Intra-subject consistency and reliability of response following 2mA transcranial direct current stimulation

Background Transcranial direct current stimulation (tDCS) is a popular non-invasive brain stimulation technique that has been shown to influence cortical excitability. While polarity specific effects have often been reported, this is not always the case, and variability in both the magnitude and direction of the effects have been observed. Objective/ hypothesis We aimed to explore the consistency and reliability of the effects of tDCS by investigating changes in cortical excitability across multiple testing sessions in the same individuals. A within subjects design was used to investigate the effects of anodal and cathodal tDCS applied to the motor cortex. Four experimental sessions were tested for each polarity in addition to two sham sessions. Methods Transcranial Magnetic Stimulation (TMS) was used to measure cortical excitability (TMS recruitment curves). Changes in excitability were measured by comparing baseline measures and those taken immediately following 20minutes of 2mA stimulation or sham stimulation. Results Anodal tDCS significantly increased cortical excitability at a group level, whereas cathodal tDCS failed to have any significant effects. The sham condition also failed to show any significant changes. Analysis of intra-subject responses to anodal stimulation across four sessions suggest that the amount of change in excitability across sessions was only weakly associated, and was found to have poor reliability across sessions (ICC=0.276). The effects of cathodal stimulation show even poorer reliability across sessions (ICC=0.137). In contrast ICC analysis for the two sessions of sham stimulation reflect a moderate level of reliability (ICC=.424). Conclusions Our findings indicate that although 2mA anodal tDCS is effective at increasing cortical excitability at group level, the effects are unreliable across repeated testing sessions within individual participants. Our results suggest that 2mA cathodal tDCS does not significantly alter cortical excitability immediately following stimulation and that there is poor reliability of the effect within the same individual across different testing sessions

Visuomotor learning and unlearning in children and adolescents with tourette syndrome

Tourette syndrome (TS) is a childhood-onset neurological condition characterised by an evolving repertoire of chronic motor tics and one or more phonic tics. Tics, like habits, are inflexible and repetitive behaviours that are acquired over a period of time. It has been proposed that tics arise in TS as a result of increased habit learning: which may bias the child to acquire automatic behaviours (i.e. tics) more readily than is normal and make it harder to unlearn maladaptive habits once they have been acquired. Using a well-established visuomotor adaptation task, we investigated motor learning in a group of children and adolescents with a clinical diagnosis of TS relative to a group of age and gender matched typically developing individuals. In particular, we quantified differences in the strength and quality of motor learning and unlearning in TS, and the consolidation of motor learning over a 24 hour washout period. We demonstrated that there was a marginally significant decrease in learning rate in the individuals with TS relative to age and gender matched typically developing controls. However, this effect was not associated with tic severity and could be entirely accounted for by the severity of co-occurring ADHD symptoms. Thus, once ADHD symptoms had been accounted for, there were no between group differences in learning rate or the degree of learning observed. By contrast, and more importantly, we found that following learning the rate of forgetting (unlearning) was significantly negatively associated with motor tic severity, such that individuals with more severe tics took longer to unlearn previously learnt motor patterns of behavior. This finding is consistent with the proposal that TS is associated with alterations in the striatal habit learning system and with the view that TS may make it harder to unlearn maladaptive motor habits once they have been acquired

Impaired forward model updating in young adults with Tourette syndrome

Current theories of motor control emphasise how the brain may use internal models of the body to ensure accurate planning and control of movements. One such internal model - a forward model - is thought to generate an estimate of the next motor state and/or the sensory consequences of an upcoming movement, thereby allowing movement errors to be monitored. In addition, forward models may provide a means by which to determine a sense of agency, i.e., the (conscious) sense of authorship and control over our actions. Tourette syndrome is a developmental neurological condition characterised by the occurrence of motor and phonic tics. The involuntary (or voluntary) nature of tics has been the subject of considerable debate, and it was recently argued that the presence of tics in Tourette syndrome could result in a blurring of any subjective boundary between voluntary and involuntary movements. In particular, it was proposed that the level of sensorimotor noise that accompanies tics may be particularly high in Tourette syndrome, and this may contribute to less efficient forward models used to determine agency. We investigated whether the internal monitoring of movements is impaired in individuals with Tourette syndrome, relative to a matched group of typically-developing individuals, using a task that involved executing double-step aiming movements using a hand-held robot manipulandum. Participants were required on each trial to execute two movements in turn, each directed to a remembered target location without visual feedback. Importantly, we assumed that to perform accurately on the second (return) movement it would be necessary to update any forward model to take account errors made during the first (outward) movement. Here we demonstrate that while the Tourette syndrome group were equally accurate, and no more variable, than the matched control group in executing aiming movements to the first (outward) target location. They were significantly less accurate, and exhibited greater movement variability, than controls when executing the second (return) movement. Furthermore, we show that for the return movement only, movement accuracy and movement variability were significantly predicted by the Tourette syndrome group’s clinical severity scores. We interpret these findings as consistent with the view that individuals with Tourette syndrome may experience a reduction in the precision of the forward model estimates thought necessary for the accurate planning and control of movements

