Functional neuroimaging in Tourette syndrome: recent perspectives

Figures & data

Table 1 Summary of the most important findings from functional neuroimaging studies on TS from the last 10 years, ie, from 2006 to 2016.

Neural events	Functional neuroimaging method	Involved structures in patients with TS
Premonitory urges	fMRI	1. Involvement of insula and cingulate cortex^Citation15 2. Gray matter thinning within sensory areas of the frontosubcortical circuitry,^Citation15 within the left insula and right sensorimotor cortex^Citation17
	PET	Prominent activation in cerebellum and insula^Citation60
Tic generation	fMRI	1. Two seconds before tic: activation of supplementary motor area, ventral primary motor cortex, primary sensorimotor cortex, parietal operculum,^Citation12 and anterior cingulate cortex^Citation13 2. One second before a tic: activation of anterior cingulate cortex, putamen, insula, amygdala, cerebellum, and the extrastriatal visual cortex^Citation12 3. During tic onset: activation in the thalamus, central operculum, primary motor and somatosensory cortices^Citation12, as well as in sensorimotor areas and cerebellum^Citation13 4. Involvement of sensorimotor cortex^Citation11
	MEG	Involvement of sensorimotor cortex^Citation11
	EEG	Spreading of neural oscillation from the left prefrontal and centroparietal regions to the left frontal regions^Citation70
	PET	Prominent activation in cerebellum and insula^Citation60
Voluntary expression of tics	EEG	Increased oscillations in the prefrontal region^Citation74
Tic suppression	fMRI	Increased activity in left inferior frontal gyrus^Citation19
	EEG	Overactivation of cortical areas^Citation71
Inhibitory motor control	fMRI	1. Decreased activity in left primary motor cortex and secondary motor areas during go trials^Citation22 2. Reduced activation in the dorsal premotor cortex for the StopSuccess^Citation21 3. Activation of prefrontal cortex during regulation of motor output^Citation24 4. Sensorimotor gating deficits during prepulse inhibition^Citation28,Citation29 5. Involvement of frontostriatal circuits in self-regulatory task^Citation25,Citation26 6. Increased activation in the direct pathway through the basal ganglia and increased compensatory activation in the prefrontal cortex and subthalamic nucleus during the performance of a cognitive control task^Citation27
	MEG	1. Sensorimotor cortex^Citation28
Voluntary motor execution	fMRI	1. Decreased regional volumes of cerebellar hemispheres during finger tapping^Citation33 2. Altered motor network activations during simple motor performance^Citation32 3. Different neurofunctional organization of motor control^Citation34 4. No differences in activation patterns during finger tapping task^Citation30
	MEG	1. Involvement of sensorimotor cortex^Citation39 2. Increased interaction between supplementary motor area and primary motor cortex^Citation40 3. Altered motor cortical reactivity^Citation41
Perception and listening	fMRI	1. Deficient frontal inhibition in the interaction of the cortico-striato-thalamo-cortical network within structures of the limbic system^Citation36 2. Different callosal functioning during listening^Citation37
Resting state fMRI	fMRI	Abnormal spontaneous neuronal activity and perturbed connectivity of cortico-subcortical networks^Citation38
	Functional connectivity	1. Abnormal functional connectivity in the bilateral prefronto-striatum-midbrain networks and in the bilateral sensorimotor and temporal cortices^Citation42 2. Altered functional connectivity of amygdala^Citation43 3. Abnormal signaling primarily in the frontoparietal network^Citation44 4. Stronger functional integration and a global functional disorganization of corticobasal ganglia networks^Citation46
	TMS	1. Abnormal functional interhemispheric connectivity^Citation51 2. Increased resting motor threshold^Citation52 3. Increased variability of motor evoked potential responses^Citation52
	MRS	1. Reduced primary sensorimotor cortex GABA concentrations^Citation53 2. No differences in GABA values in the right sensorimotor cortex^Citation11 3. Increased GABA concentrations within the supplementary motor area^Citation55
	NIRS	Reduced prefrontal hemodynamic response^Citation56
	PET	1. Hypermetabolism in various brain regions^Citation57-Citation59 2. Decreased binding of GABA receptors^Citation54 3. Abnormal dopaminergic neurotransmission^Citation61-Citation64 4. Normal dopamine receptor availability and affinity^Citation65,Citation66 5. Abnormal serotonergic neurotransmission^Citation64,Citation67-Citation69
	SPECT	1. DAT uptake ratios were significantly negatively correlated with disease duration^Citation70 2. Functional abnormality of the dopamine system in patients with TS in its early stage^Citation71 3. Normal DAT activity^Citation71,Citation72

