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Editor’s Choice Articles

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to readers, or important in the respective research area. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.

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24 pages, 1282 KiB  
Review
Endocannabinoid System and Exogenous Cannabinoids in Depression and Anxiety: A Review
by Ahmed Hasbi, Bertha K. Madras and Susan R. George
Brain Sci. 2023, 13(2), 325; https://doi.org/10.3390/brainsci13020325 - 14 Feb 2023
Cited by 32 | Viewed by 9972
Abstract
Background: There is a growing liberalization of cannabis-based preparations for medical and recreational use. In multiple instances, anxiety and depression are cited as either a primary or a secondary reason for the use of cannabinoids. Aim: The purpose of this review is to [...] Read more.
Background: There is a growing liberalization of cannabis-based preparations for medical and recreational use. In multiple instances, anxiety and depression are cited as either a primary or a secondary reason for the use of cannabinoids. Aim: The purpose of this review is to explore the association between depression or anxiety and the dysregulation of the endogenous endocannabinoid system (ECS), as well as the use of phytocannabinoids and synthetic cannabinoids in the remediation of depression/anxiety symptoms. After a brief description of the constituents of cannabis, cannabinoid receptors and the endocannabinoid system, the most important evidence is presented for the involvement of cannabinoids in depression and anxiety both in human and from animal models of depression and anxiety. Finally, evidence is presented for the clinical use of cannabinoids to treat depression and anxiety. Conclusions: Although the common belief that cannabinoids, including cannabis, its main studied components—tetrahydrocannabinol (THC) and cannabidiol (CBD)—or other synthetic derivatives have been suggested to have a therapeutic role for certain mental health conditions, all recent systematic reviews that we report have concluded that the evidence that cannabinoids improve depressive and anxiety disorders is weak, of very-low-quality, and offers no guidance on the use of cannabinoids for mental health conditions within a regulatory framework. There is an urgent need for high-quality studies examining the effects of cannabinoids on mental disorders in general and depression/anxiety in particular, as well as the consequences of long-term use of these preparations due to possible risks such as addiction and even reversal of improvement. Full article
(This article belongs to the Special Issue Cannabis and the Brain: Novel Perspectives and Understandings)
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13 pages, 951 KiB  
Review
Perampanel in Brain Tumor-Related Epilepsy: A Systematic Review
by Payam Tabaee Damavandi, Francesco Pasini, Gaia Fanella, Giulia Sofia Cereda, Gabriele Mainini, Jacopo C. DiFrancesco, Eugen Trinka and Simona Lattanzi
Brain Sci. 2023, 13(2), 326; https://doi.org/10.3390/brainsci13020326 - 14 Feb 2023
Cited by 15 | Viewed by 4480
Abstract
Brain tumor-related epilepsy (BTRE) is a common comorbidity in patients with brain neoplasms and it may be either the first symptom or develop after the tumor diagnosis. Increasing evidence suggests that brain tumors and BTRE share common pathophysiological mechanisms. Glutamatergic mechanisms can play [...] Read more.
Brain tumor-related epilepsy (BTRE) is a common comorbidity in patients with brain neoplasms and it may be either the first symptom or develop after the tumor diagnosis. Increasing evidence suggests that brain tumors and BTRE share common pathophysiological mechanisms. Glutamatergic mechanisms can play a central role in promoting both primary brain tumor growth and epileptogenesis. Perampanel (PER), which acts as a selective antagonist of glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, may play a role both in the reduction in tumor growth and the control of epileptiform activity. This systematic review aimed to summarize the pre-clinical and clinical evidence about the antitumor properties, antiseizure effects and tolerability of PER in BTRE. Eight pre-clinical and eight clinical studies were identified. The currently available evidence suggests that PER can be an effective and generally well-tolerated therapeutic option in patients with BTRE. In vitro studies demonstrated promising antitumor activity of PER, while no role in slowing tumor progression has been demonstrated in rat models; clinical data on the potential antitumor activity of PER are scarce. Additional studies are needed to explore further the effects of PER on tumor progression and fully characterize its potentialities in patients with BTRE. Full article
(This article belongs to the Section Neuropharmacology and Neuropathology)
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14 pages, 476 KiB  
Review
Evaluating the Distinction between Cool and Hot Executive Function during Childhood
by Yusuke Moriguchi and Steven Phillips
Brain Sci. 2023, 13(2), 313; https://doi.org/10.3390/brainsci13020313 - 13 Feb 2023
Cited by 16 | Viewed by 4570
Abstract
This article assesses the cool–hot executive function (EF) framework during childhood. First, conceptual analyses suggest that cool EF (cEF) is generally distinguished from hot EF (hEF). Second, both EFs can be loaded into different factors using confirmatory factor analyses. Third, the cognitive complexity [...] Read more.
This article assesses the cool–hot executive function (EF) framework during childhood. First, conceptual analyses suggest that cool EF (cEF) is generally distinguished from hot EF (hEF). Second, both EFs can be loaded into different factors using confirmatory factor analyses. Third, the cognitive complexity of EF is similar across cEF tasks, and the cognitive complexity of cEF is similar to hEF tasks. Finally, neuroimaging analysis suggests that children activate the lateral prefrontal regions during all EF tasks. Taken together, we propose that the cool–hot framework is a useful, though not definitive way of characterizing differences in EF. Full article
(This article belongs to the Special Issue Neural Basis of Executive Control)
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20 pages, 829 KiB  
Article
Machine Learning Enabled P300 Classifier for Autism Spectrum Disorder Using Adaptive Signal Decomposition
by Santhosh Peketi and Sanjay B. Dhok
Brain Sci. 2023, 13(2), 315; https://doi.org/10.3390/brainsci13020315 - 13 Feb 2023
Cited by 15 | Viewed by 4018
Abstract
Joint attention skills deficiency in Autism spectrum disorder (ASD) hinders individuals from communicating effectively. The P300 Electroencephalogram (EEG) signal-based brain–computer interface (BCI) helps these individuals in neurorehabilitation training to overcome this deficiency. The detection of the P300 signal is more challenging in ASD [...] Read more.
Joint attention skills deficiency in Autism spectrum disorder (ASD) hinders individuals from communicating effectively. The P300 Electroencephalogram (EEG) signal-based brain–computer interface (BCI) helps these individuals in neurorehabilitation training to overcome this deficiency. The detection of the P300 signal is more challenging in ASD as it is noisy, has less amplitude, and has a higher latency than in other individuals. This paper presents a novel application of the variational mode decomposition (VMD) technique in a BCI system involving ASD subjects for P300 signal identification. The EEG signal is decomposed into five modes using VMD. Thirty linear and non-linear time and frequency domain features are extracted for each mode. Synthetic minority oversampling technique data augmentation is performed to overcome the class imbalance problem in the chosen dataset. Then, a comparative analysis of three popular machine learning classifiers is performed for this application. VMD’s fifth mode with a support vector machine (fine Gaussian kernel) classifier gave the best performance parameters, namely accuracy, F1-score, and the area under the curve, as 91.12%, 91.18%, and 96.6%, respectively. These results are better when compared to other state-of-the-art methods. Full article
(This article belongs to the Section Computational Neuroscience and Neuroinformatics)
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16 pages, 367 KiB  
Review
Depression in Major Neurodegenerative Diseases and Strokes: A Critical Review of Similarities and Differences among Neurological Disorders
by Javier Pagonabarraga, Cecilio Álamo, Mar Castellanos, Samuel Díaz and Sagrario Manzano
Brain Sci. 2023, 13(2), 318; https://doi.org/10.3390/brainsci13020318 - 13 Feb 2023
Cited by 19 | Viewed by 6795
Abstract
Depression and anxiety are highly prevalent in most neurological disorders and can have a major impact on the patient’s disability and quality of life. However, mostly due to the heterogeneity of symptoms and the complexity of the underlying comorbidities, depression can be difficult [...] Read more.
Depression and anxiety are highly prevalent in most neurological disorders and can have a major impact on the patient’s disability and quality of life. However, mostly due to the heterogeneity of symptoms and the complexity of the underlying comorbidities, depression can be difficult to diagnose, resulting in limited recognition and in undertreatment. The early detection and treatment of depression simultaneously with the neurological disorder is key to avoiding deterioration and further disability. Although the neurologist should be able to identify and treat depression initially, a neuropsychiatry team should be available for severe cases and those who are unresponsive to treatment. Neurologists should be also aware that in neurodegenerative diseases, such as Alzheimer’s or Parkinson’s, different depression symptoms could develop at different stages of the disease. The treatment options for depression in neurological diseases include drugs, cognitive-behavioral therapy, and somatic interventions, among others, but often, the evidence-based efficacy is limited and the results are highly variable. Here, we review recent research on the diagnosis and treatment of depression in the context of Alzheimer’s disease, Parkinson’s disease, and strokes, with the aim of identifying common approaches and solutions for its initial management by the neurologist. Full article
(This article belongs to the Section Neuropsychiatry)
14 pages, 1533 KiB  
Article
Depression Is Associated with an Increased Risk of Subsequent Cancer Diagnosis: A Retrospective Cohort Study with 235,404 Patients
by Hannah Mössinger and Karel Kostev
Brain Sci. 2023, 13(2), 302; https://doi.org/10.3390/brainsci13020302 - 10 Feb 2023
Cited by 16 | Viewed by 9419
Abstract
Background: Depression and cancer share common risk factors and mechanisms of disease. The current literature has not explored the effect of depression on cancer risk. We assessed the difference in cancer risk in patients with and without depression in a large cohort in [...] Read more.
