.08.009] [PMID: 29017141] 
[111] 
Polyanska L, Critchley HD, Rae CL. Centrality of prefrontal and motor preparation cortices to Tourette Syndrome revealed by meta-analysis of task-based neuroimaging studies. Neuroimage Clin  2017; 16: 257-67.
[http://dx.doi.org/10.1016/j.nicl.2017.08.004] [PMID: 28831377] 
[112] 
Ganos C, Kühn S, Kahl U, et al. Action inhibition in Tourette syndrome. Mov Disord  2014; 29(12): 1532-8.
[http://dx.doi.org/10.1002/mds.25944] [PMID: 24995958] 
[113] 
Mazzone L, Yu S, Blair C, et al. An FMRI study of frontostriatal circuits during the inhibition of eye blinking in persons with Tourette syndrome. Am J Psychiatry  2010; 167(3): 341-9.
[http://dx.doi.org/10.1176/appi.ajp.2009.08121831] [PMID: 20080981] 
[114] 
Debes NM, Hansen A, Skov L, Larsson H. A functional magnetic resonance imaging study of a large clinical cohort of children with Tourette syndrome. J Child Neurol  2011; 26(5): 560-9.
[http://dx.doi.org/10.1177/0883073810387928] [PMID: 21464239] 
[115] 
Alongi P, Iaccarino L, Perani D. pet neuroimaging: insights on dystonia and tourette syndrome and potential applications. Front Neurol  2014; 5: 183.
[http://dx.doi.org/10.3389/fneur.2014.00183] [PMID: 25295029] 
[116] 
Pourfar M, Feigin A, Tang CC, et al. Abnormal metabolic brain networks in Tourette syndrome. Neurology  2011; 76(11): 944-52.
[http://dx.doi.org/10.1212/WNL.0b013e3182104106] [PMID: 21307354] 
[117] 
Gilbert DL, Bansal AS, Sethuraman G, et al. Association of cortical disinhibition with tic, ADHD, and OCD severity in Tourette syndrome. Mov Disord  2004; 19(4): 416-25.
[http://dx.doi.org/10.1002/mds.20044] [PMID: 15077239] 
[118] 
Moll GH, Wischer S, Heinrich H, Tergau F, Paulus W, Rothenberger A. Deficient motor control in children with tic disorder: evidence from transcranial magnetic stimulation. Neurosci Lett  1999; 272(1): 37-40.
[http://dx.doi.org/10.1016/S0304-3940(99)00575-3] [PMID: 10507537] 
[119] 
Finis J, Enticott PG, Pollok B, Münchau A, Schnitzler A, Fitzgerald PB. Repetitive transcranial magnetic stimulation of the supplementary motor area induces echophenomena. Cortex  2013; 49(7): 1978-82.
[http://dx.doi.org/10.1016/j.cortex.2012.08.019] [PMID: 23020900] 
[120] 
Le K, Liu L, Sun M, Hu L, Xiao N. Transcranial magnetic stimulation at 1 Hertz improves clinical symptoms in children with Tourette syndrome for at least 6 months. J Clin Neurosci  2013; 20(2): 257-62.
[http://dx.doi.org/10.1016/j.jocn.2012.01.049] [PMID: 23238046] 
[121] 
Kwon HJ, Lim WS, Lim MH, et al. 1-Hz low frequency repetitive transcranial magnetic stimulation in children with Tourette’s syndrome. Neurosci Lett  2011; 492(1): 1-4.
[http://dx.doi.org/10.1016/j.neulet.2011.01.007] [PMID: 21256925] 
[122] 
Landeros-Weisenberger A, Mantovani A, Motlagh MG, et al. Randomized Sham Controlled Double-blind Trial of Repetitive Transcranial Magnetic Stimulation for Adults With Severe Tourette Syndrome. Brain Stimul  2015; 8(3): 574-81.
[http://dx.doi.org/10.1016/j.brs.2014.11.015] [PMID: 25912296] 
[123] 
Pogorelov V, Xu M, Smith HR, Buchanan GF, Pittenger C. Corticostriatal interactions in the generation of tic-like behaviors after local striatal disinhibition. Exp Neurol  2015; 265: 122-8.
[http://dx.doi.org/10.1016/j.expneurol.2015.01.001] [PMID: 25597650] 
[124] 
Fenno L, Yizhar O, Deisseroth K. The development and application of optogenetics. Annu Rev Neurosci  2011; 34: 389-412.
[http://dx.doi.org/10.1146/annurev-neuro-061010-113817] [PMID: 21692661] 
[125] 
Burton FH. Back to the Future: Circuit-testing TS & OCD. J Neurosci Methods  2017; 292: 2-11.
[http://dx.doi.org/10.1016/j.jneumeth.2017.07.025] [PMID: 28756273] 
[126] 
Ahmari SE, Spellman T, Douglass NL, et al. Repeated cortico-striatal stimulation generates persistent OCD-like behavior. Science  2013; 340(6137): 1234-9.
[http://dx.doi.org/10.1126/science.1234733] [PMID: 23744948] 
[127] 
Burton FH, Hasel KW, Bloom FE, Sutcliffe JG. Pituitary hyperplasia and gigantism in mice caused by a cholera toxin transgene. Nature  1991; 350(6313): 74-7.
[http://dx.doi.org/10.1038/350074a0] [PMID: 1848356] 
[128] 
Campbell KM, de Lecea L, Severynse DM, et al. OCD-Like behaviors caused by a neuropotentiating transgene targeted to cortical and limbic D1+ neurons. J Neurosci  1999; 19(12): 5044-53.
[http://dx.doi.org/10.1523/JNEUROSCI.19-12-05044.1999] [PMID: 10366637] 
[129] 
Nordstrom EJ, Burton FH. A transgenic model of comorbid Tourette’s syndrome and obsessive-compulsive disorder circuitry  Mol Psychiatry 2002; 7(6): 617-625, 524.
[http://dx.doi.org/10.1038/sj.mp.4001144] [PMID: 12140785] 
[130] 
Tremblay L, Worbe Y, Thobois S, Sgambato-Faure V, Féger J. Selective dysfunction of basal ganglia subterritories: From movement to behavioral disorders. Mov Disord  2015; 30(9): 1155-70.
[http://dx.doi.org/10.1002/mds.26199] [PMID: 25772380] 
[131] 
Rae CL, Critchley HD, Seth AK. A Bayesian account of the sensory-motor interactions underlying symptoms of Tourette syndrome. Front Psychiatry  2019; 10: 29.https://www.frontiersin.org/articles/10.3389/fpsyt.2019.00029/abstract
[132] 
Kalanithi PS, Zheng W, Kataoka Y, et al. Altered parvalbumin-positive neuron distribution in basal ganglia of individuals with Tourette syndrome. Proc Natl Acad Sci USA  2005; 102(37): 13307-12.
[http://dx.doi.org/10.1073/pnas.0502624102] [PMID: 16131542] 
[133] 
Kataoka Y, Kalanithi PS, Grantz H, et al. Decreased number of parvalbumin and cholinergic interneurons in the striatum of individuals with Tourette syndrome. J Comp Neurol  2010; 518(3): 277-91.
[http://dx.doi.org/10.1002/cne.22206] [PMID: 19941350] 
[134] 
Lennington JB, Coppola G, Kataoka-Sasaki Y, et al. transcriptome analysis of the human striatum in Tourette syndrome. Biol Psychiatry  2016; 79(5): 372-82.
[http://dx.doi.org/10.1016/j.biopsych.2014.07.018] [PMID: 25199956] 
[135] 
Peterson BS, Thomas P, Kane MJ, et al. Basal Ganglia volumes in patients with Gilles de la Tourette syndrome. Arch Gen Psychiatry  2003; 60(4): 415-24.
[http://dx.doi.org/10.1001/archpsyc.60.4.415] [PMID: 12695320] 
[136] 
Hyde TM, Stacey ME, Coppola R, Handel SF, Rickler KC, Weinberger DR. Cerebral morphometric abnormalities in Tourette’s syndrome: a quantitative MRI study of monozygotic twins. Neurology  1995; 45(6): 1176-82.
[http://dx.doi.org/10.1212/WNL.45.6.1176] [PMID: 7783885] 
[137] 
Bloch MH, Leckman JF, Zhu H, Peterson BS. Caudate volumes in childhood predict symptom severity in adults with Tourette syndrome. Neurology  2005; 65(8): 1253-8.
[http://dx.doi.org/10.1212/01.wnl.0000180957.98702.69] [PMID: 16247053] 
[138] 
Ludolph AG, Juengling FD, Libal G, Ludolph AC, Fegert JM, Kassubek J. Grey-matter abnormalities in boys with Tourette syndrome: magnetic resonance imaging study using optimised voxel-based morphometry. Br J Psychiatry  2006; 188: 484-5.
