Costs of control: decreased motor cortex engagement during a Go/NoGo task in Tourette's syndrome.

Gilles de la Tourette syndrome is a neuropsychiatric disorder characterized by an impaired ability to inhibit unwanted behaviour. Although the presence of chronic motor and vocal tics defines Tourette's syndrome, other distinctive behavioural features like echo- and coprophenomena, and non-obscene socially inappropriate behaviour are also core features. We investigated neuronal activation during stimulus-driven execution and inhibition of prepared movements in Tourette's syndrome. To this end, we performed event-related functional magnetic resonance imaging and structural diffusion tensor imaging in 15 moderately affected uncomplicated patients with 'pure' Tourette's syndrome and 15 healthy control participants matched for age and gender. Subjects underwent functional magnetic resonance imaging during a Go/NoGo reaction time task. They had to withhold a prepared finger movement for a variable time until a stimulus instructed them to either execute (Go) or inhibit it (NoGo). Tics were monitored throughout the experiments, combining surface electromyogram, video recording, and clinical assessment in the scanner. Patients with Tourette's syndrome had longer reaction times than healthy controls in Go trials and made more errors in total. Their functional brain activation was decreased in left primary motor cortex and secondary motor areas during movement execution (Go trials) but not during response inhibition (NoGo trials) compared with healthy control subjects. Volume of interest analysis demonstrated less task-related activation in patients with Tourette's syndrome in primary and secondary motor cortex bilaterally, but not in the basal ganglia and cortical non-motor areas. They showed reduced co-activation between the left primary sensory-motor hand area and a network of contralateral sensory-motor areas and ipsilateral cerebellar regions. There were no between-group differences in structural connectivity of the left primary sensory-motor cortex as measured by diffusion tensor imaging-based probabilistic tractography. Our results link reduced sensory-motor cortical activation during movement execution to a decreased co-activation between the sensory-motor cortex and other brain areas involved in motor processing. These functional changes in patients with Tourette's syndrome might result from adaptive reorganization in fronto-parietal brain networks engaged in motor and behavioural control, possibly triggered by abnormal processing and presumably overactivity in cortico-striato-cortical circuits. This might enable patients with Tourette's syndrome to better suppress unwanted movements but comes at a price of behavioural deficits in other domains.

[1]  Irene Neuner,et al.  Microstructure assessment of grey matter nuclei in adult tourette patients by diffusion tensor imaging , 2011, Neuroscience Letters.

[2]  H. Benali,et al.  Functional immaturity of cortico-basal ganglia networks in Gilles de la Tourette syndrome. , 2012, Brain : a journal of neurology.

[3]  M. Heil,et al.  Echoes from childhood—imitation in Gilles de la Tourette Syndrome , 2012, Movement disorders : official journal of the Movement Disorder Society.

[4]  Alexander Münchau,et al.  Structural changes in the somatosensory system correlate with tic severity in Gilles de la Tourette syndrome. , 2009, Brain : a journal of neurology.

[5]  Janet B W Williams,et al.  Diagnostic and Statistical Manual of Mental Disorders , 2013 .

[6]  B. Peterson,et al.  Interhemispheric connectivity and executive functioning in adults with Tourette syndrome. , 2006, Neuropsychology.

[7]  S. Channon,et al.  Tourette's syndrome (TS): inhibitory performance in adults with uncomplicated TS. , 2009, Neuropsychology.

[8]  J. Bradshaw,et al.  Movement sequencing in children with Tourette's syndrome and attention deficit hyperactivity disorder , 2000, Movement disorders : official journal of the Movement Disorder Society.

[9]  H. Wittchen,et al.  Strukturiertes Klinisches Interview (und Fragebogen) für DSM-IV (SKID-II), Achse II (Persönlichkeitsstörungen). Eine deutschsprachige, erweiterte Bearbeitung der amerikanischen Originalversion des SCID-II von: M.B. First, R.L. Spitzer, M. Gibbon, J.B.W. Williams, L. Benjamin (Version 3/96) , 1996 .

[10]  H. Singer,et al.  Tourette's syndrome: from behaviour to biology , 2005, The Lancet Neurology.

[11]  A Münchau,et al.  Altered modulation of intracortical excitability during movement preparation in Gilles de la Tourette syndrome. , 2010, Brain : a journal of neurology.

[12]  A. Toga,et al.  Thinning of sensorimotor cortices in children with Tourette syndrome , 2008, Nature Neuroscience.

[13]  H. Singer,et al.  Neurobiology of Tourette's syndrome: concepts of neuroanatomic localization and neurochemical abnormalities , 2003, Brain and Development.

[14]  J. Mink,et al.  Neurobiology of basal ganglia and Tourette syndrome: basal ganglia circuits and thalamocortical outputs. , 2006, Advances in neurology.

[15]  Alexander Münchau,et al.  The pathophysiology of echopraxia/echolalia: Relevance to Gilles De La Tourette syndrome , 2012, Movement disorders : official journal of the Movement Disorder Society.

[16]  J C Gore,et al.  Regional brain and ventricular volumes in Tourette syndrome. , 2001, Archives of general psychiatry.

[17]  A. Anderson,et al.  A functional magnetic resonance imaging study of tic suppression in Tourette syndrome. , 1998, Archives of general psychiatry.

[18]  S. Petersen,et al.  Control networks in paediatric Tourette syndrome show immature and anomalous patterns of functional connectivity , 2008, Brain : a journal of neurology.

[19]  F. Schneider,et al.  Altered motor network activation and functional connectivity in adult tourette's syndrome , 2011, Human brain mapping.