Background: Depression and cancer share common risk factors and mechanisms of disease. The current literature has not explored the effect of depression on cancer risk. We assessed the difference in cancer risk in patients with and without depression in a large cohort in Germany. Methods: We compared cancer risk and incidence in patients with and without depression aged 18 or above diagnosed between 2015 and 2018 documented in the Disease Analyzer Database. Patients from a comparator group were matched 1:1 to patients with depression based on propensity scores. Patients with previous bipolar disorder (F31), mania (F30) or schizophrenia (F20–29) and cancer diagnosis 3 years prior to index date were excluded. Analyses were stratified by cancer type, age group, and gender. Results: A total of 117,702 patients with depression were included and matched 1:1, resulting in a cohort overall of 235,404. 4.9% of patients with depression compared to 4.1% without depression received at least one cancer diagnosis over 3.9 years median follow-up. The depression group showed an 18% increase in risk for a cancer diagnosis overall, with largest increased risk in lung cancer (HR: 1.39 [1.21–1.60], p < 0.0001), cancers of the gastro-intestinal-tract (HR: 1.30 [1.15–1.46], p < 0.0001), breast (HR: 1.23 [1.12–1.35], p < 0.0001) and urinary (HR: 1.23 [1.06–1.43], p < 0.01). Similarly, the incidence of cancer diagnosis overall increased by 22% for depressed patients. IRs showed no difference across cancer types. Conclusions: Depression increased the risk for cancer diagnosis consistently independent of the comparison method used. The potential mediating factors or shared mechanisms of the disease require further investigation. Full article
(This article belongs to the Section Neuropsychiatry)
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12 pages, 616 KiB  
Review
The Role of Tryptophan Metabolism in Alzheimer’s Disease
by Karl Savonije and Donald F. Weaver
Brain Sci. 2023, 13(2), 292; https://doi.org/10.3390/brainsci13020292 - 9 Feb 2023
Cited by 29 | Viewed by 4590
Abstract
The need to identify new potentially druggable biochemical mechanisms for Alzheimer’s disease (AD) is an ongoing priority. The therapeutic limitations of amyloid-based approaches are further motivating this search. Amino acid metabolism, particularly tryptophan metabolism, has the potential to emerge as a leading candidate [...] Read more.
The need to identify new potentially druggable biochemical mechanisms for Alzheimer’s disease (AD) is an ongoing priority. The therapeutic limitations of amyloid-based approaches are further motivating this search. Amino acid metabolism, particularly tryptophan metabolism, has the potential to emerge as a leading candidate and an alternative exploitable biomolecular target. Multiple avenues support this contention. Tryptophan (trp) and its associated metabolites are able to inhibit various enzymes participating in the biosynthesis of β-amyloid, and one metabolite, 3-hydroxyanthranilate, is able to directly inhibit neurotoxic β-amyloid oligomerization; however, whilst certain trp metabolites are neuroprotectant, other metabolites, such as quinolinic acid, are directly toxic to neurons and may themselves contribute to AD progression. Trp metabolites also have the ability to influence microglia and associated cytokines in order to modulate the neuroinflammatory and neuroimmune factors which trigger pro-inflammatory cytotoxicity in AD. Finally, trp and various metabolites, including melatonin, are regulators of sleep, with disorders of sleep being an important risk factor for the development of AD. Thus, the involvement of trp biochemistry in AD is multifactorial and offers a plethora of druggable targets in the continuing quest for AD therapeutics. Full article
(This article belongs to the Section Neurodegenerative Diseases)
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18 pages, 2876 KiB  
Review
Could Vitamins Have a Positive Impact on the Treatment of Parkinson’s Disease?
by Sandeep, Manas Ranjan Sahu, Linchi Rani, Arun S. Kharat and Amal Chandra Mondal
Brain Sci. 2023, 13(2), 272; https://doi.org/10.3390/brainsci13020272 - 6 Feb 2023
Cited by 21 | Viewed by 20684
Abstract
Parkinson’s disease (PD) is the second most common progressive neurodegenerative disorder after Alzheimer’s disease. Pathophysiologically, it is characterized by intracytoplasmic aggregates of α-synuclein protein in the Lewy body and loss of dopaminergic neurons from substantia nigra pars compacta and striatum regions of the [...] Read more.
Parkinson’s disease (PD) is the second most common progressive neurodegenerative disorder after Alzheimer’s disease. Pathophysiologically, it is characterized by intracytoplasmic aggregates of α-synuclein protein in the Lewy body and loss of dopaminergic neurons from substantia nigra pars compacta and striatum regions of the brain. Although the exact mechanism of neurodegeneration is not fully elucidated, it has been reported that environmental toxins such as MPTP, rotenone, paraquat, and MPP+ induce oxidative stress, which is one of the causative factors for it. To date, there is no complete cure. However, the indispensable role of oxidative stress in mediating PD indicates that antioxidant therapy could be a possible therapeutic strategy against the disease. The deficiency of vitamins has been extensively co-related to PD. Dietary supplementation of vitamins with antioxidant, anti-inflammatory, anti-apoptotic, and free radical scavenging properties could be the potential neuroprotective therapeutic strategy. This review summarizes the studies that evaluated the role of vitamins (A, B, C, D, E, and K) in PD. It will guide future studies in understanding the potential therapeutic role of vitamins in disease pathophysiology and may provide a framework for designing treatment strategies against the disease. Full article
(This article belongs to the Special Issue Updates in Parkinson's Disease)
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50 pages, 4072 KiB  
Article
OViTAD: Optimized Vision Transformer to Predict Various Stages of Alzheimer’s Disease Using Resting-State fMRI and Structural MRI Data
by Saman Sarraf, Arman Sarraf, Danielle D. DeSouza, John A. E. Anderson, Milton Kabia and The Alzheimer’s Disease Neuroimaging Initiative
Brain Sci. 2023, 13(2), 260; https://doi.org/10.3390/brainsci13020260 - 3 Feb 2023
Cited by 32 | Viewed by 5599
Abstract
Advances in applied machine learning techniques for neuroimaging have encouraged scientists to implement models to diagnose brain disorders such as Alzheimer’s disease at early stages. Predicting the exact stage of Alzheimer’s disease is challenging; however, complex deep learning techniques can precisely manage this. [...] Read more.
Advances in applied machine learning techniques for neuroimaging have encouraged scientists to implement models to diagnose brain disorders such as Alzheimer’s disease at early stages. Predicting the exact stage of Alzheimer’s disease is challenging; however, complex deep learning techniques can precisely manage this. While successful, these complex architectures are difficult to interrogate and computationally expensive. Therefore, using novel, simpler architectures with more efficient pattern extraction capabilities, such as transformers, is of interest to neuroscientists. This study introduced an optimized vision transformer architecture to predict the group membership by separating healthy adults, mild cognitive impairment, and Alzheimer’s brains within the same age group (>75 years) using resting-state functional (rs-fMRI) and structural magnetic resonance imaging (sMRI) data aggressively preprocessed by our pipeline. Our optimized architecture, known as OViTAD is currently the sole vision transformer-based end-to-end pipeline and outperformed the existing transformer models and most state-of-the-art solutions. Our model achieved F1-scores of 97%±0.0 and 99.55%±0.39 from the testing sets for the rs-fMRI and sMRI modalities in the triple-class prediction experiments. Furthermore, our model reached these performances using 30% fewer parameters than a vanilla transformer. Furthermore, the model was robust and repeatable, producing similar estimates across three runs with random data splits (we reported the averaged evaluation metrics). Finally, to challenge the model, we observed how it handled increasing noise levels by inserting varying numbers of healthy brains into the two dementia groups. Our findings suggest that optimized vision transformers are a promising and exciting new approach for neuroimaging applications, especially for Alzheimer’s disease prediction. Full article
(This article belongs to the Section Neurodegenerative Diseases)
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13 pages, 453 KiB  
Article
Perceiving Oneself to Be Integrated into the Peer Group: A Protective Factor against Victimization in Children with Learning Disabilities
by Mara Marini, Gloria Di Filippo, Marika Bonuomo, Giulia Torregiani and Stefano Livi
Brain Sci. 2023, 13(2), 263; https://doi.org/10.3390/brainsci13020263 - 3 Feb 2023
Cited by 11 | Viewed by 3244
Abstract
Bullying is still a widespread social problem that needs serious attention. To date, research on this topic has shown that understanding the phenomenon requires a psychosocial perspective. The primary goal of the study is to identify the factors that contribute to the victimization [...] Read more.
