bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurological Consequences of SARS-CoV-2 Infection and Concurrence of Treatment-Induced Neuropsychiatric Adverse Events in COVID-19 Patients: Navigating the Uncharted
Authors: Borah Pobitra , Deb Pran Kishore , Chandrasekaran Balakumar , Goyal Manoj , Bansal Monika , Hussain Snawar , Shinu Pottathil , Venugopala Katharigatta N. , Al-Shar’i Nizar A. , Deka Satyendra , Singh Vinayak
Published: February 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to the angiotensin-converting enzyme 2 (ACE2) receptor and invade the human cells to cause COVID-19-related pneumonia. Despite an emphasis on respiratory complications, the evidence of neurological manifestations of SARS-CoV-2 infection is rapidly growing, which is substantially contributing to morbidity and mortality. The neurological disorders associated with COVID-19 may have several pathophysiological underpinnings, which are yet to be explored. Hypothetically, SARS-CoV-2 may affect the central nervous system (CNS) either by direct mechanisms like neuronal retrograde dissemination and hematogenous dissemination, or via indirect pathways. CNS complications associated with COVID-19 include encephalitis, acute necrotizing encephalopathy, diffuse leukoencephalopathy, stroke (both ischemic and hemorrhagic), venous sinus thrombosis, meningitis, and neuroleptic malignant syndrome. These may result from different mechanisms, including direct virus infection of the CNS, virus-induced hyper-inflammatory states, and post-infection immune responses. On the other hand, the Guillain-Barre syndrome, hyposmia, hypogeusia, and myopathy are the outcomes of peripheral nervous system injury. Although the therapeutic potential of certain repurposed drugs has led to their off-label use against COVID-19, such as anti-retroviral drugs (remdesivir, favipiravir, and lopinavir-ritonavir combination), biologics (tocilizumab), antibiotics (azithromycin), antiparasitics (chloroquine and hydroxychloroquine), and corticosteroids (dexamethasone), unfortunately, the associated clinical neuropsychiatric adverse events remains a critical issue. Therefore, COVID-19 represents a major threat to the field of neuropsychiatry, as both the virus and the potential therapies may induce neurologic as well as psychiatric disorders. Notably, potential COVID-19 medications may also interact with the medications of pre-existing neuropsychiatric diseases, thereby further complicating the condition. From this perspective, this review will discuss the possible neurological manifestations and sequelae of SARS-CoV-2 infection with emphasis on the probable underlying neurotropic mechanisms. Additionally, we will highlight the concurrence of COVID-19 treatment-associated neuropsychiatric events and possible clinically relevant drug interactions, to provide a useful framework and help researchers, especially the neurologists in understanding the neurologic facets of the ongoing pandemic to control the morbidity and mortality.
Mitochondrial Dysfunction and Oxidative Stress in Alzheimer’s Disease
Authors: Misrani Afzal , Tabassum Sidra , Yang Li
Published: February 2021

Mitochondria play a pivotal role in bioenergetics and respiratory functions, which are essential for the numerous biochemical processes underpinning cell viability. Mitochondrial morphology changes rapidly in response to external insults and changes in metabolic status via fission and fusion processes (so-called mitochondrial dynamics) that maintain mitochondrial quality and homeostasis. Damaged mitochondria are removed by a process known as mitophagy, which involves their degradation by a specific autophagosomal pathway. Over the last few years, remarkable efforts have been made to investigate the impact on the pathogenesis of Alzheimer’s disease (AD) of various forms of mitochondrial dysfunction, such as excessive reactive oxygen species (ROS) production, mitochondrial Ca2+ dyshomeostasis, loss of ATP, and defects in mitochondrial dynamics and transport, and mitophagy. Recent research suggests that restoration of mitochondrial function by physical exercise, an antioxidant diet, or therapeutic approaches can delay the onset and slow the progression of AD. In this review, we focus on recent progress that highlights the crucial role of alterations in mitochondrial function and oxidative stress in the pathogenesis of AD, emphasizing a framework of existing and potential therapeutic approaches.
Cerebral Small Vessel Disease Load Predicts Functional Outcome and Stroke Recurrence After Intracerebral Hemorrhage: A Median Follow-Up of 5 Years
Authors: Xu Mangmang , Li Baojin , Zhong Di , Cheng Yajun , Wu Qian , Zhang Shuting , Zhang Shihong , Wu Bo , Liu Ming
Published: February 2021

Background: Uncertainty exists over the long-term prognostic significance of cerebral small vessel disease (CSVD) in primary intracerebral hemorrhage (ICH).

Methods: We performed a longitudinal analysis of CSVD and clinical outcomes in consecutive patients with primary ICH who had MRI. Baseline CSVD load (including white matter hyperintensities [WMH], cerebral microbleeds [CMBs], lacunes, and enlarged perivascular spaces [EPVS]) was evaluated. The cumulative CSVD score was calculated by combining the presence of each CSVD marker (range 0–4). We followed participants for poor functional outcome [modified Rankin scale [mRS] ≥ 4], stroke recurrence, and time-varying survival during a median follow-up of 4.9 [interquartile range [IQR] 3.1–6.0] years. Parsimonious and fuller multivariable logistic regression analysis and Cox-regression analysis were performed to estimate the association of CSVD markers, individually and collectively, with each outcome.