[http://dx.doi.org/10.1192/bjp.bp.105.008813] [PMID: 16648537] 
[139] 
Singer HS, Reiss AL, Brown JE, et al. Volumetric MRI changes in basal ganglia of children with Tourette’s syndrome. Neurology  1993; 43(5): 950-6.
[http://dx.doi.org/10.1212/WNL.43.5.950] [PMID: 8492951] 
[140] 
Makki MI, Behen M, Bhatt A, Wilson B, Chugani HT. Microstructural abnormalities of striatum and thalamus in children with Tourette syndrome. Mov Disord  2008; 23(16): 2349-56.
[http://dx.doi.org/10.1002/mds.22264] [PMID: 18759338] 
[141] 
Neuner I, Kupriyanova Y, Stöcker T, et al. Microstructure assessment of grey matter nuclei in adult tourette patients by diffusion tensor imaging. Neurosci Lett  2011; 487(1): 22-6.
[http://dx.doi.org/10.1016/j.neulet.2010.09.066] [PMID: 20888391] 
[142] 
Braun AR, Stoetter B, Randolph C, et al. The functional neuroanatomy of Tourette’s syndrome: an FDG-PET study. I. Regional changes in cerebral glucose metabolism differentiating patients and controls. Neuropsychopharmacology  1993; 9(4): 277-91.
[http://dx.doi.org/10.1038/npp.1993.64] [PMID: 8305128] 
[143] 
Baxter LR. Brain imaging as a tool in establishing a theory of brain pathology in obsessive compulsive disorder. J Clin Psychiatry  1990; 51(Suppl.): 22-5.
[PMID: 2298713] 
[144] 
Jeffries KJ, Schooler C, Schoenbach C, Herscovitch P, Chase TN, Braun AR. The functional neuroanatomy of Tourette’s syndrome: an FDG PET study III: functional coupling of regional cerebral metabolic rates. Neuropsychopharmacology  2002; 27(1): 92-104.
[http://dx.doi.org/10.1016/S0893-133X(01)00428-6] [PMID: 12062910] 
[145] 
Robinson D, Wu H, Munne RA, et al. Reduced caudate nucleus volume in obsessive-compulsive disorder. Arch Gen Psychiatry  1995; 52(5): 393-8.
[http://dx.doi.org/10.1001/archpsyc.1995.03950170067009] [PMID: 7726720] 
[146] 
Worbe Y, Baup N, Grabli D, et al. Behavioral and movement disorders induced by local inhibitory dysfunction in primate striatum. Cereb Cortex  2009; 19(8): 1844-56.
[http://dx.doi.org/10.1093/cercor/bhn214] [PMID: 19068490] 
[147] 
Worbe Y, Sgambato-Faure V, Epinat J, et al. Towards a primate model of Gilles de la Tourette syndrome: anatomo-behavioural correlation of disorders induced by striatal dysfunction. Cortex  2013; 49(4): 1126-40.
[http://dx.doi.org/10.1016/j.cortex.2012.08.020] [PMID: 23040317] 
[148] 
Bronfeld M, Yael D, Belelovsky K, Bar-Gad I. Motor tics evoked by striatal disinhibition in the rat. Front Syst Neurosci  2013; 7: 50.
[http://dx.doi.org/10.3389/fnsys.2013.00050] [PMID: 24065893] 
[149] 
McCairn KW, Nagai Y, Hori Y, et al. A primary role for nucleus accumbens and related limbic network in vocal tics. Neuron  2016; 89(2): 300-7.
[http://dx.doi.org/10.1016/j.neuron.2015.12.025] [PMID: 26796690] 
[150] 
Kønig A, Ciriachi C, Gether U, Rickhag M. Chemogenetic targeting of dorsomedial direct-pathway striatal projection neurons selectively elicits rotational behavior in mice. Neuroscience  2019; 401: 106-16.http://www.sciencedirect.com/science/article/pii/S0306452219300338
[151] 
Rodrigues S, Salum C, Ferreira TL. Dorsal striatum D1-expressing neurons are involved with sensorimotor gating on prepulse inhibition test. J Psychopharmacol  2017; 31(4): 505-13.
[http://dx.doi.org/10.1177/0269881116686879] [PMID: 28114835] 
[152] 
Tinaz S, Belluscio BA, Malone P, van der Veen JW, Hallett M, Horovitz SG. Role of the sensorimotor cortex in Tourette syndrome using multimodal imaging. Hum Brain Mapp  2014; 35(12): 5834-46.
[http://dx.doi.org/10.1002/hbm.22588] [PMID: 25044024] 
[153] 
Lerner A, Bagic A, Boudreau EA, et al. Neuroimaging of neuronal circuits involved in tic generation in patients with Tourette syndrome. Neurology  2007; 68(23): 1979-87.
[http://dx.doi.org/10.1212/01.wnl.0000264417.18604.12] [PMID: 17548547] 
[154] 
Tobe RH, Bansal R, Xu D, et al. Cerebellar morphology in Tourette syndrome and obsessive-compulsive disorder. Ann Neurol  2010; 67(4): 479-87.
[http://dx.doi.org/10.1002/ana.21918] [PMID: 20437583] 
[155] 
McCairn KW, Iriki A, Isoda M. Global dysrhythmia of cerebro-basal ganglia-cerebellar networks underlies motor tics following striatal disinhibition. J Neurosci  2013; 33(2): 697-708.
[http://dx.doi.org/10.1523/JNEUROSCI.4018-12.2013] [PMID: 23303948] 
[156] 
Moberget T, Ivry RB. Cerebellar contributions to motor control and language comprehension: searching for common computational principles. Ann N Y Acad Sci  2016; 1369(1): 154-71.
[http://dx.doi.org/10.1111/nyas.13094] [PMID: 27206249] 
[157] 
Makki MI, Govindan RM, Wilson BJ, Behen ME, Chugani HT. Altered fronto-striato-thalamic connectivity in children with Tourette syndrome assessed with diffusion tensor MRI and probabilistic fiber tracking. J Child Neurol  2009; 24(6): 669-78.
[http://dx.doi.org/10.1177/0883073808327838] [PMID: 19491113] 
[158] 
Lee JS, Yoo SS, Cho SY, Ock SM, Lim MK, Panych LP. Abnormal thalamic volume in treatment-naïve boys with Tourette syndrome. Acta Psychiatr Scand  2006; 113(1): 64-7.
[http://dx.doi.org/10.1111/j.1600-0447.2005.00666.x] [PMID: 16390372] 
[159] 
Miller AM, Bansal R, Hao X, et al. Enlargement of thalamic nuclei in Tourette syndrome. Arch Gen Psychiatry  2010; 67(9): 955-64.
[http://dx.doi.org/10.1001/archgenpsychiatry.2010.102] [PMID: 20819989] 
[160] 
Zhou N, Masterson SP, Damron JK, Guido W, Bickford ME. The mouse pulvinar nucleus links the lateral extrastriate cortex, striatum, and amygdala. J Neurosci  2018; 38(2): 347-62.
[http://dx.doi.org/10.1523/JNEUROSCI.1279-17.2017] [PMID: 29175956] 
[161] 
Bour LJ, Ackermans L, Foncke EM, et al. Tic related local field potentials in the thalamus and the effect of deep brain stimulation in Tourette syndrome: Report of three cases. Clin Neurophysiol  2015; 126(8): 1578-88.
[http://dx.doi.org/10.1016/j.clinph.2014.10.217] [PMID: 25435514] 
[162] 
Ludolph AG, Pinkhardt EH, Tebartz van Elst L, et al. Are amygdalar volume alterations in children with Tourette syndrome due to ADHD comorbidity? Dev Med Child Neurol  2008; 50(7): 524-9.
[http://dx.doi.org/10.1111/j.1469-8749.2008.03014.x] [PMID: 18611203] 
[163] 
Peterson BS, Choi HA, Hao X, et al. Morphologic features of the amygdala and hippocampus in children and adults with Tourette syndrome. Arch Gen Psychiatry  2007; 64(11): 1281-91.
[http://dx.doi.org/10.1001/archpsyc.64.11.1281] [PMID: 17984397] 
[164] 
Gruber AJ, McDonald RJ. Context, emotion, and the strategic pursuit of goals: interactions among multiple brain systems controlling motivated behavior. Front Behav Neurosci  2012; 6: 50.
[http://dx.doi.org/10.3389/fnbeh.2012.00050] [PMID: 22876225] 
[165] 
Mannella F, Gurney K, Baldassarre G. The nucleus accumbens as a nexus between values and goals in goal-directed behavior: a review and a new hypothesis. Front Behav Neurosci  2013; 7: 135.
[http://dx.doi.org/10.3389/fnbeh.2013.00135] [PMID: 24167476] 
[166] 
Albin RL. Complementary motivational roles of nigroaccumbens and nigrostriatal dopaminergic pathways. Mov Disord  2019; 34(1): 45.
