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Epilepsy is a neurological disorder characterized by recurrent seizures, affecting over 65 million people worldwide. Treatment typically commences with the use of anti-seizure medications, including both mono- and poly-therapy. Should these fail, more invasive therapies such as surgery, electrical stimulation and focal drug delivery are often considered in an attempt to render the person seizure free. Although a significant portion ultimately benefit from these treatment options, treatment responses often fluctuate over time. The physiological mechanisms underlying these temporal variations are poorly understood, making prognosis a significant challenge when treating epilepsy. Here we use a dynamic network model of seizure transition to understand how seizure propensity may vary over time as a consequence of changes in excitability. Through computer simulations, we explore the relationship between the impact of treatment on dynamic network properties and their vulnerability over time that permit a return to states of high seizure propensity. For small networks we show vulnerability can be fully characterised by the size of the first transitive component (FTC). For larger networks, we find measures of network efficiency, incoherence and heterogeneity (degree variance) correlate with robustness of networks to increasing excitability. These results provide a set of potential prognostic markers for therapeutic interventions in epilepsy. Such markers could be used to support the development of personalized treatment strategies, ultimately contributing to understanding of long-term seizure freedom. [ABSTRACT FROM AUTHOR]

In vitro fertilisation is a stressful process for women. Hypnofertility is a method that can be used to relieve stress during in vitro fertilisation. It is based on an effective and strong body-mind interaction, as well as balancing the brain and body via positive words and thoughts. This study aimed to investigate the effects of hypnofertility on fertility preparedness, stress, and coping with stress in women undergoing in vitro fertilisation. This study was conducted with a randomised controlled trial design. Hypnofertility-based relaxation, visualisation, imagination, and affirmation techniques were applied to the intervention group at four stages, and no initiative was applied to the women in the control group. The Clinical Trial Registration number of the study is NCT04755270. After the hypnofertility method, the mean score of the intervention group in the positive feelings and thoughts subscale of the Fertility Preparedness Scale was higher than that of the control group (p < 0.05). The hypnofertility method caused a significant decrease in the level of infertility stress in the intervention group, and the intervention group used the active-confronting and passive-avoidance methods more than control group did (p < 0.05). The hypnofertility method increased the levels of preparedness for fertility, reduced stress levels and provided effective strategies to cope with stress. [ABSTRACT FROM AUTHOR]

Genetically encoded optical indicators and actuators of neural activity allow for all-optical investigations of signaling in the nervous system. But commonly used indicators, actuators, and expression strategies are poorly suited for systematic measurements of signal propagation at brain scale and cellular resolution. Large-scale measurements of the brain require indicators and actuators with compatible excitation spectra to avoid optical crosstalk. They must be highly expressed in every neuron but at the same time avoid lethality and permit the animal to reach adulthood. Their expression must also be compatible with additional fluorescent labels to locate and identify neurons, such as those in the NeuroPAL cell identification system. We present TWISP, a transgenic worm for interrogating signal propagation, that addresses these needs and enables optical measurements of evoked calcium activity at brain scale and cellular resolution in the nervous system of the nematode Caenorhabditis elegans. In every neuron we express a nonconventional optical actuator, the gustatory receptor homolog GUR-3 + PRDX-2 , under the control of a drug-inducible system QF + hGR, and a calcium indicator GCAMP6s, in a background with additional fluorophores from the NeuroPAL cell ID system. We show that this combination, but not others tested, avoids optical crosstalk, creates strong expression in the adult, and generates stable transgenic lines for systematic measurements of signal propagation in the worm brain. [ABSTRACT FROM AUTHOR]

With the budding interests of structural and functional network characteristics as potential parameters for abnormal brains, an essential and thus simpler representation and evaluations have become necessary. Eigenvector centrality measure of functional magnetic resonance imaging (fMRI) offer region wise network representations through fMRI diagnostic maps. The article investigates the suitability of network node centrality values to discriminate ASD subject groups compared to typically developing controls following a boxplot formalism and a classification and regression tree model. Region wise differences between normal and ASD subjects primarily belong to the frontoparietal, limbic, ventral attention, default mode and visual networks. The reduced number of regions-of-interests (ROI) clearly suggests the benefit of automated supervised machine learning algorithm over the manual classification method. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. This is the first study in humans demonstrating noninvasive modulation of insula subregions to affect pain ratings, brain physiology related to pain (the contact heat–evoked potential), and also metrics of autonomic/cardiovascular activity including heart-rate variability. The insula is an intriguing target for pain modulation. Unfortunately, it lies deep to the cortex making spatially specific noninvasive access difficult. Here, we leverage the high spatial resolution and deep penetration depth of low-intensity focused ultrasound (LIFU) to nonsurgically modulate the anterior insula (AI) or posterior insula (PI) in humans for effect on subjective pain ratings, electroencephalographic (EEG) contact heat–evoked potentials, as well as autonomic measures including heart-rate variability (HRV). In a within-subjects, repeated-measures, pseudo-randomized trial design, 23 healthy volunteers received brief noxious heat pain stimuli to the dorsum of their right hand during continuous heart-rate, electrodermal, electrocardiography and EEG recording. Low-intensity focused ultrasound was delivered to the AI (anterior short gyrus), PI (posterior longus gyrus), or under an inert Sham condition. The primary outcome measure was pain rating. Low-intensity focused ultrasound to both AI and PI similarly reduced pain ratings but had differential effects on EEG activity. Low-intensity focused ultrasound to PI affected earlier EEG amplitudes, whereas LIFU to AI affected later EEG amplitudes. Only LIFU to the AI affected HRV as indexed by an increase in SD of N-N intervals and mean HRV low-frequency power. Taken together, LIFU is an effective noninvasive method to individually target subregions of the insula in humans for site-specific effects on brain biomarkers of pain processing and autonomic reactivity that translates to reduced perceived pain to a transient heat stimulus. [ABSTRACT FROM AUTHOR]

