Showing papers in "Frontiers in neuroscience in 2023"

Assessing the role of primary healthy microglia and gap junction blocker in hindering Alzheimer’s disease neuroinflammatory type: Early approaches for therapeutic intervention

Abstract: Alzheimer’s disease (AD) is a predominantly heterogeneous disease with a highly complex pathobiology. The presence of amyloid-beta (Aβ) depositions and the accumulation of hyperphosphorylated tau protein remain the characteristic hallmarks of AD. These hallmarks can be detected throughout the brain and other regions, including cerebrospinal fluid (CSF) and the spinal cord. Microglia cells, the brain-resident macrophage type of the brain, are implicated in maintaining healthy brain homeostasis. The localized administration of primary healthy microglia (PHM) is suggested to play a role in mitigating AD hallmark depositions and associated cognitive dysfunction. Carbenoxolone (CBX) is the most common gap junction blocker. It cannot effectively cross the blood–brain barrier (BBB) under systemic administration. Therefore, localized administration of CBX may be a recommended intervention against AD by acting as an antioxidant and anti-inflammatory agent. This study aims to determine whether the localized intracerebroventricular (ICV) administration of PHM and CBX may act as an effective therapeutic intervention for AD neuroinflammatory type. In addition, this study also aims to reveal whether detecting AD hallmarks in the spinal cord and CSF can be considered functional and effective during AD early diagnosis. Male albino rats were divided into four groups: control (group 1), lipopolysaccharide (LPS)-induced AD neuroinflammatory type (group 2), ICV injection of LPS + isolated PHM (group 3), and ICV injection of LPS + CBX (group 4). Morris water maze (MWM) was conducted to evaluate spatial working memory. The brain and spinal cord were isolated from each rat with the collection of CSF. Our findings demonstrate that the localized administration of PHM and CBX can act as promising therapeutic approaches against AD. Additionally, Aβ and tau toxic aggregates were detected in the spinal cord and the CSF of the induced AD model concomitant with the brain tissues. Overall, it is suggested that the ICV administration of PHM and CBX can restore normal brain functions and alleviate AD hallmark depositions. Detecting these depositions in the spinal cord and CSF may be considered in AD early diagnosis. As such, conducting clinical research is recommended to reveal the benefits of related therapeutic approaches compared with preclinical findings.

NeuroCARE: A generic neuromorphic edge computing framework for healthcare applications

Abstract: Highly accurate classification methods for multi-task biomedical signal processing are reported, including neural networks. However, reported works are computationally expensive and power-hungry. Such bottlenecks make it hard to deploy existing approaches on edge platforms such as mobile and wearable devices. Gaining motivation from the good performance and high energy-efficiency of spiking neural networks (SNNs), a generic neuromorphic framework for edge healthcare and biomedical applications are proposed and evaluated on various tasks, including electroencephalography (EEG) based epileptic seizure prediction, electrocardiography (ECG) based arrhythmia detection, and electromyography (EMG) based hand gesture recognition. This approach, NeuroCARE, uses a unique sparse spike encoder to generate spike sequences from raw biomedical signals and makes classifications using the spike-based computing engine that combines the advantages of both CNN and SNN. An adaptive weight mapping method specifically co-designed with the spike encoder can efficiently convert CNN to SNN without performance deterioration. The evaluation results show that the overall performance, including the classification accuracy, sensitivity and F1 score, achieve 92.7, 96.7, and 85.7% for seizure prediction, arrhythmia detection and hand gesture recognition, respectively. In comparison with CNN topologies, the computation complexity is reduced by over 80.7% while the energy consumption and area occupation are reduced by over 80% and over 64.8%, respectively, indicating that the proposed neuromorphic computing approach is energy and area efficient and of high precision, which paves the way for deployment at edge platforms.

Organotopic organization of the porcine mid-cervical vagus nerve

Abstract: Introduction Despite detailed characterization of fascicular organization of somatic nerves, the functional anatomy of fascicles evident in human and large mammal cervical vagus nerve is unknown. The vagus nerve is a prime target for intervention in the field of electroceuticals due to its extensive distribution to the heart, larynx, lungs, and abdominal viscera. However, current practice of the approved vagus nerve stimulation (VNS) technique is to stimulate the entire nerve. This produces indiscriminate stimulation of non-targeted effectors and undesired side effects. Selective neuromodulation is now a possibility with a spatially-selective vagal nerve cuff. However, this requires the knowledge of the fascicular organization at the level of cuff placement to inform selectivity of only the desired target organ or function. Methods and results We imaged function over milliseconds with fast neural electrical impedance tomography and selective stimulation, and found consistent spatially separated regions within the nerve correlating with the three fascicular groups of interest, suggesting organotopy. This was independently verified with structural imaging by tracing anatomical connections from the end organ with microCT and the development of an anatomical map of the vagus nerve. This confirmed organotopic organization. Discussion Here we show, for the first time, localized fascicles in the porcine cervical vagus nerve which map to cardiac, pulmonary and recurrent laryngeal function (N = 4). These findings pave the way for improved outcomes in VNS as unwanted side effects could be reduced by targeted selective stimulation of identified organ-specific fiber-containing fascicles and the extension of this technique clinically beyond the currently approved disorders to treat heart failure, chronic inflammatory disorders, and more.

Quality control practices in FMRI analysis: Philosophy, methods and examples using AFNI

Abstract: Quality control (QC) is a necessary, but often an under-appreciated, part of FMRI processing. Here we describe procedures for performing QC on acquired or publicly available FMRI datasets using the widely used AFNI software package. This work is part of the Research Topic, “Demonstrating Quality Control (QC) Procedures in fMRI.” We used a sequential, hierarchical approach that contained the following major stages: (1) GTKYD (getting to know your data, esp. its basic acquisition properties), (2) APQUANT (examining quantifiable measures, with thresholds), (3) APQUAL (viewing qualitative images, graphs, and other information in systematic HTML reports) and (4) GUI (checking features interactively with a graphical user interface); and for task data, and (5) STIM (checking stimulus event timing statistics). We describe how these are complementary and reinforce each other to help researchers stay close to their data. We processed and evaluated the provided, publicly available resting state data collections (7 groups, 139 total subjects) and task-based data collection (1 group, 30 subjects). As specified within the Topic guidelines, each subject’s dataset was placed into one of three categories: Include, exclude or uncertain. The main focus of this paper, however, is the detailed description of QC procedures: How to understand the contents of an FMRI dataset, to check its contents for appropriateness, to verify processing steps, and to examine potential quality issues. Scripts for the processing and analysis are freely available.

Nitric oxide signaling in ctenophores

Abstract: Nitric oxide (NO) is one of the most ancient and versatile signal molecules across all domains of life. NO signaling might also play an essential role in the origin of animal organization. Yet, practically nothing is known about the distribution and functions of NO-dependent signaling pathways in representatives of early branching metazoans such as Ctenophora. Here, we explore the presence and organization of NO signaling components using Mnemiopsis and kin as essential reference species. We show that NO synthase (NOS) is present in at least eight ctenophore species, including Euplokamis and Coeloplana, representing the most basal ctenophore lineages. However, NOS could be secondarily lost in many other ctenophores, including Pleurobrachia and Beroe. In Mnemiopsis leidyi, NOS is present both in adult tissues and differentially expressed in later embryonic stages suggesting the involvement of NO in developmental mechanisms. Ctenophores also possess soluble guanylyl cyclases as potential NO receptors with weak but differential expression across tissues. Combined, these data indicate that the canonical NO-cGMP signaling pathways existed in the common ancestor of animals and could be involved in the control of morphogenesis, cilia activities, feeding and different behaviors.

Effects of a high-prebiotic diet versus probiotic supplements versus synbiotics on adult mental health: The “Gut Feelings” randomised controlled trial

Abstract: Background Preliminary evidence supports the use of dietary interventions and gut microbiota-targeted interventions such as probiotic or prebiotic supplementation for improving mental health. We report on the first randomised controlled trial (RCT) to examine the effects of a high-prebiotic dietary intervention and probiotic supplements on mental health. Methods “Gut Feelings” was an 8-week, 2 × 2 factorial RCT of 119 adults with moderate psychological distress and low prebiotic food intake. Treatment arms: (1) probiotic supplement and diet-as-usual (probiotic group); (2) high-prebiotic diet and placebo supplement (prebiotic diet group); (3) probiotic supplement and high-prebiotic diet (synbiotic group); and (4) placebo supplement and diet-as-usual (placebo group). The primary outcome was assessment of total mood disturbance (TMD; Profile of Mood States Short Form) from baseline to 8 weeks. Secondary outcomes included anxiety, depression, stress, sleep, and wellbeing measures. Results A modified intention-to-treat analysis using linear mixed effects models revealed that the prebiotic diet reduced TMD relative to placebo at 8 weeks [Cohen’s d = −0.60, 95% confidence interval (CI) = −1.18, −0.03; p = 0.039]. There was no evidence of symptom improvement from the probiotic (d = −0.19, 95% CI = −0.75, 0.38; p = 0.51) or synbiotic treatments (d = −0.03, 95% CI = −0.59, 0.53; p = 0.92). Improved anxiety, stress, and sleep were noted in response to the prebiotic diet while the probiotic tentatively improved wellbeing, relative to placebo. No benefit was found in response to the synbiotic intervention. All treatments were well tolerated with few adverse events. Conclusion A high-prebiotic dietary intervention may improve mood, anxiety, stress, and sleep in adults with moderate psychological distress and low prebiotic intake. A synbiotic combination of high-prebiotic diet and probiotic supplement does not appear to have a beneficial effect on mental health outcomes, though further evidence is required. Results are limited by the relatively small sample size. Clinical trial registration https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372753, identifier ACTRN12617000795392.

Editorial: Functional and structural brain network construction, representation and application

Abstract: COPYRIGHT © 2023 Li, Wang, Hu, Chen and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Editorial: Functional and structural brain network construction, representation and application

Early-stage fusion of EEG and fNIRS improves classification of motor imagery

Abstract: Introduction Many research papers have reported successful implementation of hybrid brain-computer interfaces by complementarily combining EEG and fNIRS, to improve classification performance. However, modality or feature fusion of EEG and fNIRS was usually designed for specific user cases, which were generally customized and hard to be generalized. How to effectively utilize information from the two modalities was still unclear. Methods In this paper, we conducted a study to investigate the stage of bi-modal fusion based on EEG and fNIRS. A Y-shaped neural network was proposed and evaluated on an open dataset, which fuses the bimodal information in different stages. Results The results suggests that the early-stage fusion of EEG and fNIRS have significantly higher performance compared to middle-stage and late-stage fusion network configuration (N = 57, P < 0.05). With the proposed framework, the average accuracy of 29 participants reaches 76.21% in the left-or-right hand motor imagery task in leave-one-out cross-validation, using bi-modal data as network inputs respectively, which is in the same level as the state-of-the-art hybrid BCI methods based on EEG and fNIRS data.

Aging alters across-hemisphere cortical dynamics during binaural temporal processing

Abstract: Differences in the timing and intensity of sounds arriving at the two ears provide fundamental binaural cues that help us localize and segregate sounds in the environment. Neural encoding of these cues is commonly represented asymmetrically in the cortex with stronger activation in the hemisphere contralateral to the perceived spatial location. Although advancing age is known to degrade the perception of binaural cues, less is known about how the neural representation of such cues is impacted by age. Here, we use electroencephalography (EEG) to investigate age-related changes in the hemispheric distribution of interaural time difference (ITD) encoding based on cortical auditory evoked potentials (CAEPs) and derived binaural interaction component (BIC) measures in ten younger and ten older normal-hearing adults. Sensor-level analyses of the CAEP and BIC showed age-related differences in global field power, where older listeners had significantly larger responses than younger for both binaural metrics. Source-level analyses showed hemispheric differences in auditory cortex activity for left and right lateralized stimuli in younger adults, consistent with a contralateral activation model for processing ITDs. Older adults, however, showed reduced hemispheric asymmetry across ITDs, despite having overall larger responses than younger adults. Further, when averaged across ITD condition to evaluate changes in cortical asymmetry over time, there was a significant shift in laterality corresponding to the peak components (P1, N1, P2) in the source waveform that also was affected by age. These novel results demonstrate across-hemisphere cortical dynamics during binaural temporal processing that are altered with advancing age.

Nutrition and adult neurogenesis in the hippocampus: Does what you eat help you remember?

Abstract: Neurogenesis is a complex process by which neural progenitor cells (NPCs)/neural stem cells (NSCs) proliferate and differentiate into new neurons and other brain cells. In adulthood, the hippocampus is one of the areas with more neurogenesis activity, which is involved in the modulation of both emotional and cognitive hippocampal functions. This complex process is affected by many intrinsic and extrinsic factors, including nutrition. In this regard, preclinical studies performed in rats and mice demonstrate that high fats and/or sugars diets have a negative effect on adult hippocampal neurogenesis (AHN). In contrast, diets enriched with bioactive compounds, such as polyunsaturated fatty acids and polyphenols, as well as intermittent fasting or caloric restriction, can induce AHN. Interestingly, there is also growing evidence demonstrating that offspring AHN can be affected by maternal nutrition in the perinatal period. Therefore, nutritional interventions from early stages and throughout life are a promising perspective to alleviate neurodegenerative diseases by stimulating neurogenesis. The underlying mechanisms by which nutrients and dietary factors affect AHN are still being studied. Interestingly, recent evidence suggests that additional peripheral mediators may be involved. In this sense, the microbiota-gut-brain axis mediates bidirectional communication between the gut and the brain and could act as a link between nutritional factors and AHN. The aim of this mini-review is to summarize, the most recent findings related to the influence of nutrition and diet in the modulation of AHN. The importance of maternal nutrition in the AHN of the offspring and the role of the microbiota-gut-brain axis in the nutrition-neurogenesis relationship have also been included.

Experiment protocols for brain-body imaging of locomotion: A systematic review

Abstract: Introduction Human locomotion is affected by several factors, such as growth and aging, health conditions, and physical activity levels for maintaining overall health and well-being. Notably, impaired locomotion is a prevalent cause of disability, significantly impacting the quality of life of individuals. The uniqueness and high prevalence of human locomotion have led to a surge of research to develop experimental protocols for studying the brain substrates, muscle responses, and motion signatures associated with locomotion. However, from a technical perspective, reproducing locomotion experiments has been challenging due to the lack of standardized protocols and benchmarking tools, which impairs the evaluation of research quality and the validation of previous findings. Methods This paper addresses the challenges by conducting a systematic review of existing neuroimaging studies on human locomotion, focusing on the settings of experimental protocols, such as locomotion intensity, duration, distance, adopted brain imaging technologies, and corresponding brain activation patterns. Also, this study provides practical recommendations for future experiment protocols. Results The findings indicate that EEG is the preferred neuroimaging sensor for detecting brain activity patterns, compared to fMRI, fNIRS, and PET. Walking is the most studied human locomotion task, likely due to its fundamental nature and status as a reference task. In contrast, running has received little attention in research. Additionally, cycling on an ergometer at a speed of 60 rpm using fNIRS has provided some research basis. Dual-task walking tasks are typically used to observe changes in cognitive function. Moreover, research on locomotion has primarily focused on healthy individuals, as this is the scenario most closely resembling free-living activity in real-world environments. Discussion Finally, the paper outlines the standards and recommendations for setting up future experiment protocols based on the review findings. It discusses the impact of neurological and musculoskeletal factors, as well as the cognitive and locomotive demands, on the experiment design. It also considers the limitations imposed by the sensing techniques used, including the acceptable level of motion artifacts in brain-body imaging experiments and the effects of spatial and temporal resolutions on brain sensor performance. Additionally, various experiment protocol constraints that need to be addressed and analyzed are explained.