[http://dx.doi.org/10.1002/mds.27504] [PMID: 30653732] 
[167] 
Singer HS, Mink J, Gilbert DL, Jankovic J. Movement disorders in childhood.  2nd ed.  2015.https://www.elsevier.com/books/movement-disorders-in-childhood/singer/978-0-12-411573-6
[168] 
Buse J, Schoenefeld K, Münchau A, Roessner V. Neuromodulation in Tourette syndrome: dopamine and beyond. Neurosci Biobehav Rev  2013; 37(6): 1069-84.
[http://dx.doi.org/10.1016/j.neubiorev.2012.10.004] [PMID: 23085211] 
[169] 
Jones CR, Jahanshahi M. Dopamine modulates striato-frontal functioning during temporal processing. Front Integr Nuerosci  2011; 5: 70.
[http://dx.doi.org/10.3389/fnint.2011.00070] [PMID: 22046150] 
[170] 
Richard JM, Berridge KC. Nucleus accumbens dopamine/glutamate interaction switches modes to generate desire versus dread: D(1) alone for appetitive eating but D(1) and D(2) together for fear. J Neurosci  2011; 31(36): 12866-79.
[http://dx.doi.org/10.1523/JNEUROSCI.1339-11.2011] [PMID: 21900565] 
[171] 
Liang L, DeLong MR, Papa SM. Inversion of dopamine responses in striatal medium spiny neurons and involuntary movements. J Neurosci  2008; 28(30): 7537-47.
[http://dx.doi.org/10.1523/JNEUROSCI.1176-08.2008] [PMID: 18650331] 
[172] 
Hart AS, Rutledge RB, Glimcher PW, Phillips PE. Phasic dopamine release in the rat nucleus accumbens symmetrically encodes a reward prediction error term. J Neurosci  2014; 34(3): 698-704.
[http://dx.doi.org/10.1523/JNEUROSCI.2489-13.2014] [PMID: 24431428] 
[173] 
Ledonne A, Mercuri NB. Current concepts on the physiopathological relevance of dopaminergic receptors. Front Cell Neurosci  2017; 11: 27.
[http://dx.doi.org/10.3389/fncel.2017.00027] [PMID: 28228718] 
[174] 
Swerdlow NR. Update: studies of prepulse inhibition of startle, with particular relevance to the pathophysiology or treatment of Tourette Syndrome. Neurosci Biobehav Rev  2013; 37(6): 1150-6.
[http://dx.doi.org/10.1016/j.neubiorev.2012.09.002] [PMID: 23017868] 
[175] 
Hosp JA, Pekanovic A, Rioult-Pedotti MS, Luft AR. Dopaminergic projections from midbrain to primary motor cortex mediate motor skill learning. J Neurosci  2011; 31(7): 2481-7.
[http://dx.doi.org/10.1523/JNEUROSCI.5411-10.2011] [PMID: 21325515] 
[176] 
Beier KT, Gao XJ, Xie S, DeLoach KE, Malenka RC, Luo L. Topological Organization of ventral tegmental area connectivity revealed by viral-genetic dissection of input-output relations. Cell Rep  2019; 26(1): 159-167.e6.
[http://dx.doi.org/10.1016/j.celrep.2018.12.040] [PMID: 30605672] 
[177] 
Singer HS. Treatment of tics and tourette syndrome. Curr Treat Options Neurol  2010; 12(6): 539-61.
[http://dx.doi.org/10.1007/s11940-010-0095-4] [PMID: 20848326] 
[178] 
Gilbert DL, Budman CL, Singer HS, Kurlan R, Chipkin REAA. A D1 receptor antagonist, ecopipam, for treatment of tics in Tourette syndrome. Clin Neuropharmacol  2014; 37(1): 26-30.
[http://dx.doi.org/10.1097/WNF.0000000000000017] [PMID: 24434529] 
[179] 
Mogwitz S, Buse J, Wolff N, Roessner V. Update on the pharmacological treatment of tics with dopamine-modulating agents. ACS Chem Neurosci  2018; 9(4): 651-72.
[http://dx.doi.org/10.1021/acschemneuro.7b00460] [PMID: 29498507] 
[180] 
Jankovic J. Dopamine depleters in the treatment of hyperkinetic movement disorders. Expert Opin Pharmacother  2016; 17(18): 2461-70.
[http://dx.doi.org/10.1080/14656566.2016.1258063] [PMID: 27819145] 
[181] 
Gilbert DL, Dure L, Sethuraman G, Raab D, Lane J, Sallee FR. Tic reduction with pergolide in a randomized controlled trial in children. Neurology  2003; 60(4): 606-11.
[http://dx.doi.org/10.1212/01.WNL.0000044058.64647.7E] [PMID: 12601100] 
[182] 
Klawans HL, Falk DK, Nausieda PA, Weiner WJ. Gilles de la Tourette syndrome after long-term chlorpromazine therapy. Neurology  1978; 28(10): 1064-6.
[http://dx.doi.org/10.1212/WNL.28.10.1064] [PMID: 284201] 
[183] 
Karagianis JL, Nagpurkar R. A case of Tourette syndrome developing during haloperidol treatment. Can J Psychiatry  1990; 35(3): 228-32.
[http://dx.doi.org/10.1177/070674379003500305] [PMID: 2340455] 
[184] 
Qi Y, Zheng Y, Li Z, Xiong L. Progress in genetic studies of Tourette’s syndrome. Brain Sci  2017; 7(10) E134
[http://dx.doi.org/10.3390/brainsci7100134] [PMID: 29053637] 
[185] 
Brett PM, Curtis D, Robertson MM, Gurling HM. The genetic susceptibility to Gilles de la Tourette syndrome in a large multiple affected British kindred: linkage analysis excludes a role for the genes coding for dopamine D1, D2, D3, D4, D5 receptors, dopamine beta hydroxylase, tyrosinase, and tyrosine hydroxylase. Biol Psychiatry  1995; 37(8): 533-40.
[http://dx.doi.org/10.1016/0006-3223(94)00161-U] [PMID: 7619976] 
[186] 
He F, Zheng Y, Huang HH, Cheng YH, Wang CY. Association between Tourette syndrome and the dopamine D3 receptor gene rs6280. Chin Med J  2015; 128(5): 654-8.
[http://dx.doi.org/10.4103/0366-6999.151665] [PMID: 25698199] 
[187] 
Thompson M, Comings DE, Feder L, George SR, O’Dowd BF. Mutation screening of the dopamine D1 receptor gene in Tourette’s syndrome and alcohol dependent patients   Am J Med Genet 1998;
387	81(3): 241-4. http://dx.doi.org/10.1002/(SICI)1096-8628(19980508) 81:3241::AID-AJMG73.0.CO;2-Z
[PMID: 9603612] 
[188] 
Comings DE, Gade R, Muhleman D, et al. Exon and intron variants in the human tryptophan 2,3-dioxygenase gene: potential association with Tourette syndrome, substance abuse and other disorders. Pharmacogenetics  1996; 6(4): 307-18.
[http://dx.doi.org/10.1097/00008571-199608000-00004] [PMID: 8873217] 
[189] 
Lee CC, Chou IC, Tsai CH, Wang TR, Li TC, Tsai FJ. Dopamine receptor D2 gene polymorphisms are associated in Taiwanese children with Tourette syndrome. Pediatr Neurol  2005; 33(4): 272-6.
[http://dx.doi.org/10.1016/j.pediatrneurol.2005.05.005] [PMID: 16194726] 
[190] 
Nöthen MM, Hebebrand J, Knapp M, et al. Association analysis of the dopamine D2 receptor gene in Tourette’s syndrome using the haplotype relative risk method. Am J Med Genet  1994; 54(3): 249-52.
[http://dx.doi.org/10.1002/ajmg.1320540311] [PMID: 7810582] 
[191] 
Grice DE, Leckman JF, Pauls DL, et al. Linkage disequilibrium between an allele at the dopamine D4 receptor locus and Tourette syndrome, by the transmission-disequilibrium test. Am J Hum Genet  1996; 59(3): 644-52.
[PMID: 8751866] 
[192] 
Cruz C, Camarena B, King N, et al. Increased prevalence of the seven-repeat variant of the dopamine D4 receptor gene in patients with obsessive-compulsive disorder with tics. Neurosci Lett  1997; 231(1): 1-4.
[http://dx.doi.org/10.1016/S0304-3940(97)00523-5] [PMID: 9280153] 
[193] 
Barr CL, Wigg KG, Zovko E, Sandor P, Tsui LC. No evidence for a major gene effect of the dopamine D4 receptor gene in the susceptibility to Gilles de la Tourette syndrome in five Canadian families. Am J Med Genet  1996; 67(3): 301-5.
