Immersive virtual reality (IVR) may boost neglect recovery, as it can provide an engaging experience in a 3D environment. We designed an IVR rehabilitation game for neglect patients using the Oculus Rift.Multisensory cues were presented in the neglected visual field in a patient-tailored way. We acquired pilot data in 15 neurologically healthy controls and 7 stroke patients. First, we compared cybersickness before and after VR exposure. Second, we assessed the user experience through a questionnaire. Third, we tested whether neglect symptoms corresponded between the VR game and a computerized cancellation task. Fourth, we evaluated the effect of the multisensory cueing on target discrimination.Last, we tested two algorithms to tailor the game to the characteristics of the neglected visual field.Cybersickness significantly reduced after VR exposure in six stroke patients and was low in healthy controls. Patients rated the user experience neutral to positive. In addition, neglect symptoms were consistent between a computerized cancellation and VR rehabilitation task. The multisensory cue positively affected target discrimination in the game and we successfully presented sensory stimulation to the neglected visual field in a patient-tailored way. Our results show that it is promising to use gamified patient-tailored immersive VR for neglect rehabilitation.

The enteric nervous system (ENS) is the intrinsic neural network of the gastrointestinal tract, which is essential for regulating gut functions and intestinal homeostasis. The importance of the ENS is underscored by the existence of severe gastrointestinal diseases, such as Hirschsprung's disease and intestinal pseudo-obstruction, which arise when the ENS fails to develop normally or becomes dysregulated. Moreover, it is known that enteric neurons are involved in intestinal inflammation. However, the role of the ENS in colorectal cancer (CRC) carcinogenesis remains poorly understood, even though processes like perineural invasion and neoneurogenesis are important factors in CRC. Here we summarize how enteric neurons are affected during CRC and discuss the influence of enteric neurons, either direct or indirect, on the development and/or progression of CRC. Finally, we illustrate how the ENS could be targeted as a potential anti-cancer therapy, establishing the ENS as an integral part of the tumor microenvironment.

Purpose Colonoscopy and the fecal immunochemical test (FIT) are currently the most widely used screening modalities for colorectal cancer (CRC), however, both with their own limitations. Here we aim to identify and validate stool-based DNA methylation markers for the early detection of CRC and investigate the biological pathways prone to DNA methylation. Methods DNA methylation marker discovery was performed using The Cancer Genome Atlas (TCGA) colon adenocarcinoma data set consisting of normal and primary colon adenocarcinoma tissue. The performance of the five best candidate markers and a previously identified marker, NDRG4, was evaluated on tissues and whole stool samples of healthy subjects and CRC patients using quantitative MSP assays. The results were compared and combined with FIT data. Finally, pathway and gene ontology enrichment analyses were performed using ToppFun, GOrilla and clusterProfiler. Results GDNF, HAND2, SLC35F3, SNAP91 and SORCS1 were ranked as the best performing markers. Gene combinations of all five markers, NDRG4 and FIT were evaluated to establish the biomarker panel with the highest diagnostic potential, resulting in the identification of GDNF/SNAP91/NDRG4/FIT as the best performing marker panel. Pathway and gene ontology enrichment analyses revealed that genes associated with the nervous system were enriched in the set of best performing CRC-specific biomarkers. Conclusion In silico discovery analysis using TCGA-derived data yielded a novel DNA-methylation-based assay for the early detection of CRC, potentially improving current screening modalities. Additionally, nervous system-related pathways were enriched in the identified genes, indicating an epigenetic regulation of neuronal genes in CRC.

Computerized as well as paper-and-pencil tasks are applied in mapping visuospatial neglect in experimental research and clinical practice. This article presents a new kind of computer-based assessment method, using an electronic pen display and user-friendly software. The approach is tailored to specific spatial processes and highlights the usefulness of a pen display in neglect patients. The advantages of the introduced method are illustrated by a recently designed battery of classic, as well as new, types of tests. The development of the appropriate stimuli and the assorted scoring systems is addressed, as well as the resulting types of task implementation and data generation. The diagnostic value of the different visuospatial neglect tests is demonstrated by comparative analyses between a neglect group and a control group. Among the benefits of the proposed assessment method are (1) the opportunity to perform standardized repeated measurements to quantify recovery, (2) online performance monitoring, (3) flexible employment, (4) the collection of exact data over a short period, and (5) the easy availability of more refined quantitative as well as interesting qualitative information, especially as compared to classic or paper-and-pencil tasks. To indicate that this method also lends itself well to measures for treatment procedures, an illustration is given with respect to specific measurements during prism adaptation. The tasks of the Visuospatial Neglect Test Battery and the prism adaptation measures are illustrated by a case study. The outlined applications are discussed with respect to experimental as well as clinical purposes.

The N-Myc downstream-regulated gene (NDRG) family consists of four members (NDRG1, NDRG2, NDRG3, NDRG4) that are differentially expressed in various organs and function in important processes, like cell proliferation and differentiation. In the last couple of decades, interest in this family has risen due to its connection with several disorders of the nervous system including Charcot-Marie-Tooth disease and dementia, as well as nervous system cancers. By combining a literature review with in silico data analysis of publicly available datasets, such as the Mouse Brain Atlas, BrainSpan, the Genotype-Tissue Expression (GTEx) project, and Gene Expression Omnibus (GEO) datasets, this review summarizes the expression and functions of the NDRG family in the healthy and diseased nervous system. We here show that the NDRGs have a differential, relatively cell typespecific, expression pattern in the nervous system. Even though NDRGs share functionalities, like a role in vesicle trafficking, stress response, and neurite outgrowth, other functionalities seem to be unique to a specific member, e.g., the role of NDRG1 in myelination. Furthermore, mutations, phosphorylation, or changes in expression of NDRGs are related to nervous system diseases, including peripheral neuropathy and different forms of dementia. Moreover, NDRG1, NDRG2, and NDRG4 are all involved in cancers of the nervous system, such as glioma, neuroblastoma, or meningioma. All in all, our review elucidates that although the NDRGs belong to the same gene family and share some functional features, they should be considered unique in their expression patterns and functional importance for nervous system development and neuronal diseases.