Brain Sciences

Review

22 pages, 787 KiB

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 18 | Viewed by 4186

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)

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17 pages, 672 KiB

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 21 | Viewed by 18548

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)

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35 pages, 2969 KiB

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 12 | Viewed by 10157

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)

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36 pages, 1617 KiB

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 22 | Viewed by 13018

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)

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27 pages, 1281 KiB

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 39 | Viewed by 7386

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)

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10 pages, 878 KiB

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 12 | Viewed by 6338

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)

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16 pages, 701 KiB

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 13 | Viewed by 3368

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)

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15 pages, 337 KiB

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 19 | Viewed by 6634

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 KiB

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 12 | Viewed by 7371

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)

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22 pages, 5499 KiB

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 40 | Viewed by 39933

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)

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14 pages, 652 KiB

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 13 | Viewed by 3487

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)

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20 pages, 2785 KiB

Open AccessEditor’s ChoiceReview

Systematic Review and Future Direction of Neuro-Tourism Research

by Abeer Al-Nafjan, Mashael Aldayel and Amira Kharrat

Brain Sci. 2023, 13(4), 682; https://doi.org/10.3390/brainsci13040682 - 19 Apr 2023

Cited by 16 | Viewed by 4799

Abstract

Neuro-tourism is the application of neuroscience in tourism to improve marketing methods of the tourism industry by analyzing the brain activities of tourists. Neuro-tourism provides accurate real-time data on tourists’ conscious and unconscious emotions. Neuro-tourism uses the methods of neuromarketing such as brain–computer [...] Read more.

Neuro-tourism is the application of neuroscience in tourism to improve marketing methods of the tourism industry by analyzing the brain activities of tourists. Neuro-tourism provides accurate real-time data on tourists’ conscious and unconscious emotions. Neuro-tourism uses the methods of neuromarketing such as brain–computer interface (BCI), eye-tracking, galvanic skin response, etc., to create tourism goods and services to improve tourist experience and satisfaction. Due to the novelty of neuro-tourism and the dearth of studies on this subject, this study offered a comprehensive analysis of the peer-reviewed journal publications in neuro-tourism research for the previous 12 years to detect trends in this field and provide insights for academics. We reviewed 52 articles indexed in the Web of Science (WoS) core collection database and examined them using our suggested classification schema. The results reveal a large growth in the number of published articles on neuro-tourism, demonstrating a rise in the relevance of this field. Additionally, the findings indicated a lack of integrating artificial intelligence techniques in neuro-tourism studies. We believe that the advancements in technology and research collaboration will facilitate exponential growth in this field. Full article

(This article belongs to the Special Issue Emerging Trends of Biomedical Signal Processing in Intelligent Emotion Recognition)

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30 pages, 2821 KiB

Open AccessEditor’s ChoiceReview

Analysis of IoT Security Challenges and Its Solutions Using Artificial Intelligence

by Tehseen Mazhar, Dhani Bux Talpur, Tamara Al Shloul, Yazeed Yasin Ghadi, Inayatul Haq, Inam Ullah, Khmaies Ouahada and Habib Hamam

Brain Sci. 2023, 13(4), 683; https://doi.org/10.3390/brainsci13040683 - 19 Apr 2023

Cited by 79 | Viewed by 11249

Abstract

The Internet of Things (IoT) is a well-known technology that has a significant impact on many areas, including connections, work, healthcare, and the economy. IoT has the potential to improve life in a variety of contexts, from smart cities to classrooms, by automating [...] Read more.

The Internet of Things (IoT) is a well-known technology that has a significant impact on many areas, including connections, work, healthcare, and the economy. IoT has the potential to improve life in a variety of contexts, from smart cities to classrooms, by automating tasks, increasing output, and decreasing anxiety. Cyberattacks and threats, on the other hand, have a significant impact on intelligent IoT applications. Many traditional techniques for protecting the IoT are now ineffective due to new dangers and vulnerabilities. To keep their security procedures, IoT systems of the future will need AI-efficient machine learning and deep learning. The capabilities of artificial intelligence, particularly machine and deep learning solutions, must be used if the next-generation IoT system is to have a continuously changing and up-to-date security system. IoT security intelligence is examined in this paper from every angle available. An innovative method for protecting IoT devices against a variety of cyberattacks is to use machine learning and deep learning to gain information from raw data. Finally, we discuss relevant research issues and potential next steps considering our findings. This article examines how machine learning and deep learning can be used to detect attack patterns in unstructured data and safeguard IoT devices. We discuss the challenges that researchers face, as well as potential future directions for this research area, considering these findings. Anyone with an interest in the IoT or cybersecurity can use this website’s content as a technical resource and reference. Full article

(This article belongs to the Special Issue Intelligent Neural Systems for Solving Real Problems)

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13 pages, 989 KiB

Open AccessEditor’s ChoiceReview

Microglia and Astrocytes Dysfunction and Key Neuroinflammation-Based Biomarkers in Parkinson’s Disease

by Kun Chen, Haoyang Wang, Iqra Ilyas, Arif Mahmood and Lijun Hou

Brain Sci. 2023, 13(4), 634; https://doi.org/10.3390/brainsci13040634 - 7 Apr 2023

Cited by 29 | Viewed by 6157

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disease, with symptoms such as tremor, bradykinesia with rigidity, and depression appearing in the late stage of life. The key hallmark of PD is the loss or death of dopaminergic neurons in the region [...] Read more.

Parkinson’s disease (PD) is the second most common neurodegenerative disease, with symptoms such as tremor, bradykinesia with rigidity, and depression appearing in the late stage of life. The key hallmark of PD is the loss or death of dopaminergic neurons in the region substantia nigra pars compacta. Neuroinflammation plays a key role in the etiology of PD, and the contribution of immunity-related events spurred the researchers to identify anti-inflammatory agents for the treatment of PD. Neuroinflammation-based biomarkers have been identified for diagnosing PD, and many cellular and animal models have been used to explain the underlying mechanism; however, the specific cause of neuroinflammation remains uncertain, and more research is underway. So far, microglia and astrocyte dysregulation has been reported in PD. Patients with PD develop neural toxicity, inflammation, and inclusion bodies due to activated microglia and a-synuclein–induced astrocyte conversion into A1 astrocytes. Major phenotypes of PD appear in the late stage of life, so there is a need to identify key early-stage biomarkers for proper management and diagnosis. Studies are under way to identify key neuroinflammation-based biomarkers for early detection of PD. This review uses a constructive analysis approach by studying and analyzing different research studies focused on the role of neuroinflammation in PD. The review summarizes microglia, astrocyte dysfunction, neuroinflammation, and key biomarkers in PD. An approach that incorporates multiple biomarkers could provide more reliable diagnosis of PD. Full article

(This article belongs to the Special Issue Updates in Parkinson's Disease)

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22 pages, 912 KiB

Open AccessEditor’s ChoiceReview

Sleep Deprivation and Insomnia in Adolescence: Implications for Mental Health

by Sara Uccella, Ramona Cordani, Federico Salfi, Maurizio Gorgoni, Serena Scarpelli, Angelo Gemignani, Pierre Alexis Geoffroy, Luigi De Gennaro, Laura Palagini, Michele Ferrara and Lino Nobili

Brain Sci. 2023, 13(4), 569; https://doi.org/10.3390/brainsci13040569 - 28 Mar 2023

Cited by 45 | Viewed by 29346

Abstract

Sleep changes significantly throughout the human lifespan. Physiological modifications in sleep regulation, in common with many mammals (especially in the circadian rhythms), predispose adolescents to sleep loss until early adulthood. Adolescents are one-sixth of all human beings and are at high risk for [...] Read more.

Sleep changes significantly throughout the human lifespan. Physiological modifications in sleep regulation, in common with many mammals (especially in the circadian rhythms), predispose adolescents to sleep loss until early adulthood. Adolescents are one-sixth of all human beings and are at high risk for mental diseases (particularly mood disorders) and self-injury. This has been attributed to the incredible number of changes occurring in a limited time window that encompasses rapid biological and psychosocial modifications, which predispose teens to at-risk behaviors. Adolescents’ sleep patterns have been investigated as a biunivocal cause for potential damaging conditions, in which insufficient sleep may be both a cause and a consequence of mental health problems. The recent COVID-19 pandemic in particular has made a detrimental contribution to many adolescents’ mental health and sleep quality. In this review, we aim to summarize the knowledge in the field and to explore implications for adolescents’ (and future adults’) mental and physical health, as well as to outline potential strategies of prevention. Full article

(This article belongs to the Special Issue Effects of Sleep Deprivation on Cognition, Emotion, and Behavior)

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24 pages, 2414 KiB

Open AccessEditor’s ChoiceReview

Exploring Monocytes-Macrophages in Immune Microenvironment of Glioblastoma for the Design of Novel Therapeutic Strategies

by Matías Daniel Caverzán, Lucía Beaugé, Paula Martina Oliveda, Bruno Cesca González, Eugenia Micaela Bühler and Luis Exequiel Ibarra

Brain Sci. 2023, 13(4), 542; https://doi.org/10.3390/brainsci13040542 - 24 Mar 2023

Cited by 15 | Viewed by 4650

Abstract

Gliomas are primary malignant brain tumors. These tumors seem to be more and more frequent, not only because of a true increase in their incidence, but also due to the increase in life expectancy of the general population. Among gliomas, malignant gliomas and [...] Read more.