Abbreviations: TS, Tourette syndrome, fMRI, functional magnetic resonance imaging; MEG, magnetoencephalography; MRS, magnetic resonance spectroscopy; NIRS, near infrared spectroscopy; PET, positron emission tomography; EEG, electroencephalography; GABA, gamma-amino-butyric acid; DAT, dopamine transporter; SPECT, single-photon emission computed tomography.

Figure 1 Simplified diagram of the cortico-striato-thalamo-cortical circuit.

Notes: Inhibitory connections are marked by continuous lines; excitatory connections are marked by dotted lines. Green indicates connections that use glu as neurotransmitter; blue indicates connections that use GABA as neurotransmitter; red indicates connections that use dop as neurotransmitter. In the presence of dopamine, dopamine receptors in the basal ganglia stimulate the GABAergic neurons. Reprinted from Movement Disorders in Childhood, 2nd ed, Singer HS, Mink JW, Gilbert DL, Jankovic J, Copyright 2016, with permission from Elsevier.⁹²

Abbreviations: dop, dopamine; glu, glutamate.

Rajagopal S, Seri And S, Cavanna AE. Premonitory urges and sensorimotor processing in Tourette syndrome. Behav Neurol. 2013;27(1):65–73.

 Web of Science ®Google Scholar

Draper A, Jackson GM, Morgan PS, Jackson SR. Premonitory urges are associated with decreased grey matter thickness within the insula and sensorimotor cortex in young people with Tourette syndrome. J Neuropsychol. 2016;10(1):143–153.

 Web of Science ®Google Scholar

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):1979–1987.

 PubMed Web of Science ®Google Scholar

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.

 PubMed Web of Science ®Google Scholar

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):2029–2037.

 PubMedGoogle Scholar

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):5834–5846.

 Web of Science ®Google Scholar

Liu H, Meng Z, Zhang B, Tan J, Wang Y. Evaluation of Tourette’s syndrome by 99mTc-TRODAT-1 SPECT/CT imaging. Ann Nucl Med. 2010;24(7):515–521.

 Web of Science ®Google Scholar

Hong HJ, Sohn H, Cha M, et al. Increased frontomotor oscillations during tic suppression in children with Tourette syndrome. J Child Neurol. 2013;28(5):615–624.

 Web of Science ®Google Scholar

Ganos C, Kahl U, Brandt V, et al. The neural correlates of tic inhibition in Gilles de la Tourette syndrome. Neuropsychologia. 2014;65:297–301.

 PubMed Web of Science ®Google Scholar

Yeh CB, Lee CH, Chou YH, Chang CJ, Ma KH, Huang WS. Evaluating dopamine transporter activity with 99mTc-TRODAT-1 SPECT in drug naïve Tourette’s adults. Nucl Med Commun. 2006;27:779–784.

 Web of Science ®Google Scholar

Thomalla G, Jonas M, Bäumer T, et al. Costs of control: decreased motor cortex engagement during a Go/NoGo task in Tourette’s syndrome. Brain. 2014;137(Pt 1):122–136.

 Google Scholar

Ganos C, Kühn S, Kahl U, et al. Action inhibition in Tourette syndrome. Mov Disord. 2014;29(12):1532–1538.

