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The cortical development of our brains is in a hierarchical manner and promotes the emergence of large-scale functional hierarchy. However, under interindividual heterogenicity, how the spatiotemporal features of brain networks reflect brain development and mental health remains unclear. Here we collect both resting-state electroencephalography and functional magnetic resonance imaging data from the Child Mind Institute Biobank to demonstrate that during brain growth, the global dynamic patterns of brain states become more active and the dominant networks shift from sensory to higher-level networks; the individual functional network patterns become more similar to that of adults and their spatial coupling tends to be invariable. Furthermore, the properties of multimodality brain networks are sufficiently robust to identify healthy brain age and mental disorders at specific ages. Therefore, multimodality brain networks provide new insights into the functional development of the brain and a more reliable and reasonable approach for age prediction and individual diagnosis.Multimodality brain networks using EEG and fMRI reveal functional development of brain in spatio-temporal domains and help us make a more robust assessment of brain age and mental health. [ABSTRACT FROM AUTHOR]

The neural signals produced by varying electrical stimulation parameters lead to characteristic neural circuit responses. However, the characteristics of neural circuits reconstructed by electrical signals remain poorly understood, which greatly limits the application of such electrical neuromodulation techniques for the treatment of spinal cord injury. Here, we develop a dual electrical stimulation system that combines epidural electrical and muscle stimulation to mimic feedforward and feedback electrical signals in spinal sensorimotor circuits. We demonstrate that a stimulus frequency of 10−20 Hz under dual stimulation conditions is required for structural and functional reconstruction of spinal sensorimotor circuits, which not only activates genes associated with axonal regeneration of motoneurons, but also improves the excitability of spinal neurons. Overall, the results provide insights into neural signal decoding during spinal sensorimotor circuit reconstruction, suggesting that the combination of epidural electrical and muscle stimulation is a promising method for the treatment of spinal cord injury. Electrical signals with characteristic parameters for reconstructing neural circuits remain incompletely understood, limiting the therapeutic potential of electrical neuromodulation techniques. Here, the authors demonstrate that dual electrical stimulation at 10–20 Hz rebuilds the spinal sensorimotor neural circuit after spinal cord injury, indicating the characteristic signals of circuit remodeling. [ABSTRACT FROM AUTHOR]

Background: With the growing number of the aged population, the number of Parkinson’s disease (PD) affected people is also mounting. Unfortunately, due to insufficient resources and awareness in underdeveloped countries, proper and timely PD detection is highly challenged. Besides, all PD patients’ symptoms are neither the same nor they all become pronounced at the same stage of the illness. Therefore, this work aims to combine more than one symptom (rest tremor and voice degradation) by collecting data remotely using smartphones and detect PD with the help of a cloud-based machine learning system for telemonitoring the PD patients in the developing countries. Method: This proposed system receives rest tremor and vowel phonation data acquired by smartphones with built-in accelerometer and voice recorder sensors. The data are primarily collected from diagnosed PD patients and healthy people for building and optimizing machine learning models that exhibit higher performance. After that, data from newly suspected PD patients are collected, and the trained algorithms are evaluated to detect PD. Based on the majority-vote from those algorithms, PD-detected patients are connected with a nearby neurologist for consultation. Upon receiving patients’ feedback after being diagnosed by the neurologist, the system may update the model by retraining using the latest data. Also, the system requests the detected patients periodically to upload new data to track their disease progress. Result: The highest accuracy in PD detection using offline data was 98.3 % from voice data and 98.5 % from tremor data when used separately. In both cases, k-nearest neighbors (kNN) gave the highest accuracy over support vector machine (SVM) and naive Bayes (NB). The application of maximum relevance minimum redundancy (MRMR) feature selection method showed that by selecting different feature sets based on the patient’s gender, we could improve the detection accuracy. This study’s novelty is the application of ensemble averaging on the combined decisions generated from the analysis of voice and tremor data. The average accuracy of PD detection becomes 99.8 % when ensemble averaging was performed on majority-vote from kNN, SVM, and NB. Conclusion: The proposed system can detect PD using a cloud-based system for computation, data preserving, and regular monitoring of voice and tremor samples captured by smartphones. Thus, this system can be a solution for healthcare authorities to ensure the older population’s accessibility to a better medical diagnosis system in the developing countries, especially in the pandemic situation like COVID-19, when in-person monitoring is minimal. [ABSTRACT FROM AUTHOR]