[20]  S. Channon,et al.  Tourette's syndrome (TS): cognitive performance in adults with uncomplicated TS. , 2006, Neuropsychology.

[21]  S. Jackson,et al.  Motor excitability is reduced prior to voluntary movements in children and adolescents with Tourette syndrome , 2013, Journal of neuropsychology.

[22]  Karl J. Friston,et al.  Statistical parametric maps in functional imaging: A general linear approach , 1994 .

[23]  R. C. Oldfield The assessment and analysis of handedness: the Edinburgh inventory. , 1971, Neuropsychologia.

[24]  V. Roessner,et al.  Neuromodulation in Tourette syndrome: Dopamine and beyond , 2013, Neuroscience & Biobehavioral Reviews.

[25]  M Hallett,et al.  Neural correlates of tic generation in Tourette syndrome: an event-related functional MRI study. , 2006, Brain : a journal of neurology.

[26]  Daniel M. Corcos,et al.  Three-dimensional locations and boundaries of motor and premotor cortices as defined by functional brain imaging: A meta-analysis , 2006, NeuroImage.

[27]  Timothy Edward John Behrens,et al.  Characterization and propagation of uncertainty in diffusion‐weighted MR imaging , 2003, Magnetic resonance in medicine.

[28]  B S Peterson,et al.  Neuroimaging studies of Tourette syndrome: a decade of progress. , 2001, Advances in neurology.

[29]  Christian Büchel,et al.  Amygdala-prefrontal coupling depends on a genetic variation of the serotonin transporter , 2005, Nature Neuroscience.

[30]  Alan C. Evans,et al.  Somatosensory–motor bodily representation cortical thinning in Tourette: Effects of tic severity, age and gender , 2010, Cortex.

[31]  C. Gerloff,et al.  Interhemispheric motor networks are abnormal in patients with Gilles de la Tourette syndrome , 2010, Movement disorders : official journal of the Movement Disorder Society.

[32]  Aribert Rothenberger,et al.  Altered motor network recruitment during finger tapping in boys with tourette syndrome , 2012, Human brain mapping.

[33]  S. Jackson,et al.  Cognitive control over motor output in Tourette syndrome , 2013, Neuroscience & Biobehavioral Reviews.

[34]  Peter Brown,et al.  Motor inhibition in patients with Gilles de la Tourette syndrome: functional activation patterns as revealed by EEG coherence. , 2004, Brain : a journal of neurology.

[35]  Paul S. Morgan,et al.  Compensatory Neural Reorganization in Tourette Syndrome , 2011, Current Biology.

[36]  D. Cohen,et al.  Yale Global Tic Severity Scale , 2014 .

[37]  Carol L. Baym,et al.  Neural correlates of tic severity and cognitive control in children with Tourette syndrome. , 2008, Brain : a journal of neurology.

[38]  K. Hugdahl,et al.  Go/NoGo Performance in Boys with Tourette Syndrome , 2010, Child neuropsychology : a journal on normal and abnormal development in childhood and adolescence.

[39]  Tore Wentzel-Larsen,et al.  Reduced white matter connectivity in the corpus callosum of children with Tourette syndrome. , 2006, Journal of child psychology and psychiatry, and allied disciplines.

[40]  Diane Swick,et al.  Are the neural correlates of stopping and not going identical? Quantitative meta-analysis of two response inhibition tasks , 2011, NeuroImage.

[41]  W. McMahon,et al.  The Tourette Syndrome Diagnostic Confidence Index , 1999, Neurology.

[42]  J. Rothwell,et al.  Grip force behavior in Gilles de la Tourette syndrome , 2005, Movement disorders : official journal of the Movement Disorder Society.

[43]  J L Bradshaw,et al.  The Simon effect and attention deficits in Gilles de la Tourette's syndrome and Huntington's disease. , 1995, Brain : a journal of neurology.

[44]  E Stern,et al.  A functional neuroanatomy of tics in Tourette syndrome. , 2000, Archives of general psychiatry.

[45]  B S Peterson,et al.  Phenomenology of tics and natural history of tic disorders. , 2001, Advances in neurology.

[46]  J. Baudewig,et al.  Normal response inhibition in boys with Tourette syndrome , 2008, Behavioral and Brain Functions.

[47]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[48]  Mark W. Woolrich,et al.  Advances in functional and structural MR image analysis and implementation as FSL , 2004, NeuroImage.

[49]  Jan Gläscher,et al.  Visualization of Group Inference Data in Functional Neuroimaging , 2009, Neuroinformatics.

[50]  Tore Wentzel-Larsen,et al.  Altered interhemispheric connectivity in individuals with Tourette's disorder. , 2004, The American journal of psychiatry.

[51]  David L. Strayer,et al.  Inhibitory deficits in Tourette syndrome: a function of comorbidity and symptom severity. , 1998, Journal of child psychology and psychiatry, and allied disciplines.

[52]  M. Robertson,et al.  Tourette syndrome, associated conditions and the complexities of treatment. , 2000, Brain : a journal of neurology.

[53]  S. Leurgans,et al.  Advantages of a modified scoring method for the rush video‐based tic rating scale , 1999, Movement disorders : official journal of the Movement Disorder Society.

[54]  G. Jackson,et al.  Enhanced Cognitive Control in Young People with Tourette's Syndrome , 2006, Current Biology.

[55]  Alexander Münchau,et al.  The functional anatomy of Gilles de la Tourette syndrome , 2013, Neuroscience & Biobehavioral Reviews.

[56]  Steven E. Petersen,et al.  Task Control Signals in Pediatric Tourette Syndrome Show Evidence of Immature and Anomalous Functional Activity , 2009, Front. Hum. Neurosci..