Source localization using recursively applied and projected MUSIC with flexible extent estimation

Abstract: Magneto- and electroencephalography (M/EEG) are widespread techniques to measure neural activity in-vivo at a high temporal resolution but low spatial resolution. Locating the neural sources underlying the M/EEG poses an inverse problem, which is ill-posed. We developed a new method based on Recursive Application of Multiple Signal Classification (MUSIC). Our proposed method is able to recover not only the locations but, in contrast to other inverse solutions, also the extent of active brain regions flexibly (FLEX-MUSIC). This is achieved by allowing it to search not only for single dipoles but also dipole clusters of increasing extent to find the best fit during each recursion. FLEX-MUSIC achieved the highest accuracy for both single dipole and extended sources compared to all other methods tested. Remarkably, FLEX-MUSIC was capable to accurately estimate the level of sparsity in the source space (r = 0.82), whereas all other approaches tested failed to do so (r ≤ 0.18). The average computation time of FLEX-MUSIC was considerably lower compared to a popular Bayesian approach and comparable to that of another recursive MUSIC approach and eLORETA. FLEX-MUSIC produces only few errors and was capable to reliably estimate the extent of sources. The accuracy and low computation time of FLEX-MUSIC renders it an improved technique to solve M/EEG inverse problems both in neuroscience research and potentially in pre-surgery diagnostic in epilepsy.

Optical flow estimation from event-based cameras and spiking neural networks

Abstract: Event-based cameras are raising interest within the computer vision community. These sensors operate with asynchronous pixels, emitting events, or “spikes”, when the luminance change at a given pixel since the last event surpasses a certain threshold. Thanks to their inherent qualities, such as their low power consumption, low latency, and high dynamic range, they seem particularly tailored to applications with challenging temporal constraints and safety requirements. Event-based sensors are an excellent fit for Spiking Neural Networks (SNNs), since the coupling of an asynchronous sensor with neuromorphic hardware can yield real-time systems with minimal power requirements. In this work, we seek to develop one such system, using both event sensor data from the DSEC dataset and spiking neural networks to estimate optical flow for driving scenarios. We propose a U-Net-like SNN which, after supervised training, is able to make dense optical flow estimations. To do so, we encourage both minimal norm for the error vector and minimal angle between ground-truth and predicted flow, training our model with back-propagation using a surrogate gradient. In addition, the use of 3d convolutions allows us to capture the dynamic nature of the data by increasing the temporal receptive fields. Upsampling after each decoding stage ensures that each decoder's output contributes to the final estimation. Thanks to separable convolutions, we have been able to develop a light model (when compared to competitors) that can nonetheless yield reasonably accurate optical flow estimates.

Amino acids integrate behaviors in nerveless placozoans

Abstract: Placozoans are the simplest known free-living animals without recognized neurons and muscles but a complex behavioral repertoire. However, mechanisms and cellular bases of behavioral coordination are unknown. Here, using Trichoplax adhaerens as a model, we described 0.02–0.002 Hz oscillations in locomotory and feeding patterns as evidence of complex multicellular integration; and showed their dependence on the endogenous secretion of signal molecules. Evolutionary conserved low-molecular-weight transmitters (glutamate, aspartate, glycine, GABA, and ATP) acted as coordinators of distinct locomotory and feeding patterns. Specifically, L-glutamate induced and partially mimicked endogenous feeding cycles, whereas glycine and GABA suppressed feeding. ATP-modified feeding is complex, first causing feeding-like cycles and then suppressing feeding. Trichoplax locomotion was modulated by glycine, GABA, and, surprisingly, by animals’ own mucus trails. Mucus triples locomotory speed compared to clean substrates. Glycine and GABA increased the frequency of turns. The effects of the amino acids are likely mediated by numerous receptors (R), including those from ionotropic GluRs, metabotropic GluRs, and GABA-BR families. Eighty-five of these receptors are encoded in the Trichoplax genome, more than in any other animal sequenced. Phylogenetic reconstructions illuminate massive lineage-specific expansions of amino acid receptors in Placozoa, Cnidaria, and Porifera and parallel evolution of nutritional sensing. Furthermore, we view the integration of feeding behaviors in nerveless animals by amino acids as ancestral exaptations that pave the way for co-options of glutamate, glycine, GABA, and ATP as classical neurotransmitters in eumetazoans.

Severe pediatric acute encephalopathy syndromes related to SARS-CoV-2

Abstract: Background and objectives To clarify whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection cause acute encephalopathy in children and which are the most common syndromes that cause them and what are the outcomes. Methods A nationwide web-based survey among all members of the Japanese Society of Child Neurology to identify pediatric patients aged < 18 years who developed acute encephalopathy in Japan between 1 January 2020 and 31 May 2022 associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection confirmed by polymerase chain reaction or antigen tests using pharyngeal swabs. Acute encephalopathy was defined as acute onset of impaired consciousness lasting > 24 h or an altered mental state; neurological symptoms arising within 2 weeks of onset of COVID-19 or multisystem inflammatory syndrome in children (MIS-C)/pediatric inflammatory multisystem syndrome (PIMS); evidence of SARS-CoV-2 infection; and reasonable exclusion of other diseases. Patients were divided into the known clinico-radiological acute encephalopathy syndrome group and unexplained or unclassifiable acute encephalopathy group. Outcomes were assessed by pediatric cerebral performance category (PCPC) score at hospital discharge. Results Of the 3,802 society members, 217 representing institutions responded, and 39 patients with suspected acute encephalopathy were reported, of which 31 met inclusion criteria. Of these patients, 14 were diagnosed with known clinico-radiological acute encephalopathy syndromes, with acute encephalopathy with biphasic seizures and late reduced diffusion (five patients) being the most common. Five developed acute encephalopathy associated with MIS-C/PIMS. Among 31 patients, 9 (29.0%) had severe sequelae or died (PCPC ≥ 4). Two of three patients with encephalopathy with acute fulminant cerebral edema and two with hemorrhagic shock and encephalopathy syndrome died. The PCPC scores were higher in the known clinico-radiological acute encephalopathy syndrome group than in the unexplained or unclassifiable acute encephalopathy group (P < 0.01). Discussion Acute encephalopathy related to SARS-CoV-2 infection was demonstrated to be more severe than that caused by other viruses in Japan. Acute encephalopathy syndromes characterized by specific neuroradiological findings was associated with poor clinical outcomes.

