Brain Sciences

13 pages, 601 KB

Open AccessEditor’s ChoiceReview

Diagnosis and Management of Seronegative Myasthenia Gravis: Lights and Shadows

by Claudia Vinciguerra, Liliana Bevilacqua, Antonino Lupica, Federica Ginanneschi, Giuseppe Piscosquito, Nicasio Rini, Alessandro Rossi, Paolo Barone, Filippo Brighina and Vincenzo Di Stefano

Brain Sci. 2023, 13(9), 1286; https://doi.org/10.3390/brainsci13091286 - 5 Sep 2023

Cited by 35 | Viewed by 9967

Abstract

Myasthenia gravis (MG) is an antibody-mediated neuromuscular disease affecting the neuromuscular junction. In most cases, autoantibodies can be detected in the sera of MG patients, thus aiding in diagnosis and allowing for early screening. However, there is a small proportion of patients who [...] Read more.

Myasthenia gravis (MG) is an antibody-mediated neuromuscular disease affecting the neuromuscular junction. In most cases, autoantibodies can be detected in the sera of MG patients, thus aiding in diagnosis and allowing for early screening. However, there is a small proportion of patients who have no detectable auto-antibodies, a condition termed “seronegative MG” (SnMG). Several factors contribute to this, including laboratory test inaccuracies, decreased antibody production, immunosuppressive therapy, immunodeficiencies, antigen depletion, and immune-senescence. The diagnosis of SnMG is more challenging and is based on clinical features and neurophysiological tests. The early identification of these patients is needed in order to ensure early treatment and prevent complications. This narrative review aims to examine the latest updates on SnMG, defining the clinical characteristics of affected patients, diagnostic methods, management, and therapeutic scenarios. Full article

(This article belongs to the Special Issue Diagnosis, Therapy and Rehabilitation in Neuromuscular Diseases)

► Show Figures

Figure 1

11 pages, 310 KB

Open AccessEditor’s ChoiceArticle

Omega-3 Fatty Acids, Cognition, and Brain Volume in Older Adults

by Spencer Loong, Samuel Barnes, Nicole M. Gatto, Shilpy Chowdhury and Grace J. Lee

Brain Sci. 2023, 13(9), 1278; https://doi.org/10.3390/brainsci13091278 - 2 Sep 2023

Cited by 19 | Viewed by 44610

Abstract

The elderly population is growing at increased rates and is expected to double in size by 2050 in the United States and worldwide. The consumption of healthy foods and enriched diets have been associated with improved cognition and brain health. The key nutrients [...] Read more.

The elderly population is growing at increased rates and is expected to double in size by 2050 in the United States and worldwide. The consumption of healthy foods and enriched diets have been associated with improved cognition and brain health. The key nutrients common to many healthy foods and diets are the omega-3 polyunsaturated fatty acids (omega-3 FAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). We explored whether omega-3 FA levels are associated with brain volume and cognition. Forty healthy, cognitively normal, Seventh-day Adventist older adults (mean age 76.3 years at MRI scan, 22 females) completed neurocognitive testing, a blood draw, and structural neuroimaging from 2016 to 2018. EPA and an overall omega-3 index were associated with individual measures of delayed recall (RAVLT-DR) and processing speed (Stroop Color) as well as entorhinal cortex thickness. EPA, DHA, and the omega-3 index were significantly correlated with the total white matter volume. The entorhinal cortex, frontal pole, and total white matter were associated with higher scores on delayed memory recall. This exploratory study found that among healthy, cognitively older adults, increased levels of omega-3 FAs are associated with better memory, processing speed, and structural brain measures. Full article

(This article belongs to the Special Issue Lifestyle Factors in Neurological Disorders)

28 pages, 2409 KB

Open AccessEditor’s ChoiceReview

The Importance of M1-and M2-Polarized Macrophages in Glioma and as Potential Treatment Targets

by Jiangbin Ren, Bangjie Xu, Jianghao Ren, Zhichao Liu, Lingyu Cai, Xiaotian Zhang, Weijie Wang, Shaoxun Li, Luhao Jin and Lianshu Ding

Brain Sci. 2023, 13(9), 1269; https://doi.org/10.3390/brainsci13091269 - 31 Aug 2023

Cited by 37 | Viewed by 6876

Abstract

Glioma is the most common and malignant tumor of the central nervous system. Glioblastoma (GBM) is the most aggressive glioma, with a poor prognosis and no effective treatment because of its high invasiveness, metabolic rate, and heterogeneity. The tumor microenvironment (TME) contains many [...] Read more.

Glioma is the most common and malignant tumor of the central nervous system. Glioblastoma (GBM) is the most aggressive glioma, with a poor prognosis and no effective treatment because of its high invasiveness, metabolic rate, and heterogeneity. The tumor microenvironment (TME) contains many tumor-associated macrophages (TAMs), which play a critical role in tumor proliferation, invasion, metastasis, and angiogenesis and indirectly promote an immunosuppressive microenvironment. TAM is divided into tumor-suppressive M1-like (classic activation of macrophages) and tumor-supportive M2-like (alternatively activated macrophages) polarized cells. TAMs exhibit an M1-like phenotype in the initial stages of tumor progression, and along with the promotion of lysing tumors and the functions of T cells and NK cells, tumor growth is suppressed, and they rapidly transform into M2-like polarized macrophages, which promote tumor progression. In this review, we discuss the mechanism by which M1- and M2-polarized macrophages promote or inhibit the growth of glioblastoma and indicate the future directions for treatment. Full article

(This article belongs to the Section Neuro-oncology)

► Show Figures

Figure 1

16 pages, 879 KB

Open AccessEditor’s ChoiceReview

Neuroprotective Potential of Flavonoids in Brain Disorders

by Syed Hasan, Nabeel Khatri, Zainab N. Rahman, Amanda A. Menezes, Joud Martini, Faheem Shehjar, Numa Mujeeb and Zahoor A. Shah

Brain Sci. 2023, 13(9), 1258; https://doi.org/10.3390/brainsci13091258 - 29 Aug 2023

Cited by 45 | Viewed by 8712

Abstract

Flavonoids are a large subgroup of polyphenols known to be sourced from over 6000 natural products, including fruits, vegetables, bark, and herbs. Due to their antioxidant properties, flavonoids have been implicated as a therapy source for many diseases and conditions, including inflammation, vasculitis, [...] Read more.

Flavonoids are a large subgroup of polyphenols known to be sourced from over 6000 natural products, including fruits, vegetables, bark, and herbs. Due to their antioxidant properties, flavonoids have been implicated as a therapy source for many diseases and conditions, including inflammation, vasculitis, venous insufficiency, and hemorrhoids. Currently, some flavonoids are being researched for their antioxidant ability concerning neuroprotection. These flavonoids can penetrate the blood–brain barrier and, depending on the specific flavonoid, retain adequate bioavailability in certain brain regions. Further data suggest that flavonoids could have a strong anti-inflammatory effect in the brain, which not only could be a robust therapeutic source for known neuroinflammatory diseases such as Alzheimer’s Disease or Parkinson’s Disease but also could be a therapeutic source for ischemic or hemorrhagic conditions such as a stroke. While flavonoid toxicity exists, they are relatively safe and non-invasive drugs from natural origins. As such, exploring the known mechanisms and therapies may highlight and establish flavonoid therapy as a viable source of therapy for stroke patients. As stated, many flavonoids are already being isolated, purified, and implemented in both in vitro and in vivo experiments. As these flavonoids proceed to clinical trials, it will be important to understand how they function as a therapy, primarily as antioxidants, and by other secondary mechanisms. This review aims to elucidate those mechanisms and explore the neuroprotective role of flavonoids. Full article

(This article belongs to the Special Issue Cellular and Molecular Basis of Neurodegenerative Disease)

► Show Figures

Figure 1

23 pages, 1205 KB

Open AccessEditor’s ChoiceReview

Emerging Paradigms in Inflammatory Disease Management: Exploring Bioactive Compounds and the Gut Microbiota

by Tarek Benameur, Chiara Porro, Mohammed-Elfatih Twfieg, Nassima Benameur, Maria Antonietta Panaro, Francesca Martina Filannino and Abeir Hasan

Brain Sci. 2023, 13(8), 1226; https://doi.org/10.3390/brainsci13081226 - 21 Aug 2023

Cited by 40 | Viewed by 4342

Abstract

The human gut microbiota is a complex ecosystem of mutualistic microorganisms that play a critical role in maintaining human health through their individual interactions and with the host. The normal gastrointestinal microbiota plays a specific physiological function in host immunomodulation, nutrient metabolism, vitamin [...] Read more.

The human gut microbiota is a complex ecosystem of mutualistic microorganisms that play a critical role in maintaining human health through their individual interactions and with the host. The normal gastrointestinal microbiota plays a specific physiological function in host immunomodulation, nutrient metabolism, vitamin synthesis, xenobiotic and drug metabolism, maintenance of structural and functional integrity of the gut mucosal barrier, and protection against various pathogens. Inflammation is the innate immune response of living tissues to injury and damage caused by infections, physical and chemical trauma, immunological factors, and genetic derangements. Most diseases are associated with an underlying inflammatory process, with inflammation mediated through the contribution of active immune cells. Current strategies to control inflammatory pathways include pharmaceutical drugs, lifestyle, and dietary changes. However, this remains insufficient. Bioactive compounds (BCs) are nutritional constituents found in small quantities in food and plant extracts that provide numerous health benefits beyond their nutritional value. BCs are known for their antioxidant, antimicrobial, anticarcinogenic, anti-metabolic syndrome, and anti-inflammatory properties. Bioactive compounds have been shown to reduce the destructive effect of inflammation on tissues by inhibiting or modulating the effects of inflammatory mediators, offering hope for patients suffering from chronic inflammatory disorders like atherosclerosis, arthritis, inflammatory bowel diseases, and neurodegenerative diseases. The aim of the present review is to summarise the role of natural bioactive compounds in modulating inflammation and protecting human health, for their safety to preserve gut microbiota and improve their physiology and behaviour. Full article

(This article belongs to the Section Nutritional Neuroscience)

► Show Figures

Figure 1

29 pages, 5598 KB

Open AccessEditor’s ChoiceArticle

Temporal Feature Extraction and Machine Learning for Classification of Sleep Stages Using Telemetry Polysomnography

by Utkarsh Lal, Suhas Mathavu Vasanthsena and Anitha Hoblidar

Brain Sci. 2023, 13(8), 1201; https://doi.org/10.3390/brainsci13081201 - 14 Aug 2023

Cited by 19 | Viewed by 5444

Abstract

Accurate sleep stage detection is crucial for diagnosing sleep disorders and tailoring treatment plans. Polysomnography (PSG) is considered the gold standard for sleep assessment since it captures a diverse set of physiological signals. While various studies have employed complex neural networks for sleep [...] Read more.

Accurate sleep stage detection is crucial for diagnosing sleep disorders and tailoring treatment plans. Polysomnography (PSG) is considered the gold standard for sleep assessment since it captures a diverse set of physiological signals. While various studies have employed complex neural networks for sleep staging using PSG, our research emphasises the efficacy of a simpler and more efficient architecture. We aimed to integrate a diverse set of feature extraction measures with straightforward machine learning, potentially offering a more efficient avenue for sleep staging. We also aimed to conduct a comprehensive comparative analysis of feature extraction measures, including the power spectral density, Higuchi fractal dimension, singular value decomposition entropy, permutation entropy, and detrended fluctuation analysis, coupled with several machine-learning models, including XGBoost, Extra Trees, Random Forest, and LightGBM. Furthermore, data augmentation methods like the Synthetic Minority Oversampling Technique were also employed to rectify the inherent class imbalance in sleep data. The subsequent results highlighted that the XGBoost classifier, when used with a combination of all feature extraction measures as an ensemble, achieved the highest performance, with accuracies of 87%, 90%, 93%, 96%, and 97% and average F1-scores of 84.6%, 89%, 90.33%, 93.5%, and 93.5% for distinguishing between five-stage, four-stage, three-stage, and two distinct two-stage sleep configurations, respectively. This combined feature extraction technique represents a novel addition to the body of research since it achieves higher performance than many recently developed deep neural networks by utilising simpler machine-learning models. Full article

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

► Show Figures

Figure 1

40 pages, 2407 KB

Open AccessEditor’s ChoiceReview

Neurological Insights into Sleep Disorders in Parkinson’s Disease

by Subramanian Thangaleela, Bhagavathi Sundaram Sivamaruthi, Periyanaina Kesika, Subramanian Mariappan, Subramanian Rashmi, Thiwanya Choeisoongnern, Phakkharawat Sittiprapaporn and Chaiyavat Chaiyasut

Brain Sci. 2023, 13(8), 1202; https://doi.org/10.3390/brainsci13081202 - 14 Aug 2023

Cited by 32 | Viewed by 9757

Abstract

Parkinson’s disease (PD) is a common multidimensional neurological disorder characterized by motor and non-motor features and is more prevalent in the elderly. Sleep disorders and cognitive disturbances are also significant characteristics of PD. Sleep is an important physiological process for normal human cognition [...] Read more.