Results: A total of 153 patients were included in the analyses. CMBs ≥ 10 [adjusted OR [adOR] 3.252, 95% CI 1.181–8.956, p = 0.023] and periventricular WMH (PWMH) (adOR 2.053, 95% CI 1.220–3.456, p = 0.007) were significantly associated with poor functional outcome. PWMH (adOR 2.908, 95% CI 1.230–6.878, p = 0.015) and lobar CMB severity (adOR 1.811, 95% CI 1.039–3.157, p = 0.036) were associated with stroke recurrence. The cumulative CSVD score was associated with poor functional outcome (adOR 1.460, 95% CI 1.017–2.096) and stroke recurrence (adOR 2.258, 95% CI 1.080–4.723). Death occurred in 36.1% (13/36) of patients with CMBs ≥ 10 compared with 18.8% (22/117) in those with CMB < 10 (adjusted HR 2.669, 95% CI 1.248–5.707, p = 0.011). In addition, the cumulative CSVD score ≥ 2 was associated with a decreased survival rate (adjusted HR 3.140, 95% CI 1.066–9.250, p = 0.038).

Conclusions: Severe PWMH, CMB, or cumulative CSVD burden exert important influences on the long-term outcome of ICH.
Fluoxetine and Ketamine Reverse the Depressive but Not Anxiety Behavior Induced by Lesion of Cholinergic Neurons in the Horizontal Limb of the Diagonal Band of Broca in Male Rat
Authors: Chen Linghong , Ke Yuting , Ma Hong , Gao Lei , Zhou Yiying , Zhu Huaqiang , Liu Huifen , Zhang Fuqiang , Zhou Wenhua
Published: February 2021

The basal forebrain cholinergic system is involved in cognitive processes, but the role of the basal forebrain cholinergic system in depression is unknown. We investigated whether a lesion of cholinergic neurons in the horizontal limb of the diagonal band of Broca (HDB) produces depressive-like behavior and whether fluoxetine or ketamine inhibits such depressive-like behaviors. Here, in rats, we used 192 IgG-saporin to eliminate the cholinergic neurons of the HDB and evaluated depressive-like behaviors using a preference test for sucrose solution and the forced swimming test. Fourteen days after the injection of 192 IgG-saporin into the HDB, the rats exhibited a significantly fewer number of choline acetyltransferase positive cell density in HDB, accompanied with neuronal loss in the entire hippocampus. Meanwhile, these rats significantly reduced preference for sucrose solution, increased immobility time in the forced swimming test, reduced locomotor activity, decreased context dependent memory in fear conditioning and the time spent in the open arms of the plus-maze. A single dose of ketamine (10 mg/kg) increased the sucrose solution consumption, reduced the immobility time in the forced swim test (FST), and increased locomotor activity compared to vehicle-treated rats. Moreover, in rats that were continuously treated with fluoxetine (10 mg/kg/day for 11 days), the sucrose solution consumption increased, the immobility time in the FST decreased, and locomotor activity increased compared to vehicle-treated rats. The present results demonstrate that a lesion of HDB cholinergic neurons results in depressive-like and anxiety-like behaviors and that antidepressants such as fluoxetine or ketamine, can reverse these depressive-like behaviors but not anxiety-like behaviors, and suggest that a lesion of HDB cholinergic neurons and followed hippocampus damage may be involved in the pathogenesis of depression.
Emerging Evidence Highlighting the Importance of Redox Dysregulation in the Pathogenesis of Amyotrophic Lateral Sclerosis (ALS)
Authors: Jagaraj Cyril Jones , Parakh Sonam , Atkin Julie D.
Published: February 2021

The cellular redox state, or balance between cellular oxidation and reduction reactions, serves as a vital antioxidant defence system that is linked to all important cellular activities. Redox regulation is therefore a fundamental cellular process for aerobic organisms. Whilst oxidative stress is well described in neurodegenerative disorders including amyotrophic lateral sclerosis (ALS), other aspects of redox dysfunction and their contributions to pathophysiology are only just emerging. ALS is a fatal neurodegenerative disease affecting motor neurons, with few useful treatments. Hence there is an urgent need to develop more effective therapeutics in the future. Here, we discuss the increasing evidence for redox dysregulation as an important and primary contributor to ALS pathogenesis, which is associated with multiple disease mechanisms. Understanding the connection between redox homeostasis, proteins that mediate redox regulation, and disease pathophysiology in ALS, may facilitate a better understanding of disease mechanisms, and lead to the design of better therapeutic strategies.
Chronic and Acute Manipulation of Cortical Glutamate Transmission Induces Structural and Synaptic Changes in Co-cultured Striatal Neurons
Authors: Kuhlmann Naila , Wagner Valladolid Miriam , Quesada-Ramírez Lucía , Farrer Matthew J. , Milnerwood Austen J.
Published: February 2021