Microglia sense the changes in their environment. How microglia actively translate these changes into suitable cues to adapt brain physiology is unknown. We reveal an activity-dependent regulation of cortical inhibitory synapses by microglia, driven by purinergic signaling acting on P2RX7 and mediated by microglia-derived TNFα.We demonstrate that sleep induces microgliadependent synaptic enrichment of GABAARs in a manner dependent on microglial TNFα and P2RX7. We further show that microglia-specific depletion of TNFα alters slow waves during NREM sleep and blunt memory consolidation in sleep-dependent learning tasks. Together, our results reveal that microglia orchestrate sleep-intrinsic plasticity of synaptic GABAARs, sculpt sleep slow waves, and support memory consolidation. [ABSTRACT FROM AUTHOR]

Background: Health care workers (HCWs) experience abounding physical and mental exhaustion mandating a deliverable solution for their mental health care. Kriya yoga (KY) includes several relaxation techniques and offers a stress-alleviating experience. The objective signature of KY benefits needs to be investigated. Aim: To study the effects of KY practice on brain oscillations and perceived stress in health care providers. Methods: This prospective interventional study was conducted during coronavirus disease 2019 pandemic. HCWs were enrolled to the intervention group (IG) and control group (CG) after obtaining an informed consent. IG visited the yoga center for learning the KY technique. Electroencephalogram (EEG) was recorded in both the groups, at baseline, and at the end of 6 weeks in the EEG Laboratory. Perceived stress scale (PSS) scores and participants' subjective response to KY practice were also collected. Paired t-test and independent t-test were used for statistical comparison wherever applicable. Results: Age and baseline EEG powers among the IG and CG (N = 25) were statistically comparable. Absolute power analysis revealed a statistically significant increase in alpha and delta powers after 6 weeks of KY practice. The PSS scores revealed a statistically significant decrease in perceived stress after KY practice. Furthermore, 83% of the participants reported the subjective calming effects of KY practice. Conclusion: KY practice ensues relaxing effects on the brain, as evident from the EEG absolute power analysis, PSS scores, and participants' subjective response. As KY is a brief technique, it may be encouraged during short break session among the HCWs for promotive health. [ABSTRACT FROM AUTHOR]

Schizophrenia and autism spectrum disorders (ASD) were considered as two neurodevelopmental disorders and had shared clinical features. we hypothesized that they have some common atypical brain functions and the purpose of this study was to explored the shared brain spontaneous activity strength alterations in early onset schizophrenia (EOS) and ASD in the children and adolescents with a multi-center large-sample study. A total of 171 EOS patients (aged 14.25 ± 1.87), 188 ASD patients (aged 9.52 ± 5.13), and 107 healthy controls (aged 11.52 ± 2.82) had scanned with Resting-fMRI and analyzed surface-based amplitude of low-frequency fluctuations (ALFF). Results showed that both EOS and ASD had hypoactivity in the primary sensorimotor regions (bilateral primary and early visual cortex, left ventral visual stream, left primary auditory cortex) and hyperactivity in the high-order transmodal regions (bilateral SFL, bilateral DLPFC, right frontal eye fields), and bilateral thalamus. EOS had more severe abnormality than ASD. This study revealed shared functional abnormalities in the primary sensorimotor regions and the high-order transmodal regions in EOS and ASD, which provided neuroimaging evidence of common changes in EOS and ASD, and may help with better early recognition and precise treatment for EOS and ASD. [ABSTRACT FROM AUTHOR]

The "brain-cognition-behavior" process is an important pathological pathway in children with attention-deficit/hyperactivity disorder (ADHD). Symptom guided multimodal neuroimaging fusion can capture behaviorally relevant and intrinsically linked structural and functional features, which can help to construct a systematic model of the pathology. Analyzing the multimodal neuroimage fusion pattern and exploring how these brain features affect executive function (EF) and leads to behavioral impairment is the focus of this study. Based on gray matter volume (GMV) and fractional amplitude of low frequency fluctuation (fALFF) for 152 ADHD and 102 healthy controls (HC), the total symptom score (TO) was set as a reference to identify co-varying components. Based on the correlation between the identified co-varying components and EF, further mediation analysis was used to explore the relationship between brain image features, EF and clinical symptoms. This study found that the abnormalities of GMV and fALFF in ADHD are mainly located in the default mode network (DMN) and prefrontal-striatal-cerebellar circuits, respectively. GMV in ADHD influences the TO through Metacognition Index, while fALFF in HC mediates the TO through behavior regulation index (BRI). Further analysis revealed that GMV in HC influences fALFF, which further modulates BRI and subsequently affects hyperactivity-impulsivity score. To conclude, structural brain abnormalities in the DMN in ADHD may affect local brain function in the prefrontal-striatal-cerebellar circuit, making it difficult to regulate EF in terms of inhibit, shift, and emotional control, and ultimately leading to hyperactive-impulsive behavior. [ABSTRACT FROM AUTHOR]