Parkinson’s disease (PD) is a common multidimensional neurological disorder characterized by motor and non-motor features and is more prevalent in the elderly. Sleep disorders and cognitive disturbances are also significant characteristics of PD. Sleep is an important physiological process for normal human cognition and physical functioning. Sleep deprivation negatively impacts human physical, mental, and behavioral functions. Sleep disturbances include problems falling asleep, disturbances occurring during sleep, abnormal movements during sleep, insufficient sleep, and excessive sleep. The most recognizable and known sleep disorders, such as rapid-eye-movement behavior disorder (RBD), insomnia, excessive daytime sleepiness (EDS), restless legs syndrome (RLS), sleep-related breathing disorders (SRBDs), and circadian-rhythm-related sleep–wake disorders (CRSWDs), have been associated with PD. RBD and associated emotional disorders are common non-motor symptoms of PD. In individuals, sleep disorders and cognitive impairment are important prognostic factors for predicting progressing neurodegeneration and developing dementia conditions in PD. Studies have focused on RBD and its associated neurological changes and functional deficits in PD patients. Other risks, such as cognitive decline, anxiety, and depression, are related to RBD. Sleep-disorder diagnosis is challenging, especially in identifying the essential factors that disturb the sleep–wake cycle and the co-existence of other concomitant sleep issues, motor symptoms, and breathing disorders. Focusing on sleep patterns and their disturbances, including genetic and other neurochemical changes, helps us to better understand the central causes of sleep alterations and cognitive functions in PD patients. Relations between α-synuclein aggregation in the brain and gender differences in sleep disorders have been reported. The existing correlation between sleep disorders and levels of α-synuclein in the cerebrospinal fluid indicates the risk of progression of synucleinopathies. Multidirectional approaches are required to correlate sleep disorders and neuropsychiatric symptoms and diagnose sensitive biomarkers for neurodegeneration. The evaluation of sleep pattern disturbances and cognitive impairment may aid in the development of novel and effective treatments for PD. Full article

(This article belongs to the Special Issue Sleep Disorders in Parkinson’s Disease)

► Show Figures

Graphical abstract

29 pages, 2324 KB

Open AccessEditor’s ChoiceSystematic Review

The Role of Serotonin in Fear Learning and Memory: A Systematic Review of Human Studies

by Francesco Tortora, Abed L. Hadipour, Simone Battaglia, Alessandra Falzone, Alessio Avenanti and Carmelo M. Vicario

Brain Sci. 2023, 13(8), 1197; https://doi.org/10.3390/brainsci13081197 - 12 Aug 2023

Cited by 41 | Viewed by 11772

Abstract

Fear is characterized by distinct behavioral and physiological responses that are essential for the survival of the human species. Fear conditioning (FC) serves as a valuable model for studying the acquisition, extinction, and expression of fear. The serotonin (5-hydroxytryptamine, 5-HT) system is known [...] Read more.

Fear is characterized by distinct behavioral and physiological responses that are essential for the survival of the human species. Fear conditioning (FC) serves as a valuable model for studying the acquisition, extinction, and expression of fear. The serotonin (5-hydroxytryptamine, 5-HT) system is known to play a significant role in emotional and motivational aspects of human behavior, including fear learning and expression. Accumulating evidence from both animal and human studies suggests that brain regions involved in FC, such as the amygdala, hippocampus, and prefrontal cortex, possess a high density of 5-HT receptors, implicating the crucial involvement of serotonin in aversive learning. Additionally, studies exploring serotonin gene polymorphisms have indicated their potential influence on FC. Therefore, the objective of this work was to review the existing evidence linking 5-HT with fear learning and memory in humans. Through a comprehensive screening of the PubMed and Web of Science databases, 29 relevant studies were included in the final review. These studies investigated the relationship between serotonin and fear learning using drug manipulations or by studying 5-HT-related gene polymorphisms. The results suggest that elevated levels of 5-HT enhance aversive learning, indicating that the modulation of serotonin 5-HT2A receptors regulates the expression of fear responses in humans. Understanding the role of this neurochemical messenger in associative aversive learning can provide insights into psychiatric disorders such as anxiety and post-traumatic stress disorder (PTSD), among others. Full article

(This article belongs to the Special Issue Linkage among Cognition, Emotion and Behavior)

► Show Figures

Figure 1

23 pages, 375 KB

Open AccessEditor’s ChoiceReview

Novel Compounds in the Treatment of Schizophrenia—A Selective Review

by Evangelia Maria Tsapakis, Kalliopi Diakaki, Apostolos Miliaras and Konstantinos N. Fountoulakis

Brain Sci. 2023, 13(8), 1193; https://doi.org/10.3390/brainsci13081193 - 11 Aug 2023

Cited by 22 | Viewed by 11200

Abstract

Schizophrenia is a chronic neuropsychiatric syndrome that significantly impacts daily function and quality of life. All of the available guidelines suggest a combined treatment approach with pharmacologic agents and psychological interventions. However, one in three patients is a non-responder, the effect on negative [...] Read more.

Schizophrenia is a chronic neuropsychiatric syndrome that significantly impacts daily function and quality of life. All of the available guidelines suggest a combined treatment approach with pharmacologic agents and psychological interventions. However, one in three patients is a non-responder, the effect on negative and cognitive symptoms is limited, and many drug-related adverse effects complicate clinical management. As a result, discovering novel drugs for schizophrenia presents a significant challenge for psychopharmacology. This selective review of the literature aims to outline the current knowledge on the aetiopathogenesis of schizophrenia and to present the recently approved and newly discovered pharmacological substances in treating schizophrenia. We discuss ten novel drugs, three of which have been approved by the FDA (Olanzapine/Samidorphan, Lumateperone, and Pimavanserin). The rest are under clinical trial investigation (Brilaroxazine, Xanomeline/Trospium, Emraclidine, Ulotaront, Sodium Benzoate, Luvadaxistat, and Iclepertin). However, additional basic and clinical research is required not only to improve our understanding of the neurobiology and the potential novel targets in the treatment of schizophrenia, but also to establish more effective therapeutical interventions for the syndrome, including the attenuation of negative and cognitive symptoms and avoiding dopamine blockade-related adverse effects. Full article

(This article belongs to the Special Issue New Insights in Psychiatric Disorder Psychopharmacology)

23 pages, 1247 KB

Open AccessEditor’s ChoiceReview

Visual Dysfunction in Parkinson’s Disease

by Francisco Nieto-Escamez, Esteban Obrero-Gaitán and Irene Cortés-Pérez

Brain Sci. 2023, 13(8), 1173; https://doi.org/10.3390/brainsci13081173 - 7 Aug 2023

Cited by 34 | Viewed by 6317

Abstract

Non-motor symptoms in Parkinson’s disease (PD) include ocular, visuoperceptive, and visuospatial impairments, which can occur as a result of the underlying neurodegenerative process. Ocular impairments can affect various aspects of vision and eye movement. Thus, patients can show dry eyes, blepharospasm, reduced blink [...] Read more.

Non-motor symptoms in Parkinson’s disease (PD) include ocular, visuoperceptive, and visuospatial impairments, which can occur as a result of the underlying neurodegenerative process. Ocular impairments can affect various aspects of vision and eye movement. Thus, patients can show dry eyes, blepharospasm, reduced blink rate, saccadic eye movement abnormalities, smooth pursuit deficits, and impaired voluntary and reflexive eye movements. Furthermore, visuoperceptive impairments affect the ability to perceive and recognize visual stimuli accurately, including impaired contrast sensitivity and reduced visual acuity, color discrimination, and object recognition. Visuospatial impairments are also remarkable, including difficulties perceiving and interpreting spatial relationships between objects and difficulties judging distances or navigating through the environment. Moreover, PD patients can present visuospatial attention problems, with difficulties attending to visual stimuli in a spatially organized manner. Moreover, PD patients also show perceptual disturbances affecting their ability to interpret and determine meaning from visual stimuli. And, for instance, visual hallucinations are common in PD patients. Nevertheless, the neurobiological bases of visual-related disorders in PD are complex and not fully understood. This review intends to provide a comprehensive description of visual disturbances in PD, from sensory to perceptual alterations, addressing their neuroanatomical, functional, and neurochemical correlates. Structural changes, particularly in posterior cortical regions, are described, as well as functional alterations, both in cortical and subcortical regions, which are shown in relation to specific neuropsychological results. Similarly, although the involvement of different neurotransmitter systems is controversial, data about neurochemical alterations related to visual impairments are presented, especially dopaminergic, cholinergic, and serotoninergic systems. Full article

(This article belongs to the Special Issue Non-motor Disorders in Parkinson Disease: Basic Science and Advances in Treatment)

► Show Figures

Figure 1

21 pages, 4745 KB

Open AccessEditor’s ChoiceReview

Artificial Intelligence Frameworks to Detect and Investigate the Pathophysiology of Spaceflight Associated Neuro-Ocular Syndrome (SANS)

by Joshua Ong, Ethan Waisberg, Mouayad Masalkhi, Sharif Amit Kamran, Kemper Lowry, Prithul Sarker, Nasif Zaman, Phani Paladugu, Alireza Tavakkoli and Andrew G. Lee

Brain Sci. 2023, 13(8), 1148; https://doi.org/10.3390/brainsci13081148 - 30 Jul 2023

Cited by 31 | Viewed by 7601

Abstract

Spaceflight associated neuro-ocular syndrome (SANS) is a unique phenomenon that has been observed in astronauts who have undergone long-duration spaceflight (LDSF). The syndrome is characterized by distinct imaging and clinical findings including optic disc edema, hyperopic refractive shift, posterior globe flattening, and choroidal [...] Read more.

Spaceflight associated neuro-ocular syndrome (SANS) is a unique phenomenon that has been observed in astronauts who have undergone long-duration spaceflight (LDSF). The syndrome is characterized by distinct imaging and clinical findings including optic disc edema, hyperopic refractive shift, posterior globe flattening, and choroidal folds. SANS serves a large barrier to planetary spaceflight such as a mission to Mars and has been noted by the National Aeronautics and Space Administration (NASA) as a high risk based on its likelihood to occur and its severity to human health and mission performance. While it is a large barrier to future spaceflight, the underlying etiology of SANS is not well understood. Current ophthalmic imaging onboard the International Space Station (ISS) has provided further insights into SANS. However, the spaceflight environment presents with unique challenges and limitations to further understand this microgravity-induced phenomenon. The advent of artificial intelligence (AI) has revolutionized the field of imaging in ophthalmology, particularly in detection and monitoring. In this manuscript, we describe the current hypothesized pathophysiology of SANS and the medical diagnostic limitations during spaceflight to further understand its pathogenesis. We then introduce and describe various AI frameworks that can be applied to ophthalmic imaging onboard the ISS to further understand SANS including supervised/unsupervised learning, generative adversarial networks, and transfer learning. We conclude by describing current research in this area to further understand SANS with the goal of enabling deeper insights into SANS and safer spaceflight for future missions. Full article

(This article belongs to the Special Issue Recent Advances in Neuro-Opthalmology)

► Show Figures

Figure 1

23 pages, 5544 KB

Open AccessEditor’s ChoiceArticle

Involvement of Nrf2 Activation and NF-kB Pathway Inhibition in the Antioxidant and Anti-Inflammatory Effects of Hesperetin in Activated BV-2 Microglial Cells

by Jasmine A. Evans, Patricia Mendonca and Karam F. A. Soliman

Brain Sci. 2023, 13(8), 1144; https://doi.org/10.3390/brainsci13081144 - 29 Jul 2023

Cited by 22 | Viewed by 5393

Abstract

Alzheimer’s disease is a progressive neurodegenerative disorder leading to cognitive decline and memory loss. The incidence of this disease continues to increase due to the limited number of novel therapeutics that prevent or slow down its progression. Flavonoids have been investigated for their [...] Read more.

Alzheimer’s disease is a progressive neurodegenerative disorder leading to cognitive decline and memory loss. The incidence of this disease continues to increase due to the limited number of novel therapeutics that prevent or slow down its progression. Flavonoids have been investigated for their potential effects on cellular damage triggered by excessive reactive oxygen species (ROS) and neuroinflammatory conditions. This study investigated the effect of the flavonoid hesperetin on LPS-activated murine BV-2 microglial cells. Results show that hesperetin reduced nitric oxide levels and increased catalase, glutathione, and superoxide dismutase levels, suggesting its potential to reduce neuroinflammation and oxidative stress. Moreover, RT-PCR arrays showed that hesperetin modulated multiple genes that regulate oxidative stress. Hesperetin downregulated the mRNA expression of ERCC6, NOS2, and NCF1 and upregulated HMOX1 and GCLC. RT-PCR results showed that hesperetin-induced Nrf2 mRNA and protein expression in LPS-activated BV-2 microglial cells is involved in the transcription of several antioxidant genes, suggesting that hesperetin’s antioxidant effects may be exerted via the Keap1/Nrf2 signaling pathway. Furthermore, the data demonstrated that hesperetin reduced the gene expression of PD-L1, which is upregulated as an individual ages and during chronic inflammatory processes, and inhibited the expression of genes associated with NF-kB signaling activation, which is overactivated during chronic inflammation. It was concluded from this investigation that hesperetin may have therapeutic potential to prevent or slow down the progression of neurodegenerative diseases, such as Alzheimer’s disease, by reducing chronic oxidative stress and modulating neuroinflammation. Full article

(This article belongs to the Topic Nutrition in Cancer and Neurodegenerative Diseases)

► Show Figures

Graphical abstract

13 pages, 284 KB

Open AccessEditor’s ChoiceReview

Early Brain Injury and Neuroprotective Treatment after Aneurysmal Subarachnoid Hemorrhage: A Literature Review

by Xiaopeng Li, Lang Zeng, Xuanzhen Lu, Kun Chen, Maling Yu, Baofeng Wang and Min Zhao

Brain Sci. 2023, 13(7), 1083; https://doi.org/10.3390/brainsci13071083 - 17 Jul 2023

Cited by 24 | Viewed by 3807

Abstract

Early brain injury (EBI) subsequent to subarachnoid hemorrhage (SAH) is strongly associated with delayed cerebral ischemia and poor patient prognosis. Based on investigations into the molecular mechanisms underlying EBI, neurovascular dysfunction resulting from SAH can be attributed to a range of pathological processes, [...] Read more.

