Frontiers in Neuroscience

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ISSN / EISSN : 1662-453X / 1662-453X
Published by: Frontiers Media SA (10.3389)
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Xincheng Cao, , Binqiang Chen, Weifang Sun, Guowei Tan
Published: 15 October 2021
Frontiers in Neuroscience, Volume 15; https://doi.org/10.3389/fnins.2021.760987

Abstract:
Accurate identification of the type of seizure is very important for the treatment plan and drug prescription of epileptic patients. Artificial intelligence has shown considerable potential in the fields of automated EEG analysis and seizure classification. However, the highly personalized representation of epileptic seizures in EEG has led to many research results that are not satisfactory in clinical applications. In order to improve the clinical adaptability of the algorithm, this paper proposes an adversarial learning-driven domain-invariant deep feature representation method, which enables the hybrid deep networks (HDN) to reliably identify seizure types. In the train phase, we first use the labeled multi-lead EEG short samples to train squeeze-and-excitation networks (SENet) to extract short-term features, and then use the compressed samples to train the long short-term memory networks (LSTM) to extract long-time features and construct a classifier. In the inference phase, we first adjust the feature mapping of LSTM through the adversarial learning between LSTM and clustering subnet so that the EEG of the target patient and the EEG in the database obey the same distribution in the deep feature space. Finally, we use the adjusted classifier to identify the type of seizure. Experiments were carried out based on the TUH EEG Seizure Corpus and CHB-MIT seizure database. The experimental results show that the proposed domain adaptive deep feature representation improves the classification accuracy of the hybrid deep model in the target set by 5%. It is of great significance for the clinical application of EEG automatic analysis equipment.
Kyle R. Gossman, Benjamin Dykstra, Byron H. García, Arielle P. Swopes, Adam Kimbrough,
Published: 15 October 2021
Frontiers in Neuroscience, Volume 15; https://doi.org/10.3389/fnins.2021.748431

Abstract:
Complex social behaviors are governed by a neural network theorized to be the social decision-making network (SDMN). However, this theoretical network is not tested on functional grounds. Here, we assess the organization of regions in the SDMN using c-Fos, to generate functional connectivity models during specific social interactions in a socially monogamous rodent, the prairie voles (Microtus ochrogaster). Male voles displayed robust selective affiliation toward a female partner, while exhibiting increased threatening, vigilant, and physically aggressive behaviors toward novel males and females. These social interactions increased c-Fos levels in eight of the thirteen brain regions of the SDMN. Each social encounter generated a distinct correlation pattern between individual brain regions. Thus, hierarchical clustering was used to characterize interrelated regions with similar c-Fos activity resulting in discrete network modules. Functional connectivity maps were constructed to emulate the network dynamics resulting from each social encounter. Our partner functional connectivity network presents similarities to the theoretical SDMN model, along with connections in the network that have been implicated in partner-directed affiliation. However, both stranger female and male networks exhibited distinct architecture from one another and the SDMN. Further, the stranger-evoked networks demonstrated connections associated with threat, physical aggression, and other aversive behaviors. Together, this indicates that distinct patterns of functional connectivity in the SDMN can be detected during select social encounters.
Published: 14 October 2021
Frontiers in Neuroscience, Volume 15; https://doi.org/10.3389/fnins.2021.691016

Abstract:
“Chronic” periodontitis and its keystone pathogen Porphyromonas gingivalis have repeatedly been associated with Alzheimer’s disease (AD). Pathological hallmarks in AD are brain accumulations of amyloid-beta and neurofibrillary tangles consisting of aggregated and hyperphosphorylated tau. In addition, neuroinflammation induced by P. gingivalis has increasingly been recognized as a factor in the pathogenesis of AD. The present mini-review discusses possible mechanisms for the induction of neuroinflammation by P. gingivalis in AD, involving factors such as pro-inflammatory mediators, amyloid-beta, tau, microglia, cathepsin B, and protein kinase R. Inflammagens of P. gingivalis such as lipopolysaccharide and gingipains are also discussed.
, Laura Montiel-Trejo, Iván Oliver-Domínguez, , Karina Mendoza-Ángeles
Published: 14 October 2021
Frontiers in Neuroscience, Volume 15; https://doi.org/10.3389/fnins.2021.694924

Abstract:
In vertebrates like mammals and birds, two types of sleep have been identified: rapid eye movement and non-rapid eye movement sleep. Each one is associated with specific electroencephalogram patterns and is accompanied by variations in cardiac and respiratory frequencies. Sleep has been demonstrated only in a handful of invertebrates, and evidence for different sleep stages remains elusive. Previous results show that crayfish sleeps while lying on one side on the surface of the water, but it is not known if this animal has sleep phases. Heart rate and respiratory frequency are modified by diverse changes in the crayfish environment during wakefulness, and previously, we showed that variations in these variables are present during sleep despite that there are no autonomic anatomical structures described in this animal. Here, we conducted experiments to search for sleep phases in crayfish and the relationships between sleep and cardiorespiratory activity. We used the wavelet transform, grouping analysis with k-means clustering, and principal component analysis, to analyze brain and cardiorespiratory electrical activity. Our results show that (a) crayfish can sleep lying on one side or when it is motionless and (b) the depth of sleep (measured as the power of electroencephalographic activity) changes over time and is accompanied by oscillations in cardiorespiratory signal amplitude and power. Finally, we propose that in crayfish there are at least three phases of sleep.
Wanxin Chen, Xiaoxia Sun, Libin Zhan, Wen Zhou, Tingting Bi
Published: 14 October 2021
Frontiers in Neuroscience, Volume 15; https://doi.org/10.3389/fnins.2021.767560

Abstract:
Background and Purpose: Neurodegenerative diseases are associated with metabolic disturbances. Pyruvate dehydrogenase E1 component subunit alpha (PDHA1) is an essential component in the process of glucose metabolism, and its deficiency exists in various diseases such as Alzheimer’s disease (AD), epilepsy, Leigh’s syndrome, and diabetes-associated cognitive decline. However, the exact role of PDHA1 deficiency in neurodegenerative diseases remains to be elucidated. In this study, we explored the effect of PDHA1 deficiency on cognitive function and its molecular mechanism. Methods: A hippocampus-specific Pdha1 knockout (Pdha1 –/–) mouse model was established, and behavioral tests were used to evaluate the cognitive function of mice. Transmission electron microscopy (TEM) was performed to observe the morphological changes of the hippocampus. The lactate level in the hippocampus was measured. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to explore the possible mechanism of the effect of PDHA1 on cognition. Results: Pdha1 knockout damaged the spatial memory of mice and led to the ultrastructural disorder of hippocampal neurons. Lactate accumulation and abnormal lactate transport occurred in Pdha1 –/– mice, and the cyclic AMP-protein kinase A-cAMP response element-binding protein (cAMP/PKA/CREB) pathway was inhibited. Conclusion: Lactate accumulation caused by PDHA1 deficiency in the hippocampus may impair cognitive function by inhibiting the cAMP/PKA/CREB pathway.
, Elaheh Zendehrouh, Vince D. Calhoun, Jessica A. Turner
Published: 14 October 2021
Frontiers in Neuroscience, Volume 15; https://doi.org/10.3389/fnins.2021.708387

Abstract:
Introduction: Individuals with schizophrenia have consistent gray matter reduction throughout the cortex when compared to healthy individuals. However, the reduction patterns vary based on the quantity (concentration or volume) utilized by study. The objective of this study was to identify commonalities between gray matter concentration and gray matter volume effects in schizophrenia. Methods: We performed both univariate and multivariate analyses of case/control effects on 145 gray matter images from 66 participants with schizophrenia and 79 healthy controls, and processed to compare the concentration and volume estimates. Results: Diagnosis effects in the univariate analysis showed similar areas of volume and concentration reductions in the insula, occipitotemporal gyrus, temporopolar area, and fusiform gyrus. In the multivariate analysis, healthy controls had greater gray matter volume and concentration additionally in the superior temporal gyrus, prefrontal cortex, cerebellum, calcarine, and thalamus. In the univariate analyses there was moderate overlap between gray matter concentration and volume across the entire cortex (r = 0.56, p = 0.02). The multivariate analyses revealed only low overlap across most brain patterns, with the largest correlation (r = 0.37) found in the cerebellum and vermis. Conclusions: Individuals with schizophrenia showed reduced gray matter volume and concentration in previously identified areas of the prefrontal cortex, cerebellum, and thalamus. However, there were only moderate correlations across the cortex when examining the different gray matter quantities. Although these two quantities are related, concentration and volume do not show identical results, and therefore, should not be used interchangeably in the literature.
Anna Macias, Jakub Piotr Fichna, Malgorzata Topolewska, Maria J. Rȩdowicz, Anna M. Kaminska,
Published: 14 October 2021
Frontiers in Neuroscience, Volume 15; https://doi.org/10.3389/fnins.2021.692482

