Response Monitoring in De Novo Patients with Parkinson's Disease

BACKGROUND: Parkinson's disease (PD) is accompanied by dysfunctions in a variety of cognitive processes. One of these is error processing, which depends upon phasic decreases of medial prefrontal dopaminergic activity. Until now, there is no study evaluating these processes in newly diagnosed, untreated patients with PD ("de novo PD"). METHODOLOGY/PRINCIPAL FINDINGS: Here we report large changes in performance monitoring processes using event-related potentials (ERPs) in de novo PD-patients. The results suggest that increases in medial frontal dopaminergic activity after an error (Ne) are decreased, relative to age-matched controls. In contrast, neurophysiological processes reflecting general motor response monitoring (Nc) are enhanced in de novo patients. CONCLUSIONS/SIGNIFICANCE: It may be hypothesized that the Nc-increase is at costs of dopaminergic activity after an error; on a functional level errors may not always be detected and correct responses sometimes be misinterpreted as errors. This pattern differs from studies examining patients with a longer history of PD and may reflect compensatory processes, frequently occurring in pre-manifest stages of PD. From a clinical point of view the clearly attenuated Ne in the de novo PD patients may prove a useful additional tool for the early diagnosis of basal ganglia dysfunction in PD

Dopamine transporter (DAT1) and dopamine receptor D4 (DRD4) genotypes differentially impact on electrophysiological correlates of error processing

Peer reviewedPublisher PD

Aging and Error Processing: Age Related Increase in the Variability of the Error-Negativity Is Not Accompanied by Increase in Response Variability

Background: Several studies report an amplitude reduction of the error negativity (Ne or ERN), an event-related potential occurring after erroneous responses, in older participants. In earlier studies it was shown that the Ne can be explained by a single independent component. In the present study we aimed to investigate whether the Ne reduction usually found in older subjects is due to an altered component structure, i.e., a true alteration in response monitoring in older subjects. Methodology/Principal Findings: Two age groups conducted two tasks with different stimulus response mappings and task difficulty. Both groups received fully balanced speed or accuracy instructions and an individually adapted deadline in both tasks. Event-related potentials, Independent Component analysis of EEG-data and between trial variability of the Ne were combined with analysis of error rates, coefficients of variation of RT-data and ex-Gaussian fittings to reaction times. The Ne was examined by means of ICA and PCA, yielding a prominent independent component on error trials, the Ne-IC. The Ne-IC was smaller in the older than the younger subjects for both speed and accuracy instructions. Also, the Ne-IC contributed to a much lesser extent to the Ne in older than in younger subjects. RT distribution parameters were not related to Ne/ERP-variability. Conclusions/Significance: The results show a genuine reduction as well as a different component structure of the Ne in older compared to young subjects. This reduction is not reflected in behaviour, apart from a general slowing of olde

Clinical added value of MRI to CT in patients scheduled for local therapy of colorectal liver metastases (CAMINO):study protocol for an international multicentre prospective diagnostic accuracy study

Abstract Background Abdominal computed tomography (CT) is the standard imaging method for patients with suspected colorectal liver metastases (CRLM) in the diagnostic workup for surgery or thermal ablation. Diffusion-weighted and gadoxetic-acid-enhanced magnetic resonance imaging (MRI) of the liver is increasingly used to improve the detection rate and characterization of liver lesions. MRI is superior in detection and characterization of CRLM as compared to CT. However, it is unknown how MRI actually impacts patient management. The primary aim of the CAMINO study is to evaluate whether MRI has sufficient clinical added value to be routinely added to CT in the staging of CRLM. The secondary objective is to identify subgroups who benefit the most from additional MRI. Methods In this international multicentre prospective incremental diagnostic accuracy study, 298 patients with primary or recurrent CRLM scheduled for curative liver resection or thermal ablation based on CT staging will be enrolled from 17 centres across the Netherlands, Belgium, Norway, and Italy. All study participants will undergo CT and diffusion-weighted and gadoxetic-acid enhanced MRI prior to local therapy. The local multidisciplinary team will provide two local therapy plans: first, based on CT-staging and second, based on both CT and MRI. The primary outcome measure is the proportion of clinically significant CRLM (CS-CRLM) detected by MRI not visible on CT. CS-CRLM are defined as liver lesions leading to a change in local therapeutical management. If MRI detects new CRLM in segments which would have been resected in the original operative plan, these are not considered CS-CRLM. It is hypothesized that MRI will lead to the detection of CS-CRLM in ≥10% of patients which is considered the minimal clinically important difference. Furthermore, a prediction model will be developed using multivariable logistic regression modelling to evaluate the predictive value of patient, tumor and procedural variables on finding CS-CRLM on MRI. Discussion The CAMINO study will clarify the clinical added value of MRI to CT in patients with CRLM scheduled for local therapy. This study will provide the evidence required for the implementation of additional MRI in the routine work-up of patients with primary and recurrent CRLM for local therapy. Trial registration The CAMINO study was registered in the Netherlands National Trial Register under number NL8039 on September 20th 2019