Early brain injury (EBI) subsequent to subarachnoid hemorrhage (SAH) is strongly associated with delayed cerebral ischemia and poor patient prognosis. Based on investigations into the molecular mechanisms underlying EBI, neurovascular dysfunction resulting from SAH can be attributed to a range of pathological processes, such as microvascular alterations in brain tissue, ionic imbalances, blood–brain barrier disruption, immune–inflammatory responses, oxidative stress, and activation of cell death pathways. Research progress presents a variety of promising therapeutic approaches for the preservation of neurological function following SAH, including calcium channel antagonists, endothelin-1 receptor blockers, antiplatelet agents, anti-inflammatory agents, and anti-oxidative stress agents. EBI can be mitigated following SAH through neuroprotective measures. To enhance our comprehension of the relevant molecular pathways involved in brain injury, including brain ischemia–hypoxic injury, neuroimmune inflammation activation, and the activation of various cell-signaling pathways, following SAH, it is essential to investigate the evolution of these multifaceted pathophysiological processes. Facilitating neural repair following a brain injury is critical for improving patient survival rates and quality of life. Full article

(This article belongs to the Special Issue Ischemic Brain Injury: Cerebral Metabolism and Imaging)

17 pages, 957 KB

Open AccessEditor’s ChoiceReview

Rumination as a Transdiagnostic Phenomenon in the 21st Century: The Flow Model of Rumination

by Stephanie M. Y. Wong, Eric Y. H. Chen, Michelle C. Y. Lee, Y. N. Suen and Christy L. M. Hui

Brain Sci. 2023, 13(7), 1041; https://doi.org/10.3390/brainsci13071041 - 8 Jul 2023

Cited by 34 | Viewed by 9108

Abstract

Rumination and its related mental phenomena share associated impairments in cognition, such as executive functions and attentional processes across different clinical conditions (e.g., in psychotic disorders). In recent decades, however, the notion of rumination has been increasingly narrowed to the “self-focused” type in [...] Read more.

Rumination and its related mental phenomena share associated impairments in cognition, such as executive functions and attentional processes across different clinical conditions (e.g., in psychotic disorders). In recent decades, however, the notion of rumination has been increasingly narrowed to the “self-focused” type in depressive disorders. A closer review of the literature shows that rumination may be construed as a broader process characterized by repetitive thoughts about certain mental contents that interfere with one’s daily activities, not only limited to those related to “self”. A further examination of the construct of rumination beyond the narrowly focused depressive rumination would help expand intervention opportunities for mental disorders in today’s context. We first review the development of the clinical construct of rumination with regard to its historical roots and its roles in psychopathology. This builds the foundation for the introduction of the “Flow Model of Rumination (FMR)”, which conceptualizes rumination as a disruption of a smooth flow of mental contents in conscious experience that depends on the coordinated interactions between intention, memory, affect, and external events. The conceptual review concludes with a discussion of the impact of rapid technological advances (such as smartphones) on rumination. Particularly in contemporary societies today, a broader consideration of rumination not only from a cognition viewpoint, but also incorporating a human–device interaction perspective, is necessitated. The implications of the FMR in contemporary mental health practice are discussed. Full article

(This article belongs to the Special Issue Cognitive Neuroscience Approaches to the Psychopathology of Psychotic Disorders)

► Show Figures

Figure 1

13 pages, 694 KB

Open AccessEditor’s ChoiceReview

Regulatory Clearance and Approval of Therapeutic Protocols of Transcranial Magnetic Stimulation for Psychiatric Disorders

by Gonçalo Cotovio, Fabiana Ventura, Daniel Rodrigues da Silva, Patrícia Pereira and Albino J. Oliveira-Maia

Brain Sci. 2023, 13(7), 1029; https://doi.org/10.3390/brainsci13071029 - 5 Jul 2023

Cited by 35 | Viewed by 7975

Abstract

Non-invasive brain stimulation techniques (NIBS) have been widely used in both clinical and research contexts in neuropsychiatry. They are safe and well-tolerated, making NIBS an interesting option for application in different settings. Transcranial magnetic stimulation (TMS) is one of these strategies. It uses [...] Read more.

Non-invasive brain stimulation techniques (NIBS) have been widely used in both clinical and research contexts in neuropsychiatry. They are safe and well-tolerated, making NIBS an interesting option for application in different settings. Transcranial magnetic stimulation (TMS) is one of these strategies. It uses electromagnetic pulses for focal modulate ion of neuronal activity in brain cortical regions. When pulses are applied repeatedly (repetitive transcranial magnetic stimulation—rTMS), they are thought to induce long-lasting neuroplastic effects, proposed to be a therapeutic mechanism for rTMS, with efficacy and safety initially demonstrated for treatment-resistant depression (TRD). Since then, many rTMS treatment protocols emerged for other difficult to treat psychiatric conditions. Moreover, multiple clinical studies, including large multi-center trials and several meta-analyses, have confirmed its clinical efficacy in different neuropsychiatric disorders, resulting in evidence-based guidelines and recommendations. Currently, rTMS is cleared by multiple regulatory agencies for the treatment of TRD, depression with comorbid anxiety disorders, obsessive compulsive disorder, and substance use disorders, such as smoking cessation. Importantly, current research supports the potential future use of rTMS for other psychiatric syndromes, including the negative symptoms of schizophrenia and post-traumatic stress disorder. More precise knowledge of formal indications for rTMS therapeutic use in psychiatry is critical to enhance clinical decision making in this area. Full article

(This article belongs to the Special Issue Biomarkers to Guide Non-invasive Brain Stimulation in Psychiatric Disorders)

► Show Figures

Graphical abstract

8 pages, 251 KB

Open AccessEditor’s ChoiceReview

Animal Models of Ischemic Stroke with Different Forms of Middle Cerebral Artery Occlusion

by Lang Zeng, Shengqi Hu, Lingcheng Zeng, Rudong Chen, Hua Li, Jiasheng Yu and Hongkuan Yang

Brain Sci. 2023, 13(7), 1007; https://doi.org/10.3390/brainsci13071007 - 29 Jun 2023

Cited by 27 | Viewed by 8275

Abstract

Ischemic stroke is a common type of stroke that significantly affects human well-being and quality of life. In order to further characterize the pathophysiology of ischemic stroke and develop new treatment strategies, ischemic stroke models with controllable and consistent response to potential clinical [...] Read more.

Ischemic stroke is a common type of stroke that significantly affects human well-being and quality of life. In order to further characterize the pathophysiology of ischemic stroke and develop new treatment strategies, ischemic stroke models with controllable and consistent response to potential clinical treatments are urgently needed. The middle cerebral artery occlusion (MCAO) model is currently the most widely used animal model of ischemic stroke. This review discusses various methods for constructing the MCAO model and compares their advantages and disadvantages in order to provide better approaches for studying ischemic stroke. Full article

(This article belongs to the Special Issue Ischemic Brain Injury: Cerebral Metabolism and Imaging)

31 pages, 2495 KB

Open AccessEditor’s ChoiceReview

Hypothalamus and Post-Traumatic Stress Disorder: A Review

by Payman Raise-Abdullahi, Morvarid Meamar, Abbas Ali Vafaei, Maryam Alizadeh, Masoomeh Dadkhah, Sakineh Shafia, Mohadeseh Ghalandari-Shamami, Ramtin Naderian, Seyed Afshin Samaei and Ali Rashidy-Pour

Brain Sci. 2023, 13(7), 1010; https://doi.org/10.3390/brainsci13071010 - 29 Jun 2023

Cited by 51 | Viewed by 23213

Abstract

Humans have lived in a dynamic environment fraught with potential dangers for thousands of years. While fear and stress were crucial for the survival of our ancestors, today, they are mostly considered harmful factors, threatening both our physical and mental health. Trauma is [...] Read more.

Humans have lived in a dynamic environment fraught with potential dangers for thousands of years. While fear and stress were crucial for the survival of our ancestors, today, they are mostly considered harmful factors, threatening both our physical and mental health. Trauma is a highly stressful, often life-threatening event or a series of events, such as sexual assault, war, natural disasters, burns, and car accidents. Trauma can cause pathological metaplasticity, leading to long-lasting behavioral changes and impairing an individual’s ability to cope with future challenges. If an individual is vulnerable, a tremendously traumatic event may result in post-traumatic stress disorder (PTSD). The hypothalamus is critical in initiating hormonal responses to stressful stimuli via the hypothalamic–pituitary–adrenal (HPA) axis. Linked to the prefrontal cortex and limbic structures, especially the amygdala and hippocampus, the hypothalamus acts as a central hub, integrating physiological aspects of the stress response. Consequently, the hypothalamic functions have been attributed to the pathophysiology of PTSD. However, apart from the well-known role of the HPA axis, the hypothalamus may also play different roles in the development of PTSD through other pathways, including the hypothalamic–pituitary–thyroid (HPT) and hypothalamic–pituitary–gonadal (HPG) axes, as well as by secreting growth hormone, prolactin, dopamine, and oxytocin. This review aims to summarize the current evidence regarding the neuroendocrine functions of the hypothalamus, which are correlated with the development of PTSD. A better understanding of the role of the hypothalamus in PTSD could help develop better treatments for this debilitating condition. Full article

(This article belongs to the Special Issue Hypothalamic-Related Disorders)

► Show Figures

Figure 1

11 pages, 1173 KB

Open AccessEditor’s ChoiceOpinion

The Brain’s Glymphatic System: Drawing New Perspectives in Neuroscience

by Alexandru Vlad Ciurea, Aurel George Mohan, Razvan-Adrian Covache-Busuioc, Horia Petre Costin and Vicentiu Mircea Saceleanu

Brain Sci. 2023, 13(7), 1005; https://doi.org/10.3390/brainsci13071005 - 28 Jun 2023

Cited by 16 | Viewed by 7903

Abstract

This paper delves into the intricate structure and functionality of the brain’s glymphatic system, bringing forth new dimensions in its neuroscientific understanding. This paper commences by exploring the cerebrospinal fluid (CSF)—its localization, production, and pivotal role within the central nervous system, acting as [...] Read more.

This paper delves into the intricate structure and functionality of the brain’s glymphatic system, bringing forth new dimensions in its neuroscientific understanding. This paper commences by exploring the cerebrospinal fluid (CSF)—its localization, production, and pivotal role within the central nervous system, acting as a cushion and vehicle for nutrient distribution and waste elimination. We then transition into an in-depth study of the morphophysiological aspects of the glymphatic system, a recent discovery revolutionizing the perception of waste clearance from the brain, highlighting its lymphatic-like characteristics and remarkable operations. This paper subsequently emphasizes the glymphatic system’s potential implications in Alzheimer’s disease (AD), discussing the connection between inefficient glymphatic clearance and AD pathogenesis. This review also elucidates the intriguing interplay between the glymphatic system and the circadian rhythm, illustrating the optimal functioning of glymphatic clearance during sleep. Lastly, we underscore the hitherto underappreciated involvement of the glymphatic system in the tumoral microenvironment, potentially impacting tumor growth and progression. This comprehensive paper accentuates the glymphatic system’s pivotal role in multiple domains, fostering an understanding of the brain’s waste clearance mechanisms and offering avenues for further research into neuropathological conditions. Full article

(This article belongs to the Section Systems Neuroscience)

► Show Figures

Graphical abstract

17 pages, 1466 KB

Open AccessEditor’s ChoiceSystematic Review

Toxicity of Synthetic Cannabinoids in K2/Spice: A Systematic Review

by Mariana Campello de Oliveira, Mariana Capelo Vides, Dângela Layne Silva Lassi, Julio Torales, Antonio Ventriglio, Henrique Silva Bombana, Vilma Leyton, Cintia de Azevedo-Marques Périco, André Brooking Negrão, André Malbergier and João Maurício Castaldelli-Maia

Brain Sci. 2023, 13(7), 990; https://doi.org/10.3390/brainsci13070990 - 24 Jun 2023

Cited by 37 | Viewed by 18395

Abstract

(1) Background: Synthetic cannabinoids (SCs) are emerging drugs of abuse sold as ‘K2’, ‘K9’ or ‘Spice’. Evidence shows that using SCs products leads to greater health risks than cannabis. They have been associated with greater toxicity and higher addiction potential unrelated to the [...] Read more.