Objective: Binge‐eating disorder is an eating disorder characterized by recurrent binge‐eating episodes, during which individuals consume excessive amounts of highly palatable food (HPF) in a short time. This study investigates the intricate relationship between repeated binge‐eating episode and the transcriptional regulation of two key genes, adenosine A2A receptor (A2AAR) and dopamine D2 receptor (D2R), in selected brain regions of rats. Method: Binge‐like eating behavior on HPF was induced through the combination of food restrictions and frustration stress (15 min exposure to HPF without access to it) in female rats, compared to control rats subjected to only restriction or only stress or none of these two conditions. After chronic binge‐eating episodes, nucleic acids were extracted from different brain regions, and gene expression levels were assessed through real‐time quantitative PCR. The methylation pattern on genes' promoters was investigated using pyrosequencing. Results: The analysis revealed A2AAR upregulation in the amygdala and in the ventral tegmental area (VTA), and D2R downregulation in the nucleus accumbens in binge‐eating rats. Concurrently, site‐specific DNA methylation alterations at gene promoters were identified in the VTA for A2AAR and in the amygdala and caudate putamen for D2R. Discussion: The alterations on A2AAR and D2R genes regulation highlight the significance of epigenetic mechanisms in the etiology of binge‐eating behavior, and underscore the potential for targeted therapeutic interventions, to prevent the development of this maladaptive feeding behavior. These findings provide valuable insights for future research in the field of eating disorders. Public Significance: Using an animal model with face, construct, and predictive validity, in which cycles of food restriction and frustration stress evoke binge‐eating behavior, we highlight the significance of epigenetic mechanisms on adenosine A2A receptor (A2AAR) and dopamine D2 receptor (D2R) genes regulation. They could represent new potential targets for the pharmacological management of eating disorders characterized by this maladaptive feeding behavior. [ABSTRACT FROM AUTHOR]

We investigated the temporal impact of multisensory settings on children's learning of word‐object and action‐object associations at 1‐ and 2‐years of age. Specifically, we examined whether the temporal alignment of words and actions influenced the acquisition of novel word‐action‐object associations. We used a preferential looking and violation of expectation task in which infants and young children were first presented with two distinct word‐object and action‐object pairings either in a synchronous (overlapping in time) or sequential manner (one after the other). Findings revealed that 2‐year‐olds recognized both, action‐object and word‐object associations when they first saw the word‐action‐object combinations synchronously, but not sequentially, as evidenced by looking behavior. 1‐year‐olds did not show evidence for recognition for either of the word‐object and action‐object pairs, regardless of the initial temporal alignment of these cues. To control for individual differences, we explored factors that might influence associative learning based on parental reports of 1‐ and 2‐year‐olds development, however, developmental measures did not explain word‐action‐object associative learning in either group. We discuss that while young children may benefit from the temporal alignment of multisensory cues as it enables them to actively engage with the multisensory content in real‐time, infants may have been overwhelmed by the complexity of this input. [ABSTRACT FROM AUTHOR]

In recent years, the field of neuroimaging has undergone a paradigm shift, moving away from the traditional brain mapping approach towards the development of integrated, multivariate brain models that can predict categories of mental events. However, large interindividual differences in both brain anatomy and functional localization after standard anatomical alignment remain a major limitation in performing this type of analysis, as it leads to feature misalignment across subjects in subsequent predictive models. This article addresses this problem by developing and validating a new computational technique for reducing misalignment across individuals in functional brain systems by spatially transforming each subject's functional data to a common latent template map. Our proposed Bayesian functional group-wise registration approach allows us to assess differences in brain function across subjects and individual differences in activation topology. We achieve the probabilistic registration with inverse-consistency by utilizing the generalized Bayes framework with a loss function for the symmetric group-wise registration. It models the latent template with a Gaussian process, which helps capture spatial features in the template, producing a more precise estimation. We evaluate the method in simulation studies and apply it to data from an fMRI study of thermal pain, with the goal of using functional brain activity to predict physical pain. We find that the proposed approach allows for improved prediction of reported pain scores over conventional approaches. Received on 2 January 2017. Editorial decision on 8 June 2021 [ABSTRACT FROM AUTHOR]

Background: A major risk factor for neurodegenerative disorders is old age. Nutritional interventions that delay aging, such as calorie restriction (CR) and intermittent fasting (IF), as well as pharmaceuticals that affect the pathways linking nutrition and aging processes, have been developed in recent decades and have been shown to alleviate the effects of aging on the brain. Summary: CR is accomplished by alternating periods of ad libitum feeding and fasting. In animal models, IF has been shown to increase lifespan and slow the progression and severity of age-related pathologies such as cardiovascular and neurodegenerative diseases and cancer. According to recent research, dietary changes can help older people with dementia retain brain function. However, the mechanisms underlying the neuroprotective effect of IF on the aging brain and related questions in this area of study (i.e., the potential of IF to treat neurodegenerative disorders) remain to be examined. Key Messages: This review addresses the hypothesis that IF may have translational potential in protecting the aged brain while summarizing the research supporting the putative neuroprotective mechanisms of IF in animal models. Additionally, given the emerging understanding of the connection between aging and dementia, our investigations may offer a fresh perspective on the use of dietary interventions for enhancing brain function and preventing dementia in elderly individuals. Finally, the absence of guidelines regarding the application of IF in patients hampers its broad utilization in clinical practice, and further studies are needed to improve our knowledge of the long-term effects of IF on dementia before it can be widely prescribed. In conclusion, IF may be an ancillary intervention for preserving memory and cognition in elderly individuals. [ABSTRACT FROM AUTHOR]