Premonitory urges are associated with decreased grey matter thickness within the insula and sensorimotor cortex in young people with Tourette syndrome

Tourette syndrome (TS) is a neurological disorder characterized by vocal and motor tics and is associated with cortical–striatal–thalamic–cortical circuit (CSTC) dysfunction and hyperexcitability of cortical limbic and motor regions, which are thought to lead to the occurrence of tics. Importantly, individuals with TS often report that their tics are preceded by ‘premonitory sensory phenomena’ (PSP) that are described as uncomfortable cognitive or bodily sensations that precede the execution of a tic, and are experienced as a strong urge for motor discharge. While the precise role played by PSP in the occurrence of tics is controversial, PSP are nonetheless of considerable theoretical and clinical importance in TS, not least because they form the core component in many of the behavioural therapies that are currently used in the treatment of tic disorders. In this study, we investigated the brain structure correlates of PSP. Specifically, we conducted a whole-brain analysis of cortical (grey matter) thickness in 29 children and young adults with TS and investigated the association between grey matter thickness and PSP. We demonstrate for the first time that PSP are inversely associated with grey matter thickness measurements within the insula and sensori-motor cortex. We also demonstrate that grey matter thickness is significantly reduced in these areas in individuals with TS relative to a closely age- and gender-matched group of typically developing individuals and that PSP ratings are significantly correlated with tic severity

Enhanced saccadic control in young people with Tourette syndrome despite slowed pro-saccades

Tourette syndrome (TS) is a neurodevelopmental disorder characterised by motor and vocal tics. Tics are repetitive and uncontrolled behaviours that have been associated with basal ganglia dysfunction. We investigated saccadic eye movements in a group of young people with TS but without co-morbid ADHD. Participants performed two tasks. One required them to perform only pro-saccade responses (pure pro-saccade task). The other involved shifting, unpredictably, between executing pro- and anti-saccades (mixed saccade task). We show that in the mixing saccade task, the TS group make significantly fewer errors than an age-matched control group, while responding equally fast. By contrast, on the pure pro-saccade task the TS group were shown to be significantly slower to initiate and to complete the saccades (longer movement duration and decreased peak velocity) than controls, while movement amplitude and direction accuracy were not different. These findings demonstrate enhanced shifting ability despite slower reflexive responding in TS and are discussed with respect to a disorder-related adaptation for increased cognitive regulation of behaviour

Supporting students with Tourette syndrome in secondary school: a survey of staff views

Tourette syndrome is a neurological condition involving involuntary movements and sounds (tics) and is thought to affect as many as 1% of school aged children. Some young people with Tourette syndrome experience educational difficulties and social difficulties. Current clinical guidelines suggest educators can play an important role in maximising learning potential and reducing the negative impact of this condition on students’ social adjustment. Secondary school staff (N = 63) with responsibilities for special educational needs or disabilities completed a survey about support strategies for students with Tourette syndrome. Participants were first asked to suggest potentially helpful strategies and then rated how easily 17 recommended strategies could be implemented in school. The survey participants suggested a range of support strategies that were categorised as (1) promoting knowledge and understanding in school, (2) helping the student to cope with his/her tics, (3) supporting the student’s learning and (4) providing social and emotional support. All the recommended support strategies were rated as being easy to implement (or already in place) by the majority of respondents (e.g., increasing staff awareness and regular communication with home). The strategies that were identified as being least easy to implement were those requiring extra staff input (support from teaching assistants and individual/small group working). Additional challenges to providing support were also identified by the participants (e.g., getting input from outside agencies)

The normal inhibition of associations is impaired by clonidine in Tourette syndrome

Objective: We examined the inhibition of stimulus-stimulus associations (formally ‘conditioned inhibition’) in Tourette syndrome (TS). Method: The present study used video game style conditioned inhibition procedures suitable for children and adolescents. We tested 15 participants with a clinical diagnosis of TS in the absence of co-morbid attention deficit hyperactivity disorder and compared them with 19 typically developing age and sex matched controls (both groups aged 10–20 years). All children were tested for inhibition by summation test using two test stimuli in each of two conditioned inhibition tasks. Results: TS participants showed overall normal inhibition of stimulus-stimulus associations, and there was no correlation between inhibitory learning scores and symptom severity ratings. However, there was a clear reduction in conditioned inhibition in 7 TS participants medicated with clonidine. There was no significant effect of medication on excitatory learning of the stimulus-stimulus associations. Conclusions: We suggest that clonidine’s effect on inhibitory as opposed to excitatory learning could be related to reduced noradrenergic activity. In terms of clinical implications for TS, impaired conditioned inhibition could reduce the ability of susceptible individuals to learn to control tics in the presence of associative triggers

Tic frequency and behavioural measures of cognitive control are improved in individuals with Tourette syndrome by aerobic exercise training

Previous observations of improvements in cognition in typically developing children following moderate to vigorous exercise (e.g., Budde, Voelcker-Rehage, Pietrabyk-Kendziorra, Ribeiro, & Tidow, 2008; Hillman et al., 2009) have led to increased interest in the potential benefits of exercise for children with neurodevelopmental disorders, involving difficulties in self-regulation (e.g., Halperin & Healey, 2011; Archer & Kostrzewa, 2012). Using a within-sample design, the current study looked at the beneficial effects of non-aerobic movement training (Tai Chi), compared to aerobic movement training (Kick Boxing), on behavioural measures of cognitive control and clinical measures of tic severity in a group of young people with Tourette Syndrome (TS). We demonstrate that Kick Boxing, but not Tai Chi, led to a significant enhancement in cognitive control task performance. Furthermore, while tic frequency (tics per minute) was reduced during both types of exercise, this reduction was significantly greater, and sustained for longer, following Kick Boxing. Importantly, the magnitude of the increase in cognitive control following Kick Boxing predicted the degree of reduction in tic frequency. These findings suggest that aerobic exercise may be a useful intervention for improving self-regulation of tics in young people with TS, probably through enhancements in associated cognitive control circuits

Examining the neural antecedents of tics in Tourette syndrome using electroencephalography

Tourette syndrome (TS) is a neurodevelopmental disorder characterised by the occurrence of motor and vocal tics. TS is associated with cortical-striatal-thalamic-cortical circuit dysfunction and hyper-excitability of cortical limbic and motor regions that lead to the occurrence of tics. Importantly, individuals with TS often report that their tics are preceded by premonitory sensory/urge phenomena (PU) that are described as uncomfortable bodily sensations that precede the execution of a tic and are experienced as an urge for motor discharge. While tics are most often referred to as involuntary movements, it has been argued that tics should be viewed as voluntary movements that are executed in response to the presence of PU. To investigate this issue further, we conducted a study using electroencephalography (EEG). We recorded movement-related EEG (mu and beta band oscillations) during (a) the immediate period leading up to the execution of voluntary movements by a group of individuals with TS and a group of matched healthy control participants, and (b) the immediate period leading up to the execution of a tic in a group of individuals with TS. We demonstrate that movement-related mu and beta oscillations are not reliably observed prior to tics in individuals with TS. We interpret this effect as reflecting the greater involvement of a network of brain areas, including the insular and cingulate cortices, the basal ganglia and the cerebellum, in the generation of tics in TS. We also show that beta-band desynchronization does occur when individuals with TS initiate voluntary movements, but, in contrast to healthy controls, desynchronization of mu-band oscillations is not observed during the execution of voluntary movements for individuals with TS. We interpret this finding as reflecting a dysfunction of physiological inhibition in TS, thereby contributing to an impaired ability to suppress neuronal populations that may compete with movement preparation processes

Compensatory Neural Reorganization in Tourette Syndrome

Children with neurological disorders may follow unique developmental trajectories whereby they undergo compensatory neuroplastic changes in brain structure and function that help them gain control over their symptoms [1, 2, 3, 4, 5, 6]. We used behavioral and brain imaging techniques to investigate this conjecture in children with Tourette syndrome (TS). Using a behavioral task that induces high levels of intermanual conflict, we show that individuals with TS exhibit enhanced control of motor output. Then, using structural (diffusion-weighted imaging) brain imaging techniques, we demonstrate widespread differences in the white matter (WM) microstructure of the TS brain that include alterations in the corpus callosum and forceps minor (FM) WM that significantly predict tic severity in TS. Most importantly, we show that task performance for the TS group (but not for controls) is strongly predicted by the WM microstructure of the FM pathways that lead to the prefrontal cortex and by the functional magnetic resonance imaging blood oxygen level-dependent response in prefrontal areas connected by these tracts. 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