By monitoring ongoing actions and performance outcomes, we are able to detect errors or mismatches between our intentions or predictions. Disturbances in such performance-monitoring processes may... Show moreBy monitoring ongoing actions and performance outcomes, we are able to detect errors or mismatches between our intentions or predictions. Disturbances in such performance-monitoring processes may importantly contribute to impaired adaptive behavior in clinical disorders, such as excessively impulsive behavior in externalizing disorders or excessively rigid or careful behavior in anxiety- and obsessive-compulsive disorders. In daily life, performance monitoring often takes place in a social context, where our actions have consequences not only for ourselves, but also for others. The investigation of (alterations in) such (pro)social performance-monitoring processes may help explain functional and social impairments across a wide range of clinical disorders. In this dissertation, we used various neuroimaging paradigms to examine subclinical and neurochemical influences on performance monitoring when errors had consequences for oneself or others. The studies in this dissertation indicate that neural performance-monitoring correlates are modulated by social, subclinical, and neurochemical factors, including social (responsibility) context, obsessive-compulsive symptoms, ovarian hormones, and pharmacological manipulations of dopamine and oxytocin. These findings have implications for the potential and utility of error-related brain activity as a clinical biomarker or endophenotype, our insight into social symptoms and impairments in obsessive-compulsive disorder, and for our understanding of the neurochemical mechanisms underlying performance monitoring. Show less
Objective: The Utrecht Scale for Evaluation of Rehabilitation is a multi-domain measurement with good content validity, structural validity and reliability for measuring physical functioning ... Show moreObjective: The Utrecht Scale for Evaluation of Rehabilitation is a multi-domain measurement with good content validity, structural validity and reliability for measuring physical functioning (mobility, selfcare) and cognitive functioning in geriatric rehabilitation. We aimed to determine the construct validity of both Utrecht Scale for Evaluation of Rehabilitation scales and the responsiveness and interpretability of the scale for physical functioning in geriatric rehabilitation.Design: Prospective follow-up study embedded in routine care.Setting: Four care organisations in The Netherlands.Subjects: Patients admitted for inpatient geriatric rehabilitation (2021-2022).Main measures: Data collection included the Utrecht Scale for Evaluation of Rehabilitation, Mini-Mental State Examination, Barthel index, and a global rating scale anchor on recovery. Hypothesis testing was used to determine construct validity and responsiveness. For interpretability, minimal important change and floor and ceiling effects were determined.Results: The mean age of participants (n=211) was 77 (SD 10.4). Their mean length of stay was 38.6 days (SD 26.3), and 81% returned home. The Utrecht Scale for Evaluation of Rehabilitation showed adequate construct validity, as all three hypotheses were confirmed for both scales. The Utrecht Scale for Evaluation of Rehabilitation-physical function scale showed adequate responsiveness, with all five hypotheses confirmed. The mean change for physical function (scale range 0-70) was 15.5 points (SD 17.1). The minimal important change for Utrecht Scale for Evaluation of Rehabilitation-physical function was 14.5 points difference for improvement. This scale showed no floor (2%) and ceiling effects (14%) at admission and discharge.Conclusions: The Utrecht Scale for Evaluation of Rehabilitation showed to be effective for evaluating physical functioning during geriatric rehabilitation as well as screening cognitive functioning. In total, 14.5 points difference has been established as a minimal important change for physical functioning. Show less
Jansen, M.; Lockwood, P.L.; Cutler, J.; De Bruij, n E.R.A. 2023
Objective: To investigate the test-retest precision and to report the longitudinal change in cartilage thickness, the percentage of knees with progression and the predictive value of the machine... Show moreObjective: To investigate the test-retest precision and to report the longitudinal change in cartilage thickness, the percentage of knees with progression and the predictive value of the machine-learning-estimated structural progression score (s-score) for cartilage thickness loss in the IMI-APPROACH cohort - an exploratory, 5-center, 2-year prospective follow-up cohort. Design: Quantitative cartilage morphology at baseline and at least one follow-up visit was available for 270 of the 297 IMI-APPROACH participants (78% females, age: 66.4 +/- 7.1 years, body mass index (BMI): 28.1 +/- 5.3 kg/m(2), 55% with radiographic knee osteoarthritis (OA)) from 1.5T or 3T MRI. Test-retest