Objective Hydroxychloroquine (HCQ) has immunomodulatory, antithrombotic, cardiovascular, antimicrobial, and antineoplastic effects. In this study, we aimed to investigate the antiapoptotic and immunomodulator effects of intraperitoneal HCQ on hypoxic–ischemic (HI) injury in newborn rats. Study Design Wistar albino rats, 7 to 10 days old, were randomly divided into three groups: hypoxic–ischemic encephalopathy (HIE) group, HIE treated with HCQ group, and Sham group. Left common carotid artery ligation and hypoxia model were performed in HIE and HCQ groups. The HCQ group was treated with 80 mg/kg intraperitoneal HCQ every 24 hours for 3 days, while Sham and HIE groups were given physiological saline. After 72 hours, rats were decapitated and brain tissues were stained with hematoxylin and eosin, TUNEL, and IL-1β for histopathological grading and neuronal cell injury. Results Neuronal apoptosis was statistically lower in all neuroanatomical areas in the HCQ group compared with the HIE group. IL-1β-stained areas were similar in both HCQ and HIE groups but significantly higher compared with the Sham group. Histopathological grading scores were found to be lower in the HCQ group on the left parietal cortex and hippocampus region. Conclusion In this study, we have shown for the first time that HCQ treatment decreased apoptosis in HI newborn rat model in both hemispheres. HCQ may be a promising adjuvant therapy in neonatal HIE. Key Points HCQ decreased neuronal apoptosis in the ischemic penumbra of the rat brain. HCQ attenuates hypoxia–ischemia-induced brain injury in neonatal rats. HCQ has no anti-inflammatory effect on HI injury. [ABSTRACT FROM AUTHOR]

Purpose This study aimed to develop a normal brain ageing model based on magnetic resonance imaging and radiomics, therefore identifying radscore, an imaging indicator representing white matter heterogeneity and exploring the significance of radscore in detecting people's cognitive changes. Methods Three hundred sixty cognitively normal (CN) subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database and 105 CN subjects from the Parkinson's Progression Markers Initiative database were used to develop the model. In ADNI, 230 mild cognitive impairment (MCI) subjects were matched with 230 CN old-aged subjects to evaluate their heterogeneity difference. One hundred four MCI subjects with 48 months of follow-up were divided into low and high heterogeneity groups. Kaplan–Meier survival curve analysis was used to observe the importance of heterogeneity results for predicting MCI progression. Results The area under the receiver operating characteristic curve of the model in the training, internal test and external test sets was 0.7503, 0.7512 and 0.7514, respectively. There was a significantly positive correlation between age and radscore of CN subjects (r  = 0.501; P  < .001). The radscore of MCI subjects was significantly higher than that of matched CN subjects (P  < .001). The median radscore ratios of MCI to CN from four age groups (66–70y, 71–75y, 76–80y and 81–85y) were 1.611, 1.760, 1.340 and 1.266, respectively. The probability to progression of low and high heterogeneity groups had a significant difference (P  = .002). Conclusion When radscore is significantly higher than that of normal ageing, it is necessary to alert the possibility of cognitive impairment and deterioration. [ABSTRACT FROM AUTHOR]

Background: Alcohol use disorder (AUD) is commonly associated with distressing psychological symptoms. Pathologic changes associated with AUD have been described in both the gut microbiome and brain, but the mechanisms underlying gut‐brain signaling in individuals with AUD are unknown. This study examined associations among the gut microbiome, brain morphometry, and clinical symptoms in treatment‐seeking individuals with AUD. Methods: We performed a secondary analysis of data collected during inpatient treatment for AUD in subjects who provided gut microbiome samples and had structural brain magnetic resonance imaging (MRI; n = 16). Shotgun metagenomics sequencing was performed, and the morphometry of brain regions of interest was calculated. Clinical symptom severity was quantified using validated instruments. Gut‐brain modules (GBMs) used to infer neuroactive signaling potential from the gut microbiome were generated in addition to microbiome features (e.g., alpha diversity and bacterial taxa abundance). Bivariate correlations were performed between MRI and clinical features, microbiome and clinical features, and MRI and microbiome features. Results: Amygdala volume was significantly associated with alpha diversity and the abundance of several bacteria including taxa classified to Blautia,Ruminococcus, Bacteroides, and Phocaeicola. There were moderate associations between amygdala volume and GBMs, including butyrate synthesis I, glutamate synthesis I, and GABA synthesis I & II, but these relationships were not significant after false discovery rate (FDR) correction. Other bacterial taxa with shared associations to MRI features and clinical symptoms included Escherichia coli and Prevotella copri. Conclusions: We identified gut microbiome features associated with MRI morphometry and AUD‐associated symptom severity. Given the small sample size and bivariate associations performed, these results require confirmation in larger samples and controls to provide meaningful clinical inferences. Nevertheless, these results will inform targeted future research on the role of the gut microbiome in gut‐brain communication and how signaling may be altered in patients with AUD. [ABSTRACT FROM AUTHOR]

Rescuing memory deficits remains a major challenge in treating Alzheimer's disease (AD) and schizophrenia (SCZ). Parvalbumin interneurons (PVIs) mediate network activities relevant to memory functions. Current research suggests that the ability of PVIs to functionally adapt upon increased network activity underlies the generation of memories. The cell-type-specific interaction of neuronal plasticity on the cellular and network level (PVI cell-to-network plasticity) is a promising target in addressing memory deficits. Two clinically accessible strategies targeting PVI plasticity have emerged for the treatment of memory deficits in AD and SCZ: PVI-specific neuromodulation and high-frequency stimulation in the gamma frequency range (40 Hz). Research into clinically assessing PVI cell-to-network plasticity in humans will be essential to transfer current findings into clinical practice. Alzheimer's disease (AD) and schizophrenia (SCZ) represent two major neuropathological conditions with a high disease burden. Despite their distinct etiologies, patients suffering from AD or SCZ share a common burden of disrupted memory functions unattended by current therapies. Recent preclinical analyses highlight cell-type-specific contributions of parvalbumin interneurons (PVIs), particularly the plasticity of their cellular excitability, towards intact neuronal network function (cell-to-network plasticity) and memory performance. Here we argue that deficits of PVI cell-to-network plasticity may underlie memory deficits in AD and SCZ, and we explore two therapeutic avenues: the targeting of PVI-specific neuromodulation, including by neuropeptides, and the recruitment of network synchrony in the gamma frequency range (40 Hz) by external stimulation. We finally propose that these approaches be merged under consideration of recent insights into human brain physiology. [ABSTRACT FROM AUTHOR]

