精神分裂症患者及其一级亲属静息态脑功能网络的小世界属性研究

目的:探讨精神分裂症患者及其一级亲属静息态脑功能网络小世界属性特征的异同。方法:对符合DSM-IV诊断标准的33例精神分裂症患者、30例未患病一级亲属和34例健康对照进行静息态脑功能扫描,利用AAL模板将大脑划分为116个脑区并进行网络构建,比较三组被试的网络属性特征。结果:三组静息态脑功能网络均具有小世界属性,但患者组部分脑区节点属性(节点度和节点局部效率)显著异常(p<0.05, Bonferroni校正),主要位于右颞上回、左眶额皮质、左后扣带回和右小脑下叶;亲属组左后扣带回的节点度显著增加。结论:精神分裂症患者和一级亲属都存在左后扣带回节点属性异常,提示左后扣带回功能异常可能是精神分裂症的早期改变且受遗传易感性影响。     

Emerging use of machine learning and advanced technologies to assess red cell quality

Improving blood product quality and patient outcomes is an accepted goal in transfusion medicine research. Thus, there is an urgent need to understand the potential adverse effects on red blood cells (RBCs) during pre-transfusion storage. Current assessment techniques of these degradation events, termed “storage lesions”, are subjective, labor-intensive, and complex. Here we describe emerging technologies that assess the biochemical, biophysical, and morphological characteristics of RBC storage lesions. Of these emerging techniques, machine learning (ML) has shown potential to overcome the limitations of conventional RBC assessment methods. Our previous work has shown that neural networks can extract chronological progressions of morphological changes in RBCs during storage without human input. We hypothesize that, with broader training and testing of multivariate data (e.g., varying donor factors and manufacturing methods), ML can further our understanding of clinical transfusion outcomes in multiple patient groups.     

Right inferior frontal gyrus: An integrative hub in tonal bilinguals

Right hemispheric dominance in tonal bilingualism is still controversial. In this study, we investigated hemispheric dominance in 30 simultaneous Bai‐Mandarin tonal bilinguals and 28 Mandarin monolinguals using multimodal neuroimaging. Resting‐state functional connectivity (RSFC) analysis was first performed to reveal the changes of functional connections within the language‐related network. Voxel‐based morphology (VBM) and tract‐based spatial statistics (TBSS) analyses were then used to identify bilinguals' alterations in gray matter volume (GMV) and fractional anisotropy (FA) of white matter, respectively. RSFC analyses revealed significantly increased functional connections of the right pars‐orbital part of the inferior frontal gyrus (IFG) with right caudate, right pars‐opercular part of IFG, and left inferior temporal gyrus in Bai‐Mandarin bilinguals compared to monolinguals. VBM and TBSS analyses further identified significantly greater GMV in right pars‐triangular IFG and increased FA in right superior longitudinal fasciculus (SLF) in bilinguals than in monolinguals. Taken together, these results demonstrate the integrative role of the right IFG in tonal language processing of bilinguals. Our findings suggest that the intrinsic language network in simultaneous tonal bilinguals differs from that of monolinguals in terms of both function and structure.     

Sensory‐motor network topology in multiple sclerosis: Structural connectivity analysis accounting for intrinsic density discrepancy

Graph theory and network modelling have been previously applied to characterize motor network structural topology in multiple sclerosis (MS). However, between‐group differences disclosed by graph analysis might be primarily driven by discrepancy in density, which is likely to be reduced in pathologic conditions as a consequence of macroscopic damage and fibre loss that may result in less streamlines properly traced. In this work, we employed the convex optimization modelling for microstructure informed tractography (COMMIT) framework, which, given a tractogram, estimates the actual contribution (or weight) of each streamline in order to optimally explain the diffusion magnetic resonance imaging signal, filtering out those that are implausible or not necessary. Then, we analysed the topology of this ‘COMMIT‐weighted sensory‐motor network’ in MS accounting for network density. By comparing with standard connectivity analysis, we also tested if abnormalities in network topology are still identifiable when focusing on more ‘quantitative’ network properties. We found that topology differences identified with standard tractography in MS seem to be mainly driven by density, which, in turn, is strongly influenced by the presence of lesions. We were able to identify a significant difference in density but also in network global and local properties when accounting for density discrepancy. Therefore, we believe that COMMIT may help characterize the structural organization in pathological conditions, allowing a fair comparison of connectomes which considers discrepancies in network density. Moreover, discrepancy‐corrected network properties are clinically meaningful and may help guide prognosis assessment and treatment choice.     

Investigating the temporal dynamics of electroencephalogram (EEG) microstates using recurrent neural networks

Electroencephalogram (EEG) microstates that represent quasi‐stable, global neuronal activity are considered as the building blocks of brain dynamics. Therefore, the analysis of microstate sequences is a promising approach to understand fast brain dynamics that underlie various mental processes. Recent studies suggest that EEG microstate sequences are non‐Markovian and nonstationary, highlighting the importance of the sequential flow of information between different brain states. These findings inspired us to model these sequences using Recurrent Neural Networks (RNNs) consisting of long‐short‐term‐memory (LSTM) units to capture the complex temporal dependencies. Using an LSTM‐based auto encoder framework and different encoding schemes, we modeled the microstate sequences at multiple time scales (200–2,000 ms) aiming to capture stably recurring microstate patterns within and across subjects. We show that RNNs can learn underlying microstate patterns with high accuracy and that the microstate trajectories are subject invariant at shorter time scales (≤400 ms) and reproducible across sessions. Significant drop in the reconstruction accuracy was observed for longer sequence lengths of 2,000 ms. These findings indirectly corroborate earlier studies which indicated that EEG microstate sequences exhibit long‐range dependencies with finite memory content. Furthermore, we find that the latent representations learned by the RNNs are sensitive to external stimulation such as stress while the conventional univariate microstate measures (e.g., occurrence, mean duration, etc.) fail to capture such changes in brain dynamics. While RNNs cannot be configured to identify the specific discriminating patterns, they have the potential for learning the underlying temporal dynamics and are sensitive to sequence aberrations characterized by changes in metal processes. Empowered with the macroscopic understanding of the temporal dynamics that extends beyond short‐term interactions, RNNs offer a reliable alternative for exploring system level brain dynamics using EEG microstate sequences.     

Control the fate of human umbilical cord mesenchymal stem cells with dual‐enzymatically cross‐linked gelatin hydrogels for potential applications in nerve regeneration

Stem‐cell‐based therapy is a promising strategy to treat challenging neurological diseases, while its application is hindered primarily by the low viability and uncontrolled differentiation of stem cell. Hydrogel can be properly engineered to share similar characteristics with the target tissue, thus promoting cell viability and directing cell differentiation. In this study, we proposed a new dual‐enzymatically cross‐linked and injectable gelatin hydrogel for regulating survival, proliferation, and differentiation of human umbilical cord mesenchymal stem cells (hUC‐MSCs) in a three‐dimensional matrix. This injectable gelatin hydrogel was formed by oxidative coupling of gelatin–hydroxyphenyl acid conjugates catalyzed by hydrogen horseradish peroxidase (HRP) and choline oxidase (ChOx). Modulus and H₂O₂ release can be well controlled by ChOx activity. Results from calcein‐AM/PI staining and Ki67 immunofluorescence tests demonstrated that the survival and proliferation behavior of hUC‐MSCs were highly enhanced in HRP_1UChOx_0.25U hydrogel with lower modulus and less H₂O₂ release compared with other groups. Attractively, the expression of neuron‐specific markers β‐III tubulin, neurofilament light chain (NFL), and synapsin‐1 was significantly increased in HRP_1UChOx_0.25U hydrogel as well. Additionally, in vitro hemolysis test and in vivo HE staining data highlighted the good biocompatibility. Undoubtedly, this injectable gelatin hydrogel's ability to control hUC‐MSCs' fate holds enormous potentials in nervous disorders' therapy and nerve regeneration.     

An interdisciplinary approach to investigate collective cell migration in neural crest

The neural crest serves as a powerful and tractable model paradigm for understanding collective cell migration. The neural crest cell populations are well-known for their long-distance collective migration and contribution to diverse cell lineages during vertebrate development. If neural crest cells fail to reach a target or populate an incorrect location, then improper cell differentiation or uncontrolled cell proliferation can result. A wide range of interdisciplinary studies has been carried out to understand the response of neural crest cells to different stimuli and their ability to migrate to distant targets. In this critical commentary, we illustrate how an interdisciplinary collaboration involving experimental and mathematical modeling has led to a deeper understanding of cranial neural crest cell migration. We identify open questions and propose possible ways to start answering some of the challenges arising.     

Connectivity within the default mode network mediates the association between chronotype and sleep quality

A late chronotype is associated with poor sleep quality, but the fundamental neural mechanism underlying this association remains unclear. Eyes‐open resting‐state functional MRI scans were obtained from 87 participants after extended wakefulness, and four subregions of the default mode network were extracted and analysed. Partial correlation analysis revealed that the functional connectivity between the precuneus and the medial prefrontal cortex (mPFC) was significantly correlated both with sleep quality and circadian preference of the participants. Mediation analysis found that the precuneus–mPFC link fully mediated the correlation between chronotype and sleep quality. We concluded that increased neural communication in the midline cores of the default mode network (DMN) may be responsible for the poor sleep quality of late chronotypes. As late chronotypes exhibit vulnerability to many mental disorders, our results can be used to refine pathophysiological models and provide therapy for such psychological disorders.     

Optogenetic manipulation of astrocytes from synapses to neuronal networks: A potential therapeutic strategy for neurodegenerative diseases

Astrocytes are the most widespread and heterogeneous glial cells in the central nervous system and key regulators for brain development. They are capable of receiving neurotransmitters produced by synaptic activities and regulating synaptic functions by releasing gliotransmitters as part of the tripartite synapse. In addition to communicating with neurons at synaptic levels, astrocytes can integrate into inhibitory neural networks to interact with neurons in neuronal circuits. Astrocytes are closely related to the pathogenesis and pathological processes of neurodegenerative diseases (NDs). Recently, optogenetics has now been applied to reveal the function of astrocytes in physiology and pathology. Herein, we discuss the possibility whether optogenetics could be used to control the release of gliotransmitters and regulate astrocytic membrane channels. Thus, the capability of modulating the bidirectional interactions between astrocytes and neurons in both synaptic and neuronal networks via optogenetics is evaluated. Furthermore, we discuss that manipulating astrocytes via optogenetics might be an effective way to investigate the potential therapeutic strategy for NDs.     

Myopathy associated with homozygous PYROXD1 pathogenic variants detected by genome sequencing

Biallelic pathogenic variants in the gene PYROXD1 have recently been described to cause early-onset autosomal recessive myopathy. Myopathy associated with PYROXD1 pathogenic variants is rare and reported in only 17 individuals. Known pathogenic variants in PYROXD1 include missense, insertion and essential splice-site variants. Here we describe a consanguineous family of individuals affected with late-onset myopathy and homozygous PYROXD1 missense variants (NM_024854.5:c.464A>G [p.Asn155Ser]) expanding our understanding of the possible disease phenotypes of PYROXD1-associated myopathy.