Evaluation of the effectiveness of a novel brain-computer interface neuromodulative intervention to relieve neuropathic pain following spinal cord injury: Protocol for a single-case experimental design with multiple baselines

Background: Neuropathic pain is a debilitating secondary condition for many individuals with spinal cord injury. Spinal cord injury neuropathic pain often is poorly responsive to existing pharmacological and nonpharmacological treatments. A growing body of evidence supports the potential for brain-computer interface systems to reduce spinal cord injury neuropathic pain via electroencephalographic neurofeedback. However, further studies are needed to provide more definitive evidence regarding the effectiveness of this intervention. Objective: The primary objective of this study is to evaluate the effectiveness of a multiday course of a brain-computer interface neuromodulative intervention in a gaming environment to provide pain relief for individuals with neuropathic pain following spinal cord injury. Methods: We have developed a novel brain-computer interface-based neuromodulative intervention for spinal cord injury neuropathic pain. Our brain-computer interface neuromodulative treatment includes an interactive gaming interface, and a neuromodulation protocol targeted to suppress theta (4-8 Hz) and high beta (20-30 Hz) frequency powers, and enhance alpha (9-12 Hz) power. We will use a single-case experimental design with multiple baselines to examine the effectiveness of our self-developed brain-computer interface neuromodulative intervention for the treatment of spinal cord injury neuropathic pain. We will recruit 3 participants with spinal cord injury neuropathic pain. Each participant will be randomly allocated to a different baseline phase (ie, 7, 10, or 14 days), which will then be followed by 20 sessions of a 30-minute brain-computer interface neuromodulative intervention over a 4-week period. The visual analog scale assessing average pain intensity will serve as the primary outcome measure. We will also assess pain interference as a secondary outcome domain. Generalization measures will assess quality of life, sleep quality, and anxiety and depressive symptoms, as well as resting-state electroencephalography and thalamic γ-aminobutyric acid concentration. Results: This study was approved by the Human Research Committees of the University of New South Wales in July 2019 and the University of Technology Sydney in January 2020. We plan to begin the trial in October 2020 and expect to publish the results by the end of 2021. Conclusions: This clinical trial using single-case experimental design methodology has been designed to evaluate the effectiveness of a novel brain-computer interface neuromodulative treatment for people with neuropathic pain after spinal cord injury. Single-case experimental designs are considered a viable alternative approach to randomized clinical trials to identify evidence-based practices in the field of technology-based health interventions when recruitment of large samples is not feasible

Connectivity-based parcellation of the human frontal polar cortex

The frontal pole corresponds to Brodmann area (BA) 10, the largest single architectonic area in the human frontal lobe. Generally, BA10 is thought to contain two or three subregions that subserve broad functions such as multitasking, social cognition, attention, and episodic memory. However, there is a substantial debate about the functional and structural heterogeneity of this large frontal region. Previous connectivity-based parcellation studies have identified two or three subregions in the human frontal pole. Here, we used diffusion tensor imaging to assess structural connectivity of BA10 in 35 healthy subjects and delineated subregions based on this connectivity. This allowed us to determine the correspondence of structurally based subregions with the scheme previously defined functionally. Three subregions could be defined in each subject. However, these three subregions were not spatially consistent between subjects. Therefore, we accepted a solution with two subregions that encompassed the lateral and medial frontal pole. We then examined resting-state functional connectivity of the two subregions and found significant differences between their connectivities. The medial cluster was connected to nodes of the default-mode network, which is implicated in internally focused, self-related thought, and social cognition. The lateral cluster was connected to nodes of the executive control network, associated with directed attention and working memory. These findings support the concept that there are two major anatomical subregions of the frontal pole related to differences in functional connectivity

A home-based self-directed EEG neurofeedback intervention for people with chronic neuropathic pain following spinal cord injury (the StoPain Trial): description of the intervention

