bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro Dissolution Profile at Different Biological pH Conditions of Hydroxychloroquine Sulfate Tablets Is Available for the Treatment of COVID-19
Authors: Dongala Thirupathi , Katari Naresh Kumar , Ettaboina Santhosh Kumar , Krishnan Anand , Tambuwala Murtaza M. , Dua Kamal
Published: January 2021

Hydroxychloroquine sulfate is one of an extensive series of 4-aminoquinolines with antimalarial activity. Moreover, it is used for the treatment of rheumatoid arthritis. Sometimes, hydroxychloroquine sulfate is beneficial for the treatment of autoimmune diseases. Based on recent clinical experiments, it is exploited for the treatment of COVID-19, coronavirus across the globe. The chromatogram separation was achieved by using Agilent, Zorbax C8, 250 mm × 4.6 mm i.d., column. The buffer consists of 0.01 M of 1-pentane sulfonic acid and 0.02% of orthophosphoric acid in purified water. Mixed buffer, acetonitrile, and methanol (800:100:100 v/v). The flow rate was 1.0 ml min−1, and injection volume was 10 μl. Detection was made at 254 nm by using a dual absorbance detector (DAD). The reversed-phase high-performance liquid chromatography (RP-HPLC) method has been developed and validated as per the current International Conference on Harmonization (ICH) guidelines to estimate hydroxychloroquine sulfate tablets. As part of method validation, specificity, linearity, precision, and recovery parameters were verified. The concentration and area relationships were linear (R2 > 0.999) over the concentration range of 25–300 μg ml−1 for hydroxychloroquine (HCQ). The relative standard deviations for precision and intermediate precision were <1.5%. The proposed RP-HPLC generic method was applied successfully to evaluate the in vitro dissolution profile with different pH conditions such as 0.1 N HCl, pH 4.5 acetate buffer, and pH 6.8 phosphate buffers as US-marketed reference products.
Deviations in Hippocampal Subregion in Older Adults With Cognitive Frailty
Authors: Wan Mingyue , Ye Yu , Lin Huiying , Xu Ying , Liang Shengxiang , Xia Rui , He Jianquan , Qiu Pingting , Huang Chengwu , Tao Jing , Chen Lidian , Zheng Guohua
Published: January 2021

Background

Cognitive frailty is a particular state of cognitive vulnerability toward dementia with neuropathological hallmarks. The hippocampus is a complex, heterogeneous structure closely relates to the cognitive impairment in elderly which is composed of 12 subregions. Atrophy of these subregions has been implicated in a variety of neurodegenerative diseases. The aim of this study was to explore the changes in hippocampal subregions in older adults with cognitive frailty and the relationship between subregions and cognitive impairment as well as physical frailty.

Methods

Twenty-six older adults with cognitive frailty and 26 matched healthy controls were included in this study. Cognitive function was evaluated by the Montreal Cognitive Assessment (MoCA) scale (Fuzhou version) and Wechsler Memory Scale-Revised Chinese version (WMS-RC), while physical frailty was tested with the Chinese version of the Edmonton Frailty Scale (EFS) and grip strength. The volume of the hippocampal subregions was measured with structural brain magnetic resonance imaging. Partial correlation analysis was carried out between the volumes of hippocampal subregions and MoCA scores, Wechsler’s Memory Quotient and physical frailty indexes.

Results

A significant volume decrease was found in six hippocampal subregions, including the bilateral presubiculum, the left parasubiculum, molecular layer of the hippocampus proper (molecular layer of the HP), and hippocampal amygdala transition area (HATA), and the right cornu ammonis subfield 1 (CA1) area, in older adults with cognitive frailty, while the proportion of brain parenchyma and total number of white matter fibers were lower than those in the healthy controls. Positive correlations were found between Wechsler’s Memory Quotient and the size of the left molecular layer of the HP and HATA and the right presubiculum. The sizes of the left presubiculum, molecular of the layer HP, and HATA and right CA1 and presubiculum were found to be positively correlated with MoCA score. The sizes of the left parasubiculum, molecular layer of the HP and HATA were found to be negatively correlated with the physical frailty index.

Conclusion

Significant volume decrease occurs in hippocampal subregions of older adults with cognitive frailty, and these changes are correlated with cognitive impairment and physical frailty. Therefore, the atrophy of hippocampal subregions could participate in the pathological progression of cognitive frailty.
Do High Mental Demands at Work Protect Cognitive Health in Old Age via Hippocampal Volume? Results From a Community Sample
Authors: Rodriguez Francisca S. , Huhn Sebastian , Vega William A. , Aranda Maria P. , Schroeter Matthias L. , Engel Christoph , Baber Ronny , Burkhardt Ralph , Löffler Markus , Thiery Joachim , Villringer Arno , Luck Tobias , Riedel-Heller Steffi G. , Witte A. Veronica
Published: January 2021

As higher mental demands at work are associated with lower dementia risk and a key symptom of dementia is hippocampal atrophy, the study aimed at investigating the association between mental demands at work and hippocampal volume. We analyzed data from the population-based LIFE-Adult-Study in Leipzig, Germany (n = 1,409, age 40–80). Hippocampal volumes were measured via three-dimensional Magnetic resonance imaging (MRI; 3D MP-RAGE) and mental demands at work were classified via the O*NET database. Linear regression analyses adjusted for gender, age, education, APOE e4-allele, hypertension, and diabetes revealed associations between higher demands in “language and knowledge,” “information processing,” and “creativity” at work on larger white and gray matter volume and better cognitive functioning with “creativity” having stronger effects for people not yet retired. Among retired individuals, higher demands in “pattern detection” were associated with larger white matter volume as well as larger hippocampal subfields CA2/CA3, suggesting a retention effect later in life. There were no other relevant associations with hippocampal volume. Our findings do not support the idea that mental demands at work protect cognitive health via hippocampal volume or brain volume. Further research may clarify through what mechanism mentally demanding activities influence specifically dementia pathology in the brain.
Long-Term Dietary Restriction Leads to Development of Alternative Fighting Strategies
Authors: Legros Jeanne , Tang Grace , Gautrais Jacques , Fernandez Maria Paz , Trannoy Séverine
Published: January 2021

In competition for food, mates and territory, most animal species display aggressive behavior through visual threats and/or physical attacks. Such naturally-complex social behaviors have been shaped by evolution. Environmental pressure, such as the one imposed by dietary regimes, forces animals to adapt to specific conditions and ultimately to develop alternative behavioral strategies. The quality of the food resource during contests influence animals' aggression levels. However, little is known regarding the effects of a long-term dietary restriction-based environmental pressure on the development of alternative fighting strategies. To address this, we employed two lines of the wild-type Drosophila melanogaster Canton-S (CS) which originated from the same population but raised under two distinct diets for years. One diet contained both proteins and sugar, while the second one was sugar-free. We set up male-male aggression assays using both CS lines and found differences in aggression levels and the fighting strategies employed to establish dominance relationships. CS males raised on a sugar-containing diet started fights with a physical attack and employed a high number of lunges for establishing dominance but displayed few wing threats throughout the fight. In contrast, the sugar-free-raised males favored wing threats as an initial aggressive demonstration and used fewer lunges to establish dominance, but displayed a higher number of wing threats. This study demonstrates that fruit flies that have been raised under different dietary conditions have adapted their patterns of aggressive behavior and developed distinct fighting strategies: one favoring physical attacks, while the other one favoring visual threats.
The Hypothalamic-Pituitary-Adrenal Axis: Development, Programming Actions of Hormones, and Maternal-Fetal Interactions
Authors: Sheng Julietta A. , Bales Natalie J. , Myers Sage A. , Bautista Anna I. , Roueinfar Mina , Hale Taben M. , Handa Robert J.
Published: January 2021

The hypothalamic-pituitary-adrenal axis is a complex system of neuroendocrine pathways and feedback loops that function to maintain physiological homeostasis. Abnormal development of the hypothalamic-pituitary-adrenal (HPA) axis can further result in long-term alterations in neuropeptide and neurotransmitter synthesis in the central nervous system, as well as glucocorticoid hormone synthesis in the periphery. Together, these changes can potentially lead to a disruption in neuroendocrine, behavioral, autonomic, and metabolic functions in adulthood. In this review, we will discuss the regulation of the HPA axis and its development. We will also examine the maternal-fetal hypothalamic-pituitary-adrenal axis and disruption of the normal fetal environment which becomes a major risk factor for many neurodevelopmental pathologies in adulthood, such as major depressive disorder, anxiety, schizophrenia, and others.
PsyCoP – A Platform for Systematic Semi-Automated Behavioral and Cognitive Profiling Reveals Gene and Environment Dependent Impairments of Tcf4 Transgenic Mice Subjected to Social Defeat
Authors: Volkmann Paul , Stephan Marius , Krackow Sven , Jensen Niels , Rossner Moritz J.
Published: January 2021

Recently, hundreds of risk genes associated with psychiatric disorders have been identified. These are thought to interact with environmental stress factors in precipitating pathological behaviors. However, the individual phenotypes resulting from specific genotype by environment (G×E) interactions remain to be determined. Toward a more systematic approach, we developed a novel standardized and partially automatized platform for systematic behavioral and cognitive profiling (PsyCoP). Here, we assessed the behavioral and cognitive disturbances in Tcf4 transgenic mice (Tcf4tg) exposed to psychosocial stress by social defeat during adolescence using a “two-hit” G×E mouse model. Notably, TCF4 has been repeatedly identified as a candidate risk gene for different psychiatric diseases and Tcf4tg mice display behavioral endophenotypes such as fear memory impairment and hyperactivity. We use the Research Domain Criteria (RDoC) concept as framework to categorize phenotyping results in a translational approach. We propose two methods of dimension reduction, clustering, and visualization of behavioral phenotypes to retain statistical power and clarity of the overview. Taken together, our results reveal that sensorimotor gating is disturbed by Tcf4 overexpression whereas both negative and positive valence systems are primarily influenced by psychosocial stress. Moreover, we confirm previous reports showing that deficits in the cognitive domain are largely dependent on the interaction between Tcf4 and psychosocial stress. We recommend that the standardized analysis and visualization strategies described here should be applied to other two-hit mouse models of psychiatric diseases and anticipate that this will help directing future preclinical treatment trials.
Repurposing Cholinesterase Inhibitors as Antidepressants? Dose and Stress-Sensitivity May Be Critical to Opening Possibilities
Authors: Fitzgerald Paul J. , Hale Pho J. , Ghimire Anjesh , Watson Brendon O.
Published: January 2021

When stress becomes chronic it can trigger lasting brain and behavioral changes including Major Depressive Disorder (MDD). There is conflicting evidence regarding whether acetylcholinesterase inhibitors (AChEIs) may have antidepressant properties. In a recent publication, we demonstrated a strong dose-dependency of the effect of AChEIs on antidepressant-related behavior in the mouse forced swim test: whereas the AChEI donepezil indeed promotes depression-like behavior at a high dose, it has antidepressant-like properties at lower doses in the same experiment. Our data therefore suggest a Janus-faced dose-response curve for donepezil in depression-related behavior. In this review, we investigate the mood-related properties of AChEIs in greater detail, focusing on both human and rodent studies. In fact, while there have been many studies showing pro-depressant activity by AChEIs and this is a major concept in the field, a variety of other studies in both humans and rodents show antidepressant effects. Our study was one of the first to systematically vary dose to include very low concentrations while measuring behavioral effects, potentially explaining the apparent disparate findings in the field. The possibility of antidepressant roles for AChEIs in rodents may provide hope for new depression treatments. Importantly, MDD is a psychosocial stress-linked disorder, and in rodents, stress is a major experimental manipulation for studying depression mechanisms, so an important future direction will be to determine the extent to which these depression-related effects are stress-sensitive. In sum, gaining a greater understanding of the potentially therapeutic mood-related effects of low dose AChEIs, both in rodent models and in human subjects, should be a prioritized topic in ongoing translational research.
Expression and Distribution of Neuropeptide-Expressing Cells Throughout the Rodent Paraventricular Nucleus of the Thalamus
Authors: Curtis Genevieve R. , Oakes Kathleen , Barson Jessica R.
Published: January 2021

The paraventricular nucleus of the thalamus (PVT) has been shown to make significant contributions to affective and motivated behavior, but a comprehensive description of the neurochemicals expressed in the cells of this brain region has never been presented. While the PVT is believed to be composed of projection neurons that primarily use as their neurotransmitter the excitatory amino acid, glutamate, several neuropeptides have also been described in this brain region. In this review article, we combine published literature with our observations from the Allen Brain Atlas to describe in detail the expression and distribution of neuropeptides in cells throughout the mouse and rat PVT, with a special focus on neuropeptides known to be involved in behavior. Several themes emerge from this investigation. First, while the majority of neuropeptides are expressed across the antero-posterior axis of the PVT, they generally exist in a gradient, in which expression is most dense but not exclusive in either the anterior or posterior PVT, although other neuropeptides display somewhat more equal expression in the anterior and posterior PVT but have reduced expression in the middle PVT. Second, we find overall that neuropeptides involved in arousal are more highly expressed in the anterior PVT, those involved in depression-like behavior are more highly expressed in the posterior PVT, and those involved in reward are more highly expressed in the medial PVT, while those involved in the intake of food and drugs of abuse are distributed throughout the PVT. Third, the pattern and content of neuropeptide expression in mice and rats appear not to be identical, and many neuropeptides found in the mouse PVT have not yet been demonstrated in the rat. Thus, while significantly more work is required to uncover the expression patterns and specific roles of individual neuropeptides in the PVT, the evidence thus far supports the existence of a diverse yet highly organized system of neuropeptides in this nucleus. Determined in part by their location within the PVT and their network of projections, the function of the neuropeptides in this system likely involves intricate coordination to influence both affective and motivated behavior.
Neural Mechanisms Underlying Repetitive Behaviors in Rodent Models of Autism Spectrum Disorders
Authors: Gandhi Tanya , Lee Charles C.
Published: January 2021

Autism spectrum disorder (ASD) is comprised of several conditions characterized by alterations in social interaction, communication, and repetitive behaviors. Genetic and environmental factors contribute to the heterogeneous development of ASD behaviors. Several rodent models display ASD-like phenotypes, including repetitive behaviors. In this review article, we discuss the potential neural mechanisms involved in repetitive behaviors in rodent models of ASD and related neuropsychiatric disorders. We review signaling pathways, neural circuits, and anatomical alterations in rodent models that display robust stereotypic behaviors. Understanding the mechanisms and circuit alterations underlying repetitive behaviors in rodent models of ASD will inform translational research and provide useful insight into therapeutic strategies for the treatment of repetitive behaviors in ASD and other neuropsychiatric disorders.
Association Between SCN1A rs2298771, SCN1A rs10188577, SCN2A rs17183814, and SCN2A rs2304016 Polymorphisms and Responsiveness to Antiepileptic Drugs: A Meta-Analysis
Authors: Li Mengmeng , Zhong Rui , Lu Yingxue , Zhao Qian , Li Guangjian , Lin Weihong
Published: January 2021

Background:SCN1A and SCN2A genes have been reported to be associated with the efficacy of single and combined antiepileptic therapy, but the results remain contradictory. Previous meta-analyses on this topic mainly focused on the SCN1A rs3812718 polymorphism. However, meta-analyses focused on SCN1A rs2298771, SCN1A rs10188577, SCN2A rs17183814, or SCN2A rs2304016 polymorphisms are scarce or non-existent.

Objective: We aimed to conduct a meta-analysis to determine the effects of SCN1A rs2298771, SCN1A rs10188577, SCN2A rs17183814, and SCN2A rs2304016 polymorphisms on resistance to antiepileptic drugs (AEDs).

Methods: We searched the PubMed, Embase, Cochrane Library, WANFANG, and CNKI databases up to June 2020 to collect studies on the association of SCN1A and SCN2A polymorphisms with reactivity to AEDs. We calculated the pooled odds ratios (ORs) under the allelic, homozygous, heterozygous, dominant, and recessive genetic models to identify the association between the four single-nucleotide polymorphisms (SNPs) and resistance to AEDs.

Results: Our meta-analysis included 19 eligible studies. The results showed that the SCN1A rs2298771 polymorphism was related to AED resistance in the allelic, homozygous, and recessive genetic models (G vs. A: OR = 1.20, 95% CI: 1.012–1.424; GG vs. AA: OR = 1.567, 95% CI: 1.147–2.142; GG vs. AA + AG: OR = 1.408, 95% CI: 1.053–1.882). The homozygous model remained significant after Bonferroni correction (P < 0.0125). Further subgroup analyses demonstrated the significance of the correlation in the dominant model in Caucasians (South Asians) after Bonferroni correction (GG + GA vs. AA: OR = 1.620, 95% CI: 1.165–2.252). However, no association between SCN1A rs2298771 polymorphism and resistance to AEDs was found in Asians or Caucasians (non-South Asians). For SCN1A rs10188577, SCN2A rs17183814, and SCN2A rs2304016 polymorphisms, the correlations with responsiveness to AEDs were not significant in the overall population nor in any subgroup after conducting the Bonferroni correction. The results for SCN1A rs2298771, SCN1A rs10188577, and SCN2A rs2304016 polymorphisms were stable and reliable according to sensitivity analysis and Begg and Egger tests. However, the results for SCN2A rs17183814 polymorphism have to be treated cautiously owing to the significant publication bias revealed by Begg and Egger tests.

Conclusions: The present meta-analysis indicated that SCN1A rs2298771 polymorphism significantly affects resistance to AEDs in the overall population and Caucasians (South Asians). There were no significant correlations between SCN1A rs10188577, SCN2A rs17183814, and SCN2A rs2304016 polymorphisms and resistance to AEDs.
Cognitive Dysfunction and Mortality After Carotid Endarterectomy
Authors: Relander Kristiina , Hietanen Marja , Nuotio Krista , Ijäs Petra , Tikkala Irene , Saimanen Eija , Lindsberg Perttu J. , Soinne Lauri
Published: January 2021

Background: Carotid endarterectomy (CEA) has been associated with both postoperative cognitive dysfunction (POCD) and improvement (POCI). However, the prognostic significance of postoperative cognitive changes related to CEA is largely unknown. The aim of this study was to examine the associations between postoperative cognitive changes after CEA and long-term survival.

Methods: We studied 43 patients 1 day before CEA as well as 4 days and 3 months after surgery with an extensive neuropsychological test array, and followed them for up to 14 years. POCD and POCI relative to baseline were determined with the reliable change index derived from 17 healthy controls. Associations between POCD/POCI and mortality within the patient group were studied with Cox regression analyses adjusted for confounders.

Results: POCD in any functional domain was evident in 28% of patients 4 days after surgery and in 33% of patients 3 months after surgery. POCI was shown in 23% of patients at 4 days and in 44% of patients at 3 months. POCD at 3 months was associated with higher long-term mortality (hazard ratio 5.0, 95% CI 1.8–13.9, p = 0.002) compared with patients with no cognitive decline.

Conclusions: Our findings suggest that POCD in a stable phase, 3 months after CEA predicts premature death. Evaluation of postoperative cognitive changes is essential, and POCD in a stable phase after CEA should prompt scrutiny of underlying factors and better adherence to therapies to prevent recurrences and to promote early intervention in imminent deterioration.
The Human Brain Representation of Odor Identification in Amnestic Mild Cognitive Impairment and Alzheimer's Dementia of Mild Degree
Authors: Kjelvik Grete , Evensmoen Hallvard R. , Hummel Thomas , Engedal Knut , Selbæk Geir , Saltvedt Ingvild , Håberg Asta K.
Published: January 2021

Background:Odor identification (OI) ability is a suggested early biomarker of Alzheimer's disease. In this study, we investigated brain activity within the brain's olfactory network associated with OI in patients with amnestic mild cognitive impairment (aMCI) and mild Alzheimer's dementia (mAD) to uncover the neuronal basis of this impairment.

Materials and Methods:Patients with aMCI (n= 11) or mAD (n= 6) and 28 healthy older adults underwent OI functional MRI (fMRI) at 3T, OI, odor discrimination, and cognitive tests and apolipoprotein-e4 (APOE4) genotyping. Eleven patients had cerebrospinal fluid (CSF) analyzed. Those with aMCI were followed for 2 years to examine conversion to dementia.

