Valerie Brandt

The neural correlates of tic inhibition in Gilles de la Tourette syndrome

Tics in Gilles de la Tourette syndrome (GTS) resemble fragments of normal motor behaviour but appear in an intrusive, repetitive and context-inappropriate manner. Although tics can be voluntarily inhibited on demand, the neural correlates of this process remain unclear. 14 GTS adults without relevant comorbidities participated in this study. First, tic severity and voluntary tic inhibitory capacity were evaluated outside the scanner. Second, patients were examined with resting state functional magnetic resonance imaging (RS-fMRI) in two states, free ticcing and voluntary tic inhibition. Local synchronization of spontaneous fMRI-signal was analysed with regional homogeneity (ReHo) and differences between both states (free ticcing<tic inhibition) were contrasted. Clinical correlations of the resulting differential ReHo parameters between both states and clinical measures of tic frequency, voluntary tic inhibition and premonitory urges were also performed. ReHo of the left inferior frontal gyrus (IFG) was increased during voluntary tic inhibition compared to free ticcing. ReHo increases were positively correlated with participants׳ ability to inhibit their tics during scanning sessions but also outside the scanner. There was no correlation with ratings of premonitory urges. Voluntary tic inhibition is associated with increased ReHo of the left IFG. Premonitory urges are unrelated to this process.

Prefrontal cortex volume reductions and tic inhibition are unrelated in uncomplicated GTS adults.

BACKGROUND Tics in Gilles de la Tourette syndrome (GTS) are repetitive patterned movements, resembling spontaneous motor behaviour, but escaping voluntary control. Previous studies hypothesised relations between structural alterations in prefrontal cortex of GTS adults and tic severity using voxel-based morphometry (VBM), but could not demonstrate a significant association. The relation between prefrontal cortex structure and tic inhibition has not been investigated. METHODS Here, we used VBM to examine 14 GTS adults without associated comorbidities, and 15 healthy controls. We related structural alterations in GTS to clinical measures of tic severity and tic control. RESULTS Grey matter volumes in the right inferior frontal gyrus and the left frontal pole were reduced in patients relative to healthy controls. These changes were not related to tic severity and tic inhibition. CONCLUSION Prefrontal grey matter volume reductions in GTS adults are not related to state measures of tic phenomenology.

Visual feedback of own tics increases tic frequency in patients with Tourette's syndrome

Gilles de la Tourette syndrome (GTS) is characterized by motor and phonic tics. It is unknown how paying attention to one’s own tics might modulate tic frequency. We determined tic frequency in freely ticcing GTS patients while they were being filmed. In Study 1, we investigated 12 patients (1) alone in a room (baseline); (2) alone in front of a mirror. In Study 2, we replicated these conditions in 16 patients and additionally examined how watching a video, in which the individual was shown not ticcing, affected their tic frequency. In both studies, tic frequency was significantly higher when patients watched themselves in a mirror compared to baseline. In contrast, tic frequency was significantly reduced in the video condition. Paying attention to one’s own tics increases tic frequency when tics are not suppressed and appears to be specific for attention to tics, rather than attention to the self.

The Relation Between Attention and Tic Generation in Tourette Syndrome

Objective: Many neuropsychiatric disorders involve abnormal attentional processing. Systematic investigations of how attention may affect tic frequency in Tourette syndrome are lacking. Method: Patients performed rhythmic finger movements, approximately once every 2 s. Each movement triggered a unique visual color stimulus. Patients were asked to monitor and remember their finger actions, the external colors caused by their actions, or their tics. Sixteen adult Tourette syndrome patients performed each task twice: once while inhibiting tics, and once without inhibiting tics. Results: During the “freely tic” condition, patients had significantly fewer tics when attending to finger movements, or to the ensuing colors, compared with when attending to their tics. Attention to fingers produced the fewest tics overall. During tic suppression, tic frequency was reduced to an equal level in all conditions. Conclusions: Focusing attention away from tics significantly reduces tic frequency. This attentional process may operate by regulating motor noise.

Tics as a model of over-learned behavior-imitation and inhibition of facial tics

Tics are the defining feature in Tourette syndrome and can be triggered by watching tics or single voluntary movements. This automatic imitation of movements referred to as “echopraxia” has been ascribed to a failure in top‐down inhibition of imitative response tendencies. Alternatively, it could be interpreted in the context of automatic overlearned behavior. To this end, we investigated 18 Tourette patients aged 28.22 years (9.44 standard deviation; 16 male) and 24 healthy controls (mean age 29.21 years [9.1 standard deviation]; 17 male) using an adapted version of an action‐interference paradigm.

Mirror me: Imitative responses in adults with autism

Dysfunctions of the human mirror neuron system have been postulated to underlie some deficits in autism spectrum disorders including poor imitative performance and impaired social skills. Using three reaction time experiments addressing mirror neuron system functions under simple and complex conditions, we examined 20 adult autism spectrum disorder participants and 20 healthy controls matched for age, gender and education. Participants performed simple finger-lifting movements in response to (1) biological finger and non-biological dot movement stimuli, (2) acoustic stimuli and (3) combined visual-acoustic stimuli with different contextual (compatible/incompatible) and temporal (simultaneous/asynchronous) relation. Mixed model analyses revealed slower reaction times in autism spectrum disorder. Both groups responded faster to biological compared to non-biological stimuli (Experiment 1) implying intact processing advantage for biological stimuli in autism spectrum disorder. In Experiment 3, both groups had similar ‘interference effects’ when stimuli were presented simultaneously. However, autism spectrum disorder participants had abnormally slow responses particularly when incompatible stimuli were presented consecutively. Our results suggest imitative control deficits rather than global imitative system impairments.

Convergent Validity of the PUTS

Premonitory urges are a cardinal feature in Gilles de la Tourette syndrome. Severity of premonitory urges can be assessed with the “Premonitory Urge for Tic Disorders Scale” (PUTS). However, convergent validity of the measure has been difficult to assess due to the lack of other urge measures. We investigated the relationship between average real-time urge intensity assessed by an in-house developed real-time urge monitor (RUM), measuring urge intensity continuously for 5 min on a visual analog scale, and general urge intensity assessed by the PUTS in 22 adult Tourette patients (mean age 29.8 ± 10.3 SD, 19 males). Additionally, underlying factors of premonitory urges assessed by the PUTS were investigated in the adult sample using factor analysis and were replicated in 40 children and adolescents diagnosed with Tourette syndrome (mean age 12.05 ± 2.83 SD, 31 males). Cronbach’s α for the PUTS 10 was acceptable (α = 0.79) in the adult sample. Convergent validity between average real-time urge intensity scores (as assessed with the RUM) and the 10-item version of the PUTS (r = 0.64) and the 9-item version of the PUTS (r = 0.66) was good. A factor analysis including the 10 items of the PUTS and average real-time urge intensity scores revealed three factors. One factor included the average real-time urge intensity score and appeared to measure urge intensity, whereas the other two factors can be assumed to reflect the (sensory) quality of urges and subjective control, respectively. The factor structure of the 10 PUTS items alone was replicated in a sample of children and adolescents. The results indicate that convergent validity between the PUTS and the real-time urge assessment monitor is good. Furthermore, the results suggest that the PUTS might assess more than one dimension of urges, and it may be worthwhile developing different subscales of the PUTS assessing premonitory urges in terms of intensity and quality, as well as subjectively experienced control over tics and premonitory urges.

Altered perceptual binding in Gilles de la Tourette syndrome

Gilles de la Tourette syndrome (GTS) is a common multifaceted neuropsychiatric disorder. Research in GTS has traditionally focussed on mechanisms underlying changes in motor processes in these patients. There is, however, growing interest in GTS related sensory phenomena. According to the Theory of Event-coding (TEC), sensory stimuli do not only serve representational functions but also action-related functions. In the current study, we use the TEC framework to examine whether the way perceptual features are processed is altered in GTS. The results show that basic perceptual processes differ between GTS patients and healthy controls which might be central for the understanding of this disorder. Details or features of perceptual objects were less bound in GTS suggesting that perceptual features integration is attenuated in them. Behavioural findings were unrelated to patient characteristics implying that they might represent trait abnormalities. It is possible that altered perceptual processing in GTS is due to a long-range under-connectivity of parietal areas with other brain regions repeatedly been described in these patients.

Neurophysiological fingerprints of X‐linked dystonia‐parkinsonism: A model basal ganglia disease

4,6 we prescribed buspirone, with gradual increases up to 15 mg twice per day. The patient was evaluated in the off-medication/off-stimulation setting before and after 2 months treatment with buspirone (see videos; Table 1). No differences were found in dyskinesia scores or UPDRS motor scores. The patient, however, reported subjective benefits in terms of mood and general well-being, which was attributed to the antidepressant and anti-anxiolytic properties of buspirone. Higher doses (up to 40 mg/d) did not provide further benefit. Although animal studies and acute challenges suggested a potential role of buspirone in the treatment of GID, this report suggests that this strategy may not be a viable option for longterm management. This observation has significant implications for future studies in GID, but also for a more general understanding of LID pathophysiology. In fact, serotoninergic mechanisms have been advocated also for the patients not receiving grafts, but available evidence in humans is still limited. Clinical trials with serotoninergic agents for LID have led to disappointing results; likewise, a recent pathological study in humans did not find a correlation between serotoninergic markers and LID. Once again, this discrepancy between preclinical and clinical studies emphasizes the need for better models to characterize Parkinson’s disease.

Tic Phenomenology and Tic Awareness in Adults With Autism

Background: Tics are common in people with autism spectrum disorder (ASD). However, their phenomenology and characteristics have not been studied in detail. Methods: Based on video sequences of 21 adults with ASD without intellectual disability and 16 adults with Gilles de la Tourette syndrome (GTS), tic severity, tic repertoires, and tic awareness were determined. Results: Ten ASD and all GTS participants had tics during video recordings. The ASD group had significantly fewer tics, compared to GTS. Tic distribution and tic repertoires were comparable, but more restricted in ASD. All GTS participants, but only 5 of the 10 ASD participants, were aware of their tics. Conclusions: Tics are common in adults with ASD. They are indistinguishable from tics in GTS and are similarly distributed, but less severe. Tic awareness is limited in ASD.