Gilles de la Tourette syndrome (GTS) is often complicated by comorbid attention-deficit/hyperactivity disorder (ADHD) or obsessive-compulsive disorder (OCD). This study examines whether motor cortex excitability differs between uncomplicated GTS patients and those complicated by ADHD or OCD.
Motor thresholds, short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF), and short latency afferent inhibition (SAI) were measured using transcranial magnetic stimulation (TMS) in 29 untreated GTS patients (18 uncomplicated, six with comorbid ADHD, five with comorbid OCD) and 24 healthy subjects. Tic severity was rated with standard clinical scales.
Patients had slightly higher resting (RMT) and active motor thresholds (AMT). The threshold of SICI and ICF expressed as a percentage of each individual's AMT was similar in controls and GTS patients. Above threshold, GTS patients had less SICI and more ICF. SICI was similar in all subgroups, but ICF differed significantly between them. Patients with GTS+ADHD had more ICF than controls, uncomplicated GTS patients or GTS+OCD patients; ICF was similar in these other groups. GTS patients as a whole had reduced SAI. Uncomplicated GTS patients or GTS+ADHD patients had less SAI than controls or GTS+OCD patients.
GTS with ADHD comorbidity is associated with more extensive changes in the excitability of motor cortex circuits than uncomplicated GTS or GTS+OCD. The extent to which various different neuronal circuits are affected may be relevant for the phenotype of Tourette spectrum disorders.
"For example , some electrophysiological studies (using transcranial magnetic stimulation) have found reduced cortical inhibition in the primary motor cortex in TS/CTD (Ziemann et al., 1997; Gilbert et al., 2004), suggesting altered motor inhibition. However, other studies have shown that differences in cortical excitability may be more related to comorbid attention deficit hyperactivity disorder (ADHD) symptoms than to tics (Gilbert et al., 2005; Orth and Rothwell, 2009). Similarly, although behavioral studies in children and adults with TS/CTD have demonstrated impairments in response inhibition, selective attention, and cognitive flexibility (Bornstein et al., 1991; Channon et al., 2003, 2009; Watkins et al., 2005), some have argued that these impairments are driven by comorbid conditions, including ADHD and obsessive-compulsive disorder (OCD) (Ozonoff et al., 1998; Denckla, 2006). "
[Show abstract][Hide abstract] ABSTRACT: Tic disorders are childhood onset neuropsychiatric disorders characterized by motor and/or vocal tics. Research has demonstrated that children with chronic tics (including Tourette syndrome and Chronic Tic Disorder: TS/CTD) can suppress tics, particularly when an immediate, contingent reward is given for successful tic suppression. As a diagnosis of TS/CTD requires tics to be present for at least one year, children in these tic suppression studies had been living with tics for quite some time. Thus, it is unclear whether the ability to inhibit tics is learned over time or present at tic onset. Resolving that issue would inform theories of how tics develop and how behavior therapy for tics works. We investigated tic suppression in school-age children as close to the time of tic onset as possible, and no later than six months after onset. Children were asked to suppress their tics both in the presence and absence of a contingent reward. Results demonstrated that these children, like children with TS/CTD, have some capacity to suppress tics, and that immediate reward enhances that capacity. These findings demonstrate that the modulating effect of reward on inhibitory control of tics is present within months of tic onset, before tics have become chronic
[Show abstract][Hide abstract] ABSTRACT: Gilles de la Tourette syndrome (GTS) holds a prime position as a disorder transgressing the brittle boundaries of neurology and psychiatry with an entangling web of motor and behavioural problems. With tics as the disorder's hallmark and myriads of related signs such as echo-, pali- and coprophenomena, paralleled by a broad neuropsychiatric spectrum of comorbidities encompassing attention deficit hyperactivity disorder, obsessive-compulsive disorder but also self-injurious behaviour and depression, GTS pathophysiology remains enigmatic. In this review, in the light of GTS phenomenology, we will focus on current theories of tic-emergence related to aberrant activity in the basal ganglia and abnormal basal ganglia - cortex interplay through cortico-striato-thalamocortical loops from an anatomical, neurophysiological and functional-neuroimaging perspective. We will attempt a holistic view to the countless major and minor drawbacks of the GTS brain and comment on future directions of neuroscientific research to elucidate this common and complex neuropsychiatric syndrome, which merits scientific understanding and social acceptance.
"These studies show considerable consistency, and demonstrate the following. First, resting motor threshold (RMT) and active motor threshold (AMT) do not typically differ between individuals with TS and controls (Heise et al., 2010; Moll et al., 1999, 2001; Orth et al., 2005, 2008; Ziemann et al., 1997; but see Orth & Rothwell, 2009). Second, the duration of the cortical silent period (CSP) induced by TMS to motor cortex, and the magnitude of the short-interval intra-cortical inhibition (SICI) that is observed, are both significantly reduced in individuals with TS relative to matched controls (e.g., Gilbert et al., 2004; Moll et al., 1999, 2001; Orth et al., 2008; Ziemann et al., 1997). "
[Show abstract][Hide abstract] ABSTRACT: Tourette syndrome (TS) is a neuro-developmental disorder characterized by the occurrence of motor and vocal tics: involuntary, repetitive, stereotyped behaviours that occur with a limited duration, often typically many times in a single day. Previous studies suggest that children and adolescents with TS may undergo compensatory, neuroplastic changes in brain structure and function that help them gain control over their tics. In the current study we used single-pulse and dual-site paired-pulse transcranial magnetic stimulation (TMS), in conjunction with a manual choice reaction time task that induces high levels of inter-manual conflict, to investigate this conjecture in a group of children and adolescents with TS, but without co-morbid Attention Deficit Hyperactivity Disorder (ADHD). We found that performance on the behavioural response-conflict task did not differ between the adolescents with TS and a group of age-matched typically developing individuals. By contrast, our study demonstrated that cortical excitability, as measured by TMS-induced motor-evoked potentials (MEPs), was significantly reduced in the TS group in the period immediately preceding a finger movement. This effect is interpreted as consistent with previous suggestions that the cortical hyper-excitability that may give rise to tics in TS is actively suppressed by cognitive control mechanisms. Finally, we found no reliable evidence for altered patterns of functional inter-hemispheric connectivity in TS. These results provide evidence for compensatory brain reorganization that may underlie the increased self-regulation mechanisms that have been hypothesized to bring about the control of tics during adolescence.
Journal of Neuropsychology 07/2012; 7(1). DOI:10.1111/j.1748-6653.2012.02033.x · 2.49 Impact Factor
Ricardo Salvador, Cornelia Wenger, Pedro C Miranda
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