Gliomas are primary malignant brain tumors. These tumors seem to be more and more frequent, not only because of a true increase in their incidence, but also due to the increase in life expectancy of the general population. Among gliomas, malignant gliomas and more specifically glioblastomas (GBM) are a challenge in their diagnosis and treatment. There are few effective therapies for these tumors, and patients with GBM fare poorly, even after aggressive surgery, chemotherapy, and radiation. Over the last decade, it is now appreciated that these tumors are composed of numerous distinct tumoral and non-tumoral cell populations, which could each influence the overall tumor biology and response to therapies. Monocytes have been proved to actively participate in tumor growth, giving rise to the support of tumor-associated macrophages (TAMs). In GBM, TAMs represent up to one half of the tumor mass cells, including both infiltrating macrophages and resident brain microglia. Infiltrating macrophages/monocytes constituted ~ 85% of the total TAM population, they have immune functions, and they can release a wide array of growth factors and cytokines in response to those factors produced by tumor and non-tumor cells from the tumor microenvironment (TME). A brief review of the literature shows that this cell population has been increasingly studied in GBM TME to understand its role in tumor progression and therapeutic resistance. Through the knowledge of its biology and protumoral function, the development of therapeutic strategies that employ their recruitment as well as the modulation of their immunological phenotype, and even the eradication of the cell population, can be harnessed for therapeutic benefit. This revision aims to summarize GBM TME and localization in tumor niches with special focus on TAM population, its origin and functions in tumor progression and resistance to conventional and experimental GBM treatments. Moreover, recent advances on the development of TAM cell targeting and new cellular therapeutic strategies based on monocyte/macrophages recruitment to eradicate GBM are discussed as complementary therapeutics. Full article

(This article belongs to the Special Issue Advances in the Development of New Drugs and Treatment Targets for Brain Cancers)

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12 pages, 1662 KiB

Open AccessEditor’s ChoiceReview

Outcome Comparison of Drug-Resistant Trigeminal Neuralgia Surgical Treatments—An Umbrella Review of Meta-Analyses and Systematic Reviews

by Alessandro Rapisarda, Marco Battistelli, Alessandro Izzo, Manuela D’Ercole, Quintino Giorgio D’Alessandris, Filippo Maria Polli, Samuele Santi, Renata Martinelli and Nicola Montano

Brain Sci. 2023, 13(4), 530; https://doi.org/10.3390/brainsci13040530 - 23 Mar 2023

Cited by 11 | Viewed by 3351

Abstract

Medical treatment for trigeminal neuralgia (TN) is not always a feasible option due to a lack of full response or adverse effects. Open surgery or percutaneous procedures are advocated in these cases. Several articles have compared the results among different techniques. Nevertheless, the [...] Read more.

Medical treatment for trigeminal neuralgia (TN) is not always a feasible option due to a lack of full response or adverse effects. Open surgery or percutaneous procedures are advocated in these cases. Several articles have compared the results among different techniques. Nevertheless, the findings of these studies are heterogeneous. Umbrella reviews are studies sitting at the peak of the evidence pyramid. With this umbrella review, we provided a systematic review of the outcomes of the surgical procedures used for TN treatment. Only systematic reviews and meta-analyses were included following the PRISMA guidelines. Ten articles were enrolled for qualitative and quantitative assessment. Level of evidence was quantified using a specific tool (AMSTAR-2). Results were heterogenous in terms of outcome and measurements. Microvascular decompression (MVD) appeared to be the most effective procedure both in the short-term (pain relief in 85–96.6% of cases) and long-term follow-up (pain relief in 64–79% of cases), although showed the highest rate of complications. The results of percutaneous techniques were similar but radiosurgery showed the highest variation in term of pain relief and a higher rate of delayed responses. The use of the AMSTAR-2 tool to quantify the evidence level scored three studies as critically low and seven studies as low-level, revealing a lack of good quality studies on this topic. Our umbrella review evidenced the need of well-designed comparative studies and the utilization of validated scales in order to provide more homogenous data for pooled-analyses and meta-analyses in the field of TN surgical treatment. Full article

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

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13 pages, 653 KiB

Open AccessEditor’s ChoiceReview

Preventive Strategies for Cognitive Decline and Dementia: Benefits of Aerobic Physical Activity, Especially Open-Skill Exercise

by Takao Yamasaki

Brain Sci. 2023, 13(3), 521; https://doi.org/10.3390/brainsci13030521 - 21 Mar 2023

Cited by 25 | Viewed by 10214

Abstract

As there is no curative treatment for dementia, including Alzheimer’s disease (AD), it is important to establish an optimal nonpharmaceutical preventive intervention. Physical inactivity is a representative modifiable risk factor for dementia, especially for AD in later life (>65 years). As physical activity [...] Read more.

As there is no curative treatment for dementia, including Alzheimer’s disease (AD), it is important to establish an optimal nonpharmaceutical preventive intervention. Physical inactivity is a representative modifiable risk factor for dementia, especially for AD in later life (>65 years). As physical activity and exercise are inexpensive and easy to initiate, they may represent an effective nonpharmaceutical intervention for the maintenance of cognitive function. Several studies have reported that physical activity and exercise interventions are effective in preventing cognitive decline and dementia. This review outlines the effects of physical activity and exercise-associated interventions in older adults with and without cognitive impairment and subsequently summarizes their possible mechanisms. Furthermore, this review describes the differences between two types of physical exercise—open-skill exercise (OSE) and closed-skill exercise (CSE)—in terms of their effects on cognitive function. Aerobic physical activity and exercise interventions are particularly useful in preventing cognitive decline and dementia, with OSE exerting a stronger protective effect on cognitive functions than CSE. Therefore, the need to actively promote physical activity and exercise interventions worldwide is emphasized. Full article

(This article belongs to the Special Issue Advances in Research on Brain Health and Dementia: Prevention and Early Detection of Cognitive Decline and Dementia)

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15 pages, 4004 KiB

Open AccessEditor’s ChoiceReview

Current Advances in Papillary Craniopharyngioma: State-Of-The-Art Therapies and Overview of the Literature

by Gianpaolo Jannelli, Francesco Calvanese, Luca Paun, Gerald Raverot and Emmanuel Jouanneau

Brain Sci. 2023, 13(3), 515; https://doi.org/10.3390/brainsci13030515 - 20 Mar 2023

Cited by 16 | Viewed by 2739

Abstract

Craniopharyngiomas are commonly classified as low-grade tumors, although they may harbor a malignant behavior due to their high rate of recurrence and long-term morbidity. Craniopharyngiomas are classically distinguished into two histological types (adamantinomatous and papillary), which have been recently considered by the WHO [...] Read more.

Craniopharyngiomas are commonly classified as low-grade tumors, although they may harbor a malignant behavior due to their high rate of recurrence and long-term morbidity. Craniopharyngiomas are classically distinguished into two histological types (adamantinomatous and papillary), which have been recently considered by the WHO classification of CNS tumors as two independent entities, due to different epidemiological, radiological, histopathological, and genetic patterns. With regard to papillary craniopharyngioma, a BRAF V600 mutation is detected in 95% of cases. This genetic feature is opening new frontiers in the treatment of these tumors using an adjuvant or, in selected cases, a neo-adjuvant approach. In this article, we present an overview of the more recent literature, focusing on the specificities and the role of oncological treatment in the management of papillary craniopharyngiomas. Based on our research and experience, we strongly suggest a multimodal approach combining clinical, endocrinological, radiological, histological, and oncological findings in both preoperative workup and postoperative follow up to define a roadmap integrating every aspect of this challenging condition. Full article

(This article belongs to the Special Issue Advances in Diagnosis and Treatment of Brain Tumors and Nervous System Tumors)

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26 pages, 441 KiB

Open AccessEditor’s ChoiceReview

Among Gerontogens, Heavy Metals Are a Class of Their Own: A Review of the Evidence for Cellular Senescence

by Samuel T. Vielee and John P. Wise, Jr.

Brain Sci. 2023, 13(3), 500; https://doi.org/10.3390/brainsci13030500 - 16 Mar 2023

Cited by 13 | Viewed by 3303

Abstract

Advancements in modern medicine have improved the quality of life across the globe and increased the average lifespan of our population by multiple decades. Current estimates predict by 2030, 12% of the global population will reach a geriatric age and live another 3–4 [...] Read more.