In contrast to the prenatal topographic development of sensory cortices, striatal circuit organization is slow and requires the functional maturation of cortical and thalamic excitatory inputs throughout the first postnatal month. While mechanisms regulating synapse development and plasticity are quite well described at excitatory synapses of glutamatergic neurons in the neocortex, comparatively little is known of how this translates to glutamate synapses onto GABAergic neurons in the striatum. Here we investigate excitatory striatal synapse plasticity in an in vitro system, where glutamate can be studied in isolation from dopamine and other neuromodulators. We examined pre-and post-synaptic structural and functional plasticity in GABAergic striatal spiny projection neurons (SPNs), co-cultured with glutamatergic cortical neurons. After synapse formation, medium-term (24 h) TTX silencing increased the density of filopodia, and modestly decreased dendritic spine density, when assayed at 21 days in vitro (DIV). Spine reductions appeared to require residual spontaneous activation of ionotropic glutamate receptors. Conversely, chronic (14 days) TTX silencing markedly reduced spine density without any observed increase in filopodia density. Time-dependent, biphasic changes to the presynaptic marker Synapsin-1 were also observed, independent of residual spontaneous activity. Acute silencing (3 h) did not affect presynaptic markers or postsynaptic structures. To induce rapid, activity-dependent plasticity in striatal neurons, a chemical NMDA receptor-dependent “long-term potentiation (LTP)” paradigm was employed. Within 30 min, this increased spine and GluA1 cluster densities, and the percentage of spines containing GluA1 clusters, without altering the presynaptic signal. The results demonstrate that the growth and pruning of dendritic protrusions is an active process, requiring glutamate receptor activity in striatal projection neurons. Furthermore, NMDA receptor activation is sufficient to drive glutamatergic structural plasticity in SPNs, in the absence of dopamine or other neuromodulators.
The Neurophysiological Impact of Experimentally-Induced Pain on Direct Muscle Spindle Afferent Response: A Scoping Review
Authors: Lima Carla R. , Sahu Pradeep K. , Martins Daniel F. , Reed William R.
Published: February 2021

Background: Musculoskeletal pain disorders are among the leading causes of years lived with disability worldwide representing a significant burden to society. Studies investigating a “nociceptive-fusimotor” relationship using experimentally-induced pain/noxious stimuli and muscle spindle afferent (MSA) response have been published over several decades. The purpose of this scoping review was to systematically identify and summarize research findings related to the impact of experimentally-induced pain or noxious stimulation on direct MSA discharge/response.

Methods: PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane and Embase were searched from database inception to August 2020. Eligible studies were: (a) published in English; (b) clinical or pre-clinical studies; (c) original data studies; (d) included the investigation of MSA response to experimentally-induced pain or noxious stimulation; (e) included quantification of at least one direct physiological measure associated with MSA activity/response. Two-phase screening procedures were conducted by a pair of independent reviewers and data extracted from eligible studies.

Results: The literature search resulted in 195 articles of which 23 met inclusion criteria. Six studies (26%) were classified as clinical and 17 (74%) as pre-clinical. Two clinical studies investigated the effects of sacral dermatome pin-pricking on MSA response, while the remaining 4 studies investigated the effects of tonic muscle and/or skin pain induced by injection/infusion of hypertonic saline into the tibialis anterior muscle or subdermal tissues. In pre-clinical studies, muscle pain was induced by injection of noxious substances or the surgical removal of the meniscus at the knee joint.

Conclusion: Clinical studies in awake humans reported that experimentally-induced pain did not affect, or else slightly decreased MSA spontaneous discharge and/or response during weak dorsiflexor muscle contraction, thus failing to support an excitatory nociceptive-fusimotor relationship. However, a majority of pre-clinical studies indicated that ipsilateral and contralateral muscle injection of noxious substances altered MSA resting discharge and/or response to stretch predominately through static fusimotor reflex mechanisms. Methodological differences (use of anesthesia, stretch methodology, etc.) may ultimately be responsible for the discrepancies between clinical and pre-clinical findings. Additional investigative efforts are needed to reconcile these discrepancies and to clearly establish or refute the existence of nociceptive-fusimotor relationship in muscular pain.
Nicotine Enhances Amplitude and Consistency of Timing of Responses to Acoustic Trains in A1
Authors: Intskirveli Irakli , Metherate Raju
Published: February 2021

Systemic nicotine enhances neural processing in primary auditory cortex (A1) as determined using tone-evoked, current-source density (CSD) measurements. For example, nicotine enhances the characteristic frequency (CF)-evoked current sink in layer 4 of A1, increasing amplitude and decreasing latency. However, since presenting auditory stimuli within a stream of stimuli increases the complexity of response dynamics, we sought to determine the effects of nicotine on CSD responses to trains of CF stimuli (one-second trains at 2–40 Hz; each train repeated 25 times). CSD recordings were obtained using a 16-channel multiprobe inserted in A1 of urethane/xylazine-anesthetized mice, and analysis focused on two current sinks in the middle (layer 4) and deep (layers 5/6) layers. CF trains produced adaptation of the layer 4 response that was weak at 2 Hz, stronger at 5–10 Hz and complete at 20–40 Hz. In contrast, the layer 5/6 current sink exhibited less adaptation at 2–10 Hz, and simultaneously recorded auditory brainstem responses (ABRs) showed no adaptation even at 40 Hz. Systemic nicotine (2.1 mg/kg) enhanced layer 4 responses throughout the one-second stimulus train at rates ≤10 Hz. Nicotine enhanced both response amplitude within each train and the consistency of response timing across 25 trials. Nicotine did not alter the degree of adaptation over one-second trials, but its effect to increase amplitudes revealed a novel, slower form of adaptation that developed over multiple trials. Nicotine did not affect responses that were fully adapted (20–40 Hz trains), nor did nicotine affect any aspect of the layer 5/6 current sink or ABRs. The overall effect of nicotine in layer 4 was to enhance all responses within each train, to emphasize earlier trials across multiple trials, and to improve the consistency of timing across all trials. These effects may improve processing of complex acoustic streams, including speech, that contain information in the 2–10 Hz range.
Fast Simulations of Highly-Connected Spiking Cortical Models Using GPUs
Authors: Golosio Bruno , Tiddia Gianmarco , De Luca Chiara , Pastorelli Elena , Simula Francesco , Paolucci Pier Stanislao
Published: February 2021