Objectives Cognitive training (CT) has been investigated as a means of delaying age-related cognitive decline in older adults. However, its impact on biomarkers of age-related structural brain atrophy has rarely been investigated, leading to a gap in our understanding of the linkage between improvements in cognition and brain plasticity. This study aimed to explore the impact of CT on cognitive performance and brain structure in older adults. Methods One hundred twenty-four cognitively normal older adults recruited from 2 study sites were randomly assigned to either an adaptive CT (n  = 60) or a casual game training (active control, AC, n  = 64). Results After 10 weeks of training, CT participants showed greater improvements in the overall cognitive composite score (Cohen's d  = 0.66, p  < .01) with nonsignificant benefits after 6 months from the completion of training (Cohen's d  = 0.36, p  = .094). The CT group showed significant maintenance of the caudate volume as well as significant maintained fractional anisotropy in the left internal capsule and in left superior longitudinal fasciculus compared to the AC group. The AC group displayed an age-related decrease in these metrics of brain structure. Discussion Results from this multisite clinical trial demonstrate that the CT intervention improves cognitive performance and helps maintain caudate volume and integrity of white matter regions that are associated with cognitive control, adding to our understanding of the changes in brain structure contributing to changes in cognitive performance from adaptive CT. Clinical Trial Registration NCT03197454 [ABSTRACT FROM AUTHOR]

Patients with cancer receiving infusional chemotherapy show negative symptoms such as worry about their survival, anxiety, anguish, depression, fear, magnified perception of the passage of time, and difficulty managing boredom. Patients also suffer various side effects produced by chemotherapy such as nausea, vomiting, pain, and fatigue, which, together with psychological distress, drastically reduce their quality of life and adherence to therapy with a corresponding reduction in the probability of the individual's survival. Virtual Reality is one of the most innovative and promising digital health interventions, capable of quickly and effectively producing a positive influence on the psychosomatic axis, improving patients' quality of life during chemotherapy. Virtual Reality, through its 3-dimensional multisensory technology, isolates sensory channels from the negative external environment and enables an experience of being physically and psychologically present within virtual scenarios, in which patients can perceive sensations, emotions, cognitions, and interactions as if they really were in different surroundings. This article systematically expounds the scientific conditions necessary for effective, appropriate, and safe implementation of Virtual Reality interventions in holistic nursing practice, describing the underpinning conceptual framework, the types, technological characteristics, methods of use, duration, type of virtual content, and implementation procedure of Virtual Reality. [ABSTRACT FROM AUTHOR]

Dementia, or major neurocognitive disorder, is one of the most common causes of disability and dependency in older adults with far-reaching social, physical, and economic impacts. In the absence of adequate treatment, much research has been directed towards prevention. Physical exercise has been shown to increase cerebral blood flow, amplify production of neurotrophic factors, and enhance brain volume. Whether these changes on a structural and cellular level result in cognitive preservation is less clear. This systematic review synthesizes findings from seventeen randomized controlled trials that examine the effects of physical activity on global cognition, memory, and executive function in older adults. Cognitive benefits of exercise are strongest for those who are cognitively intact or with mild cognitive impairment. In studies with long-term follow up, cognitive gains tended to decay after cessation of physical intervention suggesting that sustained physical exercise may be required to preserve cognitive function in older adults prior to onset of dementia. [ABSTRACT FROM AUTHOR]

Background: The rising prevalence of mental and psychological issues among immigrants has garnered increased attention due to the significant growth in immigrant populations in recent years. In this context, exploring the connection between psychological health, cognitive flexibility, brain-behavioral systems, and sensory processing in Iranian immigrants in Canada is becoming an essential research goal. Objectives: The aim of this study was to explore the relationships between psychological health, cognitive flexibility, brain-behavioral systems, and sensory processing among Iranian immigrants in Canada. Methods: A cross-sectional study design was used, gathering data from 400 Iranian students (198 males and 202 females) enrolled at universities in Canada and Iran. We collected participants' demographic details and assessed their psychological health, cognitive flexibility, brain-behavioral systems, and sensory processing through standardized instruments. Psychological health was evaluated using the Beck Anxiety Inventory, cognitive flexibility was measured with the Dennis and Vander Wall Cognitive Flexibility Questionnaire, and sensory processing was appraised via the adolescent/adult sensory profile. The Carver and White behavioral inhibition system (BIS)/behavioral activation system (BAS) scales were utilized to measure brain-behavioral systems. Statistical analyses, including correlation analysis and multivariate regression, were conducted to investigate the relationships among these variables. Results: The correlation analysis revealed significant positive associations between anxiety and low registration (r = 0.283, P < 0.001), sensory sensitivity (r = 0.442, P < 0.001), and sensory avoiding (r = 0.307, P < 0.001) in immigrant students. Anxiety also showed nonsignificant negative correlations with the behavioral activation system-drive (r = -0.042, P = 0.551) and behavioral activation system-reward responsiveness (r = -0.090, P = 0.203). The multivariate regression analysis found that low registration (B = 0.177, P = 0.036), sensory sensitivity (B = 0.336, P < 0.001), and cognitive flexibility (B = 0.119, P = 0.025) significantly predicted anxiety levels in immigrant students. An adjusted R-squared value of 0.191 indicated that these variables together explained 19.1% of the variance in anxiety levels. Conclusions: This study underscores the significant links between sensory processing patterns, cognitive flexibility, brain-behavioral systems, and anxiety among Iranian immigrant students. These findings highlight the need for interventions focusing on teaching cognitive skills strategies and increasing awareness of sensory needs to help reduce anxiety levels in this population. [ABSTRACT FROM AUTHOR]