Global trends of traditional Chinese exercises for musculoskeletal disorders treatment research from 2000 to 2022: A bibliometric analysis

Abstract: Background Traditional Chinese exercise has been shown to be effective in relieving long-term chronic pain, physical dysfunction, decreased ability to participate in society and decreased quality of life in musculoskeletal diseases. In recent years, there has been a steady increase in publications on the treatment of musculoskeletal disorders by traditional Chinese exercises. The purpose of this study is to review the characteristics and trends of Chinese traditional exercise studies on musculoskeletal diseases published since 2000 through bibliometric analysis, and identify current research hotspots, so as to guide the direction of future research. Methods Publications regarding traditional Chinese exercises for musculoskeletal disorders from 2000 to 2022 were downloaded from the Web of Science Core Collection. VOSviewer 1.6.18 and CiteSpace V software were used for bibliometric analyses. Bibliometric visualization and comparative analysis were conducted for authors, cited authors, journals, co-cited journals, institutions, countries, references, and keywords. Results A total of 432 articles were obtained, with an upward trend over time. The most productive countries and institutions in this field are the USA (183) and Harvard University (70). Evidence-based Complementary and Alternative Medicine (20) was the most prolific journal, Cochrane Database System Review (758) was the most commonly cited journal. Wang Chenchen published the largest number of articles (18). According to high frequency keywords, the hot spot musculoskeletal disorder and the type of traditional Chinese exercise are knee osteoarthritis and Tai Chi. Conclusion This study provides a scientific perspective for the research of traditional Chinese exercises for musculoskeletal disorders and provides valuable information for researchers to discover the current research status, hot spots and new trends of future research.

Brainstem volume changes in myalgic encephalomyelitis/chronic fatigue syndrome and long COVID patients

Abstract: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID patients have overlapping neurological, autonomic, pain, and post-exertional symptoms. We compared volumes of brainstem regions for 10 ME/CFS (CCC or ICC criteria), 8 long COVID (WHO Delphi consensus), and 10 healthy control (HC) subjects on 3D, T1-weighted MRI images acquired using sub-millimeter isotropic resolution using an ultra-high field strength of 7 Tesla. Group comparisons with HC detected significantly larger volumes in ME/CFS for pons (p = 0.004) and whole brainstem (p = 0.01), and in long COVID for pons (p = 0.003), superior cerebellar peduncle (p = 0.009), and whole brainstem (p = 0.005). No significant differences were found between ME/CFS and long COVID volumes. In ME/CFS, we detected positive correlations between the pons and whole brainstem volumes with “pain” and negative correlations between the midbrain and whole brainstem volumes with “breathing difficulty.” In long COVID patients a strong negative relationship was detected between midbrain volume and “breathing difficulty.” Our study demonstrated an abnormal brainstem volume in both ME/CFS and long COVID consistent with the overlapping symptoms.

Disturbed functional connectivity and topological properties of the frontal lobe in minimally conscious state based on resting-state fNIRS

Abstract: Background Patients in minimally conscious state (MCS) exist measurable evidence of consciousness. The frontal lobe is a crucial part of the brain that encodes abstract information and is closely related to the conscious state. We hypothesized that the disturbance of the frontal functional network exists in MCS patients. Methods We collected the resting-state functional near-infrared spectroscopy (fNIRS) data of fifteen MCS patients and sixteen age- and gender-matched healthy controls (HC). The Coma Recovery Scale-Revised (CRS-R) scale of MCS patients was also composed. The topology of the frontal functional network was analyzed in two groups. Results Compared with HC, the MCS patients showed widely disrupted functional connectivity in the frontal lobe, especially in the frontopolar area and right dorsolateral prefrontal cortex. Moreover, the MCS patients displayed lower clustering coefficient, global efficiency, local efficiency, and higher characteristic path length. In addition, the nodal clustering coefficient and nodal local efficiency in the left frontopolar area and right dorsolateral prefrontal cortex were significantly reduced in MCS patients. Furthermore, the nodal clustering coefficient and nodal local efficiency in the right dorsolateral prefrontal cortex were positively correlated to auditory subscale scores. Conclusion This study reveals that MCS patients’ frontal functional network is synergistically dysfunctional. And the balance between information separation and integration in the frontal lobe is broken, especially the local information transmission in the prefrontal cortex. These findings help us to understand the pathological mechanism of MCS patients better.