Over the past decade there has been a growing interest in the development of parallel hardware systems for simulating large-scale networks of spiking neurons. Compared to other highly-parallel systems, GPU-accelerated solutions have the advantage of a relatively low cost and a great versatility, thanks also to the possibility of using the CUDA-C/C++ programming languages. NeuronGPU is a GPU library for large-scale simulations of spiking neural network models, written in the C++ and CUDA-C++ programming languages, based on a novel spike-delivery algorithm. This library includes simple LIF (leaky-integrate-and-fire) neuron models as well as several multisynapse AdEx (adaptive-exponential-integrate-and-fire) neuron models with current or conductance based synapses, different types of spike generators, tools for recording spikes, state variables and parameters, and it supports user-definable models. The numerical solution of the differential equations of the dynamics of the AdEx models is performed through a parallel implementation, written in CUDA-C++, of the fifth-order Runge-Kutta method with adaptive step-size control. In this work we evaluate the performance of this library on the simulation of a cortical microcircuit model, based on LIF neurons and current-based synapses, and on balanced networks of excitatory and inhibitory neurons, using AdEx or Izhikevich neuron models and conductance-based or current-based synapses. On these models, we will show that the proposed library achieves state-of-the-art performance in terms of simulation time per second of biological activity. In particular, using a single NVIDIA GeForce RTX 2080 Ti GPU board, the full-scale cortical-microcircuit model, which includes about 77,000 neurons and 3 · 108 connections, can be simulated at a speed very close to real time, while the simulation time of a balanced network of 1,000,000 AdEx neurons with 1,000 connections per neuron was about 70 s per second of biological activity.
Transfer of Learning in the Convolutional Neural Networks on Classifying Geometric Shapes Based on Local or Global Invariants
Authors: Zheng Yufeng , Huang Jun , Chen Tianwen , Ou Yang , Zhou Wu
Published: February 2021

The convolutional neural networks (CNNs) are a powerful tool of image classification that has been widely adopted in applications of automated scene segmentation and identification. However, the mechanisms underlying CNN image classification remain to be elucidated. In this study, we developed a new approach to address this issue by investigating transfer of learning in representative CNNs (AlexNet, VGG, ResNet-101, and Inception-ResNet-v2) on classifying geometric shapes based on local/global features or invariants. While the local features are based on simple components, such as orientation of line segment or whether two lines are parallel, the global features are based on the whole object such as whether an object has a hole or whether an object is inside of another object. Six experiments were conducted to test two hypotheses on CNN shape classification. The first hypothesis is that transfer of learning based on local features is higher than transfer of learning based on global features. The second hypothesis is that the CNNs with more layers and advanced architectures have higher transfer of learning based global features. The first two experiments examined how the CNNs transferred learning of discriminating local features (square, rectangle, trapezoid, and parallelogram). The other four experiments examined how the CNNs transferred learning of discriminating global features (presence of a hole, connectivity, and inside/outside relationship). While the CNNs exhibited robust learning on classifying shapes, transfer of learning varied from task to task, and model to model. The results rejected both hypotheses. First, some CNNs exhibited lower transfer of learning based on local features than that based on global features. Second the advanced CNNs exhibited lower transfer of learning on global features than that of the earlier models. Among the tested geometric features, we found that learning of discriminating inside/outside relationship was the most difficult to be transferred, indicating an effective benchmark to develop future CNNs. In contrast to the “ImageNet” approach that employs natural images to train and analyze the CNNs, the results show proof of concept for the “ShapeNet” approach that employs well-defined geometric shapes to elucidate the strengths and limitations of the computation in CNN image classification. This “ShapeNet” approach will also provide insights into understanding visual information processing the primate visual systems.
Repetitive Transcranial Magnetic Stimulation With H-Coil in Alzheimer's Disease: A Double-Blind, Placebo-Controlled Pilot Study
Authors: Leocani Letizia , Dalla Costa Gloria , Coppi Elisabetta , Santangelo Roberto , Pisa Marco , Ferrari Laura , Bernasconi Maria Paola , Falautano Monica , Zangen Abraham , Magnani Giuseppe , Comi Giancarlo
Published: February 2021

Focal repetitive transcranial magnetic stimulation (rTMS) has been applied to improve cognition in Alzheimer's disease (AD) with conflicting results. We applied rTMS in AD in a pilot placebo-controlled study using the H2-coil. H-coils are suitable for targeting wider neuronal structures compared with standard focal coils, in particular the H2-coil stimulates simultaneously the frontal-parietal-temporal lobes bilaterally. Thirty patients (mean age 70.9 year, SD 8.1; mean MMSE score 16.9, SD 5.5) were randomized to sham or real 10 Hz rTMS stimulation with the H2-coil. Each patient underwent 3 sessions/week for 4 weeks, followed by 4 weeks with maintenance treatment (1 session/week). Primary outcome was improvement of ADAS-cog at 4 and 8 weeks compared with baseline. A trend toward an improved ADAS-cog score over time was observed for patients undergoing real rTMS, with actively treated patients experiencing a mean decrease of −1.01 points at the ADAS-Cog scale score per time point (95% CIs −0.02 to −3.13, p < 0.04). This trend was no longer evident 2 months after the end of treatment. Real rTMS showed no significant effect on MMSE and BDI changes over time. These preliminary findings suggest that rTMS with H-coil is feasible and safe in patients with probable AD and might provide beneficial, even though transient, effects on cognition. This study prompts larger studies in the early stages of AD, combining rTMS and cognitive rehabilitation.

Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT04562506.
Impact of COVID-19 on the Speech and Language Therapy Profession and Their Patients
Authors: Chadd Katie , Moyse Kathryn , Enderby Pam
Published: February 2021

Introduction: The UK's response to the COVID-19 pandemic presented multiple challenges to healthcare services including the suspension of non-urgent care. The impact on neurorehabilitation professions, including speech and language therapy (SLT), has been substantial.

Objectives: To review the changes to SLT services triggered by the COVID-19 pandemic with respect to referral rates, service delivery and outcomes, as well as examining the contribution of SLTs to the neurorehabilitation of COVID-19 patients.

Methods: Two surveys were distributed to Royal College of Speech and Language Therapists (RCSLT) members exploring experiences of service provision at 6 weeks and 22 weeks after the pandemic was declared in the UK. Responses to closed-ended questions, including questions regarding referral numbers were analyzed descriptively and compared at the two time-points. A database comprising routine clinical data from SLT services across the UK was used to compare information on patients receiving services prior to and during the pandemic. Data on COVID-19 patients was extracted, and findings are provided descriptively.

Results: Referrals to SLT services during the acute COVID-19 period in the UK were substantially less than in the same period in 2019. A number of service changes were common including adopting more flexible approaches to provision (such as tele-therapy) and being unable to provide services to some patients. Database analysis suggests fewer patients have accessed SLT since the pandemic began, including a reduction in neurorehabilitation patients. For those who received SLT, the outcomes did not change. SLTs supported a range of needs of COVID-19 patients. Treatment outcomes for COVID-19 patients with dysphagia were positive.

Discussion: The pandemic has affected neurorehabilitation and SLT services broadly: referral patterns are different, usual care has been disrupted and interventions have been modified affecting the impact on patient outcomes both positively and negatively. Some patients with COVID-19 require and benefit from SLT intervention.
No Impact of Stochastic Galvanic Vestibular Stimulation on Arterial Pressure and Heart Rate Variability in the Elderly Population
Authors: Matsugi Akiyoshi , Nagino Koji , Shiozaki Tomoyuki , Okada Yohei , Mori Nobuhiko , Nakamura Junji , Douchi Shinya , Oku Kosuke , Nagano Kiyoshi , Tamaru Yoshiki
Published: February 2021

Objective

Noisy galvanic vestibular stimulation (nGVS) is often used to improve postural stability in disorders, such as neurorehabilitation montage. For the safe use of nGVS, we investigated whether arterial pressure (AP) and heart rate vary during static supine and slow whole-body tilt with random nGVS (0.4 mA, 0.1–640 Hz, gaussian distribution) in a healthy elderly population.

Methods

This study was conducted with a double-blind, sham-controlled, cross-over design. Seventeen healthy older adults were recruited. They were asked to maintain a static supine position on a bed for 10 min, and the bed was tilted up (TU) to 70 degrees within 30 s. After maintaining this position for 3 min, the bed was passively tilted down (TD) within 30 s. Real-nGVS or sham-nGVS was applied from 4 to 15 min. The time course of mean arterial pressure (MAP) and RR interval variability (RRIV) were analyzed to estimate the autonomic nervous activity.

Result

nGVS and/or time, including pre-/post-event (nGVS-start, TU, and TD), had no impact on MAP and RRIV-related parameters. Further, there was no evidence supporting the argument that nGVS induces pain, vertigo/dizziness, and uncomfortable feeling.

Conclusion

nGVS may not affect the AP and RRIV during static position and whole-body tilting or cause pain, vertigo/dizziness, and discomfort in the elderly.
Comparing the Electrophysiology and Morphology of Human and Mouse Layer 2/3 Pyramidal Neurons With Bayesian Networks
Authors: Mihaljević Bojan , Larrañaga Pedro , Bielza Concha
Published: February 2021

Pyramidal neurons are the most common neurons in the cerebral cortex. Understanding how they differ between species is a key challenge in neuroscience. We compared human temporal cortex and mouse visual cortex pyramidal neurons from the Allen Cell Types Database in terms of their electrophysiology and dendritic morphology. We found that, among other differences, human pyramidal neurons had a higher action potential threshold voltage, a lower input resistance, and larger dendritic arbors. We learned Gaussian Bayesian networks from the data in order to identify correlations and conditional independencies between the variables and compare them between the species. We found strong correlations between electrophysiological and morphological variables in both species. In human cells, electrophysiological variables were correlated even with morphological variables that are not directly related to dendritic arbor size or diameter, such as mean bifurcation angle and mean branch tortuosity. Cortical depth was correlated with both electrophysiological and morphological variables in both species, and its effect on electrophysiology could not be explained in terms of the morphological variables. For some variables, the effect of cortical depth was opposite in the two species. Overall, the correlations among the variables differed strikingly between human and mouse neurons. Besides identifying correlations and conditional independencies, the learned Bayesian networks might be useful for probabilistic reasoning regarding the morphology and electrophysiology of pyramidal neurons.
The Endocannabinoid System Contributes to Electroacupuncture Analgesia
Authors: MacDonald Iona J. , Chen Yi-Hung
Published: February 2021