[http://dx.doi.org/10.1002/(SICI)1096-8628(19960531)67:3301:AID-AJMG63.0.CO;2-P] [PMID: 8725747] 
[194] 
Ozbay F, Wigg KG, Turanli ET, et al. Analysis of the dopamine beta hydroxylase gene in Gilles de la Tourette syndrome. Am J Med Genet B Neuropsychiatr Genet  2006; 141B(6): 673-7.
[http://dx.doi.org/10.1002/ajmg.b.30393] [PMID: 16838359] 
[195] 
Tarnok Z, Ronai Z, Gervai J, et al. Dopaminergic candidate genes in Tourette syndrome: association between tic severity and 3′ UTR polymorphism of the dopamine transporter gene. Am J Med Genet B Neuropsychiatr Genet  2007; 144B(7): 900-5.
[http://dx.doi.org/10.1002/ajmg.b.30517] [PMID: 17508355] 
[196] 
Díaz-Anzaldúa A, Joober R, Rivière JB, et al. Montreal Tourette syndrome study group. Tourette syndrome and dopaminergic genes: a family-based association study in the French Canadian founder population. Mol Psychiatry  2004; 9(3): 272-7.
[http://dx.doi.org/10.1038/sj.mp.4001411] [PMID: 15094788] 
[197] 
Yoon DY, Rippel CA, Kobets AJ, et al. Dopaminergic polymorphisms in Tourette syndrome: association with the DAT gene (SLC6A3). Am J Med Genet B Neuropsychiatr Genet  2007; 144B(5): 605-10.
[http://dx.doi.org/10.1002/ajmg.b.30466] [PMID: 17171650] 
[198] 
Butler IJ, Koslow SH, Seifert WE Jr, Caprioli RM, Singer HS. Biogenic amine metabolism in Tourette syndrome. Ann Neurol  1979; 6(1): 37-9.
[http://dx.doi.org/10.1002/ana.410060109] [PMID: 292354] 
[199] 
Singer HS, Butler IJ, Tune LE, Seifert WE Jr, Coyle JT. Dopaminergic dsyfunction in Tourette syndrome. Ann Neurol  1982; 12(4): 361-6.
[http://dx.doi.org/10.1002/ana.410120408] [PMID: 6184010] 
[200] 
Riddle MA, Leckman JF, Anderson GM, et al. Tourette’s syndrome: clinical and neurochemical correlates. J Am Acad Child Adolesc Psychiatry  1988; 27(4): 409-12.
[http://dx.doi.org/10.1097/00004583-198807000-00004] [PMID: 3182595] 
[201] 
Singer HS, Hahn IH, Moran TH. Abnormal dopamine uptake sites in postmortem striatum from patients with Tourette’s syndrome. Ann Neurol  1991; 30(4): 558-62.
[http://dx.doi.org/10.1002/ana.410300408] [PMID: 1838678] 
[202] 
Wolf SS, Jones DW, Knable MB, et al. Tourette syndrome: prediction of phenotypic variation in monozygotic twins by caudate nucleus D2 receptor binding. Science  1996; 273(5279): 1225-7.
[http://dx.doi.org/10.1126/science.273.5279.1225] [PMID: 8703056] 
[203] 
George MS, Robertson MM, Costa DC, et al. Dopamine receptor availability in Tourette’s syndrome. Psychiatry Res  1994; 55(4): 193-203.
[http://dx.doi.org/10.1016/0925-4927(94)90014-0] [PMID: 7701034] 
[204] 
Müller-Vahl KR, Berding G, Kolbe H, et al. Dopamine D2 receptor imaging in Gilles de la Tourette syndrome. Acta Neurol Scand  2000; 101(3): 165-71.
[http://dx.doi.org/10.1034/j.1600-0404.2000.101003165.x] [PMID: 10705938] 
[205] 
Gilbert DL, Christian BT, Gelfand MJ, Shi B, Mantil J, Sallee FR. Altered mesolimbocortical and thalamic dopamine in Tourette syndrome. Neurology  2006; 67(9): 1695-7.
[http://dx.doi.org/10.1212/01.wnl.0000242733.18534.2c] [PMID: 17101911] 
[206] 
Steeves TD, Ko JH, Kideckel DM, et al. Extrastriatal dopaminergic dysfunction in tourette syndrome. Ann Neurol  2010; 67(2): 170-81.
[http://dx.doi.org/10.1002/ana.21809] [PMID: 20225192] 
[207] 
Malison RT, McDougle CJ, van Dyck CH, et al. [123I]beta-CIT SPECT imaging of striatal dopamine transporter binding in Tourette’s disorder. Am J Psychiatry  1995; 152(9): 1359-61.
[http://dx.doi.org/10.1176/ajp.152.9.1359] [PMID: 7653693] 
[208] 
Müller-Vahl KR, Berding G, Brücke T, et al. Dopamine transporter binding in Gilles de la Tourette syndrome. J Neurol  2000; 247(7): 514-20.
[http://dx.doi.org/10.1007/PL00007806] [PMID: 10993492] 
[209] 
Heinz A, Knable MB, Wolf SS, et al. Tourette’s syndrome: [I-123]beta-CIT SPECT correlates of vocal tic severity. Neurology  1998; 51(4): 1069-74.
[http://dx.doi.org/10.1212/WNL.51.4.1069] [PMID: 9781531] 
[210] 
Stamenkovic M, Schindler SD, Asenbaum S, et al. No change in striatal dopamine re-uptake site density in psychotropic drug naive and in currently treated Tourette’s disorder patients: a [(123)I]-beta-CIT SPECt-study. Eur Neuropsychopharmacol  2001; 11(1): 69-74.
[http://dx.doi.org/10.1016/S0924-977X(00)00134-6] [PMID: 11226814] 
[211] 
Serra-Mestres J, Ring HA, Costa DC, et al. Dopamine transporter binding in Gilles de la Tourette syndrome: a [123I]FP-CIT/SPECT study. Acta Psychiatr Scand  2004; 109(2): 140-6.
[http://dx.doi.org/10.1111/j.0001-690X.2004.00214.x] [PMID: 14725596] 
[212] 
Cheon KA, Ryu YH, Namkoong K, Kim CH, Kim JJ, Lee JD. Dopamine transporter density of the basal ganglia assessed with [123I]IPT SPECT in drug-naive children with Tourette’s disorder. Psychiatry Res  2004; 130(1): 85-95.
[http://dx.doi.org/10.1016/j.pscychresns.2003.06.001] [PMID: 14972371] 
[213] 
Wong DF, Brasić JR, Singer HS, et al. Mechanisms of dopaminergic and serotonergic neurotransmission in Tourette syndrome: clues from an in vivo neurochemistry study with PET. Neuropsychopharmacology  2008; 33(6): 1239-51.
[http://dx.doi.org/10.1038/sj.npp.1301528] [PMID: 17987065] 
[214] 
Meyer P, Bohnen NI, Minoshima S, et al. Striatal presynaptic monoaminergic vesicles are not increased in Tourette’s syndrome. Neurology  1999; 53(2): 371-4.
[http://dx.doi.org/10.1212/WNL.53.2.371] [PMID: 10430428] 
[215] 
Albin RL, Koeppe RA, Bohnen NI, et al. Increased ventral striatal monoaminergic innervation in Tourette syndrome. Neurology  2003; 61(3): 310-5.
[http://dx.doi.org/10.1212/01.WNL.0000076181.39162.FC] [PMID: 12913189] 
[216] 
Albin RL, Koeppe RA, Wernette K, et al. Striatal [11C]dihydrotetrabenazine and [11C]methylphenidate binding in Tourette syndrome. Neurology  2009; 72(16): 1390-6.
[http://dx.doi.org/10.1212/WNL.0b013e3181a187dd] [PMID: 19380698] 
[217] 
Ernst M, Zametkin AJ, Jons PH, Matochik JA, Pascualvaca D, Cohen RM. High presynaptic dopaminergic activity in children with Tourette’s disorder. J Am Acad Child Adolesc Psychiatry  1999; 38(1): 86-94.
[http://dx.doi.org/10.1097/00004583-199901000-00024] [PMID: 9893421] 
[218] 
Turjanski N, Sawle GV, Playford ED, et al. PET studies of the presynaptic and postsynaptic dopaminergic system in Tourette’s syndrome. J Neurol Neurosurg Psychiatry  1994; 57(6): 688-92.
[http://dx.doi.org/10.1136/jnnp.57.6.688] [PMID: 7911827] 
[219] 
Rabey JM, Oberman Z, Graff E, Korczyn AD. Decreased dopamine uptake into platelet storage granules in Gilles de la Tourette disease. Biol Psychiatry  1995; 38(2): 112-5.