Blood–brain barrier endothelial cells in neurodegenerative diseases: Signals from the “barrier”

Abstract: As blood–brain barrier (BBB) disruption emerges as a common problem in the early stages of neurodegenerative diseases, the crucial roles of barrier-type brain endothelial cells (BECs), the primary part of the BBB, have been reported in the pathophysiology of neurodegenerative diseases. The mechanisms of how early vascular dysfunction contributes to the progress of neurodegeneration are still unclear, and understanding BEC functions is a promising start. Our understanding of the BBB has gone through different stages, from a passive diffusion barrier to a mediator of central-peripheral interactions. BECs serve two seemingly paradoxical roles: as a barrier to protect the delicate brain from toxins and as an interface to constantly receive and release signals, thus maintaining and regulating the homeostasis of the brain. Most previous studies about neurodegenerative diseases focus on the loss of barrier functions, and far too little attention has been paid to the active regulations of BECs. In this review, we present the current evidence of BEC dysfunction in neurodegenerative diseases and explore how BEC signals participate in the pathogenesis of neurodegenerative diseases.

Restoring the missing person to personalized medicine and precision psychiatry

Abstract: Precision psychiatry has emerged as part of the shift to personalized medicine and builds on frameworks such as the U.S. National Institute of Mental Health Research Domain Criteria (RDoC), multilevel biological “omics” data and, most recently, computational psychiatry. The shift is prompted by the realization that a one-size-fits all approach is inadequate to guide clinical care because people differ in ways that are not captured by broad diagnostic categories. One of the first steps in developing this personalized approach to treatment was the use of genetic markers to guide pharmacotherapeutics based on predictions of pharmacological response or non-response, and the potential risk of adverse drug reactions. Advances in technology have made a greater degree of specificity or precision potentially more attainable. To date, however, the search for precision has largely focused on biological parameters. Psychiatric disorders involve multi-level dynamics that require measures of phenomenological, psychological, behavioral, social structural, and cultural dimensions. This points to the need to develop more fine-grained analyses of experience, self-construal, illness narratives, interpersonal interactional dynamics, and social contexts and determinants of health. In this paper, we review the limitations of precision psychiatry arguing that it cannot reach its goal if it does not include core elements of the processes that give rise to psychopathological states, which include the agency and experience of the person. Drawing from contemporary systems biology, social epidemiology, developmental psychology, and cognitive science, we propose a cultural-ecosocial approach to integrating precision psychiatry with person-centered care.

Effect of nutrition in Alzheimer’s disease: A systematic review

Abstract: Background and objective Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by declining cognitive ability. Currently, there are no effective treatments for this condition. However, certain measures, such as nutritional interventions, can slow disease progression. Therefore, the objective of this systematic review was to identify and map the updates of the last 5 years regarding the nutritional status and nutritional interventions associated with AD patients. Study design A systematic review. Methods A search was conducted for randomized clinical trials, systematic reviews, and meta-analyses investigating the association between nutritional interventions and AD published between 2018 and 2022 in the PubMed, Web of Science, Scopus, and Cochrane Library databases. A total of 38 studies were identified, of which 17 were randomized clinical trials, and 21 were systematic reviews and/or meta-analyses. Results The results show that the western diet pattern is a risk factor for developing AD. In contrast, the Mediterranean diet, ketogenic diet, and supplementation with omega-3 fatty acids and probiotics are protective factors. This effect is significant only in cases of mild-to-moderate AD. Conclusion Certain nutritional interventions may slow the progression of AD and improve cognitive function and quality of life. Further research is required to draw more definitive conclusions.

Neuronal representation of bimanual arm motor imagery in the motor cortex of a tetraplegia human, a pilot study

Abstract: Introduction How the human brain coordinates bimanual movements is not well-established. Methods Here, we recorded neural signals from a paralyzed individual’s left motor cortex during both unimanual and bimanual motor imagery tasks and quantified the representational interaction between arms by analyzing the tuning parameters of each neuron. Results We found a similar proportion of neurons preferring each arm during unimanual movements, however, when switching to bimanual movements, the proportion of contralateral preference increased to 71.8%, indicating contralateral lateralization. We also observed a decorrelation process for each arm’s representation across the unimanual and bimanual tasks. We further confined that these changes in bilateral relationships are mainly caused by the alteration of tuning parameters, such as the increased bilateral preferred direction (PD) shifts and the significant suppression in bilateral modulation depths (MDs), especially the ipsilateral side. Discussion These results contribute to the knowledge of bimanual coordination and thus the design of cutting-edge bimanual brain-computer interfaces.

Gut-brain axis: Mechanisms and potential therapeutic strategies for ischemic stroke through immune functions

Abstract: After an ischemic stroke (IS) occurs, immune cells begin traveling to the brain and immune system from the gut and gastrointestinal tract, where most of them typically reside. Because the majority of the body’s macrophages and more than 70% of the total immune cell pool are typically found within the gut and gastrointestinal tract, inflammation and immune responses in the brain and immune organs require the mobilization of a large number of immune cells. The bidirectional communication pathway between the brain and gut is often referred to as the gut-brain axis. IS usually leads to intestinal motility disorders, dysbiosis of intestinal microbiota, and a leaky gut, which are often associated with poor prognosis in patients with IS. In recent years, several studies have suggested that intestinal inflammation and immune responses play key roles in the development of IS, and thus may become potential therapeutic targets that can drive new therapeutic strategies. However, research on gut inflammation and immune responses after stroke remains in its infancy. A better understanding of gut inflammation and immune responses after stroke may be important for developing effective therapies. This review discusses the immune-related mechanisms of the gut-brain axis after IS and compiles potential therapeutic targets to provide new ideas and strategies for the future effective treatment of IS.

Motivation in the metaverse: A dual-process approach to consumer choices in a virtual reality supermarket

Abstract: Introduction Consumer decision-making processes involve a complex interrelation between perception, emotion, and cognition. Despite a vast and diverse literature, little effort has been invested in investigating the neural mechanism behind such processes. Methods In the present work, our interest was to investigate whether asymmetrical activation of the frontal lobe of the brain could help to characterize consumer’s choices. To obtain stronger experimental control, we devised an experiment in a virtual reality retail store, while simultaneously recording participant brain responses using electroencephalogram (EEG). During the virtual store test, participants completed two tasks; first, to choose items from a predefined shopping list, a phase we termed as “planned purchase”. Second, subjects were instructed that they could also choose products that were not on the list, which we labeled as “unplanned purchase.” We assumed that the planned purchases were associated with a stronger cognitive engagement, and the second task was more reliant on immediate emotional responses. Results By analyzing the EEG data based on frontal asymmetry measures, we find that frontal asymmetry in the gamma band reflected the distinction between planned and unplanned decisions, where unplanned purchases were accompanied by stronger asymmetry deflections (relative frontal left activity was higher). In addition, frontal asymmetry in the alpha, beta, and gamma ranges illustrate clear differences between choices and no-choices periods during the shopping tasks. Discussion These results are discussed in light of the distinction between planned and unplanned purchase in consumer situations, how this is reflected in the relative cognitive and emotional brain responses, and more generally how this can influence research in the emerging area of virtual and augmented shopping.

Ergothioneine, a dietary antioxidant improves amyloid beta clearance in the neuroretina of a mouse model of Alzheimer’s disease

Abstract: Introduction Ergothioneine (Ergo) is a naturally occurring dietary antioxidant. Ergo uptake is dependent on the transporter, organic cation transporter novel-type 1 (OCTN1) distribution. OCTN1 is highly expressed in blood cells (myeloid lineage cells), brain and ocular tissues that are likely predisposed to oxidative stress. Ergo may protect the brain and eye against oxidative damage and inflammation, however, the underlying mechanism remains unclear. Amyloid beta (Aβ) clearance is a complex process mediated by various systems and cell types including vascular transport across the blood–brain barrier, glymphatic drainage, and engulfment and degradation by resident microglia and infiltrating innate immune cells. Impaired Aβ clearance is a major cause for Alzheimer’s disease (AD). Here we investigated neuroretinas to explore the neuroprotective effect of Ergo in a transgenic AD mouse model. Methods Age-matched groups of Ergo-treated 5XFAD, non-treated 5XFAD, and C57BL/6J wildtype (WT controls) were used to assess Ergo transporter OCTN1 expression and Aβ load along with microglia/macrophage (IBA1) and astrocyte (GFAP) markers in wholemount neuroretinas (n = 26) and eye cross-sections (n = 18). Immunoreactivity was quantified by fluorescence or by semi-quantitative assessments. Results and discussion OCTN1 immunoreactivity was significantly low in the eye cross-sections of Ergo-treated and non-treated 5XFAD vs. WT controls. Strong Aβ labeling, detected in the superficial layers in the wholemounts of Ergo-treated 5XFAD vs. non-treated 5XFAD reflects the existence of an effective Aβ clearance system. This was supported by imaging of cross-sections where Aβ immunoreactivity was significantly low in the neuroretina of Ergo-treated 5XFAD vs. non-treated 5XFAD. Moreover, semi-quantitative analysis in wholemounts identified a significantly reduced number of large Aβ deposits or plaques, and a significantly increased number of IBA1(+)ve blood-derived phagocytic macrophages in Ergo-treated 5XFAD vs. non-treated 5XFAD. In sum, enhanced Aβ clearance in Ergo-treated 5XFAD suggests that Ergo uptake may promote Aβ clearance possibly by blood-derived phagocytic macrophages and via perivascular drainage.

Neurointerface with oscillator motifs for inhibitory effect over antagonist muscles

Abstract: The effect of inhibitory management is usually underestimated in artificial control systems, using biological analogy. According to our hypothesis, the muscle hypertonus could be effectively compensated via stimulation by bio-plausible patterns. We proposed an approach for the compensatory stimulation device as implementation of previously presented architecture of the neurointerface, where (1) the neuroport is implemented as a DAC and stimulator, (2) neuroterminal is used for neurosimulation of a set of oscillator motifs on one-board computer. In the set of experiments with five volunteers, we measured the efficacy of motor neuron inhibition via the antagonist muscle or nerve stimulation registering muscle force with and without antagonist stimulation. For the agonist activation, we used both voluntary activity and electrical stimulation. In the case of stimulation of both the agonist and the antagonist muscles and nerves, we experimented with delays between muscle stimulation in the range of 0–20 ms. We registered the subjective discomfort rate. We did not identify any significant difference between the antagonist muscle and nerve stimulation in both voluntary activity and electrical stimulation of cases showing agonist activity. We determined the most effective delay between the stimulation of the agonist and the antagonist muscles and nerves as 10–20 ms.

