Cortico-corticale verbindingen en visueel geleide hand- en vingerbewegingen bij de rhesus aap

Een grote verscheidenheid aan bewegingen, welke opgewekt en gereguleerd worden door visuele stimuli staat de hogere dieren ter beschikking om zich als individu en als soort te handhaven. Zo bemachtigen zij hun voedsel, ontwijken hun belagers en zoeken kontakt met soortgenoten, veelal door zich over een gekompliceerd terrein te verplaatsen. Hierbij zijn visueel geleide bewegingen van hoofd, ogen, romp en extremiteiten van groot belang. Daarnaast verwerven de primaten de rnagelijkheid tot een gedifferentieërd gebruik van arm, hand en vingers, hetwelk hen, geleid door visuele informatie, in staat stelt op korte afstand voorwerpen te grijpen en te manipuleren. Er zijn evenwel ook eenvoudiger uitingen van visuomotoriek, zoals de pupil- en akkomodatiereakties van het oog, de dreigreflex en de optokinetische nystagmus. Bij al deze reakties spelen visuele st i mul i een overwegende rol, maar daarnaast zijn veelal ook andere regulerende st i mul i van betekenis. Visuomotoriek in al zijn schakeringen is dan ook een aktiviteit, waar vele delen van het C.Z.S. bij betrokken zijn. Een samenwerking van het centrale visuele en het centrale motorische systeem moet hiervoor essentieël geacht worden. Normal i ter komt deze samenwerking tot ontwikkeling in de periode na de geboorte, mits het organisme zich aktief kan bewegen in een visueel gestruktureerde omgeving (Riesen, 1958; Held en Hein, 1963)

Artistic occupations are associated with a reduced risk of Parkinson’s disease

Parkinson’s disease (PD) is preceded by a premotor phase of unknown duration. Dopaminergic degeneration during this phase may lead to subtle cognitive and behavioural changes, such as decreased novelty seeking. Consequently, premotor subjects might be most comfortable in jobs that do not require optimal dopamine levels, leading to an overrepresentation in structured and predictable occupations, or an underrepresentation in artistic occupations. In a case–control study, 750 men with PD (onset ≥40 years) and 1300 healthy men completed a validated questionnaire about their lifetime occupational status. Occupations were classified using the RIASEC model. Odds ratios (ORs) were calculated for the conventional and artistic categories, both for the most recent occupation before symptom onset, and for the very first occupation. Because farming has been associated with a PD risk, ORs were calculated separately for farming. A reduced risk of PD was found for men with an artistic occupation late in life (OR 0.14, 95 % CI 0.04–0.53), while an artistic first occupation did not prevent PD (OR 0.72, CI 0.32–1.59). Conventional occupations showed no increased risk (recent: OR 1.07, CI 0.70–1.64; first: OR 1.14, CI 0.77–1.71). In support of previous reports, farming was associated with an increased risk of PD (recent: OR 2.6, CI 1.4–4.6; first: OR 2.7, CI 1.6–4.5). PD patients were older than controls, but various statistical corrections for age all lead to similar results. Artistic occupations late in life are associated with a reduced risk of subsequent PD, perhaps because this reflects a better preserved dopaminergic state. No initial occupation predicted PD, suggesting that the premotor phase starts later in life

Professional occupation and the risk of Parkinson's disease

Background and purpose: Creativity in Parkinson's disease (PD) is strongly related to dopaminergic activity and medication. We hypothesized that patients with PD, including those who are in the pre-diagnostic phase of PD, are prone to choose highly structured ‘conventional’ professional occupations and avoid highly creative ‘artistic’ occupations. Methods: At baseline of the population-based Rotterdam Study, we asked 12 147 individuals aged ≥45 years about their latest occupation and categorized occupations according to the RIASEC model. Participants underwent baseline and follow-up (median 11 years) examinations for PD. We determined associations of artistic (versus any other occupation) and conventional (versus any other occupation) occupations with PD. Additionally, we pooled our results with a recently published case–control study (Radboud Study). Results: At baseline, conventional occupations were common [n = 4356 (36%)], whereas artistic occupations were rare [n = 137 (1%)]. There were 217 patients with PD, including 91 with prevalent PD and 126 with incident PD. The risk of PD varied substantially across occupational categories (chi-square, 14.61; P = 0.01). The penalized odds ratio (OR) of artistic occupations for PD was 0.19 [95% confidence interval (CI), 0.00–1.31; P = 0.11], whereas the OR of conventional occupations for PD was 1.23 (95% CI, 0.95–1.66; P = 0.10). The direction and magnitude of ORs were similar in cross-sectional and longitudinal subsamples. Pooled ORs across the Rotterdam and Radboud Studies were 0.20 (95% CI, 0.08–0.52; P < 0.001) for artistic and 1.23 (95% CI, 0.92–1.67; P = 0.08) for conventional occupations. Conclusions: The risk of PD varies substantially by choice of professional occupation. Our findings suggest that dopaminergic degeneration affects choice of occupation, which may start in the pre-diagnostic phase of PD