[http://dx.doi.org/10.1016/0006-3223(94)00234-T] [PMID: 7578642] 
[220] 
Singer HS. The neurochemistry of Tourette syndrome. In: .  D. Martino & J. F. Leckman (Eds.), Tourette syndrome Oxford university press 2013; pp. 276-300.
[http://dx.doi.org/10.1093/med/9780199796267.003.0013] 
[221] 
Maia TV, Conceição VA. The roles of phasic and tonic dopamine in tic learning and expression. Biol Psychiatry  2017; 82(6): 401-12.
[http://dx.doi.org/10.1016/j.biopsych.2017.05.025] [PMID: 28734459] 
[222] 
Singer HS, Szymanski S, Giuliano J, et al. Elevated intrasynaptic dopamine release in Tourette’s syndrome measured by PET. Am J Psychiatry  2002; 159(8): 1329-36.
[http://dx.doi.org/10.1176/appi.ajp.159.8.1329] [PMID: 12153825] 
[223] 
Vernaleken I, Kuhn J, Lenartz D, et al. Bithalamical deep brain stimulation in tourette syndrome is associated with reduction in dopaminergic transmission. Biol Psychiatry  2009; 66(10): e15-7.
[http://dx.doi.org/10.1016/j.biopsych.2009.06.025] [PMID: 19709645] 
[224] 
Kuhn J, Janouschek H, Raptis M, et al. In vivo evidence of deep brain stimulation-induced dopaminergic modulation in Tourette’s syndrome. Biol Psychiatry  2012; 71(5): e11-3.
[http://dx.doi.org/10.1016/j.biopsych.2011.09.035] [PMID: 22129758] 
[225] 
Denys D, de Vries F, Cath D, et al. Dopaminergic activity in Tourette syndrome and obsessive-compulsive disorder. Eur Neuropsychopharmacol  2013; 23(11): 1423-31.
[http://dx.doi.org/10.1016/j.euroneuro.2013.05.012] [PMID: 23876376] 
[226] 
Canales JJ, Capper-Loup C, Hu D, Choe ES, Upadhyay U, Graybiel AM. Shifts in striatal responsivity evoked by chronic stimulation of dopamine and glutamate systems. Brain  2002; 125(Pt 10): 2353-63.
[http://dx.doi.org/10.1093/brain/awf239] [PMID: 12244091] 
[227] 
Marti M, Mela F, Bianchi C, Beani L, Morari M. Striatal dopamine-NMDA receptor interactions in the modulation of glutamate release in the substantia nigra pars reticulata in vivo: opposite role for D1 and D2 receptors. J Neurochem  2002; 83(3): 635-44.
[http://dx.doi.org/10.1046/j.1471-4159.2002.01169.x] [PMID: 12390525] 
[228] 
Singer HS, Morris C, Grados M. Glutamatergic modulatory therapy for Tourette syndrome. Med Hypotheses  2010; 74(5): 862-7.
[http://dx.doi.org/10.1016/j.mehy.2009.11.028] [PMID: 20022434] 
[229] 
Wu F, Orlefors H, Bergström M, et al. Uptake of 14C- and 11C-labeled glutamate, glutamine and aspartate in vitro and in vivo. Anticancer Res  2000; 20(1A): 251-6.
[PMID: 10769663] 
[230] 
Wang Y, Zhang QJ, Liu J, et al. Changes in firing rate and pattern of GABAergic neurons in subregions of the substantia nigra pars reticulata in rat models of Parkinson’s disease. Brain Res  2010; 1324: 54-63.
[http://dx.doi.org/10.1016/j.brainres.2010.02.008] [PMID: 20149784] 
[231] 
Aggarwal M, Wickens JR. A role for phasic dopamine neuron firing in habit learning. Neuron  2011; 72(6): 892-4.
[http://dx.doi.org/10.1016/j.neuron.2011.12.006] [PMID: 22196325] 
[232] 
Zheng X, Huang Z, Zhu Y, et al. Increase in glutamatergic terminals in the striatum following dopamine depletion in a rat model of Parkinson’s disease. Neurochem Res  2019; 44(5): 1079-89.
[http://dx.doi.org/10.1007/s11064-019-02739-y] [PMID: 30715657] 
[233] 
Kushner MG, Kim SW, Donahue C, et al. D-cycloserine augmented exposure therapy for obsessive-compulsive disorder. Biol Psychiatry  2007; 62(8): 835-8.
[http://dx.doi.org/10.1016/j.biopsych.2006.12.020] [PMID: 17588545] 
[234] 
Lemmon ME, Grados M, Kline T, Thompson CB, Ali SF, Singer HS. efficacy of glutamate modulators in tic suppression: a double-blind, randomized control trial of d-serine and riluzole in Tourette syndrome. Pediatr Neurol  2015; 52(6): 629-34.
[http://dx.doi.org/10.1016/j.pediatrneurol.2015.02.002] [PMID: 26002052] 
[235] 
Adamczyk A, Gause CD, Sattler R, et al. Genetic and functional studies of a missense variant in a glutamate transporter, SLC1A3, in Tourette syndrome. Psychiatr Genet  2011; 21(2): 90-7.
[http://dx.doi.org/10.1097/YPG.0b013e328341a307] [PMID: 21233784] 
[236] 
Harris K, Singer HS. Tic disorders: neural circuits, neurochemistry, and neuroimmunology. J Child Neurol  2006; 21(8): 678-89.
[http://dx.doi.org/10.1177/08830738060210080901] [PMID: 16970869] 
[237] 
Naaijen J, Forde NJ, Lythgoe DJ, Akkermans SE, Openneer TJ, Dietrich A, et al. Fronto-striatal glutamate in children with Tourette’s disorder and attention-deficit/hyperactivity disorder. Neuroimage Clin  2017; 13: 16-23.
[http://dx.doi.org/10.1016/j.nicl.2016.11.013] 
[238] 
Kanaan AS, Gerasch S, García-García I, et al. Pathological glutamatergic neurotransmission in Gilles de la Tourette syndrome. Brain  2017; 140(1): 218-34.
[http://dx.doi.org/10.1093/brain/aww285] [PMID: 28007998] 
[239] 
Dou W, Palomero-Gallagher N, van Tol MJ, et al. Systematic regional variations of GABA, glutamine, and glutamate concentrations follow receptor fingerprints of human cingulate cortex. J Neurosci  2013; 33(31): 12698-704.
[http://dx.doi.org/10.1523/JNEUROSCI.1758-13.2013] [PMID: 23904606] 
[240] 
Mekle R, Mlynárik V, Gambarota G, Hergt M, Krueger G, Gruetter R. MR spectroscopy of the human brain with enhanced signal intensity at ultrashort echo times on a clinical platform at 3T and 7T. Magn Reson Med  2009; 61(6): 1279-85.
[http://dx.doi.org/10.1002/mrm.21961] [PMID: 19319893] 
[241] 
Pradhan E, Bhandari S, Ghosh YK. The indications for and the diagnostic yield of imaging in neuro-ophthalmic and orbital disorders. Nepal J Ophthalmol  2015; 7(14): 159-63.
[PMID: 27363961] 
[242] 
Tkác I, Andersen P, Adriany G, Merkle H, Ugurbil K, Gruetter R. In vivo 1H NMR spectroscopy of the human brain at 7 T. Magn Reson Med  2001; 46(3): 451-6.
[http://dx.doi.org/10.1002/mrm.1213] [PMID: 11550235] 
[243] 
Mahone EM, Puts NA, Edden RAE, Ryan M, Singer HS. GABA and glutamate in children with Tourette syndrome: A 1H MR spectroscopy study at 7T. Psychiatry Res Neuroimaging  2018; 273: 46-53.
[http://dx.doi.org/10.1016/j.pscychresns.2017.12.005] [PMID: 29329743] 
[244] 
Dang MT, Yokoi F, Yin HH, Lovinger DM, Wang Y, Li Y. Disrupted motor learning and long-term synaptic plasticity in mice lacking NMDAR1 in the striatum. Proc Natl Acad Sci USA  2006; 103(41): 15254-9.
[http://dx.doi.org/10.1073/pnas.0601758103] [PMID: 17015831] 
[245] 
Lambot L, Chaves Rodriguez E, Houtteman D, et al. Striatopallidal neuron NMDA receptors control synaptic connectivity, locomotor, and goal-directed behaviors. J Neurosci  2016; 36(18): 4976-92.
[http://dx.doi.org/10.1523/JNEUROSCI.2717-15.2016] [PMID: 27147651] 
[246] 
Nordstrom EJ, Bittner KC, McGrath MJ, Parks CR III, Burton FH. “Hyperglutamatergic cortico-striato-thalamo-cortical circuit” breaker drugs alleviate tics in a transgenic circuit model of Tourette׳s syndrome. Brain Res  2015; 1629: 38-53.