(1) Background: Synthetic cannabinoids (SCs) are emerging drugs of abuse sold as ‘K2’, ‘K9’ or ‘Spice’. Evidence shows that using SCs products leads to greater health risks than cannabis. They have been associated with greater toxicity and higher addiction potential unrelated to the primary psychoactive component of marijuana, Δ9-tetrahydrocannabinol (Δ9-THC). Moreover, early cases of intoxication and death related to SCs highlight the inherent danger that may accompany the use of these substances. However, there is limited knowledge of the toxicology of Spice ingredients. This systematic review intends to analyze the toxicity of SCs compounds in Spice/K2 drugs. (2) Methods: Studies analyzing synthetic cannabinoid toxicity and dependence were included in the present review. We searched the PubMed database of the US National Library of Medicine, Google Scholar, CompTox Chemicals, and Web of Science up to May 2022. (3) Results: Sixty-four articles reporting the effects of synthetic cannabinoids in humans were included in our review. Ten original papers and fifty-four case studies were also included. Fourteen studies reported death associated with synthetic cannabinoid use, with AB-CHMINACA and MDMB-CHMICA being the main reported SCs. Tachycardia and seizures were the most common toxicity symptoms. The prevalence of neuropsychiatric symptoms was higher in third-generation SCs. (4) Conclusion: SCs may exhibit higher toxicity than THC and longer-lasting effects. Their use may be harmful, especially in people with epilepsy and schizophrenia, because of the increased risk of the precipitation of psychiatric and neurologic disorders. Compared to other drugs, SCs have a higher potential to trigger a convulsive crisis, a decline in consciousness, and hemodynamic changes. Therefore, it is crucial to clarify their potential harms and increase the availability of toxicology data in both clinical and research settings. Full article

(This article belongs to the Special Issue Substance Abuse and Mental Health)

► Show Figures

Figure 1

19 pages, 2057 KB

Open AccessEditor’s ChoiceArticle

Subject-Independent EEG Emotion Recognition Based on Genetically Optimized Projection Dictionary Pair Learning

by Jipu Su, Jie Zhu, Tiecheng Song and Hongli Chang

Brain Sci. 2023, 13(7), 977; https://doi.org/10.3390/brainsci13070977 - 21 Jun 2023

Cited by 27 | Viewed by 3565

Abstract

One of the primary challenges in Electroencephalogram (EEG) emotion recognition lies in developing models that can effectively generalize to new unseen subjects, considering the significant variability in EEG signals across individuals. To address the issue of subject-specific features, a suitable approach is to [...] Read more.

One of the primary challenges in Electroencephalogram (EEG) emotion recognition lies in developing models that can effectively generalize to new unseen subjects, considering the significant variability in EEG signals across individuals. To address the issue of subject-specific features, a suitable approach is to employ projection dictionary learning, which enables the identification of emotion-relevant features across different subjects. To accomplish the objective of pattern representation and discrimination for subject-independent EEG emotion recognition, we utilized the fast and efficient projection dictionary pair learning (PDPL) technique. PDPL involves the joint use of a synthesis dictionary and an analysis dictionary to enhance the representation of features. Additionally, to optimize the parameters of PDPL, which depend on experience, we applied the genetic algorithm (GA) to obtain the optimal solution for the model. We validated the effectiveness of our algorithm using leave-one-subject-out cross validation on three EEG emotion databases: SEED, MPED, and GAMEEMO. Our approach outperformed traditional machine learning methods, achieving an average accuracy of 69.89% on the SEED database, 24.11% on the MPED database, 64.34% for the two-class GAMEEMO, and 49.01% for the four-class GAMEEMO. These results highlight the potential of subject-independent EEG emotion recognition algorithms in the development of intelligent systems capable of recognizing and responding to human emotions in real-world scenarios. Full article

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

► Show Figures

Figure 1

14 pages, 702 KB

Open AccessEditor’s ChoiceReview

Is It Time for a Paradigm Shift in the Treatment of Schizophrenia? The Use of Inflammation-Reducing and Neuroprotective Drugs—A Review

by Antonino Messina, Carmen Concerto, Alessandro Rodolico, Antonino Petralia, Filippo Caraci and Maria Salvina Signorelli

Brain Sci. 2023, 13(6), 957; https://doi.org/10.3390/brainsci13060957 - 15 Jun 2023

Cited by 29 | Viewed by 6403

Abstract

Comprehending the pathogenesis of schizophrenia represents a challenge for global mental health. To date, although it is evident that alterations in dopaminergic, serotonergic, and glutamatergic neurotransmission underlie the clinical expressiveness of the disease, neuronal disconnections represent only an epiphenomenon. In recent years, several [...] Read more.

Comprehending the pathogenesis of schizophrenia represents a challenge for global mental health. To date, although it is evident that alterations in dopaminergic, serotonergic, and glutamatergic neurotransmission underlie the clinical expressiveness of the disease, neuronal disconnections represent only an epiphenomenon. In recent years, several clinical studies have converged on the hypothesis of microglia hyperactivation and a consequent neuroinflammatory state as a pathogenic substrate of schizophrenia. Prenatal, perinatal, and postnatal factors can cause microglia to switch from M2 anti-inflammatory to M1 pro-inflammatory states. A continuous mild neuroinflammatory state progressively leads to neuronal loss, a reduction in dendritic spines, and myelin degeneration. The augmentation of drugs that reduce neuroinflammation to antipsychotics could be an effective therapeutic modality in managing schizophrenia. This review will consider studies in which drugs with anti-inflammatory and neuroprotective properties have been used in addition to antipsychotic treatment in patients with schizophrenia. Full article

(This article belongs to the Special Issue New Insights in Psychiatric Disorder Psychopharmacology)

► Show Figures

Figure 1

14 pages, 7700 KB

Open AccessEditor’s ChoiceArticle

Reduced Resting-State EEG Power Spectra and Functional Connectivity after 24 and 36 Hours of Sleep Deprivation

by Jie Lian, Lin Xu, Tao Song, Ziyi Peng, Zheyuan Zhang, Xin An, Shufang Chen, Xiao Zhong and Yongcong Shao

Brain Sci. 2023, 13(6), 949; https://doi.org/10.3390/brainsci13060949 - 14 Jun 2023

Cited by 18 | Viewed by 6203

Abstract

Total sleep deprivation (TSD) leads to cognitive decline; however, the neurophysiological mechanisms underlying resting-state electroencephalogram (EEG) changes after TSD remain unclear. In this study, 42 healthy adult participants were subjected to 36 h of sleep deprivation (36 h TSD), and resting-state EEG data [...] Read more.

Total sleep deprivation (TSD) leads to cognitive decline; however, the neurophysiological mechanisms underlying resting-state electroencephalogram (EEG) changes after TSD remain unclear. In this study, 42 healthy adult participants were subjected to 36 h of sleep deprivation (36 h TSD), and resting-state EEG data were recorded at baseline, after 24 h of sleep deprivation (24 h TSD), and after 36 h TSD. The analysis of resting-state EEG at baseline, after 24 h TSD, and after 36 h TSD using source localization analysis, power spectrum analysis, and functional connectivity analysis revealed a decrease in alpha-band power and a significant increase in delta-band power after TSD and impaired functional connectivity in the default mode network, precuneus, and inferior parietal lobule. The cortical activities of the precuneus, inferior parietal lobule, and superior parietal lobule were significantly reduced, but no difference was found between the 24 h and 36 h TSD groups. This may indicate that TSD caused some damage to the participants, but this damage temporarily slowed during the 24 h to 36 h TSD period. Full article

(This article belongs to the Section Neurotechnology and Neuroimaging)

► Show Figures

Figure 1

10 pages, 16129 KB

Open AccessEditor’s ChoiceArticle

Do Individuals with Spinal Cord Injury Benefit from Semi-Immersive Virtual Reality Cognitive Training? Preliminary Results from an Exploratory Study on an Underestimated Problem

by Maria Grazia Maggio, Mirjam Bonanno, Alfredo Manuli, Maria Pia Onesta, Rosaria De Luca, Angelo Quartarone and Rocco Salvatore Calabrò

Brain Sci. 2023, 13(6), 945; https://doi.org/10.3390/brainsci13060945 - 13 Jun 2023

Cited by 12 | Viewed by 3030

Abstract

A spinal cord injury (SCI) is damage to any part of the spinal cord, caused by traumatic or non-traumatic events. Clinically, SCI is associated with partial or complete loss of motor, sensory, and autonomic functions below the site of injury. However, cognitive alterations [...] Read more.

A spinal cord injury (SCI) is damage to any part of the spinal cord, caused by traumatic or non-traumatic events. Clinically, SCI is associated with partial or complete loss of motor, sensory, and autonomic functions below the site of injury. However, cognitive alterations in specific domains can also occur. The aim of this study was to evaluate the effects of semi-immersive virtual reality (VR) cognitive training (using the BTS Nirvana, Italy) in promoting global functional recovery in patients with SCI. Forty-two SCI patients were included in this retrospective case-control study, and the analysis was carried out using an electronic data retrieval system. The enrolled patients were divided into two groups with the same demographic and medical characteristics: the control group (CG: 21 patients) participated in traditional therapy, whereas the experimental group (EG: 21 patients) received training using semi-immersive VR. In both groups, there were patients with A- or B-grade impairments according to the American Spinal Injury Association (ASIA) scale. Both study groups underwent the same amount of cognitive training (but using a different type of training: conventional vs. innovative), consisting of three weekly sessions for eight weeks (24 sessions in total), each session lasting approximately sixty minutes, as well as the same amount of physiotherapy. The effect of the two treatments (EG/CG) was significantly different in global cognitive functioning (MOCA: p = 0.001), mood (BDI: p = 0.006), and overall quality of life (SF12 Total: p < 0.001), especially in physical perception (SF12-Physics: p = 0.004). Our results suggest that SCI patients could benefit from cognitive training using semi-immersive VR. Indeed, the integration of cognitive exercises that require movement and provide increased feedback could allow for better motor and cognitive recovery in people with SCI. Full article

(This article belongs to the Section Neurorehabilitation)

► Show Figures

Figure 1

22 pages, 787 KB

Open AccessEditor’s ChoiceReview

Distribution of Iron, Copper, Zinc and Cadmium in Glia, Their Influence on Glial Cells and Relationship with Neurodegenerative Diseases

by Aleksandra Górska, Agnieszka Markiewicz-Gospodarek, Renata Markiewicz, Zuzanna Chilimoniuk, Bartosz Borowski, Mateusz Trubalski and Katarzyna Czarnek

Brain Sci. 2023, 13(6), 911; https://doi.org/10.3390/brainsci13060911 - 5 Jun 2023

Cited by 26 | Viewed by 5264

Abstract

Recent data on the distribution and influence of copper, zinc and cadmium in glial cells are summarized. This review also examines the relationship between those metals and their role in neurodegenerative diseases like Alzheimer disease, multiple sclerosis, Parkinson disease and Amyotrophic lateral sclerosis, [...] Read more.

Recent data on the distribution and influence of copper, zinc and cadmium in glial cells are summarized. This review also examines the relationship between those metals and their role in neurodegenerative diseases like Alzheimer disease, multiple sclerosis, Parkinson disease and Amyotrophic lateral sclerosis, which have become a great challenge for today’s physicians. The studies suggest that among glial cells, iron has the highest concentration in oligodendrocytes, copper in astrocytes and zinc in the glia of hippocampus and cortex. Previous studies have shown neurotoxic effects of copper, iron and manganese, while zinc can have a bidirectional effect, i.e., neurotoxic but also neuroprotective effects depending on the dose and disease state. Recent data point to the association of metals with neurodegeneration through their role in the modulation of protein aggregation. Metals can accumulate in the brain with aging and may be associated with age-related diseases. Full article

(This article belongs to the Section Neuroglia)

► Show Figures

Figure 1

21 pages, 796 KB

Open AccessEditor’s ChoiceSystematic Review

The Role of Ketamine in the Treatment of Bipolar Depression: A Scoping Review

by Muhammad Youshay Jawad, Saleha Qasim, Menglu Ni, Ziji Guo, Joshua D. Di Vincenzo, Giacomo d’Andrea, Aniqa Tabassum, Andrea Mckenzie, Sebastian Badulescu, Iria Grande and Roger S. McIntyre

Brain Sci. 2023, 13(6), 909; https://doi.org/10.3390/brainsci13060909 - 4 Jun 2023

Cited by 19 | Viewed by 9985

Abstract

Bipolar depression remains a clinical challenge with a quarter of patients failing to respond to initial conventional treatments. Although ketamine has been extensively studied in unipolar depression, its role in bipolar disorder remains inconclusive. The aim of our scoping review was to comprehensively [...] Read more.

Bipolar depression remains a clinical challenge with a quarter of patients failing to respond to initial conventional treatments. Although ketamine has been extensively studied in unipolar depression, its role in bipolar disorder remains inconclusive. The aim of our scoping review was to comprehensively synthesize the current clinical literature around ketamine use in bipolar depression. A total of 10 clinical studies (5 randomized controlled trials and 5 open label studies) were selected. The preliminary evidence, albeit weak, suggests that ketamine is a promising treatment and calls for further interest from the research community. Overall, ketamine treatment appeared to be tolerable with minimal risk for manic/hypomanic switching and showed some effectiveness across parameters of depression and suicidality. Moreover, ketamine is a potential treatment agent in patients with treatment-resistant bipolar depression with promising data extracted from extant controlled trials and real-world effectiveness studies. Future studies are needed to identify ketamine’s role in acute and maintenance treatment phases of bipolar depression. Moreover, future researchers should study the recurrence prevention and anti-suicidal effects of ketamine in the treatment of bipolar depression. Full article

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

► Show Figures

Figure 1

11 pages, 3580 KB

Open AccessEditor’s ChoiceArticle

The Use of 3D Printed Models for Surgical Simulation of Cranioplasty in Craniosynostosis as Training and Education

by Jean Francois Uhl, Albert Sufianov, Camillo Ruiz, Yuri Iakimov, Huerta Jose Mogorron, Manuel Encarnacion Ramirez, Guillermo Prat, Barbara Lorea, Matias Baldoncini, Evgeniy Goncharov, Issael Ramirez, José Rafael Cerda Céspedes, Renat Nurmukhametov and Nicola Montemurro

Brain Sci. 2023, 13(6), 894; https://doi.org/10.3390/brainsci13060894 - 1 Jun 2023

Cited by 37 | Viewed by 2692

Abstract

Background: The advance in imaging techniques is useful for 3D models and printing leading to a real revolution in many surgical specialties, in particular, neurosurgery. Methods: We report on a clinical study on the use of 3D printed models to perform cranioplasty in [...] Read more.