Study design: Randomised controlled trial. Objectives: The objective is to describe an electroencephalography (EEG) neurofeedback intervention that will be provided in a randomised controlled trial for people with neuropathic pain following spinal cord injury (SCI): the StoPain Trial. In this trial, participants in the treatment group will implement an EEG neurofeedback system as an analgesic intervention at home, while participants in the control group will continue with the treatments available to them in the community. Setting: University-based study in Sydney, Australia. Methods/results: This manuscript describes the rationale and components of the EEG neurofeedback intervention designed for individuals with SCI neuropathic pain and intended for home-based implementation. Our report is based on the criteria of the Template for Intervention Description and Replication (TIDieR) checklist, and includes why the efficacy of EEG neurofeedback will be investigated, what will be provided, who will administer it, and how, where, when, and how much the EEG neurofeedback intervention will be administered. Conclusions: This manuscript provides a detailed description of a complex intervention used in a randomised controlled trial. This description will facilitate the subsequent interpretation of the trial results and allow for the replication of the intervention in clinical practice and future trials. Sponsorship: Australian Government Medical Research Future Fund (2020 Rare Cancers Rare Diseases and Unmet Needs Scheme: 2006020)

Neighbor Overlap Is Enriched in the Yeast Interaction Network: Analysis and Implications

The yeast protein-protein interaction network has been shown to have distinct topological features such as a scale free degree distribution and a high level of clustering. Here we analyze an additional feature which is called Neighbor Overlap. This feature reflects the number of shared neighbors between a pair of proteins. We show that Neighbor Overlap is enriched in the yeast protein-protein interaction network compared with control networks carefully designed to match the characteristics of the yeast network in terms of degree distribution and clustering coefficient. Our analysis also reveals that pairs of proteins with high Neighbor Overlap have higher sequence similarity, more similar GO annotations and stronger genetic interactions than pairs with low ones. Finally, we demonstrate that pairs of proteins with redundant functions tend to have high Neighbor Overlap. We suggest that a combination of three mechanisms is the basis for this feature: The abundance of protein complexes, selection for backup of function, and the need to allow functional variation

Hubs with Network Motifs Organize Modularity Dynamically in the Protein-Protein Interaction Network of Yeast

BACKGROUND: It has been recognized that modular organization pervades biological complexity. Based on network analysis, 'party hubs' and 'date hubs' were proposed to understand the basic principle of module organization of biomolecular networks. However, recent study on hubs has suggested that there is no clear evidence for coexistence of 'party hubs' and 'date hubs'. Thus, an open question has been raised as to whether or not 'party hubs' and 'date hubs' truly exist in yeast interactome. METHODOLOGY: In contrast to previous studies focusing on the partners of a hub or the individual proteins around the hub, our work aims to study the network motifs of a hub or interactions among individual proteins including the hub and its neighbors. Depending on the relationship between a hub's network motifs and protein complexes, we define two new types of hubs, 'motif party hubs' and 'motif date hubs', which have the same characteristics as the original 'party hubs' and 'date hubs' respectively. The network motifs of these two types of hubs display significantly different features in spatial distribution (or cellular localizations), co-expression in microarray data, controlling topological structure of network, and organizing modularity. CONCLUSION: By virtue of network motifs, we basically solved the open question about 'party hubs' and 'date hubs' which was raised by previous studies. Specifically, at the level of network motifs instead of individual proteins, we found two types of hubs, motif party hubs (mPHs) and motif date hubs (mDHs), whose network motifs display distinct characteristics on biological functions. In addition, in this paper we studied network motifs from a different viewpoint. That is, we show that a network motif should not be merely considered as an interaction pattern but be considered as an essential function unit in organizing modules of networks

GAMBARAN LESI MAKROSKOPIS DAN MIKROSKOPIS EMBRIO AYAM YANG DIINFEKSI VIRUS Infectious Bursal Disease (IBD)

