Neuromodulation of Inhibitory Control in Tic Disorders

The present study aims to assess the effects of non invasive electrical stimulation of the vagus nerve via transcutaneous vagus nerve stimulation (tVNS) on cognitive functions, inhibitory and tic control in patients with tic disorders. Taking into account the role that GABA plays in inhibitory control, the presence of alteration of GABA neurotransmission in Tic disorders and the possibility to increase GABA release with tVNS, the investigators hypothesized that tVNS might improve behavioral control in Tic disorders. Moreover, as suggested by previous studies investigating the effects of tVNS in other patient populations, the investigators expected that tVNS will be safe and well tolerated. Such results would encourage the use of tVNS in Tic disorders.

The investigators planned a single centre, randomized, double-blind, sham- controlled, crossover (within subject) design.

Adults with Tic Disorders will be recruited and randomly assigned to two different groups: the active-tVNS group and the sham-tVNS group. Each group will undergo a two-sessions intervention during which active tVNS followed by sham tVNS or sham tVNS followed by active tVNS will be delivered in the active and sham tVNS group, respectively. The stimulation will be delivered during the execution of an inhibitory task and an attentional task. For the inhibitory task a Contextual Go No-Go paradigm will be used. During this task, participants will be presented with visual stimuli representing everyday actions embedded within congruent or incongruent context. For example, stimuli could consist in precision or grasping actions suggesting the intention to eat or to move the object in another place. For each stimulus, there will be a kinematic component consisting in the movement performed by the model and a contextual component, consisting in the embedding scenario of the action (a breakfast scenario, or a cleaning scenario). Participants will be instructed to press a button when a specific intention (go) will be suggested by the video and not to press a button for the opposite intention (no go), either according to the kinematics or to the context, depending on the experimental block. This way, it will be possible to assess inhibitory control at response level. Crucially, kinematics and context of the visual stimuli could point toward the same (congruent) or opposite (incongruent) intentions, thus allowing to assess inhibitory control at the stimulus level. For the attentional task, the attentional network test (ANT; Fan et al.,2002) will be used. The task is a modified version of a Flanker task and it allows measuring orienting, alerting and executive control components. To assess the clinical, neuropsychological and behavioural profiles, the Yale Global Tic Severity Rating Scale (YGTSS), the EuroQol quality of life questionnaire, the Raven Matrix, the Autism Quotient, the Barratt Impulsiveness scale and the Navon Task will be used. The effects of tVNS on patients' behavioural control (as assessed through the Contextual Go No-Go task and the ANT) will be related to clinical, neuropsychological and behavioural profile, for identifying best the features tVNS responder patients. Side effects will be tested after each session.

The protocol will allow testing the efficiency of tVNS in:

* enhancing inhibition at response level (response selection) in Tic disorders;
* enhancing inhibition at stimulus level (response inhibition) in Tic disorders;
* improving alerting, orienting or executive control in Tic disorders;
* improving patients' quality of life and Tic control;
* further investigating the safety and tolerability of tVNS.

Eligibility Criteria:
Inclusion Criteria:

* adults who aged 18-50 years;
* Diagnosis of Tic disorders

Exclusion Criteria:

* Presence of contraindication to tVNS (history of epilepsy in the last two years, severe brain trauma; presence of metal in the brain/skull or implanted neurostimulator, cardiac pacemaker; state of pregnancy);
* Recent changes in drugs therapy due to the intake of or the withdrawal from some drugs potentially changing the seizure threshold;
* Presence of comorbidity with an important medical condition;
* Severe sensorial, motor and/or behavioural problems that could interfere with the tasks