Reproducible radiomics through automated machine learning validated on twelve clinical applications

Radiomics uses quantitative medical imaging features to predict clinical outcomes. Currently, in a new clinical application, findingthe optimal radiomics method out of the wide range of available options has to be done manually through a heuristic trial-anderror process. In this study we propose a framework for automatically optimizing the construction of radiomics workflows perapplication. To this end, we formulate radiomics as a modular workflow and include a large collection of common algorithms foreach component. To optimize the workflow per application, we employ automated machine learning using a random search andensembling. We evaluate our method in twelve different clinical applications, resulting in the following area under the curves: 1)liposarcoma (0.83); 2) desmoid-type fibromatosis (0.82); 3) primary liver tumors (0.80); 4) gastrointestinal stromal tumors (0.77);5) colorectal liver metastases (0.61); 6) melanoma metastases (0.45); 7) hepatocellular carcinoma (0.75); 8) mesenteric fibrosis(0.80); 9) prostate cancer (0.72); 10) glioma (0.71); 11) Alzheimer’s disease (0.87); and 12) head and neck cancer (0.84). Weshow that our framework has a competitive performance compared human experts, outperforms a radiomics baseline, and performssimilar or superior to Bayesian optimization and more advanced ensemble approaches. Concluding, our method fully automaticallyoptimizes the construction of radiomics workflows, thereby streamlining the search for radiomics biomarkers in new applications.To facilitate reproducibility and future research, we publicly release six datasets, the software implementation of our framework,and the code to reproduce this study

A woman with hepatomegaly

A 32-year-old woman was referred because of hepatomegaly of unknown cause. CT and MRI images of the abdomen showed a markedly enlarged right liver lobe extending into the pelvis. A diagnosis of hepatomegaly due to a Riedel's lobe was made.</p

A woman with hepatomegaly

A 32-year-old woman was referred because of hepatomegaly of unknown cause. CT and MRI images of the abdomen showed a markedly enlarged right liver lobe extending into the pelvis. A diagnosis of hepatomegaly due to a Riedel's lobe was made.</p

Variations in the TNF-alpha gene ((TNF-alpha -308G->A) affect attention and action selection mechanisms in a double-dissociated fashion

There is growing interest to understand the molecular basis of complex cognitive processes. While neurotransmitter systems have frequently been examined, other, for example neuroimmunological factors have attracted much less interest. Recent evidence suggests that the A allele of the tumor necrosis factor alpha (TNF-α) 308G→A single nucleotide polymorphism (SNP; rs1800629) enhances cognitive functions. However, it is also known that TNF-α exerts divergent, region-specific effects on neuronal functioning. Thus the finding that the A allele is associated with enhanced cognitive performance may be due to regionally specific effects of TNF-α. In this study, associations between the TNF-α -308G→A single nucleotide polymorphism (rs1800629) and cognitive function in an event-related potential (ERP) study in healthy participants (n = 96) are investigated. We focus on subprocesses of stimulus-response compatibility that are known to be mediated by different brain systems. The results show a dissociative effect of the TNF- 308G→A SNP on ERPs reflecting attentional (N1) versus conflict and action selection processes [N2 and early-lateralized readiness potential (e-LRP)] between the AA/AG and the GG genotypes. Compared with the GG genotype group, attentional processes (N1) were enhanced in the combined AA/AG genotype group, while conflict processing functions (N2) and the selection of actions (LRP) were reduced. The results refine the picture of the effects of the TNF-α -308G→A SNP on cognitive functions and emphasize the known divergent effects of TNF-α on brain functions.Christian Beste, Bernhard T. Baune, Michael Falkenstein, Carsten Konra