[http://dx.doi.org/10.1016/j.brainres.2015.09.032] [PMID: 26453289] 
[247] 
Creed MC, Ntamati NR, Tan KR. VTA GABA neurons modulate specific learning behaviors through the control of dopamine and cholinergic systems. Front Behav Neurosci  2014; 8: 8.
[http://dx.doi.org/10.3389/fnbeh.2014.00008] [PMID: 24478655] 
[248] 
Singer HS, Hahn IH, Krowiak E, Nelson E, Moran T. Tourette’s syndrome: a neurochemical analysis of postmortem cortical brain tissue. Ann Neurol  1990; 27(4): 443-6.
[http://dx.doi.org/10.1002/ana.410270415] [PMID: 1972320] 
[249] 
Draper A, Stephenson MC, Jackson GM, et al. Increased GABA contributes to enhanced control over motor excitability in Tourette syndrome. Curr Biol  2014; 24(19): 2343-7.
[http://dx.doi.org/10.1016/j.cub.2014.08.038] [PMID: 25264251] 
[250] 
Freed RD, Coffey BJ, Mao X, et al. Decreased anterior cingulate cortex γ-aminobutyric acid in youth with Tourette’s disorder. Pediatr Neurol  2016; 65: 64-70.
[http://dx.doi.org/10.1016/j.pediatrneurol.2016.08.017] [PMID: 27743746] 
[251] 
Puts NA, Harris AD, Crocetti D, et al. Reduced GABAergic inhibition and abnormal sensory symptoms in children with Tourette syndrome. J Neurophysiol  2015; 114(2): 808-17.
[http://dx.doi.org/10.1152/jn.00060.2015] [PMID: 26041822] 
[252] 
Rothman DL, Petroff OA, Behar KL, Mattson RH. Localized 1H NMR measurements of gamma-aminobutyric acid in human brain in vivo. Proc Natl Acad Sci USA  1993; 90(12): 5662-6.
[http://dx.doi.org/10.1073/pnas.90.12.5662] [PMID: 8516315] 
[253] 
Rae CD. A guide to the metabolic pathways and function of metabolites observed in human brain 1H magnetic resonance spectra. Neurochem Res  2014; 39(1): 1-36.
[http://dx.doi.org/10.1007/s11064-013-1199-5] [PMID: 24258018] 
[254] 
Chen M, Liao C, Chen S, et al. Uncertainty assessment of gamma-aminobutyric acid concentration of different brain regions in individual and group using residual bootstrap analysis. Med Biol Eng Comput  2017; 55(6): 1051-9.
[http://dx.doi.org/10.1007/s11517-016-1579-5] [PMID: 27696130] 
[255] 
Lerner A, Bagic A, Simmons JM, et al. Widespread abnormality of the γ-aminobutyric acid-ergic system in Tourette syndrome. Brain  2012; 135(Pt 6): 1926-36.
[http://dx.doi.org/10.1093/brain/aws104] [PMID: 22577221] 
[256] 
Tian Y, Gunther JR, Liao IH, et al. GABA- and acetylcholine-related gene expression in blood correlate with tic severity and microarray evidence for alternative splicing in Tourette syndrome: a pilot study. Brain Res  2011; 1381: 228-36.
[http://dx.doi.org/10.1016/j.brainres.2011.01.026] [PMID: 21241679] 
[257] 
Richer P, Fernandez TV. tourette syndrome: bridging the gap between genetics and biology. Mol Neuropsychiatry  2015; 1(3): 156-64.
[http://dx.doi.org/10.1159/000439085] [PMID: 26509143] 
[258] 
Ogawa SK, Cohen JY, Hwang D, Uchida N, Watabe-Uchida M. Organization of monosynaptic inputs to the serotonin and dopamine neuromodulatory systems. Cell Rep  2014; 8(4): 1105-18.
[http://dx.doi.org/10.1016/j.celrep.2014.06.042] [PMID: 25108805] 
[259] 
Geddes SD, Assadzada S, Lemelin D, et al. Target-specific modulation of the descending prefrontal cortex inputs to the dorsal raphe nucleus by cannabinoids. Proc Natl Acad Sci USA  2016; 113(19): 5429-34.
[http://dx.doi.org/10.1073/pnas.1522754113] [PMID: 27114535] 
[260] 
Liu Z, Zhou J, Li Y, et al. Dorsal raphe neurons signal reward through 5-HT and glutamate. Neuron  2014; 81(6): 1360-74.
[http://dx.doi.org/10.1016/j.neuron.2014.02.010] [PMID: 24656254] 
[261] 
Qi J, Zhang S, Wang HL, Barker DJ, Miranda-Barrientos J, Morales M. VTA glutamatergic inputs to nucleus accumbens drive aversion by acting on GABAergic interneurons. Nat Neurosci  2016; 19(5): 725-33.
[http://dx.doi.org/10.1038/nn.4281] [PMID: 27019014] 
[262] 
Fischer AG, Ullsperger M. An Update on the Role of Serotonin and its Interplay with Dopamine for Reward. Front Hum Neurosci  2017; 11: 484.
[http://dx.doi.org/10.3389/fnhum.2017.00484] [PMID: 29075184] 
[263] 
Kayhan F, Uguz F, Kayhan A, Toktaş FI. Bupropion XL-induced motor and vocal tics. Clin Neuropharmacol  2014; 37(6): 192-3.
[http://dx.doi.org/10.1097/WNF.0000000000000056] [PMID: 25384079] 
[264] 
Müller-Vahl KR, Meyer GJ, Knapp WH, et al. Serotonin transporter binding in Tourette Syndrome. Neurosci Lett  2005; 385(2): 120-5.
[http://dx.doi.org/10.1016/j.neulet.2005.05.031] [PMID: 15936877] 
[265] 
Müller-Vahl KR, Szejko N, Wilke F, et al. Serotonin transporter binding is increased in Tourette syndrome with Obsessive Compulsive Disorder. Sci Rep  2019; 9(1): 972.
[http://dx.doi.org/10.1038/s41598-018-37710-4] 
[266] 
Haugbøl S, Pinborg LH, Regeur L, et al. Cerebral 5-HT2A receptor binding is increased in patients with Tourette’s syndrome. Int J Neuropsychopharmacol  2007; 10(2): 245-52.
[http://dx.doi.org/10.1017/S1461145706006559] [PMID: 16945163] 
[267] 
Behen M, Chugani HT, Juhász C, et al. Abnormal brain tryptophan metabolism and clinical correlates in Tourette syndrome. Mov Disord  2007; 22(15): 2256-62.
[http://dx.doi.org/10.1002/mds.21712] [PMID: 17708557] 
[268] 
Mössner R, Müller-Vahl KR, Döring N, Stuhrmann M. Role of the novel tryptophan hydroxylase-2 gene in Tourette syndrome. Mol Psychiatry  2007; 12(7): 617-9.
[http://dx.doi.org/10.1038/sj.mp.4002004] [PMID: 17592484] 
[269] 
Zhang Y, Su N, Wang G, Cui J, Yi M, Liu S. [Association of serotonin transporter linked polymorphic region 44 bp variable number of tandem repeat polymorphism with Tourette syndrome]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi  2014; 31(5): 646-9.
[PMID: 25297601] 
[270] 
Canal CE, Booth RG, Morgan D. Support for 5-HT2C receptor functional selectivity in vivo utilizing structurally diverse, selective 5-HT2C receptor ligands and the 2,5-dimethoxy-4-iodoamphetamine elicited head-twitch response model. Neuropharmacology  2013; 70: 112-21.
[http://dx.doi.org/10.1016/j.neuropharm.2013.01.007] [PMID: 23353901] 
[271] 
Nieto-Alamilla G, Márquez-Gómez R, García-Gálvez AM, Morales-Figueroa GE, Arias-Montaño JA. The histamine H3 receptor: Structure, pharmacology, and function. Mol Pharmacol  2016; 90(5): 649-73.
[http://dx.doi.org/10.1124/mol.116.104752] [PMID: 27563055] 
[272] 
Panula P, Nuutinen S. The histaminergic network in the brain: basic organization and role in disease. Nat Rev Neurosci  2013; 14(7): 472-87.
[http://dx.doi.org/10.1038/nrn3526] [PMID: 23783198] 
[273] 
Flik G, Dremencov E, Cremers TI, Folgering JH, Westerink BH. The role of cortical and hypothalamic histamine-3 receptors in the modulation of central histamine neurotransmission: an in vivo electrophysiology and microdialysis study. Eur J Neurosci  2011; 34(11): 1747-55.
[http://dx.doi.org/10.1111/j.1460-9568.2011.07893.x] [PMID: 22050612] 
[274] 
Haas HL, Sergeeva OA, Selbach O. Histamine in the nervous system. Physiol Rev  2008; 88(3): 1183-241.