The continuing challenge of improving the quality of the biocontrol of robotic wheelchairs is addressed and a solution consisting of an integrated approach based on the combined use of gaze control and neurocontrol methods is proposed; the stages in implementing this approach are considered. The problems arising in creating gaze-controlled robotic vehicles are discussed and challenges occurring in the implementation of biocontrol and ways to solve them are analyzed. A method for selecting the most effective electroencephalography leads, based on the use of an international signal database, was developed. A convolutional neural network architecture was developed for the joint classification of eye-tracking and brain signals. Results from a study of neural networks are presented, these demonstrating a maximum prediction accuracy using the pre-trained InceptionV3 model. [ABSTRACT FROM AUTHOR]

The article is devoted to the study of the psychological characteristics of self-regulation mechanisms in students in stressful situations. In the article, the theoretical analysis and generalization of works related to the problem, a set of psychodiagnostic methods were used. The research base was the requirements of Odlar Yurdu University and various faculties of Baku State University. 135 second and third year students aged 18-23 participated in the study. A systematic approach was applied to the description and study of the research object for the reliability and validity of the research results. Mathematical methods were used for empirical data processing. Thus, according to the results of the correlation analysis, a relationship between stress resistance and self-regulation was found among the respondents. We see a negative relationship (r≤0.01) between stress resistance and self-regulation and one of its styles. This shows that there is a correlation between stress resistance, self-esteem and emotional stability and self-regulation. As self-regulation increases, the impact of stressful situations decreases. We believe that the present analysis can contribute to a better understanding of the mechanisms underlying successful and unsuccessful stress regulation. It should be taken into account that this will help prevent mental disorders and improve treatment. [ABSTRACT FROM AUTHOR]

Background and Hypothesis This study investigated the role of the medial prefrontal cortex (mPFC)-basolateral amygdala (BLA) pathway in schizophrenia (SCZ)-related cognitive impairments using various techniques. Study Design This study utilized clinical scales, magnetic resonance imaging, single-cell RNA sequencing, and optogenetics to investigate the mPFC-BLA pathway in SCZ patients. In the mouse model, 6-week-old methylazoxymethanol acetate-induced mice demonstrated significant cognitive deficits, which were addressed through stereotaxic injections of an adeno-associated viral vector to unveil the neural connection between the mPFC and BLA. Study Results Significant disparities in brain volume and neural activity, particularly in the dorsolateral prefrontal cortex (DLPFC) and BLA regions, were found between SCZ patients and healthy controls. Additionally, we observed correlations indicating that reduced volumes of the DLPFC and BLA were associated with lower cognitive function scores. Activation of the mPFC-BLA pathway notably improved cognitive performance in the SCZ model mice, with the targeting of excitatory or inhibitory neurons alone failing to replicate this effect. Single-cell transcriptomic profiling revealed gene expression differences in excitatory and inhibitory neurons in the BLA of SCZ model mice. Notably, genes differentially expressed in the BLA of these model mice were also found in the blood exosomes of SCZ patients. Conclusions Our research provides a comprehensive understanding of the role of the PFC-BLA pathway in SCZ, underscoring its significance in cognitive impairment and offering novel diagnostic and therapeutic avenues. Additionally, our research highlights the potential of blood exosomal mRNAs as noninvasive biomarkers for SCZ diagnosis, underscoring the clinical feasibility and utility of this method. [ABSTRACT FROM AUTHOR]

Background Ventral striatal hypoactivation during reward anticipation has consistently been observed in patients with schizophrenia. In addition, that hypoactivation has been shown to correlate negatively with negative symptoms, and in particular with apathy. However, little is known about the stability of these results over time and their reliability across different centers. Methods In total, 67 patients with schizophrenia (15 females) and 55 healthy controls (13 females) were recruited in 2 centers in Switzerland and Germany. To assess the neural bases of reward anticipation, all participants performed a variant of the Monetary Incentive Delay task while undergoing event-related functional magnetic resonance imaging at baseline and after 3 months. Stability over time was measured using intra-class correlation (ICC(A,1)) and stability between centers was measured with mixed models. Results Results showed the expected ventral striatal hypoactivation in patients compared to controls during reward anticipation. We showed that these results were stable across centers. The primary analysis did not reveal an effect of time. Test-retest reliability was moderate for controls, and poor for patients. We did not find an association between ventral striatal hypoactivation and negative symptoms in patients. Conclusions Our results align with the hypothesis that ventral striatal activation is related to modulation of motivational saliency during reward anticipation. They also confirm that patients with schizophrenia show impaired reward anticipation. However, the poor test-retest reliability and the absence of an association with symptoms suggests that further research is needed before ventral striatal activity can be used as a biomarker on the individual patient level. [ABSTRACT FROM AUTHOR]