Infectious Bursal Disease (IBD) or well known as Gumboro disease is a disease of poultry that is often found in the field where significant losses result. Accurate diagnosis of the disease is needed in efforts to control the disease, one of which is the isolation and identification of viruses that causes disease. This research was aimed to determine the macroscopic and microscopic lesions in chickens infected by the virus of IBD. The virus isolate from the collection of Dr. drh. Michael Haryadi Wibowo, M. P and has been identified by Transciptase Reverse Polymerase Chain Reaction (RT-PCR). This research was used embryonated chicken eggs 11 day old and antibody negative to IBD. Embryonated chicken eggs was used three eggs which are divided into a control group and infected group. IBD virus inoculation was did by deposition on the chorioallantoic membrane (CAM). Embryos were monitored for mortality and observed macroscopically on CAM and embryos. The organs of chicken embryos were made into histopathologic preparations stained with Hematoxyline and eosin (H&E) for microscopic analysis. The results showed that the negative control of chicken embryos and CAM had no any change. The inoculated IBD virus isolate showed macroscopic lesions cutaneous congestion, hemorrhages on toe joints and the cerebral region. Embryos were observed edematous distention of abdominal region, delayed feathering, embryo development was stunted and CAM was hemorrhagic. The microscopic lesions showed congestion, vacuolization and cell death in the liver, tubular epithelial necrosis in kidney. The others microscopic lesions embryos were found hemorrhagic, vacuolization, and there is infiltration of lymphocytes in the heart, skin udema, congestion in lung and hemorrhages on CAM and brain

Evaluation of the Effectiveness of a Novel Brain-Computer Interface Neuromodulative Intervention to Relieve Neuropathic Pain Following Spinal Cord Injury: Protocol for a Single-Case Experimental Design With Multiple Baselines (Preprint)

BACKGROUND Neuropathic pain is a debilitating secondary condition for many individuals with spinal cord injury. Spinal cord injury neuropathic pain often is poorly responsive to existing pharmacological and nonpharmacological treatments. A growing body of evidence supports the potential for brain-computer interface systems to reduce spinal cord injury neuropathic pain via electroencephalographic neurofeedback. However, further studies are needed to provide more definitive evidence regarding the effectiveness of this intervention. OBJECTIVE The primary objective of this study is to evaluate the effectiveness of a multiday course of a brain-computer interface neuromodulative intervention in a gaming environment to provide pain relief for individuals with neuropathic pain following spinal cord injury. METHODS We have developed a novel brain-computer interface-based neuromodulative intervention for spinal cord injury neuropathic pain. Our brain-computer interface neuromodulative treatment includes an interactive gaming interface, and a neuromodulation protocol targeted to suppress theta (4-8 Hz) and high beta (20-30 Hz) frequency powers, and enhance alpha (9-12 Hz) power. We will use a single-case experimental design with multiple baselines to examine the effectiveness of our self-developed brain-computer interface neuromodulative intervention for the treatment of spinal cord injury neuropathic pain. We will recruit 3 participants with spinal cord injury neuropathic pain. Each participant will be randomly allocated to a different baseline phase (ie, 7, 10, or 14 days), which will then be followed by 20 sessions of a 30-minute brain-computer interface neuromodulative intervention over a 4-week period. The visual analog scale assessing average pain intensity will serve as the primary outcome measure. We will also assess pain interference as a secondary outcome domain. Generalization measures will assess quality of life, sleep quality, and anxiety and depressive symptoms, as well as resting-state electroencephalography and thalamic γ-aminobutyric acid concentration. RESULTS This study was approved by the Human Research Committees of the University of New South Wales in July 2019 and the University of Technology Sydney in January 2020. We plan to begin the trial in October 2020 and expect to publish the results by the end of 2021. CONCLUSIONS This clinical trial using single-case experimental design methodology has been designed to evaluate the effectiveness of a novel brain-computer interface neuromodulative treatment for people with neuropathic pain after spinal cord injury. Single-case experimental designs are considered a viable alternative approach to randomized clinical trials to identify evidence-based practices in the field of technology-based health interventions when recruitment of large samples is not feasible. CLINICALTRIAL Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12620000556943; https://bit.ly/2RY1jRx INTERNATIONAL REGISTERED REPORT PRR1-10.2196/20979 </sec