Results:The aMCI/mAD group performed significantly worse on all OI tests and the odor discrimination test compared to controls. The aMCI/mAD group had reduced activation in the right anterior piriform cortex compared to the controls during OI fMRI [Gaussian random field (GRF) corrected cluster threshold,p< 0.05]. This group difference remained after correcting for age, sex education, and brain parenchymal fraction. This difference in piriform activity was driven primarily by differences in odor discrimination ability and to a lesser extent by OI ability. There was no group by odor discrimination/identification score interaction on brain activity. Across both groups, only odor discrimination score was significantly associated with brain activity located to the right piriform cortex. Brain activity during OI was not associated with Mini Mental Status Examination scores. At the group level, the aMCI/mAD group activated only the anterior insula, while the control group had significant activation within all regions of the olfactory network during OI fMRI. There was no association between brain activity during OI fMRI and total beta-amyloid levels in the CSF in the aMCI/mAD group.

Conclusion:The OI impairment in aMCI/mAD patients is associated with significantly reduced activity in the piriform cortex compared to controls. Activation of downstream regions within the olfactory network is also significantly affected in the aMCI/mAD group, except the anterior insula, which is impinged late in the course of Alzheimer's disease. OI tests thus reflect Alzheimer's disease pathology in olfactory brain structures.
Case Report: Auditory Neuropathy and Central Auditory Processing Deficits in a Neuro-Otological Case-Study of Infratentorial Superficial Siderosis
Authors: Kharytaniuk Natallia , Cowley Peter , Werring David J. , Bamiou Doris-Eva
Published: January 2021

Hearing and balance impairment are the most frequently reported features of infratentorial (classical) superficial siderosis (iSS). There are few comprehensive descriptions of audiovestibular function in iSS and therefore limited understanding of the affected segment(s) of the audiovestibular pathway. In addition, monitoring disease progression and response to treatment is challenging and currently mainly guided by subjective patient reports and magnetic resonance imaging. To the best of our knowledge, there have been no previous reports assessing central auditory function in iSS. We describe such findings in a patient with iSS in an attempt to precisely localize the site of the audiovestibular dysfunction, determine its severity and functional impact. We confirm the presence of (asymmetrical) auditory neuropathy and identify central auditory processing deficits, suggesting involvement of the central auditory pathway beyond the brainstem. We correlate the audiological and vestibular findings with self-report measures and the siderosis appearances on brain magnetic resonance images.
A Mobile Phone App-Based Tai Chi Training in Parkinson's Disease: Protocol for a Randomized Controlled Study
Authors: Gao Song , Kaudimba Keneilwe Kenny , Cai Jiaxin , Tong Yao , Tian Qianqian , Liu Peize , Liu Tiemin , Chen Peijie , Wang Ru
Published: January 2021

Introduction: With an increasing number of China's aging population, Parkinson's disease (PD) increases year by year. Persons with PD exhibit abnormal balance functions, leading to motor skills difficulties, such as unstable walking or even falling. Therefore, activities of daily living and quality of life are affected. This study aims to explore the effectiveness of Tai Chi training based on the mobile phone app in improving the balance ability of persons with PD.

Methods and Analysis: A randomized, single-blind, parallel controlled trial will be conducted in this study. One hundred forty-four persons with PD who meet the inclusion criteria will be randomly divided into a 1:1:1 ratio: (1) control group, (2) basic experimental group (basic app with no Tai Chi training features), and (3) balanced-enhanced experimental group (basic app with Tai Chi training features). Individuals with PD will be evaluated on balance and motor function outcomes. The primary outcome measure is the limits of stability (including the maximum excursion and direction control); the secondary outcome measures include the Unified Parkinson's Disease Rating Scale III (UPDRS-III), Berg Balance Scale (BBS), Functional Reach Test (FRT), Timed Up & Go (TUG), 6-Minute Walk Test (6MWT), and 39-item Parkinson's Disease Questionnaire (PDQ-39). Each group of patients will go through an assessment at baseline, 17 and 33 weeks.

Discussion: This study will evaluate the effectiveness of the mobile phone app Tai Chi training on the balance function of persons with PD. We assume that a challenging Tai Chi project based on a mobile phone app will improve balance in the short and long term. As walking stability progresses, it is expected that daily activities and quality of life improve. These findings will be used to improve the effectiveness of future home management measures for persons with PD.

Ethics and Dissemination: This study has been approved by the ethical review committee of the Shanghai University of Sport (approval number: 102772019RT056). Informed consent will be obtained from all participants or their guardians. The authors intend to submit the study findings to peer-reviewed journals or academic conferences to be published.

Clinical Trial Registration: Chinese Clinical Trial Registry (ChiCTR2000029135).
Flow Diverter-Assisted Coil Embolization of Blood Blister-Like Aneurysm Using Semi-deploying Technique
Authors: Zhang Ping , Zhong Weiying , Li Tao , Tan Xianjun , Chen Chao , Li Mingxin , Li Zhonggang , Li Gang , Wang Yunyan
Published: January 2021

Despite many therapeutic methods were utilized to treat blood blister-like aneurysms (BBAs), the optimal treatment approach has not yet been defined. This study presents the single center experience with BBAs treated with flow diverter-assisted coiling using semi-deploying technique, and discusses the efficacy and safety of the method. The patients with subarachnoid hemorrhages (SAH) due to BBAs and treated with Pipeline Flex Embolization Device (PED) between November 2015 and February 2019 in our hospital were retrospectively reviewed. Patient demographic data, timing of treatment, angiographic details, treatment techniques, clinical outcomes and follow-up results were recorded. Ten cases (6 women and 4 men) were enrolled. The mean age of patients was 50.7 years (range 40–61 years). The aneurysm size ranged from 2 × 1.7 mm to 4.5 × 3.8 mm. Seven patients were treated with PED assisted coil embolization using semi-deploying technique, and all of the aneurysms were totally obliterated at the follow up. One patient treated with PED assisted coil embolization suffered from parenchymal hemorrhage 3 days after the treatment, and another one patient also treated with PED and coil died of severe vasospasm 10 days after the treatment. There was no reruptured cases during the follow-up. Here we showed that PED assisted coil embolization using semi-deploying technique could be a technically safe and effective treatment for BBAs.
More Than Words: Extra-Sylvian Neuroanatomic Networks Support Indirect Speech Act Comprehension and Discourse in Behavioral Variant Frontotemporal Dementia
Authors: Healey Meghan , Howard Erica , Ungrady Molly , Olm Christopher A. , Nevler Naomi , Irwin David J. , Grossman Murray
Published: January 2021

Indirect speech acts—responding “I forgot to wear my watch today” to someone who asked for the time—are ubiquitous in daily conversation, but are understudied in current neurobiological models of language. To comprehend an indirect speech act like this one, listeners must not only decode the lexical-semantic content of the utterance, but also make a pragmatic, bridging inference. This inference allows listeners to derive the speaker’s true, intended meaning—in the above dialog, for example, that the speaker cannot provide the time. In the present work, we address this major gap by asking non-aphasic patients with behavioral variant frontotemporal dementia (bvFTD, n = 21) and brain-damaged controls with amnestic mild cognitive impairment (MCI, n = 17) to judge simple question-answer dialogs of the form: “Do you want some cake for dessert?” “I’m on a very strict diet right now,” and relate the results to structural and diffusion MRI. Accuracy and reaction time results demonstrate that subjects with bvFTD, but not MCI, are selectively impaired in indirect relative to direct speech act comprehension, due in part to their social and executive limitations, and performance is related to caregivers’ judgment of communication efficacy. MRI imaging associates the observed impairment in bvFTD to cortical thinning not only in traditional language-associated regions, but also in fronto-parietal regions implicated in social and executive cerebral networks. Finally, diffusion tensor imaging analyses implicate white matter tracts in both dorsal and ventral projection streams, including superior longitudinal fasciculus, frontal aslant, and uncinate fasciculus. These results have strong implications for updated neurobiological models of language, and emphasize a core, language-mediated social disorder in patients with bvFTD.
Windows of Integration Hypothesis Revisited
Authors: Hirschhorn Rony , Kahane Ofer , Gur-Arie Inbal , Faivre Nathan , Mudrik Liad
Published: January 2021

In the ongoing research of the functions of consciousness, special emphasis has been put on integration of information: the ability to combine different signals into a coherent, unified one. Several theories of consciousness hold that this ability depends on – or at least goes hand in hand with – conscious processing. Yet some empirical findings have suggested otherwise, claiming that integration of information could take place even without awareness. Trying to reconcile this apparent contradiction, the “windows of integration” (WOI) hypothesis claims that conscious access enables signal processing over large integration windows. The hypothesis applies to integration windows defined either temporally, spatially, or semantically. In this review, we explain the hypothesis and re-examine it in light of new studies published since it was suggested. In line with the hypothesis, these studies provide compelling evidence for unconscious integration, but also demonstrate its limits with respect to time, space, and semantic distance. The review further highlights open questions that still need to be pursued to demonstrate the applicability of the WOI hypothesis as a guiding principle for understanding the depth and scope of unconscious processes.
webTDat: A Web-Based, Real-Time, 3D Visualization Framework for Mesoscopic Whole-Brain Images
Authors: Li Yuxin , Li Anan , Li Junhuai , Zhou Hongfang , Cao Ting , Wang Huaijun , Wang Kan
Published: January 2021

The popularity of mesoscopic whole-brain imaging techniques has increased dramatically, but these techniques generate teravoxel-sized volumetric image data. Visualizing or interacting with these massive data is both necessary and essential in the bioimage analysis pipeline; however, due to their size, researchers have difficulty using typical computers to process them. The existing solutions do not consider applying web visualization and three-dimensional (3D) volume rendering methods simultaneously to reduce the number of data copy operations and provide a better way to visualize 3D structures in bioimage data. Here, we propose webTDat, an open-source, web-based, real-time 3D visualization framework for mesoscopic-scale whole-brain imaging datasets. webTDat uses an advanced rendering visualization method designed with an innovative data storage format and parallel rendering algorithms. webTDat loads the primary information in the image first and then decides whether it needs to load the secondary information in the image. By performing validation on TB-scale whole-brain datasets, webTDat achieves real-time performance during web visualization. The webTDat framework also provides a rich interface for annotation, making it a useful tool for visualizing mesoscopic whole-brain imaging data.
Alternation of Resting-State Functional Connectivity Between Visual Cortex and Hypothalamus in Guinea Pigs With Experimental Glucocorticoid Enhanced Myopia After the Treatment of Electroacupuncture
Authors: Zhang Tao , Jiang Qian , Xu Furu , Zhang Ruixue , Liu Dezheng , Guo Dadong , Wu Jianfeng , Wen Ying , Wang Xingrong , Jiang Wenjun , Bi Hongsheng
Published: January 2021