Bullying is still a widespread social problem that needs serious attention. To date, research on this topic has shown that understanding the phenomenon requires a psychosocial perspective. The primary goal of the study is to identify the factors that contribute to the victimization of students with learning disabilities. The hypothesis is that the victimization experiences of this group of students can be explained by some socio-relational dynamics. Using a mediation model, this study demonstrates that perceived social integration completely mediates the association between the presence of learning disabilities and victimization experiences. This implies that students with learning disabilities are primarily victimized when they are not socially integrated into their class group. The implications for diagnosis and treatment are discussed. Full article
(This article belongs to the Special Issue Cognitive, Emotional and Social Skills in Typical and Atypical Development: Domain-Specific Abilities and Possible Overlaps for Prevention, Diagnosis and Treatment)
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19 pages, 12655 KiB  
Article
Microglia PKM2 Mediates Neuroinflammation and Neuron Loss in Mice Epilepsy through the Astrocyte C3-Neuron C3R Signaling Pathway
by Xinlin Li, Rong Zhou, Hui Peng, Jing Peng, Qiaoling Li and Meng Mei
Brain Sci. 2023, 13(2), 262; https://doi.org/10.3390/brainsci13020262 - 3 Feb 2023
Cited by 12 | Viewed by 4115
Abstract
Epilepsy is a neurological disease and approximately 30% of patients have failed to respond to current anti-epilepsy drugs. The neuroinflammation mechanism has raised increasing concerns and been regarded as the novel treatment strategy in epilepsy, but the target molecules require further research. Pyruvate [...] Read more.
Epilepsy is a neurological disease and approximately 30% of patients have failed to respond to current anti-epilepsy drugs. The neuroinflammation mechanism has raised increasing concerns and been regarded as the novel treatment strategy in epilepsy, but the target molecules require further research. Pyruvate kinase isoform 2 (PKM2) is well studied in peripheral inflammation, but its role in epilepsy neuroinflammation remains unclear. We knocked down microglia PKM2 in the hippocampus using a stereotaxic adeno-associated virus (AAV) microinjection and established a pilocarpine-induced status epilepticus (PISE) model. Racine score was used to evaluate the seizure grade. Next, we used WB, Multiplex tyramide signal amplification (TSA) staining and other methods to determine neuroinflammation and the complement component 3 (C3)–C3aR interaction in primary microglia. Results showed that microglia PKM2 knockdown reduced epilepsy grade and rescued neuron loss. Mechanistically, PKM2 knockdown inhibited microglia activation and inflammation factor secretion through suppressing p65 expression and phosphorylation. The reduced microglia C1q, TNF-α, and IL-1α were responsible for the decreased astrocyte C3 expression and the following neuron damage caused by the C3–C3aR interaction. Our data suggest that microglia PKM2 inhibition ameliorates neuroinflammation and neuron loss through C3-C3aR interaction in epilepsy, which provides an attractive target for the intervention of damaged neuron-glia crosstalk in epilepsy. Full article
(This article belongs to the Section Molecular and Cellular Neuroscience)
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15 pages, 1071 KiB  
Review
Stem Cell Therapy in Diabetic Polyneuropathy: Recent Advancements and Future Directions
by Shamima Akter, Mayank Choubey, Mohammad Mohabbulla Mohib, Shahida Arbee, Md Abu Taher Sagor and Mohammad Sarif Mohiuddin
Brain Sci. 2023, 13(2), 255; https://doi.org/10.3390/brainsci13020255 - 2 Feb 2023
Cited by 13 | Viewed by 4410
Abstract
Diabetic polyneuropathy (DPN) is the most frequent, although neglected, complication of long-term diabetes. Nearly 30% of hospitalized and 20% of community-dwelling patients with diabetes suffer from DPN; the incidence rate is approximately 2% annually. To date, there has been no curable therapy for [...] Read more.
Diabetic polyneuropathy (DPN) is the most frequent, although neglected, complication of long-term diabetes. Nearly 30% of hospitalized and 20% of community-dwelling patients with diabetes suffer from DPN; the incidence rate is approximately 2% annually. To date, there has been no curable therapy for DPN. Under these circumstances, cell therapy may be a vital candidate for the treatment of DPN. The epidemiology, classification, and treatment options for DPN are disclosed in the current review. Cell-based therapies using bone marrow-derived cells, embryonic stem cells, pluripotent stem cells, endothelial progenitor cells, mesenchymal stem cells, or dental pulp stem cells are our primary concern, which may be a useful treatment option to ease or to stop the progression of DPN. The importance of cryotherapies for treating DPN has been observed in several studies. These findings may help for the future researchers to establish more focused, accurate, effective, alternative, and safe therapy to reduce DPN. Cell-based therapy might be a permanent solution in the treatment and management of diabetes-induced neuropathy. Full article
(This article belongs to the Section Neuropathology)
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22 pages, 6893 KiB  
Review
Breathwork Interventions for Adults with Clinically Diagnosed Anxiety Disorders: A Scoping Review
by Blerida Banushi, Madeline Brendle, Anya Ragnhildstveit, Tara Murphy, Claire Moore, Johannes Egberts and Reid Robison
Brain Sci. 2023, 13(2), 256; https://doi.org/10.3390/brainsci13020256 - 2 Feb 2023
Cited by 20 | Viewed by 26241
Abstract
Anxiety disorders are the most common group of mental disorders, but they are often underrecognized and undertreated in primary care. Dysfunctional breathing is a hallmark of anxiety disorders; however, mainstays of treatments do not tackle breathing in patients suffering anxiety. This scoping review [...] Read more.
Anxiety disorders are the most common group of mental disorders, but they are often underrecognized and undertreated in primary care. Dysfunctional breathing is a hallmark of anxiety disorders; however, mainstays of treatments do not tackle breathing in patients suffering anxiety. This scoping review aims to identify the nature and extent of the available research literature on the efficacy of breathwork interventions for adults with clinically diagnosed anxiety disorders using the DSM-5 classification system. Using the PRISMA extension for scoping reviews, a search of PubMed, Embase, and Scopus was conducted using terms related to anxiety disorders and breathwork interventions. Only clinical studies using breathwork (without the combination of other interventions) and performed on adult patients diagnosed with an anxiety disorder using the DSM-5 classification system were included. From 1081 articles identified across three databases, sixteen were included for the review. A range of breathwork interventions yielded significant improvements in anxiety symptoms in patients clinically diagnosed with anxiety disorders. The results around the role of hyperventilation in treatment of anxiety were contradictory in few of the examined studies. This evidence-based review supports the clinical utility of breathwork interventions and discusses effective treatment options and protocols that are feasible and accessible to patients suffering anxiety. Current gaps in knowledge for future research directions have also been identified. Full article
(This article belongs to the Special Issue Complementary and Alternative Therapies for Mental Health)
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18 pages, 2930 KiB  
Article
Auricular Vagus Nerve Stimulation Improves Visceral Hypersensitivity and Gastric Motility and Depression-like Behaviors via Vago-Vagal Pathway in a Rat Model of Functional Dyspepsia
by Liwei Hou, Peijing Rong, Yang Yang, Jiliang Fang, Junying Wang, Yu Wang, Jinling Zhang, Shuai Zhang, Zixuan Zhang, Jiande D. Z. Chen and Wei Wei
Brain Sci. 2023, 13(2), 253; https://doi.org/10.3390/brainsci13020253 - 1 Feb 2023
Cited by 15 | Viewed by 4151
Abstract
Transcutaneous auricular vagus nerve stimulation was recently reported to have a therapeutic potential for functional dyspepsia (FD). This study aimed to explore the integrative effects and mechanisms of auricular vagus nerve stimulation (aVNS) in a rodent model of FD. Methods: We evaluated the [...] Read more.
Transcutaneous auricular vagus nerve stimulation was recently reported to have a therapeutic potential for functional dyspepsia (FD). This study aimed to explore the integrative effects and mechanisms of auricular vagus nerve stimulation (aVNS) in a rodent model of FD. Methods: We evaluated the effects of aVNS on visceral hypersensitivity, gastric motility and open field test (OFT) activity in iodoacetamide (IA)-treated rats. The autonomic function was assessed; blood samples and tissues were collected and analyzed by an enzyme-linked immunosorbent assay and western blot. Vagotomy was performed to investigate the role of vagal efferent nerve. Results: aVNS reduced the electromyography response to gastric distension, improved gastric emptying and increased the horizontal and vertical motion scores of the OFT in IA-treated rats. The sympathovagal ratio was increased in IA-treated rats but normalized with aVNS. The serum cytokines TNF-α, IL-6, IL-1β and NF-κBp65 were increased in IA-treated rats and decreased with aVNS. The hypothalamus–pituitary–adrenal axis was hyperactive in IA-treated rats but inhibited by aVNS. The expression of duodenal desmoglein 2 and occludin were all decreased in IA-treated rats and increased with aVNS but not sham-aVNS. Vagotomy abolished the ameliorating effects of aVNS on gastric emptying, horizontal motions, serum TNF-α and duodenal NF-κBp65. Conclusion: aVNS improves gastric motility and gastric hypersensitivity probably by anti-inflammatory mechanisms via the vago-vagal pathways. A better understanding on the mechanisms of action involved with aVNS would lead to the optimization of the taVNS methodology and promote taVNS as a non-pharmacological alternative therapy for FD. Full article
(This article belongs to the Section Clinical Neuroscience)
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18 pages, 3172 KiB  
Review
The Genetics of Intellectual Disability
by Sandra Jansen, Lisenka E. L. M. Vissers and Bert B. A. de Vries
Brain Sci. 2023, 13(2), 231; https://doi.org/10.3390/brainsci13020231 - 30 Jan 2023
Cited by 27 | Viewed by 11737
Abstract
Intellectual disability (ID) has a prevalence of ~2–3% in the general population, having a large societal impact. The underlying cause of ID is largely of genetic origin; however, identifying this genetic cause has in the past often led to long diagnostic Odysseys. Over [...] Read more.