Dopamine precursor depletion improves punishment prediction during reversal learning in healthy females but not males

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TNPO2 variants associate with human developmental delays, neurologic deficits, and dysmorphic features and alter TNPO2 activity in Drosophila

Transportin-2 (TNPO2) mediates multiple pathways including non-classical nucleocytoplasmic shuttling of >60 cargoes, such as developmental and neuronal proteins. We identified 15 individuals carrying de novo coding variants in TNPO2 who presented with global developmental delay (GDD), dysmorphic features, ophthalmologic abnormalities, and neurological features. To assess the nature of these variants, functional studies were performed in Drosophila. We found that fly dTnpo (orthologous to TNPO2) is expressed in a subset of neurons. dTnpo is critical for neuronal maintenance and function as downregulating dTnpo in mature neurons using RNAi disrupts neuronal activity and survival. Altering the activity and expression of dTnpo using mutant alleles or RNAi causes developmental defects, including eye and wing deformities and lethality. These effects are dosage dependent as more severe phenotypes are associated with stronger dTnpo loss. Interestingly, similar phenotypes are observed with dTnpo upregulation and ectopic expression of TNPO2, showing that loss and gain of Transportin activity causes developmental defects. Further, proband-associated variants can cause more or less severe developmental abnormalities compared to wild-type TNPO2 when ectopically expressed. The impact of the variants tested seems to correlate with their position within the protein. Specifically, those that fall within the RAN binding domain cause more severe toxicity and those in the acidic loop are less toxic. Variants within the cargo binding domain show tissue-dependent effects. In summary, dTnpo is an essential gene in flies during development and in neurons. Further, proband-associated de novo variants within TNPO2 disrupt the function of the encoded protein. Hence, TNPO2 variants are causative for neurodevelopmental abnormalities

Incidence and outcome of acquired demyelinating syndromes in Dutch children: update of a nationwide and prospective study

Introduction: Acquired demyelinating syndromes (ADS) are immune-mediated demyelinating disorders of the central nervous system in children. A nationwide, multicentre and prospective cohort study was initiated in the Netherlands in 2006, with a reported ADS incidence of 0.66/100,000 per year and MS incidence of 0.15/100,000 per year in the period between 2007 and 2010. In this study, we provide an update on the incidence and the long-term follow-up of ADS in the Netherlands. Methods: Children < 18 years with a first attack of demyelination were included consecutively from January 2006 to December 2016. Diagnoses were based on the International Paediatric MS study group consensus criteria. Outcome data were collected by neurological and neuropsychological assessments, and telephone call assessments. Results: Between 2011 and 2016, 55/165 of the ADS patients were diagnosed with MS (33%). This resulted in an increased ADS and MS incidence of 0.80/100,000 per year and 0.26/100,000 per year, respectively. Since 2006 a total of 243 ADS patients have been included. During follow-up (median 55 months, IQR 28–84), 137 patients were diagnosed with monophasic disease (56%), 89 with MS (37%) and 17 with multiphasic disease other than MS (7%). At least one form of residual deficit including cognitive impairment was observed in 69% of all ADS patients, even in monophasic ADS. An Expanded Disability Status Scale score of ≥ 5.5 was reached in 3/89 MS patients (3%). Conclusion: The reported incidence of ADS in Dutch children has increased since 2010. Residual deficits are common in this group, even in monophasic patients. Therefore, long-term follow-up in ADS patients is warranted

TNPO2 variants associate with human developmental delays, neurologic deficits, and dysmorphic features and alter TNPO2 activity in Drosophila

Transportin-2 (TNPO2) mediates multiple pathways including non-classical nucleocytoplasmic shuttling of >60 cargoes, such as developmental and neuronal proteins. We identified 15 individuals carrying de novo coding variants in TNPO2 who presented with global developmental delay (GDD), dysmorphic features, ophthalmologic abnormalities, and neurological features. To assess the nature of these variants, functional studies were performed in Drosophila. We found that fly dTnpo (orthologous to TNPO2) is expressed in a subset of neurons. dTnpo is critical for neuronal maintenance and function as downregulating dTnpo in mature neurons using RNAi disrupts neuronal activity and survival. Altering the activity and expression of dTnpo using mutant alleles or RNAi causes developmental defects, including eye and wing deformities and lethality. These effects are dosage dependent as more severe phenotypes are associated with stronger dTnpo loss. Interestingly, similar phenotypes are observed with dTnpo upregulation and ectopic expression of TNPO2, showing that loss and gain of Transportin activity causes developmental defects. Further, proband-associated variants can cause more or less severe developmental abnormalities compared to wild-type TNPO2 when ectopically expressed. The impact of the variants tested seems to correlate with their position within the protein. Specifically, those that fall within the RAN binding domain cause more severe toxicity and those in the acidic loop are less toxic. Variants within the cargo binding domain show tissue-dependent effects. In summary, dTnpo is an essential gene in flies during development and in neurons. Further, proband-associated de novo variants within TNPO2 disrupt the function of the encoded protein. Hence, TNPO2 variants are causative for neurodevelopmental abnormalities