Sphingolipids in neurodegenerative diseases

Abstract: Neurodegenerative Diseases (NDDs) are a group of disorders that cause progressive deficits of neuronal function. Recent evidence argues that sphingolipid metabolism is affected in a surprisingly broad set of NDDs. These include some lysosomal storage diseases (LSDs), hereditary sensory and autonomous neuropathy (HSAN), hereditary spastic paraplegia (HSP), infantile neuroaxonal dystrophy (INAD), Friedreich’s ataxia (FRDA), as well as some forms of amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD). Many of these diseases have been modeled in Drosophila melanogaster and are associated with elevated levels of ceramides. Similar changes have also been reported in vertebrate cells and mouse models. Here, we summarize studies using fly models and/or patient samples which demonstrate the nature of the defects in sphingolipid metabolism, the organelles that are implicated, the cell types that are initially affected, and potential therapeutics for these diseases.

An objective model for diagnosing comorbid cognitive impairment in patients with epilepsy based on the clinical-EEG functional connectivity features

Abstract: Objective Cognitive impairment (CI) is a common disorder in patients with epilepsy (PWEs). Objective assessment method for diagnosing CI in PWEs would be beneficial in reality. This study proposed to construct a diagnostic model for CI in PWEs using the clinical and the phase locking value (PLV) functional connectivity features of the electroencephalogram (EEG). Methods PWEs who met the inclusion and exclusion criteria were divided into a cognitively normal (CON) group (n = 55) and a CI group (n = 76). The 23 clinical features and 684 PLVEEG features at the time of patient visit were screened and ranked using the Fisher score. Adaptive Boosting (AdaBoost) and Gradient Boosting Decision Tree (GBDT) were used as algorithms to construct diagnostic models of CI in PWEs either with pure clinical features, pure PLVEEG features, or combined clinical and PLVEEG features. The performance of these models was assessed using a five-fold cross-validation method. Results GBDT-built model with combined clinical and PLVEEG features performed the best with accuracy, precision, recall, F1-score, and an area under the curve (AUC) of 90.11, 93.40, 89.50, 91.39, and 0.95%. The top 5 features found to influence the model performance based on the Fisher scores were the magnetic resonance imaging (MRI) findings of the head for abnormalities, educational attainment, PLVEEG in the beta (β)-band C3-F4, seizure frequency, and PLVEEG in theta (θ)-band Fp1-Fz. A total of 12 of the top 5% of features exhibited statistically different PLVEEG features, while eight of which were PLVEEG features in the θ band. Conclusion The model constructed from the combined clinical and PLVEEG features could effectively identify CI in PWEs and possess the potential as a useful objective evaluation method. The PLVEEG in the θ band could be a potential biomarker for the complementary diagnosis of CI comorbid with epilepsy.

Multi-head attention-based masked sequence model for mapping functional brain networks

Abstract: The investigation of functional brain networks (FBNs) using task-based functional magnetic resonance imaging (tfMRI) has gained significant attention in the field of neuroimaging. Despite the availability of several methods for constructing FBNs, including traditional methods like GLM and deep learning methods such as spatiotemporal self-attention mechanism (STAAE), these methods have design and training limitations. Specifically, they do not consider the intrinsic characteristics of fMRI data, such as the possibility that the same signal value at different time points could represent different brain states and meanings. Furthermore, they overlook prior knowledge, such as task designs, during training. This study aims to overcome these limitations and develop a more efficient model by drawing inspiration from techniques in the field of natural language processing (NLP). The proposed model, called the Multi-head Attention-based Masked Sequence Model (MAMSM), uses a multi-headed attention mechanism and mask training approach to learn different states corresponding to the same voxel values. Additionally, it combines cosine similarity and task design curves to construct a novel loss function. The MAMSM was applied to seven task state datasets from the Human Connectome Project (HCP) tfMRI dataset. Experimental results showed that the features acquired by the MAMSM model exhibit a Pearson correlation coefficient with the task design curves above 0.95 on average. Moreover, the model can extract more meaningful networks beyond the known task-related brain networks. The experimental results demonstrated that MAMSM has great potential in advancing the understanding of functional brain networks.

N6-methyladenosine RNA is modified in the rat hippocampus following traumatic brain injury with hypothermia treatment

Abstract: Recent studies have suggested a role for N6-methyladenosine (m6A) modification in neurological diseases. Hypothermia, a commonly used treatment for traumatic brain injury, plays a neuroprotective role by altering m6A modifications. In this study, methylated RNA immunoprecipitation sequencing (MeRIP-Seq) was applied to conduct a genome-wide analysis of RNA m6A methylation in the rat hippocampus of Sham and traumatic brain injury (TBI) groups. In addition, we identified the expression of mRNA in the rat hippocampus after TBI with hypothermia treatment. Compared with the Sham group, the sequencing results of the TBI group showed that 951 different m6A peaks and 1226 differentially expressed mRNAs were found. We performed cross-linking analysis of the data of the two groups. The result showed that 92 hyper-methylated genes were upregulated, 13 hyper-methylated genes were downregulated, 25 hypo-methylated genes were upregulated, and 10 hypo-methylated genes were downregulated. Moreover, a total of 758 differential peaks were identified between TBI and hypothermia treatment groups. Among these differential peaks, 173 peaks were altered by TBI and reversed by hypothermia treatment, including Plat, Pdcd5, Rnd3, Sirt1, Plaur, Runx1, Ccr1, Marveld1, Lmnb2, and Chd7. We found that hypothermia treatment transformed some aspects of the TBI-induced m6A methylation landscape of the rat hippocampus.