Intellectual disability (ID) has a prevalence of ~2–3% in the general population, having a large societal impact. The underlying cause of ID is largely of genetic origin; however, identifying this genetic cause has in the past often led to long diagnostic Odysseys. Over the past decades, improvements in genetic diagnostic technologies and strategies have led to these causes being more and more detectable: from cytogenetic analysis in 1959, we moved in the first decade of the 21st century from genomic microarrays with a diagnostic yield of ~20% to next-generation sequencing platforms with a yield of up to 60%. In this review, we discuss these various developments, as well as their associated challenges and implications for the field of ID, which highlight the revolutionizing shift in clinical practice from a phenotype-first into genotype-first approach. Full article
(This article belongs to the Special Issue Reviews on Developmental Brain Disorders)
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20 pages, 823 KiB  
Systematic Review
Maximal Safe Resection in Glioblastoma Surgery: A Systematic Review of Advanced Intraoperative Image-Guided Techniques
by Lapo Bonosi, Salvatore Marrone, Umberto Emanuele Benigno, Felice Buscemi, Sofia Musso, Massimiliano Porzio, Manikon Poullay Silven, Fabio Torregrossa and Giovanni Grasso
Brain Sci. 2023, 13(2), 216; https://doi.org/10.3390/brainsci13020216 - 28 Jan 2023
Cited by 31 | Viewed by 3690
Abstract
Glioblastoma multiforme (GBM) represents the most common and aggressive central nervous system tumor associated with a poor prognosis. The aim of this study was to depict the role of intraoperative imaging techniques in GBM surgery and how they can ensure the maximal extent [...] Read more.
Glioblastoma multiforme (GBM) represents the most common and aggressive central nervous system tumor associated with a poor prognosis. The aim of this study was to depict the role of intraoperative imaging techniques in GBM surgery and how they can ensure the maximal extent of resection (EOR) while preserving the functional outcome. The authors conducted a systematic review following PRISMA guidelines on the PubMed/Medline and Scopus databases. A total of 1747 articles were identified for screening. Studies focusing on GBM-affected patients, and evaluations of EOR and functional outcomes with the aid of advanced image-guided techniques were included. The resulting studies were assessed for methodological quality using the Risk of Bias in Systematic Review tool. Open Science Framework registration DOI 10.17605/OSF.IO/3FDP9. Eighteen studies were eligible for this systematic review. Among the selected studies, eight analyzed Sodium Fluorescein, three analyzed 5-aminolevulinic acid, two evaluated IoMRI imaging, two evaluated IoUS, and three evaluated multiple intraoperative imaging techniques. A total of 1312 patients were assessed. Gross Total Resection was achieved in the 78.6% of the cases. Follow-up time ranged from 1 to 52 months. All studies assessed the functional outcome based on the Karnofsky Performance Status scale, while one used the Neurologic Assessment in Neuro-Oncology score. In 77.7% of the cases, the functional outcome improved or was stable over the pre-operative assessment. Combining multiple intraoperative imaging techniques could provide better results in GBM surgery than a single technique. However, despite good surgical outcomes, patients often present a neurocognitive decline leading to a marked deterioration of the quality of life. Advanced intraoperative image-guided techniques can allow a better understanding of the anatomo-functional relationships between the tumor and the surrounding brain, thus maximizing the EOR while preserving functional outcomes. Full article
(This article belongs to the Section Neurosurgery and Neuroanatomy)
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12 pages, 277 KiB  
Review
Theories about Developmental Dyslexia
by John Stein
Brain Sci. 2023, 13(2), 208; https://doi.org/10.3390/brainsci13020208 - 26 Jan 2023
Cited by 14 | Viewed by 11888
Abstract
Despite proving its usefulness for over a century, the concept of developmental dyslexia (DD) is currently in severe disarray because of the recent introduction of the phonological theory of its causation. Since mastering the phonological principle is essential for all reading, failure to [...] Read more.
Despite proving its usefulness for over a century, the concept of developmental dyslexia (DD) is currently in severe disarray because of the recent introduction of the phonological theory of its causation. Since mastering the phonological principle is essential for all reading, failure to do so cannot be used to distinguish DD from the many other causes of such failure. To overcome this problem, many new psychological, signal detection, and neurological theories have been introduced recently. All these new theories converge on the idea that DD is fundamentally caused by impaired signalling of the timing of the visual and auditory cues that are essential for reading. These are provided by large ‘magnocellular’ neurones which respond rapidly to sensory transients. The evidence for this conclusion is overwhelming. Especially convincing are intervention studies that have shown that improving magnocellular function improves dyslexic children’s reading, together with cohort studies that have demonstrated that the magnocellular timing deficit is present in infants who later become dyslexic, long before they begin learning to read. The converse of the magnocellular deficit in dyslexics may be that they gain parvocellular abundance. This may often impart the exceptional ‘holistic’ talents that have been ascribed to them and that society needs to nurture. Full article
(This article belongs to the Special Issue Developmental Dyslexia: Theories and Experimental Approaches)
17 pages, 1471 KiB  
Article
Low Levels of Adenosine and GDNF Are Potential Risk Factors for Parkinson’s Disease with Sleep Disorders
by Li Wang, Zheng Gao, Gang Chen, Deqin Geng and Dianshuai Gao
Brain Sci. 2023, 13(2), 200; https://doi.org/10.3390/brainsci13020200 - 24 Jan 2023
Cited by 14 | Viewed by 2526
Abstract
Sleep disturbances are the most prevalent non-motor symptoms in the preclinical stage of Parkinson’s disease (PD). Adenosine, glial-derived neurotrophic factor (GDNF), and associated neurotransmitters are crucial in the control of sleep arousal. This study aimed to detect the serum levels of adenosine, GDNF, [...] Read more.
Sleep disturbances are the most prevalent non-motor symptoms in the preclinical stage of Parkinson’s disease (PD). Adenosine, glial-derived neurotrophic factor (GDNF), and associated neurotransmitters are crucial in the control of sleep arousal. This study aimed to detect the serum levels of adenosine, GDNF, and associated neurotransmitters and explored their correlations with PD with sleep disorders. Demographic characteristics and clinical information of PD patients and healthy participants were assessed. Serum concentrations of adenosine, GDNF, and related neurotransmitters were detected by ELISA and LC-MS. The correlation between serum levels of adenosine, GDNF, and associated neurotransmitters and sleep disorders was explored using logistic regression. PD patients with sleep disorders had higher scores of HAMA, HAMD, ESS, UPDRS-III, and H-Y stage. Lower levels of adenosine, GDNF, and γ-GABA were observed in PD patients who had sleep problems. Logistic regression analysis showed adenosine and GDNF were protective factors for preventing sleep disorders. Adenosine combined with GDNF had a higher diagnostic efficiency in predicting PD with sleep disorders by ROC analysis. This study revealed low adenosine and GDNF levels may be risk factors for sleep disorders in PD. The decrease of serum adenosine and GDNF levels may contribute to the diagnosis of PD with sleep disturbances. Full article
(This article belongs to the Section Sensory and Motor Neuroscience)
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11 pages, 1441 KiB  
Article
Decreased ALFF and Functional Connectivity of the Thalamus in Vestibular Migraine Patients
by Xia Zhe, Min Tang, Kai Ai, Xiaoyan Lei, Xiaoling Zhang and Chenwang Jin
Brain Sci. 2023, 13(2), 183; https://doi.org/10.3390/brainsci13020183 - 22 Jan 2023
Cited by 13 | Viewed by 2727
Abstract
Background: The thalamus has been reported to be associated with pain modulation and processing. However, the functional changes that occur in the thalamus of vestibular migraine (VM) patients remain unknown. Methods: In total, 28 VM patients and 28 healthy controls who were matched [...] Read more.
Background: The thalamus has been reported to be associated with pain modulation and processing. However, the functional changes that occur in the thalamus of vestibular migraine (VM) patients remain unknown. Methods: In total, 28 VM patients and 28 healthy controls who were matched for age and sex underwent resting-state functional magnetic resonance imaging. They also responded to standardized questionnaires aimed at assessing the clinical features associated with migraine and vertigo. Differences in the amplitude of low-frequency fluctuation (ALFF) were analyzed and brain regions with altered ALFF in the two groups were used for further analysis of whole-brain functional connectivity (FC). The relationship between clusters and clinical features was investigated by correlation analyses. Results: The ALFF in the thalamus was significantly decreased in the VM group versus the control group. In the VM group, the ALFF in the left thalamus negatively correlated with VM episode frequency. Furthermore, the left thalamus showed significantly weaker FC than both regions of the medial prefrontal cortex, both regions of the anterior cingulum cortex, the left superior/middle temporal gyrus, and the left temporal pole in the VM group. Conclusions: The thalamus plays an important role in VM patients and it is suggested that connectivity abnormalities of the thalamocortical region contribute to abnormal pain information processing and modulation, transmission, and multisensory integration in patients with VM. Full article
(This article belongs to the Section Neurotechnology and Neuroimaging)
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11 pages, 4152 KiB  
Article
Gastrodin Improves Cognitive Dysfunction in REM Sleep-Deprived Rats by Regulating TLR4/NF-κB and Wnt/β-Catenin Signaling Pathways
by Bo Liu, Fei Li, Yunyan Xu, Qin Wu and Jingshan Shi
Brain Sci. 2023, 13(2), 179; https://doi.org/10.3390/brainsci13020179 - 21 Jan 2023
Cited by 18 | Viewed by 2945
Abstract
Gastrodin is the active ingredient in Gastrodia elata. Our previous studies demonstrated that gastrodin ameliorated cerebral ischemia–reperfusion and hypoperfusion injury and improved cognitive deficit in Alzheimer’s disease. This study aims to examine the effects of gastrodin on REM sleep deprivation in rats. Gastrodin [...] Read more.
Gastrodin is the active ingredient in Gastrodia elata. Our previous studies demonstrated that gastrodin ameliorated cerebral ischemia–reperfusion and hypoperfusion injury and improved cognitive deficit in Alzheimer’s disease. This study aims to examine the effects of gastrodin on REM sleep deprivation in rats. Gastrodin (100 and 150 mg/kg) was orally administered for 7 consecutive days before REM sleep deprivation. Seventy-two hours later, pentobarbital-induced sleep tests and a Morris water maze were performed to measure REM sleep quality and learning and memory ability. Histopathology was observed with hematoxylin–eosin staining, and the expression of the NF-κB and Wnt/β-catenin signaling pathways was examined using Western blot. After REM sleep deprivation, sleep latency increased and sleep duration decreased, and the ability of learning and memory was impaired. Neurons in the hippocampal CA1 region and the cortex were damaged. Gastrodin treatment significantly improved REM sleep-deprivation-induced sleep disturbance, cognitive deficits and neuron damage in the hippocampus CA1 region and cerebral cortex. A mechanism analysis revealed that the NF-κB pathway was activated and the Wnt/β-catenin pathway was inhibited after REM sleep deprivation, and gastrodin ameliorated these aberrant changes. Gastrodin improves REM sleep-deprivation-induced sleep disturbance and cognitive dysfunction by regulating the TLR4/NF-κB and Wnt/β-catenin signaling pathways and can be considered a potential candidate for the treatment of REM sleep deprivation. Full article
(This article belongs to the Special Issue Advances in Research on Brain Health and Dementia: Prevention and Early Detection of Cognitive Decline and Dementia)
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12 pages, 312 KiB  
Review
Lethal Lust: Suicidal Behavior and Chemsex—A Narrative Review of the Literature
by Martina Strasser, Theresa Halms, Tobias Rüther, Alkomiet Hasan and Marcus Gertzen
Brain Sci. 2023, 13(2), 174; https://doi.org/10.3390/brainsci13020174 - 20 Jan 2023
Cited by 14 | Viewed by 4933
Abstract
Chemsex is described as the use of certain drugs—commonly methamphetamine, gamma-butyrolactone (GBL)/gammahydroxybutyrate (GHB), and mephedrone—before or during planned sexual activity primarily among men who have sex with men (MSM). Evidence shows that MSM who engage in chemsex are at increased risk of physical [...] Read more.
Chemsex is described as the use of certain drugs—commonly methamphetamine, gamma-butyrolactone (GBL)/gammahydroxybutyrate (GHB), and mephedrone—before or during planned sexual activity primarily among men who have sex with men (MSM). Evidence shows that MSM who engage in chemsex are at increased risk of physical harm, such as sexually transmittable infections (STIs), and are more likely to experience mental health symptoms. To further assess this, we reviewed the recent literature to evaluate whether the psychological impact of chemsex behavior includes suicidal ideation and suicidal attempts. Pubmed/MEDLINE was searched for articles reporting suicidal ideation and behavior among chemsex users with the terms “chemsex”, “sexualized drug use”, “suicide”, and “mental health”. Twelve articles (three case reports and nine cross-sectional studies) were included in the final narrative review. Overall, we retrieved mixed results regarding the relationship between chemsex practice and suicidality outcomes. Considering the inhomogeneous nature of the studies, the findings indicate that suicidality could be an issue of concern among MSM in general but among chemsex users in particular. Possible risk factors for suicidality among chemsex participants may include adversities experienced due to one’s sexual orientation and an increased risk for HIV and other STI infections and the resulting negative impact on mental well-being. These aspects warrant further investigations. Full article
(This article belongs to the Section Neuropsychiatry)
12 pages, 1343 KiB  
Article
Cognitive Performance in Short Sleep Young Adults with Different Physical Activity Levels: A Cross-Sectional fNIRS Study
by Yanwei You, Jianxiu Liu, Dizhi Wang, Yingyao Fu, Ruidong Liu and Xindong Ma
Brain Sci. 2023, 13(2), 171; https://doi.org/10.3390/brainsci13020171 - 19 Jan 2023
Cited by 48 | Viewed by 5129
Abstract
Short sleep is a common issue nowadays. The purpose of this study was to investigate prefrontal cortical hemodynamics by evaluating changes in concentrations of oxygenated hemoglobin (HbO) in cognitive tests among short-sleep young adults and to explore the relationship between sleep duration, physical [...] Read more.
Short sleep is a common issue nowadays. The purpose of this study was to investigate prefrontal cortical hemodynamics by evaluating changes in concentrations of oxygenated hemoglobin (HbO) in cognitive tests among short-sleep young adults and to explore the relationship between sleep duration, physical activity level, and cognitive function in this specific population. A total of 46 participants (25 males and 21 females) were included in our study, and among them, the average sleep duration was 358 min/day. Stroop performance in the short sleep population was linked to higher levels cortical activation in distinct parts of the left middle frontal gyrus. This study found that moderate-to-vigorous physical activity (MVPA) was significantly associated with lower accuracy of incongruent Stroop test. The dose-response relationship between sleep duration and Stroop performance under different levels of light-intensity physical activity (LPA) and MVPA was further explored, and increasing sleep time for different PA level was associated with better Stroop performance. In summary, this present study provided neurobehavioral evidence between cortical hemodynamics and cognitive function in the short sleep population. Furthermore, our findings indicated that, in younger adults with short sleep, more MVPA was associated with worse cognitive performance. Short sleep young adults should increase sleep time, rather than more MVPA, to achieve better cognitive function. Full article
(This article belongs to the Special Issue The Mechanisms of Sleep Function and Regulation for Health and Cognitive Performance)
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20 pages, 975 KiB  
Review
The Role of Brain-Derived Neurotrophic Factor (BDNF) in Diagnosis and Treatment of Epilepsy, Depression, Schizophrenia, Anorexia Nervosa and Alzheimer’s Disease as Highly Drug-Resistant Diseases: A Narrative Review
by Aleksandra Gliwińska, Justyna Czubilińska-Łada, Gniewko Więckiewicz, Elżbieta Świętochowska, Andrzej Badeński, Marta Dworak and Maria Szczepańska
Brain Sci. 2023, 13(2), 163; https://doi.org/10.3390/brainsci13020163 - 18 Jan 2023
Cited by 33 | Viewed by 8012
Abstract
Brain-derived neurotrophic factor (BDNF) belongs to the family of neurotrophins, which are growth factors with trophic effects on neurons. BDNF is the most widely distributed neurotrophin in the central nervous system (CNS) and is highly expressed in the prefrontal cortex (PFC) and hippocampus. [...] Read more.
Brain-derived neurotrophic factor (BDNF) belongs to the family of neurotrophins, which are growth factors with trophic effects on neurons. BDNF is the most widely distributed neurotrophin in the central nervous system (CNS) and is highly expressed in the prefrontal cortex (PFC) and hippocampus. Its distribution outside the CNS has also been demonstrated, but most studies have focused on its effects in neuropsychiatric disorders. Despite the advances in medicine in recent decades, neurological and psychiatric diseases are still characterized by high drug resistance. This review focuses on the use of BDNF in the developmental assessment, treatment monitoring, and pharmacotherapy of selected diseases, with a particular emphasis on epilepsy, depression, anorexia, obesity, schizophrenia, and Alzheimer’s disease. The limitations of using a molecule with such a wide distribution range and inconsistent method of determination are also highlighted. Full article
(This article belongs to the Section Neuropsychiatry)
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23 pages, 4934 KiB  
Review
Predictive Value of CT Perfusion in Hemorrhagic Transformation after Acute Ischemic Stroke: A Systematic Review and Meta-Analysis
by Jie Xu, Fangyu Dai, Binda Wang, Yiming Wang, Jiaqian Li, Lulan Pan, Jingjing Liu, Haipeng Liu and Songbin He
Brain Sci. 2023, 13(1), 156; https://doi.org/10.3390/brainsci13010156 - 16 Jan 2023
Cited by 14 | Viewed by 3831
Abstract
Background: Existing studies indicate that some computed tomography perfusion (CTP) parameters may predict hemorrhagic transformation (HT) after acute ischemic stroke (AIS), but there is an inconsistency in the conclusions alongside a lack of comprehensive comparison. Objective: To comprehensively evaluate the predictive value of [...] Read more.