The extensive involvement of the endocannabinoid system (ECS) in vital physiological and cognitive processes of the human body has inspired many investigations into the role of the ECS and drugs, and therapies that target this system and its receptors. Activation of cannabinoid receptors 1 and 2 (CB1 and CB2) by cannabinoid treatments, including synthetic cannabinoids, alleviates behavioral responses to inflammatory and neuropathic pain. An increasing body of scientific evidence details how electroacupuncture (EA) treatments achieve effective analgesia and reduce inflammation by modulating cannabinoid signaling, without the adverse effects resulting from synthetic cannabinoid administration. CB1 receptors in the ventrolateral area of the periaqueductal gray are critically important for the mechanisms of the EA antinociceptive effect, while peripheral CB2 receptors are related to the anti-inflammatory effects of EA. This review explores the evidence detailing the endocannabinoid mechanisms involved in EA antinociception.
Optimal Approach for Signal Detection in Steady-State Visual Evoked Potentials in Humans Using Single-Channel EEG and Stereoscopic Stimuli
Authors: Derzsi Zoltan
Published: February 2021

In EEG studies, one of the most common ways to detect a weak periodic signal in the steady-state visual evoked potential (SSVEP) is spectral evaluation, a process that detects peaks of power present at notable temporal frequencies. However, the presence of noise decreases the signal-to-noise ratio (SNR), which in turn lowers the probability of successful detection of these spectral peaks. In this paper, using a single EEG channel, we compare the detection performance of four different metrics to analyse the SSVEP: two metrics that use spectral power density, and two other metrics that use phase coherency. We employ these metrics find weak signals with a known temporal frequency hidden in the SSVEP, using both simulation and real data from a stereoscopic apparent depth movement perception task. We demonstrate that out of these metrics, the phase coherency analysis is the most sensitive way to find weak signals in the SSVEP, provided that the phase information of the stimulus eliciting the SSVEP is preserved.
Altered Light Sensitivity of Circadian Clock in Shank3+/– Mouse
Authors: Alamilla Javier , Ramiro-Cortés Yazmín , Mejía-López Adriana , Chavez José-Luis , Rivera Dulce Olivia , Felipe Víctor , Aguilar-Roblero Raúl
Published: February 2021

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairment in communication and social interaction, repetitive or stereotypical behaviors, altered sensory perception, and sleep disorders. In general, the causes of ASD remain unknown, but in Phelan–McDermid syndrome, it is known that the disorder is related to the haploinsufficiency of the Shank3 gene. We used an autism model with compromised glutamatergic signaling, the Shank3+/–mouse, to study the circadian rhythm architecture of locomotion behavior and its entrainment to light. We also analyzed the synapse between the retinohypothalamic tract (RHT) and the suprachiasmatic nucleus (SCN), employing tract tracing and immunohistochemical techniques. We found that Shank3+/–mice were not impaired in the SCN circadian clock, as indicated by a lack of differences between groups in the circadian architecture in entrained animals to either long or short photoperiods. Circadian rhythm periodicity (tau) was unaltered between genotypes in constant darkness (DD, dim red light). Similar results were obtained in the re-entrainment to shifts in the light–dark cycle and in the entrainment to a skeleton photoperiod from DD. However, Shank3+/–mice showed larger phase responses to light pulses, both delays and advances, and rhythm disorganization induced by constant bright light. Immunohistochemical analyses indicated no differences in the RHT projection to the SCN or the number of SCN neurons expressing theN-methyl-D-aspartate (NMDA) receptor subunit NR2A, whereas the Shank3+/–animals showed decreased c-Fos induction by brief light pulses at CT14, but increased number of vasoactive intestinal polypeptide (VIP)-positive neurons. These results indicate alterations in light sensitivity in Shank3+/–mice. Further studies are necessary to understand the mechanisms involved in such increased light sensitivity, probably involving VIP neurons.
Morphometric and Functional Brain Connectivity Differentiates Chess Masters From Amateur Players
Authors: RaviPrakash Harish , Anwar Syed Muhammad , Biassou Nadia M. , Bagci Ulas
Published: February 2021

A common task in brain image analysis includes diagnosis of a certain medical condition wherein groups of healthy controls and diseased subjects are analyzed and compared. On the other hand, for two groups of healthy participants with different proficiency in a certain skill, a distinctive analysis of the brain function remains a challenging problem. In this study, we develop new computational tools to explore the functional and anatomical differences that could exist between the brain of healthy individuals identified on the basis of different levels of task experience/proficiency. Toward this end, we look at a dataset of amateur and professional chess players, where we utilize resting-state functional magnetic resonance images to generate functional connectivity (FC) information. In addition, we utilize T1-weighted magnetic resonance imaging to estimate morphometric connectivity (MC) information. We combine functional and anatomical features into a new connectivity matrix, which we term as the functional morphometric similarity connectome (FMSC). Since, both the FC and MC information is susceptible to redundancy, the size of this information is reduced using statistical feature selection. We employ off-the-shelf machine learning classifier, support vector machine, for both single- and multi-modality classifications. From our experiments, we establish that the saliency and ventral attention network of the brain is functionally and anatomically different between two groups of healthy subjects (chess players). We argue that, since chess involves many aspects of higher order cognition such as systematic thinking and spatial reasoning and the identified network is task-positive to cognition tasks requiring a response, our results are valid and supporting the feasibility of the proposed computational pipeline. Moreover, we quantitatively validate an existing neuroscience hypothesis that learning a certain skill could cause a change in the brain (functional connectivity and anatomy) and this can be tested via our novel FMSC algorithm.
APOE and Alzheimer’s Disease: From Lipid Transport to Physiopathology and Therapeutics
Authors: Husain Mohammed Amir , Laurent Benoit , Plourde Mélanie
Published: February 2021