Purpose: Dysautonomia can be a debilitating feature of Parkinson disease (PD). Pedunculopontine nucleus (PPN) stimulation may improve gait disorders in PD, and may also result in changes in autonomic performance. Methods: To determine whether pedunculopontine nucleus stimulation improves cardiovascular responses to autonomic challenges of postural tilt and Valsalva manoeuver, eight patients with pedunculopontine nucleus deep brain stimulation were recruited to the study; two were excluded for technical reasons during testing. Participants underwent head up tilt and Valsalva manoeuver with stimulation turned ON and OFF. Continuous blood pressure and ECG waveforms were recorded during these tests. In a single patient, local field potential activity was recorded from the implanted electrode during tilt. Results: The fall in systolic blood pressure after tilt was significantly smaller with stimulation ON (mean − 8.3% versus − 17.2%, p = 0.044). Valsalva ratio increased with stimulation from median 1.15 OFF to 1.20 ON (p = 0.028). Baroreflex sensitivity increased during Valsalva compared to rest with stimulation ON versus OFF (p = 0.028). The increase in baroreflex sensitivity correlated significantly with the mean depth of PPN stimulating electrode contacts. This accounted for 89% of its variance (r = 0.943, p = 0.005). Conclusion: PPN stimulation can modulate the cardiovascular system in patients with PD. In this study, it reduced the postural fall in systolic blood pressure during head-up tilt and improved the cardiovascular response during Valsalva, presumably by altering the neural control of baroreflex activation. [ABSTRACT FROM AUTHOR]

Enhancers and super-enhancers exert indispensable roles in maintaining cell identity through spatiotemporally regulating gene transcription. Meanwhile, active enhancers and super-enhancers also produce transcripts termed enhancer RNAs (eRNAs) from their DNA elements. Although enhancers have been identified for more than 30 years, widespread transcription from enhancers are just discovered by genome-wide sequencing and considered as the key to understand longstanding questions in gene transcription. RNA-transcribed enhancers are marked by histone modifications such as H3K4m1/2 and H3K27Ac, and enriched with transcription regulatory factors such as LDTFs, P300, CBP, BRD4 and MED1. Those regulatory factors might constitute a Mega-Trans-like complex to potently activate enhancers. Compared to mRNAs, eRNAs are quite unstable and play roles at local. Functionally, it has been shown that eRNAs promote formation of enhancer-promoter loops. Several studies also demonstrated that eRNAs help the binding of RNA polymerase II (RNAPII) or transition of paused RNAPII by de-association of the negative elongation factor (NELF) complex. Nevertheless, these proposed mechanisms are not universally accepted and still under controversy. Here, we comprehensively summarize the reported findings and make perspectives for future exploration. We also believe that super-enhancer derived RNAs (seRNAs) might be informative to understand the nature of super-enhancers. [ABSTRACT FROM AUTHOR]

Pain perception can be altered by activity in the periaqueductal gray (PAG). The PAG can decrease the incoming nociceptive signals at the level of the spinal dorsal horn, but it is not clear whether the PAG can also affect the sensory thalamus, ventral posterolateral and ventral posteromedial thalamic nuclei, to modulate pain. However, the PAG and the thalamus have direct connections with each other; so we postulated that the PAG may also modulate pain by inhibiting the sensory nuclei in the thalamus, and that these may also reciprocally influence the PAG. Here, by analyzing the local field potentials recorded from the sensory thalamus and the PAG in chronic pain patients with deep brain stimulation electrodes, we show that PAG stimulation inhibited the sensory thalamus with decreasing thalamic delta, theta, alpha and beta power, and sensory thalamus stimulation excited the PAG with increasing PAG delta and theta power. We demonstrate that the PAG and the sensory thalamus interact reciprocally at short latency, which may be related to pain modulation. [ABSTRACT FROM AUTHOR]

Objective: Kawasaki disease (KD) is characterized by systemic vasculitis of an unknown cause. A previous study has indicated that a polymorphism of the inositol 1,4,5-trisphosphate 3-kinase C ( ITPKC) gene is involved in the susceptibility to KD. ORAI (also known as CRACM1) is one of the components of store-operated calcium channels involved in regulating immune and inflammatory reactions. This study was conducted to investigate if polymorphisms in ORAI1/CRACM1, a gene downstream from ITPKC, are associated with KD susceptibility and clinical outcomes. Materials and Methods: A total of 1,056 subjects (341 KD patients and 715 controls) were investigated to identify five tagging single nucleotide polymorphisms (tSNPs) in ORAI1/CRACM1 (rs12313273, rs6486795, rs7135617, rs12320939, and rs712853) by using the TaqMan Allelic Discrimination assay. Results: No significant associations between genotype and allele frequency of the five ORAI1/CRACM1 tSNPs were observed in the KD patients and controls. In KD patients, no significant associations between ORAI1/CRACM1 polymorphisms and coronary artery lesion (CAL) formation or intravenous immunoglobulin (IVIG) treatment response were observed. The results from haplotype analysis were insignificant. Conclusions: This study showed for the first time that ORAI1/CRACM1 polymorphisms are not associated with KD susceptibility, CAL formation, or IVIG treatment response in the Taiwanese population. [ABSTRACT FROM AUTHOR]