Background: Existing studies indicate that some computed tomography perfusion (CTP) parameters may predict hemorrhagic transformation (HT) after acute ischemic stroke (AIS), but there is an inconsistency in the conclusions alongside a lack of comprehensive comparison. Objective: To comprehensively evaluate the predictive value of CTP parameters in HT after AIS. Data sources: A systematical literature review of existing studies was conducted up to 1st October 2022 in six mainstream databases that included original data on the CTP parameters of HT and non-HT groups or on the diagnostic performance of relative cerebral blood flow (rCBF), relative permeability-surface area product (rPS), or relative cerebral blood volume (rCBV) in patients with AIS that completed CTP within 24 h of onset. Data Synthesis: Eighteen observational studies were included. HT and non-HT groups had statistically significant differences in CBF, CBV, PS, rCBF, rCBV, and rPS (p < 0.05 for all). The hierarchical summary receiver operating characteristic (HSROC) revealed that rCBF (area under the curve (AUC) = 0.9), rPS (AUC = 0.89), and rCBV (AUC = 0.85) had moderate diagnostic performances in predicting HT. The pooled sensitivity and specificity of rCBF were 0.85 (95% CI, 0.75–0.91) and 0.83 (95% CI, 0.63–0.94), respectively. Conclusions: rCBF, rPS, and rCBV had moderate diagnostic performances in predicting HT, and rCBF had the best pooled sensitivity and specificity. Full article
(This article belongs to the Topic Diagnosis and Management of Acute Ischemic Stroke)
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12 pages, 958 KiB  
Review
α-Synuclein and Mechanisms of Epigenetic Regulation
by Andrei Surguchov
Brain Sci. 2023, 13(1), 150; https://doi.org/10.3390/brainsci13010150 - 15 Jan 2023
Cited by 19 | Viewed by 4956
Abstract
Synucleinopathies are a group of neurodegenerative diseases with common pathological lesions associated with the excessive accumulation and abnormal intracellular deposition of toxic species of α-synuclein. The shared clinical features are chronic progressive decline of motor, cognitive, and behavioral functions. These disorders include Parkinson’s [...] Read more.
Synucleinopathies are a group of neurodegenerative diseases with common pathological lesions associated with the excessive accumulation and abnormal intracellular deposition of toxic species of α-synuclein. The shared clinical features are chronic progressive decline of motor, cognitive, and behavioral functions. These disorders include Parkinson’s disease, dementia with Lewy body, and multiple system atrophy. Vigorous research in the mechanisms of pathology of these illnesses is currently under way to find disease-modifying treatment and molecular markers for early diagnosis. α-Synuclein is a prone-to-aggregate, small amyloidogenic protein with multiple roles in synaptic vesicle trafficking, neurotransmitter release, and intracellular signaling events. Its expression is controlled by several mechanisms, one of which is epigenetic regulation. When transmitted to the nucleus, α-synuclein binds to DNA and histones and participates in epigenetic regulatory functions controlling specific gene transcription. Here, we discuss the various aspects of α-synuclein involvement in epigenetic regulation in health and diseases. Full article
(This article belongs to the Section Molecular and Cellular Neuroscience)
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15 pages, 3068 KiB  
Article
Resolvin D2 Reduces Chronic Neuropathic Pain and Bone Cancer Pain via Spinal Inhibition of IL-17 Secretion, CXCL1 Release and Astrocyte Activation in Mice
by Jun Pang, Pengfei Xin, Ying Kong, Zhe Wang and Xiaopeng Wang
Brain Sci. 2023, 13(1), 152; https://doi.org/10.3390/brainsci13010152 - 15 Jan 2023
Cited by 12 | Viewed by 3010
Abstract
Chronic pain burdens patients and healthcare systems worldwide. Pain control remains urgently required. IL-17 (interleukin-17)-mediated neuroinflammation is of unique importance in spinal nociceptive transduction in pathological pain development. Recently, resolvin D2 (RvD2), as a bioactive, specialized pro-resolving mediator derived from docosahexaenoic acid, exhibits [...] Read more.
Chronic pain burdens patients and healthcare systems worldwide. Pain control remains urgently required. IL-17 (interleukin-17)-mediated neuroinflammation is of unique importance in spinal nociceptive transduction in pathological pain development. Recently, resolvin D2 (RvD2), as a bioactive, specialized pro-resolving mediator derived from docosahexaenoic acid, exhibits potent resolution of inflammation in several neurological disorders. This preclinical study evaluates the therapeutic potential and underlying targets of RvD2 in two mouse models of chronic pain, including sciatic nerve ligation-caused neuropathic pain and sarcoma-caused bone cancer pain. Herein, we report that repetitive injections of RvD2 (intrathecal, 500 ng) reduce the initiation of mechanical allodynia and heat hyperalgesia following sciatic nerve damage and bone cancer. Single exposure to RvD2 (intrathecal, 500 ng) attenuates the established neuropathic pain and bone cancer pain. Furthermore, systemic RvD2 (intravenous, 5 μg) therapy is effective in attenuating chronic pain behaviors. Strikingly, RvD2 treatment suppresses spinal IL-17 overexpression, chemokine CXCL1 release and astrocyte activation in mice undergoing sciatic nerve trauma and bone cancer. Pharmacological neutralization of IL-17 ameliorates chronic neuropathic pain and persistent bone cancer pain, as well as reducing spinal CXCL1 release. Recombinant IL-17-evoked acute pain behaviors and spinal CXCL1 release are mitigated after RvD2 administration. In addition, RvD2 treatment dampens exogenous CXCL1-caused transient pain phenotypes. Overall, these current findings identify that RvD2 therapy is effective against the initiation and persistence of long-lasting neuropathic pain and bone cancer pain, which may be through spinal down-modulation of IL-17 secretion, CXCL1 release and astrocyte activation. Full article
(This article belongs to the Special Issue Advances in Study of Molecular and Cellular Mechanisms Underlying Pain and Itch)
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27 pages, 1502 KiB  
Review
The Neuroprotective Effects and Therapeutic Potential of the Chalcone Cardamonin for Alzheimer’s Disease
by Kimberly Barber, Patricia Mendonca and Karam F. A. Soliman
Brain Sci. 2023, 13(1), 145; https://doi.org/10.3390/brainsci13010145 - 14 Jan 2023
Cited by 26 | Viewed by 4945
Abstract
Neurodegenerative diseases (ND) include a wide range of conditions that result from progressive damage to the neurons. Alzheimer’s disease (AD) is one of the most common NDs, and neuroinflammation and oxidative stress (OS) are the major factors in the development and progression of [...] Read more.
Neurodegenerative diseases (ND) include a wide range of conditions that result from progressive damage to the neurons. Alzheimer’s disease (AD) is one of the most common NDs, and neuroinflammation and oxidative stress (OS) are the major factors in the development and progression of the disease. Many naturally occurring phytochemical compounds exhibit antioxidant and anti-inflammatory activities with potential neuroprotective effects. Several plant species, including Alpinia katsumadai and Alpinia conchigera, contain cardamonin (CD). CD (2′,4′-dihydroxy-6′methoxychalcone) has many therapeutic properties, including anticancer, anti-inflammatory, antioxidant, antiviral, and antibiotic activities. CD is a potent compound that can reduce OS and modulate the inflammatory processes that play a significant part in developing neurodegenerative diseases. CD has been shown to modulate a variety of signaling molecules involved in the development and progression of ND, including transcription factors (NF-kB and STAT3), cytokines (TNF-α, IL-1, and IL-6), enzymes (COX-2, MMP-9, and ALDH1), and other proteins and genes (Bcl-2, XIAP, and cyclin D1). Additionally, CD effectively modulates miRNA levels and autophagy-related CD-protective mechanisms against neurodegeneration. In summary, this review provides mechanistic insights into CD’s ability to modify multiple oxidative stress–antioxidant system pathways, Nrf2, and neuroinflammation. Additionally, it points to the possible therapeutic potential and preventive utilization of CD in neurodegenerative diseases, most specifically AD. Full article
(This article belongs to the Topic Memory-Enhancing Activity of Bioactive Compounds: From Natural Sources to Brain)
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12 pages, 2345 KiB  
Article
Abnormalities of EEG Functional Connectivity and Effective Connectivity in Children with Autism Spectrum Disorder
by Xinling Geng, Xiwang Fan, Yiwen Zhong, Manuel F. Casanova, Estate M. Sokhadze, Xiaoli Li and Jiannan Kang
Brain Sci. 2023, 13(1), 130; https://doi.org/10.3390/brainsci13010130 - 12 Jan 2023
Cited by 14 | Viewed by 3589
Abstract
Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder that interferes with normal brain development. Brain connectivity may serve as a biomarker for ASD in this respect. This study enrolled a total of 179 children aged 3−10 years (90 typically developed (TD) and [...] Read more.
Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder that interferes with normal brain development. Brain connectivity may serve as a biomarker for ASD in this respect. This study enrolled a total of 179 children aged 3−10 years (90 typically developed (TD) and 89 with ASD). We used a weighted phase lag index and a directed transfer function to investigate the functional and effective connectivity in children with ASD and TD. Our findings indicated that patients with ASD had local hyper-connectivity of brain regions in functional connectivity and simultaneous significant decrease in effective connectivity across hemispheres. These connectivity abnormalities may help to find biomarkers of ASD. Full article
(This article belongs to the Special Issue Advanced Functional Connectivity Analysis in Neuropsychiatric Disorders)
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10 pages, 1149 KiB  
Article
Long-Term Lithium Therapy and Thyroid Disorders in Bipolar Disorder: A Historical Cohort Study
by Boney Joseph, Nicolas A. Nunez, Vanessa Pazdernik, Rakesh Kumar, Mehak Pahwa, Mete Ercis, Aysegul Ozerdem, Alfredo B. Cuellar-Barboza, Francisco Romo-Nava, Susan L. McElroy, Brandon J. Coombes, Joanna M. Biernacka, Marius N. Stan, Mark A. Frye and Balwinder Singh
Brain Sci. 2023, 13(1), 133; https://doi.org/10.3390/brainsci13010133 - 12 Jan 2023
Cited by 14 | Viewed by 5891
Abstract
Lithium has been a cornerstone treatment for bipolar disorder (BD). Despite descriptions in the literature regarding associations between long-term lithium therapy (LTLT) and development of a thyroid disorder (overt/subclinical hypo/hyperthyroidism, thyroid nodule, and goiter) in BD, factors such as time to onset of [...] Read more.
