BACKGROUND: Despite considerable heritability, previous smaller genome-wide association studies (GWASs) have not identified any robust genetic risk factors for isolated dystonia. OBJECTIVE: The objective of this study was to perform a large-scale GWAS in a well-characterized, multicenter sample of >6000 individuals to identify genetic risk factors for isolated dystonia. METHODS: Array-based GWASs were performed on autosomes for 4303 dystonia participants and 2362 healthy control subjects of European ancestry with subgroup analysis based on age at onset, affected body regions, and a newly developed clinical score. Another 736 individuals were used for validation. RESULTS: This GWAS identified no common genome-wide significant loci that could be replicated despite sufficient power to detect meaningful effects. Power analyses imply that the effects of individual variants are likely very small. CONCLUSIONS: Moderate single-nucleotide polymorphism-based heritability indicates that common variants do not contribute to isolated dystonia in this cohort. Sequence-based GWASs (eg, by whole-genome sequencing) might help to better understand the genetic basis. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

• Klíčová slova
• GWAS, age at onset, case–control, clinical score, isolated dystonia,
• MeSH
• celogenomová asociační studie * MeSH
• dospělí MeSH
• dystonické poruchy genetika   MeSH
• dystonie * genetika   MeSH
• genetická predispozice k nemoci * genetika   MeSH
• jednonukleotidový polymorfismus * genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• rizikové faktory MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

Cognitive control is relevant when distracting information induces behavioral conflicts. Such conflicts can be produced consciously and by subliminally processed information. Interestingly, both sources of conflict interact suggesting that they share neural mechanisms. Here, we ask whether conjoint effects between different sources of conflict are modulated by microstructural basal ganglia dysfunction. To this end, we carried out an electroencephalography study and examined event-related potentials (ERPs) including source localization using a combined flanker-subliminal priming task in patients with X-linked dystonia Parkinsonism (XDP) and a group of healthy controls. XDP in its early stages is known to predominantly affect the basal ganglia striosomes. The results suggest that conjoint effects between subliminal and conscious sources of conflicts are modulated by the striosomes and were stronger in XDP patients. The neurophysiological data indicate that this effect is related to modulations in conflict monitoring and response selection (N2 ERP) mechanisms engaging the anterior cingulate cortex. Bottom-up perceptual gating, attentional selection, and motor response activation processes in response to the stimuli (P1, N1, and lateralized readiness potential ERPs) were unaffected. Taken together, these data indicate that striosomes modulate the processing of conscious and subliminal sources of conflict suggesting that microstructural basal ganglia properties are relevant for cognitive control.

• MeSH
• analýza rozptylu MeSH
• antiparkinsonika terapeutické užití   MeSH
• bazální ganglia patofyziologie   MeSH
• dospělí MeSH
• dystonické poruchy farmakoterapie   patologie   patofyziologie   psychologie   MeSH
• elektroencefalografie MeSH
• evokované potenciály fyziologie   MeSH
• funkční lateralita MeSH
• genetické nemoci vázané na chromozom X farmakoterapie   patologie   patofyziologie   psychologie   MeSH
• konflikt (psychologie) * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mapování mozku MeSH
• mozkové vlny fyziologie   MeSH
• psychomotorický výkon fyziologie   MeSH
• reakční čas fyziologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antiparkinsonika MeSH

• Klíčová slova
• Tourette syndrome, action, attention, basal ganglia, perception,
• MeSH
• kognitivní poruchy etiologie   MeSH
• lidé MeSH
• mozek patologie   MeSH
• tiky diagnóza   patofyziologie   MeSH
• Tourettův syndrom diagnóza   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

An important brain function is to predict upcoming events on the basis of extracted regularities of previous inputs. These predictive coding processes can disturb performance in concurrent perceptual decision-making and are known to depend on fronto-striatal circuits. However, it is unknown whether, and if so, to what extent striatal microstructural properties modulate these processes. We addressed this question in a human disease model of striosomal dysfunction, i.e. X-linked dystonia-parkinsonism (XDP), using high-density EEG recordings and source localization. The results show faster and more accurate perceptual decision-making performance during distraction in XDP patients compared to healthy controls. The electrophysiological data show that sensory memory and predictive coding processes reflected by the mismatch negativity related to lateral prefrontal brain regions were weakened in XDP patients and thus induced less cognitive conflict than in controls as reflected by the N2 event-related potential (ERP). Consequently, attentional shifting (P3a ERP) and reorientation processes (RON ERP) were less pronounced in the XDP group. Taken together, these results suggests that striosomal dysfunction is related to predictive coding deficits leading to a better performance in concomitant perceptual decision-making, probably because predictive coding does not interfere with perceptual decision-making processes. These effects may reflect striatal imbalances between the striosomes and the matrix compartment.