Advancements in modern medicine have improved the quality of life across the globe and increased the average lifespan of our population by multiple decades. Current estimates predict by 2030, 12% of the global population will reach a geriatric age and live another 3–4 decades. This swelling geriatric population will place critical stress on healthcare infrastructures due to accompanying increases in age-related diseases and comorbidities. While much research focused on long-lived individuals seeks to answer questions regarding how to age healthier, there is a deficit in research investigating what aspects of our lives accelerate or exacerbate aging. In particular, heavy metals are recognized as a significant threat to human health with links to a plethora of age-related diseases, and have widespread human exposures from occupational, medical, or environmental settings. We believe heavy metals ought to be classified as a class of gerontogens (i.e., chemicals that accelerate biological aging in cells and tissues). Gerontogens may be best studied through their effects on the “Hallmarks of Aging”, nine physiological hallmarks demonstrated to occur in aged cells, tissues, and bodies. Evidence suggests that cellular senescence—a permanent growth arrest in cells—is one of the most pertinent hallmarks of aging and is a useful indicator of aging in tissues. Here, we discuss the roles of heavy metals in brain aging. We briefly discuss brain aging in general, then expand upon observations for heavy metals contributing to age-related neurodegenerative disorders. We particularly emphasize the roles and observations of cellular senescence in neurodegenerative diseases. Finally, we discuss the observations for heavy metals inducing cellular senescence. The glaring lack of knowledge about gerontogens and gerontogenic mechanisms necessitates greater research in the field, especially in the context of the global aging crisis. Full article

(This article belongs to the Special Issue Advance in Study of Neurotoxic Chemicals in the Environment)

21 pages, 2801 KiB

Open AccessEditor’s ChoiceReview

Biological Factors Underpinning Suicidal Behaviour: An Update

by Maya N. Abou Chahla, Mahmoud I. Khalil, Stefano Comai, Lena Brundin, Sophie Erhardt and Gilles J. Guillemin

Brain Sci. 2023, 13(3), 505; https://doi.org/10.3390/brainsci13030505 - 16 Mar 2023

Cited by 17 | Viewed by 6037

Abstract

Suicide, a global health burden, represents the 17th leading cause of death worldwide (1.3%), but the 4th among young people aged between 15 and 29 years of age, according to World Health Organization (WHO), 2019. Suicidal behaviour is a complex, multi-factorial, polygenic and [...] Read more.

Suicide, a global health burden, represents the 17th leading cause of death worldwide (1.3%), but the 4th among young people aged between 15 and 29 years of age, according to World Health Organization (WHO), 2019. Suicidal behaviour is a complex, multi-factorial, polygenic and independent mental health problem caused by a combination of alterations and dysfunctions of several biological pathways and disruption of normal mechanisms in brain regions that remain poorly understood and need further investigation to be deciphered. Suicide complexity and unpredictability gained international interest as a field of research. Several studies have been conducted at the neuropathological, inflammatory, genetic, and molecular levels to uncover the triggers behind suicidal behaviour and develop convenient and effective therapeutic or at least preventive procedures. This review aims to summarise and focus on current knowledge of diverse biological pathways involved in the neurobiology of suicidal behaviour, and briefly highlights future potential therapeutic pathways to prevent or even treat this significant public health problem. Full article

(This article belongs to the Section Behavioral Neuroscience)

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23 pages, 1476 KiB

Open AccessEditor’s ChoiceReview

An Analysis of Deep Learning Models in SSVEP-Based BCI: A Survey

by Dongcen Xu, Fengzhen Tang, Yiping Li, Qifeng Zhang and Xisheng Feng

Brain Sci. 2023, 13(3), 483; https://doi.org/10.3390/brainsci13030483 - 13 Mar 2023

Cited by 24 | Viewed by 6401

Abstract

The brain–computer interface (BCI), which provides a new way for humans to directly communicate with robots without the involvement of the peripheral nervous system, has recently attracted much attention. Among all the BCI paradigms, BCIs based on steady-state visual evoked potentials (SSVEPs) have [...] Read more.

The brain–computer interface (BCI), which provides a new way for humans to directly communicate with robots without the involvement of the peripheral nervous system, has recently attracted much attention. Among all the BCI paradigms, BCIs based on steady-state visual evoked potentials (SSVEPs) have the highest information transfer rate (ITR) and the shortest training time. Meanwhile, deep learning has provided an effective and feasible solution for solving complex classification problems in many fields, and many researchers have started to apply deep learning to classify SSVEP signals. However, the designs of deep learning models vary drastically. There are many hyper-parameters that influence the performance of the model in an unpredictable way. This study surveyed 31 deep learning models (2011–2023) that were used to classify SSVEP signals and analyzed their design aspects including model input, model structure, performance measure, etc. Most of the studies that were surveyed in this paper were published in 2021 and 2022. This survey is an up-to-date design guide for researchers who are interested in using deep learning models to classify SSVEP signals. Full article

(This article belongs to the Special Issue Brain-Computer Interfaces and Their Applications in Rehabilitation, Robotics, and Control of Human Brain States)

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15 pages, 301 KiB

Open AccessEditor’s ChoiceReview

Measuring Social Camouflaging in Individuals with High Functioning Autism: A Literature Review

by Ivan Mirko Cremone, Barbara Carpita, Benedetta Nardi, Danila Casagrande, Rossella Stagnari, Giulia Amatori and Liliana Dell’Osso

Brain Sci. 2023, 13(3), 469; https://doi.org/10.3390/brainsci13030469 - 10 Mar 2023

Cited by 21 | Viewed by 8394

Abstract

In the recent years, growing attention has been paid to the use of camouflaging strategies by adult populations suffering from autism spectrum disorder (ASD) with milder manifestations and without intellectual impairment, which may lead to a delay in diagnosis or even a misdiagnosis. [...] Read more.

In the recent years, growing attention has been paid to the use of camouflaging strategies by adult populations suffering from autism spectrum disorder (ASD) with milder manifestations and without intellectual impairment, which may lead to a delay in diagnosis or even a misdiagnosis. In fact, high-functioning ASD individuals were reported to be more aware of their communication difficulties and were more likely make considerable efforts to adjust their behavior to conventional rules of non-autistic individuals, learning to imitate other non-ASD individuals. Moreover, females reported a higher frequency of camouflaging strategies, suggesting a role of camouflaging in the gender gap of the ASD diagnosis. Although camouflaging strategies can sometimes grant a better level of adjustment, even resulting in a hyper-adaptive behavior, they are also often correlated with negative mental health consequences due to the long-term stress associated with continuous attempts to adapt in day-to-day life. In this framework, the aim of the present work was to review the available studies that assessed the presence and correlates of camouflaging strategies in individuals with ASD. Although the literature available on the topic is still scarce, some interesting correlations between camouflaging and anxious and depressive symptoms, as well as suicidality, were highlighted. In particular, the controversial and sometime opposite thoughts and results about camouflaging may be clarified and integrated in light of a dimensional approach to psychopathology. Full article

(This article belongs to the Section Neuropsychiatry)

19 pages, 3297 KiB

Open AccessEditor’s ChoiceReview

Carotenoids: Role in Neurodegenerative Diseases Remediation

by Kumaraswamy Gandla, Ancha Kishore Babu, Aziz Unnisa, Indu Sharma, Laliteshwar Pratap Singh, Mahammad Akiful Haque, Neelam Laxman Dashputre, Shahajan Baig, Falak A. Siddiqui, Mayeen Uddin Khandaker, Abdullah Almujally, Nissren Tamam, Abdelmoneim Sulieman, Sharuk L. Khan and Talha Bin Emran

Brain Sci. 2023, 13(3), 457; https://doi.org/10.3390/brainsci13030457 - 8 Mar 2023

Cited by 17 | Viewed by 3862

Abstract

Numerous factors can contribute to the development of neurodegenerative disorders (NDs), such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and multiple sclerosis. Oxidative stress (OS), a fairly common ND symptom, can be caused by more reactive oxygen species being made. [...] Read more.

Numerous factors can contribute to the development of neurodegenerative disorders (NDs), such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and multiple sclerosis. Oxidative stress (OS), a fairly common ND symptom, can be caused by more reactive oxygen species being made. In addition, the pathological state of NDs, which includes a high number of protein aggregates, could make chronic inflammation worse by activating microglia. Carotenoids, often known as “CTs”, are pigments that exist naturally and play a vital role in the prevention of several brain illnesses. CTs are organic pigments with major significance in ND prevention. More than 600 CTs have been discovered in nature, and they may be found in a wide variety of creatures. Different forms of CTs are responsible for the red, yellow, and orange pigments seen in many animals and plants. Because of their unique structure, CTs exhibit a wide range of bioactive effects, such as anti-inflammatory and antioxidant effects. The preventive effects of CTs have led researchers to find a strong correlation between CT levels in the body and the avoidance and treatment of several ailments, including NDs. To further understand the connection between OS, neuroinflammation, and NDs, a literature review has been compiled. In addition, we have focused on the anti-inflammatory and antioxidant properties of CTs for the treatment and management of NDs. Full article

(This article belongs to the Topic Translational Advances in Neurodegenerative Dementias)

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20 pages, 362 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Attachment, Mentalizing and Trauma: Then (1992) and Now (2022)

by Peter Fonagy, Chloe Campbell and Patrick Luyten

Brain Sci. 2023, 13(3), 459; https://doi.org/10.3390/brainsci13030459 - 8 Mar 2023

Cited by 33 | Viewed by 14935

Abstract

This article reviews the current status of research on the relationship between attachment and trauma in developmental psychopathology. Beginning with a review of the major issues and the state-of-the-art in relation to current thinking in the field of attachment about the impact of [...] Read more.

This article reviews the current status of research on the relationship between attachment and trauma in developmental psychopathology. Beginning with a review of the major issues and the state-of-the-art in relation to current thinking in the field of attachment about the impact of trauma and the inter-generational transmission of trauma, the review then considers recent neurobiological work on mentalizing and trauma and suggests areas of new development and implications for clinical practice. Full article

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

22 pages, 448 KiB

Open AccessEditor’s ChoiceReview

Noninvasive Brain Stimulation for Neurorehabilitation in Post-Stroke Patients

by Kun-Peng Li, Jia-Jia Wu, Zong-Lei Zhou, Dong-Sheng Xu, Mou-Xiong Zheng, Xu-Yun Hua and Jian-Guang Xu

Brain Sci. 2023, 13(3), 451; https://doi.org/10.3390/brainsci13030451 - 6 Mar 2023

Cited by 22 | Viewed by 9059

Abstract

Characterized by high morbidity, mortality, and disability, stroke usually causes symptoms of cerebral hypoxia due to a sudden blockage or rupture of brain vessels, and it seriously threatens human life and health. Rehabilitation is the essential treatment for post-stroke patients suffering from functional [...] Read more.

Characterized by high morbidity, mortality, and disability, stroke usually causes symptoms of cerebral hypoxia due to a sudden blockage or rupture of brain vessels, and it seriously threatens human life and health. Rehabilitation is the essential treatment for post-stroke patients suffering from functional impairments, through which hemiparesis, aphasia, dysphagia, unilateral neglect, depression, and cognitive dysfunction can be restored to various degrees. Noninvasive brain stimulation (NIBS) is a popular neuromodulatory technology of rehabilitation focusing on the local cerebral cortex, which can improve clinical functions by regulating the excitability of corresponding neurons. Increasing evidence has been obtained from the clinical application of NIBS, especially repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). However, without a standardized protocol, existing studies on NIBS show a wide variation in terms of stimulation site, frequency, intensity, dosage, and other parameters. Its application for neurorehabilitation in post-stroke patients is still limited. With advances in neuronavigation technologies, functional near-infrared spectroscopy, and functional MRI, specific brain regions can be precisely located for stimulation. On the basis of our further understanding on neural circuits, neuromodulation in post-stroke rehabilitation has also evolved from single-target stimulation to co-stimulation of two or more targets, even circuits and the network. The present study aims to review the findings of current research, discuss future directions of NIBS application, and finally promote the use of NIBS in post-stroke rehabilitation. Full article

(This article belongs to the Section Neurorehabilitation)

11 pages, 552 KiB

Open AccessEditor’s ChoiceReview

The Impact of Motor-Cognitive Dual-Task Training on Physical and Cognitive Functions in Parkinson’s Disease

by Yi Xiao, Tianmi Yang and Huifang Shang

Brain Sci. 2023, 13(3), 437; https://doi.org/10.3390/brainsci13030437 - 3 Mar 2023

Cited by 25 | Viewed by 7237

Abstract

Rehabilitation is a high-potential approach to improving physical and cognitive functions in Parkinson’s disease (PD). Dual-task training innovatively combines motor and cognitive rehabilitation in a comprehensive module. Patients perform motor and cognitive tasks at the same time in dual-task training. The previous studies [...] Read more.

Rehabilitation is a high-potential approach to improving physical and cognitive functions in Parkinson’s disease (PD). Dual-task training innovatively combines motor and cognitive rehabilitation in a comprehensive module. Patients perform motor and cognitive tasks at the same time in dual-task training. The previous studies of dual-task training in PD had high heterogeneity and achieved controversial results. In the current review, we aim to summarize the current evidence of the effect of dual-task training on motor and cognitive functions in PD patients to support the clinical practice of dual-task training. In addition, we also discuss the current opinions regarding the mechanism underlying the interaction between motor and cognitive training. In conclusion, dual-task training is suitable for PD patients with varied disease duration to improve their motor function. Dual-task training can improve motor symptoms, single-task gait speed, single-task steep length, balance, and objective experience of freezing of gait in PD. The improvement in cognitive function after dual-task training is mild. Full article

(This article belongs to the Special Issue From Bench to Bedside: Motor-Cognitive Interactions)

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21 pages, 383 KiB

Open AccessEditor’s ChoiceReview

Epigenetic Targets in Schizophrenia Development and Therapy

by Agnieszka Wawrzczak-Bargieła, Wiktor Bilecki and Marzena Maćkowiak

Brain Sci. 2023, 13(3), 426; https://doi.org/10.3390/brainsci13030426 - 1 Mar 2023

Cited by 17 | Viewed by 6257

Abstract

Schizophrenia is regarded as a neurodevelopmental disorder with its course progressing throughout life. However, the aetiology and development of schizophrenia are still under investigation. Several data suggest that the dysfunction of epigenetic mechanisms is known to be involved in the pathomechanism of this [...] Read more.

Schizophrenia is regarded as a neurodevelopmental disorder with its course progressing throughout life. However, the aetiology and development of schizophrenia are still under investigation. Several data suggest that the dysfunction of epigenetic mechanisms is known to be involved in the pathomechanism of this mental disorder. The present article revised the epigenetic background of schizophrenia based on the data available in online databases (PubMed, Scopus). This paper focused on the role of epigenetic regulation, such as DNA methylation, histone modifications, and interference of non-coding RNAs, in schizophrenia development. The article also reviewed the available data related to epigenetic regulation that may modify the severity of the disease as a possible target for schizophrenia pharmacotherapy. Moreover, the effects of antipsychotics on epigenetic malfunction in schizophrenia are discussed based on preclinical and clinical results. The obtainable data suggest alterations of epigenetic regulation in schizophrenia. Moreover, they also showed the important role of epigenetic modifications in antipsychotic action. There is a need for more data to establish the role of epigenetic mechanisms in schizophrenia therapy. It would be of special interest to find and develop new targets for schizophrenia therapy because patients with schizophrenia could show little or no response to current pharmacotherapy and have treatment-resistant schizophrenia. Full article

(This article belongs to the Special Issue Psychopharmacology and Biological Studies of Psychosis)

14 pages, 312 KiB

Open AccessEditor’s ChoiceReview

Application of Antipsychotic Drugs in Mood Disorders

by Janusz K. Rybakowski

Brain Sci. 2023, 13(3), 414; https://doi.org/10.3390/brainsci13030414 - 27 Feb 2023

Cited by 23 | Viewed by 7234

Abstract

Since their first application in psychiatry seventy years ago, antipsychotic drugs, besides schizophrenia, have been widely used in the treatment of mood disorders. Such an application of antipsychotics is the subject of this narrative review. Antipsychotic drugs can be arbitrarily classified into three [...] Read more.

Since their first application in psychiatry seventy years ago, antipsychotic drugs, besides schizophrenia, have been widely used in the treatment of mood disorders. Such an application of antipsychotics is the subject of this narrative review. Antipsychotic drugs can be arbitrarily classified into three generations. First-generation antipsychotics (FGAs), such as phenothiazines and haloperidol, were mainly applied for the treatment of acute mania, as well as psychotic depression when combined with antidepressants. The second-generation, so-called atypical antipsychotics (SGAs), such as clozapine, risperidone, olanzapine, and quetiapine, have antimanic activity and are also effective for the maintenance treatment of bipolar disorder. Additionally, quetiapine exerts therapeutic action in bipolar depression. Third-generation antipsychotics (TGAs) started with aripiprazole, a partial dopamine D2 receptor agonist, followed by brexpiprazole, lurasidone, cariprazine, and lumateperone. Out of these drugs, aripiprazole and cariprazine have antimanic activity, lurasidone, cariprazine, and lumateperone exert a significant antidepressant effect on bipolar depression, while there is evidence for the efficacy of aripiprazole and lurasidone in the prevention of recurrence in bipolar disorder. Therefore, successive generations of antipsychotic drugs present a diverse spectrum for application in mood disorders. Such a pharmacological overlap in the treatment of schizophrenia and bipolar illness stands in contrast to the dichotomous Kraepelinian division of schizophrenia and mood disorders. Full article

(This article belongs to the Special Issue Psychopharmacology and Biological Studies of Psychosis)

13 pages, 969 KiB

Open AccessEditor’s ChoiceReview

Neural Correlates of Delay Discounting in the Light of Brain Imaging and Non-Invasive Brain Stimulation: What We Know and What Is Missed

by Andrea Stefano Moro, Daniele Saccenti, Mattia Ferro, Simona Scaini, Antonio Malgaroli and Jacopo Lamanna

Brain Sci. 2023, 13(3), 403; https://doi.org/10.3390/brainsci13030403 - 26 Feb 2023

Cited by 13 | Viewed by 3305

Abstract

In decision making, the subjective value of a reward declines with the delay to its receipt, describing a hyperbolic function. Although this phenomenon, referred to as delay discounting (DD), has been extensively characterized and reported in many animal species, still, little is known [...] Read more.

In decision making, the subjective value of a reward declines with the delay to its receipt, describing a hyperbolic function. Although this phenomenon, referred to as delay discounting (DD), has been extensively characterized and reported in many animal species, still, little is known about the neuronal processes that support it. Here, after drawing a comprehensive portrait, we consider the latest neuroimaging and lesion studies, the outcomes of which often appear contradictory among comparable experimental settings. In the second part of the manuscript, we focus on a more recent and effective route of investigation: non-invasive brain stimulation (NIBS). We provide a comprehensive review of the available studies that applied transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) to affect subjects’ performance in DD tasks. The aim of our survey is not only to highlight the superiority of NIBS in investigating DD, but also to suggest targets for future experimental studies, since the regions considered in these studies represent only a fraction of the possible ones. In particular, we argue that, based on the available neurophysiological evidence from lesion and brain imaging studies, a very promising and underrepresented region for future neuromodulation studies investigating DD is the orbitofrontal cortex. Full article

(This article belongs to the Special Issue Neural Basis of Executive Control)

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14 pages, 584 KiB

Open AccessEditor’s ChoiceReview

Brexpiprazole—Pharmacologic Properties and Use in Schizophrenia and Mood Disorders

by Marcin Siwek, Krzysztof Wojtasik-Bakalarz, Anna Julia Krupa and Adrian Andrzej Chrobak

Brain Sci. 2023, 13(3), 397; https://doi.org/10.3390/brainsci13030397 - 25 Feb 2023

Cited by 20 | Viewed by 7482

Abstract

In 2002, the first III generation antipsychotic drug was registered—aripiprazole. Its partial dopaminergic agonism underlies its unique mechanism of action and the potentially beneficial influence on the positive, negative, or cognitive symptoms. Due to its relatively high intrinsic activity, the drug could often [...] Read more.

In 2002, the first III generation antipsychotic drug was registered—aripiprazole. Its partial dopaminergic agonism underlies its unique mechanism of action and the potentially beneficial influence on the positive, negative, or cognitive symptoms. Due to its relatively high intrinsic activity, the drug could often cause agitation, anxiety, or akathisia. For this reason, efforts were made to develop a drug which would retain the positive favorable actions of aripiprazole but present a more advantageous clinical profile. This turned out to be brexpiprazole, which was registered in 2015. Its pharmacodynamic and pharmacokinetic profile (similarly to the other most recent antipsychotics, i.e., lurasidone or cariprazine) shows promise of increasing the effectiveness of schizophrenia treatment in the dimensions in which the previous antipsychotics were not sufficiently effective, including negative, depressive, or cognitive symptoms. Like other new antipsychotics, it can also be useful in the treatment of mood disorders, for instance drug-resistant depression. Previous reviews focused on the use of brexpiprazole in specific diagnostic groups. The aim of this article is to provide the readers with an overview of data on the mechanism of action, clinical effectiveness in all studied diagnostic groups, as well as potential drug–food interactions, and the safety of brexpiprazole. Full article

(This article belongs to the Special Issue Psychopharmacology and Biological Studies of Psychosis)

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12 pages, 279 KiB

Open AccessEditor’s ChoiceReview

Impact of Physical Exercise Alone or in Combination with Cognitive Remediation on Cognitive Functions in People with Schizophrenia: A Qualitative Critical Review

by Giacomo Deste, Daniele Corbo, Gabriele Nibbio, Mauro Italia, Dario Dell'Ovo, Irene Calzavara-Pinton, Jacopo Lisoni, Stefano Barlati, Roberto Gasparotti and Antonio Vita

Brain Sci. 2023, 13(2), 320; https://doi.org/10.3390/brainsci13020320 - 14 Feb 2023

Cited by 26 | Viewed by 4351

Abstract

Physical exercise and cognitive remediation represent the psychosocial interventions with the largest basis of evidence attesting their effectiveness in improving cognitive performance in people living with schizophrenia according to recent international guidance. The aims of this review are to provide an overview of [...] Read more.

Physical exercise and cognitive remediation represent the psychosocial interventions with the largest basis of evidence attesting their effectiveness in improving cognitive performance in people living with schizophrenia according to recent international guidance. The aims of this review are to provide an overview of the literature on physical exercise as a treatment for cognitive impairment in schizophrenia and of the studies that have combined physical exercise and cognitive remediation as an integrated rehabilitation intervention. Nine meta-analyses and systematic reviews on physical exercise alone and seven studies on interventions combining physical exercise and cognitive remediation are discussed. The efficacy of physical exercise in improving cognitive performance in people living with schizophrenia is well documented, but more research focused on identifying moderators of participants response and optimal modalities of delivery is required. Studies investigating the effectiveness of integrated interventions report that combining physical exercise and cognitive remediation provides superior benefits and quicker improvements compared to cognitive remediation alone, but most studies included small samples and did not explore long-term effects. While physical exercise and its combination with cognitive remediation appear to represent effective treatments for cognitive impairment in people living with schizophrenia, more evidence is currently needed to better understand how to implement these treatments in psychiatric rehabilitation practice. Full article

(This article belongs to the Special Issue From Bench to Bedside: Motor-Cognitive Interactions)

24 pages, 1282 KiB

Open AccessEditor’s ChoiceReview

Endocannabinoid System and Exogenous Cannabinoids in Depression and Anxiety: A Review

by Ahmed Hasbi, Bertha K. Madras and Susan R. George

Brain Sci. 2023, 13(2), 325; https://doi.org/10.3390/brainsci13020325 - 14 Feb 2023

Cited by 33 | Viewed by 10267

Abstract

Background: There is a growing liberalization of cannabis-based preparations for medical and recreational use. In multiple instances, anxiety and depression are cited as either a primary or a secondary reason for the use of cannabinoids. Aim: The purpose of this review is to [...] Read more.

Background: There is a growing liberalization of cannabis-based preparations for medical and recreational use. In multiple instances, anxiety and depression are cited as either a primary or a secondary reason for the use of cannabinoids. Aim: The purpose of this review is to explore the association between depression or anxiety and the dysregulation of the endogenous endocannabinoid system (ECS), as well as the use of phytocannabinoids and synthetic cannabinoids in the remediation of depression/anxiety symptoms. After a brief description of the constituents of cannabis, cannabinoid receptors and the endocannabinoid system, the most important evidence is presented for the involvement of cannabinoids in depression and anxiety both in human and from animal models of depression and anxiety. Finally, evidence is presented for the clinical use of cannabinoids to treat depression and anxiety. Conclusions: Although the common belief that cannabinoids, including cannabis, its main studied components—tetrahydrocannabinol (THC) and cannabidiol (CBD)—or other synthetic derivatives have been suggested to have a therapeutic role for certain mental health conditions, all recent systematic reviews that we report have concluded that the evidence that cannabinoids improve depressive and anxiety disorders is weak, of very-low-quality, and offers no guidance on the use of cannabinoids for mental health conditions within a regulatory framework. There is an urgent need for high-quality studies examining the effects of cannabinoids on mental disorders in general and depression/anxiety in particular, as well as the consequences of long-term use of these preparations due to possible risks such as addiction and even reversal of improvement. Full article

(This article belongs to the Special Issue Cannabis and the Brain: Novel Perspectives and Understandings)

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13 pages, 951 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Perampanel in Brain Tumor-Related Epilepsy: A Systematic Review

by Payam Tabaee Damavandi, Francesco Pasini, Gaia Fanella, Giulia Sofia Cereda, Gabriele Mainini, Jacopo C. DiFrancesco, Eugen Trinka and Simona Lattanzi

Brain Sci. 2023, 13(2), 326; https://doi.org/10.3390/brainsci13020326 - 14 Feb 2023

Cited by 15 | Viewed by 4576

Abstract

Brain tumor-related epilepsy (BTRE) is a common comorbidity in patients with brain neoplasms and it may be either the first symptom or develop after the tumor diagnosis. Increasing evidence suggests that brain tumors and BTRE share common pathophysiological mechanisms. Glutamatergic mechanisms can play [...] Read more.

Brain tumor-related epilepsy (BTRE) is a common comorbidity in patients with brain neoplasms and it may be either the first symptom or develop after the tumor diagnosis. Increasing evidence suggests that brain tumors and BTRE share common pathophysiological mechanisms. Glutamatergic mechanisms can play a central role in promoting both primary brain tumor growth and epileptogenesis. Perampanel (PER), which acts as a selective antagonist of glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, may play a role both in the reduction in tumor growth and the control of epileptiform activity. This systematic review aimed to summarize the pre-clinical and clinical evidence about the antitumor properties, antiseizure effects and tolerability of PER in BTRE. Eight pre-clinical and eight clinical studies were identified. The currently available evidence suggests that PER can be an effective and generally well-tolerated therapeutic option in patients with BTRE. In vitro studies demonstrated promising antitumor activity of PER, while no role in slowing tumor progression has been demonstrated in rat models; clinical data on the potential antitumor activity of PER are scarce. Additional studies are needed to explore further the effects of PER on tumor progression and fully characterize its potentialities in patients with BTRE. Full article

(This article belongs to the Section Neuropharmacology and Neuropathology)

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14 pages, 476 KiB

Open AccessEditor’s ChoiceReview

Evaluating the Distinction between Cool and Hot Executive Function during Childhood

by Yusuke Moriguchi and Steven Phillips

Brain Sci. 2023, 13(2), 313; https://doi.org/10.3390/brainsci13020313 - 13 Feb 2023

Cited by 17 | Viewed by 4711

Abstract

This article assesses the cool–hot executive function (EF) framework during childhood. First, conceptual analyses suggest that cool EF (cEF) is generally distinguished from hot EF (hEF). Second, both EFs can be loaded into different factors using confirmatory factor analyses. Third, the cognitive complexity [...] Read more.

This article assesses the cool–hot executive function (EF) framework during childhood. First, conceptual analyses suggest that cool EF (cEF) is generally distinguished from hot EF (hEF). Second, both EFs can be loaded into different factors using confirmatory factor analyses. Third, the cognitive complexity of EF is similar across cEF tasks, and the cognitive complexity of cEF is similar to hEF tasks. Finally, neuroimaging analysis suggests that children activate the lateral prefrontal regions during all EF tasks. Taken together, we propose that the cool–hot framework is a useful, though not definitive way of characterizing differences in EF. Full article

(This article belongs to the Special Issue Neural Basis of Executive Control)

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16 pages, 367 KiB

Open AccessEditor’s ChoiceReview

Depression in Major Neurodegenerative Diseases and Strokes: A Critical Review of Similarities and Differences among Neurological Disorders

by Javier Pagonabarraga, Cecilio Álamo, Mar Castellanos, Samuel Díaz and Sagrario Manzano

Brain Sci. 2023, 13(2), 318; https://doi.org/10.3390/brainsci13020318 - 13 Feb 2023

Cited by 19 | Viewed by 6996

Abstract

Depression and anxiety are highly prevalent in most neurological disorders and can have a major impact on the patient’s disability and quality of life. However, mostly due to the heterogeneity of symptoms and the complexity of the underlying comorbidities, depression can be difficult [...] Read more.

Depression and anxiety are highly prevalent in most neurological disorders and can have a major impact on the patient’s disability and quality of life. However, mostly due to the heterogeneity of symptoms and the complexity of the underlying comorbidities, depression can be difficult to diagnose, resulting in limited recognition and in undertreatment. The early detection and treatment of depression simultaneously with the neurological disorder is key to avoiding deterioration and further disability. Although the neurologist should be able to identify and treat depression initially, a neuropsychiatry team should be available for severe cases and those who are unresponsive to treatment. Neurologists should be also aware that in neurodegenerative diseases, such as Alzheimer’s or Parkinson’s, different depression symptoms could develop at different stages of the disease. The treatment options for depression in neurological diseases include drugs, cognitive-behavioral therapy, and somatic interventions, among others, but often, the evidence-based efficacy is limited and the results are highly variable. Here, we review recent research on the diagnosis and treatment of depression in the context of Alzheimer’s disease, Parkinson’s disease, and strokes, with the aim of identifying common approaches and solutions for its initial management by the neurologist. Full article

(This article belongs to the Section Neuropsychiatry)

12 pages, 616 KiB

Open AccessEditor’s ChoiceReview

The Role of Tryptophan Metabolism in Alzheimer’s Disease

by Karl Savonije and Donald F. Weaver

Brain Sci. 2023, 13(2), 292; https://doi.org/10.3390/brainsci13020292 - 9 Feb 2023

Cited by 31 | Viewed by 4710

Abstract

The need to identify new potentially druggable biochemical mechanisms for Alzheimer’s disease (AD) is an ongoing priority. The therapeutic limitations of amyloid-based approaches are further motivating this search. Amino acid metabolism, particularly tryptophan metabolism, has the potential to emerge as a leading candidate [...] Read more.

The need to identify new potentially druggable biochemical mechanisms for Alzheimer’s disease (AD) is an ongoing priority. The therapeutic limitations of amyloid-based approaches are further motivating this search. Amino acid metabolism, particularly tryptophan metabolism, has the potential to emerge as a leading candidate and an alternative exploitable biomolecular target. Multiple avenues support this contention. Tryptophan (trp) and its associated metabolites are able to inhibit various enzymes participating in the biosynthesis of β-amyloid, and one metabolite, 3-hydroxyanthranilate, is able to directly inhibit neurotoxic β-amyloid oligomerization; however, whilst certain trp metabolites are neuroprotectant, other metabolites, such as quinolinic acid, are directly toxic to neurons and may themselves contribute to AD progression. Trp metabolites also have the ability to influence microglia and associated cytokines in order to modulate the neuroinflammatory and neuroimmune factors which trigger pro-inflammatory cytotoxicity in AD. Finally, trp and various metabolites, including melatonin, are regulators of sleep, with disorders of sleep being an important risk factor for the development of AD. Thus, the involvement of trp biochemistry in AD is multifactorial and offers a plethora of druggable targets in the continuing quest for AD therapeutics. Full article

(This article belongs to the Section Neurodegenerative Diseases)

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18 pages, 2876 KiB

Open AccessEditor’s ChoiceReview

Could Vitamins Have a Positive Impact on the Treatment of Parkinson’s Disease?

by Sandeep, Manas Ranjan Sahu, Linchi Rani, Arun S. Kharat and Amal Chandra Mondal

Brain Sci. 2023, 13(2), 272; https://doi.org/10.3390/brainsci13020272 - 6 Feb 2023

Cited by 21 | Viewed by 21122

Abstract

Parkinson’s disease (PD) is the second most common progressive neurodegenerative disorder after Alzheimer’s disease. Pathophysiologically, it is characterized by intracytoplasmic aggregates of α-synuclein protein in the Lewy body and loss of dopaminergic neurons from substantia nigra pars compacta and striatum regions of the [...] Read more.

Parkinson’s disease (PD) is the second most common progressive neurodegenerative disorder after Alzheimer’s disease. Pathophysiologically, it is characterized by intracytoplasmic aggregates of α-synuclein protein in the Lewy body and loss of dopaminergic neurons from substantia nigra pars compacta and striatum regions of the brain. Although the exact mechanism of neurodegeneration is not fully elucidated, it has been reported that environmental toxins such as MPTP, rotenone, paraquat, and MPP⁺ induce oxidative stress, which is one of the causative factors for it. To date, there is no complete cure. However, the indispensable role of oxidative stress in mediating PD indicates that antioxidant therapy could be a possible therapeutic strategy against the disease. The deficiency of vitamins has been extensively co-related to PD. Dietary supplementation of vitamins with antioxidant, anti-inflammatory, anti-apoptotic, and free radical scavenging properties could be the potential neuroprotective therapeutic strategy. This review summarizes the studies that evaluated the role of vitamins (A, B, C, D, E, and K) in PD. It will guide future studies in understanding the potential therapeutic role of vitamins in disease pathophysiology and may provide a framework for designing treatment strategies against the disease. Full article

(This article belongs to the Special Issue Updates in Parkinson's Disease)

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15 pages, 1071 KiB

Open AccessEditor’s ChoiceReview

Stem Cell Therapy in Diabetic Polyneuropathy: Recent Advancements and Future Directions

by Shamima Akter, Mayank Choubey, Mohammad Mohabbulla Mohib, Shahida Arbee, Md Abu Taher Sagor and Mohammad Sarif Mohiuddin

Brain Sci. 2023, 13(2), 255; https://doi.org/10.3390/brainsci13020255 - 2 Feb 2023

Cited by 13 | Viewed by 4622

Abstract

Diabetic polyneuropathy (DPN) is the most frequent, although neglected, complication of long-term diabetes. Nearly 30% of hospitalized and 20% of community-dwelling patients with diabetes suffer from DPN; the incidence rate is approximately 2% annually. To date, there has been no curable therapy for [...] Read more.

Diabetic polyneuropathy (DPN) is the most frequent, although neglected, complication of long-term diabetes. Nearly 30% of hospitalized and 20% of community-dwelling patients with diabetes suffer from DPN; the incidence rate is approximately 2% annually. To date, there has been no curable therapy for DPN. Under these circumstances, cell therapy may be a vital candidate for the treatment of DPN. The epidemiology, classification, and treatment options for DPN are disclosed in the current review. Cell-based therapies using bone marrow-derived cells, embryonic stem cells, pluripotent stem cells, endothelial progenitor cells, mesenchymal stem cells, or dental pulp stem cells are our primary concern, which may be a useful treatment option to ease or to stop the progression of DPN. The importance of cryotherapies for treating DPN has been observed in several studies. These findings may help for the future researchers to establish more focused, accurate, effective, alternative, and safe therapy to reduce DPN. Cell-based therapy might be a permanent solution in the treatment and management of diabetes-induced neuropathy. Full article

(This article belongs to the Section Neuropathology)

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22 pages, 6893 KiB

Open AccessEditor’s ChoiceReview

Breathwork Interventions for Adults with Clinically Diagnosed Anxiety Disorders: A Scoping Review

by Blerida Banushi, Madeline Brendle, Anya Ragnhildstveit, Tara Murphy, Claire Moore, Johannes Egberts and Reid Robison

Brain Sci. 2023, 13(2), 256; https://doi.org/10.3390/brainsci13020256 - 2 Feb 2023

Cited by 21 | Viewed by 27663

Abstract

Anxiety disorders are the most common group of mental disorders, but they are often underrecognized and undertreated in primary care. Dysfunctional breathing is a hallmark of anxiety disorders; however, mainstays of treatments do not tackle breathing in patients suffering anxiety. This scoping review [...] Read more.

Anxiety disorders are the most common group of mental disorders, but they are often underrecognized and undertreated in primary care. Dysfunctional breathing is a hallmark of anxiety disorders; however, mainstays of treatments do not tackle breathing in patients suffering anxiety. This scoping review aims to identify the nature and extent of the available research literature on the efficacy of breathwork interventions for adults with clinically diagnosed anxiety disorders using the DSM-5 classification system. Using the PRISMA extension for scoping reviews, a search of PubMed, Embase, and Scopus was conducted using terms related to anxiety disorders and breathwork interventions. Only clinical studies using breathwork (without the combination of other interventions) and performed on adult patients diagnosed with an anxiety disorder using the DSM-5 classification system were included. From 1081 articles identified across three databases, sixteen were included for the review. A range of breathwork interventions yielded significant improvements in anxiety symptoms in patients clinically diagnosed with anxiety disorders. The results around the role of hyperventilation in treatment of anxiety were contradictory in few of the examined studies. This evidence-based review supports the clinical utility of breathwork interventions and discusses effective treatment options and protocols that are feasible and accessible to patients suffering anxiety. Current gaps in knowledge for future research directions have also been identified. Full article

(This article belongs to the Special Issue Complementary and Alternative Therapies for Mental Health)

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18 pages, 3172 KiB

Open AccessEditor’s ChoiceReview

The Genetics of Intellectual Disability

by Sandra Jansen, Lisenka E. L. M. Vissers and Bert B. A. de Vries

Brain Sci. 2023, 13(2), 231; https://doi.org/10.3390/brainsci13020231 - 30 Jan 2023

Cited by 30 | Viewed by 12254

Abstract

Intellectual disability (ID) has a prevalence of ~2–3% in the general population, having a large societal impact. The underlying cause of ID is largely of genetic origin; however, identifying this genetic cause has in the past often led to long diagnostic Odysseys. Over [...] Read more.

Intellectual disability (ID) has a prevalence of ~2–3% in the general population, having a large societal impact. The underlying cause of ID is largely of genetic origin; however, identifying this genetic cause has in the past often led to long diagnostic Odysseys. Over the past decades, improvements in genetic diagnostic technologies and strategies have led to these causes being more and more detectable: from cytogenetic analysis in 1959, we moved in the first decade of the 21st century from genomic microarrays with a diagnostic yield of ~20% to next-generation sequencing platforms with a yield of up to 60%. In this review, we discuss these various developments, as well as their associated challenges and implications for the field of ID, which highlight the revolutionizing shift in clinical practice from a phenotype-first into genotype-first approach. Full article

(This article belongs to the Special Issue Reviews on Developmental Brain Disorders)

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12 pages, 277 KiB

Open AccessEditor’s ChoiceReview

Theories about Developmental Dyslexia

by John Stein

Brain Sci. 2023, 13(2), 208; https://doi.org/10.3390/brainsci13020208 - 26 Jan 2023

Cited by 15 | Viewed by 12279

Abstract

Despite proving its usefulness for over a century, the concept of developmental dyslexia (DD) is currently in severe disarray because of the recent introduction of the phonological theory of its causation. Since mastering the phonological principle is essential for all reading, failure to [...] Read more.

Despite proving its usefulness for over a century, the concept of developmental dyslexia (DD) is currently in severe disarray because of the recent introduction of the phonological theory of its causation. Since mastering the phonological principle is essential for all reading, failure to do so cannot be used to distinguish DD from the many other causes of such failure. To overcome this problem, many new psychological, signal detection, and neurological theories have been introduced recently. All these new theories converge on the idea that DD is fundamentally caused by impaired signalling of the timing of the visual and auditory cues that are essential for reading. These are provided by large ‘magnocellular’ neurones which respond rapidly to sensory transients. The evidence for this conclusion is overwhelming. Especially convincing are intervention studies that have shown that improving magnocellular function improves dyslexic children’s reading, together with cohort studies that have demonstrated that the magnocellular timing deficit is present in infants who later become dyslexic, long before they begin learning to read. The converse of the magnocellular deficit in dyslexics may be that they gain parvocellular abundance. This may often impart the exceptional ‘holistic’ talents that have been ascribed to them and that society needs to nurture. Full article

(This article belongs to the Special Issue Developmental Dyslexia: Theories and Experimental Approaches)

12 pages, 312 KiB

Open AccessEditor’s ChoiceReview

Lethal Lust: Suicidal Behavior and Chemsex—A Narrative Review of the Literature

by Martina Strasser, Theresa Halms, Tobias Rüther, Alkomiet Hasan and Marcus Gertzen

Brain Sci. 2023, 13(2), 174; https://doi.org/10.3390/brainsci13020174 - 20 Jan 2023

Cited by 15 | Viewed by 5037

Abstract

Chemsex is described as the use of certain drugs—commonly methamphetamine, gamma-butyrolactone (GBL)/gammahydroxybutyrate (GHB), and mephedrone—before or during planned sexual activity primarily among men who have sex with men (MSM). Evidence shows that MSM who engage in chemsex are at increased risk of physical [...] Read more.

Chemsex is described as the use of certain drugs—commonly methamphetamine, gamma-butyrolactone (GBL)/gammahydroxybutyrate (GHB), and mephedrone—before or during planned sexual activity primarily among men who have sex with men (MSM). Evidence shows that MSM who engage in chemsex are at increased risk of physical harm, such as sexually transmittable infections (STIs), and are more likely to experience mental health symptoms. To further assess this, we reviewed the recent literature to evaluate whether the psychological impact of chemsex behavior includes suicidal ideation and suicidal attempts. Pubmed/MEDLINE was searched for articles reporting suicidal ideation and behavior among chemsex users with the terms “chemsex”, “sexualized drug use”, “suicide”, and “mental health”. Twelve articles (three case reports and nine cross-sectional studies) were included in the final narrative review. Overall, we retrieved mixed results regarding the relationship between chemsex practice and suicidality outcomes. Considering the inhomogeneous nature of the studies, the findings indicate that suicidality could be an issue of concern among MSM in general but among chemsex users in particular. Possible risk factors for suicidality among chemsex participants may include adversities experienced due to one’s sexual orientation and an increased risk for HIV and other STI infections and the resulting negative impact on mental well-being. These aspects warrant further investigations. Full article

(This article belongs to the Section Neuropsychiatry)

20 pages, 975 KiB

Open AccessEditor’s ChoiceReview

The Role of Brain-Derived Neurotrophic Factor (BDNF) in Diagnosis and Treatment of Epilepsy, Depression, Schizophrenia, Anorexia Nervosa and Alzheimer’s Disease as Highly Drug-Resistant Diseases: A Narrative Review

by Aleksandra Gliwińska, Justyna Czubilińska-Łada, Gniewko Więckiewicz, Elżbieta Świętochowska, Andrzej Badeński, Marta Dworak and Maria Szczepańska

Brain Sci. 2023, 13(2), 163; https://doi.org/10.3390/brainsci13020163 - 18 Jan 2023

Cited by 38 | Viewed by 8298

Abstract

Brain-derived neurotrophic factor (BDNF) belongs to the family of neurotrophins, which are growth factors with trophic effects on neurons. BDNF is the most widely distributed neurotrophin in the central nervous system (CNS) and is highly expressed in the prefrontal cortex (PFC) and hippocampus. [...] Read more.

Brain-derived neurotrophic factor (BDNF) belongs to the family of neurotrophins, which are growth factors with trophic effects on neurons. BDNF is the most widely distributed neurotrophin in the central nervous system (CNS) and is highly expressed in the prefrontal cortex (PFC) and hippocampus. Its distribution outside the CNS has also been demonstrated, but most studies have focused on its effects in neuropsychiatric disorders. Despite the advances in medicine in recent decades, neurological and psychiatric diseases are still characterized by high drug resistance. This review focuses on the use of BDNF in the developmental assessment, treatment monitoring, and pharmacotherapy of selected diseases, with a particular emphasis on epilepsy, depression, anorexia, obesity, schizophrenia, and Alzheimer’s disease. The limitations of using a molecule with such a wide distribution range and inconsistent method of determination are also highlighted. Full article

(This article belongs to the Section Neuropsychiatry)

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23 pages, 4934 KiB

Open AccessEditor’s ChoiceReview

Predictive Value of CT Perfusion in Hemorrhagic Transformation after Acute Ischemic Stroke: A Systematic Review and Meta-Analysis

by Jie Xu, Fangyu Dai, Binda Wang, Yiming Wang, Jiaqian Li, Lulan Pan, Jingjing Liu, Haipeng Liu and Songbin He

Brain Sci. 2023, 13(1), 156; https://doi.org/10.3390/brainsci13010156 - 16 Jan 2023

Cited by 14 | Viewed by 3923

Abstract

Background: Existing studies indicate that some computed tomography perfusion (CTP) parameters may predict hemorrhagic transformation (HT) after acute ischemic stroke (AIS), but there is an inconsistency in the conclusions alongside a lack of comprehensive comparison. Objective: To comprehensively evaluate the predictive value of [...] Read more.

Background: Existing studies indicate that some computed tomography perfusion (CTP) parameters may predict hemorrhagic transformation (HT) after acute ischemic stroke (AIS), but there is an inconsistency in the conclusions alongside a lack of comprehensive comparison. Objective: To comprehensively evaluate the predictive value of CTP parameters in HT after AIS. Data sources: A systematical literature review of existing studies was conducted up to 1st October 2022 in six mainstream databases that included original data on the CTP parameters of HT and non-HT groups or on the diagnostic performance of relative cerebral blood flow (rCBF), relative permeability-surface area product (rPS), or relative cerebral blood volume (rCBV) in patients with AIS that completed CTP within 24 h of onset. Data Synthesis: Eighteen observational studies were included. HT and non-HT groups had statistically significant differences in CBF, CBV, PS, rCBF, rCBV, and rPS (p < 0.05 for all). The hierarchical summary receiver operating characteristic (HSROC) revealed that rCBF (area under the curve (AUC) = 0.9), rPS (AUC = 0.89), and rCBV (AUC = 0.85) had moderate diagnostic performances in predicting HT. The pooled sensitivity and specificity of rCBF were 0.85 (95% CI, 0.75–0.91) and 0.83 (95% CI, 0.63–0.94), respectively. Conclusions: rCBF, rPS, and rCBV had moderate diagnostic performances in predicting HT, and rCBF had the best pooled sensitivity and specificity. Full article

(This article belongs to the Topic Diagnosis and Management of Acute Ischemic Stroke)

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12 pages, 958 KiB

Open AccessEditor’s ChoiceReview

α-Synuclein and Mechanisms of Epigenetic Regulation

by Andrei Surguchov

Brain Sci. 2023, 13(1), 150; https://doi.org/10.3390/brainsci13010150 - 15 Jan 2023

Cited by 20 | Viewed by 5070

Abstract

Synucleinopathies are a group of neurodegenerative diseases with common pathological lesions associated with the excessive accumulation and abnormal intracellular deposition of toxic species of α-synuclein. The shared clinical features are chronic progressive decline of motor, cognitive, and behavioral functions. These disorders include Parkinson’s [...] Read more.

Synucleinopathies are a group of neurodegenerative diseases with common pathological lesions associated with the excessive accumulation and abnormal intracellular deposition of toxic species of α-synuclein. The shared clinical features are chronic progressive decline of motor, cognitive, and behavioral functions. These disorders include Parkinson’s disease, dementia with Lewy body, and multiple system atrophy. Vigorous research in the mechanisms of pathology of these illnesses is currently under way to find disease-modifying treatment and molecular markers for early diagnosis. α-Synuclein is a prone-to-aggregate, small amyloidogenic protein with multiple roles in synaptic vesicle trafficking, neurotransmitter release, and intracellular signaling events. Its expression is controlled by several mechanisms, one of which is epigenetic regulation. When transmitted to the nucleus, α-synuclein binds to DNA and histones and participates in epigenetic regulatory functions controlling specific gene transcription. Here, we discuss the various aspects of α-synuclein involvement in epigenetic regulation in health and diseases. Full article

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

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27 pages, 1502 KiB

Open AccessEditor’s ChoiceReview

The Neuroprotective Effects and Therapeutic Potential of the Chalcone Cardamonin for Alzheimer’s Disease

by Kimberly Barber, Patricia Mendonca and Karam F. A. Soliman

Brain Sci. 2023, 13(1), 145; https://doi.org/10.3390/brainsci13010145 - 14 Jan 2023

Cited by 28 | Viewed by 5042

Abstract

Neurodegenerative diseases (ND) include a wide range of conditions that result from progressive damage to the neurons. Alzheimer’s disease (AD) is one of the most common NDs, and neuroinflammation and oxidative stress (OS) are the major factors in the development and progression of [...] Read more.

Neurodegenerative diseases (ND) include a wide range of conditions that result from progressive damage to the neurons. Alzheimer’s disease (AD) is one of the most common NDs, and neuroinflammation and oxidative stress (OS) are the major factors in the development and progression of the disease. Many naturally occurring phytochemical compounds exhibit antioxidant and anti-inflammatory activities with potential neuroprotective effects. Several plant species, including Alpinia katsumadai and Alpinia conchigera, contain cardamonin (CD). CD (2′,4′-dihydroxy-6′methoxychalcone) has many therapeutic properties, including anticancer, anti-inflammatory, antioxidant, antiviral, and antibiotic activities. CD is a potent compound that can reduce OS and modulate the inflammatory processes that play a significant part in developing neurodegenerative diseases. CD has been shown to modulate a variety of signaling molecules involved in the development and progression of ND, including transcription factors (NF-kB and STAT3), cytokines (TNF-α, IL-1, and IL-6), enzymes (COX-2, MMP-9, and ALDH1), and other proteins and genes (Bcl-2, XIAP, and cyclin D1). Additionally, CD effectively modulates miRNA levels and autophagy-related CD-protective mechanisms against neurodegeneration. In summary, this review provides mechanistic insights into CD’s ability to modify multiple oxidative stress–antioxidant system pathways, Nrf2, and neuroinflammation. Additionally, it points to the possible therapeutic potential and preventive utilization of CD in neurodegenerative diseases, most specifically AD. Full article

(This article belongs to the Topic Memory-Enhancing Activity of Bioactive Compounds: From Natural Sources to Brain)

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14 pages, 1469 KiB

Open AccessEditor’s ChoiceReview

Modulating Brain Activity with Invasive Brain–Computer Interface: A Narrative Review

by Zhi-Ping Zhao, Chuang Nie, Cheng-Teng Jiang, Sheng-Hao Cao, Kai-Xi Tian, Shan Yu and Jian-Wen Gu

Brain Sci. 2023, 13(1), 134; https://doi.org/10.3390/brainsci13010134 - 12 Jan 2023

Cited by 39 | Viewed by 11617

Abstract

Brain-computer interface (BCI) can be used as a real-time bidirectional information gateway between the brain and machines. In particular, rapid progress in invasive BCI, propelled by recent developments in electrode materials, miniature and power-efficient electronics, and neural signal decoding technologies has attracted wide [...] Read more.

Brain-computer interface (BCI) can be used as a real-time bidirectional information gateway between the brain and machines. In particular, rapid progress in invasive BCI, propelled by recent developments in electrode materials, miniature and power-efficient electronics, and neural signal decoding technologies has attracted wide attention. In this review, we first introduce the concepts of neuronal signal decoding and encoding that are fundamental for information exchanges in BCI. Then, we review the history and recent advances in invasive BCI, particularly through studies using neural signals for controlling external devices on one hand, and modulating brain activity on the other hand. Specifically, regarding modulating brain activity, we focus on two types of techniques, applying electrical stimulation to cortical and deep brain tissues, respectively. Finally, we discuss the related ethical issues concerning the clinical application of this emerging technology. Full article

(This article belongs to the Special Issue Human Brain Dynamics: Latest Advances and Prospects—2nd Edition)

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24 pages, 1227 KiB

Open AccessEditor’s ChoiceReview

A Comprehensive Review on Anti-Inflammatory Response of Flavonoids in Experimentally-Induced Epileptic Seizures

by Shyam Sunder Rabidas, Chandra Prakash, Jyoti Tyagi, Jyoti Suryavanshi, Pavan Kumar, Jaydeep Bhattacharya and Deepak Sharma

Brain Sci. 2023, 13(1), 102; https://doi.org/10.3390/brainsci13010102 - 5 Jan 2023

Cited by 17 | Viewed by 5545

Abstract

Flavonoids, a group of natural compounds with phenolic structure, are becoming popular as alternative medicines obtained from plants. These compounds are reported to have various pharmacological properties, including attenuation of inflammatory responses in multiple health issues. Epilepsy is a disorder of the central [...] Read more.

Flavonoids, a group of natural compounds with phenolic structure, are becoming popular as alternative medicines obtained from plants. These compounds are reported to have various pharmacological properties, including attenuation of inflammatory responses in multiple health issues. Epilepsy is a disorder of the central nervous system implicated with the activation of the inflammatory cascade in the brain. The aim of the present study was to summarize the role of various neuroinflammatory mediators in the onset and progression of epilepsy, and, thereafter, to discuss the flavonoids and their classes, including their biological properties. Further, we highlighted the modulation of anti-inflammatory responses achieved by these substances in different forms of epilepsy, as evident from preclinical studies executed on multiple epilepsy models. Overall, the review summarizes the available evidence of the anti-inflammatory potential of various flavonoids in epilepsy. Full article

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

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20 pages, 399 KiB

Open AccessEditor’s ChoiceReview

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

by Dmitrii D. Markov

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

Cited by 68 | Viewed by 8239

Abstract

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

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

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

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