precision (root mean square coefficient of variation) was assessed from 34 participants. To define progressor knees, smallest detectable change (SDC) thresholds were computed from 11 participants with longitudinal test-retest scans. Binary logistic regression was used to evaluate the odds of progression in femorotibial cartilage thickness (threshold: similar to 211 mu m) for the quartile with the highest vs the quartile with the lowest s-scores. Results: The test-retest precision was 69 mu m for the entire femorotibial joint. Over 24 months, mean cartilage thickness loss in the entire femorotibial joint reached -174 mu m (95% CI: [-207, -141] mu m, 32.7% with progression). The s-score was not associated with 24-month progression rates by MRI (OR: 1.30, 95% CI: [0.52, 3.28]). Conclusion: IMI-APPROACH successfully enrolled participants with substantial cartilage thickness loss, although the machine-learning-estimated s-score was not observed to be predictive of cartilage thickness loss. IMI-APPROACH data will be used in subsequent analyses to evaluate the impact of clinical, imaging, biomechanical and biochemical biomarkers on cartilage thickness loss and to refine the machine-learning-based s-score. (c) 2022 The Author(s). Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Jansen, M.; Does, A.J.W. van der; Rover, M. de; Bruijn, E.R.A. de; Hamstra, D.A. 2023
Background: The IMI-APPROACH cohort is an exploratory, 5-centre, 2-year prospective follow-up study of knee osteoarthritis (OA). Aim was to describe baseline multi-tissue semiquantitative MRI... Show moreBackground: The IMI-APPROACH cohort is an exploratory, 5-centre, 2-year prospective follow-up study of knee osteoarthritis (OA). Aim was to describe baseline multi-tissue semiquantitative MRI evaluation of index knees and to describe change for different MRI features based on number of subregion-approaches and change in maximum grades over a 24-month period.Methods: MRIs were acquired using 1.5 T or 3 T MRI systems and assessed using the semi-quantitative MRI OA Knee Scoring (MOAKS) system. MRIs were read at baseline and 24-months for cartilage damage, bone marrow lesions (BML), osteophytes, meniscal damage and extrusion, and Hoffa- and effusion-synovitis. In descriptive fashion, the frequencies of MRI features at baseline and change in these imaging biomarkers over time are presented for the entire sample in a subregional and maximum score approach for most features. Differences between knees without and with structural radiographic (R) OA are analyzed in addition.Results: Two hundred eighty-nine participants had readable baseline MRI examinations. Mean age was 66.6 +/- 7.1 years and participants had a mean BMI of 28.1 +/- 5.3 kg/m(2). The majority (55.3%) of included knees had radiographic OA. Any change in total cartilage MOAKS score was observed in 53.1% considering full-grade changes only, and in 73.9% including full-grade and within-grade changes. Any medial cartilage progression was seen in 23.9% and any lateral progression on 22.1%. While for the medial and lateral compartments numbers of subregions with improvement and worsening of BMLs were very similar, for the PFJ more improvement was observed compared to worsening (15.5% vs. 9.0%). Including within grade changes, the number of knees showing BML worsening increased from 42.2% to 55.6%. While for some features 24-months change was rare, frequency of change was much more common in knees with vs. without ROA (e.g. worsening of total MOAKS score cartilage in 68.4% of ROA knees vs. 36.7% of no-ROA knees, and 60.7% vs. 21.8% for an increase in maximum BML score per knee).Conclusions: A wide range of MRI-detected structural pathologies was present in the IMI-APPROACH cohort. Baseline prevalence and change of features was substantially more common in the ROA subgroup compared to the knees without ROA. Show less
Introduction: : Establish content and structural validity, internal consistency, inter-rater reliability, and measurement error of the physical and cognitive scales of the Utrecht Scale for... Show moreIntroduction: : Establish content and structural validity, internal consistency, inter-rater reliability, and measurement error of the physical and cognitive scales of the Utrecht Scale for Evaluation clinical Rehabilitation (USER) in geriatric rehabilitation. Material and methods: : First, an expert consensus-meeting (N=7) was organised for content validity wherein scale content validity index (CVI) was measured. Second, in a sample of geriatric rehabilitation patient structural validity (N=616) was assessed by confirmatory factor analyses for exploring unidimensionality. Cut-off criteria were: Root Mean Square Error of Approximation (RMSEA) <= 0.08; Comparative Fit Index (CFI) and Tucker Lewis Index (TLI) >0.95. Local independence (residual correlation<0.20) and monotonicity (Hi-coefficient >0.30 and Hs-coefficient >0.50) were also calculated. Cronbach alphas were calculated for internal consistency. Alpha's > 0.7 was considered