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder characterized by extracellular amyloid β (Aβ) and intraneuronal tau protein aggregations. One risk factor for developing AD is the APOE gene coding for the apolipoprotein E protein (apoE). Humans have three versions of APOE gene: ε2, ε3, and ε4 allele. Carrying the ε4 allele is an AD risk factor while carrying the ε2 allele is protective. ApoE is a component of lipoprotein particles in the plasma at the periphery, as well as in the cerebrospinal fluid (CSF) and in the interstitial fluid (ISF) of brain parenchyma in the central nervous system (CNS). ApoE is a major lipid transporter that plays a pivotal role in the development, maintenance, and repair of the CNS, and that regulates multiple important signaling pathways. This review will focus on the critical role of apoE in AD pathogenesis and some of the currently apoE-based therapeutics developed in the treatment of AD.
Phenotypic Characterization and Brain Structure Analysis of Calcium Channel Subunit α2δ-2 Mutant (Ducky) and α2δ Double Knockout Mice
Authors: Geisler Stefanie M. , Benedetti Ariane , Schöpf Clemens L. , Schwarzer Christoph , Stefanova Nadia , Schwartz Arnold , Obermair Gerald J.
Published: February 2021

Auxiliary α2δ subunits of voltage-gated calcium channels modulate channel trafficking, current properties, and synapse formation. Three of the four isoforms (α2δ-1, α2δ-2, and α2δ-3) are abundantly expressed in the brain; however, of the available knockout models, only α2δ-2 knockout or mutant mice display an obvious abnormal neurological phenotype. Thus, we hypothesize that the neuronal α2δ isoforms may have partially specific as well as redundant functions. To address this, we generated three distinct α2δ double knockout mouse models by crossbreeding single knockout (α2δ-1 and -3) or mutant (α2δ-2/ducky) mice. Here, we provide a first phenotypic description and brain structure analysis. We found that genotypic distribution of neonatal litters in distinct α2δ-1/-2, α2δ-1/-3, and α2δ-2/-3 breeding combinations did not conform to Mendel’s law, suggesting premature lethality of single and double knockout mice. Notably, high occurrences of infant mortality correlated with the absence of specific α2δ isoforms (α2Δ-2 > α2δ-1 > α2δ-3), and was particularly observed in cages with behaviorally abnormal parenting animals of α2δ-2/-3 cross-breedings. Juvenile α2δ-1/-2 and α2δ-2/-3 double knockout mice displayed a waddling gate similar to ducky mice. However, in contrast to ducky and α2δ-1/-3 double knockout animals, α2δ-1/-2 and α2δ-2/-3 double knockout mice showed a more severe disease progression and highly impaired development. The observed phenotypes within the individual mouse lines may be linked to differences in the volume of specific brain regions. Reduced cortical volume in ducky mice, for example, was associated with a progressively decreased space between neurons, suggesting a reduction of total synaptic connections. Taken together, our findings show that α2δ subunits differentially regulate premature survival, postnatal growth, brain development, and behavior, suggesting specific neuronal functions in health and disease.
Exploring External Factors Affecting the Intention-Behavior Gap When Trying to Adopt a Sustainable Diet: A Think Aloud Study
Authors: Fink Leonie , Strassner Carola , Ploeger Angelika
Published: February 2021

Not least from an ecological and health perspective, it can be posited that a broader part of consumers should practice sustainable diets. People who are already willing to do so are often confronted with the intention-behavior gap, caused by a range of internal and external factors. To eliminate these barriers requires a deeper and more comprehensive understanding of these factors and their interplay. Therefore, a think aloud study with 20 adult German participants was conducted to explore the four chosen external factors of availability, education, advertising and price. Furthermore, questionnaires for all four factors were handed out and a follow-up interview was conducted to gain additional qualitative data. Results show that these four external factors seem to have a major impact on the intention-behavior relation. According to the participants all factors interact in some way with other internal and external factors, making practicing sustainable diets a complex activity. In conclusion, the four external factors availability, education, advertising and price need to be addressed by various stakeholders within our food systems in order to move forward in the process of making sustainable diets practicable and sustainable food systems firmly established.
Cognitive Behavioral Approach to Treat Obesity: A Randomized Clinical Trial
Authors: Moraes Amanda dos Santos , Padovani Ricardo da Costa , La Scala Teixeira Cauê Vazquez , Cuesta Maria Gabriela Soria , Gil Silvandro dos Santos , de Paula Bárbara , dos Santos Gilberto Monteiro , Gonçalves Rodrigo Tributino , Dâmaso Ana Raimunda , Oyama Lila Missae , Gomes Ricardo José , Caranti Danielle Arisa
Published: February 2021

Our aim was to analyze and compare the effects of three different long-term treatments on anthropometric profiles, eating behaviors, anxiety and depression levels, and quality of life of groups of adults with obesity.