Lithium has been a cornerstone treatment for bipolar disorder (BD). Despite descriptions in the literature regarding associations between long-term lithium therapy (LTLT) and development of a thyroid disorder (overt/subclinical hypo/hyperthyroidism, thyroid nodule, and goiter) in BD, factors such as time to onset of thyroid abnormalities and impact on clinical outcomes in the course of illness have not been fully characterized. In this study we aimed to compare clinical characteristics of adult BD patients with and without thyroid disorders who were on LTLT. We aimed to identify the incidence of thyroid disorders in patients with BD on LTLT and response to lithium between patients with and without thyroid disorders in BD. The Cox proportional model was used to find the median time to the development of a thyroid disorder. Our results showed that up to 32% of patients with BD on LTLT developed a thyroid disorder, of which 79% developed hypothyroidism, which was corrected with thyroid hormone replacement. We did not find significant differences in lithium response between patients with or without thyroid disorders in BD. Findings from this study suggest that patients with BD and comorbid thyroid disorders when adequately treated have a response to lithium similar to patients with BD and no thyroid disorders. Full article
(This article belongs to the Special Issue Bipolar Disorders: Progressing from Bench to Bedside)
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14 pages, 1469 KiB  
Review
Modulating Brain Activity with Invasive Brain–Computer Interface: A Narrative Review
by Zhi-Ping Zhao, Chuang Nie, Cheng-Teng Jiang, Sheng-Hao Cao, Kai-Xi Tian, Shan Yu and Jian-Wen Gu
Brain Sci. 2023, 13(1), 134; https://doi.org/10.3390/brainsci13010134 - 12 Jan 2023
Cited by 37 | Viewed by 10961
Abstract
Brain-computer interface (BCI) can be used as a real-time bidirectional information gateway between the brain and machines. In particular, rapid progress in invasive BCI, propelled by recent developments in electrode materials, miniature and power-efficient electronics, and neural signal decoding technologies has attracted wide [...] Read more.
Brain-computer interface (BCI) can be used as a real-time bidirectional information gateway between the brain and machines. In particular, rapid progress in invasive BCI, propelled by recent developments in electrode materials, miniature and power-efficient electronics, and neural signal decoding technologies has attracted wide attention. In this review, we first introduce the concepts of neuronal signal decoding and encoding that are fundamental for information exchanges in BCI. Then, we review the history and recent advances in invasive BCI, particularly through studies using neural signals for controlling external devices on one hand, and modulating brain activity on the other hand. Specifically, regarding modulating brain activity, we focus on two types of techniques, applying electrical stimulation to cortical and deep brain tissues, respectively. Finally, we discuss the related ethical issues concerning the clinical application of this emerging technology. Full article
(This article belongs to the Special Issue Human Brain Dynamics: Latest Advances and Prospects—2nd Edition)
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16 pages, 8532 KiB  
Article
Eyes-Open and Eyes-Closed Resting State Network Connectivity Differences
by Junrong Han, Liwei Zhou, Hang Wu, Yujuan Huang, Mincong Qiu, Likai Huang, Chia Lee, Timothy Joseph Lane and Pengmin Qin
Brain Sci. 2023, 13(1), 122; https://doi.org/10.3390/brainsci13010122 - 10 Jan 2023
Cited by 17 | Viewed by 4540
Abstract
Resting state networks comprise several brain regions that exhibit complex patterns of interaction. Switching from eyes closed (EC) to eyes open (EO) during the resting state modifies these patterns of connectivity, but precisely how these change remains unclear. Here we use functional magnetic [...] Read more.
Resting state networks comprise several brain regions that exhibit complex patterns of interaction. Switching from eyes closed (EC) to eyes open (EO) during the resting state modifies these patterns of connectivity, but precisely how these change remains unclear. Here we use functional magnetic resonance imaging to scan healthy participants in two resting conditions (viz., EC and EO). Seven resting state networks were chosen for this study: salience network (SN), default mode network (DMN), central executive network (CEN), dorsal attention network (DAN), visual network (VN), motor network (MN) and auditory network (AN). We performed functional connectivity (FC) analysis for each network, comparing the FC maps for both EC and EO. Our results show increased connectivity between most networks during EC relative to EO, thereby suggesting enhanced integration during EC and greater modularity or specialization during EO. Among these networks, SN is distinctive: during the transition from EO to EC it evinces increased connectivity with DMN and decreased connectivity with VN. This change might imply that SN functions in a manner analogous to a circuit switch, modulating resting state relations with DMN and VN, when transitioning between EO and EC. Full article
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24 pages, 1227 KiB  
Review
A Comprehensive Review on Anti-Inflammatory Response of Flavonoids in Experimentally-Induced Epileptic Seizures
by Shyam Sunder Rabidas, Chandra Prakash, Jyoti Tyagi, Jyoti Suryavanshi, Pavan Kumar, Jaydeep Bhattacharya and Deepak Sharma
Brain Sci. 2023, 13(1), 102; https://doi.org/10.3390/brainsci13010102 - 5 Jan 2023
Cited by 15 | Viewed by 5346
Abstract
Flavonoids, a group of natural compounds with phenolic structure, are becoming popular as alternative medicines obtained from plants. These compounds are reported to have various pharmacological properties, including attenuation of inflammatory responses in multiple health issues. Epilepsy is a disorder of the central [...] Read more.
Flavonoids, a group of natural compounds with phenolic structure, are becoming popular as alternative medicines obtained from plants. These compounds are reported to have various pharmacological properties, including attenuation of inflammatory responses in multiple health issues. Epilepsy is a disorder of the central nervous system implicated with the activation of the inflammatory cascade in the brain. The aim of the present study was to summarize the role of various neuroinflammatory mediators in the onset and progression of epilepsy, and, thereafter, to discuss the flavonoids and their classes, including their biological properties. Further, we highlighted the modulation of anti-inflammatory responses achieved by these substances in different forms of epilepsy, as evident from preclinical studies executed on multiple epilepsy models. Overall, the review summarizes the available evidence of the anti-inflammatory potential of various flavonoids in epilepsy. Full article
(This article belongs to the Special Issue Recent Advances in Pathophysiology and Therapeutic Approaches in Epilepsy)
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14 pages, 1945 KiB  
Systematic Review
Balance Rehabilitation through Robot-Assisted Gait Training in Post-Stroke Patients: A Systematic Review and Meta-Analysis
by Alberto Loro, Margherita Beatrice Borg, Marco Battaglia, Angelo Paolo Amico, Roberto Antenucci, Paolo Benanti, Michele Bertoni, Luciano Bissolotti, Paolo Boldrini, Donatella Bonaiuti, Thomas Bowman, Marianna Capecci, Enrico Castelli, Loredana Cavalli, Nicoletta Cinone, Lucia Cosenza, Rita Di Censo, Giuseppina Di Stefano, Francesco Draicchio, Vincenzo Falabella, Mirko Filippetti, Silvia Galeri, Francesca Gimigliano, Mauro Grigioni, Marco Invernizzi, Johanna Jonsdottir, Carmelo Lentino, Perla Massai, Stefano Mazzoleni, Stefano Mazzon, Franco Molteni, Sandra Morelli, Giovanni Morone, Antonio Nardone, Daniele Panzeri, Maurizio Petrarca, Federico Posteraro, Andrea Santamato, Lorenza Scotti, Michele Senatore, Stefania Spina, Elisa Taglione, Giuseppe Turchetti, Valentina Varalta, Alessandro Picelli and Alessio Baricichadd Show full author list remove Hide full author list
Brain Sci. 2023, 13(1), 92; https://doi.org/10.3390/brainsci13010092 - 3 Jan 2023
Cited by 21 | Viewed by 6967
Abstract
Background: Balance impairment is a common disability in post-stroke survivors, leading to reduced mobility and increased fall risk. Robotic gait training (RAGT) is largely used, along with traditional training. There is, however, no strong evidence about RAGT superiority, especially on balance. This study [...] Read more.
