Brain Sciences

16 pages, 3107 KiB

Open AccessEditor’s ChoiceReview

The Interplay between Glioblastoma Cells and Tumor Microenvironment: New Perspectives for Early Diagnosis and Targeted Cancer Therapy

by Assunta Virtuoso, Giuseppa D’Amico, Federica Scalia, Ciro De Luca, Michele Papa, Grazia Maugeri, Velia D’Agata, Celeste Caruso Bavisotto and Agata Grazia D’Amico

Brain Sci. 2024, 14(4), 331; https://doi.org/10.3390/brainsci14040331 - 29 Mar 2024

Cited by 10 | Viewed by 3034

Abstract

Glioblastoma multiforme (GBM) stands out as the most tremendous brain tumor, constituting 60% of primary brain cancers, accompanied by dismal survival rates. Despite advancements in research, therapeutic options remain limited to chemotherapy and surgery. GBM molecular heterogeneity, the intricate interaction with the tumor [...] Read more.

Glioblastoma multiforme (GBM) stands out as the most tremendous brain tumor, constituting 60% of primary brain cancers, accompanied by dismal survival rates. Despite advancements in research, therapeutic options remain limited to chemotherapy and surgery. GBM molecular heterogeneity, the intricate interaction with the tumor microenvironment (TME), and non-selective treatments contribute to the neoplastic relapse. Diagnostic challenges arise from GBM advanced-stage detection, necessitating the exploration of novel biomarkers for early diagnosis. Using data from the literature and a bioinformatic tool, the current manuscript delineates the molecular interplay between human GBM, astrocytes, and myeloid cells, underscoring selected protein pathways belonging to astroglia and myeloid lineage, which can be considered for targeted therapies. Moreover, the pivotal role of extracellular vesicles (EVs) in orchestrating a favorable microenvironment for cancer progression is highlighted, suggesting their utility in identifying biomarkers for GBM early diagnosis. Full article

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

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18 pages, 769 KiB

Open AccessEditor’s ChoiceReview

Synthetic Cathinones: Epidemiology, Toxicity, Potential for Abuse, and Current Public Health Perspective

by Shanshan Chen, Wenhua Zhou and Miaojun Lai

Brain Sci. 2024, 14(4), 334; https://doi.org/10.3390/brainsci14040334 - 29 Mar 2024

Cited by 10 | Viewed by 7033

Abstract

Synthetic cathinones, derived from cathinone found in the plant Catha edulis, represent the second largest and most frequently seized group of new psychoactive substances. They are considered as β-keto analogs of amphetamine, sharing pharmacological effects with amphetamine and cocaine. This review describes the [...] Read more.

Synthetic cathinones, derived from cathinone found in the plant Catha edulis, represent the second largest and most frequently seized group of new psychoactive substances. They are considered as β-keto analogs of amphetamine, sharing pharmacological effects with amphetamine and cocaine. This review describes the neurotoxic properties of synthetic cathinones, encompassing their capacity to induce neuroinflammation, dysregulate neurotransmitter systems, and alter monoamine transporters and receptors. Additionally, it discusses the rewarding and abuse potential of synthetic cathinones drawing from findings obtained through various preclinical animal models, contextualized with other classical psychostimulants. The review also offers an overview of current abuse trends of synthetic cathinones on the illicit drug market, specifying the aspects covered, and underscores the risks they pose to public health. Finally, the review discusses public health initiatives and efforts to reduce the hazards of synthetic cathinones, including harm reduction methods, education, and current clinical management strategies. Full article

(This article belongs to the Special Issue Abuse Liability and Toxic Potential of Synthetic Psychoactive Cathinones)

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18 pages, 3679 KiB

Open AccessEditor’s ChoiceArticle

Breathing Right… or Left! The Effects of Unilateral Nostril Breathing on Psychological and Cognitive Wellbeing: A Pilot Study

by Maria Elide Vanutelli, Chiara Grigis and Claudio Lucchiari

Brain Sci. 2024, 14(4), 302; https://doi.org/10.3390/brainsci14040302 - 23 Mar 2024

Viewed by 8180

Abstract

The impact of controlled breathing on cognitive and affective processing has been recognized since ancient times, giving rise to multiple practices aimed at achieving different psychophysical states, mostly related to mental clarity and focus, stress reduction, and relaxation. Previous scientific research explored the [...] Read more.

The impact of controlled breathing on cognitive and affective processing has been recognized since ancient times, giving rise to multiple practices aimed at achieving different psychophysical states, mostly related to mental clarity and focus, stress reduction, and relaxation. Previous scientific research explored the effects of forced unilateral nostril breathing (UNB) on brain activity and emotional and cognitive functions. Some evidence concluded that it had a contralateral effect, while other studies presented controversial results, making it difficult to come to an unambiguous interpretation. Also, a few studies specifically addressed wellbeing. In the present study, we invited a pilot sample of 20 participants to take part in an 8-day training program for breathing, and each person was assigned to either a unilateral right nostril (URNB) or left nostril breathing condition (ULNB). Then, each day, we assessed the participants’ wellbeing indices using their moods and mind wandering scales. The results revealed that, after the daily practice, both groups reported improved wellbeing perception. However, the effect was specifically related to the nostril involved. URNB produced more benefits in terms of stress reduction and relaxation, while ULNB significantly and increasingly reduced mind-wandering occurrences over time. Our results suggest that UNB can be effectively used to increase wellbeing in the general population. Additionally, they support the idea that understanding the effects of unilateral breathing on wellbeing and cognition requires a complex interpretive model with multiple brain networks to address bottom-up and top-down processes. Full article

(This article belongs to the Section Neuropsychology)

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14 pages, 283 KiB

Open AccessEditor’s ChoiceReview

Cognitive Decline: Current Intervention Strategies and Integrative Therapeutic Approaches for Alzheimer’s Disease

by Kate S. Branigan and Blake T. Dotta

Brain Sci. 2024, 14(4), 298; https://doi.org/10.3390/brainsci14040298 - 22 Mar 2024

Cited by 4 | Viewed by 4450

Abstract

Alzheimer’s disease (AD) represents a pressing global health challenge, with an anticipated surge in diagnoses over the next two decades. This progressive neurodegenerative disorder unfolds gradually, with observable symptoms emerging after two decades of imperceptible brain changes. While traditional therapeutic approaches, such as [...] Read more.

Alzheimer’s disease (AD) represents a pressing global health challenge, with an anticipated surge in diagnoses over the next two decades. This progressive neurodegenerative disorder unfolds gradually, with observable symptoms emerging after two decades of imperceptible brain changes. While traditional therapeutic approaches, such as medication and cognitive therapy, remain standard in AD management, their limitations prompt exploration into novel integrative therapeutic approaches. Recent advancements in AD research focus on entraining gamma waves through innovative methods, such as light flickering and electromagnetic fields (EMF) stimulation. Flickering light stimulation (FLS) at 40 Hz has demonstrated significant reductions in AD pathologies in both mice and humans, providing improved cognitive functioning. Additionally, recent experiments have demonstrated that APOE mutations in mouse models substantially reduce tau pathologies, with microglial modulation playing a crucial role. EMFs have also been demonstrated to modulate microglia. The exploration of EMFs as a therapeutic approach is gaining significance, as many recent studies have showcased their potential to influence microglial responses. Th article concludes by speculating on the future directions of AD research, emphasizing the importance of ongoing efforts in understanding the complexities of AD pathogenesis through a holistic approach and developing interventions that hold promise for improved patient outcomes. Full article

(This article belongs to the Special Issue Reviews in Neuropsychology)

12 pages, 1099 KiB

Open AccessEditor’s ChoiceArticle

Individualised Transcranial Magnetic Stimulation Targeting of the Left Dorsolateral Prefrontal Cortex for Enhancing Cognition: A Randomised Controlled Trial

by Donel M. Martin, Yon Su, Ho Fung Chan, Victoria Dielenberg, Esther Chow, Mei Xu, Ashley Wang, Stevan Nikolin, Adriano H. Moffa and Colleen K. Loo

Brain Sci. 2024, 14(4), 299; https://doi.org/10.3390/brainsci14040299 - 22 Mar 2024

Cited by 7 | Viewed by 3274

Abstract

Repetitive transcranial magnetic stimulation (rTMS) has been demonstrated to produce cognitive enhancing effects across different neuropsychiatric disorders; however, so far, these effects have been limited. This trial investigated the efficacy of using a novel individualised approach to target the left dorsolateral prefrontal cortex [...] Read more.

Repetitive transcranial magnetic stimulation (rTMS) has been demonstrated to produce cognitive enhancing effects across different neuropsychiatric disorders; however, so far, these effects have been limited. This trial investigated the efficacy of using a novel individualised approach to target the left dorsolateral prefrontal cortex (L-DLPFC) for enhancing cognitive flexibility based on performance on a cognitive task. First, forty healthy participants had their single target site at the L-DLPFC determined based on each individual’s performance on a random letter generation task. Participants then received, in a cross-over single-blinded experimental design, a single session of intermittent theta burst stimulation (iTBS) to their individualised DLPFC target site, an active control site and sham iTBS. Following each treatment condition, participants completed the Task Switching task and Colour–Word Stroop test. There was no significant main effect of treatment condition on the primary outcome measure of switch reaction times from the Task Switching task [F = 1.16 (2, 21.6), p = 0.33] or for any of the secondary cognitive outcome measures. The current results do not support the use of our novel individualised targeting methodology for enhancing cognitive flexibility in healthy participants. Research into alternative methodological targeting approaches is required to further improve rTMS’s cognitive enhancing effects. Full article

(This article belongs to the Special Issue Brain Stimulation for Psychiatric Disorders: Emerging Evidence and New Perspectives)

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24 pages, 643 KiB

Open AccessEditor’s ChoiceReview

A Narrative Review of Current and Emerging Trends in the Treatment of Alcohol Use Disorder

by Muhammet Celik, Mark S. Gold and Brian Fuehrlein

Brain Sci. 2024, 14(3), 294; https://doi.org/10.3390/brainsci14030294 - 20 Mar 2024

Cited by 6 | Viewed by 9213

Abstract

Alcohol use disorder (AUD) is a significant contributor to morbidity and mortality in the United States. It contributes to over 140,000 annual deaths, to over 200 related diseases and health conditions globally, and accounts for 5.1% of the global disease burden. Despite its [...] Read more.

Alcohol use disorder (AUD) is a significant contributor to morbidity and mortality in the United States. It contributes to over 140,000 annual deaths, to over 200 related diseases and health conditions globally, and accounts for 5.1% of the global disease burden. Despite its substantial impact, AUD remains undertreated, marked by a scarcity of approved medications. This paper explores the current treatment landscape and novel strategies for both alcohol withdrawal syndrome and AUD. Promising results, including the use of psychedelics alongside psychotherapy, noninvasive neural-circuit-based interventions, phosphodiesterase-4 inhibitors, and GLP-1 receptor agonists, have emerged from recent studies. While these advancements show potential, further research is crucial for a comprehensive understanding of their effectiveness. The clear shortage of approved medications and other treatment modalities underscores the pressing need for ongoing research. Full article

(This article belongs to the Section Behavioral Neuroscience)

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20 pages, 5997 KiB

Open AccessEditor’s ChoiceCase Report

Effects of Cervical Spinal Manipulation on Saccadic Eye Movements

by Adam Klotzek, Monem Jemni, Shad James Groves and Frederick Robert Carrick

Brain Sci. 2024, 14(3), 292; https://doi.org/10.3390/brainsci14030292 - 20 Mar 2024

Cited by 1 | Viewed by 5660

Abstract

Quantifying saccadic eye movements can assist in identifying dysfunctional brain networks in both healthy and diseased people. Infrared Oculography is a simple and non-invasive approach to capturing and quantifying saccades, providing information that might aid in diagnosis and outcome assessments. The effect of [...] Read more.

Quantifying saccadic eye movements can assist in identifying dysfunctional brain networks in both healthy and diseased people. Infrared Oculography is a simple and non-invasive approach to capturing and quantifying saccades, providing information that might aid in diagnosis and outcome assessments. The effect of spinal manipulation on quantified saccadic performance parameters has not been fully studied despite known post-manipulative effects on the brain and brainstem regions controlling them. This case study investigates spinal manipulation’s immediate and long-term effects on saccadic eye movements by quantifying the saccades of a male patient diagnosed with post-concussion syndrome. The patient performed horizontal saccades that were quantified before and immediately following cervical spinal manipulation both at the case study’s start and following a 2-week interim, during which the subject received six manipulative treatments. Immediate and long-term post-manipulative effects were observed, and the results revealed various post-manipulative effects across all quantified parameters in addition to between right and leftward saccades. The immediate post-manipulative effect was greatest at the case study’s onset, while the long-term right and leftward saccadic symmetry were most affected. The observations in this case study demonstrate that cervical spinal manipulation influences saccadic eye movements, providing new insights into its central neurological effects and therapeutic applications beyond its most commonly known use in pain management. More importantly, it encourages scientists to undertake further clinical investigations on wider scales. Full article

(This article belongs to the Section Neurorehabilitation)

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16 pages, 279 KiB

Open AccessEditor’s ChoiceReview

Clustering Functional Magnetic Resonance Imaging Time Series in Glioblastoma Characterization: A Review of the Evolution, Applications, and Potentials

by Matteo De Simone, Giorgio Iaconetta, Giuseppina Palermo, Alessandro Fiorindi, Karl Schaller and Lucio De Maria

Brain Sci. 2024, 14(3), 296; https://doi.org/10.3390/brainsci14030296 - 20 Mar 2024

Cited by 19 | Viewed by 2683

Abstract

In this paper, we discuss how the clustering analysis technique can be applied to analyze functional magnetic resonance imaging (fMRI) time-series data in the context of glioblastoma (GBM), a highly heterogeneous brain tumor. The precise characterization of GBM is challenging and requires advanced [...] Read more.

In this paper, we discuss how the clustering analysis technique can be applied to analyze functional magnetic resonance imaging (fMRI) time-series data in the context of glioblastoma (GBM), a highly heterogeneous brain tumor. The precise characterization of GBM is challenging and requires advanced analytical approaches. We have synthesized the existing literature to provide an overview of how clustering algorithms can help identify unique patterns within the dynamics of GBM. Our review shows that the clustering of fMRI time series has great potential for improving the differentiation between various subtypes of GBM, which is pivotal for developing personalized therapeutic strategies. Moreover, this method proves to be effective in capturing temporal changes occurring in GBM, enhancing the monitoring of disease progression and response to treatment. By thoroughly examining and consolidating the current research, this paper contributes to the understanding of how clustering techniques applied to fMRI data can refine the characterization of GBM. This article emphasizes the importance of incorporating cutting-edge data analysis techniques into neuroimaging and neuro-oncology research. By providing a detailed perspective, this approach may guide future investigations and boost the development of tailored therapeutic strategies for GBM. Full article

(This article belongs to the Special Issue Perfusion and Functional MRI in Basic and Clinical Neuroscience)

17 pages, 507 KiB

Open AccessEditor’s ChoiceSystematic Review

Auditory Processing and Speech-Sound Disorders

by Konstantinos Drosos, Alexandra Papanicolaou, Louiza Voniati, Klea Panayidou and Chryssoula Thodi

Brain Sci. 2024, 14(3), 291; https://doi.org/10.3390/brainsci14030291 - 19 Mar 2024

Cited by 4 | Viewed by 6869

Abstract

Background: Speech-sound disorders (SSD) have been linked to auditory processing difficulties, and auditory processing disorders (APD) have been related to phonological awareness and literacy development. To this date, there has not been a systematic literature review investigating the results of psychophysiology and language [...] Read more.

Background: Speech-sound disorders (SSD) have been linked to auditory processing difficulties, and auditory processing disorders (APD) have been related to phonological awareness and literacy development. To this date, there has not been a systematic literature review investigating the results of psychophysiology and language assessments related to SSD and APD in children. Methods: The literature search was conducted in PubMed, Medline EBSCO, and Scopus to identify studies with children diagnosed/suspected of having APDs and SSDs. The quality of methodology in the selected articles was evaluated with the Newcastle Ottawa Scale. Results: Seven out of 378 relevant studies met the selection criteria. The findings were summarized for children with SSD and APD based on (a) metalinguistic and literacy skills, (b) cognitive abilities, and (c) temporal processing abilities. Three articles indicated that children with APD and SSD exhibit lower temporal task accuracy and reaction time. In two studies, children with SSD exhibited lower scores in discrimination, sequencing, and recall of brief stimuli in rapid succession. Conclusions: This review revealed associations between SSD severity and APD that may underline low performance in metalinguistic skills. Diagnostic assessments have been proposed based on the review to adequately identify children with SSD and APD and provide useful information for more suitable intervention. Full article

(This article belongs to the Section Neurolinguistics)

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15 pages, 2033 KiB

Open AccessEditor’s ChoiceReview

Sensory Integration: A Novel Approach for Healthy Ageing and Dementia Management

by Ongart Maneemai, Maira Cristina Cujilan Alvarado, Lina Graciela Calderon Intriago, Alicia Jeanette Donoso Triviño, Joicy Anabel Franco Coffré, Domenico Pratico, Kristof Schwartz, Tadele Tesfaye and Takao Yamasaki

Brain Sci. 2024, 14(3), 285; https://doi.org/10.3390/brainsci14030285 - 18 Mar 2024

Cited by 6 | Viewed by 7258

Abstract

Sensory processing is a fundamental aspect of the nervous system that plays a pivotal role in the cognitive decline observed in older individuals with dementia. The “sensory diet”, derived from sensory integration theory, may provide a tailored approach to modulating sensory experiences and [...] Read more.

Sensory processing is a fundamental aspect of the nervous system that plays a pivotal role in the cognitive decline observed in older individuals with dementia. The “sensory diet”, derived from sensory integration theory, may provide a tailored approach to modulating sensory experiences and triggering neuroplastic changes in the brain in individuals with dementia. Therefore, this review aimed to investigate the current knowledge regarding the sensory diet and its potential application to dementia. This review encompassed an extensive search across multiple databases, including PubMed, Google Scholar, covering articles published from 2010 to 2023. Keywords such as “sensory integration”, “sensory modulation”, “healthy aging”, and “dementia” were utilized to identify relevant studies. The types of materials retrieved included peer-reviewed articles, systematic reviews, and meta-analyses, ensuring a comprehensive overview of the current research landscape. This article offers a comprehensive exploration of the effectiveness of sensory diets such as tactile stimulation, auditory therapies, and visual interventions, which have demonstrated noteworthy efficacy in addressing challenges linked to aging and dementia. Research findings consistently report positive outcomes, such as improved cognitive function, elevated emotional well-being, and enhanced overall quality of life in older individuals. Furthermore, we found that the integration of sensory diets with the metaverse, augmented reality, and virtual reality opens up personalized experiences, fostering cognitive stimulation and emotional well-being for individuals during aging. Therefore, we conclude that customized sensory diets, based on interdisciplinary cooperation and leveraging technological advancements, are effective in optimizing sensory processing and improve the overall well-being of older individuals contending with sensory modulation challenges and dementia. 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: Series II)

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18 pages, 638 KiB

Open AccessEditor’s ChoiceSystematic Review

Cognitive, Emotional, and Daily Functioning Domains Involved in Decision-Making among Patients with Mild Cognitive Impairment: A Systematic Review

by Federica Alfeo, Tiziana Lanciano, Chiara Abbatantuono, Giorgia Gintili, Maria Fara De Caro, Antonietta Curci and Paolo Taurisano

Brain Sci. 2024, 14(3), 278; https://doi.org/10.3390/brainsci14030278 - 14 Mar 2024

Cited by 9 | Viewed by 4741

Abstract

Mild cognitive impairment (MCI) is a transitional or prodromal stage of dementia in which autonomies are largely preserved (autonomies are not particularly affected). However, this condition may entail a depletion of decision-making (DM) abilities likely due to a gradual deterioration of the prefrontal [...] Read more.

Mild cognitive impairment (MCI) is a transitional or prodromal stage of dementia in which autonomies are largely preserved (autonomies are not particularly affected). However, this condition may entail a depletion of decision-making (DM) abilities likely due to a gradual deterioration of the prefrontal cortex and subcortical brain areas underlying cognitive–emotional processing. Given the clinical implications of a decline in self-determination observed in some MCI sufferers, the present systematic review was aimed at investigating the literature addressing DM processes in patients with MCI, consistent with PRISMA guidelines. The six online databases inquired yielded 1689 research articles that were screened and then assessed based on eligibility and quality criteria. As a result, 41 studies were included and classified following the PICOS framework. Overall, patients with MCI who underwent neuropsychological assessment were found to be slightly or moderately impaired in DM abilities related to financial management, medical adherence, specific cognitive performances, risky conditions, and especially uncertain life circumstances. Comparative cross-sectional studies indicated not only mid-stage cognitive functioning in MCI but also borderline or deficit DM patterns evaluated through different tasks and procedures. Further research addressing MCI profiles suggested an association between explicit memory, executive functions, and DM performance. These findings highlight the diversity of MCI manifestations, in addition to the critical importance of DM features and correlates in patients’ daily functioning. Due to a lack of consensus on both MCI and DM, this review paper sought to shed light on assessment and intervention strategies accounting for the interplay between emotion, motivation, and learning to foster DM in cognitively impaired individuals. 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: Series II)

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24 pages, 685 KiB

Open AccessEditor’s ChoiceReview

Neurofilaments Light Chain in Neurodegenerative Dementias: A Review of Imaging Correlates

by Chiara Gallingani, Chiara Carbone, Manuela Tondelli and Giovanna Zamboni

Brain Sci. 2024, 14(3), 272; https://doi.org/10.3390/brainsci14030272 - 13 Mar 2024

Cited by 12 | Viewed by 3041

Abstract

Neurofilaments light chain (NfLs) are currently recognized as a marker of axonal injury and degeneration. Their measurement in biological fluids has a promising role in the diagnosis, prognosis, and monitoring of the therapeutic response in neurological diseases, including neurodegenerative dementias. In recent years, [...] Read more.

Neurofilaments light chain (NfLs) are currently recognized as a marker of axonal injury and degeneration. Their measurement in biological fluids has a promising role in the diagnosis, prognosis, and monitoring of the therapeutic response in neurological diseases, including neurodegenerative dementias. In recent years, their relationship with clinical phenotypes and measures of disease severity has been extensively studied. Here, we reviewed studies investigating the association between NfLs and imaging measures of grey matter (GM) and white matter (WM) damage in neurodegenerative dementias. We identified a large number of studies investigating this association in Alzheimer’s disease (AD) and disorders of the frontotemporal dementia (FTD) spectrum. Results were heterogeneous, possibly due to different methodological approaches—both in NfL measurements and imaging analyses—and inclusion criteria. However, a positive association between NfL levels and GM atrophy, WM microstructural disruption, glucose hypometabolism, and protein accumulation emerged invariably, confirming the role of NfLs as a reliable biomarker for neurodegenerative dementias, albeit not specific. Full article

(This article belongs to the Special Issue Brain Magnetic Resonance Imaging in Neurological Disorders)

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19 pages, 2507 KiB

Open AccessEditor’s ChoiceArticle

Subject-Independent Emotion Recognition Based on EEG Frequency Band Features and Self-Adaptive Graph Construction

by Jinhao Zhang, Yanrong Hao, Xin Wen, Chenchen Zhang, Haojie Deng, Juanjuan Zhao and Rui Cao

Brain Sci. 2024, 14(3), 271; https://doi.org/10.3390/brainsci14030271 - 12 Mar 2024

Cited by 10 | Viewed by 3545

Abstract

Emotion is one of the most important higher cognitive functions of the human brain and plays an important role in transaction processing and decisions. In traditional emotion recognition studies, the frequency band features in EEG signals have been shown to have a high [...] Read more.

Emotion is one of the most important higher cognitive functions of the human brain and plays an important role in transaction processing and decisions. In traditional emotion recognition studies, the frequency band features in EEG signals have been shown to have a high correlation with emotion production. However, traditional emotion recognition methods cannot satisfactorily solve the problem of individual differences in subjects and data heterogeneity in EEG, and subject-independent emotion recognition based on EEG signals has attracted extensive attention from researchers. In this paper, we propose a subject-independent emotion recognition model based on adaptive extraction of layer structure based on frequency bands (BFE-Net), which is adaptive in extracting EEG map features through the multi-graphic layer construction module to obtain a frequency band-based multi-graphic layer emotion representation. To evaluate the performance of the model in subject-independent emotion recognition studies, extensive experiments are conducted on two public datasets including SEED and SEED-IV. The experimental results show that in most experimental settings, our model has a more advanced performance than the existing studies of the same type. In addition, the visualization of brain connectivity patterns reveals that some of the findings are consistent with previous neuroscientific validations, further validating the model in subject-independent emotion recognition studies. Full article

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

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15 pages, 3691 KiB

Open AccessEditor’s ChoiceArticle

Emotion Classification Based on Transformer and CNN for EEG Spatial–Temporal Feature Learning

by Xiuzhen Yao, Tianwen Li, Peng Ding, Fan Wang, Lei Zhao, Anmin Gong, Wenya Nan and Yunfa Fu

Brain Sci. 2024, 14(3), 268; https://doi.org/10.3390/brainsci14030268 - 11 Mar 2024

Cited by 15 | Viewed by 5792

Abstract

Objectives: The temporal and spatial information of electroencephalogram (EEG) signals is crucial for recognizing features in emotion classification models, but it excessively relies on manual feature extraction. The transformer model has the capability of performing automatic feature extraction; however, its potential has not [...] Read more.

Objectives: The temporal and spatial information of electroencephalogram (EEG) signals is crucial for recognizing features in emotion classification models, but it excessively relies on manual feature extraction. The transformer model has the capability of performing automatic feature extraction; however, its potential has not been fully explored in the classification of emotion-related EEG signals. To address these challenges, the present study proposes a novel model based on transformer and convolutional neural networks (TCNN) for EEG spatial–temporal (EEG ST) feature learning to automatic emotion classification. Methods: The proposed EEG ST-TCNN model utilizes position encoding (PE) and multi-head attention to perceive channel positions and timing information in EEG signals. Two parallel transformer encoders in the model are used to extract spatial and temporal features from emotion-related EEG signals, and a CNN is used to aggregate the EEG’s spatial and temporal features, which are subsequently classified using Softmax. Results: The proposed EEG ST-TCNN model achieved an accuracy of 96.67% on the SEED dataset and accuracies of 95.73%, 96.95%, and 96.34% for the arousal–valence, arousal, and valence dimensions, respectively, for the DEAP dataset. Conclusions: The results demonstrate the effectiveness of the proposed ST-TCNN model, with superior performance in emotion classification compared to recent relevant studies. Significance: The proposed EEG ST-TCNN model has the potential to be used for EEG-based automatic emotion recognition. Full article

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

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20 pages, 491 KiB

Open AccessEditor’s ChoiceSystematic Review

A Systematic Review of the Neurocognitive Effects of Psychedelics in Healthy Populations: Implications for Depressive Disorders and Post-Traumatic Stress Disorder

by Mario Renato Velit-Salazar, Paulo R. Shiroma and Eloise Cherian

Brain Sci. 2024, 14(3), 248; https://doi.org/10.3390/brainsci14030248 - 3 Mar 2024

Cited by 3 | Viewed by 6120

Abstract

Objective: This study aims to provide an overview of pharmacological trials that examine the neurocognitive effects of psychedelics among healthy individuals and patients with post-traumatic stress disorder (PTSD) or major depressive disorder (MDD). Methods: The Preferred Reporting Items for Systematic Reviews (PRISMA) was [...] Read more.

Objective: This study aims to provide an overview of pharmacological trials that examine the neurocognitive effects of psychedelics among healthy individuals and patients with post-traumatic stress disorder (PTSD) or major depressive disorder (MDD). Methods: The Preferred Reporting Items for Systematic Reviews (PRISMA) was used as a guide to structure and report the findings for this review. A literature search included the MEDLINE database up until December 2022. We included randomized or open-label human studies of MDMA, psilocybin, mescaline, LSD, DMT, or cannabis reporting non-emotionally charged neurocognitive outcomes (“cold cognition”) measured through validated neuropsychological tests. Results: A total of 43 full-text papers on MDMA (15), cannabis (12), LSD (6), psilocybin (9), DMT/ayahuasca (1), and mescaline (0) were included, mostly on healthy subjects. A single article on MDMA’s effects on cognition in subjects with PTSD was included; there were no studies on psychedelics and neurocognition in MDD. Most of the studies on healthy subjects reported detrimental or neutral effects on cognition during the peak effect of psychedelics with a few exceptions (e.g., MDMA improved psychomotor function). Performance on the type of neurocognitive dimension (e.g., attention, memory, executive function, psychomotor) varies by type of psychedelic, dosage, and cognitive testing. Conclusions: Small samples and a lack of uniformed methods across studies preclude unequivocal conclusions on whether psychedelics enhance, decrease, or have no significant effect on cognitive performance. It is foreseen that psychedelics will soon become an available treatment for various psychiatric disorders. The acute and long-term effects on cognition caused by psychedelics should be assessed in future studies. Full article

(This article belongs to the Special Issue Reviews in Neuropsychology)

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19 pages, 5627 KiB

Open AccessEditor’s ChoiceArticle

Akkermansia muciniphila Is Beneficial to a Mouse Model of Parkinson’s Disease, via Alleviated Neuroinflammation and Promoted Neurogenesis, with Involvement of SCFAs

by Chen-Meng Qiao, Wen-Yan Huang, Yu Zhou, Wei Quan, Gu-Yu Niu, Ting Li, Mei-Xuan Zhang, Jian Wu, Li-Ping Zhao, Wei-Jiang Zhao, Chun Cui and Yan-Qin Shen

Brain Sci. 2024, 14(3), 238; https://doi.org/10.3390/brainsci14030238 - 29 Feb 2024

Cited by 14 | Viewed by 2870

Abstract

Increasing evidence suggests that the gut microbiota may represent potential strategies for Parkinson’s disease (PD) treatment. Our previous research revealed a decreased abundance of Akkermansia muciniphila (Akk) in PD mice; however, whether Akk is beneficial to PD is unknown. To answer this question, [...] Read more.

Increasing evidence suggests that the gut microbiota may represent potential strategies for Parkinson’s disease (PD) treatment. Our previous research revealed a decreased abundance of Akkermansia muciniphila (Akk) in PD mice; however, whether Akk is beneficial to PD is unknown. To answer this question, the mice received MPTP intraperitoneally to construct a subacute model of PD and were then supplemented with Akk orally for 21 consecutive days. Motor function, dopaminergic neurons, neuroinflammation, and neurogenesis were examined. In addition, intestinal inflammation, and serum and fecal short-chain fatty acids (SCFAs) analyses, were assessed. We found that Akk treatment effectively inhibited the reduction of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and partially improved the motor function in PD mice. Additionally, Akk markedly alleviated neuroinflammation in the striatum and hippocampus and promoted hippocampal neurogenesis. It also decreased the level of colon inflammation. Furthermore, these aforementioned changes are mainly accompanied by alterations in serum and fecal isovaleric acid levels, and lower intestinal permeability. Our research strongly suggests that Akk is a potential neuroprotective agent for PD therapy. Full article

(This article belongs to the Special Issue Molecular Mechanism and Pathology of Parkinson's Disease)

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18 pages, 432 KiB

Open AccessEditor’s ChoiceSystematic Review

Treatments for Cannabis Use Disorder across the Lifespan: A Systematic Review

by Mohammad Ghafouri, Sabrina Correa da Costa, Ali Zare Dehnavi, Mark S. Gold and Teresa A. Rummans

Brain Sci. 2024, 14(3), 227; https://doi.org/10.3390/brainsci14030227 - 28 Feb 2024

Cited by 4 | Viewed by 6739

Abstract

Cannabis use disorder (CUD) is a growing public health concern, with rising prevalence and significant impact on individuals across age groups. This systematic review examines 24 studies investigating pharmacological and non-pharmacological interventions for CUD among adolescents (up to 17), young adults (18–24), and [...] Read more.

Cannabis use disorder (CUD) is a growing public health concern, with rising prevalence and significant impact on individuals across age groups. This systematic review examines 24 studies investigating pharmacological and non-pharmacological interventions for CUD among adolescents (up to 17), young adults (18–24), and older adults (25–65). Database searches were conducted for randomized controlled trials of CUD interventions reporting outcomes such as cannabis use, abstinence, withdrawal symptoms, and treatment retention. For adolescents, interventions such as contingent rewards and family engagement have shown promise, while young adults benefit from technology-based platforms and peer support. In older adults, pharmacological adjuncts combined with counseling have shown promise in enhancing treatment outcomes. However, optimal treatment combinations remain uncertain, highlighting the need for further research. Addressing CUD requires tailored interventions that acknowledge developmental stages and challenges across the lifespan. Although promising interventions exist, further comparative effectiveness research is needed to delineate the most efficacious approaches. Full article

(This article belongs to the Section Neuropsychiatry)

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20 pages, 1104 KiB

Open AccessEditor’s ChoiceArticle

The Optimization of a Natural Language Processing Approach for the Automatic Detection of Alzheimer’s Disease Using GPT Embeddings

by Benjamin S. Runde, Ajit Alapati and Nicolas G. Bazan

Brain Sci. 2024, 14(3), 211; https://doi.org/10.3390/brainsci14030211 - 25 Feb 2024

Cited by 10 | Viewed by 4344

Abstract

The development of noninvasive and cost-effective methods of detecting Alzheimer’s disease (AD) is essential for its early prevention and mitigation. We optimize the detection of AD using natural language processing (NLP) of spontaneous speech through the use of audio enhancement techniques and novel [...] Read more.

The development of noninvasive and cost-effective methods of detecting Alzheimer’s disease (AD) is essential for its early prevention and mitigation. We optimize the detection of AD using natural language processing (NLP) of spontaneous speech through the use of audio enhancement techniques and novel transcription methodologies. Specifically, we utilized Boll Spectral Subtraction to improve audio fidelity and created transcriptions using state-of-the-art AI services—locally-based Wav2Vec and Whisper, alongside cloud-based IBM Cloud and Rev AI—evaluating their performance against traditional manual transcription methods. Support Vector Machine (SVM) classifiers were then trained and tested using GPT-based embeddings of transcriptions. Our findings revealed that AI-based transcriptions largely outperformed traditional manual ones, with Wav2Vec (enhanced audio) achieving the best accuracy and F-1 score (0.99 for both metrics) for locally-based systems and Rev AI (standard audio) performing the best for cloud-based systems (0.96 for both metrics). Furthermore, this study revealed the detrimental effects of interviewer speech on model performance in addition to the minimal effect of audio enhancement. Based on our findings, current AI transcription and NLP technologies are highly effective at accurately detecting AD with available data but struggle to classify probable AD and mild cognitive impairment (MCI), a prodromal stage of AD, due to a lack of training data, laying the groundwork for the future implementation of an automatic AD detection system. Full article

(This article belongs to the Special Issue Deep into the Brain: Artificial Intelligence in Brain Diseases)

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33 pages, 754 KiB

Open AccessEditor’s ChoiceReview

Neuromodulation of Eating Disorders: A Review of Underlying Neural Network Activity and Neuromodulatory Treatments

by Kevin Wu, Yu Tung Lo, Jonathon Cavaleri, Matthew Bergosh, Jennifer Ipe, Robert G. Briggs, Kay B. Jann, Stuart B. Murray, Xenos L. Mason, Charles Y. Liu and Darrin J. Lee

Brain Sci. 2024, 14(3), 200; https://doi.org/10.3390/brainsci14030200 - 22 Feb 2024

Cited by 4 | Viewed by 4842

Abstract

Eating disorders are a group of psychiatric conditions that involve pathological relationships between patients and food. The most prolific of these disorders are anorexia nervosa, bulimia nervosa, and binge eating disorder. The current standard of care involves psychotherapy, pharmacotherapy, and the management of [...] Read more.

Eating disorders are a group of psychiatric conditions that involve pathological relationships between patients and food. The most prolific of these disorders are anorexia nervosa, bulimia nervosa, and binge eating disorder. The current standard of care involves psychotherapy, pharmacotherapy, and the management of comorbid conditions, with nutritional rehabilitation reserved for severe cases of anorexia nervosa. Unfortunately, many patients often fail to respond, leaving a concerning treatment gap between the current and requisite treatments for eating disorders. To better understand the neurobiology underlying these eating disorders, investigations have been undertaken to characterize the activity of various neural networks, primarily those activated during tasks of executive inhibition, reward processing, and self-reference. Various neuromodulatory techniques have been proposed to stimulate these networks with the goal of improving patients’ BMI and mental health. The aim of this review is to compile a comprehensive summarization of the current literature regarding the underlying neural connectivity of anorexia nervosa, bulimia nervosa, and binge eating disorder as well as the numerous neuromodulatory modalities that have been investigated. Importantly, we aimed to summarize the most significant clinical trials to date as well as to provide an updated assessment of the role of deep brain stimulation, summarizing numerous recently published clinical studies that have greatly contributed to the literature. In this review, we found therapeutic evidence for transcranial magnetic stimulation and transcranial direct current stimulation in treating individuals suffering from anorexia nervosa, bulimia nervosa, and binge eating disorder. We also found significant evidence for the role of deep brain stimulation, particularly as an escalatory therapy option for the those who failed standard therapy. Finally, we hope to provide promising directions for future clinical investigations. Full article

(This article belongs to the Section Behavioral Neuroscience)

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20 pages, 10515 KiB

Open AccessEditor’s ChoiceArticle

A Novel EEG-Based Assessment of Distraction in Simulated Driving under Different Road and Traffic Conditions

by Vincenzo Ronca, Francois Brambati, Linda Napoletano, Cyril Marx, Sandra Trösterer, Alessia Vozzi, Pietro Aricò, Andrea Giorgi, Rossella Capotorto, Gianluca Borghini, Fabio Babiloni and Gianluca Di Flumeri

Brain Sci. 2024, 14(3), 193; https://doi.org/10.3390/brainsci14030193 - 21 Feb 2024

Cited by 9 | Viewed by 2310

Abstract

The drivers’ distraction plays a crucial role in road safety as it is one of the main impacting causes of road accidents. The phenomenon of distraction encompasses both psychological and environmental factors and, therefore, addressing the complex interplay contributing to human distraction in [...] Read more.

The drivers’ distraction plays a crucial role in road safety as it is one of the main impacting causes of road accidents. The phenomenon of distraction encompasses both psychological and environmental factors and, therefore, addressing the complex interplay contributing to human distraction in automotive is crucial for developing technologies and interventions for improving road safety. In scientific literature, different works were proposed for the distraction characterization in automotive, but there is still the lack of a univocal measure to assess the degree of distraction, nor a gold-standard tool that allows to “detect” eventual events, road traffic, and additional driving tasks that might contribute to the drivers’ distraction. Therefore, the present study aimed at developing an EEG-based “Distraction index” obtained by the combination of the driver’s mental workload and attention neurometrics and investigating and validating its reliability by analyzing together subjective and behavioral measures. A total of 25 licensed drivers were involved in this study, where they had to drive in two different scenarios, i.e., City and Highway, while different secondary tasks were alternatively proposed in addition to the main one to modulate the driver’s attentional demand. The statistical analysis demonstrated the reliability of the proposed EEG-based distraction index in identifying the drivers’ distraction when driving along different roads and traffic conditions (all p < 0.001). More importantly, the proposed index was demonstrated to be reliable in identifying which are the most impacting additional driving tasks on the drivers’ distraction (all p < 0.01). Full article

(This article belongs to the Section Neurotechnology and Neuroimaging)

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20 pages, 823 KiB

Open AccessEditor’s ChoiceSystematic Review

Effects and Mechanisms of Exercise on Brain-Derived Neurotrophic Factor (BDNF) Levels and Clinical Outcomes in People with Parkinson’s Disease: A Systematic Review and Meta-Analysis

by Daan G. M. Kaagman, Erwin E. H. van Wegen, Natalie Cignetti, Emily Rothermel, Tim Vanbellingen and Mark A. Hirsch

Brain Sci. 2024, 14(3), 194; https://doi.org/10.3390/brainsci14030194 - 21 Feb 2024

Cited by 11 | Viewed by 7226

Abstract

Introduction: Exercise therapy may increase brain-derived neurotrophic factor (BDNF) levels and improve clinical outcomes in people living with Parkinson’s disease (PD). This systematic review was performed to investigate the effect of exercise therapy on BDNF levels and clinical outcomes in human PD and [...] Read more.

Introduction: Exercise therapy may increase brain-derived neurotrophic factor (BDNF) levels and improve clinical outcomes in people living with Parkinson’s disease (PD). This systematic review was performed to investigate the effect of exercise therapy on BDNF levels and clinical outcomes in human PD and to discuss mechanisms proposed by authors. Method: A search on the literature was performed on PubMed up to December 2023 using the following key words: Parkinson’s disease AND exercise, exercise therapy, neurological rehabilitation AND brain-derived neurotrophic factor, brain-derived neurotrophic factor/blood, brain-derived neurotrophic factor/cerebrospinal fluid AND randomized clinical trial, intervention study. Only randomized clinical trials comparing an exercise intervention to treatment as usual, usual care (UC), sham intervention, or no intervention were included. Results: A meta-analysis of BDNF outcomes with pooled data from five trials (N = 216 participants) resulted in a significant standardized mean difference (SMD) of 1.20 [95% CI 0.53 to 1.87; Z = 3.52, p = 0.0004, I² = 77%], favoring exercise using motorized treadmill, Speedflex machine, rowing machine, and non-specified exercise. Significant improvements were found in Unified Parkinson’s Disease Rating Scale (UPDRS), UPDRS-III, 6 Minute Walk Test (6MWT), and Berg Balance Scale (BBS). Methodological quality of trials was categorized as “good” in three trials, “fair” in one trial, and “poor” in one trial. Conclusion: Key results of this systematic review are that exercise therapy is effective in raising serum BDNF levels and seems effective in alleviating PD motor symptoms. Exercise therapy confers neuroplastic effects on Parkinson brain, mediated, in part, by BDNF. Full article

(This article belongs to the Special Issue Biomarkers Identification for Neurological Diseases and Neurorehabilitation)

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11 pages, 1741 KiB

Open AccessEditor’s ChoiceArticle

Changes in Structural Neural Networks in the Recovery Process of Motor Paralysis after Stroke

by Ikuo Kimura, Atsushi Senoo and Masahiro Abo

Brain Sci. 2024, 14(3), 197; https://doi.org/10.3390/brainsci14030197 - 21 Feb 2024

Cited by 6 | Viewed by 1911

Abstract

In recent years, neurorehabilitation has been actively used to treat motor paralysis after stroke. However, the impacts of rehabilitation on neural networks in the brain remain largely unknown. Therefore, we investigated changes in structural neural networks after rehabilitation therapy in patients who received [...] Read more.

In recent years, neurorehabilitation has been actively used to treat motor paralysis after stroke. However, the impacts of rehabilitation on neural networks in the brain remain largely unknown. Therefore, we investigated changes in structural neural networks after rehabilitation therapy in patients who received a combination of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) and intensive occupational therapy (intensive-OT) as neurorehabilitation. Fugl-Meyer assessment (FMA) for upper extremity (FMA-UE) and Action Research Arm Test (ARAT), both of which reflected upper limb motor function, were conducted before and after rehabilitation therapy. At the same time, diffusion tensor imaging (DTI) and three-dimensional T1-weighted imaging (3D T1WI) were performed. After analyzing the structural connectome based on DTI data, measures related to connectivity in neural networks were calculated using graph theory. Rehabilitation therapy prompted a significant increase in connectivity with the isthmus of the cingulate gyrus in the ipsilesional hemisphere (p < 0.05) in patients with left-sided paralysis, as well as a significant decrease in connectivity with the ipsilesional postcentral gyrus (p < 0.05). These results indicate that LF-rTMS combined with intensive-OT may facilitate motor function recovery by enhancing the functional roles of networks in motor-related areas of the ipsilesional cerebral hemisphere. Full article

(This article belongs to the Special Issue Clinical Application of Neuroimaging in Cerebral Vascular Diseases)

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15 pages, 2625 KiB

Open AccessEditor’s ChoiceArticle

Exploring the Acquisition of Social Communication Skills in Children with Autism: Preliminary Findings from Applied Behavior Analysis (ABA), Parent Training, and Video Modeling

by Daniela Bordini, Ana Cláudia Moya, Graccielle Rodrigues da Cunha Asevedo, Cristiane Silvestre Paula, Décio Brunoni, Helena Brentani, Sheila Cavalcante Caetano, Jair de Jesus Mari and Leila Bagaiolo

Brain Sci. 2024, 14(2), 172; https://doi.org/10.3390/brainsci14020172 - 9 Feb 2024

Cited by 4 | Viewed by 6770

Abstract

Social communication skills, especially eye contact and joint attention, are frequently impaired in autism spectrum disorder (ASD) and predict functional outcomes. Applied behavior analysis is one of the most common evidence-based treatments for ASD, but it is not accessible to most families in [...] Read more.

Social communication skills, especially eye contact and joint attention, are frequently impaired in autism spectrum disorder (ASD) and predict functional outcomes. Applied behavior analysis is one of the most common evidence-based treatments for ASD, but it is not accessible to most families in low- and middle-income countries (LMICs) as it is an expensive and intensive treatment and needs to be delivered by highly specialized professionals. Parental training has emerged as an effective alternative. This is an exploratory study to assess a parental intervention group via video modeling to acquire eye contact and joint attention. Four graded measures of eye contact and joint attention (full physical prompt, partial physical prompt, gestural prompt, and independent) were assessed in 34 children with ASD and intellectual disability (ID). There was a progressive reduction in the level of prompting required over time to acquire eye contact and joint attention, as well as a positive correlation between the time of exposure to the intervention and the acquisition of abilities. This kind of parent training using video modeling to teach eye contact and joint attention skills to children with ASD and ID is a low-cost intervention that can be applied in low-resource settings. Full article

(This article belongs to the Special Issue Autism Spectrum Disorders (ASD) in Low- and Middle-Income Countries (LMICs) and among Immigrants and Minority Groups in High-Income Countries (HICs))

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24 pages, 2837 KiB

Open AccessEditor’s ChoiceReview

Social Brain Perspectives on the Social and Evolutionary Neuroscience of Human Language

by Nathan Oesch

Brain Sci. 2024, 14(2), 166; https://doi.org/10.3390/brainsci14020166 - 7 Feb 2024

Cited by 6 | Viewed by 5458

Abstract

Human language and social cognition are two key disciplines that have traditionally been studied as separate domains. Nonetheless, an emerging view suggests an alternative perspective. Drawing on the theoretical underpinnings of the social brain hypothesis (thesis of the evolution of brain size and [...] Read more.

Human language and social cognition are two key disciplines that have traditionally been studied as separate domains. Nonetheless, an emerging view suggests an alternative perspective. Drawing on the theoretical underpinnings of the social brain hypothesis (thesis of the evolution of brain size and intelligence), the social complexity hypothesis (thesis of the evolution of communication), and empirical research from comparative animal behavior, human social behavior, language acquisition in children, social cognitive neuroscience, and the cognitive neuroscience of language, it is argued that social cognition and language are two significantly interconnected capacities of the human species. Here, evidence in support of this view reviews (1) recent developmental studies on language learning in infants and young children, pointing to the important crucial benefits associated with social stimulation for youngsters, including the quality and quantity of incoming linguistic information, dyadic infant/child-to-parent non-verbal and verbal interactions, and other important social cues integral for facilitating language learning and social bonding; (2) studies of the adult human brain, suggesting a high degree of specialization for sociolinguistic information processing, memory retrieval, and comprehension, suggesting that the function of these neural areas may connect social cognition with language and social bonding; (3) developmental deficits in language and social cognition, including autism spectrum disorder (ASD), illustrating a unique developmental profile, further linking language, social cognition, and social bonding; and (4) neural biomarkers that may help to identify early developmental disorders of language and social cognition. In effect, the social brain and social complexity hypotheses may jointly help to describe how neurotypical children and adults acquire language, why autistic children and adults exhibit simultaneous deficits in language and social cognition, and why nonhuman primates and other organisms with significant computational capacities cannot learn language. But perhaps most critically, the following article argues that this and related research will allow scientists to generate a holistic profile and deeper understanding of the healthy adult social brain while developing more innovative and effective diagnoses, prognoses, and treatments for maladies and deficits also associated with the social brain. Full article

(This article belongs to the Special Issue Neurodevelopmental Disorders and Early Language Acquisition)

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21 pages, 926 KiB

Open AccessEditor’s ChoiceReview

The Diverse Roles of Reactive Astrocytes in the Pathogenesis of Amyotrophic Lateral Sclerosis

by Kangqin Yang, Yang Liu and Min Zhang

Brain Sci. 2024, 14(2), 158; https://doi.org/10.3390/brainsci14020158 - 4 Feb 2024

Cited by 8 | Viewed by 5769

Abstract

Astrocytes displaying reactive phenotypes are characterized by their ability to remodel morphologically, molecularly, and functionally in response to pathological stimuli. This process results in the loss of their typical astrocyte functions and the acquisition of neurotoxic or neuroprotective roles. A growing body of [...] Read more.

Astrocytes displaying reactive phenotypes are characterized by their ability to remodel morphologically, molecularly, and functionally in response to pathological stimuli. This process results in the loss of their typical astrocyte functions and the acquisition of neurotoxic or neuroprotective roles. A growing body of research indicates that these reactive astrocytes play a pivotal role in the pathogenesis of amyotrophic lateral sclerosis (ALS), involving calcium homeostasis imbalance, mitochondrial dysfunction, abnormal lipid and lactate metabolism, glutamate excitotoxicity, etc. This review summarizes the characteristics of reactive astrocytes, their role in the pathogenesis of ALS, and recent advancements in astrocyte-targeting strategies. Full article

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

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20 pages, 8080 KiB

Open AccessEditor’s ChoiceArticle

Mental Workload Classification and Tasks Detection in Multitasking: Deep Learning Insights from EEG Study

by Miloš Pušica, Aneta Kartali, Luka Bojović, Ivan Gligorijević, Jelena Jovanović, Maria Chiara Leva and Bogdan Mijović

Brain Sci. 2024, 14(2), 149; https://doi.org/10.3390/brainsci14020149 - 31 Jan 2024

Cited by 7 | Viewed by 5031

Abstract

While the term task load (TL) refers to external task demands, the amount of work, or the number of tasks to be performed, mental workload (MWL) refers to the individual’s effort, mental capacity, or cognitive resources utilized while performing a task. MWL in [...] Read more.

While the term task load (TL) refers to external task demands, the amount of work, or the number of tasks to be performed, mental workload (MWL) refers to the individual’s effort, mental capacity, or cognitive resources utilized while performing a task. MWL in multitasking scenarios is often closely linked with the quantity of tasks a person is handling within a given timeframe. In this study, we challenge this hypothesis from the perspective of electroencephalography (EEG) using a deep learning approach. We conducted an EEG experiment with 50 participants performing NASA Multi-Attribute Task Battery II (MATB-II) under 4 different task load levels. We designed a convolutional neural network (CNN) to help with two distinct classification tasks. In one setting, the CNN was used to classify EEG segments based on their task load level. In another setting, the same CNN architecture was trained again to detect the presence of individual MATB-II subtasks. Results show that, while the model successfully learns to detect whether a particular subtask is active in a given segment (i.e., to differentiate between different subtasks-related EEG patterns), it struggles to differentiate between the two highest levels of task load (i.e., to distinguish MWL-related EEG patterns). We speculate that the challenge comes from two factors: first, the experiment was designed in a way that these two highest levels differed only in the quantity of work within a given timeframe; and second, the participants’ effective adaptation to increased task demands, as evidenced by low error rates. Consequently, this indicates that under such conditions in multitasking, EEG may not reflect distinct enough patterns to differentiate higher levels of task load. Full article

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

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15 pages, 294 KiB

Open AccessEditor’s ChoiceArticle

The Interplay of Anxiety, Depression, Sleep Quality, and Socioeconomic Factors in Somali Hemodialysis Patients

by Samet Kose and Nur Adam Mohamed

Brain Sci. 2024, 14(2), 144; https://doi.org/10.3390/brainsci14020144 - 30 Jan 2024

Cited by 7 | Viewed by 2365

Abstract

Objective: This study aimed to assess anxiety, depression, and sleep quality in kidney failure patients receiving hemodialysis (HD) in Somalia and examine the relationship between anxiety, depression, and sleep quality. Methods: We conducted a study with 200 kidney failure patients on HD treatment [...] Read more.

Objective: This study aimed to assess anxiety, depression, and sleep quality in kidney failure patients receiving hemodialysis (HD) in Somalia and examine the relationship between anxiety, depression, and sleep quality. Methods: We conducted a study with 200 kidney failure patients on HD treatment for over 3 months. Participants completed sociodemographic questionnaires, the Patient Health Questionnaire-9 (PHQ-9), the Hospital Anxiety and Depression Scale (HADS), the Insomnia Severity Index (ISI), and the Pittsburgh Sleep Quality Index (PSQI). Results: Among the 200 participants (mean age = 52.3; SD = 14.13), 58.5% were men, 64% had CKD for 1–5 years, and 52.6% received HD for 1–5 years. Depressive symptoms were found in 61.5% (PHQ-9) and 37.5% (HADS depression subscale) of HD patients. Poor sleep quality (PSQI) was observed in 31.5% and significantly correlated with PHQ-9 (r_s = 0.633), HADS anxiety (r_s = 0.491), and HADS depression (r_s = 0.529). The ISI score correlated significantly with PHQ-9 (r_s = 0.611), HADS anxiety (r_s = 0.494), and HADS depression (r_s = 0.586). All PSQI components correlated with depression and anxiety, except sleep medication use. Hierarchical regression analysis revealed that HADS anxiety (β = 0.342) and HADS depression (β = 0.372) predicted ISI scores. HADS anxiety (β = 0.307) and HADS depression (β = 0.419) predicted PSQI scores. Conclusions: Higher anxiety and depression levels negatively correlated with various dimensions of sleep quality in kidney failure patients. Early identification and appropriate management of these psychological disturbances are crucial for enhancing patients’ overall quality of life. Full article

(This article belongs to the Section Sleep and Circadian Neuroscience)

18 pages, 1062 KiB

Open AccessEditor’s ChoiceArticle

Improving Outcomes in People with Spinal Cord Injury: Encouraging Results from a Multidisciplinary Advanced Rehabilitation Pathway

by Maria Grazia Maggio, Mirjam Bonanno, Alfredo Manuli and Rocco Salvatore Calabrò

Brain Sci. 2024, 14(2), 140; https://doi.org/10.3390/brainsci14020140 - 28 Jan 2024

Cited by 7 | Viewed by 3669

Abstract

Spinal cord injury (SCI) consists of damage to any segment of the spinal cord extending to potential harm to nerves in the cauda equina. Rehabilitative efforts for SCI can involve conventional physiotherapy, innovative technologies, as well as cognitive treatment and psychological support. The [...] Read more.

Spinal cord injury (SCI) consists of damage to any segment of the spinal cord extending to potential harm to nerves in the cauda equina. Rehabilitative efforts for SCI can involve conventional physiotherapy, innovative technologies, as well as cognitive treatment and psychological support. The aim of this study is to evaluate the feasibility of a dedicated, multidisciplinary, and integrated intervention path for SCI, encompassing both conventional and technological interventions, while observing their impact on cognitive, motor, and behavioral outcomes and the overall quality of life for individuals with SCI. Forty-two patients with SCI were included in the analysis utilizing electronic recovery system data. The treatment regimen included multidisciplinary rehabilitation approaches, such as traditional physiotherapy sessions, speech therapy, psychological support, robotic devices, advanced cognitive rehabilitation, and other interventions. Pre–post comparisons showed a significant improvement in lower limb function (Fugl Meyer Assessment-FMA < 0.001), global cognitive functioning (Montreal Cognitive Assessment-MoCA p < 0.001), and perceived quality of life at both a physical and mental level (Short Form-12-SF-12 p < 0.001). Furthermore, we found a significant reduction in depressive state (Beck Depression Inventory-BDI p < 0.001). In addition, we assessed patient satisfaction using the Short Form of the Patient Satisfaction Questionnaire (PSQ), offering insights into the subjective evaluation of the intervention. In conclusion, this retrospective study provides positive results in terms of improvements in motor function, cognitive functions, and quality of life, highlighting the importance of exploring multidisciplinary approaches. Full article

(This article belongs to the Special Issue The Use of Robotics and Artificial Intelligence in Neurorehabilitation: From Diagnosis to Treatment)

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26 pages, 2406 KiB

Open AccessEditor’s ChoiceReview

Mitochondrial Chronic Progressive External Ophthalmoplegia

by Ali Ali, Ali Esmaeil and Raed Behbehani

Brain Sci. 2024, 14(2), 135; https://doi.org/10.3390/brainsci14020135 - 27 Jan 2024

Cited by 1 | Viewed by 5683

Abstract

Background: Chronic progressive external ophthalmoplegia (CPEO) is a rare disorder that can be at the forefront of several mitochondrial diseases. This review overviews mitochondrial CPEO encephalomyopathies to enhance accurate recognition and diagnosis for proper management. Methods: This study is conducted based on publications [...] Read more.

Background: Chronic progressive external ophthalmoplegia (CPEO) is a rare disorder that can be at the forefront of several mitochondrial diseases. This review overviews mitochondrial CPEO encephalomyopathies to enhance accurate recognition and diagnosis for proper management. Methods: This study is conducted based on publications and guidelines obtained by selective review in PubMed. Randomized, double-blind, placebo-controlled trials, Cochrane reviews, and literature meta-analyses were particularly sought. Discussion: CPEO is a common presentation of mitochondrial encephalomyopathies, which can result from alterations in mitochondrial or nuclear DNA. Genetic sequencing is the gold standard for diagnosing mitochondrial encephalomyopathies, preceded by non-invasive tests such as fibroblast growth factor-21 and growth differentiation factor-15. More invasive options include a muscle biopsy, which can be carried out after uncertain diagnostic testing. No definitive treatment option is available for mitochondrial diseases, and management is mainly focused on lifestyle risk modification and supplementation to reduce mitochondrial load and symptomatic relief, such as ptosis repair in the case of CPEO. Nevertheless, various clinical trials and endeavors are still at large for achieving beneficial therapeutic outcomes for mitochondrial encephalomyopathies. Key Messages: Understanding the varying presentations and genetic aspects of mitochondrial CPEO is crucial for accurate diagnosis and management. Full article

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

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50 pages, 2491 KiB

Open AccessEditor’s ChoiceReview

Short-Term Effect of Auditory Stimulation on Neural Activities: A Scoping Review of Longitudinal Electroencephalography and Magnetoencephalography Studies

by Kanon Kobayashi, Yasushi Shiba, Shiori Honda, Shinichiro Nakajima, Shinya Fujii, Masaru Mimura and Yoshihiro Noda

Brain Sci. 2024, 14(2), 131; https://doi.org/10.3390/brainsci14020131 - 26 Jan 2024

Cited by 3 | Viewed by 4811

Abstract

Explored through EEG/MEG, auditory stimuli function as a suitable research probe to reveal various neural activities, including event-related potentials, brain oscillations and functional connectivity. Accumulating evidence in this field stems from studies investigating neuroplasticity induced by long-term auditory training, specifically cross-sectional studies comparing [...] Read more.

Explored through EEG/MEG, auditory stimuli function as a suitable research probe to reveal various neural activities, including event-related potentials, brain oscillations and functional connectivity. Accumulating evidence in this field stems from studies investigating neuroplasticity induced by long-term auditory training, specifically cross-sectional studies comparing musicians and non-musicians as well as longitudinal studies with musicians. In contrast, studies that address the neural effects of short-term interventions whose duration lasts from minutes to hours are only beginning to be featured. Over the past decade, an increasing body of evidence has shown that short-term auditory interventions evoke rapid changes in neural activities, and oscillatory fluctuations can be observed even in the prestimulus period. In this scoping review, we divided the extracted neurophysiological studies into three groups to discuss neural activities with short-term auditory interventions: the pre-stimulus period, during stimulation, and a comparison of before and after stimulation. We show that oscillatory activities vary depending on the context of the stimuli and are greatly affected by the interplay of bottom-up and top-down modulational mechanisms, including attention. We conclude that the observed rapid changes in neural activitiesin the auditory cortex and the higher-order cognitive part of the brain are causally attributed to short-term auditory interventions. Full article

(This article belongs to the Section Neuropsychology)

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41 pages, 911 KiB

Open AccessEditor’s ChoiceReview

Brain Functional Correlates of Resting Hypnosis and Hypnotizability: A Review

by Vilfredo De Pascalis

Brain Sci. 2024, 14(2), 115; https://doi.org/10.3390/brainsci14020115 - 24 Jan 2024

Cited by 7 | Viewed by 7508

Abstract

This comprehensive review delves into the cognitive neuroscience of hypnosis and variations in hypnotizability by examining research employing functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and electroencephalography (EEG) methods. Key focus areas include functional brain imaging correlations in hypnosis, EEG band [...] Read more.

This comprehensive review delves into the cognitive neuroscience of hypnosis and variations in hypnotizability by examining research employing functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and electroencephalography (EEG) methods. Key focus areas include functional brain imaging correlations in hypnosis, EEG band oscillations as indicators of hypnotic states, alterations in EEG functional connectivity during hypnosis and wakefulness, drawing critical conclusions, and suggesting future research directions. The reviewed functional connectivity findings support the notion that disruptions in the available integration between different components of the executive control network during hypnosis may correspond to altered subjective appraisals of the agency during the hypnotic response, as per dissociated and cold control theories of hypnosis. A promising exploration avenue involves investigating how frontal lobes’ neurochemical and aperiodic components of the EEG activity at waking-rest are linked to individual differences in hypnotizability. Future studies investigating the effects of hypnosis on brain function should prioritize examining distinctive activation patterns across various neural networks. Full article

(This article belongs to the Special Issue Brain Mechanism of Hypnosis)

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21 pages, 1541 KiB

Open AccessEditor’s ChoiceReview

The Impact of Inotropes and Vasopressors on Cerebral Oxygenation in Patients with Traumatic Brain Injury and Subarachnoid Hemorrhage: A Narrative Review

by Michele Salvagno, Federico Geraldini, Giacomo Coppalini, Chiara Robba, Elisa Gouvea Bogossian, Filippo Annoni, Eva Vitali, Elda Diletta Sterchele, Costantino Balestra and Fabio Silvio Taccone

Brain Sci. 2024, 14(2), 117; https://doi.org/10.3390/brainsci14020117 - 24 Jan 2024

Cited by 7 | Viewed by 5317

Abstract

Traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) are critical neurological conditions that necessitate specialized care in the Intensive Care Unit (ICU). Managing cerebral perfusion pressure (CPP) and mean arterial pressure (MAP) is of primary importance in these patients. To maintain targeted MAP [...] Read more.

Traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) are critical neurological conditions that necessitate specialized care in the Intensive Care Unit (ICU). Managing cerebral perfusion pressure (CPP) and mean arterial pressure (MAP) is of primary importance in these patients. To maintain targeted MAP and CPP, vasopressors and/or inotropes are commonly used. However, their effects on cerebral oxygenation are not fully understood. The aim of this review is to provide an up-to date review regarding the current uses and pathophysiological issues related to the use of vasopressors and inotropes in TBI and SAH patients. According to our findings, despite achieving similar hemodynamic parameters and CPP, the effects of various vasopressors and inotropes on cerebral oxygenation, local CBF and metabolism are heterogeneous. Therefore, a more accurate understanding of the cerebral activity of these medications is crucial for optimizing patient management in the ICU setting. Full article

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

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21 pages, 1844 KiB

Open AccessEditor’s ChoiceReview

Rett Syndrome and the Role of MECP2: Signaling to Clinical Trials

by Adele Gaspar Lopes, Sampath Kumar Loganathan and Jayalakshmi Caliaperumal

Brain Sci. 2024, 14(2), 120; https://doi.org/10.3390/brainsci14020120 - 24 Jan 2024

Cited by 4 | Viewed by 6631

Abstract

Rett syndrome (RTT) is a neurological disorder that mostly affects females, with a frequency of 1 in 10,000 to 20,000 live birth cases. Symptoms include stereotyped hand movements; impaired learning, language, and communication skills; sudden loss of speech; reduced lifespan; retarded growth; disturbance [...] Read more.

Rett syndrome (RTT) is a neurological disorder that mostly affects females, with a frequency of 1 in 10,000 to 20,000 live birth cases. Symptoms include stereotyped hand movements; impaired learning, language, and communication skills; sudden loss of speech; reduced lifespan; retarded growth; disturbance of sleep and breathing; seizures; autism; and gait apraxia. Pneumonia is the most common cause of death for patients with Rett syndrome, with a survival rate of 77.8% at 25 years of age. Survival into the fifth decade is typical in Rett syndrome, and the leading cause of death is cardiorespiratory compromise. Rett syndrome progression has multiple stages; however, most phenotypes are associated with the nervous system and brain. In total, 95% of Rett syndrome cases are due to mutations in the MECP2 gene, an X-linked gene that encodes for the methyl CpG binding protein, a regulator of gene expression. In this review, we summarize the recent developments in the field of Rett syndrome and therapeutics targeting MECP2. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Brain Development and Psychiatric Diseases)

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21 pages, 342 KiB

Open AccessEditor’s ChoiceArticle

Associations between Gross and Fine Motor Skills, Physical Activity, Executive Function, and Academic Achievement: Longitudinal Findings from the UK Millennium Cohort Study

by Yuxi Zhou and Andrew Tolmie

Brain Sci. 2024, 14(2), 121; https://doi.org/10.3390/brainsci14020121 - 24 Jan 2024

Cited by 11 | Viewed by 9301

Abstract

Accumulating evidence from behavioral studies and neuroscience suggests that motor and cognitive development are intrinsically intertwined. To explore the underlying mechanisms of this motor–cognition link, our study examined the longitudinal relationship of early motor skills and physical activity with later cognitive skills. The [...] Read more.

Accumulating evidence from behavioral studies and neuroscience suggests that motor and cognitive development are intrinsically intertwined. To explore the underlying mechanisms of this motor–cognition link, our study examined the longitudinal relationship of early motor skills and physical activity with later cognitive skills. The sample was 3188 children from the United Kingdom Millennium Cohort Study, followed at 9 months and 5, 7, and 11 years. Early motor skills were examined at 9 months. Children’s daily physical activity level was measured using accelerometers at 7 years and a questionnaire was conducted at 11 years. Cognitive skills, including executive function and academic achievement, were measured at age 11. The results suggest that gross motor skills were positively associated with spatial working memory, whereas fine motor skills were predictive of good English and science outcomes. Moderate-to-vigorous activity was found to be negatively associated with English performance, although self-reported activity frequency was positively linked to math. Our results highlight the significant role of both gross and fine motor skills in cognitive development. This study also elucidates the limitations of using activity intensity to assess the impact of motor activity on children’s cognitive development, suggesting that attention to the effects of specific types of physical activity would better elucidate the motor/cognition link. Full article

(This article belongs to the Special Issue Executive Functioning Development—Measurements and Promotion in Naturalistic Setups)

14 pages, 823 KiB

Open AccessEditor’s ChoiceSystematic Review

Dual-Process Theory of Thought and Inhibitory Control: An ALE Meta-Analysis

by Giorgio Gronchi, Gioele Gavazzi, Maria Pia Viggiano and Fabio Giovannelli

Brain Sci. 2024, 14(1), 101; https://doi.org/10.3390/brainsci14010101 - 20 Jan 2024

Cited by 1 | Viewed by 6384

Abstract

The dual-process theory of thought rests on the co-existence of two different thinking modalities: a quick, automatic, and associative process opposed to a slow, thoughtful, and deliberative process. The increasing interest in determining the neural foundation of the dual-process distinction has yielded mixed [...] Read more.

The dual-process theory of thought rests on the co-existence of two different thinking modalities: a quick, automatic, and associative process opposed to a slow, thoughtful, and deliberative process. The increasing interest in determining the neural foundation of the dual-process distinction has yielded mixed results, also given the difficulty of applying the fMRI standard approach to tasks usually employed in the cognitive literature. We report an activation likelihood estimation (ALE) meta-analysis to investigate the neural foundation of the dual-process theory of thought. Eligible studies allowed for the identification of cerebral areas associated with dual-process theory-based tasks without differentiating between fast and slow thinking. The ALE algorithm converged on the medial frontal cortex, superior frontal cortex, anterior cingulate cortex, insula, and left inferior frontal gyrus. These structures partially overlap with the cerebral areas recurrently reported in the literature about the neural basis of the dual-process distinction, where the PARCS theory-based interpretation emphasizes the role of the right inferior gyrus. The results confirm the potential (but still almost unexplored) common ground between the dual-process literature and the cognitive control literature. Full article

(This article belongs to the Section Behavioral Neuroscience)

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15 pages, 318 KiB

Open AccessEditor’s ChoiceReview

Single-Sided Deafness and Hearing Rehabilitation Modalities: Contralateral Routing of Signal Devices, Bone Conduction Devices, and Cochlear Implants

by Alessandra Pantaleo, Alessandra Murri, Giada Cavallaro, Vito Pontillo, Debora Auricchio and Nicola Quaranta

Brain Sci. 2024, 14(1), 99; https://doi.org/10.3390/brainsci14010099 - 20 Jan 2024

Cited by 6 | Viewed by 5011

Abstract

Single sided deafness (SSD) is characterized by significant sensorineural hearing loss, severe or profound, in only one ear. SSD adversely affects various aspects of auditory perception, including causing impairment in sound localization, difficulties with speech comprehension in noisy environments, and decreased spatial awareness, [...] Read more.

Single sided deafness (SSD) is characterized by significant sensorineural hearing loss, severe or profound, in only one ear. SSD adversely affects various aspects of auditory perception, including causing impairment in sound localization, difficulties with speech comprehension in noisy environments, and decreased spatial awareness, resulting in a significant decline in overall quality of life (QoL). Several treatment options are available for SSD, including cochlear implants (CI), contralateral routing of signal (CROS), and bone conduction devices (BCD). The lack of consensus on outcome domains and measurement tools complicates treatment comparisons and decision-making. This narrative overview aims to summarize the treatment options available for SSD in adult and pediatric populations, discussing their respective advantages and disadvantages. Rerouting devices (CROS and BCD) attenuate the effects of head shadow and improve sound awareness and signal-to-noise ratio in the affected ear; however, they cannot restore binaural hearing. CROS devices, being non-implantable, are the least invasive option. Cochlear implantation is the only strategy that can restore binaural hearing, delivering significant improvements in speech perception, spatial localization, tinnitus control, and overall QoL. Comprehensive preoperative counseling, including a discussion of alternative technologies, implications of no treatment, expectations, and auditory training, is critical to optimizing therapeutic outcomes. Full article

(This article belongs to the Special Issue Middle Ear and Bone Conduction Implants)

27 pages, 1067 KiB

Open AccessEditor’s ChoiceReview

International Trends in Lithium Use for Pharmacotherapy and Clinical Correlates in Bipolar Disorder: A Scoping Review

by Yao Kang Shuy, Sanjana Santharan, Qian Hui Chew and Kang Sim

Brain Sci. 2024, 14(1), 102; https://doi.org/10.3390/brainsci14010102 - 20 Jan 2024

Cited by 9 | Viewed by 3363

Abstract

Lithium remains an effective option in the treatment of bipolar disorder (BD). Thus, we aim to characterize the pharmaco-epidemiological patterns of lithium use internationally over time and elucidate clinical correlates associated with BD using a scoping review, which was conducted using the methodological [...] Read more.

Lithium remains an effective option in the treatment of bipolar disorder (BD). Thus, we aim to characterize the pharmaco-epidemiological patterns of lithium use internationally over time and elucidate clinical correlates associated with BD using a scoping review, which was conducted using the methodological framework by Arksey and O’Malley (2005). We searched several databases for studies that examined the prescriptions for lithium and clinical associations in BD from inception until December 2023. This review included 55 articles from 1967 to 2023, which collected data from North America (n = 24, 43.6%), Europe (n = 20, 36.4%), and Asia (n = 11, 20.0%). The overall prescription rates ranged from 3.3% to 84% (33.4% before and 30.6% after the median year cutoffs). Over time, there was a decline in lithium use in North America (27.7% before 2010 to 17.1% after 2010) and Europe (36.7% before 2003 to 35.7% after 2003), and a mild increase in Asia (25.0% before 2003 to 26.2% after 2003). Lithium use was associated with specific demographic (e.g., age, male gender) and clinical factors (e.g., lower suicide risk). Overall, we found a trend of declining lithium use internationally, particularly in the West. Specific clinical correlates can support clinical decision-making for continued lithium use. Full article

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

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29 pages, 498 KiB

Open AccessEditor’s ChoiceReview

Rethinking Clozapine: Lights and Shadows of a Revolutionary Drug

by Liliana Dell’Osso, Chiara Bonelli, Benedetta Nardi, Federico Giovannoni, Cristiana Pronestì, Ivan Mirko Cremone, Giulia Amatori, Stefano Pini and Barbara Carpita

Brain Sci. 2024, 14(1), 103; https://doi.org/10.3390/brainsci14010103 - 20 Jan 2024

Cited by 8 | Viewed by 7021

Abstract

The current literature globally highlights the efficacy of Clozapine in several psychiatric disorders all over the world, with an FDA indication for reducing the risk of repeated suicidal behavior in patients with schizophrenia or schizoaffective disorder. A growing field of research is also [...] Read more.

The current literature globally highlights the efficacy of Clozapine in several psychiatric disorders all over the world, with an FDA indication for reducing the risk of repeated suicidal behavior in patients with schizophrenia or schizoaffective disorder. A growing field of research is also stressing a possible broader beneficial effect of Clozapine in promoting neuroprotection and neurotrophism. However, this drug is linked to several life-threatening side effects, such as agranulocytosis, myocarditis and seizures, that limit its use in daily clinical practice. For this work, a search was performed on PubMed using the terms “Clozapine indications”, “Clozapine adverse effects”, “Clozapine regenerative effects”, and “Clozapine neuroplasticity” with the aim of reviewing the scientific literature on Clozapine’s treatment indications, adverse effects and potential regenerative role. The results confirmed the efficacy of clozapine in clinical practice, although limited by its adverse effects. It appears crucial to raise awareness among clinicians about the potential benefits of using Clozapine, as well educating medical personnel about its risks and the early identification of possible adverse effects and their management. Full article

(This article belongs to the Section Neuropsychiatry)

15 pages, 5109 KiB

Open AccessEditor’s ChoiceReview

The Role of Calcium and Iron Homeostasis in Parkinson’s Disease

by Ji Wang, Jindong Zhao, Kunying Zhao, Shangpeng Wu, Xinglong Chen and Weiyan Hu

Brain Sci. 2024, 14(1), 88; https://doi.org/10.3390/brainsci14010088 - 17 Jan 2024

Cited by 12 | Viewed by 4502

Abstract

Calcium and iron are essential elements that regulate many important processes of eukaryotic cells. Failure to maintain homeostasis of calcium and iron causes cell dysfunction or even death. PD (Parkinson’s disease) is the second most common neurological disorder in humans, for which there [...] Read more.

Calcium and iron are essential elements that regulate many important processes of eukaryotic cells. Failure to maintain homeostasis of calcium and iron causes cell dysfunction or even death. PD (Parkinson’s disease) is the second most common neurological disorder in humans, for which there are currently no viable treatment options or effective strategies to cure and delay progression. Pathological hallmarks of PD, such as dopaminergic neuronal death and intracellular α-synuclein deposition, are closely involved in perturbations of iron and calcium homeostasis and accumulation. Here, we summarize the mechanisms by which Ca²⁺ signaling influences or promotes PD progression and the main mechanisms involved in ferroptosis in Parkinson’s disease. Understanding the mechanisms by which calcium and iron imbalances contribute to the progression of this disease is critical to developing effective treatments to combat this devastating neurological disorder. Full article

(This article belongs to the Special Issue Molecular Mechanism and Pathology of Parkinson's Disease)

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13 pages, 2296 KiB

Open AccessEditor’s ChoiceReview

Update on How to Approach a Patient with Locked-In Syndrome and Their Communication Ability

by Kaitlyn Voity, Tara Lopez, Jessie P. Chan and Brian D. Greenwald

Brain Sci. 2024, 14(1), 92; https://doi.org/10.3390/brainsci14010092 - 17 Jan 2024

Cited by 6 | Viewed by 5374

Abstract

Locked-in syndrome (LIS) is a rare and challenging condition that results in tetraplegia and cranial nerve paralysis while maintaining consciousness and variable cognitive function. Once acute management is completed, it is important to work with the patient on developing a plan to maintain [...] Read more.

Locked-in syndrome (LIS) is a rare and challenging condition that results in tetraplegia and cranial nerve paralysis while maintaining consciousness and variable cognitive function. Once acute management is completed, it is important to work with the patient on developing a plan to maintain and improve their quality of life (QOL). A key component towards increasing or maintaining QOL within this population involves the establishment of a functional communication system. Evaluating cognition in patients with LIS is vital for evaluating patients’ communication needs along with physical rehabilitation to maximize their QOL. In the past decade or so, there has been an increase in research surrounding brain–computer interfaces to improve communication abilities for paralyzed patients. This article provides an update on the available technology and the protocol for finding the best way for patients with this condition to communicate. This article aims to increase knowledge of how to enhance and manage communication among LIS patients. Full article

(This article belongs to the Special Issue Recent Advances in Assessment and Rehabilitation of Individuals with Communication and Language Disorders)

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15 pages, 278 KiB

Open AccessEditor’s ChoiceReview

The Clinical Relevance of Artificial Intelligence in Migraine

by Angelo Torrente, Simona Maccora, Francesco Prinzi, Paolo Alonge, Laura Pilati, Antonino Lupica, Vincenzo Di Stefano, Cecilia Camarda, Salvatore Vitabile and Filippo Brighina

Brain Sci. 2024, 14(1), 85; https://doi.org/10.3390/brainsci14010085 - 16 Jan 2024

Cited by 11 | Viewed by 3801

Abstract

Migraine is a burdensome neurological disorder that still lacks clear and easily accessible diagnostic biomarkers. Furthermore, a straightforward pathway is hard to find for migraineurs’ management, so the search for response predictors has become urgent. Nowadays, artificial intelligence (AI) has pervaded almost every [...] Read more.

Migraine is a burdensome neurological disorder that still lacks clear and easily accessible diagnostic biomarkers. Furthermore, a straightforward pathway is hard to find for migraineurs’ management, so the search for response predictors has become urgent. Nowadays, artificial intelligence (AI) has pervaded almost every aspect of our lives, and medicine has not been missed. Its applications are nearly limitless, and the ability to use machine learning approaches has given researchers a chance to give huge amounts of data new insights. When it comes to migraine, AI may play a fundamental role, helping clinicians and patients in many ways. For example, AI-based models can increase diagnostic accuracy, especially for non-headache specialists, and may help in correctly classifying the different groups of patients. Moreover, AI models analysing brain imaging studies reveal promising results in identifying disease biomarkers. Regarding migraine management, AI applications showed value in identifying outcome measures, the best treatment choices, and therapy response prediction. In the present review, the authors introduce the various and most recent clinical applications of AI regarding migraine. Full article

(This article belongs to the Special Issue Deep into the Brain: Artificial Intelligence in Brain Diseases)

38 pages, 4875 KiB

Open AccessEditor’s ChoiceReview

Minimal Clinically Important Difference of Scales Reported in Stroke Trials: A Review

by Biswamohan Mishra, Pachipala Sudheer, Ayush Agarwal, Nilima Nilima, Madakasira Vasantha Padma Srivastava and Venugopalan Y. Vishnu

Brain Sci. 2024, 14(1), 80; https://doi.org/10.3390/brainsci14010080 - 13 Jan 2024

Cited by 10 | Viewed by 4958

Abstract

There is a growing awareness of the significance of using minimum clinically important differences (MCIDs) in stroke research. An MCID is the smallest change in an outcome measure that is considered clinically meaningful. This review is the first to provide a comprehensive summary [...] Read more.

There is a growing awareness of the significance of using minimum clinically important differences (MCIDs) in stroke research. An MCID is the smallest change in an outcome measure that is considered clinically meaningful. This review is the first to provide a comprehensive summary of various scales and patient-reported outcome measures (PROMs) used in stroke research and their MCID values reported in the literature, including a concise overview of the concept of and methods for determining MCIDs in stroke research. Despite the controversies and limitations surrounding the estimation of MCIDs, their importance in modern clinical trials cannot be overstated. Anchor-based and distribution-based methods are recommended for estimating MCIDs, with patient self-evaluation being a crucial component in capturing the patient’s perspective on their health. A combination of methods can provide a more comprehensive understanding of the clinical relevance of treatment effects, and incorporating the patient’s perspective can enhance the care of stroke patients. Full article

(This article belongs to the Section Neurorehabilitation)

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10 pages, 1982 KiB

Open AccessEditor’s ChoiceOpinion

Adaptation of the Concept of Brain Reserve for the Prediction of Stroke Outcome: Proxies, Neural Mechanisms, and Significance for Research

by Roza M. Umarova, Laura Gallucci, Arsany Hakim, Roland Wiest, Urs Fischer and Marcel Arnold

Brain Sci. 2024, 14(1), 77; https://doi.org/10.3390/brainsci14010077 - 12 Jan 2024

Cited by 6 | Viewed by 1916

Abstract

The prediction of stroke outcome is challenging due to the high inter-individual variability in stroke patients. We recently suggested the adaptation of the concept of brain reserve (BR) to improve the prediction of stroke outcome. This concept was initially developed alongside the one [...] Read more.

The prediction of stroke outcome is challenging due to the high inter-individual variability in stroke patients. We recently suggested the adaptation of the concept of brain reserve (BR) to improve the prediction of stroke outcome. This concept was initially developed alongside the one for the cognitive reserve for neurodegeneration and forms a valuable theoretical framework to capture high inter-individual variability in stroke patients. In the present work, we suggest and discuss (i) BR-proxies—quantitative brain characteristics at the time stroke occurs (e.g., brain volume, hippocampus volume), and (ii) proxies of brain pathology reducing BR (e.g., brain atrophy, severity of white matter hyperintensities), parameters easily available from a routine MRI examination that might improve the prediction of stroke outcome. Though the influence of these parameters on stroke outcome has been partly reported individually, their independent and combined impact is yet to be determined. Conceptually, BR is a continuous measure determining the amount of brain structure available to mitigate and compensate for stroke damage, thus reflecting individual differences in neural resources and a capacity to maintain performance and recover after stroke. We suggest that stroke outcome might be defined as an interaction between BR at the time stroke occurs and lesion load. BR in stroke can potentially be influenced, e.g., by modifying cardiovascular risk factors. In addition to the potential power of the BR concept in a mechanistic understanding of inter-individual variability in stroke outcome and establishing individualized therapeutic approaches, it might help to strengthen the synergy of preventive measures in stroke, neurodegeneration, and healthy aging. Full article

(This article belongs to the Section Behavioral Neuroscience)

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30 pages, 1472 KiB

Open AccessEditor’s ChoiceReview

Pathophysiology to Risk Factor and Therapeutics to Treatment Strategies on Epilepsy

by Ana Paula de Araújo Boleti, Pedro Henrique de Oliveira Cardoso, Breno Emanuel Farias Frihling, Luiz Filipe Ramalho Nunes de Moraes, Ellynes Amancio Correia Nunes, Lincoln Takashi Hota Mukoyama, Ellydberto Amancio Correia Nunes, Cristiano Marcelo Espinola Carvalho, Maria Lígia Rodrigues Macedo and Ludovico Migliolo

Brain Sci. 2024, 14(1), 71; https://doi.org/10.3390/brainsci14010071 - 10 Jan 2024

Cited by 12 | Viewed by 7973

Abstract

Epilepsy represents a condition in which abnormal neuronal discharges or the hyperexcitability of neurons occur with synchronicity, presenting a significant public health challenge. Prognostic factors, such as etiology, electroencephalogram (EEG) abnormalities, the type and number of seizures before treatment, as well as the [...] Read more.

Epilepsy represents a condition in which abnormal neuronal discharges or the hyperexcitability of neurons occur with synchronicity, presenting a significant public health challenge. Prognostic factors, such as etiology, electroencephalogram (EEG) abnormalities, the type and number of seizures before treatment, as well as the initial unsatisfactory effects of medications, are important considerations. Although there are several third-generation antiepileptic drugs currently available, their multiple side effects can negatively affect patient quality of life. The inheritance and etiology of epilepsy are complex, involving multiple underlying genetic and epigenetic mechanisms. Different neurotransmitters play crucial roles in maintaining the normal physiology of different neurons. Dysregulations in neurotransmission, due to abnormal transmitter levels or changes in their receptors, can result in seizures. In this review, we address the roles played by various neurotransmitters and their receptors in the pathophysiology of epilepsy. Furthermore, we extensively explore the neurological mechanisms involved in the development and progression of epilepsy, along with its risk factors. Furthermore, we highlight the new therapeutic targets, along with pharmacological and non-pharmacological strategies currently employed in the treatment of epileptic syndromes, including drug interventions employed in clinical trials related to epilepsy. Full article

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

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24 pages, 3328 KiB

Open AccessEditor’s ChoiceReview

Being in Virtual Reality and Its Influence on Brain Health—An Overview of Benefits, Limitations and Prospects

by Beata Sokołowska

Brain Sci. 2024, 14(1), 72; https://doi.org/10.3390/brainsci14010072 - 10 Jan 2024

Cited by 13 | Viewed by 8524

Abstract

Background: Dynamic technological development and its enormous impact on modern societies are posing new challenges for 21st-century neuroscience. A special place is occupied by technologies based on virtual reality (VR). VR tools have already played a significant role in both basic and clinical [...] Read more.

Background: Dynamic technological development and its enormous impact on modern societies are posing new challenges for 21st-century neuroscience. A special place is occupied by technologies based on virtual reality (VR). VR tools have already played a significant role in both basic and clinical neuroscience due to their high accuracy, sensitivity and specificity and, above all, high ecological value. Objective: Being in a digital world affects the functioning of the body as a whole and its individual systems. The data obtained so far, both from experimental and modeling studies, as well as (clinical) observations, indicate their great and promising potential, but apart from the benefits, there are also losses and negative consequences for users. Methods: This review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework across electronic databases (such as Web of Science Core Collection; PubMed; and Scopus, Taylor & Francis Online and Wiley Online Library) to identify beneficial effects and applications, as well as adverse impacts, especially on brain health in human neuroscience. Results: More than half of these articles were published within the last five years and represent state-of-the-art approaches and results (e.g., 54.7% in Web of Sciences and 63.4% in PubMed), with review papers accounting for approximately 16%. The results show that in addition to proposed novel devices and systems, various methods or procedures for testing, validation and standardization are presented (about 1% of articles). Also included are virtual developers and experts, (bio)(neuro)informatics specialists, neuroscientists and medical professionals. Conclusions: VR environments allow for expanding the field of research on perception and cognitive and motor imagery, both in healthy and patient populations. In this context, research on neuroplasticity phenomena, including mirror neuron networks and the effects of applied virtual (mirror) tasks and training, is of interest in virtual prevention and neurogeriatrics, especially in neurotherapy and neurorehabilitation in basic/clinical and digital neuroscience. Full article

(This article belongs to the Special Issue Perception, Motor Imagery, and Action in Real Research and Virtual Environments)

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18 pages, 1338 KiB

Open AccessEditor’s ChoiceArticle

Autistic Traits as Predictors of Increased Obsessive–Compulsive Disorder Severity: The Role of Inflexibility and Communication Impairment

by Liliana Dell’Osso, Benedetta Nardi, Chiara Bonelli, Giulia Amatori, Maria Alessandra Pereyra, Enrico Massimetti, Ivan Mirko Cremone, Stefano Pini and Barbara Carpita

Brain Sci. 2024, 14(1), 64; https://doi.org/10.3390/brainsci14010064 - 9 Jan 2024

Cited by 6 | Viewed by 4551

Abstract

Due to similar manifestations, some authors have proposed a potential correlation between autism spectrum disorder (ASD) and obsessive–compulsive disorder (OCD). This link has long been recognized and debated, with some authors arguing that these disorders frequently occur comorbid but distinct while others believe [...] Read more.

Due to similar manifestations, some authors have proposed a potential correlation between autism spectrum disorder (ASD) and obsessive–compulsive disorder (OCD). This link has long been recognized and debated, with some authors arguing that these disorders frequently occur comorbid but distinct while others believe they are part of the same spectrum. The aim of our study was to explore the prevalence and correlates of autistic traits in 55 OCD patients and 55 matched controls and to assess possible autistic dimensions predictive of higher OCD symptoms. All participants were assessed with the Obsessive–Compulsive Spectrum-Short Version (OBS-SV) and the Adult Autism Subthreshold Spectrum (AdAS Spectrum). The OCD group scored significantly higher in both questionnaires. Total OBS-SV scores and domains were significantly correlated with all AdAS Spectrum domains and total score. The AdAS Spectrum total, Verbal Communication and Inflexibility and adherence to routine domain scores were significant positive predictors of higher OBS-SV scores. Lastly, when two clusters of subjects (high and low autism) were determined, Inflexibility and adherence to routine domain presented the greatest influence in forming the clusters. Our findings support the association between OCD and autistic traits in the adult population, supporting the hypothesis of a neurodevelopmental basis for these psychiatric conditions. Full article

(This article belongs to the Section Neuropsychiatry)

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11 pages, 865 KiB

Open AccessEditor’s ChoiceArticle

The Association between Working Memory and Divergent Thinking: The Moderating Role of Formal Musical Background

by Maria Chiara Pino, Marco Giancola, Massimiliano Palmiero and Simonetta D’Amico

Brain Sci. 2024, 14(1), 61; https://doi.org/10.3390/brainsci14010061 - 8 Jan 2024

Viewed by 5056

Abstract

Divergent thinking (DT) is widely considered an essential cognitive dimension of creativity, which involves goal-oriented processes, including working memory (WM), which allows for retrieving and loading of information into the attentional stream and, consequently, enhancing divergence of thinking. Despite the critical role of [...] Read more.

Divergent thinking (DT) is widely considered an essential cognitive dimension of creativity, which involves goal-oriented processes, including working memory (WM), which allows for retrieving and loading of information into the attentional stream and, consequently, enhancing divergence of thinking. Despite the critical role of WM in DT, little work has been done on the mechanism affecting this interplay. The current study addressed the involvement of a formal musical background in the relationship between WM and DT and was conducted with 83 healthy young adults (M = 19.64 years; SD = 0.52 years; 33 females). The participants were requested to indicate if they had a formal background in music in the conservatory (M = 4.78 years; SD = 5.50 years) as well as perform the digit span forward test (DSFT) and the alternative uses task—AUT from the Torrance test of creative thinking (TTCT). The results indicated that years of formal musical background moderated the association between WM and DT. These findings suggest that music enhances the positive effect of high-order cognitive processes, such as WM, on the ability to think divergently. Theoretical and practical implications as well as limitations were discussed. Full article

(This article belongs to the Special Issue The Role of Sounds and Music in Emotion and Cognition)

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14 pages, 662 KiB

Open AccessEditor’s ChoiceSystematic Review

Effects of Resistance Training on Spasticity in People with Stroke: A Systematic Review

by Juan Carlos Chacon-Barba, Jose A. Moral-Munoz, Amaranta De Miguel-Rubio and David Lucena-Anton

Brain Sci. 2024, 14(1), 57; https://doi.org/10.3390/brainsci14010057 - 6 Jan 2024

Cited by 3 | Viewed by 6509

Abstract

Resistance training induces neuromuscular adaptations and its impact on spasticity remains inadequately researched. This systematic review (PROSPERO: CRD42022322164) aimed to analyze the effects of resistance training, compared with no treatment, conventional therapy, or other therapies, in people with stroke-related spasticity. A comprehensive search [...] Read more.

Resistance training induces neuromuscular adaptations and its impact on spasticity remains inadequately researched. This systematic review (PROSPERO: CRD42022322164) aimed to analyze the effects of resistance training, compared with no treatment, conventional therapy, or other therapies, in people with stroke-related spasticity. A comprehensive search was conducted up to October 2023 in PubMed, PEDro, Cochrane, Web of Science, and Scopus databases. Selection criteria were randomized controlled trials involving participants with stroke-related spasticity intervened with resistance training. The PEDro scale was used to evaluate the methodological quality. From a total of 274 articles, 23 full-text articles were assessed for eligibility and nine articles were included in the systematic review, involving 225 participants (155 males, 70 females; mean age: 59.4 years). Benefits were found to spasticity after resistance training. Furthermore, studies measuring spasticity also reported benefits to function, strength, gait, and balance. In conclusion, resistance training was superior to, or at least equal to, conventional therapy, other therapies, or no intervention for improving spasticity, as well as function, strength, gait, and balance. However, the results should be taken with caution because of the heterogeneity of the protocols used. Further research is needed to explore the effects of resistance training programs on people with stroke. Full article

(This article belongs to the Special Issue Post-stroke Rehabilitation)

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16 pages, 1928 KiB

Open AccessEditor’s ChoiceReview

Brain Health and Cognition in Older Adults: Roadmap and Milestones towards the Implementation of Preventive Strategies

by Federico Emanuele Pozzi, Giulia Remoli, Lucio Tremolizzo, Ildebrando Appollonio, Carlo Ferrarese and Luca Cuffaro

Brain Sci. 2024, 14(1), 55; https://doi.org/10.3390/brainsci14010055 - 6 Jan 2024

Cited by 2 | Viewed by 5633

Abstract

In this narrative review, we delve into the evolving concept of brain health, as recognized by the WHO, focusing on its intersection with cognitive decline. We emphasize the imperative need for preventive strategies, particularly in older adults. We describe the target population that [...] Read more.

In this narrative review, we delve into the evolving concept of brain health, as recognized by the WHO, focusing on its intersection with cognitive decline. We emphasize the imperative need for preventive strategies, particularly in older adults. We describe the target population that might benefit the most from risk-based approaches—namely, people with subjective cognitive decline. Additionally, we consider universal prevention in cognitively unimpaired middle-aged and older adults. Delving into multidomain personalized preventive strategies, we report on empirical evidence surrounding modifiable risk factors and interventions crucial in mitigating cognitive decline. Next, we highlight the emergence of brain health services (BHS). We explain their proposed role in risk assessment, risk communication, and tailored interventions to reduce the risk of dementia. Commenting on ongoing BHS pilot experiences, we present the inception and framework of our own BHS in Monza, Italy, outlining its operational structure and care pathways. We emphasize the need for global collaboration and intensified research efforts to address the intricate determinants of brain health and their potential impact on healthcare systems worldwide. 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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30 pages, 1610 KiB

Open AccessEditor’s ChoiceReview

Understanding the Neurotrophic Virus Mechanisms and Their Potential Effect on Systemic Lupus Erythematosus Development

by Felipe R. Uribe, Valentina P. I. González, Alexis M. Kalergis, Jorge A. Soto and Karen Bohmwald

Brain Sci. 2024, 14(1), 59; https://doi.org/10.3390/brainsci14010059 - 6 Jan 2024

Cited by 3 | Viewed by 6016

Abstract

Central nervous system (CNS) pathologies are a public health concern, with viral infections one of their principal causes. These viruses are known as neurotropic pathogens, characterized by their ability to infiltrate the CNS and thus interact with various cell populations, inducing several diseases. [...] Read more.

Central nervous system (CNS) pathologies are a public health concern, with viral infections one of their principal causes. These viruses are known as neurotropic pathogens, characterized by their ability to infiltrate the CNS and thus interact with various cell populations, inducing several diseases. The immune response elicited by neurotropic viruses in the CNS is commanded mainly by microglia, which, together with other local cells, can secrete inflammatory cytokines to fight the infection. The most relevant neurotropic viruses are adenovirus (AdV), cytomegalovirus (CMV), enterovirus (EV), Epstein–Barr Virus (EBV), herpes simplex virus type 1 (HSV-1), and herpes simplex virus type 2 (HSV-2), lymphocytic choriomeningitis virus (LCMV), and the newly discovered SARS-CoV-2. Several studies have associated a viral infection with systemic lupus erythematosus (SLE) and neuropsychiatric lupus (NPSLE) manifestations. This article will review the knowledge about viral infections, CNS pathologies, and the immune response against them. Also, it allows us to understand the relevance of the different viral proteins in developing neuronal pathologies, SLE and NPSLE. Full article

(This article belongs to the Special Issue Immune Responses to Viruses in the Central Nervous System)

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