• Klíčová slova
• Basal ganglia, EEG, Perceptual decision making, Predictive coding, Sensory memory, Striosomes, X-linked dystonia parkinsonism,
• MeSH
• corpus striatum patofyziologie   MeSH
• dospělí MeSH
• dystonické poruchy patofyziologie   psychologie   MeSH
• elektroencefalografie MeSH
• evokované potenciály MeSH
• genetické nemoci vázané na chromozom X patofyziologie   psychologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mozek patofyziologie   MeSH
• reakční čas MeSH
• rozhodování fyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Evidence suggests that Tourette syndrome is characterized by an increase in dopamine transmission and structural as well as functional changes in fronto-striatal circuits that might lead to enhanced multi-component behaviour integration. Behavioural and neurophysiological data regarding multi-component behaviour was collected from 15 patients with Tourette syndrome (mean age = 30.40 ± 11.10) and 15 healthy controls (27.07 ± 5.44), using the stop-change task. In this task, participants are asked to sometimes withhold responses to a Go stimulus (stop cue) and change hands to respond to an alternative Go stimulus (change cue). Different onset asynchronies between stop and change cues were implemented (0 and 300 ms) in order to vary task difficulty. Tourette patients responded more accurately than healthy controls when there was no delay between stop and change stimulus, while there was no difference in the 300 ms delay condition. This performance advantage was reflected in a smaller P3 event related potential. Enhanced multi-component behaviour in Tourette syndrome is likely based on an enhanced ability to integrate information from multiple sources and translate it into an appropriate response sequence. This may be a consequence of chronic tic control in these patients, or a known fronto-striatal networks hyperconnectivity in Tourette syndrome.

• MeSH
• chování * MeSH
• dospělí MeSH
• elektroencefalografie MeSH
• evokované potenciály MeSH
• fyzikální stimulace MeSH
• lidé MeSH
• mladý dospělý MeSH
• neurofyziologický monitoring MeSH
• počítačové zpracování obrazu MeSH
• průzkumy a dotazníky MeSH
• studie případů a kontrol MeSH
• Tourettův syndrom diagnóza   patofyziologie   psychologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Executive functions including behavioral adaptation and impulse control are commonly impaired in movement disorders caused by striatal pathology. However, as yet it is unclear what aspects of behavioral abnormalities are related to pathology in which striatal subcomponent, that is, the matrix and the striosomes. We therefore studied cognitive control in X-linked dystonia-parkinsonism, a model disease of striosomal degeneration, using behavioral paradigms and EEG. METHODS: We studied genetically confirmed X-linked dystonia-parkinsonism patients (N = 21) in their early disease stages and healthy matched controls. Error-related behavioral adaptation was tested in a flanker task and response inhibition in a Go/Nogo paradigm during EEG. We focused on error-related negativity during error processing and the Nogo-N2 and Nogo-P3 in the response inhibition task. Source localization analyses were calculated. In addition, total wavelet power and phase-locking factor reflecting neural synchronization processes in time and frequency across trials were calculated. RESULTS: Error processing and behavioral adaptation predominantly engaging the anterior cingulate cortex was markedly impaired in X-linked dystonia-parkinsonism. This was reflected in abnormal reaction times correlating with error-related negativity amplitudes, error related theta band activity, and the phase-locking factor. Also, abnormal error processing correlated with dystonia severity but not with parkinsonism. Response inhibition and corresponding EEG activity were normal. CONCLUSIONS: This dissociable pattern of cognitive deficits most likely reflects predominant dysfunction of the striosomal compartment and its connections to the anterior cingulate cortex in X-linked dystonia-parkinsonism. The results underscore the importance of striosomes for cognitive function in humans and suggest that striosomes are relays of error-related behavioral adaptation but not inhibitory control. © 2017 International Parkinson and Movement Disorder Society.

• Klíčová slova
• EEG, X-linked dystonia-parkinsonism, basal ganglia, cognitive control, striosomes,
• MeSH
• dospělí MeSH
• dystonické poruchy komplikace   diagnostické zobrazování   MeSH
• elektroencefalografie MeSH
• fyziologická adaptace fyziologie   MeSH
• genetické nemoci vázané na chromozom X komplikace   diagnostické zobrazování   MeSH
• impulzivní chování fyziologie   MeSH
• inhibice (psychologie) MeSH
• kognitivní poruchy etiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek diagnostické zobrazování   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

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.

• Klíčová slova
• Feature integration, Gilles de la Tourette syndrome, Object file, Perception, Theory of Event-coding,
• MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• orientace fyziologie   MeSH
• reakční čas fyziologie   MeSH
• světelná stimulace MeSH
• Tourettův syndrom patofyziologie   MeSH
• vnímání barev fyziologie   MeSH
• zraková percepce fyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Mechanisms responsible for the integration of perceptual events and appropriate actions (sensorimotor processes) have been subject to intense research. Different theoretical frameworks have been put forward with the "Theory of Event Coding (TEC)" being one of the most influential. In the current study, we focus on the concept of 'event files' within TEC and examine what sub-processes being dissociable by means of cognitive-neurophysiological methods are involved in voluntary event coding. This was combined with EEG source localization. We also introduce reward manipulations to delineate the neurophysiological sub-processes most relevant for performance variations during event coding. The results show that processes involved in voluntary event coding included predominantly stimulus categorization, feature unbinding and response selection, which were reflected by distinct neurophysiological processes (the P1, N2 and P3 ERPs). On a system's neurophysiological level, voluntary event-file coding is thus related to widely distributed parietal-medial frontal networks. Attentional selection processes (N1 ERP) turned out to be less important. Reward modulated stimulus categorization in parietal regions likely reflecting aspects of perceptual decision making but not in other processes. The perceptual categorization stage appears central for voluntary event-file coding.

• Klíčová slova
• Categorization, EEG, Event files, Perception, Response selection, Source localization, Theory of event coding,
• MeSH
• dospělí MeSH
• kognice fyziologie   MeSH
• lidé MeSH
• modely neurologické * MeSH
• odměna * MeSH
• plnění a analýza úkolů * MeSH
• počítačová simulace MeSH
• somatosenzorické korové centrum fyziologie   MeSH
• ukládání a vyhledávání informací metody   MeSH
• vůle fyziologie   MeSH
• zraková percepce fyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH