Brain Sciences

10 pages, 744 KiB

Open AccessEditor’s ChoiceArticle

The Burden of Respiratory Alterations during Sleep on Comorbidities in Obstructive Sleep Apnoea (OSA)

by Pasquale Tondo, Francesco Fanfulla, Giulia Scioscia, Roberto Sabato, Michela Salvemini, Cosimo C. De Pace, Maria Pia Foschino Barbaro and Donato Lacedonia

Brain Sci. 2022, 12(10), 1359; https://doi.org/10.3390/brainsci12101359 - 06 Oct 2022

Cited by 9 | Viewed by 1437

Abstract

Background: Obstructive sleep apnoea (OSA) has an important impact on the risk of morbidity and mortality, so we have designed the present study to understand which factor is most involved in the risk of developing a comorbidity between OSA severity and nocturnal hypoxemia. [...] Read more.

Background: Obstructive sleep apnoea (OSA) has an important impact on the risk of morbidity and mortality, so we have designed the present study to understand which factor is most involved in the risk of developing a comorbidity between OSA severity and nocturnal hypoxemia. Methods: A retrospective study was conducted on 617 adult subjects who were referred to our unit for a suspicion of OSA between January 2018 and January 2020. Results: Sleep investigations performed by participants (72% male and obese in 70% of cases) reported an overall mean apnoea–hypopnoea index (AHI) of 44.0 ± 24.8 events·h⁻¹. Overall, 66% were classified as severe OSA and 76% experienced nocturnal hypoxemia. By analysing the burden of OSA severity and nocturnal hypoxemia on the comorbidities risk, multivariate analysis highlighted the predominant role of age and obesity. Accordingly, after the exclusion of the older and obese participants from the analyses, we noticed that severe OSA was related to the risk of hypertension (odds ratio (OR) = 3.0 [95% confidence interval [CI] 1.4–6.2], p = 0.004) as well as nocturnal hypoxemia (OR = 2.6 [95% CI 1.2–5.4], p = 0.01). Conclusions: The study seems to suggest that in young, non-obese subjects, OSA is a predisposing factor for the risk of developing hypertension. Full article

(This article belongs to the Section Developmental Neuroscience)

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16 pages, 1218 KiB

Open AccessEditor’s ChoiceReview

Impulsivity in Bipolar Disorder: State or Trait?

by Rachel Primo Santana, Jess Kerr-Gaffney, Anda Ancane and Allan H. Young

Brain Sci. 2022, 12(10), 1351; https://doi.org/10.3390/brainsci12101351 - 05 Oct 2022

Cited by 11 | Viewed by 2082

Abstract

Impulsive behaviour is a key characteristic of mania in bipolar disorder (BD). However, there is mixed evidence as to whether impulsivity is a trait feature of the disorder, present in the euthymic state in the absence of mania. The aim of this systematic [...] Read more.

Impulsive behaviour is a key characteristic of mania in bipolar disorder (BD). However, there is mixed evidence as to whether impulsivity is a trait feature of the disorder, present in the euthymic state in the absence of mania. The aim of this systematic review and meta-analysis was to examine whether impulsivity is elevated in euthymic BD in comparison to controls. Electronic databases were searched for papers published until April 2022 reporting data on a self-report or behavioural measure of impulsivity in a euthymic BD group and a healthy control group. In total, 46 studies were identified. Euthymic BD showed significantly higher levels of self-reported impulsivity compared to controls (large effect size). Euthymic BD also showed significantly higher levels of impulsivity on response inhibition and inattention tasks, with moderate and large effect sizes, respectively. Only two studies measured delay of gratification, finding no significant differences between groups. Our results suggest impulsivity may be a trait feature of BD, however longitudinal cohort studies are required to confirm whether elevated impulsivity is present before illness onset. Future research should establish whether cognitive interventions are beneficial in improving impulsivity in BD. Full article

(This article belongs to the Special Issue Bipolar Disorders: Progressing from Bench to Bedside)

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18 pages, 5350 KiB

Open AccessEditor’s ChoiceArticle

A Bioinformatics-Based Analysis of an Anoikis-Related Gene Signature Predicts the Prognosis of Patients with Low-Grade Gliomas

by Songyun Zhao, Hao Chi, Wei Ji, Qisheng He, Guichuan Lai, Gaoge Peng, Xiaoyu Zhao and Chao Cheng

Brain Sci. 2022, 12(10), 1349; https://doi.org/10.3390/brainsci12101349 - 05 Oct 2022

Cited by 33 | Viewed by 2874

Abstract

Low-grade glioma (LGG) is a highly aggressive disease in the skull. On the other hand, anoikis, a specific form of cell death induced by the loss of cell contact with the extracellular matrix, plays a key role in cancer metastasis. In this study, [...] Read more.

Low-grade glioma (LGG) is a highly aggressive disease in the skull. On the other hand, anoikis, a specific form of cell death induced by the loss of cell contact with the extracellular matrix, plays a key role in cancer metastasis. In this study, anoikis-related genes (ANRGs) were used to identify LGG subtypes and to construct a prognostic model for LGG patients. In addition, we explored the immune microenvironment and enrichment pathways between different subtypes. We constructed an anoikis-related gene signature using the TCGA (The Cancer Genome Atlas) cohort and investigated the differences between different risk groups in clinical features, mutational landscape, immune cell infiltration (ICI), etc. Kaplan–Meier analysis showed that the characteristics of ANRGs in the high-risk group were associated with poor prognosis in LGG patients. The risk score was identified as an independent prognostic factor. The high-risk group had higher ICI, tumor mutation load (TMB), immune checkpoint gene expression, and therapeutic response to immune checkpoint blockers (ICB). Functional analysis showed that these high-risk and low-risk groups had different immune statuses and drug sensitivity. Risk scores were used together with LGG clinicopathological features to construct a nomogram, and Decision Curve Analysis (DCA) showed that the model could enable patients to benefit from clinical treatment strategies. Full article

(This article belongs to the Section Molecular and Cellular Neuroscience)

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17 pages, 1631 KiB

Open AccessEditor’s ChoiceReview

Statins Use in Alzheimer Disease: Bane or Boon from Frantic Search and Narrative Review

by Nawal Alsubaie, Hayder M. Al-kuraishy, Ali I. Al-Gareeb, Bandar Alharbi, Michel De Waard, Jean-Marc Sabatier, Hebatallah M. Saad and Gaber El-Saber Batiha

Brain Sci. 2022, 12(10), 1290; https://doi.org/10.3390/brainsci12101290 - 24 Sep 2022

Cited by 31 | Viewed by 4976

Abstract

Alzheimer’s disease (AD) was used to describe pre-senile dementia to differentiate it from senile dementia, which develops in the adult age group of more than 65 years. AD is characterized by the deposition of amyloid beta (Aβ) plaque and tau-neurofibrillary tangles (TNTs) in [...] Read more.

Alzheimer’s disease (AD) was used to describe pre-senile dementia to differentiate it from senile dementia, which develops in the adult age group of more than 65 years. AD is characterized by the deposition of amyloid beta (Aβ) plaque and tau-neurofibrillary tangles (TNTs) in the brain. The neuropathological changes in AD are related to the deposition of amyloid plaques, neurofibrillary tangles, and progression of neuroinflammation, neuronal mitochondrial dysfunction, autophagy dysfunction, and cholinergic synaptic dysfunction. Statins are one of the main cornerstone drugs for the management of cardiovascular disorders regardless of dyslipidemia status. Increasing the use of statins, mainly in the elderly groups for primary and secondary prevention of cardiovascular diseases, may affect their cognitive functions. Extensive and prolonged use of statins may affect cognitive functions in healthy subjects and dementia patients. Statins-induced cognitive impairments in both patients and health providers had been reported according to the post-marketing survey. This survey depends mainly on sporadic cases, and no cognitive measures were used. Evidence from prospective and observational studies gives no robust conclusion regarding the beneficial or detrimental effects of statins on cognitive functions in AD patients. Therefore, this study is a narrative review aimed with evidences to the beneficial, detrimental, and neutral effects of statins on AD. Full article

(This article belongs to the Section Neuropharmacology and Neuropathology)

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20 pages, 399 KiB

Open AccessEditor’s ChoiceReview

Sucrose Preference Test as a Measure of Anhedonic Behavior in a Chronic Unpredictable Mild Stress Model of Depression: Outstanding Issues

by Dmitrii D. Markov

Brain Sci. 2022, 12(10), 1287; https://doi.org/10.3390/brainsci12101287 - 24 Sep 2022

Cited by 23 | Viewed by 5028

Abstract

Despite numerous studies on the neurobiology of depression, the etiological and pathophysiological mechanisms of this disorder remain poorly understood. A large number of animal models and tests to evaluate depressive-like behavior have been developed. Chronic unpredictable mild stress (CUMS) is the most common [...] Read more.

Despite numerous studies on the neurobiology of depression, the etiological and pathophysiological mechanisms of this disorder remain poorly understood. A large number of animal models and tests to evaluate depressive-like behavior have been developed. Chronic unpredictable mild stress (CUMS) is the most common and frequently used model of depression, and the sucrose preference test (SPT) is one of the most common tests for assessing anhedonia. However, not all laboratories can reproduce the main effects of CUMS, especially when this refers to a decrease in sucrose preference. It is also unknown how the state of anhedonia, assessed by the SPT, relates to the state of anhedonia in patients with depression. We analyzed the literature available in the PubMed database using keywords relevant to the topic of this narrative review. We hypothesize that the poor reproducibility of the CUMS model may be due to differences in sucrose consumption, which may be influenced by such factors as differences in sucrose preference concentration threshold, water and food deprivation, and differences in animals’ susceptibility to stress. We also believe that comparisons between animal and human states of anhedonia should be made with caution because there are many inconsistencies between the two, including in assessment methods. We also tried to offer some recommendations that should improve the reproducibility of the CUMS model and provide a framework for future research. Full article

(This article belongs to the Special Issue Hedonic, Motivation and Learning Mechanisms of Ingestive Behavior)

13 pages, 1591 KiB

Open AccessEditor’s ChoiceArticle

High-Intensity Interval Training-Induced Hippocampal Molecular Changes Associated with Improvement in Anxiety-like Behavior but Not Cognitive Function in Rats with Type 2 Diabetes

by Amin Orumiyehei, Kayvan Khoramipour, Maryam Hossein Rezaei, Elham Madadizadeh, Manzumeh Shamsi Meymandi, Fatemeh Mohammadi, Mohsen Chamanara, Hamideh Bashiri and Katsuhiko Suzuki

Brain Sci. 2022, 12(10), 1280; https://doi.org/10.3390/brainsci12101280 - 23 Sep 2022

Cited by 14 | Viewed by 2301

Abstract

(1) Background: Exercise exerts many neuroprotective effects in diabetes-induced brain disorders. In this study, we investigated the effect of high-intensity interval training (HIIT) on brain molecular changes and cognitive and anxiety-like behaviors in rats with type 2 diabetes. (2) Methods: Twenty-eight adult male [...] Read more.

(1) Background: Exercise exerts many neuroprotective effects in diabetes-induced brain disorders. In this study, we investigated the effect of high-intensity interval training (HIIT) on brain molecular changes and cognitive and anxiety-like behaviors in rats with type 2 diabetes. (2) Methods: Twenty-eight adult male rats were divided into four groups (n = 7): control (C), exercise + control (C+EX), diabetes (DM), and diabetes + exercise (DM+EX). Diabetes was induced using a two-month high-fat diet and a single dose of streptozotocin (35 mg/kg) in the DM and DM+EX groups. After, the C+EX and DM+EX groups performed HIIT for eight weeks (five sessions per week, running at 80–100% of V_Max, 4–10 intervals) on a motorized treadmill. Then, the elevated plus maze (EPM) and open field test (OFT) were performed to evaluate anxiety-like behaviors. The Morris water maze (MWM) and shuttle box were used to assess cognitive function. The hippocampal levels of beta-amyloid and tau protein were also assessed using Western blot. (3) Results: The hippocampal levels of beta-amyloid and tau protein were increased in the DM group, but HIIT restored these changes. While diabetes led to a significant decrease in open arm time percentage (%OAT) and open arm enters percentage (%OAE) in the EPM, indicating anxiety-like behavior, HIIT restored them. In the OFT, grooming was decreased in diabetic rats, which was restored by HIIT. No significant difference between groups was seen in the latency time in the shuttle box or for learning and memory in the MWM. (4) Conclusions: HIIT-induced hippocampal molecular changes were associated with anxiety-like behavior improvement but not cognitive function in rats with type 2 diabetes. Full article

(This article belongs to the Section Behavioral Neuroscience)

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14 pages, 4765 KiB

Open AccessEditor’s ChoiceArticle

Hydrogen Sulfide Attenuates Neuroinflammation by Inhibiting the NLRP3/Caspase-1/GSDMD Pathway in Retina or Brain Neuron following Rat Ischemia/Reperfusion

by Kun-Li Yang, Wen-Hong Li, Ya-Jie Liu, Ying-Juan Wei, Yan-Kai Ren, Chen-Di Mai, Si-Yu Zhang, Yue Zuo, Zhen-Zhou Sun, Dong-Liang Li and Chih-Huang Yang

Brain Sci. 2022, 12(9), 1245; https://doi.org/10.3390/brainsci12091245 - 15 Sep 2022

Cited by 10 | Viewed by 2323

Abstract

Gasdermin D-executing pyroptosis mediated by NLRP3 inflammasomes has been recognized as a key pathogenesis during stroke. Hydrogen sulfide (H₂S) could protect CNS against ischemia/reperfusion (I/R)-induced neuroinflammation, while the underlying mechanism remains unclear. The study applied the middle cerebral artery occlusion/reperfusion (MCAO/R) [...] Read more.

Gasdermin D-executing pyroptosis mediated by NLRP3 inflammasomes has been recognized as a key pathogenesis during stroke. Hydrogen sulfide (H₂S) could protect CNS against ischemia/reperfusion (I/R)-induced neuroinflammation, while the underlying mechanism remains unclear. The study applied the middle cerebral artery occlusion/reperfusion (MCAO/R) model to investigate how the brain and the retinal injuries were alleviated in sodium hydrogen sulfide (NaHS)-treated rats. The rats were assigned to four groups and received an intraperitoneal injection of 50 μmol/kg NaHS or NaCl 15 min after surgery. Neurological deficits were evaluated using the modified neurologic severity score. The quantification of pro-inflammatory cytokines, NLRP3, caspase-1, and GSDMD were determined by ELISA and Western blot. Cortical and retinal neurodegeneration and cell pyroptosis were determined by histopathologic examination. Results showed that NaHS rescued post-stroke neurological deficits and infarct progression, improved retina injury, and attenuated neuroinflammation in the brain cortexes and the retinae. NaHS administration inhibits inflammation by blocking the NLRP3/caspase-1/GSDMD pathway and further suppressing neuronal pyroptosis. This is supported by the fact that it reversed the high-level of NLRP3, caspase-1, and GSDMD following I/R. Our findings suggest that compounds with the ability to donate H₂S could constitute a novel therapeutic strategy for ischemic stroke. Full article

(This article belongs to the Topic Brain Injury, Microcirculation and Tissue Perfusion)

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24 pages, 1225 KiB

Open AccessEditor’s ChoiceReview

Alzheimer’s Disease and Inflammaging

by Anna Mikhailovna Kosyreva, Alexandra Vladislavovna Sentyabreva, Ivan Sergeevich Tsvetkov and Olga Vasilievna Makarova

Brain Sci. 2022, 12(9), 1237; https://doi.org/10.3390/brainsci12091237 - 13 Sep 2022

Cited by 27 | Viewed by 3907

Abstract

Alzheimer’s disease is one of the most common age-related neurodegenerative disorders. The main theory of Alzheimer’s disease progress is the amyloid-β cascade hypothesis. However, the initial mechanisms of insoluble forms of amyloid-β formation and hyperphosphorylated tau protein in neurons remain unclear. One of [...] Read more.

Alzheimer’s disease is one of the most common age-related neurodegenerative disorders. The main theory of Alzheimer’s disease progress is the amyloid-β cascade hypothesis. However, the initial mechanisms of insoluble forms of amyloid-β formation and hyperphosphorylated tau protein in neurons remain unclear. One of the factors, which might play a key role in senile plaques and tau fibrils generation due to Alzheimer’s disease, is inflammaging, i.e., systemic chronic low-grade age-related inflammation. The activation of the proinflammatory cell phenotype is observed during aging, which might be one of the pivotal mechanisms for the development of chronic inflammatory diseases, e.g., atherosclerosis, metabolic syndrome, type 2 diabetes mellitus, and Alzheimer’s disease. This review discusses the role of the inflammatory processes in developing neurodegeneration, activated during physiological aging and due to various diseases such as atherosclerosis, obesity, type 2 diabetes mellitus, and depressive disorders. Full article

(This article belongs to the Section Neuropharmacology and Neuropathology)

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20 pages, 5181 KiB

Open AccessEditor’s ChoiceReview

What Do We Know about Social and Non-Social Factors Influencing the Pathway from Cognitive Health to Dementia? A Systematic Review of Reviews

by Marta Lenart-Bugla, Mateusz Łuc, Marcin Pawłowski, Dorota Szcześniak, Imke Seifert, Henrik Wiegelmann, Ansgar Gerhardus, Karin Wolf-Ostermann, Etiënne A. J. A. Rouwette, M. Arfan Ikram, Henry Brodaty, Yun-Hee Jeon, Jane Maddock, Anna Marseglia, René J. F. Melis, Suraj Samtani, Hui-Xin Wang, Anna-Karin Welmer, Myrra Vernooij-Dassen and Joanna Rymaszewska

Brain Sci. 2022, 12(9), 1214; https://doi.org/10.3390/brainsci12091214 - 08 Sep 2022

Cited by 12 | Viewed by 4128

Abstract

The heterogeneous and multi-factorial nature of dementia requires the consideration of all health aspects when predicting the risk of its development and planning strategies for its prevention. This systematic review of reviews provides a comprehensive synthesis of those factors associated with cognition in [...] Read more.

The heterogeneous and multi-factorial nature of dementia requires the consideration of all health aspects when predicting the risk of its development and planning strategies for its prevention. This systematic review of reviews provides a comprehensive synthesis of those factors associated with cognition in the context of dementia, identifying the role of social aspects and evidencing knowledge gaps in this area of research. Systematic reviews and meta-analyses from 2009–2021 were searched for within Medline, PsycINFO, CINAHL Complete, Cochrane, and Epistemonikos. Reviewers independently screened, reviewed, and assessed the records, following the PRISMA-2020 guidelines. From 314 included studies, 624 cognitive-related factors were identified, most of them risk factors (61.2%), mainly belonging to the group of ‘somatic comorbidities’ (cardiovascular disease and diabetes) and ‘genetic predispositions’. The protective factors (20%) were mainly related to lifestyle, pointing to the Mediterranean diet, regular physical activity, and cognitively stimulating activities. Social factors constituted 9.6% of all identified factors. Research on biological and medical factors dominates the reviewed literature. Greater social support and frequent contact may confer some protection against cognitive decline and dementia by delaying its onset or reducing the overall risk; however, overall, our findings are inconsistent. Further research is needed in the fields of lifestyle, psychology, social health, and the protective factors against cognitive decline and dementia. Full article

(This article belongs to the Special Issue Social Cognition across Healthy and Neuropsychiatric Conditions)

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10 pages, 1178 KiB

Open AccessEditor’s ChoiceBrief Report

Safety Evaluation of Employing Temporal Interference Transcranial Alternating Current Stimulation in Human Studies

by Yi Piao, Ru Ma, Yaohao Weng, Chuan Fan, Xinzhao Xia, Wei Zhang, Ginger Qinghong Zeng, Yan Wang, Zhuo Lu, Jiangtian Cui, Xiaoxiao Wang, Li Gao, Bensheng Qiu and Xiaochu Zhang

Brain Sci. 2022, 12(9), 1194; https://doi.org/10.3390/brainsci12091194 - 05 Sep 2022

Cited by 9 | Viewed by 3296

Abstract

Temporal interference transcranial alternating current stimulation (TI-tACS) is a new technique of noninvasive brain stimulation. Previous studies have shown the effectiveness of TI-tACS in stimulating brain areas in a selective manner. However, its safety in modulating human brain neurons is still untested. In [...] Read more.

Temporal interference transcranial alternating current stimulation (TI-tACS) is a new technique of noninvasive brain stimulation. Previous studies have shown the effectiveness of TI-tACS in stimulating brain areas in a selective manner. However, its safety in modulating human brain neurons is still untested. In this study, 38 healthy adults were recruited to undergo a series of neurological and neuropsychological measurements regarding safety concerns before and after active (2 mA, 20/70 Hz, 30 min) or sham (0 mA, 0 Hz, 30 min) TI-tACS. The neurological and neuropsychological measurements included electroencephalography (EEG), serum neuron-specific enolase (NSE), the Montreal Cognitive Assessment (MoCA), the Purdue Pegboard Test (PPT), an abbreviated version of the California Computerized Assessment Package (A-CalCAP), a revised version of the Visual Analog Mood Scale (VAMS-R), a self-assessment scale (SAS), and a questionnaire about adverse effects (AEs). We found no significant difference between the measurements of the active and sham TI-tACS groups. Meanwhile, no serious or intolerable adverse effects were reported or observed in the active stimulation group of 19 participants. These results support that TI-tACS is safe and tolerable in terms of neurological and neuropsychological functions and adverse effects for use in human brain stimulation studies under typical transcranial electric stimulation (TES) conditions (2 mA, 20/70 Hz, 30 min). Full article

(This article belongs to the Special Issue Neuromodulation, Brain Plasticity and Psychiatric Diseases)

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10 pages, 577 KiB

Open AccessEditor’s ChoiceArticle

Testing the Impact of Depressive and Anxiety Features on the Association between Attention-Deficit/Hyperactivity Disorder Symptoms and Academic Performance among University Students: A Mediation Analysis

by Ilaria Riboldi, Cristina Crocamo, Tommaso Callovini, Chiara Alessandra Capogrosso, Susanna Piacenti, Angela Calabrese, Susanna Lucini Paioni, Federico Moretti, Francesco Bartoli and Giuseppe Carrà

Brain Sci. 2022, 12(9), 1155; https://doi.org/10.3390/brainsci12091155 - 30 Aug 2022

Cited by 12 | Viewed by 2837

Abstract

Attention deficit/hyperactivity disorder (ADHD) is associated with poor academic performance also among university students. This relationship may be made more complex by comorbid conditions. The aim of this study was to evaluate the mediating role of anxiety and depressive symptoms in the relationship [...] Read more.

Attention deficit/hyperactivity disorder (ADHD) is associated with poor academic performance also among university students. This relationship may be made more complex by comorbid conditions. The aim of this study was to evaluate the mediating role of anxiety and depressive symptoms in the relationship between ADHD and academic performance. Data were drawn from the CAMPUS study (registration number: 0058642/21), an ongoing survey on university students’ mental health. Using a logit model, mediation analyses were carried out to test whether the relationship between ADHD symptoms (assessed by ASRS-5) and academic performance might be mediated by depressive (assessed by PHQ-9) and anxiety (assessed by GAD-7) symptoms. Our results showed that worse academic performance is associated with ADHD symptoms (p < 0.001). However, about 24% of the overall association between ADHD symptoms and academic performance was mediated by depressive symptoms (indirect effect: 0.065, 95%CI 0.022; 0.100), whereas the contribution of anxiety symptoms to the model was not significant. Along with the association between ADHD symptoms and poor academic performance, our findings highlight the key mediating role of depressive symptoms, which may be targeted with tailored support, ultimately improving both the academic performance and the well-being of university students with ADHD. Full article

(This article belongs to the Special Issue Advances in ADHD)

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16 pages, 374 KiB

Open AccessEditor’s ChoiceArticle

Functional Relationship between Inhibitory Control, Cognitive Flexibility, Psychomotor Speed and Obesity

by Marco La Marra, Ciro Rosario Ilardi, Ines Villano, Mario Carosella, Maria Staiano, Alessandro Iavarone, Sergio Chieffi, Giovanni Messina, Rita Polito, Alessia Scarinci, Vincenzo Monda, Girolamo Di Maio and Antonietta Messina

Brain Sci. 2022, 12(8), 1080; https://doi.org/10.3390/brainsci12081080 - 15 Aug 2022

Cited by 12 | Viewed by 2297

Abstract

In the last decades, it has been proposed that executive functions may be particularly vulnerable to weight-related issues. However, evidence on the matter is mixed, especially when the effects of sociodemographic variables are weighted. Thus, the current study aimed at further examining the [...] Read more.

In the last decades, it has been proposed that executive functions may be particularly vulnerable to weight-related issues. However, evidence on the matter is mixed, especially when the effects of sociodemographic variables are weighted. Thus, the current study aimed at further examining the relationship between executive functions and obesity. To this aim, we compared treatment-seeking overweight, obese, and morbidly obese patients with normal-weight control participants. We examined general executive functioning (Frontal Assessment Battery–15) and different executive subdomains (e.g., inhibitory control, verbal fluency, and psychomotor speed) in a clinical sample including 208 outpatients with different degrees of BMI (52 overweight, BMI 25–30, M age = 34.38; 76 obese, BMI 30–40, M age = 38.00; 80 morbidly obese, BMI > 40, M age = 36.20). Ninety-six normal-weight subjects served as controls. No difference on executive scores was detected when obese patients were compared with over- or normal-weight subjects. Morbidly obese patients reported lower performance on executive scores than obese, overweight, and normal-weight subjects. Between-group difference emerged also when relevant covariates were taken into account. Our results support the view that morbid obesity is associated with lower executive performance, also considering the critical role exerted by sociodemographic (i.e., sex, age, and education) variables. Our results support the view that executive functioning should be accounted into the management of the obese patient because of non-negligible clinical relevance in diagnostic, therapeutic, and prognostic terms. Full article

(This article belongs to the Special Issue Cognitive Functioning in Obesity: New Evidence from Neuropsychology)

14 pages, 2197 KiB

Open AccessEditor’s ChoiceSystematic Review

The Impact of Practicing Open- vs. Closed-Skill Sports on Executive Functions—A Meta-Analytic and Systematic Review with a Focus on Characteristics of Sports

by Florian Heilmann, Henrietta Weinberg and Rainer Wollny

Brain Sci. 2022, 12(8), 1071; https://doi.org/10.3390/brainsci12081071 - 12 Aug 2022

Cited by 17 | Viewed by 3792

Abstract

Exercise modes can be categorized based on the skills required (open vs. closed skills), which implicates various demands on cognitive skills, especially executive functions (EFs). Thus, their practice may have varying effects on EFs. There is a lack of detailed analysis of cognitive [...] Read more.

Exercise modes can be categorized based on the skills required (open vs. closed skills), which implicates various demands on cognitive skills, especially executive functions (EFs). Thus, their practice may have varying effects on EFs. There is a lack of detailed analysis of cognitive requirements and suitable classification of sports. It is hypothesized that the amount and type of cognitive requirements of sports lead to small effect sizes when comparing open-skill exercising (OSE) and closed-skill exercising (CSE) athletes. The current meta-analysis evaluates the variances in EFs skills caused by particular sport modes. Four research databases (Web of Science, PubMed, ScienceDirect, PsychINFO) were searched for cross-sectional studies in which the authors compare the performance in EF tasks of OSE and CSE athletes. Risk of bias assessment was conducted using funnel plots and two reviewer selection process (overall and subgroup analysis; low risk of publication and selection bias). A total of 19 studies were included, revealing an overall effect size of Hedge’s g = 0.174 (p = 0.157), favoring OSE for the development of EFs. The subgroup analysis revealed the effects for the subdomains of EFs (cognitive flexibility: Hedge’s g = 0.210 > inhibitory control: Hedge’s g = 0.191 > working memory: Hedge’s g = 0.138; p > 0.05), which could be characterized as low to moderate. The hypothesis that studies with the smallest effect sizes compare sport modes with similar cognitive demands was rejected. The paper discusses the differentiation of sports into OSE and CSE and presents new approaches for their categorization. Full article

(This article belongs to the Section Neuropsychology)

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12 pages, 1054 KiB

Open AccessEditor’s ChoiceArticle

Neutrophil-to-Lymphocyte, Monocyte-to-Lymphocyte, Platelet-to-Lymphocyte Ratio and Systemic Immune-Inflammatory Index in Different States of Bipolar Disorder

by Katerina Dadouli, Michel B. Janho, Apostolia Hatziefthimiou, Ioanna Voulgaridi, Konstantina Piaha, Lemonia Anagnostopoulos, Panagiotis Ntellas, Varvara A. Mouchtouri, Konstantinos Bonotis, Nikolaos Christodoulou, Matthaios Speletas and Christos Hadjichristodoulou

Brain Sci. 2022, 12(8), 1034; https://doi.org/10.3390/brainsci12081034 - 04 Aug 2022

Cited by 17 | Viewed by 2259

Abstract

The neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammatory (SII) index, which provide a simple, rapid, inexpensive method to measure the level of inflammation, have been examined as potential inflammatory biomarkers of bipolar disorder (BD) in several studies. We [...] Read more.

The neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammatory (SII) index, which provide a simple, rapid, inexpensive method to measure the level of inflammation, have been examined as potential inflammatory biomarkers of bipolar disorder (BD) in several studies. We conducted a case-control study recruiting 180 BD patients and 407 healthy controls. BD patients who met the inclusion criteria and were hospitalized due to BD at the psychiatry clinic of the University General Hospital of Larisa, Greece, until September 2021 were included in the study. Among them, 111 patients experienced a manic episode and 69 patients experienced a depressive episode. Data including a complete blood count were retrieved from their first admission to the hospital. Bipolar patients had a higher NLR, MLR and SII index compared to healthy controls when they were experiencing a manic episode (p < 0.001) and a depressive episode (p < 0.001). MLR was increased with large effect size only in patients expressing manic episodes. Neutrophils and NLR had the highest area under the curve with a cutoff of 4.38 and 2.15 in the ROC curve, respectively. Gender-related differences were mainly observed in the SII index, with males who were expressing manic episodes and females expressing depressive episodes having an increased index compared to healthy controls. The NLR, MLR and SII index were significantly higher in patients with BD than in healthy controls, which implies a higher grade of inflammation in BD patients. Full article

(This article belongs to the Special Issue The Biomarkers in Neuropsychiatric Disorders)

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15 pages, 3537 KiB

Open AccessEditor’s ChoiceArticle

Effects of Stimulus Frequency, Intensity, and Sex on the Autonomic Response to Transcutaneous Vagus Nerve Stimulation

by Hirotake Yokota, Mutsuaki Edama, Ryo Hirabayashi, Chie Sekine, Naofumi Otsuru, Kei Saito, Sho Kojima, Shota Miyaguchi and Hideaki Onishi

Brain Sci. 2022, 12(8), 1038; https://doi.org/10.3390/brainsci12081038 - 04 Aug 2022

Cited by 13 | Viewed by 3703

Abstract

This study aimed to determine how transcutaneous vagus nerve stimulation (tVNS) alters autonomic nervous activity by comparing the effects of different tVNS frequencies and current intensities. We also investigated the sex-dependent autonomic response to tVNS. Thirty-five healthy adult participants were stimulated using a [...] Read more.

This study aimed to determine how transcutaneous vagus nerve stimulation (tVNS) alters autonomic nervous activity by comparing the effects of different tVNS frequencies and current intensities. We also investigated the sex-dependent autonomic response to tVNS. Thirty-five healthy adult participants were stimulated using a tVNS stimulator at the left cymba conchae while sitting on a reclining chair; tVNS-induced waveform changes were then recorded for different stimulus frequencies (Experiment 1: 3.0 mA at 100 Hz, 25 Hz, 10 Hz, 1 Hz, and 0 Hz (no stimulation)) and current intensities (Experiment 2: 100 Hz at 3.0 mA, 1.0 mA, 0.2 mA (below sensory threshold), and 0 mA (no stimulation)) using an electrocardiogram. Pulse widths were set at 250 µs in both experiment 1 and 2. Changes in heart rate (HR), root-mean-square of the difference between two successive R waves (RMSSD), and the ratio between low-frequency (LF) (0.04–0.15 Hz) and high-frequency (HF) (0.15–0.40 Hz) bands (LF/HF) in spectral analysis, which indicates sympathetic and parasympathetic activity, respectively, in heart rate variability (HRV), were recorded for analysis. Although stimulation at all frequencies significantly reduced HR (p = 0.001), stimulation at 100 Hz had the most pronounced effect (p = 0.001) in Experiment 1 and was revealed to be required to deliver at 3.0 mA in Experiment 2 (p = 0.003). Additionally, participants with higher baseline sympathetic activity experienced higher parasympathetic response during stimulation, and sex differences may exist in the autonomic responses by the application of tVNS. Therefore, our findings suggest that optimal autonomic changes induced by tVNS to the left cymba conchae vary depending on stimulating parameters and sex. Full article

(This article belongs to the Section Systems Neuroscience)

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16 pages, 4358 KiB

Open AccessEditor’s ChoiceArticle

Integrated Analysis of Cortex Single-Cell Transcriptome and Serum Proteome Reveals the Novel Biomarkers in Alzheimer’s Disease

by Qing-Shan Yu, Wan-Qing Feng, Lan-Lan Shi, Rui-Ze Niu and Jia Liu

Brain Sci. 2022, 12(8), 1022; https://doi.org/10.3390/brainsci12081022 - 01 Aug 2022

Cited by 7 | Viewed by 2916

Abstract

Blood-based proteomic analysis is a routine practice for detecting the biomarkers of human disease. The results obtained from blood alone cannot fully reflect the alterations of nerve cells, including neurons and glia cells, in Alzheimer’s disease (AD) brains. Therefore, the present study aimed [...] Read more.

Blood-based proteomic analysis is a routine practice for detecting the biomarkers of human disease. The results obtained from blood alone cannot fully reflect the alterations of nerve cells, including neurons and glia cells, in Alzheimer’s disease (AD) brains. Therefore, the present study aimed to investigate novel potential AD biomarker candidates, through an integrated multi-omics approach in AD. We propose a comprehensive strategy to identify high-confidence candidate biomarkers by integrating multi-omics data from AD, including single-nuclei RNA sequencing (snRNA-seq) datasets of the prefrontal and entorhinal cortices, as wells as serum proteomic datasets. We first quantified a total of 124,658 nuclei, 8 cell types, and 3701 differentially expressed genes (DEGs) from snRNA-seq dataset of 30 human cortices, as well as 1291 differentially expressed proteins (DEPs) from serum proteomic dataset of 11 individuals. Then, ten DEGs/DEPs (NEBL, CHSY3, STMN2, MARCKS, VIM, FGD4, EPB41L2, PLEKHG1, PTPRZ1, and PPP1R14A) were identified by integration analysis of snRNA-seq and proteomics data. Finally, four novel candidate biomarkers (NEBL, EPB41L2, FGD4, and MARCKS) for AD further stood out, according to bioinformatics analysis, and they were verified by enzyme-linked immunosorbent assay (ELISA) verification. These candidate biomarkers are related to the regulation process of the actin cytoskeleton, which is involved in the regulation of synaptic loss in the AD brain tissue. Collectively, this study identified novel cell type-related biomarkers for AD by integrating multi-omics datasets from brains and serum. Our findings provided new targets for the clinical treatment and prognosis of AD. Full article

(This article belongs to the Section Molecular and Cellular Neuroscience)

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38 pages, 2769 KiB

Open AccessEditor’s ChoiceSystematic Review

Risk of Developing Non-Cancerous Central Nervous System Diseases Due to Ionizing Radiation Exposure during Adulthood: Systematic Review and Meta-Analyses

by Julie Lopes, Klervi Leuraud, Dmitry Klokov, Christelle Durand, Marie-Odile Bernier and Clémence Baudin

Brain Sci. 2022, 12(8), 984; https://doi.org/10.3390/brainsci12080984 - 26 Jul 2022

Cited by 14 | Viewed by 2588

Abstract

Background: High-dose ionizing radiation (IR) (>0.5 Gy) is an established risk factor for cognitive impairments, but this cannot be concluded for low-to-moderate IR exposure (<0.5 Gy) in adulthood as study results are inconsistent. The objectives are to summarize relevant epidemiological studies of low-to-moderate [...] Read more.

Background: High-dose ionizing radiation (IR) (>0.5 Gy) is an established risk factor for cognitive impairments, but this cannot be concluded for low-to-moderate IR exposure (<0.5 Gy) in adulthood as study results are inconsistent. The objectives are to summarize relevant epidemiological studies of low-to-moderate IR exposure in adulthood and to assess the risk of non-cancerous CNS diseases. Methods: A systematic literature search of four electronic databases was performed to retrieve relevant epidemiological studies published from 2000 to 2022. Pooled standardized mortality ratios, relative risks, and excess relative risks (ERR) were estimated with a random effect model. Results: Forty-five publications were included in the systematic review, including thirty-three in the quantitative meta-analysis. The following sources of IR-exposure were considered: atomic bomb, occupational, environmental, and medical exposure. Increased dose-risk relationships were found for cerebrovascular diseases incidence and mortality (ERR_pooled per 100 mGy = 0.04; 95% CI: 0.03–0.05; ERR_pooled at 100 mGy = 0.01; 95% CI: −0.00–0.02, respectively) and for Parkinson’s disease (ERR_pooled at 100 mGy = 0.11; 95% CI: 0.06–0.16); Conclusions: Our findings suggest that adult low-to-moderate IR exposure may have effects on non-cancerous CNS diseases. Further research addressing inherent variation issues is encouraged. Full article

(This article belongs to the Section Environmental Neuroscience)

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13 pages, 1415 KiB

Open AccessEditor’s ChoiceArticle

Interhemispheric Facilitatory Effect of High-Frequency rTMS: Perspective from Intracortical Facilitation and Inhibition

by Dongting Tian and Shin-Ichi Izumi

Brain Sci. 2022, 12(8), 970; https://doi.org/10.3390/brainsci12080970 - 23 Jul 2022

Cited by 6 | Viewed by 1585

Abstract

The activity of excitatory and inhibitory neural circuits in the motor cortex can be probed and modified by transcranial magnetic stimulation (TMS) and repetitive TMS (rTMS), noninvasively. At present, not only has a consensus regarding the interhemispheric effect of high frequency rTMS not [...] Read more.

The activity of excitatory and inhibitory neural circuits in the motor cortex can be probed and modified by transcranial magnetic stimulation (TMS) and repetitive TMS (rTMS), noninvasively. At present, not only has a consensus regarding the interhemispheric effect of high frequency rTMS not been reached, but the attributes of these TMS-related circuits are also poorly understood. To address this question comprehensively, we integrated a single- and paired-pulse TMS evaluation with excitatory 20-Hz rTMS intervention in order to probe the interhemispheric effect on the intracortical circuits by high-frequency rTMS. In the rest state, after 20-Hz rTMS, a significant increase of single-pulse MEP and paired-pulse intracortical facilitation (ICF) in the non-stimulated hemisphere was observed with good test–retest reliability. Intracortical inhibition (measured by the cortical silent period) in the unstimulated hemisphere also increased after rTMS. No significant time–course change was observed in the sham-rTMS group. The results provide the evidence that 20-Hz rTMS induced a reliable interhemispheric facilitatory effect. Findings from the present study suggest that the glutamatergic facilitatory system and the GABAergic inhibitory system may vary synchronously. Full article

(This article belongs to the Section Social Cognitive and Affective Neuroscience)

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10 pages, 985 KiB

Open AccessEditor’s ChoiceReview

The Prevalence of Dizziness and Vertigo in COVID-19 Patients: A Systematic Review

by George Korres, Dimitrios K. Kitsos, Diego Kaski, Anthi Tsogka, Sotirios Giannopoulos, Vasileios Giannopapas, Giorgos Sideris, Giorgos Tyrellis and Konstantine Voumvourakis

Brain Sci. 2022, 12(7), 948; https://doi.org/10.3390/brainsci12070948 - 20 Jul 2022

Cited by 9 | Viewed by 5414

Abstract

Clinical manifestations of COVID-19 include symptoms of vertigo and dizziness, which is rather unsurprising, since SARS-CoV-2 neurotropism may inflict a broad spectrum of neuropathic effects. The widespread nature of central and peripheral audiovestibular pathways suggests that there may be several probable pathophysiological mechanisms. [...] Read more.

Clinical manifestations of COVID-19 include symptoms of vertigo and dizziness, which is rather unsurprising, since SARS-CoV-2 neurotropism may inflict a broad spectrum of neuropathic effects. The widespread nature of central and peripheral audiovestibular pathways suggests that there may be several probable pathophysiological mechanisms. The cytokine storm, CNS infiltration of the virus through ACE 2 receptors, and other systemic factors can be responsible for the significant number of COVID-19 patients reported to experience symptoms of vertigo and dizziness. In this paper, we present a systematic review of clinical studies reporting the detection of dizziness and vertigo as clinical manifestations of COVID-19 and discuss their etiopathogenesis. Full article

(This article belongs to the Special Issue Vestibular Neurology)

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13 pages, 1544 KiB

Open AccessEditor’s ChoiceArticle

PS-NPs Induced Neurotoxic Effects in SHSY-5Y Cells via Autophagy Activation and Mitochondrial Dysfunction

by Qisheng Tang, Tianwen Li, Kezhu Chen, Xiangyang Deng, Quan Zhang, Hailiang Tang, Zhifeng Shi, Tongming Zhu and Jianhong Zhu

Brain Sci. 2022, 12(7), 952; https://doi.org/10.3390/brainsci12070952 - 20 Jul 2022

Cited by 17 | Viewed by 2615

Abstract

Polystyrene nanoparticles (PS-NPs) are organic pollutants that are widely detected in the environment and organisms, posing potential threats to both ecosystems and human health. PS-NPs have been proven to penetrate the blood–brain barrier and increase the incidence of neurodegenerative diseases. However, information relating [...] Read more.

Polystyrene nanoparticles (PS-NPs) are organic pollutants that are widely detected in the environment and organisms, posing potential threats to both ecosystems and human health. PS-NPs have been proven to penetrate the blood–brain barrier and increase the incidence of neurodegenerative diseases. However, information relating to the pathogenic molecular mechanism is still unclear. This study investigated the neurotoxicity and regulatory mechanisms of PS-NPs in human neuroblastoma SHSY-5Y cells. The results show that PS-NPs caused obvious mitochondrial damages, as evidenced by inhibited cell proliferation, increased lactate dehydrogenase release, stimulated oxidative stress responses, elevated Ca²⁺ level and apoptosis, and reduced mitochondrial membrane potential and adenosine triphosphate levels. The increased release of cytochrome c and the overexpression of apoptosis-related proteins apoptotic protease activating factor-1 (Apaf-1), cysteinyl aspartate specific proteinase-3 (caspase-3), and caspase-9 indicate the activation of the mitochondrial apoptosis pathway. In addition, the upregulation of autophagy markers light chain 3-II (LC3-II), Beclin-1, and autophagy-related protein (Atg) 5/12/16L suggests that PS-NPs could promote autophagy in SHSY-5Y cells. The RNA interference of Beclin-1 confirms the regulatory role of autophagy in PS-NP-induced neurotoxicity. The administration of antioxidant N-acetylcysteine (NAC) significantly attenuated the cytotoxicity and autophagy activation induced by PS-NP exposure. Generally, PS-NPs could induce neurotoxicity in SHSY-5Y cells via autophagy activation and mitochondria dysfunction, which was modulated by mitochondrial oxidative stress. Mitochondrial damages caused by oxidative stress could potentially be involved in the pathological mechanisms for PS-NP-induced neurodegenerative diseases. Full article

(This article belongs to the Special Issue Pathogenesis Study of Glioma: From Glioma Stem Cells, Genomic Tags, to Rodent Models)

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32 pages, 1607 KiB

Open AccessEditor’s ChoiceReview

Evidence of Neuroplastic Changes after Transcranial Magnetic, Electric, and Deep Brain Stimulation

by Julius Kricheldorff, Katharina Göke, Maximilian Kiebs, Florian H. Kasten, Christoph S. Herrmann, Karsten Witt and Rene Hurlemann

Brain Sci. 2022, 12(7), 929; https://doi.org/10.3390/brainsci12070929 - 15 Jul 2022

Cited by 20 | Viewed by 5419

Abstract

Electric and magnetic stimulation of the human brain can be used to excite or inhibit neurons. Numerous methods have been designed over the years for this purpose with various advantages and disadvantages that are the topic of this review. Deep brain stimulation (DBS) [...] Read more.

Electric and magnetic stimulation of the human brain can be used to excite or inhibit neurons. Numerous methods have been designed over the years for this purpose with various advantages and disadvantages that are the topic of this review. Deep brain stimulation (DBS) is the most direct and focal application of electric impulses to brain tissue. Electrodes are placed in the brain in order to modulate neural activity and to correct parameters of pathological oscillation in brain circuits such as their amplitude or frequency. Transcranial magnetic stimulation (TMS) is a non-invasive alternative with the stimulator generating a magnetic field in a coil over the scalp that induces an electric field in the brain which, in turn, interacts with ongoing brain activity. Depending upon stimulation parameters, excitation and inhibition can be achieved. Transcranial electric stimulation (tES) applies electric fields to the scalp that spread along the skull in order to reach the brain, thus, limiting current strength to avoid skin sensations and cranial muscle pain. Therefore, tES can only modulate brain activity and is considered subthreshold, i.e., it does not directly elicit neuronal action potentials. In this review, we collect hints for neuroplastic changes such as modulation of behavior, the electric activity of the brain, or the evolution of clinical signs and symptoms in response to stimulation. Possible mechanisms are discussed, and future paradigms are suggested. Full article

(This article belongs to the Special Issue Brain Stimulation and Neuroplasticity—Series II)

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32 pages, 365 KiB

Open AccessEditor’s ChoiceCommentary

Sex Differences in Parkinson’s Disease: From Bench to Bedside

by Maria Claudia Russillo, Valentina Andreozzi, Roberto Erro, Marina Picillo, Marianna Amboni, Sofia Cuoco, Paolo Barone and Maria Teresa Pellecchia

Brain Sci. 2022, 12(7), 917; https://doi.org/10.3390/brainsci12070917 - 13 Jul 2022

Cited by 17 | Viewed by 2940

Abstract

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease and gender differences have been described on several aspects of PD. In the present commentary, we aimed to collect and discuss the currently available evidence on gender differences in [...] Read more.

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease and gender differences have been described on several aspects of PD. In the present commentary, we aimed to collect and discuss the currently available evidence on gender differences in PD regarding biomarkers, genetic factors, motor and non-motor symptoms, therapeutic management (including pharmacological and surgical treatment) as well as preclinical studies. Methods: A systematic literature review was performed by searching the Pubmed and Scopus databases with the search strings “biomarkers”, “deep brain stimulation”, “female”, “gender”, “genetic”, “levodopa”, “men”, “male”, “motor symptoms”, “non-motor symptoms”, “Parkinson disease”, “sex”, “surgery”, and “women”. Results: The present review confirms the existence of differences between men and women in Parkinson Disease, pointing out new information regarding evidence from animal models, genetic factors, biomarkers, clinical features and pharmacological and surgical treatment. Conclusions: The overall goal is to acquire new informations about sex and gender differences in Parkinson Disease, in order to develop tailored intervetions. Full article

(This article belongs to the Collection Hot Topics in Parkinson’s Disease: State of the Art and Future Perspectives)

30 pages, 1747 KiB

Open AccessEditor’s ChoiceReview

Spiking Neural Networks and Their Applications: A Review

by Kashu Yamazaki, Viet-Khoa Vo-Ho, Darshan Bulsara and Ngan Le

Brain Sci. 2022, 12(7), 863; https://doi.org/10.3390/brainsci12070863 - 30 Jun 2022

Cited by 96 | Viewed by 17481

Abstract

The past decade has witnessed the great success of deep neural networks in various domains. However, deep neural networks are very resource-intensive in terms of energy consumption, data requirements, and high computational costs. With the recent increasing need for the autonomy of machines [...] Read more.

The past decade has witnessed the great success of deep neural networks in various domains. However, deep neural networks are very resource-intensive in terms of energy consumption, data requirements, and high computational costs. With the recent increasing need for the autonomy of machines in the real world, e.g., self-driving vehicles, drones, and collaborative robots, exploitation of deep neural networks in those applications has been actively investigated. In those applications, energy and computational efficiencies are especially important because of the need for real-time responses and the limited energy supply. A promising solution to these previously infeasible applications has recently been given by biologically plausible spiking neural networks. Spiking neural networks aim to bridge the gap between neuroscience and machine learning, using biologically realistic models of neurons to carry out the computation. Due to their functional similarity to the biological neural network, spiking neural networks can embrace the sparsity found in biology and are highly compatible with temporal code. Our contributions in this work are: (i) we give a comprehensive review of theories of biological neurons; (ii) we present various existing spike-based neuron models, which have been studied in neuroscience; (iii) we detail synapse models; (iv) we provide a review of artificial neural networks; (v) we provide detailed guidance on how to train spike-based neuron models; (vi) we revise available spike-based neuron frameworks that have been developed to support implementing spiking neural networks; (vii) finally, we cover existing spiking neural network applications in computer vision and robotics domains. The paper concludes with discussions of future perspectives. Full article

(This article belongs to the Section Neural Engineering, Neuroergonomics and Neurorobotics)

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11 pages, 860 KiB

Open AccessEditor’s ChoiceArticle

Motoric Cognitive Risk Syndrome, Subtypes and 8-Year All-Cause Mortality in Aging Phenotypes: The Salus in Apulia Study

by Ilaria Bortone, Roberta Zupo, Fabio Castellana, Simona Aresta, Luisa Lampignano, Sabrina Sciarra, Chiara Griseta, Tommaso Antonio Stallone, Giancarlo Sborgia, Madia Lozupone, Francesco Panza, Gianvito Lagravinese, Petronilla Battista and Rodolfo Sardone

Brain Sci. 2022, 12(7), 861; https://doi.org/10.3390/brainsci12070861 - 29 Jun 2022

Cited by 7 | Viewed by 1825

Abstract

Background: This study aims to establish the key clinical features of different motoric cognitive risk (MCR) subtypes based on individual quantitative measures of cognitive impairment and to compare their predictive power on survival over an 8-year observation time. Methods: We analyzed data from [...] Read more.

Background: This study aims to establish the key clinical features of different motoric cognitive risk (MCR) subtypes based on individual quantitative measures of cognitive impairment and to compare their predictive power on survival over an 8-year observation time. Methods: We analyzed data from a population-based study of 1138 subjects aged 65 years and older in south Italy. These individuals were targeted and allocated to subtypes of the MCR phenotype according to the slowness criterion plus one other different cognitive domain for each characterized phenotype (Subjective Cognitive Complaint [SCC]; Global Function [Mini Mental State Examination (MMSE) < 24]; or a combination of both). Clinical evaluation and laboratory assays, along with a comprehensive battery of neuropsychological and physical tests, completed the sample investigation. Results: MCR prevalence was found to be 9.8% (n = 112), 3.6% (n = 41), 3.4% (n = 39) and 1.8% (n = 21) for the MCR, MCR-GlobalFunction, MCR-StructuredSCC and MCR-SCC and GlobalFunction, respectively. Univariate Cox survival analysis showed an association only of the MCR-GlobalFunction subtype with an almost three-fold increased risk of overall death as compared to the other counterparts (HR 2.53, 95%CI 1.28 to 4.99) over an 8-year observation period. Using Generalized Estimating Equations (GEE) for clustered survival data, we found that MCR males had an increased and significant mortality risk with respect to MCR female subjects. Conclusions: MCR phenotypes assigned to the MMSE cognitive domain are more likely to have an increased risk of overall mortality, and gender showed a huge effect on the risk of death for MCR subjects over the 8-year observation. Full article

(This article belongs to the Section Sensory and Motor Neuroscience)

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10 pages, 1244 KiB

Open AccessEditor’s ChoiceArticle

The Effect of Severity of Obstructive Sleep Apnea on Sleep Bruxism in Respiratory Polygraphy Study

by Klaudia Kazubowska-Machnowska, Anna Jodkowska, Monika Michalek-Zrabkowska, Mieszko Wieckiewicz, Rafal Poreba, Marzena Dominiak, Pawel Gac, Grzegorz Mazur, Justyna Kanclerska and Helena Martynowicz

Brain Sci. 2022, 12(7), 828; https://doi.org/10.3390/brainsci12070828 - 25 Jun 2022

Cited by 6 | Viewed by 1737

Abstract

Obstructive sleep apnea (OSA) and sleep bruxism (SB) may appear concomitantly. Data on the relationship between OSA and SB are limited. It was shown that in a population with an increased risk of OSA, OSA was dependently correlated with SB on the degree [...] Read more.

Obstructive sleep apnea (OSA) and sleep bruxism (SB) may appear concomitantly. Data on the relationship between OSA and SB are limited. It was shown that in a population with an increased risk of OSA, OSA was dependently correlated with SB on the degree of OSA severity only in mild and moderate cases of OSA. We aimed to confirm this relationship and affecting factors in a group of dental office patients in a prospective, observational study. Adult patients (n = 119) were evaluated using respiratory polygraphy. The risk of OSA was assessed using a STOP-Bang questionnaire (SBQ). The episodes of bruxism and respiratory events were scored according to the standards of the American Academy of Sleep Medicine. The prevalence of OSA and SB was found to be 63.02% and 41.17%, respectively. The bruxism episode index (BEI) was increased in the group with a higher risk of OSA (SBQ ≥ 3) compared to the group with a lower risk of OSA (3.49 ± 3.63 vs. 2.27 ± 2.50, p = 0.03). The sensitivity and specificity of the SBQ were not sufficient to predict SB. A positive linear correlation between AHI and BEI in the group with AHI < 23/h was found. The study confirmed that OSA was associated with SB in the group of patients with OSA and/or SB risk. The relationship between OSA and SB depended on the degree of severity of OSA and occurred in mild and moderate cases of OSA. Full article

(This article belongs to the Special Issue Controversies in Obstructive Sleep Apnea (OSA) Pathophysiology, Diagnosis and Treatment)

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48 pages, 1944 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Dopamine, Erectile Function and Male Sexual Behavior from the Past to the Present: A Review

by Maria Rosaria Melis, Fabrizio Sanna and Antonio Argiolas

Brain Sci. 2022, 12(7), 826; https://doi.org/10.3390/brainsci12070826 - 24 Jun 2022

Cited by 11 | Viewed by 4532

Abstract

Early and recent studies show that dopamine through its neuronal systems and receptor subtypes plays different roles in the control of male sexual behavior. These studies show that (i) the mesolimbic/mesocortical dopaminergic system plays a key role in the preparatory phase of sexual [...] Read more.

Early and recent studies show that dopamine through its neuronal systems and receptor subtypes plays different roles in the control of male sexual behavior. These studies show that (i) the mesolimbic/mesocortical dopaminergic system plays a key role in the preparatory phase of sexual behavior, e.g., in sexual arousal, motivation and reward, whereas the nigrostriatal system controls the sensory-motor coordination necessary for copulation, (ii) the incertohypothalamic system is involved in the consummatory aspects of sexual behavior (penile erection and copulation), but evidence for its role in sexual motivation is also available, (iii) the pro-sexual effects of dopamine occur in concert with neural systems interconnecting the hypothalamus and preoptic area with the spinal cord, ventral tegmental area and other limbic brain areas and (iv) D₂ and D₄ receptors play a major role in the pro-sexual effects of dopamine. Despite some controversy, increases or decreases, respectively, of brain dopamine activity induced by drugs or that occur physiologically, usually improves or worsens, respectively, sexual activity. These findings suggest that an altered central dopaminergic tone plays a role in mental pathologies characterized by aberrant sexual behavior, and that pro-erectile D₄ receptor agonists may be considered a new strategy for the treatment of erectile dysfunction in men. Full article

(This article belongs to the Section Neural Control of Peripheral Function)

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10 pages, 272 KiB

Open AccessEditor’s ChoiceReview

Effects of Long-Term Exposure to High Altitude Hypoxia on Cognitive Function and Its Mechanism: A Narrative Review

by Yuan Li and Yan Wang

Brain Sci. 2022, 12(6), 808; https://doi.org/10.3390/brainsci12060808 - 20 Jun 2022

Cited by 14 | Viewed by 3343

Abstract

Cognitive function is affected by low pressure and hypoxia in high-altitude environments, and is regulated by altitude and exposure time. With the economic development in the Qinghai-Tibet Plateau, the increase in work and study activities, as well as the development of plateau tourism, [...] Read more.

Cognitive function is affected by low pressure and hypoxia in high-altitude environments, and is regulated by altitude and exposure time. With the economic development in the Qinghai-Tibet Plateau, the increase in work and study activities, as well as the development of plateau tourism, mountaineering, and other activities, the number of plateau immigrants is increasing daily. Long-term hypoxia challenges human physical and mental health, restricts work efficiency, and thus affects plateau economic development and human wellbeing. Therefore, it is of scientific and social significance to study how long-term exposure to the hypoxic plateau environment affects the physical and mental health of lowlanders as part of the ongoing development of the current plateau region. In this paper, we reviewed the research progress and mechanism of the effects of long-term (≥1 year) high-altitude (>2500 m) hypoxia exposure on the cognitive function of lowlanders, and suggested that the scope and sample size of the research should be expanded in the future, and that follow-up studies should be carried out to explore the time threshold of cognitive impairment and its compensatory or repair mechanism. Full article

(This article belongs to the Section Environmental Neuroscience)

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9 pages, 1977 KiB

Open AccessEditor’s ChoiceArticle

The Prophylactic and Multimodal Activity of Two Isatin Thiosemicarbazones against Alzheimer’s Disease In Vitro

by Barbara Mavroidi, Archontia Kaminari, Dimitris Matiadis, Dimitra Hadjipavlou-Litina, Maria Pelecanou, Athina Tzinia and Marina Sagnou

Brain Sci. 2022, 12(6), 806; https://doi.org/10.3390/brainsci12060806 - 19 Jun 2022

Cited by 15 | Viewed by 1848

Abstract

Alzheimer’s disease (AD) is a multifactorial disorder strongly involving the formation of amyloid-β (Aβ) oligomers, which subsequently aggregate into the disease characteristic insoluble amyloid plaques, in addition to oxidative stress, inflammation and increased acetylcholinesterase activity. Moreover, Aβ oligomers interfere with the expression and [...] Read more.

Alzheimer’s disease (AD) is a multifactorial disorder strongly involving the formation of amyloid-β (Aβ) oligomers, which subsequently aggregate into the disease characteristic insoluble amyloid plaques, in addition to oxidative stress, inflammation and increased acetylcholinesterase activity. Moreover, Aβ oligomers interfere with the expression and activity of Glycogen synthase kinase-3 (GSK3) and Protein kinase B (PKB), also known as AKT. In the present study, the potential multimodal effect of two synthetic isatin thiosemicarbazones (ITSCs), which have been previously shown to prevent Aβ aggregation was evaluated. Both compounds resulted in fully reversing the Aβ-mediated toxicity in SK-NS-H cells treated with exogenous Aβ peptides at various pre-incubation time points and at 1 μM. Cell survival was not recovered when compounds were applied after Aβ cell treatment. The ITSCs were non-toxic against wild type and 5xFAD primary hippocampal cells. They reversed the inhibition of Akt and GSK-3β phosphorylation in 5xFAD cells. Finally, they exhibited good antioxidant potential and moderate lipoxygenase and acetylcholinesterase inhibition activity. Overall, these results suggest that isatin thiosemicarbazone is a suitable scaffold for the development of multimodal anti-AD agents. Full article

(This article belongs to the Topic Mechanisms and Treatments of Neurodegenerative Diseases)

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13 pages, 4982 KiB

Open AccessEditor’s ChoiceProtocol

Dissection of Mouse Hippocampus with Its Dorsal, Intermediate and Ventral Subdivisions Combined with Molecular Validation

by Aneta Jaszczyk, Adrian M. Stankiewicz and Grzegorz R. Juszczak

Brain Sci. 2022, 12(6), 799; https://doi.org/10.3390/brainsci12060799 - 18 Jun 2022

Cited by 9 | Viewed by 5446

Abstract

Many research methods applied in molecular neuroscience require the collection of hippocampal samples, but a still poorly recognized problem is contamination with the choroid plexus during brain dissection. Because of a distinct pattern of gene expression, its inclusion in brain samples can obscure [...] Read more.

Many research methods applied in molecular neuroscience require the collection of hippocampal samples, but a still poorly recognized problem is contamination with the choroid plexus during brain dissection. Because of a distinct pattern of gene expression, its inclusion in brain samples can obscure or even confound conclusions drawn from molecular studies. Therefore, we tested our dissection method designed for removal of tissue contamination using expression of the transthyretin gene (Ttr) as a marker of the choroid plexus. Additionally, we also validated dissection of the entire hippocampus into its dorsal, intermediate and ventral subdivisions using the expression of Trhr and Lct genes as molecular markers of anatomical subdivisions. The PCR analysis showed that Ttr is expressed at a residual level in hippocampal samples that display an mRNA level several hundred lower than the adjacent control tissue colocalized with the choroid plexus. This indicates that the applied method for dissecting the hippocampus from a fresh brain allows for replicable removal of the majority of choroid plexus from hippocampal samples. In turn, differences in expression of Lct and Trhr confirmed the proper dissection of dorsal, intermediate and ventral subdivisions from fresh brain tissue. Therefore, a special emphasis on the removal of tissue contamination and avoidance of tissue distortions makes our protocol especially suitable for molecular experiments performed either on the entire hippocampus or its subdivisions. Full article

(This article belongs to the Section Neurosurgery and Neuroanatomy)

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15 pages, 2321 KiB

Open AccessEditor’s ChoiceArticle

SwinBTS: A Method for 3D Multimodal Brain Tumor Segmentation Using Swin Transformer

by Yun Jiang, Yuan Zhang, Xin Lin, Jinkun Dong, Tongtong Cheng and Jing Liang

Brain Sci. 2022, 12(6), 797; https://doi.org/10.3390/brainsci12060797 - 17 Jun 2022

Cited by 61 | Viewed by 7158

Abstract

Brain tumor semantic segmentation is a critical medical image processing work, which aids clinicians in diagnosing patients and determining the extent of lesions. Convolutional neural networks (CNNs) have demonstrated exceptional performance in computer vision tasks in recent years. For 3D medical image tasks, [...] Read more.

Brain tumor semantic segmentation is a critical medical image processing work, which aids clinicians in diagnosing patients and determining the extent of lesions. Convolutional neural networks (CNNs) have demonstrated exceptional performance in computer vision tasks in recent years. For 3D medical image tasks, deep convolutional neural networks based on an encoder–decoder structure and skip-connection have been frequently used. However, CNNs have the drawback of being unable to learn global and remote semantic information well. On the other hand, the transformer has recently found success in natural language processing and computer vision as a result of its usage of a self-attention mechanism for global information modeling. For demanding prediction tasks, such as 3D medical picture segmentation, local and global characteristics are critical. We propose SwinBTS, a new 3D medical picture segmentation approach, which combines a transformer, convolutional neural network, and encoder–decoder structure to define the 3D brain tumor semantic segmentation job as a sequence-to-sequence prediction challenge in this research. To extract contextual data, the 3D Swin Transformer is utilized as the network’s encoder and decoder, and convolutional operations are employed for upsampling and downsampling. Finally, we achieve segmentation results using an improved Transformer module that we built for increasing detail feature extraction. Extensive experimental results on the BraTS 2019, BraTS 2020, and BraTS 2021 datasets reveal that SwinBTS outperforms state-of-the-art 3D algorithms for brain tumor segmentation on 3D MRI scanned images. Full article

(This article belongs to the Section Computational Neuroscience and Neuroinformatics)

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18 pages, 360 KiB

Open AccessEditor’s ChoiceReview

Vitamin D Status and Parkinson’s Disease

by Michela Barichella, Federica Garrì, Serena Caronni, Carlotta Bolliri, Luciano Zocchi, Maria Carmela Macchione, Valentina Ferri, Daniela Calandrella and Gianni Pezzoli

Brain Sci. 2022, 12(6), 790; https://doi.org/10.3390/brainsci12060790 - 16 Jun 2022

Cited by 17 | Viewed by 3353

Abstract

Parkinson’s disease (PD) is a complex and progressive neurodegenerative disease, characterized by resting tremor, rigidity, slowness of movement, and postural instability. Furthermore, PD is associated with a wide spectrum of non-motor symptoms that add to overall disability. In recent years, some investigations, from [...] Read more.

