Volitional action as perceptual detection: Predictors of conscious intention in adolescents with tic disorders

AbstractVoluntary actions are accompanied by a distinctive subjective experience, so that they feel quite different from physically similar involuntary movements. However, the nature and origin of this experience of volition remain unclear. Voluntary actions emerge during early childhood, in parallel with reduction of involuntary movements. However, the available markers of the experience of volition, notably Libet's mental chronometry of intention, cannot readily be used in young children. In Gilles de la Tourette syndrome (GTS), however, involuntary tic movements may coexist with voluntary control into adulthood. Therefore, adolescents with GTS could potentially confuse the two classes of movement. We have measured the temporal experience of voluntary action in a well-characterised group of adolescents with GTS, and age-matched controls. We replicated previous reports of a conscious intention occurring a few hundred milliseconds prior to voluntary keypress actions. Multiple regression across 25 patients' results showed that age and trait tic severity did not influence the experience of conscious intention. However, patients with stronger premonitory urges prior to tics showed significantly later conscious intentions, suggesting that the anticipatory experience of one's own volition involves a perceptual discrimination between potentially competing pre-movement signals. Patients who were more able to voluntarily suppress their tics showed significantly earlier conscious intention, suggesting that the perceptual discrimination between different action classes may also contribute to voluntary control of tics. We suggest that the brain learns voluntary control by perceptually discriminating a special class of internal ‘intentional’ signals, allowing them to emerge from motor noise

ε-sarcoglycan myoclonus-dystonia—overview of neurophysiological, behavioral, and imaging characteristics

Myoclonus-Dystonia is a rare, neurological movement disorder, clinically characterized by myoclonic jerks and dystonic symptoms, such as cervical dystonia and writer’s cramp. Psychiatric symptoms, like anxiety, depression, and addiction, are frequently reported. Monogenic Myoclonus-Dystonia is mostly caused by pathogenic variants in the ε-sarcoglycan gene, which is among other regions highly expressed in the cerebellum. The current pharmacological treatment is not satisfactory. Neurophysiological and imaging studies in this patient population are scarce with partly heterogeneous results and sometimes important limitations. However, some studies point towards subcortical alterations, e.g., of the cerebellum and its connections. Further studies addressing previous limitations are important for a better understanding of the underlying pathology of Myoclonus-Dystonia and might build a bridge for the development of future treatment

Observing repetitive finger movements modulates response times of auditorily cued finger movements

Our motor and perceptual representations of actions seem to be intimately linked and the human mirror neuron system (MNS) has been proposed as the mediator. In two experiments, we presented biological or non-biological movement stimuli that were either congruent or incongruent to a required response prompted by a tone. When the tone occurred with the onset of the last movement in a series, i.e., it was perceived during the movement presentation, congruent biological stimuli resulted in faster reaction times than congruent non-biological stimuli. The opposite was observed for incongruent stimuli. When the tone was presented after visual movement stimulation, however, no such interaction was present. This implies that biological movement stimuli only affect motor behaviour during visual processing but not thereafter. These data suggest that the MNS is an “online” system; longstanding repetitive visual stimulation (Experiment 1) has no benefit in comparison to only one or two repetitions (Experiment 2)

Psychogenic paroxysmal movement disorders – Clinical features and diagnostic clues

AbstractBackgroundThe diagnosis of psychogenic paroxysmal movement disorders (PPMD) can be challenging, in particular their distinction from the primary paroxysmal dyskinesias (PxD) remains difficult.MethodsHere we present a large series of 26 PPMD cases, describe their characteristics, contrast them with primary PxD and focus on their distinguishing diagnostic features.ResultsMean age at onset was 38.6 years, i.e. much later than primary PxD. Women were predominantly affected (73%). Most subjects (88.4%) had long attacks, and unlike primary PxD there was a very high within-subject variability for attack phenomenology, duration and frequency. Dystonia was the most common single movement disorder presentation, but 69.2% of the patients had mixed or complex PxD. In 50% of PPMD cases attack triggers could be identified but these were unusual for primary PxD. 42.3% of patients employed unusual strategies to alleviate or stop the attacks. Response to typical medication used for primary PxD was poor. Precipitation of the disorder due to physical or emotional life events and stressors were documented in 57.6% and 65.3% of the cases respectively. Additional interictal psychogenic signs were documented in 34.6% and further medically unexplained somatic symptoms were present in 50% of the cases. 19.2% of patients had a comorbid organic movement disorder and 26.9% had pre-existing psychiatric comorbidities.ConclusionAlthough the phenotypic presentation of PPMD can be highly diverse, certain clinical characteristics help in distinguishing this condition from the primary forms of PxD. Recognition is important as multidisciplinary treatment approaches led to significant improvement in most cases