Background: The advance in imaging techniques is useful for 3D models and printing leading to a real revolution in many surgical specialties, in particular, neurosurgery. Methods: We report on a clinical study on the use of 3D printed models to perform cranioplasty in patients with craniosynostosis. The participants were recruited from various medical institutions and were divided into two groups: Group A (n = 5) received traditional surgical education (including cadaveric specimens) but without using 3D printed models, while Group B (n = 5) received training using 3D printed models. Results: Group B surgeons had the opportunity to plan different techniques and to simulate the cranioplasty. Group B surgeons reported that models provided a realistic and controlled environment for practicing surgical techniques, allowed for repetitive practice, and helped in visualizing the anatomy and pathology of craniosynostosis. Conclusion: 3D printed models can provide a realistic and controlled environment for neurosurgeons to develop their surgical skills in a safe and efficient manner. The ability to practice on 3D printed models before performing the actual surgery on patients may potentially improve the surgeons’ confidence and competence in performing complex craniosynostosis surgeries. Full article

(This article belongs to the Special Issue Scientific and Clinical Advances in Neurological Surgery)

► Show Figures

Figure 1

43 pages, 1126 KB

Open AccessEditor’s ChoiceSystematic Review

by Dirk W. Eilert and Anna Buchheim

Brain Sci. 2023, 13(6), 884; https://doi.org/10.3390/brainsci13060884 - 31 May 2023

Cited by 43 | Viewed by 23061

Abstract

In recent years, there has been an increase in the prevalence of mental disorders connected with affective dysregulation and insecure attachment. Therefore, it is even more important to understand the interplay between an individual’s attachment representation and patterns of emotion regulation. To our [...] Read more.

In recent years, there has been an increase in the prevalence of mental disorders connected with affective dysregulation and insecure attachment. Therefore, it is even more important to understand the interplay between an individual’s attachment representation and patterns of emotion regulation. To our knowledge, this is the first systematic review to examine this association. PsycInfo, PsyArticles, and PubMed were searched for studies that examined attachment-related differences in emotion regulation in adults. To examine the unconscious attachment representation, only studies using the Adult Attachment Interview or the Adult Attachment Projective Picture System were included. Thirty-seven peer-reviewed studies (with a total of 2006 subjects) matched the PICO criteria. Emotion regulation was measured via four objective approaches: autonomic nervous system, brain activity, biochemistry, or nonverbal behavior. Across all measurements, results reveal a significant correlation between attachment representation and emotion regulation. Secure attachment correlates consistently with balanced emotion regulation, whereas it is impaired in insecure and dysfunctional in unresolved attachment. Specifically, unresolved individuals display counterintuitive responses and fail to use attachment as a resource. Insecure-dismissing attachment is associated with an emotionally deactivating strategy, while on a physiological, biochemical, and nonverbal level, emotional stress is still present. There is still a lack of studies examining preoccupied individuals. In addition to interpreting the results, we also discuss the risk of bias, implications for psychotherapy and coaching, and an outlook for future research. Full article

(This article belongs to the Special Issue State of the Art in Human Attachment)

► Show Figures

Graphical abstract

17 pages, 1965 KB

Open AccessEditor’s ChoiceArticle

fMRI-Based Alzheimer’s Disease Detection Using the SAS Method with Multi-Layer Perceptron Network

by Aarthi Chelladurai, Dayanand Lal Narayan, Parameshachari Bidare Divakarachari and Umasankar Loganathan

Brain Sci. 2023, 13(6), 893; https://doi.org/10.3390/brainsci13060893 - 31 May 2023

Cited by 56 | Viewed by 5201

Abstract

In the present scenario, Alzheimer’s Disease (AD) is one of the incurable neuro-degenerative disorders, which accounts for nearly 60% to 70% of dementia cases. Currently, several machine-learning approaches and neuroimaging modalities are utilized for diagnosing AD. Among the available neuroimaging modalities, functional Magnetic [...] Read more.

In the present scenario, Alzheimer’s Disease (AD) is one of the incurable neuro-degenerative disorders, which accounts for nearly 60% to 70% of dementia cases. Currently, several machine-learning approaches and neuroimaging modalities are utilized for diagnosing AD. Among the available neuroimaging modalities, functional Magnetic Resonance Imaging (fMRI) is extensively utilized for studying brain activities related to AD. However, analyzing complex brain structures in fMRI is a time-consuming and complex task; so, a novel automated model was proposed in this manuscript for early diagnosis of AD using fMRI images. Initially, the fMRI images are acquired from an online dataset: Alzheimer’s Disease Neuroimaging Initiative (ADNI). Further, the quality of the acquired fMRI images was improved by implementing a normalization technique. Then, the Segmentation by Aggregating Superpixels (SAS) method was implemented for segmenting the brain regions (AD, Normal Controls (NC), Mild Cognitive Impairment (MCI), Early Mild Cognitive Impairment (EMCI), Late Mild Cognitive Impairment (LMCI), and Significant Memory Concern (SMC)) from the denoised fMRI images. From the segmented brain regions, feature vectors were extracted by employing Gabor and Gray Level Co-Occurrence Matrix (GLCM) techniques. The obtained feature vectors were dimensionally reduced by implementing Honey Badger Optimization Algorithm (HBOA) and fed to the Multi-Layer Perceptron (MLP) model for classifying the fMRI images as AD, NC, MCI, EMCI, LMCI, and SMC. The extensive investigation indicated that the presented model attained 99.44% of classification accuracy, 88.90% of Dice Similarity Coefficient (DSC), 90.82% of Jaccard Coefficient (JC), and 88.43% of Hausdorff Distance (HD). The attained results are better compared with the conventional segmentation and classification models. Full article

► Show Figures

Figure 1

17 pages, 672 KB

Open AccessEditor’s ChoiceReview

Comorbidity and Overlaps between Autism Spectrum and Borderline Personality Disorder: State of the Art

by Liliana Dell’Osso, Ivan Mirko Cremone, Benedetta Nardi, Valeria Tognini, Lucrezia Castellani, Paola Perrone, Giulia Amatori and Barbara Carpita

Brain Sci. 2023, 13(6), 862; https://doi.org/10.3390/brainsci13060862 - 26 May 2023

Cited by 31 | Viewed by 25975

Abstract

Despite the relationship between Autism spectrum disorder (ASD) and personality disorders (PD) still being scarcely understood, recent investigations increased awareness about significant overlaps between some PD and autism spectrum conditions. In this framework, several studies suggested the presence of similarities between BPD and [...] Read more.

Despite the relationship between Autism spectrum disorder (ASD) and personality disorders (PD) still being scarcely understood, recent investigations increased awareness about significant overlaps between some PD and autism spectrum conditions. In this framework, several studies suggested the presence of similarities between BPD and ASD symptoms and traits, based on the recent literature that increasingly reported increased comorbidity rates and significant symptomatologic overlaps between the two conditions. The aim of this review is to describe the available studies about the prevalence of the association between different forms of autism spectrum (full-fledged clinical conditions as well as subthreshold autistic traits) and BPD. Despite some controversial results and lack of homogeneity in the methods used for the diagnostic assessment, the reviewed literature highlighted how subjects with BPD reported higher scores on tests evaluating the presence of AT compared to a non-clinical population and hypothesized the presence of unrecognized ASD in some BPD patients or vice versa, while also describing a shared vulnerability towards traumatic events, and a greater risk of suicidality in BPD subjects with high autistic traits. However, the specific measure and nature of this association remain to be explored in more depth. Full article

(This article belongs to the Section Neuropsychiatry)

► Show Figures

Figure 1

19 pages, 3586 KB

Open AccessEditor’s ChoiceArticle

Association of Peripheral Inflammatory Biomarkers and Growth Factors Levels with Sex, Therapy and Other Clinical Factors in Schizophrenia and Patient Stratification Based on These Data

by Evgeny A. Ermakov, Mark M. Melamud, Anastasiia S. Boiko, Daria A. Kamaeva, Svetlana A. Ivanova, Georgy A. Nevinsky and Valentina N. Buneva

Brain Sci. 2023, 13(5), 836; https://doi.org/10.3390/brainsci13050836 - 22 May 2023

Cited by 24 | Viewed by 3394

Abstract

Multiple lines of evidence are known to confirm the pro-inflammatory state of some patients with schizophrenia and the involvement of inflammatory mechanisms in the pathogenesis of psychosis. The concentration of peripheral biomarkers is associated with the severity of inflammation and can be used [...] Read more.

Multiple lines of evidence are known to confirm the pro-inflammatory state of some patients with schizophrenia and the involvement of inflammatory mechanisms in the pathogenesis of psychosis. The concentration of peripheral biomarkers is associated with the severity of inflammation and can be used for patient stratification. Here, we analyzed changes in serum concentrations of cytokines (IL-1β, IL-2, IL-4, IL-6, IL-10, IL-21, APRIL, BAFF, PBEF/Visfatin, IFN-α, and TNF-α) and growth/neurotrophic factors (GM-CSF, NRG1-β1, NGF-β, and GDNF) in patients with schizophrenia in an exacerbation phase. IL-1β, IL-2, IL-4, IL-6, BAFF, IFN-α, GM-CSF, NRG1-β1, and GDNF increased but TNF-α and NGF-β decreased in schizophrenia compared to healthy individuals. Subgroup analysis revealed the effect of sex, prevalent symptoms, and type of antipsychotic therapy on biomarker levels. Females, patients with predominantly negative symptoms, and those taking atypical antipsychotics had a more pro-inflammatory phenotype. Using cluster analysis, we classified participants into “high” and “low inflammation” subgroups. However, no differences were found in the clinical data of patients in these subgroups. Nevertheless, more patients (17% to 25.5%) than healthy donors (8.6% to 14.3%) had evidence of a pro-inflammatory condition depending on the clustering approach used. Such patients may benefit from personalized anti-inflammatory therapy. Full article

(This article belongs to the Section Neuropsychiatry)

► Show Figures

Figure 1

15 pages, 2126 KB

Open AccessEditor’s ChoiceArticle

Early Hemorrhagic Transformation after Reperfusion Therapy in Patients with Acute Ischemic Stroke: Analysis of Risk Factors and Predictors

by Aida Iancu, Florina Buleu, Dana Simona Chita, Adrian Tutelca, Raluca Tudor and Silviu Brad

Brain Sci. 2023, 13(5), 840; https://doi.org/10.3390/brainsci13050840 - 22 May 2023

Cited by 24 | Viewed by 7957

Abstract

Background: The standard reperfusion therapy for acute ischemic stroke (AIS) is considered to be thrombolysis, but its application is limited by the high risk of hemorrhagic transformation (HT). This study aimed to analyze risk factors and predictors of early HT after reperfusion [...] Read more.

Background: The standard reperfusion therapy for acute ischemic stroke (AIS) is considered to be thrombolysis, but its application is limited by the high risk of hemorrhagic transformation (HT). This study aimed to analyze risk factors and predictors of early HT after reperfusion therapy (intravenous thrombolysis or mechanical thrombectomy). Material and methods: Patients with acute ischemic stroke who developed HT in the first 24 h after receiving rtPA thrombolysis or performing mechanical thrombectomy were retrospectively reviewed. They were divided into two groups, respectively, the early-HT group and the without-early-HT group based on cranial computed tomography performed at 24 h, regardless of the type of hemorrhagic transformation. Results: A total of 211 consecutive patients were enrolled in this study. Among these patients, 20.37% (n = 43; age: median 70.00 years; 51.2% males) had early HT. Multivariate analysis of independent risk factors associated with early HT found that male gender increased the risk by 2.7-fold, the presence of baseline high blood pressure by 2.4-fold, and high glycemic values by 1.2-fold. Higher values of NIHSS at 24 h increased the risk of hemorrhagic transformation by 1.18-fold, while higher values of ASPECTS at 24 h decreased the risk of hemorrhagic transformation by 0.6-fold. Conclusions: In our study, male gender, baseline high blood pressure, and high glycemic values, along with higher values of NIHSS were associated with the increased risk of early HT. Furthermore, the identification of early-HT predictors is critical in patients with AIS for the clinical outcome after reperfusion therapy. Predictive models to be used in the future to select more careful patients with a low risk of early HT need to be developed in order to minimize the impact of HT associated with reperfusion techniques. Full article

(This article belongs to the Section Neurorehabilitation)

► Show Figures

Figure 1

36 pages, 3304 KB

Open AccessEditor’s ChoiceSystematic Review

Evidence of Chaos in Electroencephalogram Signatures of Human Performance: A Systematic Review

by Shaida Kargarnovin, Christopher Hernandez, Farzad V. Farahani and Waldemar Karwowski

Brain Sci. 2023, 13(5), 813; https://doi.org/10.3390/brainsci13050813 - 17 May 2023

Cited by 31 | Viewed by 4949

Abstract

(1) Background: Chaos, a feature of nonlinear dynamical systems, is well suited for exploring biological time series, such as heart rates, respiratory records, and particularly electroencephalograms. The primary purpose of this article is to review recent studies using chaos theory and nonlinear dynamical [...] Read more.