Parkinson’s disease (PD) is a complex and progressive neurodegenerative disease, characterized by resting tremor, rigidity, slowness of movement, and postural instability. Furthermore, PD is associated with a wide spectrum of non-motor symptoms that add to overall disability. In recent years, some investigations, from basic science to clinical applications, have focused on the role of vitamin D in PD, often with controversial findings. Vitamin D has widespread effects on several biological processes in the central nervous system, including neurotransmission in dopaminergic neural circuits. Various studies have recorded lower levels of vitamin D in PD patients than in healthy controls. Low vitamin D status has also been correlated with the risk for PD and motor severity, whereas less is known about the effects vitamin D has on cognitive function and other non-motor symptoms. This review aims to better characterize the correlation between vitamin D and PD, clarify the role of vitamin D in PD prevention and treatment, and discuss avenues for future research in this field. Full article

(This article belongs to the Collection Hot Topics in Parkinson’s Disease: State of the Art and Future Perspectives)

21 pages, 3837 KiB

Open AccessEditor’s ChoiceReview

A Brief Introduction to Magnetoencephalography (MEG) and Its Clinical Applications

by Alfred Lenin Fred, Subbiahpillai Neelakantapillai Kumar, Ajay Kumar Haridhas, Sayantan Ghosh, Harishita Purushothaman Bhuvana, Wei Khang Jeremy Sim, Vijayaragavan Vimalan, Fredin Arun Sedly Givo, Veikko Jousmäki, Parasuraman Padmanabhan and Balázs Gulyás

Brain Sci. 2022, 12(6), 788; https://doi.org/10.3390/brainsci12060788 - 15 Jun 2022

Cited by 15 | Viewed by 5599

Abstract

Magnetoencephalography (MEG) plays a pivotal role in the diagnosis of brain disorders. In this review, we have investigated potential MEG applications for analysing brain disorders. The signal-to-noise ratio (SNR_MEG = 2.2 db, SNR_EEG < 1 db) and spatial resolution (SR_MEG [...] Read more.

Magnetoencephalography (MEG) plays a pivotal role in the diagnosis of brain disorders. In this review, we have investigated potential MEG applications for analysing brain disorders. The signal-to-noise ratio (SNR_MEG = 2.2 db, SNR_EEG < 1 db) and spatial resolution (SR_MEG = 2–3 mm, SR_EEG = 7–10 mm) is higher for MEG than EEG, thus MEG potentially facilitates accurate monitoring of cortical activity. We found that the direct electrophysiological MEG signals reflected the physiological status of neurological disorders and play a vital role in disease diagnosis. Single-channel connectivity, as well as brain network analysis, using MEG data acquired during resting state and a given task has been used for the diagnosis of neurological disorders such as epilepsy, Alzheimer’s, Parkinsonism, autism, and schizophrenia. The workflow of MEG and its potential applications in the diagnosis of disease and therapeutic planning are also discussed. We forecast that computer-aided algorithms will play a prominent role in the diagnosis and prediction of neurological diseases in the future. The outcome of this narrative review will aid researchers to utilise MEG in diagnostics. Full article

(This article belongs to the Special Issue Recent Advances in Neuroimaging and Neurophysiology in Psychiatry)

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12 pages, 343 KiB

Open AccessEditor’s ChoiceArticle

Executive Functions in Overweight and Obese Treatment-Seeking Patients: Cross-Sectional Data and Longitudinal Perspectives

by Marco La Marra, Ines Villano, Ciro Rosario Ilardi, Mario Carosella, Maria Staiano, Alessandro Iavarone, Sergio Chieffi, Giovanni Messina, Rita Polito, Chiara Porro, Alessia Scarinci, Vincenzo Monda, Marco Carotenuto, Girolamo Di Maio and Antonietta Messina

Brain Sci. 2022, 12(6), 777; https://doi.org/10.3390/brainsci12060777 - 14 Jun 2022

Cited by 14 | Viewed by 1986

Abstract

Background: Recent evidence suggests that a higher body weight may be linked to cognitive impairment in different domains involving executive/frontal functioning. However, challenging results are also available. Accordingly, our study was designed to verify whether (i) poor executive functions are related to a [...] Read more.

Background: Recent evidence suggests that a higher body weight may be linked to cognitive impairment in different domains involving executive/frontal functioning. However, challenging results are also available. Accordingly, our study was designed to verify whether (i) poor executive functions are related to a higher body weight and (ii) executive functioning could contribute to weight loss in treatment-seeking overweight and obese patients. Methods: We examined general executive functioning, inhibitory control, verbal fluency, and psychomotor speed in a sample including 104 overweight and obese patients. Forty-eight normal-weight subjects participated in the study as controls. Results: Univariate Analysis of Variance showed that obese patients obtained lower scores than overweight and normal-weight subjects in all executive measures, except for errors in the Stroop test. However, when sociodemographic variables entered the model as covariates, no between-group difference was detected. Furthermore, an adjusted multiple linear regression model highlighted no relationship between weight loss and executive scores at baseline. Conclusions: Our results provide further evidence for the lack of association between obesity and the executive domains investigated. Conflicting findings from previous literature may likely be due to the unchecked confounding effects exerted by sociodemographic variables and inclusion/exclusion criteria. Full article

(This article belongs to the Special Issue Hypothalamic Control in Inflammation and Metabolic Functions)

18 pages, 3905 KiB

Open AccessEditor’s ChoiceArticle

Selective Probiotic Treatment Positively Modulates the Microbiota–Gut–Brain Axis in the BTBR Mouse Model of Autism

by Angela Pochakom, Chunlong Mu, Jong M. Rho, Thomas A. Tompkins, Shyamchand Mayengbam and Jane Shearer

Brain Sci. 2022, 12(6), 781; https://doi.org/10.3390/brainsci12060781 - 14 Jun 2022

Cited by 11 | Viewed by 3361

Abstract

Recent studies have shown promise for the use of probiotics in modulating behaviour through the microbiota–gut–brain axis. In the present study, we assessed the impact of two probiotic strains in mitigating autism-related symptomology in the BTBR T⁺ Itpr3^tf/J mouse model [...] Read more.

Recent studies have shown promise for the use of probiotics in modulating behaviour through the microbiota–gut–brain axis. In the present study, we assessed the impact of two probiotic strains in mitigating autism-related symptomology in the BTBR T⁺ Itpr3^tf/J mouse model of autism spectrum disorder (ASD). Male juvenile BTBR mice were randomized into: (1) control, (2) Lr probiotic (1 × 10⁹ CFU/mL Lacticaseibacillus rhamnosus HA-114), and (3) Ls probiotic groups (1 × 10⁹ CFU/mL Ligilactobacillus salivarius HA-118) (n = 18–21/group), receiving treatments in drinking water for 4 weeks. Gut microbiota profiling by 16S rRNA showed Lr, but not Ls supplementation, to increase microbial richness and phylogenetic diversity, with a rise in potential anti-inflammatory and butyrate-producing taxa. Assessing serum and brain metabolites, Lr and Ls supplementation produced distinct metabolic profiles, with Lr treatment elevating concentrations of potentially beneficial neuroactive compounds, such as 5-aminovaleric acid and choline. As mitochondrial dysfunction is often observed in ASD, we assessed mitochondrial oxygen consumption rates in the prefrontal cortex and hippocampus. No differences were observed for either treatment. Both Lr and Ls treatment reduced behavioural deficits in social novelty preference. However, no changes in hyperactivity, repetitive behaviour, and sociability were observed. Results show Lr to impart positive changes along the microbiota–gut–brain axis, exhibiting beneficial effects on selected behaviour, gut microbial diversity, and metabolism in BTBR mice. Full article

(This article belongs to the Special Issue Brain–Microbiome Interactions)

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16 pages, 2189 KiB

Open AccessEditor’s ChoiceArticle

Changes in Tyrosine Hydroxylase Activity and Dopamine Synthesis in the Nigrostriatal System of Mice in an Acute Model of Parkinson’s Disease as a Manifestation of Neurodegeneration and Neuroplasticity

by Anna Kolacheva, Leyla Alekperova, Ekaterina Pavlova, Alyona Bannikova and Michael V. Ugrumov

Brain Sci. 2022, 12(6), 779; https://doi.org/10.3390/brainsci12060779 - 14 Jun 2022

Cited by 10 | Viewed by 2363

Abstract

The progressive degradation of the nigrostriatal system leads to the development of Parkinson’s disease (PD). The synthesis of dopamine, the neurotransmitter of the nigrostriatal system, depends on the rate-limiting enzyme, tyrosine hydroxylase (TH). In this study, we evaluated the synthesis of dopamine during [...] Read more.

The progressive degradation of the nigrostriatal system leads to the development of Parkinson’s disease (PD). The synthesis of dopamine, the neurotransmitter of the nigrostriatal system, depends on the rate-limiting enzyme, tyrosine hydroxylase (TH). In this study, we evaluated the synthesis of dopamine during periods of neurodegradation and neuroplasticity in the nigrostriatal system on a model of the early clinical stage of PD. It was shown that the concentration of dopamine correlated with activity of TH, while TH activity did not depend on total protein content either in the SN or in the striatum. Both during the period of neurodegeneration and neuroplasticity, TH activity in SN was determined by the content of P19-TH, and in the striatum it was determined by P31-TH and P40-TH (to a lesser extent). The data obtained indicate a difference in the regulation of dopamine synthesis between DA-neuron bodies and their axons, which must be considered for the further development of symptomatic pharmacotherapy aimed at increasing TH activity. Full article

(This article belongs to the Special Issue New Insights into Molecular Mechanisms Underlying Neurodegenerative Disorders)

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20 pages, 5261 KiB

Open AccessEditor’s ChoiceArticle

Homology Modelling, Molecular Docking and Molecular Dynamics Simulation Studies of CALMH1 against Secondary Metabolites of Bauhinia variegata to Treat Alzheimer’s Disease

by Noopur Khare, Sanjiv Kumar Maheshwari, Syed Mohd Danish Rizvi, Hind Muteb Albadrani, Suliman A. Alsagaby, Wael Alturaiki, Danish Iqbal, Qamar Zia, Chiara Villa, Saurabh Kumar Jha, Niraj Kumar Jha and Abhimanyu Kumar Jha

Brain Sci. 2022, 12(6), 770; https://doi.org/10.3390/brainsci12060770 - 12 Jun 2022

Cited by 12 | Viewed by 2741

Abstract

Calcium homeostasis modulator 1 (CALHM1) is a protein responsible for causing Alzheimer’s disease. In the absence of an experimentally designed protein molecule, homology modelling was performed. Through homology modelling, different CALHM1 models were generated and validated through Rampage. To carry out further in [...] Read more.

Calcium homeostasis modulator 1 (CALHM1) is a protein responsible for causing Alzheimer’s disease. In the absence of an experimentally designed protein molecule, homology modelling was performed. Through homology modelling, different CALHM1 models were generated and validated through Rampage. To carry out further in silico studies, through molecular docking and molecular dynamics simulation experiments, various flavonoids and alkaloids from Bauhinia variegata were utilised as inhibitors to target the protein (CALHM1). The sequence of CALHM1 was retrieved from UniProt and the secondary structure prediction of CALHM1 was done through CFSSP, GOR4, and SOPMA methods. The structure was identified through LOMETS, MUSTER, and MODELLER and finally, the structures were validated through Rampage. Bauhinia variegata plant was used to check the interaction of alkaloids and flavonoids against CALHM1. The protein and protein–ligand complex were also validated through molecular dynamics simulations studies. The model generated through MODELLER software with 6VAM A was used because this model predicted the best results in the Ramachandran plot. Further molecular docking was performed, quercetin was found to be the most appropriate candidate for the protein molecule with the minimum binding energy of −12.45 kcal/mol and their ADME properties were analysed through Molsoft and Molinspiration. Molecular dynamics simulations showed that CALHM1 and CALHM1–quercetin complex became stable at 2500 ps. It may be seen through the study that quercetin may act as a good inhibitor for treatment. With the help of an in silico study, it was easier to analyse the 3D structure of the protein, which may be scrutinized for the best-predicted model. Quercetin may work as a good inhibitor for treating Alzheimer’s disease, according to in silico research using molecular docking and molecular dynamics simulations, and future in vitro and in vivo analysis may confirm its effectiveness. Full article

(This article belongs to the Special Issue New Insights into Molecular Mechanisms Underlying Neurodegenerative Disorders)

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18 pages, 1951 KiB

Open AccessEditor’s ChoiceReview

Efficacy of Overground Robotic Gait Training on Balance in Stroke Survivors: A Systematic Review and Meta-Analysis

by Matteo Lorusso, Marco Tramontano, Matteo Casciello, Andrea Pece, Nicola Smania, Giovanni Morone and Federica Tamburella

Brain Sci. 2022, 12(6), 713; https://doi.org/10.3390/brainsci12060713 - 31 May 2022

Cited by 9 | Viewed by 2602

Abstract

Strokes often lead to a deficit in motor control that contributes to a reduced balance function. Impairments in the balance function severely limit the activities of daily living (ADL) in stroke survivors. The present systematic review and meta-analysis primarily aims to explore the [...] Read more.