Excessive glucocorticoids (GC) may lead to the aggravation of several basic diseases including myopia, due to plasma hormone imbalances associated with the hypothalamic–pituitary–adrenal axis (HPAA). Electroacupuncture (EA) is an effective therapeutic method to treat many diseases, although it remains unclear whether EA at acupoints on the foot or back would be effective in treating eye diseases. It was recently found that visual cortex activity for responses to visual stimuli with spatial frequency and resting-state functional connectivity (FC) between the supramarginal gyrus and rostrolateral prefrontal cortex was significantly reduced in patients with high myopia. The present study aims to investigate the role of the alternation of resting-state FC among the bilateral visual cortex and hypothalamus in exerting anti-myopia effects of EA in GC-enhanced lens-induced myopic (LIM) guinea pigs such that the mechanisms of EA to treat GC-enhanced myopia at Shenshu (BL23) acupoints can be probed. To confirm the effects of EA, ocular parameters including axial length and GC-associated physiological parameters such as animal appearance, behavior, bodyweight, and levels of four HPAA-associated plasma hormones [free triiodothyronine (FT3), free thyroxine (FT4), estradiol (E2), and testosterone (T)] were also collected. Increased resting-state FC between the left and right visual cortex was detected in GC-enhanced lens-induced myopic guinea pigs with EA at BL23 acupoints (LIM+GC+EA) guinea pigs compared to GC-enhanced lens-induced myopic guinea pigs with EA at sham acupoints (LIM+GC+Sham) guinea pigs, as well as suppressed myopia and recovery of symptoms initially caused by overdose of GC. Recovered symptoms included improved animal appearance, behavior, bodyweight, and HPAA-associated plasma hormone levels were observed after 4 weeks of EA treatment. In contrast, the LIM+GC+Sham group showed decreased FC with elongation of axial length for myopization as compared to the control group and LIM group and exhibited a deterioration in physiological parameters including reduced body weight and balance disruption in the four measured HPAA-associated plasma hormones. Our findings suggest that EA could effectively treat GC-enhanced myopia by increasing resting-state FC between the left and right visual cortices, which may be pivotal to further understanding the application and mechanisms of EA in treating GC-enhanced myopia.
A Dynamic Multi-Scale Network for EEG Signal Classification
Authors: Zhang Guokai , Luo Jihao , Han Letong , Lu Zhuyin , Hua Rong , Chen Jianqing , Che Wenliang
Published: January 2021

Accurate and automatic classification of the speech imagery electroencephalography (EEG) signals from a Brain-Computer Interface (BCI) system is highly demanded in clinical diagnosis. The key factor in designing an automatic classification system is to extract essential features from the original input; though many methods have achieved great success in this domain, they may fail to process the multi-scale representations from different receptive fields and thus hinder the model from achieving a higher performance. To address this challenge, in this paper, we propose a novel dynamic multi-scale network to achieve the EEG signal classification. The whole classification network is based on ResNet, and the input signal first encodes the features by the Short-time Fourier Transform (STFT); then, to further improve the multi-scale feature extraction ability, we incorporate a dynamic multi-scale (DMS) layer, which allows the network to learn multi-scale features from different receptive fields at a more granular level. To validate the effectiveness of our designed network, we conduct extensive experiments on public dataset III of BCI competition II, and the experimental results demonstrate that our proposed dynamic multi-scale network could achieve promising classification performance in this task.
MicroRNA-138 Overexpression Alters Aβ42 Levels and Behavior in Wildtype Mice
Authors: Boscher Emmanuelle , Goupil Claudia , Petry Serena , Keraudren Rémi , Loiselle Andréanne , Planel Emmanuel , Hébert Sébastien S.
Published: January 2021

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by changes in cognitive and behavioral functions. With the exception or rare mutations in PSEN and APP genes causing early-onset autosomal dominant AD (EOADAD), little is known about the genetic factors that underlie the vast majority (>95%) of early onset AD (EOAD) cases. We have previously identified copy number variations (CNVs) in microRNA genes in patients with EOAD, including a duplication of the MIR-138-2 gene. Overexpression of miR-138 in cultured cells increased Aβ production and tau phosphorylation, similar to what is seen in AD brain. In this study, we sought to determine if miR-138 overexpression could recapitulate certain features of disease in vivo in non-transgenic mice. A mild overexpression of pre-miR-138 in the brain of C57BL/6J wildtype mice altered learning and memory in a novel object recognition test and in the Barnes Maze. Increased levels of anxiety were also observed in the open-field test. MiR-138 upregulation in vivo caused an increase in endogenous Aβ42 production as well as changes in synaptic and inflammation markers. Tau expression was significantly lower with no overt effects on phosphorylation. We finally observed that Sirt1, a direct target of miR-138 involved in Aβ production, learning and memory as well as anxiety, is decreased following miR-138 overexpression. In sum, this study further strengthens a role for increased gene dosage of MIR-138-2 gene in modulating AD risk, possibly by acting on different biological pathways. Further studies will be required to better understand the role of CNVs in microRNA genes in AD and related neurodegenerative disorders.
Multi-Hops Functional Connectivity Improves Individual Prediction of Fusiform Face Activation via a Graph Neural Network
Authors: Wu Dongya , Li Xin , Feng Jun
Published: January 2021

Brain connectivity plays an important role in determining the brain region’s function. Previous researchers proposed that the brain region’s function is characterized by that region’s input and output connectivity profiles. Following this proposal, numerous studies have investigated the relationship between connectivity and function. However, this proposal only utilizes direct connectivity profiles and thus is deficient in explaining individual differences in the brain region’s function. To overcome this problem, we proposed that a brain region’s function is characterized by that region’s multi-hops connectivity profile. To test this proposal, we used multi-hops functional connectivity to predict the individual face activation of the right fusiform face area (rFFA) via a multi-layer graph neural network and showed that the prediction performance is essentially improved. Results also indicated that the two-layer graph neural network is the best in characterizing rFFA’s face activation and revealed a hierarchical network for the face processing of rFFA.
LatLRR-FCNs: Latent Low-Rank Representation With Fully Convolutional Networks for Medical Image Fusion
Authors: Xu Zhengyuan , Xiang Wentao , Zhu Songsheng , Zeng Rui , Marquez-Chin Cesar , Chen Zhen , Chen Xianqing , Liu Bin , Li Jianqing
Published: January 2021

Medical image fusion, which aims to derive complementary information from multi-modality medical images, plays an important role in many clinical applications, such as medical diagnostics and treatment. We propose the LatLRR-FCNs, which is a hybrid medical image fusion framework consisting of the latent low-rank representation (LatLRR) and the fully convolutional networks (FCNs). Specifically, the LatLRR module is used to decompose the multi-modality medical images into low-rank and saliency components, which can provide fine-grained details and preserve energies, respectively. The FCN module aims to preserve both global and local information by generating the weighting maps for each modality image. The final weighting map is obtained using the weighted local energy and the weighted sum of the eight-neighborhood-based modified Laplacian method. The fused low-rank component is generated by combining the low-rank components of each modality image according to the guidance provided by the final weighting map within pyramid-based fusion. A simple sum strategy is used for the saliency components. The usefulness and efficiency of the proposed framework are thoroughly evaluated on four medical image fusion tasks, including computed tomography (CT) and magnetic resonance (MR), T1- and T2-weighted MR, positron emission tomography and MR, and single-photon emission CT and MR. The results demonstrate that by leveraging the LatLRR for image detail extraction and the FCNs for global and local information description, we can achieve performance superior to the state-of-the-art methods in terms of both objective assessment and visual quality in some cases. Furthermore, our method has a competitive performance in terms of computational costs compared to other baselines.
A Heterogeneous Spiking Neural Network for Unsupervised Learning of Spatiotemporal Patterns
Authors: She Xueyuan , Dash Saurabh , Kim Daehyun , Mukhopadhyay Saibal
Published: January 2021

This paper introduces a heterogeneous spiking neural network (H-SNN) as a novel, feedforward SNN structure capable of learning complex spatiotemporal patterns with spike-timing-dependent plasticity (STDP) based unsupervised training. Within H-SNN, hierarchical spatial and temporal patterns are constructed with convolution connections and memory pathways containing spiking neurons with different dynamics. We demonstrate analytically the formation of long and short term memory in H-SNN and distinct response functions of memory pathways. In simulation, the network is tested on visual input of moving objects to simultaneously predict for object class and motion dynamics. Results show that H-SNN achieves prediction accuracy on similar or higher level than supervised deep neural networks (DNN). Compared to SNN trained with back-propagation, H-SNN effectively utilizes STDP to learn spatiotemporal patterns that have better generalizability to unknown motion and/or object classes encountered during inference. In addition, the improved performance is achieved with 6x fewer parameters than complex DNNs, showing H-SNN as an efficient approach for applications with constrained computation resources.
Spatiotemporal Processing of Bimodal Odor Lateralization in the Brain Using Electroencephalography Microstates and Source Localization
Authors: Hucke Christine Ida , Heinen Rebekka Margret , Pacharra Marlene , Wascher Edmund , van Thriel Christoph
Published: January 2021

The neuronal cascade related to the perception of either purely olfactory or trigeminal airborne chemicals has been investigated using electroencephalography (EEG) microstate analyses and source localization. However, most airborne chemicals are bimodal in nature, encompassing both properties. Moreover, there is an ongoing debate regarding whether there is one dominant nostril, and this could be investigated using these multichannel EEG methods. In this study, 18 right-handed, healthy participants (13 females) were monorhinally stimulated using an olfactometer with the bimodal component acetic acid during continuous EEG recording. Participants indicated the side of stimulation, the confidence in their decision, and rated the strength of the evoked perception. EEG microstate clustering determined four distinct maps and successive backfitting procedures, and source estimations revealed a network that evolved from visual-spatial processing areas to brain areas related to basic olfactory and trigeminal sensations (e.g., thalamus, cingulate cortex, insula, parahippocampal, and pre-/post-central gyri) and resulted in activation of areas involved in multisensory integration (e.g., frontal-temporal areas). Right-nostril stimulation was associated with faster microstate transition and longer involvement of the superior temporal gyrus, which was previously linked to chemical localization and provides evidence for a potential nostril dominance. The results describe for the first time the processing cascade of bimodal odor perception using microstate analyses and demonstrate its feasibility to further investigate potential nostril dominance.