A global neuronal workspace model of functional neurological disorders.

We introduce here a general model of Functional Neurological Disorders based on the following hypothesis: a Functional Neurological Disorder could correspond to a consciously initiated voluntary top-down process causing involuntary lasting consequences that are consciously experienced and subjectively interpreted by the patient as involuntary. We develop this central hypothesis according to Global Neuronal Workspace theory of consciousness, that is particularly suited to describe interactions between conscious and non-conscious cognitive processes. We then present a list of predictions defining a research program aimed at empirically testing their validity. Finally, this general model leads us to reinterpret the long-debated links between hypnotic suggestion and functional neurological disorders. Driven by both scientific and therapeutic goals, this theoretical paper aims at bringing closer the psychiatric and neurological worlds of functional neurological disorders with the latest developments of cognitive neuroscience of consciousness.

Advancing Neurological Health: Insights into Aging, Immunity, and Vascular Dynamics.

This editorial provides an overview of recent advancements in the understanding and treatment of neurological disorders, focusing on aging, immunity, and blood flow, as featured in this special issue. The first section explores the importance of identifying biomarkers of aging and aging-related diseases, such as Alzheimer's Disease, highlighting the emerging role of saliva-based biomarkers and the gut-brain axis in disease diagnosis and management. In the subsequent section, the dysregulated immune systems associated with aging are discussed, emphasizing the intricate landscape of the immune system during aging and its bidirectional relationship with neuroinflammation. Additionally, insights into the involvement of Myeloid-Derived Suppressor Cells (MDSCs) in Multiple Sclerosis (MS) pathogenesis are presented. The third section examines the role of microglia in neuroinflammation and various neurological diseases, including age-related macular degeneration (AMD) and Tuberculous Meningitis (TBM). Furthermore, the therapeutic potential of stem cell and extracellular vesicle-based therapies for stroke is explored, along with molecular mechanism of how inflammation regulates cerebral and myocardial ischemia. Finally, the importance of blood flow in maintaining vascular health and its impact on neurological disorders are discussed, highlighting the potential of novel assessment methods for optimizing patient care. Overall, this special issue offers valuable insights into the complex mechanisms underlying neurological disorders and identifies potential avenues for therapeutic intervention.

Exploring intricate connectivity patterns for cognitive functioning and neurological disorders: incorporating frequency-domain NC method into fMRI analysis.

This study extends the application of the frequency-domain new causality method to functional magnetic resonance imaging analysis. Strong causality, weak causality, balanced causality, cyclic causality, and transitivity causality were constructed to simulate varying degrees of causal associations among multivariate functional-magnetic-resonance-imaging blood-oxygen-level-dependent signals. Data from 1,252 groups of individuals with different degrees of cognitive impairment were collected. The frequency-domain new causality method was employed to construct directed efficient connectivity networks of the brain, analyze the statistical characteristics of topological variations in brain regions related to cognitive impairment, and utilize these characteristics as features for training a deep learning model. The results demonstrated that the frequency-domain new causality method accurately detected causal associations among simulated signals of different degrees. The deep learning tests also confirmed the superior performance of new causality, surpassing the other three methods in terms of accuracy, precision, and recall rates. Furthermore, consistent significant differences were observed in the brain efficiency networks, where several subregions defined by the multimodal parcellation method of Human Connectome Project simultaneously appeared in the topological statistical results of different patient groups. This suggests a significant association between these fine-grained cortical subregions, driven by multimodal data segmentation, and human cognitive function, making them potential biomarkers for further analysis of Alzheimer's disease.

CaMKII activity and metabolic imbalance-related neurological diseases: Focus on vascular dysfunction, synaptic plasticity, amyloid beta accumulation, and lipid metabolism.

Metabolic syndrome (MetS) is characterized by insulin resistance, hyperglycemia, excessive fat accumulation and dyslipidemia, and is known to be accompanied by neuropathological symptoms such as memory loss, anxiety, and depression. As the number of MetS patients is rapidly increasing globally, studies on the mechanisms of metabolic imbalance-related neuropathology are emerging as an important issue. Ca2+/calmodulin-dependent kinase II (CaMKII) is the main Ca2+ sensor and contributes to diverse intracellular signaling in peripheral organs and the central nervous system (CNS). CaMKII exerts diverse functions in cells, related to mechanisms such as RNA splicing, reactive oxygen species (ROS) generation, cytoskeleton, and protein-protein interactions. In the CNS, CaMKII regulates vascular function, neuronal circuits, neurotransmission, synaptic plasticity, amyloid beta toxicity, lipid metabolism, and mitochondrial function. Here, we review recent evidence for the role of CaMKII in neuropathologic issues associated with metabolic disorders.

Modeling a neurological disorder as the result of an operator acting on the brain: A first sketch based on network channel modeling.

The brain is a complex network, and diseases can alter its structures and connections between regions. Therefore, we can try to formalize the action of diseases by using operators acting on the brain network. Here, we propose a conceptual model of the brain, seen as a multilayer network, whose intra-lobe interactions are formalized as the diagonal blocks of an adjacency matrix. We propose a general and abstract definition of disease as an operator altering the weights of the connections between neural agglomerates, that is, the elements of the brain matrix. As models, we consider examples from three neurological disorders: epilepsy, Alzheimer-Perusini's disease, and schizophrenia. The alteration of neural connections can be seen as alterations of communication pathways, and thus, they can be described with a new channel model.

Misperception of body verticality in neurological disorders: A systematic review and meta-analysis.

INTRODUCTION: The internal representation of verticality could be disturbed when a lesion in the central nervous system (CNS) affects the centers where information from the vestibular, visual, and/or somatosensory systems, increasing the risk of falling. OBJECTIVE: The aim was to evaluate the vestibular and somatosensory contribution to the verticality pattern in patients with stroke and other neurological disorders. METHODS: A literature search was performed in PubMed, Scopus, Web of Science, and CINAHL databases. Cross-sectional, case-control, and cohort studies comparing body verticality in patients with stroke or CNS diseases (CNSD) versus healthy controls were selected. Subjective postural vertical (SPV) in roll and pitch planes was used as the primary variable. RESULTS: Ten studies reporting data from 390 subjects were included. The overall effect for CNSD patients showed a misperception of body verticality in roll (standardized mean difference [SMD] = 1.05; 95% confidence interval [CI] .84-1.25) and pitch planes (SMD = 1.03; 95% CI .51-1.55). In subgroup analyses, a high effect was observed in the perception of SPV both in roll and pitch planes in stroke (p = .002) and other CNSD (p < .001). CONCLUSION: These findings suggest a potential misperception of SPV in patients with stroke and other neurological disturbances. Patients with CNSD could present an alteration of vestibular and somatosensory contribution to verticality construction, particularly stroke patients with pusher syndrome (PS), followed by those with PS combined with hemineglect.

Beyond the brain: General intensive care considerations in pediatric neurocritical care.

Managing children with critical neurological conditions requires a comprehensive understanding of several principles of critical care. Providing a holistic approach that addresses not only the acute interactions between the brain and different organ systems, but also critical illness-associated complications and recovery is essential for improving outcomes in these patients. The brain reacts to an insult with autonomic responses designed to optimize cardiac output and perfusion, which can paradoxically be detrimental. Managing neuro-cardiac interactions therefore requires balancing adequate cerebral perfusion and minimizing complications. The need for intubation and airway protection in patients with acute encephalopathy should be individualized following careful risk/benefit deliberations. Ventilatory strategies can have profound impact on cerebral perfusion. Therefore, understanding neuro-pulmonary interactions is vital to optimize ventilation and oxygenation to support a healing brain. Gastrointestinal dysfunction is common and often complicates the care of patients with critical neurological conditions. Kidney function, along with fluid status and electrolyte derangements, should also be carefully managed in the acutely injured brain. While in the pediatric intensive care unit, prevention of critical illness-associated complications such as healthcare-associated infections and deep vein thrombosis is vital in improving outcomes. As the brain emerges from the acute injury, rehabilitation and management of delirium and paroxysmal sympathetic hyperactivity is paramount for optimal recovery. All these considerations provide a foundation for the care of pediatric patients with critical neurological conditions in the intensive care unit.

C. elegans: a prominent platform for modeling and drug screening in neurological disorders.

INTRODUCTION: Human neurodevelopmental and neurodegenerative diseases (NDevDs and NDegDs, respectively) encompass a broad spectrum of disorders affecting the nervous system with an increasing incidence. In this context, the nematode C. elegans, has emerged as a benchmark model for biological research, especially in the field of neuroscience. AREAS COVERED: The authors highlight the numerous advantages of this tiny worm as a model for exploring nervous system pathologies and as a platform for drug discovery. There is a particular focus given to describing the existing models of C. elegans for the study of NDevDs and NDegDs. Specifically, the authors underscore their strong applicability in preclinical drug development. Furthermore, they place particular emphasis on detailing the common techniques employed to explore the nervous system in both healthy and diseased states. EXPERT OPINION: Drug discovery constitutes a long and expensive process. The incorporation of invertebrate models, such as C. elegans, stands as an exemplary strategy for mitigating costs and expediting timelines. The utilization of C. elegans as a platform to replicate nervous system pathologies and conduct high-throughput automated assays in the initial phases of drug discovery is pivotal for rendering therapeutic options more attainable and cost-effective.

The intricate brain-body interaction in psychiatric and neurological diseases.

A harmonic brain-body communication is fundamental to individual wellbeing and is the basis of human cognition and behavior. In the last 2 decades, the interaction between the brain and body functioning has become a central area of study for neurologists and neuroscientists in clinical and non-clinical contexts. Indeed, brain-body axis dysfunctions occur in many psychiatric, neurological and neurodegenerative diseases. This editorial will focus on recent advances and future therapeutic perspectives for studying brain-body interactions in health and diseases.

Serial electrodiagnostic testing: Utility and indications in adult neurological disorders.

Although existing guidelines address electrodiagnostic (EDX) testing in identifying neuromuscular conditions, guidance regarding the uses and limitations of serial (or repeat) EDX testing is limited. By assessing neurophysiological change longitudinally across time, serial electrodiagnosis can clarify a diagnosis and potentially provide valuable prognostic information. This monograph presents four broad indications for serial electrodiagnosis in adult peripheral neurological disorders. First, where clinical change has raised suspicion for a new or ongoing lesion, EDX reassessment for spatial spread of abnormality, involvement of previously normal muscle or nerve, and/or evolving pathophysiology can clarify a diagnosis. Second, where diagnosis of a progressive neuromuscular condition is uncertain, electrophysiological data from a second time point can confirm or refute suspicion. Third, to establish prognosis after a static nerve injury, a repeat study can assess the presence and extent of reinnervation. Finally, faced with a limited initial study (as when complicated by patient or environmental factors), a repeat EDX study can supplement missing or limited data to provide needed clarity. Repeat EDX studies carry certain limitations, however, such as with prognostication in the setting of remote or chronic lesions, sensory predominant fascicular injury, or mild axonal injury. Nevertheless, serial electrodiagnosis remains a valuable and underused tool in the diagnostic and prognostic evaluation of neuromuscular conditions.

The Evaluation of Gastric Emptying Using the 13 C-Acetate Breath Test in Neurologically Impaired Patients - A Focus on the Stomach Function and Morphology.

PURPOSE: We explored factors affecting gastric emptying in neurologically impaired (NI) patients using the 13C-acetate breath test. METHODS: Twenty-four NI patients were classified by the presence of gastroesophageal reflux disease (GERD), which was treated by fundoplication plus gastrostomy, or the absence of GERD, which was treated by gastrostomy alone, along with gastric malposition involving cascade stomach and organoaxial gastric volvulus (OGV). Gastric emptying parameters (GEPs), which were the emptying half time (T 1/2 , minute), the lag phase time (T lag , minute), and the gastric emptying coefficient (GEC), were measured before and after surgery. We evaluated the relationship between GEPs and GERD, gastric malposition, and surgical intervention. All data were expressed as the median (interquartile range). RESULTS: The T1/2 and GEC of patients with OGV were significantly worse than in those without OGV before surgery (T1/2 with OGV: 241.3 [154.9, 314.3] vs. T1/2 without OGV: 113.7 [105.2, 151.4], p = 0.01, GEC with OGV: 3.19 [2.46, 3.28] vs. GEC without OGV: 3.65 [3.24, 3.90], p = 0.02). GERD and cascade stomach were not associ ated with GEPs. The GEPs of all NI patients showed no significant difference between before and after surgery. The surgical change in T1/2 (ΔT 1/2 ) in the patients with OGV was significantly lower than in those without OGV (ΔT1/2 with OGV: -47.1 [-142.7, -22.1] vs. ΔT1/2 without OGV: -3.78 [-26.6, 12.0], p = 0.03). CONCLUSION: Stomach malposition, such as OGV, seems to affect gastric emptying and may be improved by surgi cal intervention.

Neurotransmitter systems in the etiology of major neurological disorders: Emerging insights and therapeutic implications.

Neurotransmitters serve as chemical messengers playing a crucial role in information processing throughout the nervous system, and are essential for healthy physiological and behavioural functions in the body. Neurotransmitter systems are classified as cholinergic, glutamatergic, GABAergic, dopaminergic, serotonergic, histaminergic, or aminergic systems, depending on the type of neurotransmitter secreted by the neuron, allowing effector organs to carry out specific functions by sending nerve impulses. Dysregulation of a neurotransmitter system is typically linked to a specific neurological disorder. However, more recent research points to a distinct pathogenic role for each neurotransmitter system in more than one neurological disorder of the central nervous system. In this context, the review provides recently updated information on each neurotransmitter system, including the pathways involved in their biochemical synthesis and regulation, their physiological functions, pathogenic roles in diseases, current diagnostics, new therapeutic targets, and the currently used drugs for associated neurological disorders. Finally, a brief overview of the recent developments in neurotransmitter-based therapeutics for selected neurological disorders is offered, followed by future perspectives in that area of research.

New Alzheimer Disease Drugs, Long COVID and the Central Nervous System, and a Nasal Spray for Migraines-Highlights From the 2023 American Academy of Neurology Conference.

This Medical News article discusses research presented at the recent American Academy of Neurology Conference.

Personality traits related to cognitive functioning in patients with functional neurological disorder.

Cognitive symptoms are prevalent in patients with functional neurological disorder (FND). Several studies have suggested that personality traits such as neuroticism may play a pivotal role in the development of FND. FND has also been associated with alexithymia: patients with FND report difficulties in identifying, analyzing, and verbalizing emotions. Whether or not alexithymia and other personality traits are associated with cognitive symptomatology in patients with FND is unknown. In the current study, we explored whether the Big Five personality model factors (neuroticism, extraversion, openness, agreeableness, and conscientiousness) and alexithymia were associated with cognitive functioning in FND. Twenty-three patients with FND were assessed using a neuropsychological assessment and questionnaire assessment to explore personality traits (Neuroticism-Extraversion-Openness Five-Factor Inventory) and alexithymia (Bermond-Vorst Alexithymia Questionnaire). The results indicated that high conscientiousness was associated with lower planning scores (ρ = -0.52, p = .012) and high scores on alexithymia were associated with lower scores on verbal memory scores (ρ = -0.46, p = .032) and lower sustained attention scores (ρ = -0.45, p = .046). The results did not remain significant after controlling for multiple testing. The preliminary results of our study suggest that personality and cognitive symptomatology in patients with FND are topics that should be further explored in future studies, as cognitive symptomology can affect treatment results.

Brain borders at the central stage of neuroimmunology.

The concept of immune privilege suggests that the central nervous system is isolated from the immune system. However, recent studies have highlighted the borders of the central nervous system as central sites of neuro-immune interactions. Although the nervous and immune systems both function to maintain homeostasis, under rare circumstances, they can develop pathological interactions that lead to neurological or psychiatric diseases. Here we discuss recent findings that dissect the key anatomical, cellular and molecular mechanisms that enable neuro-immune responses at the borders of the brain and spinal cord and the implications of these interactions for diseases of the central nervous system.

Animal Model of Neonatal Immune Challenge by Lipopolysaccharide: A Study of Sex Influence in Behavioral and Immune/Neurotrophic Alterations in Juvenile Mice.

INTRODUCTION: The prenatal/perinatal exposure to infections may trigger neurodevelopmental alterations that lead to neuropsychiatric disorders such as autism spectrum disorder (ASD). Previous evidence points to long-term behavioral consequences, such as autistic-like behaviors in rodents induced by lipopolysaccharide (LPS) pre- and postnatal (PN) exposure during critical neurodevelopmental periods. Additionally, sex influences the prevalence and symptoms of ASD. Despite this, the mechanisms underlying this influence are poorly understood. We aim to study sex influences in behavioral and neurotrophic/inflammatory alterations triggered by LPS neonatal exposure in juvenile mice at an approximate age of ASD diagnosis in humans. METHODS: Swiss male and female mice on PN days 5 and 7 received a single daily injection of 500 µg/kg LPS from Escherichia coli or sterile saline (control group). We conducted behavioral determinations of locomotor activity, repetitive behavior, anxiety-like behavior, social interaction, and working memory in animals on PN25 (equivalent to 3-5 years old of the human). To determine BDNF levels in the prefrontal cortex and hippocampus, we used animals on PN8 (equivalent to a human term infant) and PN25. In addition, we evaluated iba-1 (microglia marker), TNFα, and parvalbumin expression on PN25. RESULTS: Male juvenile mice presented repetitive behavior, anxiety, and working memory deficits. Females showed social impairment and working memory deficits. In the neurochemical analysis, we detected lower BDNF levels in brain areas of female mice that were more evident in juvenile mice. Only LPS-challenged females presented a marked hippocampal expression of the microglial activation marker, iba-1, and increased TNFα levels, accompanied by a lower parvalbumin expression. DISCUSSION/CONCLUSION: Male and female mice presented distinct behavioral alterations. However, LPS-challenged juvenile females showed the most prominent neurobiological alterations related to autism, such as increased microglial activation and parvalbumin impairment. Since these sex-sensitive alterations seem to be age-dependent, a better understanding of changes induced by the exposure to specific risk factors throughout life represents essential targets for developing strategies for autism prevention and precision therapy.

Restoration Algorithm-Based Ultrasound Image in Evaluating the Effect of Dexmedetomidine on Patients with Neurological Disorder Anesthetized by Sevoflurane.

The study focused on the application value of ultrasound images processed by restoration algorithm in evaluating the effect of dexmedetomidine in preventing neurological disorder in patients undergoing sevoflurane anesthesia. 90 patients undergoing tonsillectomy anesthesia were randomly divided into normal saline group, propofol group, and dexmedetomidine group. The ultrasound images were processed by restoration algorithm, and during the postoperative recovery period, ultrasound images were used to evaluate. The results showed that the original ultrasonic image was fuzzy and contained interference noise, and that the image optimized by restoration algorithm was clear, without excess noise, and the image quality was significantly improved. In the dexmedetomidine group, the extubation time was 10.6 ± 2.3 minutes, the recovery time was 8.4 ± 2.2 minutes, the average pain score during the recovery period was 2.6 ± 0.7, and the average agitation score was 7.2 ± 2.4. Of 30 patients, there were 13 cases with vertigo and 1 case with nausea and vomiting. The vascular ultrasound imaging showed that, in the dexmedetomidine group, the peak systolic velocities (PSV) of the bilateral vertebral arteries during the recovery period were 67.7 ± 14.3 and 67.9 ± 15.2 cm/s, respectively; the end-diastolic velocities (EDV) of the bilateral vertebral arteries were 27.8 ± 6.7 and 24.69 ± 5.9 cm/s, respectively; the PSV in bilateral internal carotid artery systolic peak velocities were 67.2 ± 13.9 and 67.8 ± 12.7 cm/s, respectively; the EDV in bilateral internal carotid arteries were 27.7 ± 5.3 and 26.9 ± 4.9 cm/s, respectively; bilateral vertebral artery resistance indexes (RIs) were 0.6 ± 0.02 and 0.71 ± 0.08, respectively; the bilateral internal carotid artery RIs were 0.57 ± 0.04 and 0.58 ± 0.06, respectively, all better than the normal saline group (12.1 ± 2.5 minutes, 10.1 ± 2.3 minutes, 3.9 ± 0.6, 10.6 ± 3.7, 15 cases, 11 cases, 81.5 ± 13.6, 80.7 ± 11.6 cm/s, 29.3 ± 6.8, 28.9 ± 6.7 cm/s, 74.3 ± 10.2, 73.9 ± 12.5 cm/s, 29.1 ± 4.3, 29 ± 4.5 cm/s, 0.84 ± 0.06, 0.83 ± 0.05, 0.8 ± 0.04, and 0.81 ± 0.05) and the propofol group (11.4 ± 2.1 minutes, 9.0 ± 2.1 minutes, 3.4 ± 0.8, 8.5 ± 2.3, 12 cases, 9 cases, 72.5 ± 12.9, 73.4 ± 11.8 cm/s, 28.6 ± 5.4, 26.5 ± 5.1 cm/s, 72.1 ± 11.4, 73.5 ± 10.6 cm/s, 28.8 ± 5.6, 27.3 ± 4.7 cm/s, 0.78 ± 0.07, 0.82 ± 0.06, 0.76 ± 0.03, and 0.78 ± 0.05), and the differences were statistically significant (P < 0.05). In conclusion, ultrasound images processed by restoration algorithm have high image quality and high resolution. The dexmedetomidine can prevent neurological disorder in patients with sevoflurane anesthesia and is suggested in postoperative rehabilitation.