[http://dx.doi.org/10.1152/physrev.00043.2007] [PMID: 18626069] 
[275] 
Ercan-Sencicek AG, Stillman AA, Ghosh AK, et al. L-histidine decarboxylase and Tourette’s syndrome. N Engl J Med  2010; 362(20): 1901-8.
[http://dx.doi.org/10.1056/NEJMoa0907006] [PMID: 20445167] 
[276] 
Fernandez TV, Sanders SJ, Yurkiewicz IR, et al. Rare copy number variants in tourette syndrome disrupt genes in histaminergic pathways and overlap with autism. Biol Psychiatry  2012; 71(5): 392-402.
[http://dx.doi.org/10.1016/j.biopsych.2011.09.034] [PMID: 22169095] 
[277] 
Schlicker E, Fink K, Detzner M, Göthert M. Histamine inhibits dopamine release in the mouse striatum via presynaptic H3 receptors. J Neural Transm  1993; 93(1): 1-10.
[http://dx.doi.org/10.1007/BF01244933] [PMID: 8396945] 
[278] 
Garcia M, Floran B, Arias-Montaño JA, Young JM, Aceves J. Histamine H3 receptor activation selectively inhibits dopamine D1 receptor-dependent [3H]GABA release from depolarization-stimulated slices of rat substantia nigra pars reticulata. Neuroscience  1997; 80(1): 241-9.
[http://dx.doi.org/10.1016/S0306-4522(97)00100-0] [PMID: 9252235] 
[279] 
Baldan LC, Williams KA, Gallezot JD, et al. Histidine decarboxylase deficiency causes tourette syndrome: parallel findings in humans and mice. Neuron  2014; 81(1): 77-90.
[http://dx.doi.org/10.1016/j.neuron.2013.10.052] [PMID: 24411733] 
[280] 
Bolam JP, Ellender TJ. Histamine and the striatum. Neuropharmacology  2016; 106: 74-84.
[http://dx.doi.org/10.1016/j.neuropharm.2015.08.013] [PMID: 26275849] 
[281] 
Vanhanen J, Kinnunen M, Nuutinen S, Panula P. Histamine H3 receptor antagonist JNJ-39220675 modulates locomotor responses but not place conditioning by dopaminergic drugs. Psychopharmacology  2015; 232(6): 1143-53.
[http://dx.doi.org/10.1007/s00213-014-3751-7] [PMID: 25308376] 
[282] 
Rapanelli M, Frick L, Pogorelov V, Ohtsu H, Bito H, Pittenger C. Histamine H3R receptor activation in the dorsal striatum triggers stereotypies in a mouse model of tic disorders. Transl Psychiatry  2017; 7(1) e1013
[http://dx.doi.org/10.1038/tp.2016.290] [PMID: 28117842] 
[283] 
Parmentier R, Ohtsu H, Djebbara-Hannas Z, Valatx JL, Watanabe T, Lin JS. Anatomical, physiological, and pharmacological characteristics of histidine decarboxylase knock-out mice: evidence for the role of brain histamine in behavioral and sleep-wake control. J Neurosci  2002; 22(17): 7695-711.
[http://dx.doi.org/10.1523/JNEUROSCI.22-17-07695.2002] [PMID: 12196593] 
[284] 
Shan L, Dauvilliers Y, Siegel JM. Interactions of the histamine and hypocretin systems in CNS disorders. Nat Rev Neurol  2015; 11(7): 401-13.
[http://dx.doi.org/10.1038/nrneurol.2015.99] [PMID: 26100750] 
[285] 
Pittenger C. Histidine decarboxylase knockout mice as a model of the pathophysiology of Tourette syndrome and related conditions. Handb Exp Pharmacol  2017; 241: 189-215.
[http://dx.doi.org/10.1007/164_2016_127] [PMID: 28233179] 
[286] 
Zhang YF, Cragg SJ. Pauses in striatal cholinergic interneurons: What is revealed by their common themes and variations? Front Syst Neurosci  2017; 11: 80.
[http://dx.doi.org/10.3389/fnsys.2017.00080] [PMID: 29163075] 
[287] 
Nelson AB, Hammack N, Yang CF, Shah NM, Seal RP, Kreitzer AC. Striatal cholinergic interneurons Drive GABA release from dopamine terminals. Neuron  2014; 82(1): 63-70.
[http://dx.doi.org/10.1016/j.neuron.2014.01.023] [PMID: 24613418] 
[288] 
Barbeau A. Emerging treatments: replacement therapy with choline or lecithin in neurological diseases. Can J Neurol Sci  1978; 5(1): 157-60.
[http://dx.doi.org/10.1017/S0317167100024963] [PMID: 148319] 
[289] 
Polinsky RJ, Ebert MH, Caine ED, Ludlow C, Bassich CJ. Cholinergic treatment in the Tourette syndrome. N Engl J Med  1980; 302(23): 1310.
[http://dx.doi.org/10.1056/NEJM198006053022313] [PMID: 6929034] 
[290] 
Stahl SM, Berger PA. Physostigmine in Tourette syndrome: evidence for cholinergic underactivity. Am J Psychiatry  1981; 138(2): 240-2.
[http://dx.doi.org/10.1176/ajp.138.2.240] [PMID: 6935977] 
[291] 
Tanner CM, Goetz CG, Klawans HL. Cholinergic mechanisms in Tourette syndrome. Neurology  1982; 32(11): 1315-7.
[http://dx.doi.org/10.1212/WNL.32.11.1315] [PMID: 6957735] 
[292] 
Silver AA, Shytle RD, Sanberg PR. Mecamylamine in Tourette’s syndrome: a two-year retrospective case study. J Child Adolesc Psychopharmacol  2000; 10(2): 59-68.
[http://dx.doi.org/10.1089/cap.2000.10.59] [PMID: 10933116] 
[293] 
Singer HS, Oshida L, Coyle JT. CSF cholinesterase activity in Gilles de la Tourette’s syndrome. Arch Neurol  1984; 41(7): 756-7.
[http://dx.doi.org/10.1001/archneur.1984.04050180078022] [PMID: 6588929] 
[294] 
Xu M, Kobets A, Du JC, et al. Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome. Proc Natl Acad Sci USA  2015; 112(3): 893-8.
[http://dx.doi.org/10.1073/pnas.1419533112] [PMID: 25561540] 
[295] 
Bouret S, Richmond BJ. Sensitivity of locus ceruleus neurons to reward value for goal-directed actions. J Neurosci  2015; 35(9): 4005-14.
[http://dx.doi.org/10.1523/JNEUROSCI.4553-14.2015] [PMID: 25740528] 
[296] 
Gobert A, Rivet JM, Audinot V, Newman-Tancredi A, Cistarelli L, Millan MJ. Simultaneous quantification of serotonin, dopamine and noradrenaline levels in single frontal cortex dialysates of freely-moving rats reveals a complex pattern of reciprocal auto- and heteroreceptor-mediated control of release. Neuroscience  1998; 84(2): 413-29.
[http://dx.doi.org/10.1016/S0306-4522(97)00565-4] [PMID: 9539213] 
[297] 
Alsene KM, Rajbhandari AK, Ramaker MJ, Bakshi VP. Discrete forebrain neuronal networks supporting noradrenergic regulation of sensorimotor gating. Neuropsychopharmacology  2011; 36(5): 1003-14.
[http://dx.doi.org/10.1038/npp.2010.238] [PMID: 21248721] 
[298] 
Shinomura T, Nakao S, Adachi T, Shingu K. Clonidine inhibits and phorbol acetate activates glutamate release from rat spinal synaptoneurosomes. Anesth Analg  1999; 88(6): 1401-5.
[http://dx.doi.org/10.1213/00000539-199906000-00037] [PMID: 10357352] 
[299] 
Jellish WS, Murdoch J, Kindel G, Zhang X, White FA. The effect of clonidine on cell survival, glutamate, and aspartate release in normo- and hyperglycemic rats after near complete forebrain ischemia. Exp Brain Res  2005; 167(4): 526-34.
[http://dx.doi.org/10.1007/s00221-005-0064-4] [PMID: 16044300] 
[300] 
Wang Y, Liu J, Gui ZH, et al. α2-Adrenoceptor regulates the spontaneous and the GABA/glutamate modulated firing activity of the rat medial prefrontal cortex pyramidal neurons. Neuroscience  2011; 182: 193-202.
[http://dx.doi.org/10.1016/j.neuroscience.2011.03.016] [PMID: 21402127] 
[301] 
Leckman JF, Goodman WK, Anderson GM, et al. Cerebrospinal fluid biogenic amines in obsessive compulsive disorder, Tourette’s syndrome, and healthy controls. Neuropsychopharmacology  1995; 12(1): 73-86.