Background and Hypothesis The brain-predicted age difference (brain-PAD) may serve as a biomarker for neurodegeneration. We investigated the brain-PAD in patients with schizophrenia (SCZ), first-episode schizophrenia spectrum disorders (FE-SSDs), and treatment-resistant schizophrenia (TRS) using structural magnetic resonance imaging (sMRI). Study Design We employed a convolutional network-based regression (SFCNR), and compared its performance with models based on three machine learning (ML) algorithms. We pretrained the SFCNR with sMRI data of 7590 healthy controls (HCs) selected from the UK Biobank. The parameters of the pretrained model were transferred to the next training phase with a new set of HCs (n  = 541). The brain-PAD was analyzed in independent HCs (n  = 209) and patients (n  = 233). Correlations between the brain-PAD and clinical measures were investigated. Study Results The SFCNR model outperformed three commonly used ML models. Advanced brain aging was observed in patients with SCZ, FE-SSDs, and TRS compared to HCs. A significant difference in brain-PAD was observed between FE-SSDs and TRS with ridge regression but not with the SFCNR model. Chlorpromazine equivalent dose and cognitive function were correlated with the brain-PAD in SCZ and FE-SSDs. Conclusions Our findings indicate that there is advanced brain aging in patients with SCZ and higher brain-PAD in SCZ can be used as a surrogate marker for cognitive dysfunction. These findings warrant further investigations on the causes of advanced brain age in SCZ. In addition, possible psychosocial and pharmacological interventions targeting brain health should be considered in early-stage SCZ patients with advanced brain age. [ABSTRACT FROM AUTHOR]

Background and Hypothesis Schizophrenia involves microstructural changes in white matter (WM) tracts. Oxidative stress is a key factor causing WM damage by hindering oligodendrocyte development and myelin maturation. Uric acid (UA), an endogenous antioxidant, may protect against oxidative stress. We investigated the effect of UA on WM connectivity in antipsychotic-naive or -free patients with early- or chronic-stage schizophrenia. Study Design A total of 192 patients with schizophrenia (122 recent-onset [ROS] and 70 chronic [CS]) and 107 healthy controls (HCs) participated in this study. Diffusion tensor imaging data and serum UA levels at baseline were obtained. Study Results Fractional anisotropy was lower in the widespread WM regions across the whole brain, and diffusivity measures were higher in both schizophrenia groups than in HCs. The CS group showed lower diffusivity in some WM tracts than the ROS or HC groups. The linear relationship of serum UA levels with axial and mean diffusivity in the right frontal region was significantly different between schizophrenia stages, which was driven by a negative association in the CS group. WM diffusivity associated with serum UA levels correlated with 8-week treatment responses only in patients with CS, suggesting UA to be protective against long-term schizophrenia. Conclusions UA may protect against the WM damage associated with the progression of schizophrenia by reducing oxidative stress and supporting WM repair against oxidative damage. These results provide insights into the positive role of UA and may facilitate the development of novel disease-modifying therapies. [ABSTRACT FROM AUTHOR]

Osteopathic manipulative treatment (OMT) is a hands-on therapy aiming to achieve the global homeostasis of the patient. OMT focuses on treating the somatic dysfunctions characterized by tissue modifications, body asymmetry, and range-of-motion restrictions. The benefits related to OMT are thought to be associated with the interconnectedness of the body's systems and the inherent capacity for self-healing. However, whether OMT can influence brain activity, and, consequently, neurophysiological responses is an open research question. Our research investigates the literature to identify the effects of OMT on brain activity. The main purpose of the research question is: can OMT influence brain activity and consequently neurophysiological responses? A scoping review was conducted, searching the following databases: PubMed, Google Scholar, and OSTEOMED.DR (Osteopathic Medical Digital Repository), Scopus, Web of Science (WoS), and Science Direct. The initial search returned 114 articles, and after removing duplicates, 69 were considered eligible to be included in the final sample. In the end, eight studies (six randomized controlled trials, one pilot study, and one cross-over study) were finally included and analyzed in this review. In conclusion, OMT seems to have a role in influencing functional changes in brain activity in healthy individuals and even more in patients with chronic musculoskeletal pain. However, further RCT studies are needed to confirm these findings. Registration protocol: CRD42024525390. [ABSTRACT FROM AUTHOR]

The molecular mechanisms underlying neuronal dysfunction in Alzheimer's disease (AD) remain uncharacterized. Here, we identify genes, molecular pathways and cellular components associated with whole-brain dysregulation caused by amyloid-beta (Aβ) and tau deposits in the living human brain. We obtained in-vivo resting-state functional MRI (rs-fMRI), Aβ- and tau-PET for 47 cognitively unimpaired and 16 AD participants from the Translational Biomarkers in Aging and Dementia cohort. Adverse neuronal activity impacts by Aβ and tau were quantified with personalized dynamical models by fitting pathology-mediated computational signals to the participant's real rs-fMRIs. Then, we detected robust brain-wide associations between the spatial profiles of Aβ-tau impacts and gene expression in the neurotypical transcriptome (Allen Human Brain Atlas). Within the obtained distinctive signature of in-vivo neuronal dysfunction, several genes have prominent roles in microglial activation and in interactions with Aβ and tau. Moreover, cellular vulnerability estimations revealed strong association of microglial expression patterns with Aβ and tau's synergistic impact on neuronal activity (q < 0.001). These results further support the central role of the immune system and neuroinflammatory pathways in AD pathogenesis. Neuronal dysregulation by AD pathologies also associated with neurotypical synaptic and developmental processes. In addition, we identified drug candidates from the vast LINCS library to halt or reduce the observed Aβ-tau effects on neuronal activity. Top-ranked pharmacological interventions target inflammatory, cancer and cardiovascular pathways, including specific medications undergoing clinical evaluation in AD. Our findings, based on the examination of molecular-pathological-functional interactions in humans, may accelerate the process of bringing effective therapies into clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: The clinical symptoms of Lumbar Disc Herniation (LDH) can be effectively ameliorated through Lever Positioning Manipulation (LPM), which is closely linked to the brain's pain-regulating mechanisms. Magnetic Resonance Imaging (MRI) offers an objective and visual means to study how the brain orchestrates the characteristics of analgesic effects. From the perspective of multimodal MRI, we applied functional MRI (fMRI) and Magnetic Resonance Spectrum (MRS) techniques to comprehensively evaluate the characteristics of the effects of LPM on the brain region of LDH from the aspects of brain structure, brain function and brain metabolism. This multimodal MRI technique provides a biological basis for the clinical application of LPM in LDH. Methods and analysis: A total of 60 LDH patients and 30 healthy controls, matched by gender, age, and years of education, will be enrolled in this study. The LDH patients will be divided into two groups (Group 1, n = 30; Group 2, n = 30) using a random number table method. Group 1 will receive LPM treatment once every two days, for a total of 12 times over 4 weeks. Group 2 will receive sham LPM treatment during the same period as Group 1. All 30 healthy controls will be divided into Group 3. Multimodal MRI will be performed on Group 1 and Group 2 at three time points (TPs): before LPM (TP1), after one LPM session (TP2), and after a full course of LPM treatment. The healthy controls (Group 3) will not undergo LPM and will be subject to only a single multimodal MRI scan. Participants in both Group 1 and Group 2 will be required to complete clinical questionnaires. These assessments will focus on pain intensity and functional disorders, using the Visual Analog Scale (VAS) and the Japanese Orthopaedic Association (JOA) scoring systems, respectively. Discussion: The purpose of this study is to investigate the multimodal brain response characteristics of LDH patients after treatment with LPM, with the goal of providing a biological basis for clinical applications. Trial registration number: https://clinicaltrials.gov/ct2/show/NCT05613179, identifier: NCT05613179. [ABSTRACT FROM AUTHOR]