 PubMed Web of Science ®Google Scholar

Jackson SR, Parkinson A, Jung J, et al. Compensatory neural reorganization in Tourette syndrome. Curr Biol. 2011;21(7):580–585.

 PubMed Web of Science ®Google Scholar

Zebardast N, Crowley MJ, Bloch MH, et al. Brain mechanisms for prepulse inhibition in adults with Tourette syndrome: initial findings. Psychiatry Res. 2013;214(1):33–41.

 Web of Science ®Google Scholar

Buse J, Beste C, Herrmann E, Roessner V. Neural correlates of altered sensorimotor gating in boys with Tourette Syndrome: a combined EMG/fMRI study. World J Biol Psychiatry. 2016;17(3)187–197.

 PubMed Web of Science ®Google Scholar

Raz A, Zhu H, Yu S, et al. Neural substrates of self-regulatory control in children and adults with Tourette syndrome. Can J Psychiatry. 2009;54(9):579–588.

 PubMed Web of Science ®Google Scholar

Marsh R, Zhu H, Wang Z, Skudlarski P, Peterson BS. A developmental fMRI study of self-regulatory control in Tourette’s syndrome. Am J Psychiatry. 2007;164(6):955–966.

 PubMed Web of Science ®Google Scholar

Baym CL, Corbett BA, Wright SB, Bunge SA. Neural correlates of tic severity and cognitive control in children with Tourette syndrome. Brain. 2008;131(Pt 1):165–179.

 PubMedGoogle Scholar

Tobe RH, Bansal R, Xu D, et al. Cerebellar morphology in Tourette syndrome and obsessive-compulsive disorder. Ann Neurol. 2010;67(4):479–487.

 Web of Science ®Google Scholar

Roessner V, Wittfoth M, August JM, Rothenberger A, Baudewig J, Dechent P. Finger tapping-related activation differences in treatment-naïve pediatric Tourette syndrome: a comparison of the preferred and nonpreferred hand. J Child Psychol Psychiatry. 2013;54(3):273–279.

 Web of Science ®Google Scholar

Zapparoli L, Porta M, Gandola M, et al. A functional magnetic resonance imaging investigation of motor control in Gilles de la Tourette syndrome during imagined and executed movements. Eur J Neurosci. 2016;43(4):494–508.

 PubMed Web of Science ®Google Scholar

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):560–569.

 PubMed Web of Science ®Google Scholar

Biermann-Ruben K, Miller A, Franzkowiak S, et al. Increased sensory feedback in Tourette syndrome. Neuroimage. 2012;63(1),119–125.

 Web of Science ®Google Scholar

Franzkowiak S, Pollok B, Biermann-Ruben K, et al. Motor-cortical interaction in Gilles de la Tourette syndrome. PLoS ONE. 2012;7(1):e27850.

 Web of Science ®Google Scholar

Franzkowiak S, Pollok B, Biermann-Ruben K, et al. Altered pattern of motor cortical activation-inhibition during voluntary movements in Tourette syndrome. Mov Disord. 2010;25(12):1960–1966.

 Web of Science ®Google Scholar

Neuner I, Kellermann T, Stöcker T, et al. Amygdala hypersensitivity in response to emotional faces in Tourette’s patients. World J Biol Psychiatry. 2010;11(7):858–872.

 PubMed Web of Science ®Google Scholar

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):767–774.

 PubMed Web of Science ®Google Scholar

Cui Y, Jin Z, Chen X, He Y, Liang X, Zheng Y. Abnormal baseline brain activity in drug-naïve patients with Tourette syndrome: a resting-state fMRI study. Front Hum Neurosci. 2014;7:913.

 Web of Science ®Google Scholar

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. In press 2016.

 Google Scholar

Werner CJ, Stöcker T, Kellermann T, et al. Altered amygdala functional connectivity in adult Tourette’s syndrome. Eur Arch Psychiatry Clin Neurosci. 2010;260(Suppl 2):S95–S99.