Background: Balance impairment is a common disability in post-stroke survivors, leading to reduced mobility and increased fall risk. Robotic gait training (RAGT) is largely used, along with traditional training. There is, however, no strong evidence about RAGT superiority, especially on balance. This study aims to determine RAGT efficacy on balance of post-stroke survivors. Methods: PubMed, Cochrane Library, and PeDRO databases were investigated. Randomized clinical trials evaluating RAGT efficacy on post-stroke survivor balance with Berg Balance Scale (BBS) or Timed Up and Go test (TUG) were searched. Meta-regression analyses were performed, considering weekly sessions, single-session duration, and robotic device used. Results: A total of 18 trials have been included. BBS pre-post treatment mean difference is higher in RAGT-treated patients, with a pMD of 2.17 (95% CI 0.79; 3.55). TUG pre-post mean difference is in favor of RAGT, but not statistically, with a pMD of −0.62 (95%CI − 3.66; 2.43). Meta-regression analyses showed no relevant association, except for TUG and treatment duration (β = −1.019, 95% CI − 1.827; −0.210, p-value = 0.0135). Conclusions: RAGT efficacy is equal to traditional therapy, while the combination of the two seems to lead to better outcomes than each individually performed. Robot-assisted balance training should be the focus of experimentation in the following years, given the great results in the first available trials. Given the massive heterogeneity of included patients, trials with more strict inclusion criteria (especially time from stroke) must be performed to finally define if and when RAGT is superior to traditional therapy. 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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20 pages, 399 KiB  
Review
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 60 | Viewed by 7970
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)
30 pages, 1747 KiB  
Review
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 291 | Viewed by 36412
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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15 pages, 2321 KiB  
Article
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 132 | Viewed by 12260
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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17 pages, 1200 KiB  
Review
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 59 | Viewed by 10357
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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28 pages, 933 KiB  
Review
Inter-Individual Variability in tDCS Effects: A Narrative Review on the Contribution of Stable, Variable, and Contextual Factors
by Alessandra Vergallito, Sarah Feroldi, Alberto Pisoni and Leonor J. Romero Lauro
Brain Sci. 2022, 12(5), 522; https://doi.org/10.3390/brainsci12050522 - 20 Apr 2022
Cited by 72 | Viewed by 6225
Abstract
Due to its safety, portability, and cheapness, transcranial direct current stimulation (tDCS) use largely increased in research and clinical settings. Despite tDCS’s wide application, previous works pointed out inconsistent and low replicable results, sometimes leading to extreme conclusions about tDCS’s ineffectiveness in modulating [...] Read more.
Due to its safety, portability, and cheapness, transcranial direct current stimulation (tDCS) use largely increased in research and clinical settings. Despite tDCS’s wide application, previous works pointed out inconsistent and low replicable results, sometimes leading to extreme conclusions about tDCS’s ineffectiveness in modulating behavioral performance across cognitive domains. Traditionally, this variability has been linked to significant differences in the stimulation protocols across studies, including stimulation parameters, target regions, and electrodes montage. Here, we reviewed and discussed evidence of heterogeneity emerging at the intra-study level, namely inter-individual differences that may influence the response to tDCS within each study. This source of variability has been largely neglected by literature, being results mainly analyzed at the group level. Previous research, however, highlighted that only a half—or less—of studies’ participants could be classified as responders, being affected by tDCS in the expected direction. Stable and variable inter-individual differences, such as morphological and genetic features vs. hormonal/exogenous substance consumption, partially account for this heterogeneity. Moreover, variability comes from experiments’ contextual elements, such as participants’ engagement/baseline capacity and individual task difficulty. We concluded that increasing knowledge on inter-dividual differences rather than undermining tDCS effectiveness could enhance protocols’ efficiency and reproducibility. Full article
(This article belongs to the Special Issue The Modulatory Role of Non-invasive Brain Stimulation Techniques on Cognitive Functions: Hints from Significant and Null Results)
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26 pages, 3917 KiB  
Systematic Review
Prevalence of Developmental Dyslexia in Primary School Children: A Systematic Review and Meta-Analysis
by Liping Yang, Chunbo Li, Xiumei Li, Manman Zhai, Qingqing An, You Zhang, Jing Zhao and Xuchu Weng
Brain Sci. 2022, 12(2), 240; https://doi.org/10.3390/brainsci12020240 - 10 Feb 2022
Cited by 87 | Viewed by 17657
Abstract
Background: Developmental dyslexia (DD) is a specific learning disorder concerning reading acquisition that may has a lifelong negative impact on individuals. A reliable estimate of the prevalence of DD serves as the basis for diagnosis, intervention, and evidence-based health resource allocation and policy-making. [...] Read more.
Background: Developmental dyslexia (DD) is a specific learning disorder concerning reading acquisition that may has a lifelong negative impact on individuals. A reliable estimate of the prevalence of DD serves as the basis for diagnosis, intervention, and evidence-based health resource allocation and policy-making. Hence, the present meta-analysis aims to generate a reliable prevalence estimate of DD worldwide in primary school children and explore the potential variables related to that prevalence. Methods: Studies from the 1950s to June 2021 were collated using a combination of search terms related to DD and prevalence. Study quality was assessed using the STROBE guidelines according to the study design, with study heterogeneity assessed using the I2 statistic, and random-effects meta-analyses were conducted. Variations in the prevalence of DD in different subgroups were assessed via subgroup meta-analysis and meta-regression. Results: The pooled prevalence of DD was 7.10% (95% CI: 6.27–7.97%). The prevalence in boys was significantly higher than that in girls (boys: 9.22%, 95%CI, 8.07–10.44%; girls: 4.66%, 95% CI, 3.84–5.54%; p < 0.001), but no significant difference was found in the prevalence across different writing systems (alphabetic scripts: 7.26%, 95%CI, 5.94–8.71%; logographic scripts: 6.97%, 95%CI, 5.86–8.16%; p > 0.05) or across different orthographic depths (shallow: 7.13%, 95% CI, 5.23–9.30%; deep: 7.55%, 95% CI, 4.66–11.04%; p > 0.05). It is worth noting that most articles had small sample sizes with diverse operational definitions, making comparisons challenging. Conclusions: This study provides an estimation of worldwide DD prevalence in primary school children. The prevalence was higher in boys than in girls but was not significantly different across different writing systems. Full article
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25 pages, 615 KiB  
Review
Heart Rate Variability and Pain: A Systematic Review
by Giuseppe Forte, Giovanna Troisi, Mariella Pazzaglia, Vilfredo De Pascalis and Maria Casagrande
Brain Sci. 2022, 12(2), 153; https://doi.org/10.3390/brainsci12020153 - 24 Jan 2022
Cited by 100 | Viewed by 16615
Abstract
Background and Objective: Heart rate variability (HRV) as an index of the autonomic nervous system appears to be related to reactivity to experimental pain stimuli. HRV could better explain the contributions of sympathetic and parasympathetic activity response to nociceptive stimulation. The aim of [...] Read more.
Background and Objective: Heart rate variability (HRV) as an index of the autonomic nervous system appears to be related to reactivity to experimental pain stimuli. HRV could better explain the contributions of sympathetic and parasympathetic activity response to nociceptive stimulation. The aim of this study was to systematically review and synthesize the current evidence on HRV in relation to the experience of pain in experimental tasks. Databases and Data Treatment: Studies indexed in the PubMed, PsycINFO, MEDLINE, WebOfScience, and Scopus databases were reviewed for eligibility. Studies on the autonomic response (i.e., HRV) to experimentally induced pain in healthy adults were included. Different methods of pain induction were considered (e.g., thermal, pressure, and electrical). Data were synthesized considering the association between HRV and both pain induction and subjective measures of pain. Results: Seventy-one studies were included. The results underline significant change in both the sympathetic and parasympathetic autonomic nervous systems during the painful stimulation independent of the pain induction method. The autonomic reaction to pain could be affected by several factors, such as sex, age, body mass index, breathing patterns, the intensity of the stimulation, and the affective state. Moreover, an association between the autonomic nervous system and the subjective experience of pain was found. Higher parasympathetic activity was associated with better self-regulation capacities and, accordingly, a higher pain inhibition capacity. Conclusions: HRV appears to be a helpful marker to evaluate nociceptive response in experimentally induced pain. Future studies are also needed in clinical samples to understand better the interindividual changes of autonomic response due to pain stimuli. Full article
(This article belongs to the Section Sensory and Motor Neuroscience)
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16 pages, 4000 KiB  
Article
Identification of Autism in Children Using Static Facial Features and Deep Neural Networks
by K. K. Mujeeb Rahman and M. Monica Subashini
Brain Sci. 2022, 12(1), 94; https://doi.org/10.3390/brainsci12010094 - 12 Jan 2022
Cited by 75 | Viewed by 20889
Abstract
Autism spectrum disorder (ASD) is a complicated neurological developmental disorder that manifests itself in a variety of ways. The child diagnosed with ASD and their parents’ daily lives can be dramatically improved with early diagnosis and appropriate medical intervention. The applicability of static [...] Read more.
Autism spectrum disorder (ASD) is a complicated neurological developmental disorder that manifests itself in a variety of ways. The child diagnosed with ASD and their parents’ daily lives can be dramatically improved with early diagnosis and appropriate medical intervention. The applicability of static features extracted from autistic children’s face photographs as a biomarker to distinguish them from typically developing children is investigated in this study paper. We used five pre-trained CNN models: MobileNet, Xception, EfficientNetB0, EfficientNetB1, and EfficientNetB2 as feature extractors and a DNN model as a binary classifier to identify autism in children accurately. We used a publicly available dataset to train the suggested models, which consisted of face pictures of children diagnosed with autism and controls classed as autistic and non-autistic. The Xception model outperformed the others, with an AUC of 96.63%, a sensitivity of 88.46%, and an NPV of 88%. EfficientNetB0 produced a consistent prediction score of 59% for autistic and non-autistic groups with a 95% confidence level. Full article
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