Not to Miss: Intronic Variants, Treatment, and Review of the Phenotypic Spectrum in VPS13D-Related Disorder

VPS13D is one of four human homologs of the vacuolar sorting protein 13 gene (VPS13). Biallelic pathogenic variants in the gene are associated with spastic ataxia or spastic paraplegia. Here, we report two patients with intronic pathogenic variants: one patient with early onset severe spastic ataxia and debilitating tremor, which is compound-heterozygous for a canonical (NM_018156.4: c.2237−1G > A) and a non-canonical (NM_018156.4: c.941+3G>A) splice site variant. The second patient carries the same non-canonical splice site variant in the homozygous state and is affected by late-onset spastic paraplegia. We confirmed altered splicing as a result of the intronic variants and demonstrated disturbed mitochondrial integrity. Notably, tremor in the first patient improved significantly by bilateral deep brain stimulation (DBS) in the ventralis intermedius (VIM) nucleus of the thalamus. We also conducted a literature review and summarized the phenotypical spectrum of reported VPS13D-related disorders. Our study underscores that looking for mutations outside the canonical splice sites is important not to miss a genetic diagnosis, especially in disorders with a highly heterogeneous presentation without specific red flags

Developing the Premonitory Urges for Tic Disorders Scale–Revised (PUTS-R)

Background: Patients with Gilles de la Tourette syndrome (GTS) or chronic tic disorders frequently experience premonitory urges prior to tics. The ‘Premonitory Urges for Tic Disorders Scale’ (PUTS) is commonly used in order to assess urge severity in patients with tics. Several studies suggest that the PUTS might measure more than one dimension of urges. These include the quality and severity of premonitory urges. Methods: This study aims to replicate and extend previous findings concerning the psychometric properties of the PUTS and its underlying dimensions in a large sample of 241 patients with GTS including both adults (n=93; mean age=34.2±12.84; 73 male) and minors (n=148; mean age=11.8±2.86; 123 male), pooled from three different recruitment sites. Results: Data analysis confirmed good reliability across the PUTS items for both minors and adults and acceptable item characteristics for items 2–8. A factor analysis of items 1–8 confirmed the existence of two factors in both age groups. Conclusions: The results suggest that the PUTS might benefit from several further small modifications, such as rephrasing items 1 and 9 to increase convergence with the overall construct of the scale. Finally, we propose a revised version of the PUTS, consisting of two subscales: one for urge severity and another one for urge quality by including several new items

Responsiveness of the Scale for the Assessment and Rating of Ataxia and Natural History in 884 Recessive and Early Onset Ataxia Patients

The Scale for the Assessment and Rating of Ataxia (SARA) is the most widely applied clinical outcome assessment (COA) for genetic ataxias, but presents metrological and regulatory challenges. To facilitate trial planning, we characterize its responsiveness (including subitem-level relations to ataxia severity and patient-focused outcomes) across a large number of ataxias, and provide first natural history data for several of them.Subitem-level correlation- and distribution-based analysis of 1637 SARA assessments in 884 patients with autosomal-recessive/early-onset ataxia (370 with 2-8 longitudinal assessments), complemented by linear mixed-effects modeling to estimate progression and sample sizes.While SARA subitem responsiveness varied between ataxia severities, gait/stance showed a robust granular linear scaling across the broadest range (SARA25; 2.7-fold sample size). Use of a novel rank-optimized SARA without subitems finger-chase and nose-finger reduces sample sizes by 20-25%.This study comprehensively characterizes COA properties and annualized changes of the SARA across and within a large number of ataxias. It suggests specific approaches for optimizing its responsiveness that might facilitate regulatory qualification and trial design. This article is protected by copyright. All rights reserved