Strokes often lead to a deficit in motor control that contributes to a reduced balance function. Impairments in the balance function severely limit the activities of daily living (ADL) in stroke survivors. The present systematic review and meta-analysis primarily aims to explore the efficacy of overground robot-assisted gait training (o-RAGT) on balance recovery in individuals with stroke. In addition, the efficacy on ADL is also investigated. This systematic review identified nine articles investigating the effects of o-RAGT on balance, four of which also assessed ADL. The results of the meta-analysis suggest that o-RAGT does not increase balance and ADL outcomes more than conventional therapy in individuals after stroke. The data should not be overestimated due to the low number of studies included in the meta-analysis and the wide confidence intervals. Subgroup analyses to investigate the influence of participant’s characteristics and training dosage were not performed due to lack of data availability. Further well-designed randomized controlled trials are needed to investigate the efficacy of o-RAGT on balance in individuals with stroke. Full article

(This article belongs to the Special Issue Robot-, Virtual Reality- and Sensor-Based Therapies Boosting Neuroplasticity in the Context of Motor and Cognitive Neurorehabilitation: Current State of the Art and Applications)

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22 pages, 19077 KiB

Open AccessEditor’s ChoiceArticle

Characterization of Ex Vivo and In Vitro Wnt Transcriptome Induced by Spinal Cord Injury in Rat Microglial Cells

by Carlos González-Fernández, Pau González, Francisco González-Pérez and Francisco Javier Rodríguez

Brain Sci. 2022, 12(6), 708; https://doi.org/10.3390/brainsci12060708 - 30 May 2022

Cited by 9 | Viewed by 1942

Abstract

It is well known that inflammation is crucial in the onset and progression of neurodegenerative diseases and traumatic central nervous system (CNS) injuries, and that microglia and monocyte-derived macrophages (MDMs) play a pivotal role in neuroinflammation. Therefore, the exploration of molecular signaling pathways [...] Read more.

It is well known that inflammation is crucial in the onset and progression of neurodegenerative diseases and traumatic central nervous system (CNS) injuries, and that microglia and monocyte-derived macrophages (MDMs) play a pivotal role in neuroinflammation. Therefore, the exploration of molecular signaling pathways that are involved in the microglia/macrophage response might help us to shed light on their eventual therapeutic modulation. Interestingly, there is growing evidence showing that the Wnt family of proteins is involved in different neuropathologies that are characterized by a dysregulated neuroinflammatory response, including spinal cord injury (SCI). Here, we aimed to validate a methodology with competence to assess the physiologically relevant Wnt expression patterns of active microglia and MDMs in a rat model of SCI. For that purpose, we have selected and adapted an in vitro system of primary microglia culture that were stimulated with a lesioned spinal cord extract (SCE), together with an ex vivo protocol of flow cytometry sorting of rat microglia/MDMs at different time-points after contusive SCI. Our study demonstrates that the expression profile of Wnt-related genes in microglia/MDM cells exhibit important differences between these particular scenarios which would be in line with previous studies where similar discrepancies have been described for other molecules. Moreover, our results provide for a first experimental report of the Wnt transcriptome in rat microglia and MDMs after SCI which, together with the research platform that was used in the study, and considering its limitations, we expect might contribute to foster the research on Wnt-driven immunomodulatory therapies. Full article

(This article belongs to the Special Issue The Function of Microglia in Neurodegenerative Diseases)

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19 pages, 9583 KiB

Open AccessEditor’s ChoiceArticle

A Novel Classification Model for Lower-Grade Glioma Patients Based on Pyroptosis-Related Genes

by Yusheng Shen, Hao Chi, Ke Xu, Yandong Li, Xisheng Yin, Shi Chen, Qian Yang, Miao He, Guohua Zhu and Xiaosong Li

Brain Sci. 2022, 12(6), 700; https://doi.org/10.3390/brainsci12060700 - 28 May 2022

Cited by 15 | Viewed by 2232

Abstract

Recent studies demonstrated that pyroptosis plays a crucial role in shaping the tumor-immune microenvironment. However, the influence of pyroptosis on lower-grade glioma regarding immunotherapy and targeted therapy is still unknown. This study analyzed the variations of 33 pyroptosis-related genes in lower-grade glioma and [...] Read more.

Recent studies demonstrated that pyroptosis plays a crucial role in shaping the tumor-immune microenvironment. However, the influence of pyroptosis on lower-grade glioma regarding immunotherapy and targeted therapy is still unknown. This study analyzed the variations of 33 pyroptosis-related genes in lower-grade glioma and normal tissues. Our study found considerable genetic and expression alterations in heterogeneity among lower-grade gliomas and normal brain tissues. There are two pyroptosis phenotypes in lower-grade glioma, and they exhibited differences in cell infiltration characteristics and clinical characters. Then, a PyroScore model using the lasso-cox method was constructed to measure the level of pyroptosis in each patient. PyroScore can refine the lower-grade glioma patients with a stratified prognosis and a distinct tumor immune microenvironment. Pyscore may also be an effective factor in predicting potential therapeutic benefits. In silico analysis showed that patients with a lower PyroScore are expected to be more sensitive to targeted therapy and immunotherapy. These findings may enhance our understanding of pyroptosis in lower-grade glioma and might help optimize risk stratification for the survival and personalized management of lower-grade glioma patients. Full article

(This article belongs to the Section Molecular and Cellular Neuroscience)

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25 pages, 2938 KiB

Open AccessEditor’s ChoiceSystematic Review

Effects of Ten Different Exercise Interventions on Motor Function in Parkinson’s Disease Patients—A Network Meta-Analysis of Randomized Controlled Trials

by Zikang Hao, Xiaodan Zhang and Ping Chen

Brain Sci. 2022, 12(6), 698; https://doi.org/10.3390/brainsci12060698 - 27 May 2022

Cited by 12 | Viewed by 3807

Abstract

Objective: The aim of this study was to evaluate ten exercise interventions (YOGA: yoga training, RT: resistance training, AQU: aquatic training, TAI: Taiji Qigong training, TRD: treadmill training, VR: virtual reality training, DANCE: musical dance training, WKT: walking training, CYC: cycling training, BDJ: [...] Read more.

Objective: The aim of this study was to evaluate ten exercise interventions (YOGA: yoga training, RT: resistance training, AQU: aquatic training, TAI: Taiji Qigong training, TRD: treadmill training, VR: virtual reality training, DANCE: musical dance training, WKT: walking training, CYC: cycling training, BDJ: Baduanjin Qigong training) on motor function in Parkinson’s disease (PD) patients. Design: Through searching PubMed, Embase, Cochrane Library, Web of Science, and CNKI, only randomized controlled trials (RCTs) were collected to study the effects of the ten exercise interventions on motor function in patients with Parkinson’s disease. The included studies were evaluated for methodological quality by the Cochrane bias risk assessment tool. Results: The RCTs were collected between the earliest available date and April 2022. Sixty RCTs were included and the total sample size used in the study was 2859. The results of the network meta-analysis showed that DANCE can significantly improve patients’ Berg Balance Scale (BBS) (SUCRA = 78.4%); DANCE can significantly decline patients’ Unified Parkinson’s Disease Rating Scale score (UPDRS) (SUCRA = 72.3%) and YOGA can significantly decline patients’ Timed-Up-and-Go score (TUGT) (SUCRA = 78.0%). Conclusion: Based on the network meta-analysis and SUCRA ranking, we can state that dance, yoga, virtual reality training and resistance training offers better advantages than other exercise interventions for patients’ motor function. Full article

(This article belongs to the Special Issue Beneficial Effects of Exercise on the Brain and in Neurodegenerative Diseases)

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17 pages, 1200 KiB

Open AccessEditor’s ChoiceReview

Immediate Early Gene c-fos in the Brain: Focus on Glial Cells

by Fernando Cruz-Mendoza, Fernando Jauregui-Huerta, Adriana Aguilar-Delgadillo, Joaquín García-Estrada and Sonia Luquin

Brain Sci. 2022, 12(6), 687; https://doi.org/10.3390/brainsci12060687 - 24 May 2022

Cited by 27 | Viewed by 6107

Abstract

The c-fos gene was first described as a proto-oncogene responsible for the induction of bone tumors. A few decades ago, activation of the protein product c-fos was reported in the brain after seizures and other noxious stimuli. Since then, multiple studies have used [...] Read more.

The c-fos gene was first described as a proto-oncogene responsible for the induction of bone tumors. A few decades ago, activation of the protein product c-fos was reported in the brain after seizures and other noxious stimuli. Since then, multiple studies have used c-fos as a brain activity marker. Although it has been attributed to neurons, growing evidence demonstrates that c-fos expression in the brain may also include glial cells. In this review, we collect data showing that glial cells also express this proto-oncogene. We present evidence demonstrating that at least astrocytes, oligodendrocytes, and microglia express this immediate early gene (IEG). Unlike neurons, whose expression changes used to be associated with depolarization, glial cells seem to express the c-fos proto-oncogene under the influence of proliferation, differentiation, growth, inflammation, repair, damage, plasticity, and other conditions. The collected evidence provides a complementary view of c-fos as an activity marker and urges the introduction of the glial cell perspective into brain activity studies. This glial cell view may provide additional information related to the brain microenvironment that is difficult to obtain from the isolated neuron paradigm. Thus, it is highly recommended that detection techniques are improved in order to better differentiate the phenotypes expressing c-fos in the brain and to elucidate the specific roles of c-fos expression in glial cells. Full article

(This article belongs to the Collection Systematic Reviews and Meta-Analyses Collection on Molecular and Cellular Neuroscience)

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15 pages, 3139 KiB

Open AccessEditor’s ChoiceReview

Histone Deacetylases as Epigenetic Targets for Treating Parkinson’s Disease

by Yan Li, Zhicheng Gu, Shuxian Lin, Lei Chen, Valentina Dzreyan, Moez Eid, Svetlana Demyanenko and Bin He

Brain Sci. 2022, 12(5), 672; https://doi.org/10.3390/brainsci12050672 - 21 May 2022

Cited by 12 | Viewed by 2901

Abstract

Parkinson’s disease (PD) is a chronic progressive neurodegenerative disease that is increasingly becoming a global threat to the health and life of the elderly worldwide. Although there are some drugs clinically available for treating PD, these treatments can only alleviate the symptoms of [...] Read more.

Parkinson’s disease (PD) is a chronic progressive neurodegenerative disease that is increasingly becoming a global threat to the health and life of the elderly worldwide. Although there are some drugs clinically available for treating PD, these treatments can only alleviate the symptoms of PD patients but cannot completely cure the disease. Therefore, exploring other potential mechanisms to develop more effective treatments that can modify the course of PD is still highly desirable. Over the last two decades, histone deacetylases, as an important group of epigenetic targets, have attracted much attention in drug discovery. This review focused on the current knowledge about histone deacetylases involved in PD pathophysiology and their inhibitors used in PD studies. Further perspectives related to small molecules that can inhibit or degrade histone deacetylases to treat PD were also discussed. Full article

(This article belongs to the Section Neuropharmacology and Neuropathology)

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11 pages, 978 KiB

Open AccessEditor’s ChoiceReview

Supramarginal Resection for Glioblastoma: It Is Time to Set Boundaries! A Critical Review on a Hot Topic

by Francesco Guerrini, Elena Roca and Giannantonio Spena

Brain Sci. 2022, 12(5), 652; https://doi.org/10.3390/brainsci12050652 - 16 May 2022

Cited by 13 | Viewed by 2381

Abstract

Glioblastoma are the most common primary malignant brain tumors with a highly infiltrative behavior. The extent of resection of the enhancing component has been shown to be correlated to survival. Recently, it has been proposed to move the resection beyond the contrast-enhanced portion [...] Read more.

Glioblastoma are the most common primary malignant brain tumors with a highly infiltrative behavior. The extent of resection of the enhancing component has been shown to be correlated to survival. Recently, it has been proposed to move the resection beyond the contrast-enhanced portion into the MR hyper intense tissue which typically surrounds the tumor, the so-called supra marginal resection (SMR). Though it should be associated with better overall survival (OS), a potential harmful resection must be avoided in order not to create new neurological deficits. Through this work, we aimed to perform a critical review of SMR in patients with Glioblastoma. A Medline database search and a pooled meta-analysis of HRs were conducted; 19 articles were included. Meta-analysis revealed a pooled OS HR of 0.64 (p = 0.052). SMR is generally considered as the resection of any T1w gadolinium-enhanced tumor exceeding FLAIR volume, but no consensus exists about the amount of volume that must be resected to have an OS gain. Equally, the role and the weight of several pre-operative features (tumor volume, location, eloquence, etc.), the intraoperative methods to extend resection, and the post-operative deficits, need to be considered more deeply in future studies. Full article

(This article belongs to the Special Issue Frontiers in Neurooncology and Neurosurgery)

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10 pages, 509 KiB

Open AccessEditor’s ChoiceArticle

The Role of Stress and Cognitive Absorption in Predicting Social Network Addiction

by Loreta Cannito, Eugenia Annunzi, Caterina Viganò, Bernardo Dell’Osso, Matteo Vismara, Pier Luigi Sacco, Riccardo Palumbo and Claudio D’Addario

Brain Sci. 2022, 12(5), 643; https://doi.org/10.3390/brainsci12050643 - 13 May 2022

Cited by 13 | Viewed by 3414

Abstract

Nowadays, the use of social networks (SNs) is pervasive and ubiquitous. Among other things, SNs have become a key resource for establishing and maintaining personal relationships, as further demonstrated by the emergence of the pandemic. However, easy access to SNs may be a [...] Read more.