Methods: The 43 participants in the study were randomly assigned to one of three groups: the education and health group (EH, n = 12), which received lectures on health topics; the physical exercise group (PE, n = 13), which underwent physical training; and the interdisciplinary therapy plus cognitive behavioral therapy (IT + CBT) (n = 18) group, which received physical training, nutritional advice, and physical and psychological therapy.

Results: Total quality of life increased significantly in the EH group (△ = 2.00); in the PE group, body weight significantly decreased (△ = −1.42) and the physical domain of quality of life improved (△ = 1.05). However, the most significant changes were seen in the IT + CBT group, in which the anthropometric profile improved; there were an increase in quality of life in all domains (physical, psychological, social, and environmental), an improvement in eating behaviors [Dutch Eating Behavior Questionnaire (DEBQ), total △ = −8.39], and a reduction in depression [Beck Depression Inventory (BDI), △ = −10.13).

Conclusion: The IT + CBT program was more effective than the PE and EH programs.

Clinical Trial Registration Number:NCT02573688.
Nutritional Status of Pre-school Children and Determinant Factors of Autism: A Case-Control Study
Authors: Alkhalidy Hana , Abushaikha Amal , Alnaser Khadeejah , Obeidat Mohammad D. , Al-Shami Islam
Published: February 2021

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder triggered by several factors, including those of genetic and environmental nature. ASD can alter communication, behavior, and children's nutritional status, placing them at high risk for nutritional imbalances. Therefore, this study aims to assess preschool autistic children's nutritional status as compared to that of Typically Developing (TD) children of the same age. The study also revealed some of the ASD risk factors among the Jordanian population. It included 52 ASD and 51 TD children (3–6 years), and considered sociodemographic, obstetric, and nutritional factors of the two groups, stratified by gender. Nutritional status was evaluated through a comprehensive questionnaire, 3-day food record, and anthropometric and biochemical measurements. Differences between groups were identified using the chi-square and independent-sample t-test. The logistic regression model was used after the adjustment of confounders to detect an autistic child's determinants. The study showed little difference between ASD and TD children with respect to nutrients' intake inadequacy and biochemical-nutritional deficiencies, but did reveal gender-based differences. Autistic girls were at higher risk of inadequate carbohydrate intake, while autistic boys were at higher risk of inadequate vitamin E, vitamin K, and fluoride compared to TD children. More autistic children had been treated in neonatal care units after birth than had TD children. The regression analysis revealed that lower maternal education level (OR, 12.25; 95% CI, 1.18–126.91), vaginal delivery (OR, 0.273; 95% CI, 0.105–0.712), family history of autism (OR, 0.189; 95% CI, 0.059–0.612), and taking dietary supplements during pregnancy (OR, 4.665; 95% CI, 1.158–18.79) were all determinants of ASD in children. In conclusion, maternal nutrition, postnatal conditions, and nutritional status might be contributors to ASD in children. Pre-school children are at high risk for developing nutritional deficiencies. It is therefore important to maintain optimal nutritional status in pregnant patients, and in children after delivery and during early childhood. Future studies that investigate the role of nutrient deficiencies and nutritional interventions in ASD are necessary. Also required are studies that focus on gender differences in the prevalence of ASD, types and severity of symptoms, and ASD nutrition-related problems.
MiR-1539 and Its Potential Role as a Novel Biomarker for Colorectal Cancer
Authors: Cui Xueyang , Lv Zhi , Ding Hanxi , Xing Chengzhong , Yuan Yuan
Published: February 2021

Purpose

We investigated microRNA (miR) 1539 as a potential biomarker for predicting the risk and pathobiological behavior of colorectal cancer (CRC).

Methods

Our strategy consisted of analyzing 100 serum samples from 51 CRC patients, 49 healthy controls (HCs), and another 56 CRC tissue and matched normal adjacent to tumor (NAT) samples. The relative expression levels of miR-1539 in exosomes, serum and tissues were detected and compared in the different groups, using reverse transcription-polymerase chain reaction (RT-qPCR). The diagnostic value and potential function of miR-1539 were investigated using clinicopathological data combined with bioinformatics analysis.

Results

MiR-1539 expression was significantly up-regulated in exosomes (p = 0.003) and cancer tissue (p < 0.001) from CRC patients. MiR-1539 expression levels in serum varied according to different tumor sites (right-sided vs. left-sided, p = 0.047; left-side CRC vs. HCs, p = 0.031). In terms of diagnostic efficacy, miR-1539 expression in exosomes may help distinguish CRC cases from HCs with a sensitivity of 92.2%, and miR-1539 expression in serum may improve the specificity to 96.6% for left-sided CRC diagnosis. When combined with clinicopathological data, serum miR-1539 levels were positively associated with vascular endothelial growth factor (VEGF) expression (p = 0.028), whilst levels in CRC tissue were positively associated with increased Ki-67 levels (p = 0.035). Poorer pathologic differentiation was potentially related to an increased tendency of miR-1539 expression in CRC tissue (p = 0.071). Based on our bioinformatics analysis, miR-1539 may have a significant mechanistic influence on CRC genesis and progression.

Conclusions

Circulating or tissue based miR-1539 may be used as a novel potential biomarker for CRC screening, and a predictor of poor clinicopathological behavior in tumors.