(1) Background: Chaos, a feature of nonlinear dynamical systems, is well suited for exploring biological time series, such as heart rates, respiratory records, and particularly electroencephalograms. The primary purpose of this article is to review recent studies using chaos theory and nonlinear dynamical methods to analyze human performance in different brain processes. (2) Methods: Several studies have examined chaos theory and related analytical tools for describing brain dynamics. The present study provides an in-depth analysis of the computational methods that have been proposed to uncover brain dynamics. (3) Results: The evidence from 55 articles suggests that cognitive function is more frequently assessed than other brain functions in studies using chaos theory. The most frequently used techniques for analyzing chaos include the correlation dimension and fractal analysis. Approximate, Kolmogorov and sample entropy account for the largest proportion of entropy algorithms in the reviewed studies. (4) Conclusions: This review provides insights into the notion of the brain as a chaotic system and the successful use of nonlinear methods in neuroscience studies. Additional studies of brain dynamics would aid in improving our understanding of human cognitive performance. Full article

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

► Show Figures

Figure 1

35 pages, 2969 KB

Open AccessEditor’s ChoiceReview

Shared Mechanisms of GABAergic and Opioidergic Transmission Regulate Corticolimbic Reward Systems and Cognitive Aspects of Motivational Behaviors

by Oveis Hosseinzadeh Sahafi, Maryam Sardari, Sakineh Alijanpour and Ameneh Rezayof

Brain Sci. 2023, 13(5), 815; https://doi.org/10.3390/brainsci13050815 - 17 May 2023

Cited by 18 | Viewed by 15603

Abstract

The functional interplay between the corticolimbic GABAergic and opioidergic systems plays a crucial role in regulating the reward system and cognitive aspects of motivational behaviors leading to the development of addictive behaviors and disorders. This review provides a summary of the shared mechanisms [...] Read more.

The functional interplay between the corticolimbic GABAergic and opioidergic systems plays a crucial role in regulating the reward system and cognitive aspects of motivational behaviors leading to the development of addictive behaviors and disorders. This review provides a summary of the shared mechanisms of GABAergic and opioidergic transmission, which modulate the activity of dopaminergic neurons located in the ventral tegmental area (VTA), the central hub of the reward mechanisms. This review comprehensively covers the neuroanatomical and neurobiological aspects of corticolimbic inhibitory neurons that express opioid receptors, which act as modulators of corticolimbic GABAergic transmission. The presence of opioid and GABA receptors on the same neurons allows for the modulation of the activity of dopaminergic neurons in the ventral tegmental area, which plays a key role in the reward mechanisms of the brain. This colocalization of receptors and their immunochemical markers can provide a comprehensive understanding for clinicians and researchers, revealing the neuronal circuits that contribute to the reward system. Moreover, this review highlights the importance of GABAergic transmission-induced neuroplasticity under the modulation of opioid receptors. It discusses their interactive role in reinforcement learning, network oscillation, aversive behaviors, and local feedback or feedforward inhibitions in reward mechanisms. Understanding the shared mechanisms of these systems may lead to the development of new therapeutic approaches for addiction, reward-related disorders, and drug-induced cognitive impairment. Full article

(This article belongs to the Special Issue Advances in the Diversity of GABAergic Neurons)

► Show Figures

Figure 1

10 pages, 793 KB

Open AccessEditor’s ChoiceArticle

Machine Learning for Early Diagnosis of ATTRv Amyloidosis in Non-Endemic Areas: A Multicenter Study from Italy

by Vincenzo Di Stefano, Francesco Prinzi, Marco Luigetti, Massimo Russo, Stefano Tozza, Paolo Alonge, Angela Romano, Maria Ausilia Sciarrone, Francesca Vitali, Anna Mazzeo, Luca Gentile, Giovanni Palumbo, Fiore Manganelli, Salvatore Vitabile and Filippo Brighina

Brain Sci. 2023, 13(5), 805; https://doi.org/10.3390/brainsci13050805 - 16 May 2023

Cited by 18 | Viewed by 4381

Abstract

Background: Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv) is an adult-onset multisystemic disease, affecting the peripheral nerves, heart, gastrointestinal tract, eyes, and kidneys. Nowadays, several treatment options are available; thus, avoiding misdiagnosis is crucial to starting therapy in early disease stages. However, clinical diagnosis [...] Read more.

Background: Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv) is an adult-onset multisystemic disease, affecting the peripheral nerves, heart, gastrointestinal tract, eyes, and kidneys. Nowadays, several treatment options are available; thus, avoiding misdiagnosis is crucial to starting therapy in early disease stages. However, clinical diagnosis may be difficult, as the disease may present with unspecific symptoms and signs. We hypothesize that the diagnostic process may benefit from the use of machine learning (ML). Methods: 397 patients referring to neuromuscular clinics in 4 centers from the south of Italy with neuropathy and at least 1 more red flag, as well as undergoing genetic testing for ATTRv, were considered. Then, only probands were considered for analysis. Hence, a cohort of 184 patients, 93 with positive and 91 (age- and sex-matched) with negative genetics, was considered for the classification task. The XGBoost (XGB) algorithm was trained to classify positive and negative TTR mutation patients. The SHAP method was used as an explainable artificial intelligence algorithm to interpret the model findings. Results: diabetes, gender, unexplained weight loss, cardiomyopathy, bilateral carpal tunnel syndrome (CTS), ocular symptoms, autonomic symptoms, ataxia, renal dysfunction, lumbar canal stenosis, and history of autoimmunity were used for the model training. The XGB model showed an accuracy of 0.707 ± 0.101, a sensitivity of 0.712 ± 0.147, a specificity of 0.704 ± 0.150, and an AUC-ROC of 0.752 ± 0.107. Using the SHAP explanation, it was confirmed that unexplained weight loss, gastrointestinal symptoms, and cardiomyopathy showed a significant association with the genetic diagnosis of ATTRv, while bilateral CTS, diabetes, autoimmunity, and ocular and renal involvement were associated with a negative genetic test. Conclusions: Our data show that ML might potentially be a useful instrument to identify patients with neuropathy that should undergo genetic testing for ATTRv. Unexplained weight loss and cardiomyopathy are relevant red flags in ATTRv in the south of Italy. Further studies are needed to confirm these findings. Full article

(This article belongs to the Special Issue Attention to Neuromuscular Diseases)

► Show Figures

Figure 1

36 pages, 1617 KB

Open AccessFeature PaperEditor’s ChoiceReview

Erectile Dysfunction: Treatments, Advances and New Therapeutic Strategies

by Antonio Argiolas, Francesco Mario Argiolas, Giacomo Argiolas and Maria Rosaria Melis

Brain Sci. 2023, 13(5), 802; https://doi.org/10.3390/brainsci13050802 - 15 May 2023

Cited by 33 | Viewed by 21250

Abstract

Erectile dysfunction (ED) is the inability to get and maintain an adequate penile erection for satisfactory sexual intercourse. Due to its negative impacts on men’s life quality and increase during aging (40% of men between 40 and 70 years), ED has always attracted [...] Read more.

Erectile dysfunction (ED) is the inability to get and maintain an adequate penile erection for satisfactory sexual intercourse. Due to its negative impacts on men’s life quality and increase during aging (40% of men between 40 and 70 years), ED has always attracted researchers of different disciplines, from urology, andrology and neuropharmacology to regenerative medicine, and vascular and prosthesis implant surgery. Locally and/or centrally acting drugs are used to treat ED, e.g., phosphodiesterase 5 inhibitors (first in the list) given orally, and phentolamine, prostaglandin E1 and papaverine injected intracavernously. Preclinical data also show that dopamine D₄ receptor agonists, oxytocin and α-MSH analogues may have a role in ED treatment. However, since pro-erectile drugs are given on demand and are not always efficacious, new strategies are being tested for long lasting cures of ED. These include regenerative therapies, e.g., stem cells, plasma-enriched platelets and extracorporeal shock wave treatments to cure damaged erectile tissues. Although fascinating, these therapies are laborious, expensive and not easily reproducible. This leaves old vacuum erection devices and penile prostheses as the only way to get an artificial erection and sexual intercourse with intractable ED, with penile prosthesis used only by accurately selected patients. Full article

(This article belongs to the Section Behavioral Neuroscience)

► Show Figures

Figure 1

14 pages, 4838 KB

Open AccessEditor’s ChoiceArticle

Trimethylamine N-Oxide Exacerbates Neuroinflammation and Motor Dysfunction in an Acute MPTP Mice Model of Parkinson’s Disease

by Wei Quan, Chen-Meng Qiao, Gu-Yu Niu, Jian Wu, Li-Ping Zhao, Chun Cui, Wei-Jiang Zhao and Yan-Qin Shen

Brain Sci. 2023, 13(5), 790; https://doi.org/10.3390/brainsci13050790 - 12 May 2023

Cited by 30 | Viewed by 4114

Abstract

Observational studies have shown abnormal changes in trimethylamine N-oxide (TMAO) levels in the peripheral circulatory system of Parkinson’s disease (PD) patients. TMAO is a gut microbiota metabolite that can cross the blood–brain barrier and is strongly related to neuroinflammation. Neuroinflammation is one of [...] Read more.

Observational studies have shown abnormal changes in trimethylamine N-oxide (TMAO) levels in the peripheral circulatory system of Parkinson’s disease (PD) patients. TMAO is a gut microbiota metabolite that can cross the blood–brain barrier and is strongly related to neuroinflammation. Neuroinflammation is one of the pathological drivers of PD. Herein, we investigated the effect of TMAO on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model mice. TMAO pretreatment was given by adding 1.5% (w/v) TMAO to the drinking water of the mice for 21 days; then, the mice were administered MPTP (20 mg/kg, i.p.) four times a day to construct an acute PD model. Their serum TMAO concentrations, motor function, dopaminergic network integrity, and neuroinflammation were then assayed. The results showed that TMAO partly aggravated the motor dysfunction of the PD mice. Although TMAO had no effect on the dopaminergic neurons, TH protein content, and striatal DA level in the PD mice, it significantly reduced the striatal 5-HT levels and aggravated the metabolism of DA and 5-HT. Meanwhile, TMAO significantly activated glial cells in the striatum and the hippocampi of the PD mice and promoted the release of inflammatory cytokines in the hippocampus. In summary, higher-circulating TMAO had adverse effects on the motor capacity, striatum neurotransmitters, and striatal and hippocampal neuroinflammation in PD mice. Full article

(This article belongs to the Section Neurodegenerative Diseases)

► Show Figures

Graphical abstract

27 pages, 1281 KB

Open AccessEditor’s ChoiceReview

Therapeutic Strategies to Ameliorate Neuronal Damage in Epilepsy by Regulating Oxidative Stress, Mitochondrial Dysfunction, and Neuroinflammation

by Sahithi Madireddy and Samskruthi Madireddy

Brain Sci. 2023, 13(5), 784; https://doi.org/10.3390/brainsci13050784 - 11 May 2023

Cited by 63 | Viewed by 10649

Abstract

Epilepsy is a central nervous system disorder involving spontaneous and recurring seizures that affects 50 million individuals globally. Because approximately one-third of patients with epilepsy do not respond to drug therapy, the development of new therapeutic strategies against epilepsy could be beneficial. Oxidative [...] Read more.

Epilepsy is a central nervous system disorder involving spontaneous and recurring seizures that affects 50 million individuals globally. Because approximately one-third of patients with epilepsy do not respond to drug therapy, the development of new therapeutic strategies against epilepsy could be beneficial. Oxidative stress and mitochondrial dysfunction are frequently observed in epilepsy. Additionally, neuroinflammation is increasingly understood to contribute to the pathogenesis of epilepsy. Mitochondrial dysfunction is also recognized for its contributions to neuronal excitability and apoptosis, which can lead to neuronal loss in epilepsy. This review focuses on the roles of oxidative damage, mitochondrial dysfunction, NAPDH oxidase, the blood–brain barrier, excitotoxicity, and neuroinflammation in the development of epilepsy. We also review the therapies used to treat epilepsy and prevent seizures, including anti-seizure medications, anti-epileptic drugs, anti-inflammatory therapies, and antioxidant therapies. In addition, we review the use of neuromodulation and surgery in the treatment of epilepsy. Finally, we present the role of dietary and nutritional strategies in the management of epilepsy, including the ketogenic diet and the intake of vitamins, polyphenols, and flavonoids. By reviewing available interventions and research on the pathophysiology of epilepsy, this review points to areas of further development for therapies that can manage epilepsy. Full article

(This article belongs to the Special Issue Recent Advances in Pathophysiology and Therapeutic Approaches in Epilepsy)

► Show Figures

Figure 1

32 pages, 992 KB

Open AccessEditor’s ChoiceSystematic Review

A Systematic Review of Structural and Functional MRI Studies Investigating Social Networking Site Use

by Michael Wadsley and Niklas Ihssen

Brain Sci. 2023, 13(5), 787; https://doi.org/10.3390/brainsci13050787 - 11 May 2023

Cited by 23 | Viewed by 11163

Abstract

An understanding of the neurocognitive profile underlying the use of social networking sites (SNSs) can help inform decisions about the classification of problematic SNS use as an addictive disorder and elucidate how/when ‘SNS addiction’ might develop. The present review aimed to synthesize structural [...] Read more.

An understanding of the neurocognitive profile underlying the use of social networking sites (SNSs) can help inform decisions about the classification of problematic SNS use as an addictive disorder and elucidate how/when ‘SNS addiction’ might develop. The present review aimed to synthesize structural and functional MRI research investigating problematic/compulsive forms of SNS use or regular (non-addicted) SNS use behaviours. We conducted a systematic search for research articles published in English using the Web of Science, PubMed, and Scopus databases up to October 2022. Studies meeting our inclusion criteria were assessed for quality and a narrative synthesis of the results was conducted. Twenty-eight relevant articles were identified comprising structural MRI (n = 9), resting-state fMRI (n = 6) and task-based fMRI studies (n = 13). Current evidence suggests that problematic SNS use might be characterised by (1) reduced volume of the ventral striatum, amygdala, subgenual anterior cingulate cortex, orbitofrontal cortex and posterior insula; (2) increased ventral striatum and precuneus activity in response to SNS cues; (3) abnormal functional connectivity involving the dorsal attention network; (4) inter-hemispheric communication deficits. Regular SNS use behaviours appear to recruit regions involved in the mentalising network, the self-referential cognition network, the salience network, the reward network and the default mode network. Such findings are at least partially consistent with observations from the substance addiction literature and provide some provisional support for the addictive potential of SNSs. Nonetheless, the present review is limited by the small number of eligible studies and large heterogeneity in the methods employed, and so our conclusions should remain tentative. Moreover, there is a lack of longitudinal evidence suggesting SNSs cause neuroadaptations and thus conclusions that problematic SNS use represents a disease process akin to substance use addictions are premature. More well-powered longitudinal research is needed to establish the neural consequences of excessive and problematic SNS use. Full article

(This article belongs to the Section Neuropsychology)

► Show Figures

Figure 1

12 pages, 1087 KB

Open AccessEditor’s ChoiceArticle

Abnormal Brain Structure Is Associated with Social and Communication Deficits in Children with Autism Spectrum Disorder: A Voxel-Based Morphometry Analysis

by Ming-Xiang Xu and Xing-Da Ju

Brain Sci. 2023, 13(5), 779; https://doi.org/10.3390/brainsci13050779 - 10 May 2023

Cited by 21 | Viewed by 7547

Abstract

Structural magnetic resonance imaging (sMRI) studies have shown abnormalities in the brain structure of ASD patients, but the relationship between structural changes and social communication problems is still unclear. This study aims to explore the structural mechanisms of clinical dysfunction in the brain [...] Read more.

Structural magnetic resonance imaging (sMRI) studies have shown abnormalities in the brain structure of ASD patients, but the relationship between structural changes and social communication problems is still unclear. This study aims to explore the structural mechanisms of clinical dysfunction in the brain of ASD children through voxel-based morphometry (VBM). After screening T1 structural images from the Autism Brain Imaging Data Exchange (ABIDE) database, 98 children aged 8–12 years old with ASD were matched with 105 children aged 8–12 years old with typical development (TD). Firstly, this study compared the differences in gray matter volume (GMV) between the two groups. Then, this study evaluated the relationship between GMV and the subtotal score of communications and social interaction on the Autism Diagnostic Observation Schedule (ADOS) in ASD children. Research has found that abnormal brain structures in ASD include the midbrain, pontine, bilateral hippocampus, left parahippocampal gyrus, left superior temporal gyrus, left temporal pole, left middle temporal gyrus and left superior occipital gyrus. In addition, in ASD children, the subtotal score of communications and social interaction on the ADOS were only significantly positively correlated with GMV in the left hippocampus, left superior temporal gyrus and left middle temporal gyrus. In summary, the gray matter structure of ASD children is abnormal, and different clinical dysfunction in ASD children is related to structural abnormalities in specific regions. Full article

(This article belongs to the Section Behavioral Neuroscience)

► Show Figures

Figure 1

10 pages, 878 KB

Open AccessFeature PaperEditor’s ChoiceReview

The Role of The Rostral Ventromedial Medulla in Stress Responses

by Marco Pagliusi, Jr. and Felipe V. Gomes

Brain Sci. 2023, 13(5), 776; https://doi.org/10.3390/brainsci13050776 - 9 May 2023

Cited by 15 | Viewed by 9606

Abstract

The rostral ventromedial medulla (RVM) is a brainstem structure critical for the descending pain modulation system involved in both pain facilitation and inhibition through its projection to the spinal cord. Since the RVM is well connected with pain- and stress-engaged brain structures, such [...] Read more.

The rostral ventromedial medulla (RVM) is a brainstem structure critical for the descending pain modulation system involved in both pain facilitation and inhibition through its projection to the spinal cord. Since the RVM is well connected with pain- and stress-engaged brain structures, such as the anterior cingulate cortex, nucleus accumbens, and amygdala, its involvement in stress responses has become a matter of great interest. While chronic stress has been proposed as a trigger of pain chronification and related psychiatric comorbidities due to maladaptive stress responses, acute stress triggers analgesia and other adaptative responses. Here we reviewed and highlighted the critical role of the RVM in stress responses, mainly in acute stress-induced analgesia (SIA) and chronic stress-induced hyperalgesia (SIH), providing insights into pain chronification processes and comorbidity between chronic pain and psychiatric disorders. Full article

(This article belongs to the Section Behavioral Neuroscience)

► Show Figures

Figure 1

16 pages, 1467 KB

Open AccessEditor’s ChoiceArticle

Somatosensory Event-Related Potential as an Electrophysiological Correlate of Endogenous Spatial Tactile Attention: Prospects for Electrotactile Brain-Computer Interface for Sensory Training

by Marija Novičić and Andrej M. Savić

Brain Sci. 2023, 13(5), 766; https://doi.org/10.3390/brainsci13050766 - 5 May 2023

Cited by 13 | Viewed by 4077

Abstract

Tactile attention tasks are used in the diagnosis and treatment of neurological and sensory processing disorders, while somatosensory event-related potentials (ERP) measured by electroencephalography (EEG) are used as neural correlates of attention processes. Brain-computer interface (BCI) technology provides an opportunity for the training [...] Read more.

Tactile attention tasks are used in the diagnosis and treatment of neurological and sensory processing disorders, while somatosensory event-related potentials (ERP) measured by electroencephalography (EEG) are used as neural correlates of attention processes. Brain-computer interface (BCI) technology provides an opportunity for the training of mental task execution via providing online feedback based on ERP measures. Our recent work introduced a novel electrotactile BCI for sensory training, based on somatosensory ERP; however, no previous studies have addressed specific somatosensory ERP morphological features as measures of sustained endogenous spatial tactile attention in the context of BCI control. Here we show the morphology of somatosensory ERP responses induced by a novel task introduced within our electrotactile BCI platform i.e., the sustained endogenous spatial electrotactile attention task. By applying pulsed electrical stimuli to the two proximal stimulation hotspots at the user’s forearm, stimulating sequentially the mixed branches of radial and median nerves with equal probability of stimuli occurrence, we successfully recorded somatosensory ERPs for both stimulation locations, in the attended and unattended conditions. Waveforms of somatosensory ERP responses for both mixed nerve branches showed similar morphology in line with previous reports on somatosensory ERP components obtained by stimulation of exclusively sensory nerves. Moreover, we found statistically significant increases in ERP amplitude on several components, at both stimulation hotspots, while sustained endogenous spatial electrotactile attention task is performed. Our results revealed the existence of general ERP windows of interest and signal features that can be used to detect sustained endogenous tactile attention and classify between spatial attention locations in 11 healthy subjects. The current results show that features of N140, P3a and P3b somatosensory ERP components are the most prominent global markers of sustained spatial electrotactile attention, over all subjects, within our novel electrotactile BCI task/paradigm, and this work proposes the features of those components as markers of sustained endogenous spatial tactile attention in online BCI control. Immediate implications of this work are the possible improvement of online BCI control within our novel electrotactile BCI system, while these finding can be used for other tactile BCI applications in the diagnosis and treatment of neurological disorders by employing mixed nerve somatosensory ERPs and sustained endogenous electrotactile attention task as control paradigms. Full article

(This article belongs to the Special Issue Emerging Topics in Brain-Computer Interface)

► Show Figures

Graphical abstract

16 pages, 701 KB

Open AccessEditor’s ChoiceReview

Motor-Related Mu/Beta Rhythm in Older Adults: A Comprehensive Review

by Takashi Inamoto, Masaya Ueda, Keita Ueno, China Shiroma, Rin Morita, Yasuo Naito and Ryouhei Ishii

Brain Sci. 2023, 13(5), 751; https://doi.org/10.3390/brainsci13050751 - 30 Apr 2023

Cited by 18 | Viewed by 5866

Abstract

Mu rhythm, also known as the mu wave, occurs on sensorimotor cortex activity at rest, and the frequency range is defined as 8–13Hz, the same frequency as the alpha band. Mu rhythm is a cortical oscillation that can be recorded from the scalp [...] Read more.

Mu rhythm, also known as the mu wave, occurs on sensorimotor cortex activity at rest, and the frequency range is defined as 8–13Hz, the same frequency as the alpha band. Mu rhythm is a cortical oscillation that can be recorded from the scalp over the primary sensorimotor cortex by electroencephalogram (EEG) and magnetoencephalography (MEG). The subjects of previous mu/beta rhythm studies ranged widely from infants to young and older adults. Furthermore, these subjects were not only healthy people but also patients with various neurological and psychiatric diseases. However, very few studies have referred to the effect of mu/beta rhythm with aging, and there was no literature review about this theme. It is important to review the details of the characteristics of mu/beta rhythm activity in older adults compared with young adults, focusing on age-related mu rhythm changes. By comprehensive review, we found that, compared with young adults, older adults showed mu/beta activity change in four characteristics during voluntary movement, increased event-related desynchronization (ERD), earlier beginning and later end, symmetric pattern of ERD and increased recruitment of cortical areas, and substantially reduced beta event-related desynchronization (ERS). It was also found that mu/beta rhythm patterns of action observation were changing with aging. Future work is needed in order to investigate not only the localization but also the network of mu/beta rhythm in older adults. Full article

(This article belongs to the Section Neurorehabilitation)

► Show Figures

Figure 1

15 pages, 337 KB

Open AccessEditor’s ChoiceReview

Mood Stabilizers of First and Second Generation

by Janusz K. Rybakowski

Brain Sci. 2023, 13(5), 741; https://doi.org/10.3390/brainsci13050741 - 29 Apr 2023

Cited by 24 | Viewed by 8899

Abstract

The topic of this narrative review is mood stabilizers. First, the author’s definition of mood-stabilizing drugs is provided. Second, mood-stabilizing drugs meeting this definition that have been employed until now are described. They can be classified into two generations based on the chronology [...] Read more.

The topic of this narrative review is mood stabilizers. First, the author’s definition of mood-stabilizing drugs is provided. Second, mood-stabilizing drugs meeting this definition that have been employed until now are described. They can be classified into two generations based on the chronology of their introduction into the psychiatric armamentarium. First-generation mood stabilizers (FGMSs), such as lithium, valproates, and carbamazepine, were introduced in the 1960s and 1970s. Second-generation mood stabilizers (SGMSs) started in 1995, with a discovery of the mood-stabilizing properties of clozapine. The SGMSs include atypical antipsychotics, such as clozapine, olanzapine, quetiapine, aripiprazole, and risperidone, as well as a new anticonvulsant drug, lamotrigine. Recently, as a candidate for SGMSs, a novel antipsychotic, lurasidone, has been suggested. Several other atypical antipsychotics, anticonvulsants, and memantine showed some usefulness in the treatment and prophylaxis of bipolar disorder; however, they do not fully meet the author’s criteria for mood stabilizers. The article presents clinical experiences with mood stabilizers of the first and second generations and with “insufficient” ones. Further, current suggestions for their use in preventing recurrences of bipolar mood disorder are provided. Full article

(This article belongs to the Special Issue Neuropsychopharmacology in Mood Disorders)

14 pages, 14680 KB

Open AccessEditor’s ChoiceReview

Agomelatine: A Potential Multitarget Compound for Neurodevelopmental Disorders

by Rosa Savino, Anna Nunzia Polito, Gabriella Marsala, Antonio Ventriglio, Melanie Di Salvatore, Maria Ida De Stefano, Anna Valenzano, Luigi Marinaccio, Antonello Bellomo, Giuseppe Cibelli, Marcellino Monda, Vincenzo Monda, Antonietta Messina, Rita Polito, Marco Carotenuto and Giovanni Messina

Brain Sci. 2023, 13(5), 734; https://doi.org/10.3390/brainsci13050734 - 27 Apr 2023

Cited by 18 | Viewed by 12268

Abstract

Agomelatine (AGM) is one of the latest atypical antidepressants, prescribed exclusively for the treatment of depression in adults. AGM belongs to the pharmaceutical class of melatonin agonist and selective serotonin antagonist (“MASS”), as it acts both as a selective agonist of melatonin receptors [...] Read more.

Agomelatine (AGM) is one of the latest atypical antidepressants, prescribed exclusively for the treatment of depression in adults. AGM belongs to the pharmaceutical class of melatonin agonist and selective serotonin antagonist (“MASS”), as it acts both as a selective agonist of melatonin receptors MT1 and MT2, and as a selective antagonist of 5-HT2C/5-HT2B receptors. AGM is involved in the resynchronization of interrupted circadian rhythms, with beneficial effects on sleep patterns, while antagonism on serotonin receptors increases the availability of norepinephrine and dopamine in the prefrontal cortex, with an antidepressant and nootropic effect. The use of AGM in the pediatric population is limited by the scarcity of data. In addition, few studies and case reports have been published on the use of AGM in patients with attention deficit and hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Considering this evidence, the purpose of this review is to report the potential role of AGM in neurological developmental disorders. AGM would increase the expression of the cytoskeleton-associated protein (ARC) in the prefrontal cortex, with optimization of learning, long-term memory consolidation, and improved survival of neurons. Another important feature of AGM is the ability to modulate glutamatergic neurotransmission in regions associated with mood and cognition. With its synergistic activity a melatoninergic agonist and an antagonist of 5-HT2C, AGM acts as an antidepressant, psychostimulant, and promoter of neuronal plasticity, regulating cognitive symptoms, resynchronizing circadian rhythms in patients with autism, ADHD, anxiety, and depression. Given its good tolerability and good compliance, it could potentially be administered to adolescents and children. Full article

(This article belongs to the Section Developmental Neuroscience)

► Show Figures

Figure 1

20 pages, 4690 KB

Open AccessEditor’s ChoiceArticle

Differentiated Neurons Are More Vulnerable to Organophosphate and Carbamate Neurotoxicity than Undifferentiated Neurons Due to the Induction of Redox Stress and Accumulate Oxidatively-Damaged Proteins

by Anusha W. Mudyanselage, Buddhika C. Wijamunige, Artur Kocon and Wayne G. Carter

Brain Sci. 2023, 13(5), 728; https://doi.org/10.3390/brainsci13050728 - 26 Apr 2023

Cited by 12 | Viewed by 2890

Abstract

Organophosphate (OP) and carbamate pesticides are toxic to pests through targeted inhibition of acetylcholinesterase (AChE). However, OPs and carbamates may be harmful to non-target species including humans and could induce developmental neurotoxicity if differentiated or differentiating neurons are particularly vulnerable to neurotoxicant exposures. [...] Read more.

Organophosphate (OP) and carbamate pesticides are toxic to pests through targeted inhibition of acetylcholinesterase (AChE). However, OPs and carbamates may be harmful to non-target species including humans and could induce developmental neurotoxicity if differentiated or differentiating neurons are particularly vulnerable to neurotoxicant exposures. Hence, this study compared the neurotoxicity of OPs, chlorpyrifos-oxon (CPO), and azamethiphos (AZO) and the carbamate pesticide, aldicarb, to undifferentiated versus differentiated SH-SY5Y neuroblastoma cells. OP and carbamate concentration-response curves for cell viability were undertaken using 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays and cellular bioenergetic capacity assessed via quantitation of cellular ATP levels. Concentration-response curves for inhibition of cellular AChE activity were also generated and the production of reactive oxygen species (ROS) was monitored using a 2′,7′-dichlorofluorescein diacetate (DCFDA) assay. The OPs and aldicarb reduced cell viability, cellular ATP levels, and neurite outgrowth in a concentration-dependent fashion, from a threshold concentration of ≥10 µM. Neurotoxic potency was in the order AZO > CPO > aldicarb for undifferentiated cells but CPO > AZO > aldicarb for differentiated cells and this toxic potency of CPO reflected its more extensive induction of reactive oxygen species (ROS) and generation of carbonylated proteins that were characterized by western blotting. Hence, the relative neurotoxicity of the OPs and aldicarb in part reflects non-cholinergic mechanisms that are likely to contribute to developmental neurotoxicity. Full article

(This article belongs to the Special Issue The Neurotoxicity of Pesticides)

► Show Figures

Figure 1

22 pages, 5499 KB

Open AccessEditor’s ChoiceReview

A Comprehensive Review of Physical Therapy Interventions for Stroke Rehabilitation: Impairment-Based Approaches and Functional Goals

by Jawaria Shahid, Ayesha Kashif and Muhammad Kashif Shahid

Brain Sci. 2023, 13(5), 717; https://doi.org/10.3390/brainsci13050717 - 25 Apr 2023

Cited by 77 | Viewed by 59140

Abstract

Stroke is the fourth leading cause of mortality and is estimated to be one of the major reasons for long-lasting disability worldwide. There are limited studies that describe the application of physical therapy interventions to prevent disabilities in stroke survivors and promote recovery [...] Read more.

Stroke is the fourth leading cause of mortality and is estimated to be one of the major reasons for long-lasting disability worldwide. There are limited studies that describe the application of physical therapy interventions to prevent disabilities in stroke survivors and promote recovery after a stroke. In this review, we have described a wide range of interventions based on impairments, activity limitations, and goals in recovery during different stages of a stroke. This article mainly focuses on stroke rehabilitation tactics, including those for sensory function impairments, motor learning programs, hemianopia and unilateral neglect, flexibility and joint integrity, strength training, hypertonicity, postural control, and gait training. We conclude that, aside from medicine, stroke rehabilitation must address specific functional limitations to allow for group activities and superior use of a hemiparetic extremity. Medical doctors are often surprised by the variety of physiotherapeutic techniques available; they are unfamiliar with the approaches of researchers such as Bobath, Coulter, and Brunnstrom, among others, as well as the scientific reasoning behind these techniques. Full article

(This article belongs to the Section Neurorehabilitation)

► Show Figures

Graphical abstract

14 pages, 652 KB

Open AccessEditor’s ChoiceReview

Study on the Mechanism for SIRT1 during the Process of Exercise Improving Depression

by Xiao Qiu, Pengcheng Lu, Xinyu Zeng, Shengjie Jin and Xianghe Chen

Brain Sci. 2023, 13(5), 719; https://doi.org/10.3390/brainsci13050719 - 25 Apr 2023

Cited by 17 | Viewed by 4781

Abstract

The mechanism behind the onset of depression has been the focus of current research in the neuroscience field. Silent information regulator 1 (SIRT1) is a key player in regulating energy metabolism, and it can regulate depression by mediating the inflammatory response (e.g., nuclear [...] Read more.

The mechanism behind the onset of depression has been the focus of current research in the neuroscience field. Silent information regulator 1 (SIRT1) is a key player in regulating energy metabolism, and it can regulate depression by mediating the inflammatory response (e.g., nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β)), gene expression in the nucleus accumben (NAc) and CA1 region of the hippocampus (e.g., nescient helix-loop-helix2 (NHLH2), monoamine oxidase (MAO-A), and 5-Hydroxyindole-3-acetic acid (5-HIAA)), and neuronal regeneration in the CA3 region of the hippocampus. Exercise is an important means to improve energy metabolism and depression, but it remains to be established how SIRT1 acts during exercise and improves depression. By induction and analysis, SIRT1 can be activated by exercise and then improve the function of the hypothalamic–pituitary–adrenal (HPA) axis by upregulating brain-derived neurotrophic factors (BDNF), inhibit the inflammatory response (suppression of the NF-κB and TNF-α/indoleamine 2,3-dioxygenase (IDO)/5-Hydroxytryptamine (5-HT) pathways), and promote neurogenesis (activation of the insulin-like growth factor1 (IGF-1) and growth-associated protein-43 (GAP-43) pathways, etc.), thereby improving depression. The present review gives a summary and an outlook based on this finding and makes an analysis, which will provide a new rationale and insight for the mechanism by which exercise improves depression. Full article

(This article belongs to the Section Neuropsychiatry)

► Show Figures

Figure 1

20 pages, 2172 KB

Open AccessEditor’s ChoiceArticle

Research and Diagnostic Algorithmic Rules (RADAR) and RADAR Plots for the First Episode of Major Depressive Disorder: Effects of Childhood and Recent Adverse Experiences on Suicidal Behaviors, Neurocognition and Phenome Features

by Michael Maes and Abbas F. Almulla

Brain Sci. 2023, 13(5), 714; https://doi.org/10.3390/brainsci13050714 - 24 Apr 2023

Cited by 16 | Viewed by 3469

Abstract

Recent studies have proposed valid precision models and valid Research and Diagnostic Algorithmic Rules (RADAR) for recurrent major depressive disorder (MDD). The aim of the current study was to construct precision models and RADAR scores in patients experiencing first-episode MDD and to examine [...] Read more.

Recent studies have proposed valid precision models and valid Research and Diagnostic Algorithmic Rules (RADAR) for recurrent major depressive disorder (MDD). The aim of the current study was to construct precision models and RADAR scores in patients experiencing first-episode MDD and to examine whether adverse childhood experiences (ACE) and negative life events (NLE) are associated with suicidal behaviors (SB), cognitive impairment, and phenome RADAR scores. This study recruited 90 patients with major depressive disorder (MDD) in an acute phase, of whom 71 showed a first-episode MDD (FEM), and 40 controls. We constructed RADAR scores for ACE; NLE encountered in the last year; SB; and severity of depression, anxiety, chronic fatigue, and physiosomatic symptoms using the Hamilton Depression and Anxiety Rating Scales and the FibroFatigue scale. The partial least squares analysis showed that in FEM, one latent vector (labeled the phenome of FEM) could be extracted from depressive, anxiety, fatigue, physiosomatic, melancholia, and insomnia symptoms, SB, and cognitive impairments. The latter were conceptualized as a latent vector extracted from the Verbal Fluency Test, the Mini-Mental State Examination, and ratings of memory and judgement, indicating a generalized cognitive decline (G-CoDe). We found that 60.8% of the variance in the FEM phenome was explained by the cumulative effects of NLE and ACE, in particular emotional neglect and, to a lesser extent, physical abuse. In conclusion, the RADAR scores and plots constructed here should be used in research and clinical settings, rather than the binary diagnosis of MDD based on the DSM-5 or ICD. Full article

(This article belongs to the Special Issue Anxious Brain: Stress Influence on the Nervous System)

► Show Figures

Figure 1

17 pages, 880 KB

Open AccessEditor’s ChoiceSystematic Review

Exploring the Social Determinants of Health and Health Disparities in Traumatic Brain Injury: A Scoping Review

by Leslie W. Johnson and Isabella Diaz

Brain Sci. 2023, 13(5), 707; https://doi.org/10.3390/brainsci13050707 - 23 Apr 2023

Cited by 61 | Viewed by 6524

Abstract

Traumatic brain injury (TBI) is a global health concern, that can leave lasting physical, cognitive, and/or behavioral changes for many who sustain this type of injury. Because of the heterogeneity of this population, development of appropriate intervention tools can be difficult. Social determinants [...] Read more.

Traumatic brain injury (TBI) is a global health concern, that can leave lasting physical, cognitive, and/or behavioral changes for many who sustain this type of injury. Because of the heterogeneity of this population, development of appropriate intervention tools can be difficult. Social determinants of health (SDoH) are factors that may impact TBI incidence, recovery, and outcome. The purpose of this study is to describe and analyze the existing literature regarding the prevailing SDoH and health disparities (HDs) associated with TBI in adults. A scoping review, guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework was used to explore three electronic databases—PubMed, Medline, and CINAHL. Searches identified peer-reviewed empirical literature addressing aspects of SDoH and HDs related to TBI. A total of 123 records were identified and reduced to 27 studies based on inclusion criteria. Results revealed race/ethnicity was the most commonly reported SDoH impacting TBI, followed by an individual’s insurance status. Health disparities were noted to occur across the continuum of TBI, including TBI risk, acute hospitalization, rehabilitation, and recovery. The most frequently reported HD was that Whites are more likely to be discharged to inpatient rehabilitation compared to racial/ethnic minorities. Health disparities associated with TBI are most commonly associated with the race/ethnicity SDoH, though insurance status and socioeconomic status commonly influence health inequities as well. The additional need for evidence related to the impact of other, lesser researched, SDoH is discussed, as well as clinical implications that can be used to target intervention for at-risk groups using an individual’s known SDoH. Full article

(This article belongs to the Section Behavioral Neuroscience)

► Show Figures

Figure 1

11 pages, 5717 KB

Open AccessEditor’s ChoiceArticle

Prolonged Intrinsic Neural Timescales Dissociate from Phase Coherence in Schizophrenia

by Stephan Lechner and Georg Northoff

Brain Sci. 2023, 13(4), 695; https://doi.org/10.3390/brainsci13040695 - 21 Apr 2023

Cited by 24 | Viewed by 2926

Abstract

Input processing in the brain is mediated by phase synchronization and intrinsic neural timescales, both of which have been implicated in schizophrenia. Their relationship remains unclear, though. Recruiting a schizophrenia EEG sample from the B-SNIP consortium dataset (n = 134, 70 schizophrenia [...] Read more.

Input processing in the brain is mediated by phase synchronization and intrinsic neural timescales, both of which have been implicated in schizophrenia. Their relationship remains unclear, though. Recruiting a schizophrenia EEG sample from the B-SNIP consortium dataset (n = 134, 70 schizophrenia patients, 64 controls), we investigate phase synchronization, as measured by intertrial phase coherence (ITPC), and intrinsic neural timescales, as measured by the autocorrelation window (ACW) during both the rest and oddball-task states. The main goal of our paper was to investigate whether reported shifts from shorter to longer timescales are related to decreased ITPC. Our findings show (i) decreases in both theta and alpha ITPC in response to both standard and deviant tones; and (iii) a negative correlation of ITPC and ACW in healthy subjects while such correlation is no longer present in SCZ participants. Together, we demonstrate evidence of abnormally long intrinsic neural timescales (ACW) in resting-state EEG of schizophrenia as well as their dissociation from phase synchronization (ITPC). Our data suggest that, during input processing, the resting state’s abnormally long intrinsic neural timescales tilt the balance of temporal segregation and integration towards the latter. That results in temporal imprecision with decreased phase synchronization in response to inputs. Our findings provide further evidence for a basic temporal disturbance in schizophrenia on the different timescales (longer ACW and shorter ITPC), which, in the future, might be able to explain common symptoms related to the temporal experience in schizophrenia, for example temporal fragmentation. Full article

(This article belongs to the Special Issue Cognitive Neuroscience Approaches to the Psychopathology of Psychotic Disorders)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Editor’s Choice Articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI