Neurological Mechanisms Research Articles

Exploring the Link between Premature Ovarian Insufficiency, Insomnia and Circadian Pathways.

To establish an interaction network for genes related to premature ovarian insufficiency (POI) and insomnia, and to identify biological processes that connect POI to the physiological clock. Previously reported lists of genes associated to POI and insomnia were contrasted and their intersection was used as input on protein-protein interaction analyses. POI-associated genes were contrasted with gene expression markers for neural circadian control and enriched pathways among their shared content were dissected. The functional network generated from the intersection between POI and insomnia gene lists pointed to the central nervous system as the most relevant cellular context for this connection. After identifying POI-associated genes that play a role in neural circadian patterns, we observed the disruption of pathways related to the hypothalamic-pituitary-gonadal axis as the major genetic link between ovarian function and circadian neural circuits. These findings highlight neurological mechanisms that support the POI-insomnia interplay.

Cross-Species Convergence of Functional Connectivity Changes in Thalamic Pain Across Human Patients and Model Macaques

Thalamic pain can be understood as a network reorganization disorder. This study aimed to investigate functional connectivity (FC) in human patients and a macaque model of thalamic pain. In humans, resting-state FC was compared between patients with thalamic pain and healthy individuals. Furthermore, resting-state FC was compared in macaques, before and after the induction of thalamic pain in the same individuals. FC between the amygdala of the unaffected hemisphere and the brainstem was significantly higher in patients with thalamic pain. More specifically, a significantly higher FC was observed between the basolateral amygdala and the ventral tegmental area, which also significantly predicted the value of a visual analog scale of pain intensity in individual patients. The macaque model of thalamic pain also exhibited a significantly higher FC between the amygdala of the unaffected hemisphere and the brainstem, particularly between the basolateral amygdala and the midbrain. Furthermore, the previously reported significantly higher FC between the amygdala and the mediodorsal nucleus of the thalamus in macaques with thalamic pain was also reproduced in the human patients. Therefore, the present results suggest that the FC changes in the regions associated with emotion, memory, motivation, and reward are part of the underlying mechanisms of thalamic pain onset present in both human patients and model macaques. This cross-species convergence provides new insights into the neurological mechanisms underlying thalamic pain, paving the way for further studies and the development of therapeutic strategies. PerspectiveThis article presents that the FC changes in the regions associated with emotion, motivation, and reward are part of the underlying mechanisms of thalamic pain in humans and macaques.

Shaping corticospinal pathways in virtual reality: effects of task complexity and sensory feedback during mirror therapy in neurologically intact individuals

BackgroundRestoration of limb function for individuals with unilateral weakness typically requires volitional muscle control, which is often not present for individuals with severe impairment. Mirror therapy—interventions using a mirror box to reflect the less-impaired limb onto the more-impaired limb—can facilitate corticospinal excitability, leading to enhanced recovery in severely impaired clinical populations. However, the mirror box applies limitations on mirror therapy, namely that all movements appear bilateral and are confined to a small area, impeding integration of complex activities and multisensory feedback (e.g., visuo-tactile stimulation). These limitations can be addressed with virtual reality, but the resulting effect on corticospinal excitability is unclear.ObjectiveExamine how virtual reality-based unilateral mirroring, complex activities during mirroring, and visuo-tactile stimulation prior to mirroring affect corticospinal excitability.Materials and methodsParticipants with no known neurological conditions (n = 17) donned a virtual reality system (NeuRRoVR) that displayed a first-person perspective of a virtual avatar that matched their motions. Transcranial magnetic stimulation-induced motor evoked potentials in the nondominant hand muscles were used to evaluate corticospinal excitability in four conditions: resting, mirroring, mirroring with prior visuo-tactile stimulation (mirroring + TACT), and control. During mirroring, the movements of each participant’s dominant limb were reflected onto the nondominant limb of the virtual avatar, and the avatar’s dominant limb was kept immobile (i.e., unilateral mirroring). The mirroring + TACT condition was the same as the mirroring condition, except that mirroring was preceded by visuo-tactile stimulation of the nondominant limb. During the control condition, unilateral mirroring was disabled. During all conditions, participants performed simple (flex/extend fingers) and complex (stack virtual blocks) activities.ResultsWe found that unilateral mirroring increased corticospinal excitability compared to no mirroring (p < 0.001), complex activities increased excitability compared to simple activities during mirroring (p < 0.001), and visuo-tactile stimulation prior to mirroring decreased excitability (p = 0.032). We also found that these features did not interact with each other.DiscussionsThe findings of this study shed light onto the neurological mechanisms of mirror therapy and demonstrate the unique ways in which virtual reality can augment mirror therapy. The findings have important implications for rehabilitation for design of virtual reality systems for clinical populations.

Integration of basic and clinical researches to develop the biomarker of ‍depression

Because of absence of the objective biomarker for major depressive disorder (MDD) or depressive state, psychiatrists depend on subjective examinations in order to properly diagnose their patients. We recently identified the candidates of the objective biomarker of depressive state of late-onset MDD by profiling gene expressions in white blood cells of patients and model mice. We also investigated whether gene expression profiling of white blood cells was useful to elucidate the biological alterations in the brain. Furthermore, we newly developed transgenic mice which will be useful for elucidating the neurological mechanisms of emotional abnormalities in psychiatric disorder. In this review, I introduce our recent research to help for understanding of translational approaches to develop the biomarker of depression.

Research progress on intestinal flora and depression

In recent years, the prevalence of depression and suicide rates have continued to increase, especially among adolescents, and existing treatment methods are still incomplete and have certain limitations. Although some progress has been made in studying the relationship between gut microbiota and depression, a clear explanation of the physiological mechanisms of the "Microbiota-Gut-Brain Axis" (MGBA) and a review of treatments for depression based on MGBA regulation are still lacking. This article examines the traits of the gut microbiota in patients with depression, highlighting that their richness and diversity are significantly lower compared to healthy controls. The neurological, endocrine and immune mechanisms of MGBA and its role in the pathogenesis of depression were further explored. This article also reviews MGBA-based treatments, such as Fecal Microbiota Transplantation (FMT) and probiotic therapy, noting their potential efficacy in alleviating depressive symptoms. This article unveils the pivotal role of gut microbiota in the development of depression, offering a new avenue for researching the pathological mechanisms of the disorder and laying a scientific foundation for creating novel antidepressant treatments. At present, there is no consistent conclusion about the changes in the composition of the intestinal flora in depression. Future studies can expand the sample size and conduct experiments on different groups to deeply reveal the changes in the intestinal flora of patients with depression.

Association of medullary reticular formation ventral part with spasticity in mice suffering from photothrombotic stroke

Strokes cause spasticity via stretch reflex hyperexcitability in the spinal cord, and spastic paralysis due to involuntary muscle contraction in the hands and fingers can severely restrict skilled hand movements. However, the underlying neurological mechanisms remain unknown. Using a mouse model of spasticity after stroke, we demonstrate changes in neuronal activity with and without electrostimulation of the afferent nerve to induce the stretch reflex, measured using quantitative activation-induced manganese-enhanced magnetic resonance imaging. Neuronal activity increased within the ventral medullary reticular formation (MdV) in the contralesional brainstem during the acute post-stroke phase, and this increase was characterised by activation of circuits involved in spasticity. Interestingly, ascending electrostimulation inhibited the MdV activity on the stimulation side in normal conditions.Moreover, immunohistochemical staining showed that, in the acute phase, the density of GluA1, one of the α-amino-3 hydroxy‑5 methyl -4 isoxazolepropionic acid receptor (AMPAR) subunits, at the synapses of MdV neurons was significantly increased. In addition, the GluA1/GluA2 ratio in these receptors was altered at 2 weeks post-stroke, confirming homeostatic plasticity as the underlying mechanisms of spasticity. These results provide new insights into the relationship between impaired skilled movements and spasticity at the acute post-stroke phase.

Effects of cerebellar transcranial direct current stimulation on the excitability of spinal motor neurons and vestibulospinal tract in healthy individuals.

Cerebellar transcranial direct current stimulation (ctDCS) modulates cerebellar cortical excitability in a polarity-dependent manner and affects inhibitory pathways from the cerebellum. The cerebellum modulates spinal reflex excitability via the vestibulospinal tract and other pathways projecting to the spinal motor neurons; however, the effects of ctDCS on the excitability of spinal motor neurons and vestibulospinal tract remain unclear. The experiment involved 13 healthy individuals. ctDCS (sham-ctDCS, anodal-ctDCS, and cathodal-ctDCS) was applied to the cerebellar vermis at 2mA with an interval of at least 3 days between each condition. We measured the maximal M-wave (Mmax) and maximal H-reflex (Hmax) in the right soleus muscle to assess the excitability of spinal motor neurons. We applied galvanic vestibular stimulation (GVS) for 200 ms at 100 ms before tibial nerve stimulation to measure Hmax conditioned by GVS (GVS-Hmax) and calculated the change rate of Hmax by GVS as the excitability of vestibulospinal tract. We measured the Mmax, Hmax, and GVS-Hmax before, during, and after ctDCS in the sitting posture. No main effects of tDCS condition, main effects of time, or interaction effects were observed in Hmax/Mmax or the change rate of Hmax by GVS. It has been suggested that ctDCS does not affect the excitability of spinal motor neurons and vestibulospinal tract, as measured by neurophysiological methods, such as the H-reflex, in healthy individuals in a sitting posture. Effect of ctDCS on other descending pathways to spinal motor neurons, the neurological mechanism of tDCS and the cerebellar activity during the experiment may have contributed to these results. Therefore, we need to investigate the involvement of the cerebellum in Hmax/Mmax and the change rate of Hmax by GVS under different neuromodulation techniques and postural conditions.

Setting the scene for boundary extension: Methods, findings, connections, and theories.

A previously viewed scene is often remembered as containing a larger extent of the background than was actually present, and information that was likely present just outside the boundaries of that view is often incorporated into the representation of that scene. This has been referred to as boundary extension. Methodologies used in studies on boundary extension (terminology, stimulus presentation, response measures) are described. Empirical findings regarding effects of characteristics of the stimulus (whether the stimulus depicts a scene, semantics of the scene, view angle, object size, object cropping, object orientation, object color, number of objects, depth of field, object distance, viewpoint production, scene orientation, motion, faces, emotions, modality, whether the scene is multimodal), characteristics of the display (aperture shape, aperture size, target duration, retention interval), and characteristics of the observer (allocation of attention, imagination, age, expectations and strategies, eye fixation, eye movements, monocular or binocular view, vantage point, confinement, prior exposure, expertise, arousal, pathology) on boundary extension are reviewed. Connections of boundary extension to other cognitive phenomena and processes (evolutionary adaptation, Gestalt principles, illusions, psychophysics, invariant physical principles, aesthetics, temporal boundary extension, normalization) are noted, and theories and theoretical considerations regarding boundary extension (multisource model, boundary transformation, mental imagery, 4E cognition, cognitive modularity, neurological mechanisms of scene representation) are discussed.

Deciphering Mechanisms, Prevention Strategies, Management Plans, Medications, and Research Techniques for Strokes in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune rheumatic condition characterized by an unpredictable course and a wide spectrum of manifestations varying in severity. Individuals with SLE are at an increased risk of cerebrovascular events, particularly strokes. These strokes manifest with a diverse range of symptoms that cannot be solely attributed to conventional risk factors, underscoring their significance among the atypical risk factors in the context of SLE. This complexity complicates the identification of optimal management plans and the selection of medication combinations for individual patients. This susceptibility is further complicated by the nuances of neuropsychiatric SLE, which reveals a diverse array of neurological symptoms, particularly those associated with ischemic and hemorrhagic strokes. Given the broad range of clinical presentations and associated risks linking strokes to SLE, ongoing research and comprehensive care strategies are essential. These efforts are critical for improving patient outcomes by optimizing management strategies and discovering new medications. This review aims to elucidate the pathological connection between SLE and strokes by examining neurological manifestations, risk factors, mechanisms, prediction and prevention strategies, management plans, and available research tools and animal models. It seeks to explore this medical correlation and discover new medication options that can be tailored to individual SLE patients at risk of stroke.

Voluntary Exercise Ameliorates Chronic Ethanol Withdrawal-Induced Adaptations of Opioid Receptor Expression in the Nucleus Accumbens, Dopamine Release, and Ethanol Consumption.

Exercise has increasingly been recognized as an adjunctive therapy for alcohol-use disorder (AUD), yet our understanding of its underlying neurological mechanisms remains limited. This knowledge gap impedes the development of evidence-based exercise guidelines for AUD treatment. Chronic ethanol (EtOH) exposure has been shown to upregulate and sensitize kappa opioid receptors (KORs) in the nucleus accumbens (NAc), which is innervated by dopamine (DA) neurons in the midbrain ventral tegmental area (VTA), which may contribute to AUD-related behaviors. In this study, we investigated the impact of voluntary exercise in EtOH-dependent mice on EtOH consumption, KOR and delta opioid receptor (DOR) expression in the NAc and VTA, and functional effects on EtOH-induced alterations in DA release in the NAc. Our findings reveal that voluntary exercise reduces EtOH consumption, reduces KOR and enhances DOR expression in the NAc, and modifies EtOH-induced adaptations in DA release, suggesting a competitive interaction between exercise-induced and EtOH-induced alterations in KOR expression. We also found changes to DOR expression in the NAc and VTA with voluntary exercise but no significant changes to DA release. These findings elucidate the complex interplay of AUD-related neurobiological processes, highlighting the potential for exercise as a therapeutic intervention for AUD.

Pro-inflammatory cytokine activity: The root cause of catamenial seizures

About 40% of women with epilepsy experience catamenial seizures, which can be mentally and physically debilitating. Catamenial epilepsy (CE) refers to the relationship between the timing of a woman’s seizures and the monthly hormonal changes that occur throughout her menstrual cycle. The prevailing hypothesis theorizes that these hormonal changes cause CE seizures. However, researchers have not isolated the catamenial seizure neurological trigger mechanism; as a result, standard anti-seizure medications (ASMs) mostly are ineffective. Recent research substantiates the significant role inflammatory cytokines play in epilepsy, menstrual disorders, and the female reproductive system. This paper poses a new hypothesis that the direct trigger of catamenial seizures is an increase in pro-inflammatory cytokines that occurs at several times during the menstrual cycle. The hypothesis is evaluated using published evidence that the occurrences of catamenial seizures during the menstrual cycle align temporally with the surges in pro-inflammatory cytokines. Consequently, the anti-inflammatory benefits of exercise, endocannabinoid-based drugs and safe, neuroprotective dietary supplements could enable hundreds of thousands of women with catamenial epilepsy to enjoy more productive lives from a much reduced risk of seizures.

Desire to eat and the biology of obesity

Human nutrition constitutes a complex neurophysiological process determined by environmental, genetic, and hormonal factors. Human biology has neuroendocrine signals that trigger hunger, satiety, and determines the extent to which nutrients and certain foods are ingested. The homeostatic system that regulates appetite responds to the energy reserves in the body and to the functional mass of the same. In this participant various tissues, organs, hormones, and neural circuits throughout the body in a feedback loop between the brain and peripheral tissues. In addition, higher mental functions such as memory, attention and emotions are also involved in human nutrition, essential when determining the eating behavior of individuals. The understanding of these neurological mechanisms through chemical neurotransmitters that will be used for emergency cases in diseases related to the desire to eat such as obesity and its comorbidities

The Food Addiction Clinical Treatment (FACT) Manual: A Harm Reduction Treatment Approach.

While the construct of food addiction has been controversial, there is growing evidence that certain foods can activate biobehavioral and neurological mechanisms consistent with addiction to other substances. Despite increased evidence and acceptance of certain foods as addictive substances amongst the scientific community, there is a paucity of interventions available that are uniquely suited for the treatment of this condition. Further, many of the addiction and disordered eating treatment models currently utilized for food addiction are seemingly at odds, with the former often recommending complete abstinence from trigger foods and the latter promoting intake of all foods in moderation. The Food Addiction Clinical Treatment (FACT) manual was created as an alternative using an empirically supported harm-reduction model specifically targeted to treat the addiction and disordered eating features of food addiction. The purpose of the current article is to expose readers to the key tenets of the FACT manual, demonstrate the feasibility of this intervention with a sample of participants with severe food addiction, and discuss future directions for the treatment of food addiction. Positive outcomes from this intervention provide preliminary evidence for the efficacy of FACT for the treatment of food addiction with minimal negative adverse effects. Future research using randomized control trials and longer follow-up is needed to validate the FACT manual as an empirically supported treatment for food addiction.

Screening for optimal parameters for modified pharyngeal electrical stimulation for the treatment of dysphagia after stroke in rats

Pharyngeal electrical stimulation (PES), a novel noninvasive peripheral nerve stimulation technique, can effectively improve neurogenic dysphagia and increase the safety and effectiveness of swallowing in the clinic. However, the lack of animal models for dysphagia has limited the mechanistic research on PES, which affects its wide application. Therefore, determining optimal parameters for PES in rats is needed to enable mechanistic studies. Modified PES (mPES), which has different waves and pulse widths from PES, was used; in previous studies mPES was found to have a neurological mechanism like that of PES. A poststroke dysphagia (PSD) model was established, and rats with dysphagia were grouped into three different intensities (0.1 mA, 0.5 mA, and 1 mA) for the selection of optimal intensity and three different frequencies (1 Hz, 2 Hz, and 5 Hz) for the selection of optimal frequency based on a stimulation duration of 10 min in the clinic. A Videofluroscopic Swallow Screen (VFSS) was used to assess swallowing function in rats before and after mPES treatment. The results showed that the 1 mA group had better swallowing function (p < 0.05) than the model group. Compared with the model group, the 1 Hz and 5 Hz groups had the same improvement in swallowing function (p < 0.05). However, the increase in excitatory signals in the sensorimotor cortex was more pronounced in the 5 Hz group than in the other frequency stimulation groups (p < 0.05). Combining the clinical findings with the above results, we concluded that the optimal stimulation parameter for mPES in rats is “frequency: 5 Hz, current intensity: 1 mA for 10 min/day”, which provides a basis for future basic experimental studies of mPES in animals.

Comparing point‐wise and pair‐wise relevance judgment with brain signals

AbstractHow to collect relevance judgment has long been an important problem in Information Retrieval (IR). A popular method is to collect relevance judgment in a point‐wise manner, in which assessors examine and give an absolute relevance score for each item independently of the others. As an alternative, pair‐wise relevance judgment, also named preference judgment, allows an assessor to compare two items side‐by‐side and express their preference for one over the other. Previous work has explored the differences between these two paradigms of relevance judgments from many different aspects. Most of these works are conducted through explicit/implicit feedback. However, few works investigate the underlying neurological mechanisms of the two paradigms. In this paper, we conduct a lab study to investigate and compare point‐wise and pair‐wise relevance judgment in image search scenarios. We study the neurological mechanisms of the two paradigms through an event‐related potential (ERP) analysis of the users' brain signals while viewing images during a search process. We have obtained several observations, such as search engine users tend to pay more attention to preferred items in the point‐wise paradigm but unpreferred items in the pair‐wise paradigm. Furthermore, we test the adoption of brain signals as implicit feedback for predicting pair‐wise relevance judgment, highlighting the feasibility of leveraging brain signals to understand users' relevance judgments.

(088) CONTRALATERAL SYMMETRY IN THE TOPOGRAPHY OF SELF-REPORTED VULVAR PAIN

Abstract Introduction Vulvar pain is a transdiagnostic symptom that is associated with diverse end organs, neurological, and musculoskeletal mechanisms. A better understanding of the neural mechanisms behind the spreading/worsening of vulvar pain across different sites on the vulva, could guide future research, classification, and treatment of vulvar pain-related conditions. Objective Examine the topographic correlations of vulvar pain and provide insights regarding the involvement of neural pathways underlying the topographic distribution of such pain. Methods Self-reports of sexual and genital health were collected from 2199 women through online questionnaires, as part of a larger study. Efforts were made to recruit a heterogenous sample, oversampling for women with genito-pelvic pain. Participants were asked about the presence and location of vulvar and/or vaginal pain. In addition, participants were asked about history and types of non-genital injuries. If a participant reported chronic vulvar pain, they were then presented with a drawing of a vulva divided into 24 areas, asking them to indicate the location(s) of their pain (localization of vaginal pain not included). Correlations were conducted on the presence of pain across vulvar areas that were contralaterally distributed (horizontal) vs spatially close but ipsilaterally distributed (vertical and radial), and distinguishing between women with vs without a history of back and/or pelvic injury. Results 911 women reported experiencing chronic vulvar or vulvar-vaginal pain. Results from correlations across vulvar areas are reported in Figure 1, 2 and 3, distinguishing between women with and without a history of back/pelvic injury. In both groups, horizontal correlations across left and right sides of the same tissue/structure were the strongest (Figure 1), whereas areas that were spatially close on the ipsilateral side (vertical and radial) showed weaker correlations (Figures 2 &amp; 3). Statistical tests confirmed differences in correlations both between-groups and within-groups, across different spatial relations (horizontal, vertical, radial). Conclusions The observed pattern of topographic correlations suggests specific constraints on the mechanisms involved in the spreading of vulvar pain, showing a horizontally symmetrical distribution of correlations (within tissue/structure), as opposed to a proximity-based distribution of correlations. This appears to reflect symmetrically contralateral sensitization within the same structure, even if the areas were relatively distant (e.g., right and left labia minora). According to our results, this applies more to women without a history of back/pelvic injury, compared to women with a history back/pelvic injury. Consistent with past research showing that a temporary nociceptive stimulus induces hyperalgesia and allodynia in the ipsilateral and symmetrically contralateral site of noxious stimulation (Shenker et al.,2008), our results suggest that similar neural mechanism(s) might be involved in chronic vulvar pain. The pattern of correlations found could be mediated by chronic pain-induced activation of the commissural fibers that connect, and perhaps sprout into, the symmetrically contralateral sides at the level of the dorsal horn. This would constitute a form of central sensitization (Latremoliere &amp; Woolf, 2007). Whether a comparable central sensitization process also occurs at the level of the sensory cortex (or other brain regions), or whether different forms of synaptic potentiation at the neural level are involved, must also be considered. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Adamo Bioscience.

Engineered 3D Immuno-Glial-Neurovascular Human miBrain Model.

Patient-specific, human-based cellular models integrating a biomimetic blood-brain barrier (BBB), immune, and myelinated neuron components are critically needed to enable accelerated, translationally relevant discovery of neurological disease mechanisms and interventions. By engineering a novel brain-mimicking 3D hydrogel and co-culturing all six major brain cell types derived from patient iPSCs, we have constructed, characterized, and utilized a multicellular integrated brain (miBrain) immuno-glial-neurovascular model with in vivo- like hallmarks inclusive of neuronal activity, functional connectivity, barrier function, myelin-producing oligodendrocyte engagement with neurons, multicellular interactions, and transcriptomic profiles. We implemented the model to study Alzheimer's Disease pathologies associated with APOE4 genetic risk. APOE4 miBrains differentially exhibit amyloid aggregation, tau phosphorylation, and astrocytic GFAP. Unlike the co-emergent fate specification of glia and neurons in organoids, miBrains integrate independently differentiated cell types, a feature we harnessed to identify that APOE4 in astrocytes promotes neuronal tau pathogenesis and dysregulation through crosstalk with microglia.

SpaDE: Semantic Locality Preserving Biclustering for Neuroimaging Data.

The most discriminative and revealing patterns in the neuroimaging population are often confined to smaller subdivisions of the samples and features. Especially in neuropsychiatric conditions, symptoms are expressed within micro subgroups of individuals and may only underly a subset of neurological mechanisms. As such, running a whole-population analysis yields suboptimal outcomes leading to reduced specificity and interpretability. Biclustering is a potential solution since subject heterogeneity makes one-dimensional clustering less effective in this realm. Yet, high dimensional sparse input space and semantically incoherent grouping of attributes make post hoc analysis challenging. Therefore, we propose a deep neural network called semantic locality preserving auto decoder (SpaDE), for unsupervised feature learning and biclustering. SpaDE produces coherent subgroups of subjects and neural features preserving semantic locality and enhancing neurobiological interpretability. Also, it regularizes for sparsity to improve representation learning. We employ SpaDE on human brain connectome collected from schizophrenia (SZ) and healthy control (HC) subjects. The model outperforms several state-of-the-art biclustering methods. Our method extracts modular neural communities showing significant (HC/SZ) group differences in distinct brain networks including visual, sensorimotor, and subcortical. Moreover, these bi-clustered connectivity substructures exhibit substantial relations with various cognitive measures such as attention, working memory, and visual learning.

Functional Connectivity-Based Searchlight Multivariate Pattern Analysis for Discriminating Schizophrenia Patients and Predicting Clinical Variables.

Schizophrenia, a multifaceted psychiatric disorder characterized by functional dysconnectivity, poses significant challenges in clinical practice. This study explores the potential of functional connectivity (FC)-based searchlight multivariate pattern analysis (CBS-MVPA) to discriminate between schizophrenia patients and healthy controls while also predicting clinical variables. We enrolled 112 schizophrenia patients and 119 demographically matched healthy controls. Resting-state functional magnetic resonance imaging data were collected, and whole-brain FC subnetworks were constructed. Additionally, clinical assessments and cognitive evaluations yielded a dataset comprising 36 clinical variables. Finally, CBS-MVPA was utilized to identify subnetworks capable of effectively distinguishing between the patient and control groups and predicting clinical scores. The CBS-MVPA approach identified 63 brain subnetworks exhibiting significantly high classification accuracies, ranging from 62.2% to 75.6%, in distinguishing individuals with schizophrenia from healthy controls. Among them, 5 specific subnetworks centered on the dorsolateral superior frontal gyrus, orbital part of inferior frontal gyrus, superior occipital gyrus, hippocampus, and parahippocampal gyrus showed predictive capabilities for clinical variables within the schizophrenia cohort. This study highlights the potential of CBS-MVPA as a valuable tool for localizing the information related to schizophrenia in terms of brain network abnormalities and capturing the relationship between these abnormalities and clinical variables, andthus, deepens our understanding of the neurological mechanisms of schizophrenia.

Can Stem Cell Therapy be an Effective Therapeutic Option for Complex and Neurological Conditions?

This article explores the feasibility and potential benefits of stem cell therapy as a promising therapeutic intervention for individuals facing severe behavioral and cognitive impairments, targeting underlying neurological mechanisms to offer potential symptom improvement and function restoration, thereby enhancing the quality of life for patients and potentially alleviating stress and burnout among caregivers. The aims of the study include investigating the efficacy of stem cell therapy in addressing these impairments and evaluating its potential to alleviate caregiver burden. Through a comprehensive review of existing literature, clinical trials, and studies, this research synthesizes the mechanisms of stem cell therapy, potential applications, clinical trial outcomes, caregiver experiences, and economic implications. The methods employed involve analyzing diverse data sources to provide a holistic understanding of the possibilities and challenges associated with stem cell therapy. Key outcomes of the study include highlighting promising results from clinical trials targeting conditions such as autism spectrum disorder, Parkinson's disease, and Crohn's disease, which underscore the transformative potential of stem cell therapy in patient care. Additionally, economic implications suggest potential reductions in healthcare costs and alleviation of financial strain on individuals, families, and healthcare providers. Stem cell therapy represents a paradigm shift in healthcare, promising to redefine treatment approaches and alleviate broader societal burdens associated with complex neurological conditions. The relevance of the study lies in emphasizing the need for continued research, ethical considerations, and multidisciplinary collaboration to ensure the safe and effective integration of stem cell therapy into clinical practice, ultimately offering new hope and improved care for patients, caregivers, and healthcare systems worldwide.