adequate. T hird, two nurses independently administered the USER to 37 patients. Intraclass-correlation coefficients (ICC) were calculated for inter-rater reliability (IRR), standard error of measurement (SEM) and Smallest Detectable Change (SDC). Results: : The CVI for physical functioning was moderate (0.73) and excellent for cognitive functioning (0.97). Structural validity physical scale was acceptable (CFI;0.95, TLI;0.93, RMSEA;0.07, ECV;0.78, OmegaH;0.87; Monotonicity;(Hi;0.52-0.75 and Hs;0.63)). Cognitive scale was good (CFI;0.98, TLI;0.96, RMSEA;0.05, ECV;0.66 and OmegaH;0.90. Monotonicity;(Hi;0.30 -0.70 and Hs;0.61)). Cronbach's alpha were high: physical scale;0.92 and cognitive scale;0.94. Reliability physical scale ICC;0.94, SEM;5 and SDC;14 and cognitive scale ICC;0.88, SEM;5 and SDC;13. Conclusion: : The observational scales of the USER have shown sufficient content and structural validity, internal consistency, and interrater reliability for measuring physical and cognitive function in geriatric rehabilitation. Trial registration: : N/A Show less
Schuldt, M.; Driel, B. van; Alguel, S.; Parbhudayal, R.Y.; Barge-Schaapveld, D.Q.C.M.; Gueclue, A.; ... ; Velden, J. van der 2021
Hypertrophic Cardiomyopathy (HCM) is a common inherited heart disease with poor risk prediction due to incomplete penetrance and a lack of clear genotype-phenotype correlations. Advanced imaging... Show moreHypertrophic Cardiomyopathy (HCM) is a common inherited heart disease with poor risk prediction due to incomplete penetrance and a lack of clear genotype-phenotype correlations. Advanced imaging techniques have shown altered myocardial energetics already in preclinical gene variant carriers. To determine whether disturbed myocardial energetics with the potential to serve as biomarkers are also reflected in the serum metabolome, we analyzed the serum metabolome of asymptomatic carriers in comparison to healthy controls and obstructive HCM patients (HOCM). We performed non-quantitative direct-infusion high-resolution mass spectrometry-based untargeted metabolomics on serum from fasted asymptomatic gene variant carriers, symptomatic HOCM patients and healthy controls (n = 31, 14 and 9, respectively). Biomarker panels that discriminated the groups were identified by performing multivariate modeling with gradient-boosting classifiers. For all three group-wise comparisons we identified a panel of 30 serum metabolites that best discriminated the groups. These metabolite panels performed equally well as advanced cardiac imaging modalities in distinguishing the groups. Seven metabolites were found to be predictive in two different comparisons and may play an important role in defining the disease stage. This study reveals unique metabolic signatures in serum of preclinical carriers and HOCM patients that may potentially be used for HCM risk stratification and precision therapeutics. Show less
Pouw, R.E.; Bisschops, R.; Gecse, K.B.; Hertogh, G. de; Iacucci, M.; Rutter, M.; ... ; Hooft, J.E. van 2021
Introduction/Aims: As life expectancy improves for patients with Duchenne muscular dystrophy (DMD), new symptoms are likely to arise. This aims of this study are: (1) to explore the prevalence of a... Show moreIntroduction/Aims: As life expectancy improves for patients with Duchenne muscular dystrophy (DMD), new symptoms are likely to arise. This aims of this study are: (1) to explore the prevalence of a broad variety of symptoms in the various stages of DMD (with and without steroid use); (2) to explore the prevalence of common secondary diagnoses; and (3) to evaluate the social participation level of patients with DMD older than 16 y of age; and to explore correlations between social participation and symptoms.Methods A cross-sectional self-report questionnaire, including questions on functional level and health status, as well as a standardized participation scale was distributed among Dutch patients with DMD.Results Eighty-four male patients with a mean age of 22.0 (SD = 10.0) y were enrolled. The most prevalent and limiting symptoms were difficulty coughing (58%), coldness of hands (57%), contractures (51%), stiffness (49%), fatigue (40%), myalgia (38%), and low speech volume (33%). Prevalent secondary diagnoses included cardiac disease (14%), neurobehavioral diagnosis (13%), low blood pressure (13%), and arthrosis (5%). Social participation correlated negatively with coldness of hands (r = - .29; P < .03), decreased intelligibility (r = - .40; P < .003), and chewing problems (r = - .33; P < .02).Discussion The prevalence of a broad spectrum of symptoms and secondary diagnoses is high in patients with DMD, and some of these symptoms are correlated with social participation. Growing awareness of new symptoms and secondary diagnoses among patients, caregivers, and professionals can enhance their recognition, possibly facilitating prevention and early treatment. Show less
Pei, J.; Schuldt, M.; Nagyova, E.; Gu, Z.; Bouhaddani, S. el; Yiangou, L.; ... ; Harakalova, M. 2021
Background Hypertrophic cardiomyopathy (HCM) is the most common genetic disease of the cardiac muscle, frequently caused by mutations in MYBPC3. However, little is known about the upstream pathways... Show moreBackground Hypertrophic cardiomyopathy (HCM) is the most common genetic disease of the cardiac muscle, frequently caused by mutations in MYBPC3. However, little is known about the upstream pathways and key regulators causing the disease. Therefore, we employed a multi-omics approach to study the pathomechanisms underlying HCM comparing patient hearts harboring MYBPC3 mutations to control hearts. Results Using H3K27ac ChIP-seq and RNA-seq we obtained 9310 differentially acetylated regions and 2033 differentially expressed genes, respectively, between 13 HCM and 10 control hearts. We obtained 441 differentially expressed proteins between 11 HCM and 8 control hearts using proteomics. By integrating multi-omics datasets, we identified a set of DNA regions and genes that differentiate HCM from control hearts and 53 protein-coding genes as the major contributors. This comprehensive analysis consistently points toward altered extracellular matrix formation, muscle contraction, and metabolism. Therefore, we studied enriched transcription factor (TF) binding motifs and identified 9 motif-encoded TFs, including KLF15, ETV4, AR, CLOCK, ETS2, GATA5, MEIS1, RXRA, and ZFX. Selected candidates were examined in stem cell-derived cardiomyocytes with and without mutated MYBPC3. Furthermore, we observed an abundance of acetylation signals and transcripts derived from cardiomyocytes compared to non-myocyte populations. Conclusions By integrating histone acetylome, transcriptome, and proteome profiles, we identified major effector genes and protein networks that drive the pathological changes in HCM with mutated MYBPC3. Our work identifies 38 highly affected protein-coding genes as potential plasma HCM biomarkers and 9 TFs as potential upstream regulators of these pathomechanisms that may serve as possible therapeutic targets. Show less
Heutinck, L.; Gameren, M. van; Verschuuren, J.J.G.M.; Geurts, A.C.H.; Jansen, M.; Groot, I.J.M. de 2021
Background: In order to successfully implement the international clinical care guidelines for Duchenne muscular dystrophy (DMD) in the Netherlands, it is essential to know what barriers are... Show moreBackground: In order to successfully implement the international clinical care guidelines for Duchenne muscular dystrophy (DMD) in the Netherlands, it is essential to know what barriers are experienced by healthcare practitioners regarding guideline adherence and organization of care. In the Netherlands, academic medical centers provide follow up visits and work together with peripheral hospitals, rehabilitation centers, centers for home ventilation and primary care centers for treatment.Objective: To investigate perceived barriers to international clinical DMD guideline adherence and identify potential areas of improvement for implementation in the Dutch 'shared care' organization.Methods: Semi-structured in-depth interviews with healthcare practitioners of academic medical hospitals and questionnaires for healthcare practitioners of rehabilitation centers, based on the framework of Cabana.Results: The analyses identified 4 barriers for non-adherence to the DMD guideline: (i) lack of familiarity/awareness, (ii) lack of agreement with specific guideline, (iii) lack of outcome expectancy, (iv) external barriers.Conclusions: A heterogeneous set of barriers is present. Therefore, a multifaceted intervention strategy is proposed to overcome these barriers, including a clear division of roles, allowing for local (Dutch) adaptations per specialism by local consensus groups, and the facilitation of easy communication with experts/opinion leaders as well as between care professionals. Show less
Heutinck, L.; Houwen-van Opstal, S.L.S.; Krom, Y.D.; Niks, E.H.; Verschuuren, J.J.G.M.; Jansen, M.; Groot, I.J.M. de 2021
Background and objective: To optimize care for patients with DMD, it is essential to know to what extent current care complies with the recommended monitoring frequencies suggested by the DMD care... Show moreBackground and objective: To optimize care for patients with DMD, it is essential to know to what extent current care complies with the recommended monitoring frequencies suggested by the DMD care considerations. The objective of this study was to investigate the current care for patients with DMD in the Netherlands and to what extent the care complies with the international care considerations.Methods: A cross-sectional questionnaire was carried out among the Dutch DMD patients and caregivers about the patients' functional and health status, visits to healthcare professionals, clinical tests and assessments, therapy, medication use and access to medical aids and devices. Compliance to guidelines was defined by comparing the frequency of visits to health care providers and clinical tests with the recommended frequencies derived from the care considerations of 2010.Results: Eighty-four participants completed the questionnaire. The majority of participants met the recommended visit frequencies to a neuromuscular specialist and cardiologist. Compliance was suboptimal for respiratory assessments in the non-ambulatory phase, monitoring of side effects of corticosteroid use and neuromuscular assessments. Disease specific information supply was perceived as sufficient and participants were satisfied with the received care.Conclusions: This study identifies areas in which compliance is lacking. Countries, such as the Netherlands, working according to a shared care system require easy and low-threshold communication between health care centers and a clear division of roles and responsibilities to reach optimal compliance. In the Netherlands the Duchenne Center Netherlands has the coordinating role. Show less
Our mistakes often have negative consequences for ourselves, but may also harm the people around us. Continuous monitoring of our performance is therefore crucial for both our own and others’ well... Show moreOur mistakes often have negative consequences for ourselves, but may also harm the people around us. Continuous monitoring of our performance is therefore crucial for both our own and others’ well-being. Here, we investigated how modulations in responsibility for other’s harm affects electrophysiological correlates of performance-monitoring, viz. the error-related negativity (ERN) and error positivity (Pe). Healthy participants (N = 27) performed a novel social performance-monitoring paradigm in two responsibility contexts. Mistakes made in the harmful context resulted in a negative consequence for a co-actor, i.e., hearing a loud aversive sound, while errors in the non-harmful context were followed by a soft non-aversive sound. Although participants themselves did not receive auditory feedback in either context, they did experience harmful mistakes as more distressing and reported higher effort to perform well in the harmful context. ERN amplitudes were enhanced for harmful compared to non-harmful mistakes. Pe amplitudes were unaffected. The present study shows that performing in a potentially harmful social context amplifies early automatic performance-monitoring processes and increases the impact of the resulting harmful mistakes. These outcomes not only further our theoretical knowledge of social performance monitoring, but also demonstrate a novel and useful paradigm to investigate aberrant responsibility attitudes in various clinical populations. Show less
Overgaauw, S.; Jansen, M.; Korbee, N.J.; Bruijn, E.R.A. de 2019
Aligning behavior in favor of group norms, i.e., social conformity, can help to successfully adapt to uncertain environments and may result in social approval. This may lead to enhanced feelings of... Show moreAligning behavior in favor of group norms, i.e., social conformity, can help to successfully adapt to uncertain environments and may result in social approval. This may lead to enhanced feelings of belongingness and is found to be associated with reward-related activations in the brain. Individuals high on psychopathic traits violate group norms regularly. Yet, it is unclear how psychopathic traits are related to neural mechanisms involved in social conformity. This functional magnetic resonance imaging (fMRI) study includes 42 healthy females scoring low or high on the Psychopathic Personality Inventory questionnaire (PPI). Participants were asked to rate the trustworthiness of 120 faces while lying in the scanner. After rating each face, participants were presented with the group rating of European students. In an unanticipated second part participants rated all faces again, allowing us to focus on two main contrasts: (1) “Social conflict”: group opinion in conflict with the participant’s rating vs. group opinion aligned with participant rating; and (2) “Conformity”: conflict trials followed by conformity vs. conflict trials followed by non-conformity. Behaviorally, the two groups showed similar conformity behavior. fMRI results showed that both groups activated the nucleus accumbens (NAc) following alignment, suggesting the central role of prediction errors and reward. The data also showed a significant interaction between group and conformity in the amygdala. Following conflicts, females scoring low on psychopathic traits showed a trend in enhanced amygdala activation for conformity relative to non-conformity. Additionally, results showed a trend significant group effect for non-conformity. Females scoring high on psychopathic traits showed more activation for non-conformity compared to females scoring low on psychopathic traits, suggesting altered emotional salience of experiencing conflict depending on psychopathic traits. Taken together, these results support the importance of investigating the role of relevant traits in adaptive behavior when facing uncertain social situations and the neural mechanisms involved in this process. Show less
