Editor’s Choice Articles

Bisphenol A diglycidyl ether (BADGE) is the main component of epoxy resin and is used for the inner coating of canned foods and plastic food containers. BADGE can easily migrate from containers and result in food contamination; the compound is known as an endocrine-disrupting chemical. We previously reported that maternal exposure to bisphenol A bis (2,3-dihydroxypropyl) ether (BADGE·2H₂O), which is the most detected BADGE derivative not only in canned foods but also in human specimens, during gestation and lactation, could accelerate neuronal differentiation in the cortex of fetuses and induce anxiety-like behavior in juvenile mice. In this study, we investigated the effects of low-dose BADGE·2H₂O (1–100 pM) treatment on neurites and the mechanism of neurite outgrowth in cortical neurons. BADGE·2H₂O exposure significantly increased the number of dendrites and neurite length in cortical neurons; these accelerating effects were inhibited by estrogen receptor (ER) antagonist ICI 182,780 and G-protein-coupled estrogen receptor (GPER) antagonist G15. BADGE·2H₂O down-regulated Hes1 expression, which is a transcriptional repressor, and increased levels of neuritogenic factor neurogenin-3 (Ngn3) in the cortical neurons; the changes were significantly blocked by G15. These data suggest that direct BADGE·2H₂O exposure can accelerate neuritogenesis and outgrowth in cortical neurons through down-regulation of Hes1 and by increasing Ngn3 levels through ERs, particularly GPER. Full article

In recent years, in the pathogenesis of multiple sclerosis, emphasis has been placed on mitochondrial processes that influence the onset of the disease. Oxidative stress would be one of the consequences of mitochondrial dysfunction, and its impact on brain tissue is well described. Microglia, as a brain macrophage, have an important function in removing unwanted metabolites, as well as iron, which is an amplifier of oxidative stress. There are novelties in terms of the connection between these processes, which have redirected research more towards the process of neurodegeneration itself, so that the emphasis is no longer on neuroinflammation, which would initiate the pathological process itself and still exist in the vicinity of lesions with reduced intensity. The aim of this review is to summarize the current knowledge from the literature regarding oxidative stress, mitochondrial dysfunction and iron metabolism and how microglia are involved in these processes in multiple sclerosis. Full article

Alzheimer’s disease is the most common form of dementia. Benzodiazepines are the most widely used pharmacological class in the treatment of insomnia and other sleep disorders. Some literature suggests that the chronic use of benzodiazepines is associated with the development of cognitive decline. This review aims to evaluate the use of benzodiazepines and its association with the development of Alzheimer’s disease. A systematic review of the literature was carried out using the MEDLINE and Embase databases. Protocols followed the PRISMA-P 2020 methodology, and, after the analysis of the included studies, a narrative synthesis of the results was carried out. Only two cohort studies were identified that met defined eligibility criteria. In the retrospective study, a significant risk of developing Alzheimer’s disease after treatment with benzodiazepines was found. In the prospective study, the prevalence of Alzheimer’s disease was not associated with treatment with benzodiazepines. Results suggest that only the largest study presented a significant risk of developing Alzheimer’s disease. Given the scarce scientific evidence found, it is concluded that further research on this topic is necessary. Full article

Background: Hypokinetic dysarthria is a speech disorder observed in almost 90% of PD patients that can appear at any stage of the disease, usually worsening as the disease progresses. Today, speech therapy intervention in PD is seen as a possible therapeutic option to alleviate and slow down the progression of symptoms. This study aims to investigate the validity of traditional speech therapy in dysarthria with the aim of improving the quality of life of PD patients, by comparing subjective clinical assessment with objective instrumental measures (IOPI and voice analysis). Methods: This is an observational study of 30 patients with hypokinetic dysarthria due to PD. The patients underwent speech therapy treatment with a frequency of three times per week for 12 consecutive weeks. Patients were evaluated at the time of enrollment (T0), at the start of treatment (T1), and at the end of the same (T2). Six months after the end of treatment (T3), a follow-up was performed based on disability and phonatory evaluation. Results: This study showed significant improvements (<0.001) from the start (T1) to the end of treatment (T2), with increases in the Barthel Index score, Robertson Dysarthria Profile, and IOPI measurements for tongue and lip strength, along with enhanced phonometer scores and tongue endurance. Correlations highlighted that tongue endurance decreased with age, CIRS, and MDS-UPDRS, while showing a positive association with MoCA scores. Conclusions: Significant improvements were observed in tongue and lip strength, phonatory duration, intensity, and vocal quality between pre- (T1) and post-treatment (T2). This study underscores the importance of early and continuous speech therapy treatment for comprehensive speech function enhancement. Full article

Dementia, including Alzheimer’s disease (AD) and frontotemporal dementia (FTD), presents critical challenges for correctional systems, particularly as global populations age. AD, affecting 60–80% of dementia cases, primarily impairs memory and cognition in individuals over 65. In contrast, FTD, rarer than AD but not uncommon in those under 65, affects the frontal and temporal brain regions, leading to deficits in social behavior, language, and impulse control, often resulting in antisocial actions and legal consequences. Behavioral variant FTD is especially associated with socially inappropriate and impulsive behaviors due to frontal lobe degeneration. The prevalence of cognitive impairment in incarcerated populations is high, exacerbated by prison environments that compound distress and limited access to specialized healthcare. Studies indicate that up to 11% of United States state prison inmates over the age of 55 exhibit cognitive impairments, often undiagnosed, resulting in punitive rather than rehabilitative responses to symptoms like disinhibition and aggression. Ethical concerns around criminal responsibility for individuals with dementia are increasingly prominent, particularly regarding their ability to comprehend and engage in legal proceedings. The growing elderly prison population necessitates reform in correctional healthcare to include early cognitive assessment, targeted intervention, and tailored post-release programs. Addressing these needs is essential to ensure appropriate treatments, alleviate healthcare demands, and support reintegration for cognitively impaired inmates. Full article

Trehalose is a naturally occurring disaccharide that has recently gained significant attention for its neuroprotective properties in various models of neurodegeneration. This review provides an overview of available experimental data on the beneficial properties of trehalose for central nervous system pathological conditions. Trehalose’s impact on neuronal cell survival and function was also examined. As a result, we identified that trehalose’s neuroprotection includes autophagy modulation as well as its capability to stabilize proteins and inhibit the formation of misfolded ones. Moreover, trehalose mitigates oxidative stress-induced neuronal damage by stabilizing cellular membranes and modulating mitochondrial function. Furthermore, trehalose attenuates excitotoxicity-induced neuroinflammation by suppressing pro-inflammatory cytokine release and inhibiting inflammasome activation. A possible connection of trehalose with the gut–brain axis was also examined. These findings highlight the potential therapeutic effects of trehalose in neurodegenerative diseases. According to the conclusions drawn from this study, trehalose is a promising neuroprotective agent as a result of its distinct mechanism of action, which makes this compound a candidate for further research and the development of therapeutic strategies to combat neuronal damage and promote neuroprotection in various neurological diseases. Full article

Detecting stress is important for improving human health and potential, because moderate levels of stress may motivate people towards better performance at cognitive tasks, while chronic stress exposure causes impaired performance and health risks. We propose a Brain–Computer Interface (BCI) system to detect stress in the context of high-pressure work environments. The BCI system includes an electroencephalogram (EEG) headband with dry electrodes and an electrocardiogram (ECG) chest belt. We collected EEG and ECG data from 40 participants during two stressful cognitive tasks: the Cognitive Vigilance Task (CVT), and the Multi-Modal Integration Task (MMIT) we designed. We also recorded self-reported stress levels using the Dundee Stress State Questionnaire (DSSQ). The DSSQ results indicated that performing the MMIT led to significant increases in stress, while performing the CVT did not. Subsequently, we trained two different models to classify stress from non-stress states, one using EEG features, and the other using heart rate variability (HRV) features extracted from the ECG. Our EEG-based model achieved an overall accuracy of 81.0% for MMIT and 77.2% for CVT. However, our HRV-based model only achieved 62.1% accuracy for CVT and 56.0% for MMIT. We conclude that EEG is an effective predictor of stress in the context of stressful cognitive tasks. Our proposed BCI system shows promise in evaluating mental stress in high-pressure work environments, particularly when utilizing an EEG-based BCI. Full article

Over the last decade there has been increasing interest in the links between the consumption of ultra-processed foods and various neuropsychiatric disorders, aggression, and antisocial behavior. Neurolaw is an interdisciplinary field that seeks to translate the rapid and voluminous advances in brain science into legal decisions and policy. An enhanced understanding of biophysiological mechanisms by which ultra-processed foods influence brain and behavior allows for a historical reexamination of one of forensic neuropsychiatry’s most famous cases—The People v. White and its associated ‘Twinkie Defense’. Here in this Viewpoint article, we pair original court transcripts with emergent research in neurolaw, including nutritional neuroscience, microbiome sciences (legalome), pre-clinical mechanistic research, and clinical intervention trials. Advances in neuroscience, and related fields such as the microbiome, are challenging basic assumptions in the criminal justice system, including notions of universal free will. Recent dismissals of criminal charges related to auto-brewery syndrome demonstrate that courts are open to advances at the intersection of neuromicrobiology and nutritional neuroscience, including those that relate to criminal intent and diminished capacity. As such, it is our contention that experts in the neurosciences will play an increasing role in shaping research that underpins 21st-century courtroom discourse, policy, and decision-making. Full article

The maintenance of energetic homeostasis relies on a tight balance between glycolysis and mitochondrial oxidative phosphorylation. The case of the brain is a peculiar one, as although entailing a constant demand for energy, it is believed to rely mostly on glucose, particularly at the level of neurons. Nonetheless, this has been challenged by studies that show that alternatives such as lactate, ketone bodies, and glutamate can be used as fuels to sustain neuronal activity. The importance of fatty acid (FA) metabolism to this extent is still unclear, albeit sustaining a significant energetic output when compared to glucose. While several authors postulate a possible role of FA for the energetic homeostasis of the brain, several others point out the intrinsic features of this pathway that make its contribution difficult to explain in the context of neuronal bioenergetics. Moreover, fueling preference at the synapse level is yet to be uncovered. In this review, we discuss in detail the arguments for and against the brain usage of FA. Furthermore, we postulate that the importance of this fuel may be greater at the synapse, where local mitochondria possess a set of features that enable a more effective usage of this fuel source. Full article

People with Huntington’s disease (HD) often experience psychological difficulties linked with disease progression and the adjustment to living with a chronic condition, which are also frequently shared by their informal caregivers (e.g., partners). Although limited, the current literature on psychological care for people with HD shows that interventions have the potential to drive improvements in mental health and quality of life. However, the experience of accessing and receiving psychological support for HD remains unclear across several countries. This study adopted a qualitative design to explore the experiences of psychological support for HD from the perspectives of patients and caregivers living in Italy. Semi-structured interviews were carried out with 14 participants—7 patients with early-manifest HD and 7 partners acting as their caregivers. The resulting data were analysed through thematic analysis. Four overarching themes were identified: (1) the availability of psychological support for HD, (2) barriers to accessing psychological support, (3) enablers to accessing psychological support, and (4) the future development of public psychological provision for HD. In Italy, patients and caregivers perceive public psychological support for HD as unavailable or inadequate, and private therapy is often seen as unaffordable. Barriers such as distrust in public healthcare and preconceptions about therapy may limit access, while advice from HD organisations and seeking therapy for other reasons may act as enablers. A strong emphasis is put on the need for accessible public psychological support throughout all the stages of the condition. Full article

The search for new therapies to reduce symptoms and find a cure for Parkinson’s disease has focused attention on two key points: the accumulation of alpha-synuclein aggregates and astrocytes. The former is a hallmark of the disease, while the latter corresponds to a type of glial cell with an important role in both the prevention and development of this neurodegenerative disorder. Traditionally, research has focused on therapies targeting dopaminergic neurons. Currently, as more is known about the genetic and molecular factors and the neuroglial interaction in the disease, great emphasis has been placed on the neuroprotective role of astrocytes in the early stages of the disease and on the astrocytic capture of alpha-synuclein under both physiological and pathological conditions. This review aims to analyze the contribution of alpha-synuclein and astrocytes to the development and progression of Parkinson’s disease, as well as to evaluate recent therapeutic proposals specifically focused on synucleopathies and astroglial cells as potential therapies for the disease. Full article

Evidence has been provided for a clear structural distinction between the dorsal and ventral portions of the inferior frontal occipital fasciculus (IFOF). As such, there is reason to propose that there might also be a functional differentiation of the dorsal and ventral components of the IFOF. Here, we explored three main hypotheses/schools of thought with regards to the functional frameworks of the dorsal and ventral components of the IFOF: (1) the phonological vs. semantic processing hypothesis, (2) the difficult vs. non-difficult task processing hypothesis and (3) the automatic vs. non-automatic processing hypothesis. Methods: Participants (N = 32) completed a series of behavioral tasks that aligned with each of the main hypotheses. Using a regression-based approach, we assessed the unique contribution of behavioral performance to dorsal and ventral IFOF white matter indicators (i.e., fractional anisotropy and mean diffusivity). Results: We found significant relationships between ventral IFOF indices and orthographic awareness (p = 0.018) and accuracy (p = 0.009). Overall, our results provide converging evidence that the IFOF primarily operates as a ventral language tract in adults. Thus, the structural distinction between dorsal and ventral IFOF does not manifest as a parallel functional distinction. Full article

Narcolepsy is a chronic sleep disorder that disrupts the regulation of a person’s sleep–wake cycle, leading to significant challenges in daily functioning. It is characterized by excessive daytime sleepiness, sudden muscle weakness (cataplexy), sleep paralysis, and vivid hypnagogic hallucinations. A literature search was conducted in different databases to identify relevant studies on various aspects of narcolepsy. The main search terms included “narcolepsy”, “excessive daytime sleepiness”, “cataplexy”, and related terms. The search was limited to studies published until May 2023. This literature review aims to provide an overview of narcolepsy, encompassing its causes, diagnosis, treatment options, impact on individuals’ lives, prevalence, and recommendations for future research. The review reveals several important findings regarding narcolepsy: 1. the classification of narcolepsy—type 1 narcolepsy, previously known as narcolepsy with cataplexy, and type 2 narcolepsy, also referred to as narcolepsy without cataplexy; 2. the genetic component of narcolepsy and the complex nature of the disorder, which is characterized by excessive daytime sleepiness, disrupted sleep patterns, and potential impacts on daily life activities and social functioning; and 3. the important implications for clinical practice in the management of narcolepsy. Healthcare professionals should be aware of the different types of narcolepsies and their associated symptoms, as this can aid in accurate diagnosis and treatment planning. The review underscores the need for a multidisciplinary approach to narcolepsy management, involving specialists in sleep medicine, neurology, psychiatry, and psychology. Clinicians should consider the impact of narcolepsy on a person’s daily life, including their ability to work, study, and participate in social activities, and provide appropriate support and interventions. There are several gaps in knowledge regarding narcolepsy. Future research should focus on further elucidating the genetic causes and epigenetic mechanisms of narcolepsy and exploring potential biomarkers for early detection and diagnosis. Long-term studies assessing the effectiveness of different treatment approaches, including pharmacological interventions and behavioral therapies, are needed. Additionally, there is a need for research on strategies to improve the overall well-being and quality of life of individuals living with narcolepsy, including the development of tailored support programs and interventions. Full article

Multiple sclerosis (MS) is an immune inflammatory disease that causes demyelination of the white matter of the central nervous system. It is generally accepted that the etiology of MS is multifactorial and believed to be a complex interplay between genetic susceptibility, environmental factors, and infectious agents. While the exact cause of MS is still unknown, increasing evidence suggests that disease development is the result of interactions between genetically susceptible individuals and the environment that lead to immune dysregulation and CNS inflammation. Genetic factors are not sufficient on their own to cause MS, and environmental factors such as viral infections, smoking, and vitamin D deficiency also play important roles in disease development. Several pathogens have been implicated in the etiology of MS, including Epstein–Barr virus, human herpesvirus 6, varicella-zoster virus, cytomegalovirus, Helicobacter pylori, Chlamydia pneumoniae, and Borrelia burgdorferi. Although vastly different, viruses and bacteria can manipulate host gene expression, causing immune dysregulation, myelin destruction, and neuroinflammation. This review emphasizes the pathogenic triggers that should be considered in MS progression. Full article

Parkinson’s disease (PD) is known for its motor alterations, but the importance of non-motor symptoms (NMSs), such as olfactory dysfunction (OD), is increasingly recognized. OD may manifest during the prodromal period of the disease, even before motor symptoms appear. Therefore, it is suggested that this symptom could be considered a marker of PD. This article briefly describes PD, the evolution of the knowledge about OD in PD, the prevalence of this NMS and its role in diagnosis and as a marker of PD progression, the assessment of olfaction in patients with PD, the role of α-synuclein and its aggregates in the pathophysiology of PD, and then describes some functional, morphological, and histological alterations observed in different structures related to the olfactory system, such as the olfactory epithelium, olfactory bulb, anterior olfactory nucleus, olfactory tract, piriform cortex, hippocampus, orbitofrontal cortex, and amygdala. In addition, considering the growing evidence that suggests that the cerebellum is also involved in the olfactory system, it has also been included in this work. Comprehending the existing functional and neuroanatomical alterations in PD could be relevant for a better understanding of the mechanisms behind OD in patients with this neurodegenerative disorder. Full article

What is the significance of a touch encoded by slow-conducted unmyelinated C-tactile (CT) fibers? It is the so-called affiliative touch, which has a fundamental social impact. In humans, it has been demonstrated that the affiliative valence of this kind of touch is encoded by a dedicated central network, not involved in the encoding of discriminative touch, namely, the “social brain”. Moreover, CT-related touch has significant consequences on the human autonomic system, not present in the case of discriminative touch, which does not involve CT fibers as the modulation of vagal tone. In addition, CT-related touch provokes central effects as well. An interesting finding is that CT-related touch can elicit “mirror-like responses” since there is evidence that we would have the same perception of a caress regardless of whether it would be felt or seen and that the same brain areas would be activated. Information from CT afferents in the posterior insular cortex likely provides a basis for encoding observed caresses. We also explored the application of this kind of touch in unphysiological conditions and in premature newborns. In the present literature review, we aim to (1) examine the effects of CT-related touch at autonomic and central levels and (2) highlight CT-related touch and mirror networks, seeking to draw a line of connection between them. Finally, the review aims to give an overview of the involvement of the CT system in some neurologic and psychiatric diseases. Full article

In this perspective article, we show that a morphospace, based on information-theoretic measures, can be a useful construct for comparing biological agents with artificial intelligence (AI) systems. The axes of this space label three kinds of complexity: (i) autonomic, (ii) computational and (iii) social complexity. On this space, we map biological agents such as bacteria, bees, C. elegans, primates and humans; as well as AI technologies such as deep neural networks, multi-agent bots, social robots, Siri and Watson. A complexity-based conceptualization provides a useful framework for identifying defining features and classes of conscious and intelligent systems. Starting with cognitive and clinical metrics of consciousness that assess awareness and wakefulness, we ask how AI and synthetically engineered life-forms would measure on homologous metrics. We argue that awareness and wakefulness stem from computational and autonomic complexity. Furthermore, tapping insights from cognitive robotics, we examine the functional role of consciousness in the context of evolutionary games. This points to a third kind of complexity for describing consciousness, namely, social complexity. Based on these metrics, our morphospace suggests the possibility of additional types of consciousness other than biological; namely, synthetic, group-based and simulated. This space provides a common conceptual framework for comparing traits and highlighting design principles of minds and machines. Full article

(1) Background: Fluorescein sodium (Na-Fl) has been described as a safe and useful neurosurgical adjunct in adult neurooncology. However, its use has yet to be fully established in children. We designed a study to investigate the use of intraoperative Na-Fl in pediatric brain tumor surgery. (2) Methods: This is a single-institution study for pediatric brain tumor patients managed by the Neurosurgical Service, KK Women’s and Children’s Hospital. Inclusion criteria consists of patients undergoing surgery for suspected brain tumors from 3 to 19 years old. A predefined intravenous dose of 2 mg/kg of 10% Na-Fl is administered per patient. Following craniotomy, surgery is performed under alternating white light and YELLOW-560 nm filter illumination. (3) Results: A total of 21 patients with suspected brain tumours were included. Median age was 12.1 years old. For three patients (14.3%), there was no significant Na-Fl fluorescence detected and their final histologies reported a cavernoma and two radiation-induced high grade gliomas. The remaining patients (85.7%) had adequate intraoperative fluorescence for their lesions. No adverse side effects were encountered with the use of Na-Fl. (4) Conclusions: Preliminary findings demonstrate the safe and efficacious use of intraoperative Na-Fl for brain tumors as a neurosurgical adjunct in our pediatric patients. Full article

The new science called Sentiomics aims to identify the dynamic patterns that endow living systems with the capacity to feel and become conscious. One of the most promising fields of investigation in Sentiomics is the development and ‘education’ of human brain organoids to become sentient and useful for the promotion of human health in the (also new) field of Regenerative Neuromedicine. Here, we discuss the type of informational-rich input necessary to make a brain organoid sentient in experimental settings. Combining this research with the ecological preoccupation of preserving ways of sentience in the Amazon Rainforest, we also envisage the development of a new generation of biosensors to capture dynamic patterns from the forest, and use them in the ‘education’ of brain organoids to afford them a ‘mental health’ quality that is likely to be important in future advances in ‘post-humanist’ procedures in regenerative medicine. This study is closely related to the psychophysical approach to human mental health therapy, in which we have proposed the use of dynamic patterns in electric and magnetic brain stimulation protocols, addressing electrochemical waves in neuro-astroglial networks. Full article

Foveal (central) and peripheral vision are strongly interconnected to provide an integrated experience of the world around us. Recently, it has been suggested that there is a feedback mechanism that links foveal and peripheral vision. This peripheral-to-foveal feedback differs from other feedback mechanisms in that during visual processing a novel representation of a stimulus is formed in a different cortical region than that of the feedforward representation. The functional role of foveal feedback is not yet completely understood, but some evidence from neuroimaging studies suggests a link with peripheral shape processing. Behavioural and transcranial magnetic stimulation studies show impairment in peripheral shape discrimination when the foveal retinotopic cortex is disrupted post stimulus presentation. This review aims to link these findings to the visual sketchpad hypothesis. According to this hypothesis, foveal retinotopic cortex stores task-relevant information to aid identification of peripherally presented objects. We discuss how the characteristics of foveal feedback support this hypothesis and rule out other possible explanations. We also discuss the possibility that the foveal feedback may be independent of the sensory modality of the stimulation. Full article

For years, the biochemical processes that are triggered by harmful and non-harmful stimuli at the central nervous system level have been extensively studied by the scientific community through numerous techniques and animal models. For example, one of these techniques is the use of immediate expression genes, which is a useful, accessible, and reliable method for observing and quantifying cell activation. It has been shown that both the c-fos gene and its protein c-Fos have rapid activation after stimulus, with the length of time that they remain active depending on the type of stimulus and the activation time depending on the stimulus and the structure studied. Fos requires the participation of other genes (such as c-jun) for its expression (during hetero-dimer forming). c-Fos dimerizes with c-Jun protein to form factor AP-1, which promotes the transcription of various genes. The production and removal of c-Fos is part of cellular homeostasis, but its overexpression results in increased cell proliferation. Although Fos has been used as a marker of cellular activity since the 1990s, which molecular mechanism participates in the regulation of the expression of this protein is still unknown because the gene and the protein are not specific to neurons or glial cells. For these reasons, this work has the objective of gathering information about this protein and its use in neuroscience. Full article

Cognitive impairment (CI) is a core feature of multiple sclerosis (MS) and affects up to 65% of patients in every phase of the disease, having a deep impact on all aspects of patients’ lives. Cognitive functions most frequently involved include information processing speed, learning and memory, visuospatial abilities, and executive function. The precise pathogenetic mechanisms underpinning CI in MS are still largely unknown, but are deemed to be mainly related to pathological changes in lesioned and normal-appearing white matter, specific neuronal grey matter structures, and immunological alterations, with particular impact on synaptic transmission and plasticity. Moreover, much research is needed on therapeutic strategies. Small to moderate efficacy has been reported for disease-modifying therapies, particularly high-efficacy drugs, and symptomatic therapies (dalfampridine), while the strongest benefit emerged after cognitive training. The present narrative review provides a concise, updated overview of more recent evidence on the prevalence, profile, pathogenetic mechanisms, and treatment of CI in people with MS. CI should be screened on a regular basis as part of routine clinical assessments, and brief tools are now widely available (such as the Symbol Digit Modalities Test). The main goal of cognitive assessment in MS is the prompt implementation of preventive and treatment interventions. Full article

Cognitive impairment (CI) represents a common symptom in patients suffering from multiple sclerosis (MS), which can affect every stage of the disease course. Recent studies seem to support cognitive rehabilitation (CR) for minimizing the CI consequences. We reviewed the currently available evidence on the non-pharmacological approaches to CI, with the aim of giving an overview of the treatments used worldwide, from the traditional methods to the most recent techniques. A search of the literature was conducted on PubMed (articles in English performed in the last five years on humans). A total of 37 articles met our eligibility criteria after screening titles, abstracts and full-text and were divided into three main groups: in-presence interventions; studies performed via tele-rehabilitation and miscellaneous. Despite the great heterogeneity of the intervention and assessment methods, the evidence suggests that a non-pharmacological approach can improve MS-related CI. Cognitive rehabilitation seems effective and well established, as well as the use of computerized CR having the benefit of being even more appealing. Limited conclusions can be drawn on group CR due to the small number of studies focused on this kind of intervention. Some of the innovative approaches (virtual reality, EEG-based neurofeedback, brain stimulation, exercise, diet modification) may play a role in future studies and should be deeply explored. Full article

Reactive oxygen species (ROS) have emerged as regulators of key processes supporting neuronal growth, function, and plasticity across lifespan. At normal physiological levels, ROS perform important roles as secondary messengers in diverse molecular processes such as regulating neuronal differentiation, polarization, synapse maturation, and neurotransmission. In contrast, high levels of ROS are toxic and can ultimately lead to cell death. Excitable cells, such as neurons, often require high levels of metabolic activity to perform their functions. As a consequence, these cells are more likely to produce high levels of ROS, potentially enhancing their susceptibility to oxidative damage. In addition, because neurons are generally post-mitotic, they may be subject to accumulating oxidative damage. Thus, maintaining tight control over ROS concentration in the nervous system is essential for proper neuronal development and function. We are developing a more complete understanding of the cellular and molecular mechanisms for control of ROS in these processes. This review focuses on ROS regulation of the developmental and functional properties of neurons, highlighting recent in vivo studies. We also discuss the current evidence linking oxidative damage to pathological conditions associated with neurodevelopmental and neurodegenerative disorders. Full article

The blood-spinal cord barrier (BSCB) has been long thought of as a functional equivalent to the blood-brain barrier (BBB), restricting blood flow into the spinal cord. The spinal cord is supported by various disc tissues that provide agility and has different local immune responses compared to the brain. Though physiologically, structural components of the BSCB and BBB share many similarities, the clinical landscape significantly differs. Thus, it is crucial to understand the composition of BSCB and also to establish the cause–effect relationship with aberrations and spinal cord dysfunctions. Here, we provide a descriptive analysis of the anatomy, current techniques to assess the impairment of BSCB, associated risk factors and impact of spinal disorders such as spinal cord injury (SCI), amyotrophic lateral sclerosis (ALS), peripheral nerve injury (PNI), ischemia reperfusion injury (IRI), degenerative cervical myelopathy (DCM), multiple sclerosis (MS), spinal cavernous malformations (SCM) and cancer on BSCB dysfunction. Along with diagnostic and mechanistic analyses, we also provide an up-to-date account of available therapeutic options for BSCB repair. We emphasize the need to address BSCB as an individual entity and direct future research towards it. Full article

The conscious electromagnetic information (cemi) field theory proposes that the seat of consciousness is the brain’s electromagnetic (EM) field that integrates information from trillions of firing neurons. What we call free will is its output. The cemi theory also proposes that the brain has two streams. Most actions are initiated by the first non-conscious stream that is composed of neurons that are insulated from EM field influences. These non-conscious involuntary actions are thereby invisible to our EM field-located thoughts. The theory also proposes that voluntary actions are driven by neurons that receive EM field inputs and are thereby visible to our EM field-located thoughts. I review the extensive evidence for EM field/ephaptic coupling between neurons and the increasing evidence that EM fields in the brain are a cause of behaviour. I conclude by arguing that though this EM field-driven will is not free, in the sense of being acausal, it nevertheless corresponds to the very real experience of our conscious mind being in control of our voluntary actions. Will is not an illusion. It is our experience of control by our EM field-located mind. It is an immaterial, yet physical, will. Full article

Fluoroquinolones (FQs) are a broad class of antibiotics typically prescribed for bacterial infections, including infections for which their use is discouraged. The FDA has proposed the existence of a permanent disability (Fluoroquinolone Associated Disability; FQAD), which is yet to be formally recognized. Previous studies suggest that FQs act as selective GABA_A receptor inhibitors, preventing the binding of GABA in the central nervous system. GABA is a key regulator of the vagus nerve, involved in the control of gastrointestinal (GI) function. Indeed, GABA is released from the Nucleus of the Tractus Solitarius (NTS) to the Dorsal Motor Nucleus of the vagus (DMV) to tonically regulate vagal activity. The purpose of this review is to summarize the current knowledge on FQs in the context of the vagus nerve and examine how these drugs could lead to dysregulated signaling to the GI tract. Since there is sufficient evidence to suggest that GABA transmission is hindered by FQs, it is reasonable to postulate that the vagal circuit could be compromised at the NTS-DMV synapse after FQ use, possibly leading to the development of permanent GI disorders in FQAD. Full article

The article describes the practical use of Unity technology in neurogaming. For this purpose, the article describes Unity technology and brain–computer interface (BCI) technology based on the Emotiv EPOC + NeuroHeadset device. The process of creating the game world and the test results for the use of a device based on the BCI as a control interface for the created game are also presented. The game was created in the Unity graphics engine and the Visual Studio environment in C#. The game presented in the article is called “NeuroBall” due to the player’s object, which is a big red ball. The game will require full focus to make the ball move. The game will aim to improve the concentration and training of the user’s brain in a user-friendly environment. Through neurogaming, it will be possible to exercise and train a healthy brain, as well as diagnose and treat various symptoms of brain disorders. The project was entirely created in the Unity graphics engine in Unity version 2020.1. Full article

The neurovascular niche is crucial for constant blood supply and blood-brain barrier (BBB) function and is altered in a number of different neurological conditions, making this an intensely active field of research. Brain vasculature is unique for its tight association of endothelial cells with astrocytic endfeet processes. Separation of the vascular compartment by centrifugation-based methods confirmed enrichment of astrocytic endfeet processes, making it possible to study the entire vascular niche with such methods. Several centrifugation-based separation protocols are found in the literature; however, with some constraints which limit their applicability and the scope of the studies. Here, we describe and validate a protocol for physically separating the neurovascular niche from the parenchyma, which is optimized for smaller tissue quantities. Using endothelial, neuronal, and astrocyte markers, we show that quantitative Western blot-based target detection can be performed of both the vessel-enriched and parenchymal fractions using as little as a single mouse brain hemisphere. Validation of our protocol in rodent stroke models by detecting changes in tight junction protein expression, serum albumin signals and astrocyte activation, i.e., increased glial fibrillary acidic protein expression, between the ipsilateral and the lesion-free contralateral hemisphere demonstrates this protocol as a new way of detecting BBB breakdown and astrogliosis, respectively. Full article

Parkinson’s disease (PD) is a complex, multi-system, neurodegenerative disorder; PD patients exhibit motor symptoms (such as akinesia/bradykinesia, tremor, rigidity, and postural instability) due to a loss of nigrostriatal dopaminergic neurons, and non-motor symptoms such as hyposmia, autonomic disturbance, depression, and REM sleep behavior disorder (RBD), which precedes motor symptoms. Pathologically, α-synuclein deposition is observed in the central and peripheral nervous system of sporadic PD patients. To clarify the mechanism of neurodegeneration in PD and to develop treatment to slow or stop PD progression, there is a great need for experimental models which reproduce neurological features of PD. Animal models exposed to rotenone, a commonly used pesticide, have received most attention since Greenamyre and his colleagues reported that chronic exposure to rotenone could reproduce the anatomical, neurochemical, behavioral, and neuropathological features of PD. In addition, recent studies demonstrated that rotenone induced neuropathological change not only in the central nervous system but also in the peripheral nervous system in animals. In this article, we review rotenone models especially focused on reproducibility of central and peripheral multiple features of PD. This review also highlights utility of rotenone models for investigation of PD pathogenesis and development of disease-modifying drugs for PD in future. Full article