Nowadays, the use of social networks (SNs) is pervasive and ubiquitous. Among other things, SNs have become a key resource for establishing and maintaining personal relationships, as further demonstrated by the emergence of the pandemic. However, easy access to SNs may be a source of addictive behaviour, especially among the younger population. The literature highlights various psychological and physiological factors as possible predictors of vulnerability to SN addiction. This paper explores the joint effects of stress level and cognitive absorption, in the form of temporal dissociation while on SNs, on the addiction of university students to SNs. Here, 312 participants were involved in an online survey. About 14% of the sample presented a risk for SN addiction. Moreover, it was found that stress level predicted SN addiction both directly and indirectly through the effect of individual temporal dissociation, as experienced during SN usage. These results suggest a significant role of perceived stress level on addiction risk, while also pointing out additional vulnerability to SN addiction for cognitive profiles that are relatively more prone to temporal dissociation while online. Full article

(This article belongs to the Section Behavioral Neuroscience)

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20 pages, 314 KiB

Open AccessEditor’s ChoiceArticle

Elderly Gliobastoma Patients: The Impact of Surgery and Adjuvant Treatments on Survival: A Single Institution Experience

by Francesco Bruno, Alessia Pellerino, Edoardo Pronello, Rosa Palmiero, Luca Bertero, Cristina Mantovani, Andrea Bianconi, Antonio Melcarne, Diego Garbossa and Roberta Rudà

Brain Sci. 2022, 12(5), 632; https://doi.org/10.3390/brainsci12050632 - 11 May 2022

Cited by 10 | Viewed by 1591

Abstract

Introduction. Elderly glioblastoma (GBM) patients often show limited response to treatment and poor outcome. Here, we provide a case series of elderly GBM patients from our Institution, in whom we assessed the clinical characteristics, feasibility of surgical resection, response to adjuvant treatments, [...] Read more.

Introduction. Elderly glioblastoma (GBM) patients often show limited response to treatment and poor outcome. Here, we provide a case series of elderly GBM patients from our Institution, in whom we assessed the clinical characteristics, feasibility of surgical resection, response to adjuvant treatments, and outcome, along with the impact of comorbidities and clinical status on survival. Patients and Methods. We included patients ≥ 65-year-old. We collected information about clinical and molecular features, extent of resection, adjuvant treatments, treatment-related complications, and outcome. Results. We included 135 patients. Median age was 71 years. In total, 127 patients (94.0%) had a Karnofsky Performance Status (KPS) ≥70 and 61/135 (45.2%) a Charlson Comorbidity Score (CCI) > 3. MGMTp methylation was found in 70/135 (51.9%). Subtotal resections (STRs), gross-total resections (GTRs), and biopsies were 102 (75.6%), 10 (7.4%) and 23 (17.0%), respectively. Median progression-free survival and overall survival (mOS) were 8.0 and 10.5 months for the whole cohort. Notably, GTR and radio-chemotherapy with temozolomide in patients with MGMTp methylation were associated with significantly longer mOS (32.8 and 44.8 months, respectively). In a multivariable analysis, risk of death was affected by STR vs. GTR (HR 2.8, p = 0.002), MGMTp methylation (HR 0.55, p = 0.007), and KPS at baseline ≥70 (HR 0.43, p = 0.031). Conversely, CCI and post-surgical complications were not significant. Conclusions. Elderly GBM patients often have a dismal prognosis. However, it is possible to identify a subgroup with favourable clinical and molecular features, who benefit from GTR and radio-chemotherapy with temozolomide. A comprehensive prognostic score is needed to guide treatment modality and predict the outcome. Full article

(This article belongs to the Special Issue Frontiers in Neurooncology and Neurosurgery)

13 pages, 2199 KiB

Open AccessEditor’s ChoiceArticle

The Effect of Task Performance and Partnership on Interpersonal Brain Synchrony during Cooperation

by Shujin Zhou, Yuxuan Zhang, Yiwen Fu, Lingling Wu, Xiaodie Li, Ningning Zhu, Dan Li and Mingming Zhang

Brain Sci. 2022, 12(5), 635; https://doi.org/10.3390/brainsci12050635 - 11 May 2022

Cited by 10 | Viewed by 2748

Abstract

Interpersonal brain synchrony (IBS) during cooperation has not been systematically investigated. To address this research gap, this study assessed neural synchrony during a cooperative jigsaw puzzle solving task using functional near-infrared spectroscopy (fNIRS)-based hyperscanning. IBS was measured for successful and failed tasks in [...] Read more.

Interpersonal brain synchrony (IBS) during cooperation has not been systematically investigated. To address this research gap, this study assessed neural synchrony during a cooperative jigsaw puzzle solving task using functional near-infrared spectroscopy (fNIRS)-based hyperscanning. IBS was measured for successful and failed tasks in 31 dyads in which the partners were familiar or unknown to each other. No significant difference in IBS was observed between the different types of cooperative partnership; however, stronger IBS within regions of the pars triangularis Broca’s area, right frontopolar cortex, and right temporoparietal junction was observed during task success. These results highlight the effect of better task performance on cooperative IBS for the first time and further extend understanding of the neural basis of cooperation. Full article

(This article belongs to the Section Neurotechnology and Neuroimaging)

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13 pages, 1958 KiB

Open AccessEditor’s ChoiceArticle

A Depression Prediction Algorithm Based on Spatiotemporal Feature of EEG Signal

by Wei Liu, Kebin Jia, Zhuozheng Wang and Zhuo Ma

Brain Sci. 2022, 12(5), 630; https://doi.org/10.3390/brainsci12050630 - 11 May 2022

Cited by 15 | Viewed by 3695

Abstract

Depression has gradually become the most common mental disorder in the world. The accuracy of its diagnosis may be affected by many factors, while the primary diagnosis seems to be difficult to define. Finding a way to identify depression by satisfying both objective [...] Read more.

Depression has gradually become the most common mental disorder in the world. The accuracy of its diagnosis may be affected by many factors, while the primary diagnosis seems to be difficult to define. Finding a way to identify depression by satisfying both objective and effective conditions is an urgent issue. In this paper, a strategy for predicting depression based on spatiotemporal features is proposed, and is expected to be used in the auxiliary diagnosis of depression. Firstly, electroencephalogram (EEG) signals were denoised through the filter to obtain the power spectra of the three corresponding frequency ranges, Theta, Alpha and Beta. Using orthogonal projection, the spatial positions of the electrodes were mapped to the brainpower spectrum, thereby obtaining three brain maps with spatial information. Then, the three brain maps were superimposed on a new brain map with frequency domain and spatial characteristics. A Convolutional Neural Network (CNN) and Gated Recurrent Unit (GRU) were applied to extract the sequential feature. The proposed strategy was validated with a public EEG dataset, achieving an accuracy of 89.63% and an accuracy of 88.56% with the private dataset. The network had less complexity with only six layers. The results show that our strategy is credible, less complex and useful in predicting depression using EEG signals. Full article

(This article belongs to the Topic Applications of Biomedical Technology and Molecular Biological Approach in Brain Diseases)

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15 pages, 1288 KiB

Open AccessEditor’s ChoiceArticle

BDNF and Pro-BDNF in Amyotrophic Lateral Sclerosis: A New Perspective for Biomarkers of Neurodegeneration

by Giulia Riolo, Claudia Ricci, Nicoletta De Angelis, Carlotta Marzocchi, Gisella Guerrera, Giovanna Borsellino, Fabio Giannini and Stefania Battistini

Brain Sci. 2022, 12(5), 617; https://doi.org/10.3390/brainsci12050617 - 09 May 2022

Cited by 8 | Viewed by 2006

Abstract

Amyotrophic Lateral Sclerosis (ALS) is characterized by the progressive degeneration of upper or lower motor neurons, leading to muscle wasting and paralysis, resulting in respiratory failure and death. The precise ALS aetiology is poorly understood, mainly due to clinical and genetic heterogeneity. Thus, [...] Read more.

Amyotrophic Lateral Sclerosis (ALS) is characterized by the progressive degeneration of upper or lower motor neurons, leading to muscle wasting and paralysis, resulting in respiratory failure and death. The precise ALS aetiology is poorly understood, mainly due to clinical and genetic heterogeneity. Thus, the identification of reliable biomarkers of disease could be helpful in clinical practice. In this study, we investigated whether the levels of brain-derived neurotrophic factor (BDNF) and its precursor Pro-BDNF in serum and cerebrospinal fluid (CSF) may reflect the pathological changes related to ALS. We found higher BDNF and lower Pro-BDNF levels in ALS sera compared to healthy controls. BDNF/Pro-BDNF ratio turned out to be accurate in distinguishing ALS patients from controls. Then, the correlations of these markers with several ALS clinical variables were evaluated. This analysis revealed three statistically significant associations: (1) Patients carrying the C9orf72 expansion significantly differed from non-carrier patients and showed serum BDNF levels comparable to control subjects; (2) BDNF levels in CSF were significantly higher in ALS patients with faster disease progression; (3) lower serum levels of Pro-BDNF were associated with a shorter survival. Therefore, we suggest that BDNF and Pro-BDNF, alone or in combination, might be used as ALS prognostic biomarkers. Full article

(This article belongs to the Special Issue Frontiers in Amyotrophic Lateral Sclerosis)

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14 pages, 2419 KiB

Open AccessEditor’s ChoiceArticle

A Computer-Assisted System for Early Mortality Risk Prediction in Patients with Traumatic Brain Injury Using Artificial Intelligence Algorithms in Emergency Room Triage

by Kuan-Chi Tu, Tee-Tau Eric Nyam, Che-Chuan Wang, Nai-Ching Chen, Kuo-Tai Chen, Chia-Jung Chen, Chung-Feng Liu and Jinn-Rung Kuo

Brain Sci. 2022, 12(5), 612; https://doi.org/10.3390/brainsci12050612 - 07 May 2022

Cited by 10 | Viewed by 2063

Abstract

Traumatic brain injury (TBI) remains a critical public health challenge. Although studies have found several prognostic factors for TBI, a useful early predictive tool for mortality has yet to be developed in the triage of the emergency room. This study aimed to use [...] Read more.

Traumatic brain injury (TBI) remains a critical public health challenge. Although studies have found several prognostic factors for TBI, a useful early predictive tool for mortality has yet to be developed in the triage of the emergency room. This study aimed to use machine learning algorithms of artificial intelligence (AI) to develop predictive models for TBI patients in the emergency room triage. We retrospectively enrolled 18,249 adult TBI patients in the electronic medical records of three hospitals of Chi Mei Medical Group from January 2010 to December 2019, and undertook the 12 potentially predictive feature variables for predicting mortality during hospitalization. Six machine learning algorithms including logistical regression (LR) random forest (RF), support vector machines (SVM), LightGBM, XGBoost, and multilayer perceptron (MLP) were used to build the predictive model. The results showed that all six predictive models had high AUC from 0.851 to 0.925. Among these models, the LR-based model was the best model for mortality risk prediction with the highest AUC of 0.925; thus, we integrated the best model into the existed hospital information system for assisting clinical decision-making. These results revealed that the LR-based model was the best model to predict the mortality risk in patients with TBI in the emergency room. Since the developed prediction system can easily obtain the 12 feature variables during the initial triage, it can provide quick and early mortality prediction to clinicians for guiding deciding further treatment as well as helping explain the patient’s condition to family members. Full article

(This article belongs to the Section Computational Neuroscience and Neuroinformatics)

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9 pages, 942 KiB

Open AccessEditor’s ChoiceArticle

Neurological Pupil Index for the Early Prediction of Outcome in Severe Acute Brain Injury Patients

by Federico Romagnosi, Adriano Bernini, Filippo Bongiovanni, Carolina Iaquaniello, John-Paul Miroz, Giuseppe Citerio, Fabio Silvio Taccone and Mauro Oddo

Brain Sci. 2022, 12(5), 609; https://doi.org/10.3390/brainsci12050609 - 06 May 2022

Cited by 16 | Viewed by 2387

Abstract

In this study, we examined the early value of automated quantitative pupillary examination, using the Neurological Pupil index (NPi), to predict the long-term outcome of acute brain injured (ABI) patients. We performed a single-centre retrospective study (October 2016–March 2019) in ABI patients who [...] Read more.

In this study, we examined the early value of automated quantitative pupillary examination, using the Neurological Pupil index (NPi), to predict the long-term outcome of acute brain injured (ABI) patients. We performed a single-centre retrospective study (October 2016–March 2019) in ABI patients who underwent NPi measurement during the first 3 days following brain insult. We examined the performance of NPi—alone or in combination with other baseline demographic (age) and radiologic (CT midline shift) predictors—to prognosticate unfavourable 6-month outcome (Glasgow Outcome Scale 1–3). A total of 145 severely brain-injured subjects (65 traumatic brain injury, TBI; 80 non-TBI) were studied. At each time point tested, NPi <3 was highly predictive of unfavourable outcome, with highest specificity (100% (90–100)) at day 3 (sensitivity 24% (15–35), negative predictive value 36% (34–39)). The addition of NPi, from day 1 following ABI to age and cerebral CT scan, provided the best prognostic performance (AUROC curve 0.85 vs. 0.78 without NPi, p = 0.008; DeLong test) for 6-month neurological outcome prediction. NPi, assessed at the early post-injury phase, has a superior ability to predict unfavourable long-term neurological outcomes in severely brain-injured patients. The added prognostic value of NPi was most significant when complemented with baseline demographic and radiologic information. Full article

(This article belongs to the Section Neurotechnology and Neuroimaging)

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