Abstract:
Limb–girdle muscular dystrophy type R1 (LGMDR1) is caused by mutations in CAPN3 and is the most common type of recessive LGMD. Even with the use of whole-exome sequencing (WES), only one mutant allele of CAPN3 is found in a significant number of LGMDR patients. This points to a role of non-coding, intronic or regulatory, sequence variants in the disease pathogenesis. Targeted sequencing of the whole CAPN3 gene including not only intronic, 3′ and 5′ UTRs but also potential regulatory regions was performed in 27 patients suspected with LGMDR1. This group included 13 patients with only one mutated CAPN3 allele detected previously with exome sequencing. A second rare variant in the non-coding part of CAPN3 was found in 11 of 13 patients with previously identified single mutation. Intronic mutations were found in 10 cases, with c.1746-20C>G variant present in seven patients. In addition, a large deletion of exons 2–8 was found in one patient. In the patients with no causative mutation previously found, we detected rare CAPN3 variants in 5 out of 10 patients and in two of them in a compound heterozygous state. Rare variants within putative regulatory sequences distant from the CAPN3 gene were found in 15 patients, although in 11 of these cases, other variants are deemed causative. The results indicate that intronic mutations are common in Polish LGMDR patients, and testing for non-coding mutations in CAPN3 should be performed in apparently single heterozygous patients.
Tianwen Chen, Jun Huang, Yue Yu, Xuehui Tang, Chunming Zhang, Youguo Xu, Alberto Arteaga, Jerome Allison, William Mustain, Matthew C. Donald, et al.
Published: 14 October 2021
Frontiers in Neuroscience, Volume 15; https://doi.org/10.3389/fnins.2021.741571

Abstract:
Vestibular evoked myogenic potentials (VEMP) have been used to assess otolith function in clinics worldwide. However, there are accumulating evidence suggesting that the clinically used sound stimuli activate not only the otolith afferents, but also the canal afferents, indicating canal contributions to the VEMPs. To better understand the neural mechanisms underlying the VEMPs and develop discriminative VEMP protocols, we further examined sound-evoked responses of the vestibular nucleus neurons and the abducens neurons, which have the interneurons and motoneurons of the vestibulo-ocular reflex (VOR) pathways. Air-conducted clicks (50–80 dB SL re ABR threshold, 0.1 ms duration) or tone bursts (60–80 dB SL, 125–4,000 Hz, 8 ms plateau, 1 ms rise/fall) were delivered to the ears of Sprague-Dawley or Long-Evans rats. Among 425 vestibular nucleus neurons recorded in anesthetized rats and 18 abducens neurons recorded in awake rats, sound activated 35.9% of the vestibular neurons that increased discharge rates for ipsilateral head rotation (Type I neuron), 15.7% of the vestibular neurons that increased discharge rates for contralateral head rotation (Type II neuron), 57.2% of the vestibular neurons that did not change discharge rates during head rotation (non-canal neuron), and 38.9% of the abducens neurons. Sound sensitive vestibular nucleus neurons and abducens neurons exhibited characteristic tuning curves that reflected convergence of canal and otolith inputs in the VOR pathways. Tone bursts also evoked well-defined eye movements that increased with tone intensity and duration and exhibited peak frequency of ∼1,500 Hz. For the left eye, tone bursts evoked upward/rightward eye movements for ipsilateral stimulation, and downward/leftward eye movements for contralateral stimulation. These results demonstrate that sound stimulation results in activation of the canal and otolith VOR pathways that can be measured by eye tracking devices to develop discriminative tests of vestibular function in animal models and in humans.
Ke Song, Yong Wang, Mei-Xia Ren, Jiao Li, Ting Su, Si-Yi Chen, Yi Shao, Ya-Li Lv
Published: 14 October 2021
Frontiers in Neuroscience, Volume 15; https://doi.org/10.3389/fnins.2021.718973

Abstract:
Background: Using resting-state functional connectivity (rsFC), we investigated alternations in spontaneous brain activities reflected by functional connectivity density (FCD) in patients with optic neuritis (ON). Methods: We enrolled 28 patients with ON (18 males, 10 females) and 24 healthy controls (HCs; 16 males, 8 females). All subjects underwent functional magnetic resonance imaging (fMRI) in a quiet state to determine the values of rsFC, long-range FCD (longFCD), and short-range FCD (IFCD). Receiver operating characteristic (ROC) curves were generated to distinguish patients from HCs. Results: The ON group exhibited obviously lower longFCD values in the left inferior frontal gyrus triangle, the right precuneus and the right anterior cingulate, and paracingulate gyri/median cingulate and paracingulate gyri. The left median cingulate and paracingulate gyri and supplementary motor area (SMA) were also significantly lower. Obviously reduced IFCD values were observed in the left middle temporal gyrus/angular gyrus/SMA and right cuneus/SMA compared with HCs. Conclusion: Abnormal neural activities were found in specific brain regions in patients with ON. Specifically, they showed significant changes in rsFC, longFCD, and IFCD values. These may be useful to identify the specific mechanism of change in brain function in ON.
, David J. Brinkman, Claire Mackaaij, Peter G. J. Nikkels, Martijn A. Nolte, Misha D. Luyer, Wouter J. de Jonge, Ronald L. A. W. Bleys
Published: 14 October 2021
Frontiers in Neuroscience, Volume 15; https://doi.org/10.3389/fnins.2021.726825

Abstract:
Introduction: The cholinergic anti-inflammatory pathway (CAIP) has been proposed as an efferent neural pathway dampening the systemic inflammatory response via the spleen. The CAIP activates the splenic neural plexus and a subsequent series of intrasplenic events, which at least require a close association between sympathetic nerves and T cells. Knowledge on this pathway has mostly been derived from rodent studies and only scarce information is available on the innervation of the human spleen. This study aimed to investigate the sympathetic innervation of different structures of the human spleen, the topographical association of nerves with T cells and age-related variations in nerve distribution. Materials and Methods: Spleen samples were retrieved from a diagnostic archive and were allocated to three age groups; neonates, 10–25 and 25–70 years of age. Sympathetic nerves and T cells were identified by immunohistochemistry for tyrosine hydroxylase (TH) and the membrane marker CD3, respectively. The overall presence of sympathetic nerves and T cells was semi-automatically quantified and expressed as total area percentage. A predefined scoring system was used to analyze the distribution of nerves within different splenic structures. Results: Sympathetic nerves were observed in all spleens and their number appeared to slightly increase from birth to adulthood and to decrease afterward. Irrespective to age, more than halve of the periarteriolar lymphatic sheaths (PALSs) contained sympathetic nerves in close association with T cells. Furthermore, discrete sympathetic nerves were observed in the capsule, trabeculae and red pulp and comparable to the total amount of sympathetic nerves, showed a tendency to decrease with age. No correlation was found between the number of T cells and sympathetic nerves. Conclusion: The presence of discrete sympathetic nerves in the splenic parenchyma, capsule and trabecular of human spleens could suggest a role in functions other than vasoregulation. In the PALS, sympathetic nerves were observed to be in proximity to T cells and is suggestive for the existence of the CAIP in humans. Since sympathetic nerve distribution shows interspecies and age-related variation, and our general understanding of the relative and spatial contribution of splenic innervation in immune regulation is incomplete, it remains difficult to estimate the anti-inflammatory potential of targeting splenic nerves in patients.
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