 Google Scholar

Church JA, Fair DA, Dosenbach NU, et al. Control networks in paediatric Tourette syndrome show immature and anomalous patterns of functional connectivity. Brain. 2009;132(Pt 1):225–238.

 Google Scholar

Worbe Y, Malherbe C, Hartmann A, et al. Functional immaturity of cortico-basal ganglia networks in Gilles de la Tourette syndrome. Brain. 2012;135(Pt 6):1937–1946.

 Google Scholar

Bäumer T, Thomalla G, Kroeger J, et al. Interhemispheric motor networks are abnormal in patients with Gilles de la Tourette syndrome. Mov Disord. 2010;25(16):2828–2837.

 Web of Science ®Google Scholar

Pépés SE, Draper A, Jackson GM, Jackson SR. Effects of age on motor excitability measures from children and adolescents with Tourette syndrome. Dev Cogn Neurosci. 2016;19:78–86.

 Web of Science ®Google Scholar

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):808–817.

 PubMed Web of Science ®Google Scholar

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):2343–2347.

 PubMed Web of Science ®Google Scholar

Yamamuro K, Ota T, Iida J, et al. Prefrontal dysfunction in pediatric Tourette’s disorder as measured by near-infrared spectroscopy. BMC Psychiatry. 2015;15:102.

 Web of Science ®Google Scholar

Alongi P, Iaccarino L, Perani D. PET neuroimaging: insights on dystonia and Tourette syndrome and potential applications. Front Neurol. 2014;5:183.

 Web of Science ®Google Scholar

De Vries FE, van den Heuvel OA, Cath DC, et al. Limbic and motor circuits involved in symmetry behavior in Tourette´s syndrome. CNS Spectr. 2013;18(1):34–42.

 Web of Science ®Google Scholar

Lerner A, Bagic A, Simmons JM, et al. Widespread abnormality of the gamma aminobutyric acid-ergic system in Tourette syndrome. Brain. 2012;135;1926–1936.

 Web of Science ®Google Scholar

Denys D, de Vries F, Cath D, Figee M, Vulink N, Veltman DJ. Dopaminergic activity in Tourette syndrome and obsessive-compulsive disorder. Eur Neuropsychopharmacol. 2013;23(11):1423–1431.

 Web of Science ®Google Scholar

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):1239–1251.

 PubMed Web of Science ®Google Scholar

Abi-Jaoude E, Segura B, Obeso I, et al. Similar striatal D2/D3 dopamine receptor availability in adults with Tourette syndrome compared with healthy controls: A [(11) C]-(+)-PHNO and [(11) C]raclopride positron emission tomography imaging study. Hum Brain Mapp. 2015;36(7):2592–2601.

 Web of Science ®Google Scholar

Albin RL, Koeppe RA, Wernette K, et al. Striatal [11C]dihydrotetrabenazine and [11C]methylphenidate binding in Tourette syndrome. Neurology. 2009;72(16):1390–1396.

 Web of Science ®Google Scholar

Saporta AS, Chugani HT, Juhász C, et al. Multimodality neuroimaging in Tourette syndrome: alpha-[11C] methyl-L-tryptophan positron emission tomography and diffusion tensor imaging studies. J Child Neurol. 2010;25(3):336–342.

 Web of Science ®Google Scholar

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):245–252.

 PubMed Web of Science ®Google Scholar

Hwang WJ, Yao WJ, Fu YK, Yang AS. 99mTc-TRODAT-1/[123 I]IBZM SPECT studies of the dopaminergic system in Tourette Syndrome. Psychiatry Res. 2008;162(2):159–166.

 Web of Science ®Google Scholar

Singer HS, Mink JW, Gilbert DL, Jankovic J. Movement Disorders in Childhood. 2nd ed. Philadelphia, PA: Elsevier Inc; 2016.

 Google Scholar