[http://dx.doi.org/10.1038/sj.npp.1380241] [PMID: 7766289] 
[302] 
Chappell P, Riddle M, Anderson G, et al. Enhanced stress responsivity of Tourette syndrome patients undergoing lumbar puncture. Biol Psychiatry  1994; 36(1): 35-43.
[http://dx.doi.org/10.1016/0006-3223(94)90060-4] [PMID: 8080901] 
[303] 
Ang L, Borison R, Dysken M, Davis JM. Reduced excretion of MHPG in Tourette syndrome. Adv Neurol  1982; 35: 171-5.
[PMID: 6959487] 
[304] 
Bornstein RA, Baker GB. Urinary amines in Tourette’s syndrome patients with and without phenylethylamine abnormality. Psychiatry Res  1990; 31(3): 279-86.
[http://dx.doi.org/10.1016/0165-1781(90)90097-O] [PMID: 2333359] 
[305] 
Silverstein F, Smith CB, Johnston MV. Effect of clonidine on platelet alpha 2-adrenoreceptors and plasma norepinephrine of children with Tourette syndrome. Dev Med Child Neurol  1985; 27(6): 793-9.
[http://dx.doi.org/10.1111/j.1469-8749.1985.tb03804.x] [PMID: 3005096] 
[306] 
Befort K. Interactions of the opioid and cannabinoid systems in reward: Insights from knockout studies. Front Pharmacol  2015; 6: 6.
[PMID: 25698968] 
[307] 
Müller-Vahl KR. Treatment of Tourette syndrome with cannabinoids. Behav Neurol  2013; 27(1): 119-24.
[http://dx.doi.org/10.1155/2013/294264] [PMID: 23187140] 
[308] 
Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for Medical Use: A Systematic Review and Meta-analysis. JAMA  2015; 313(24): 2456-73.
[http://dx.doi.org/10.1001/jama.2015.6358] [PMID: 26103030] 
[309] 
2018 Emerging Science Abstracts. Neurology  2018; 90(24)e2182
[http://dx.doi.org/10.1212/WNL.0000000000005692] 
[310] 
http://abidetx.com/news/abide-therapeutics-reports-positive-topline-data-from-phase-1b-study-of-abx-1431-in-tourette-syndrome/
[311] 
Trainor D, Evans L, Bird R. Severe motor and vocal tics controlled with Sativex®. Australas Psychiatry  2016; 24(6): 541-4.
[http://dx.doi.org/10.1177/1039856216663737] [PMID: 27558217] 
[312] 
Kanaan AS, Jakubovski E, Müller-Vahl K. Significant tic reduction in an otherwise treatment-resistant patient with gilles de la tourette syndrome following treatment with nabiximols. Brain Sci  2017; 7(5) pii: E47
[http://dx.doi.org/10.3390/brainsci7050047] 
[313] 
Berding G, Müller-Vahl K, Schneider U, et al. [123I]AM281 single-photon emission computed tomography imaging of central cannabinoid CB1 receptors before and after Delta9-tetrahydrocannabinol therapy and whole-body scanning for assessment of radiation dose in tourette patients. Biol Psychiatry  2004; 55(9): 904-15.
[http://dx.doi.org/10.1016/j.biopsych.2004.01.005] [PMID: 15110734] 
[314] 
Gadzicki D, Müller-Vahl KR, Heller D, et al. Tourette syndrome is not caused by mutations in the central cannabinoid receptor (CNR1) gene. Am J Med Genet B Neuropsychiatr Genet  2004; 127B(1): 97-103.
[http://dx.doi.org/10.1002/ajmg.b.20159] [PMID: 15108190] 
[315] 
Ceci C, Proietti Onori M, Macrì S, Laviola G. Interaction between the endocannabinoid and serotonergic system in the exhibition of head twitch response in four mouse strains. Neurotox Res  2015; 27(3): 275-83.
[http://dx.doi.org/10.1007/s12640-014-9510-z] [PMID: 25516122] 
[316] 
Presti MF, Lewis MH. Striatal opioid peptide content in an animal model of spontaneous stereotypic behavior. Behav Brain Res  2005; 157(2): 363-8.
[http://dx.doi.org/10.1016/j.bbr.2004.08.003] [PMID: 15639187] 
[317] 
Sandyk R. Naloxone abolishes obsessive-compulsive behavior in Tourette’s syndrome. Int J Neurosci  1987; 35(1-2): 93-4.
[http://dx.doi.org/10.3109/00207458708987115] [PMID: 3476477] 
[318] 
Kurlan R, Majumdar L, Deeley C, Mudholkar GS, Plumb S, Como PG. A controlled trial of propoxyphene and naltrexone in patients with Tourette’s syndrome. Ann Neurol  1991; 30(1): 19-23.
[http://dx.doi.org/10.1002/ana.410300105] [PMID: 1681781] 
[319] 
Erenberg G, Lederman RJ. Naltrexone and Tourette’s syndrome. Ann Neurol  1992; 31(5): 574.
[http://dx.doi.org/10.1002/ana.410310521] [PMID: 1596095] 
[320] 
van Wattum PJ, Chappell PB, Zelterman D, Scahill LD, Leckman JF. Patterns of response to acute naloxone infusion in Tourette’s syndrome. Mov Disord  2000; 15(6): 1252-4.
[http://dx.doi.org/10.1002/1531-8257(200011)15:61252:AID-MDS10303.0.CO;2-I] [PMID: 11104215] 
[321] 
Haber SN, Kowall NW, Vonsattel JP, Bird ED, Richardson EP Jr. Gilles de la Tourette’s syndrome. A postmortem neuropathological and immunohistochemical study. J Neurol Sci  1986; 75(2): 225-41.
[http://dx.doi.org/10.1016/0022-510X(86)90097-3] [PMID: 2428943] 
[322] 
Haber SN, Wolfer D. Basal ganglia peptidergic staining in Tourette syndrome. A follow-up study. Adv Neurol  1992; 58: 145-50.
[PMID: 1414617] 
[323] 
Leckman JF, Riddle MA, Berrettini WH, et al. Elevated CSF dynorphin A [1-8] in Tourette’s syndrome. Life Sci  1988; 43(24): 2015-23.
[http://dx.doi.org/10.1016/0024-3205(88)90575-9] [PMID: 2463450] 
[324] 
Elghaba R, Bracci E. Dichotomous Effects of Mu Opioid receptor activation on striatal low-threshold spike interneurons. Front Cell Neurosci  2017; 11: 385.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5723306/
[325] 
Capasso A, Sorrentino L. Differential influence of D1 and D2 dopamine receptors on acute opiate withdrawal in guinea-pig isolated ileum. Br J Pharmacol  1997; 120(6): 1001-6.
[http://dx.doi.org/10.1038/sj.bjp.0700995] [PMID: 9134209] 
[326] 
Rodríguez De Fonseca F, Rubio P, Martín-Calderón JL, Caine SB, Koob GF, Navarro M. The dopamine receptor agonist 7-OH-DPAT modulates the acquisition and expression of morphine-induced place preference. Eur J Pharmacol  1995; 274(1-3): 47-55.
[http://dx.doi.org/10.1016/0014-2999(94)00708-F] [PMID: 7768280] 
[327] 
Chakos MH, Shirakawa O, Lieberman J, Lee H, Bilder R, Tamminga CA. Striatal enlargement in rats chronically treated with neuroleptic. Biol Psychiatry  1998; 44(8): 675-84.
[http://dx.doi.org/10.1016/S0006-3223(98)00029-8] [PMID: 9798070] 
[328] 
Min HK, Ross EK, Jo HJ, et al. Dopamine release in the nonhuman primate caudate and putamen depends upon site of stimulation in the subthalamic nucleus. J Neurosci  2016; 36(22): 6022-9.
[http://dx.doi.org/10.1523/JNEUROSCI.0403-16.2016] [PMID: 27251623] 
[329] 
Izquierdo A. Functional heterogeneity within rat orbitofrontal cortex in reward learning and decision making. J Neurosci  2017; 37(44): 10529-40.
[http://dx.doi.org/10.1523/JNEUROSCI.1678-17.2017] [PMID: 29093055] 
[330] 
Dyke K, Pépés SE, Chen C, et al. Comparing GABA-dependent physiological measures of inhibition with proton magnetic resonance spectroscopy measurement of GABA using ultra-high-field MRI. Neuroimage  2017; 152: 360-70.
[http://dx.doi.org/10.1016/j.neuroimage.2017.03.011] [PMID: 28284797] 
[331] 
Draper A, Jackson SR. Alterations in structural connectivity may contribute both to the occurrence of tics in Gilles de la Tourette syndrome and to their subsequent control. Brain  2015; 138(Pt 2): 244-5.
[http://dx.doi.org/10.1093/brain/awu338] [PMID: 25627236] 
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DOI https://dx.doi.org/10.2174/1574885514666191121143930	Print ISSN 1574-8855
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