Chronic low back pain patients often experience recurrent episodes due to various peripheral and central factors, leading to physical and mental impairments, affecting their daily life and work, and increasing the healthcare burden. With the continuous advancement of neuropathological research, changes in brain structure and function in chronic low back pain patients have been revealed. Neuroplasticity is an important mechanism of self-regulation in the brain and plays a key role in neural injury repair. Targeting neuroplasticity and regulating the central nervous system to improve functional impairments has become a research focus in rehabilitation medicine. Recent studies have shown that exercise can have beneficial effects on the body, such as improving cognition, combating depression, and enhancing athletic performance. Exercise-induced neuroplasticity may be a potential mechanism through which exercise affects the brain. This article systematically introduces the theory of exercise-induced neuroplasticity, explores the central effects mechanism of exercise on patients with chronic low back pain, and further looks forward to new directions in targeted neuroplasticity-based rehabilitation treatment for chronic low back pain. [ABSTRACT FROM AUTHOR]

The optical brain imaging method functional near-infrared spectroscopy (fNIRS) is a promising tool for real-time applications such as neurofeedback and brain-computer interfaces. Its combination of spatial specificity and mobility makes it particularly attractive for clinical use, both at the bedside and in patients' homes. Despite these advantages, optimizing fNIRS for real-time use requires careful attention to two key aspects: ensuring good spatial specificity and maintaining high signal quality. While fNIRS detects superficial cortical brain regions, consistently and reliably targeting specific regions of interest can be challenging, particularly in studies that require repeated measurements. Variations in cap placement coupled with limited anatomical information may further reduce this accuracy. Furthermore, it is important tomaintain good signal quality in real-time contexts to ensure that they reflect the true underlying brain activity. However, fNIRS signals are susceptible to contamination by cerebral and extracerebral systemic noise as well as motion artifacts. Insufficient real-time preprocessing can therefore cause the system to run on noise instead of brain activity. The aim of this review article is to help advance the progress of fNIRS-based real-time applications. It highlights the potential challenges in improving spatial specificity and signal quality, discusses possible options to overcome these challenges, and addresses further considerations relevant to real-time applications. By addressing these topics, the article aims to help improve the planning and execution of future real-time studies, thereby increasing their reliability and repeatability. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are membrane-bound vesicles secreted by all cell types that play a central role in cell-to-cell communication. Since these vesicles serve as vehicles of cellular content (nucleic acids, proteins and lipids) with the potential to cross biological barriers, they represent a novel attractive window into an otherwise inaccessible organ, such as the brain. The composition of EVs is cell-type specific and mirrors the physiological condition of the cell-of-origin. Consequently, during viral infection, EVs undergo significant changes in their content and morphology, thereby reflecting alterations in the cellular state. Here, we briefly summarize the potential of brain-derived EVs as a lens into viral infection in the central nervous system, thereby: 1) uncovering underlying pathophysiological processes at play and 2) serving as liquid biopsies of the brain, representing a non-invasive source of biomarkers for monitoring disease activity. Although translating the potential of EVs from research to diagnosis poses complexities, characterizing brain-derived EVs in the context of viral infections holds promise to enhance diagnostic and therapeutic strategies, offering new avenues for managing infectious neurological diseases. [ABSTRACT FROM AUTHOR]

Forward head posture (FHP) is a common postural problem experienced by most people. However, its effect on brain activity is still unknown. Accordingly, we aimed to observe changes in brain waves at rest to determine the effect of FHP on the nervous systems. A total of 33 computer users (Male = 17; Female = 16; age = 22.18 ± 1.88) were examined in both FHP and neutral posture. For each session, brain waves were measured for 5 min, and then muscle mechanical properties and cranio-vertebral angle (CVA) were measured. Changes in brain waves between the neutral posture and FHP were prominent in gamma waves. A notable increase was confirmed in the frontal and parietal lobes. That is, eight channels in the frontal lobe and all channels in the parietal lobe showed a significant increase in FHP compared to neutral posture. Additionally, FHP changes were associated with a decrease in CVA (p < 0.001), an increase in levator scapulae tone (Right, p = 0.014; Left, p = 0.001), and an increase in right sternocleidomastoid stiffness (p = 0.002), and a decrease in platysma elasticity (Right, p = 0.039; Left, p = 0.017). The change in CVA was found to have a negative correlation with the gamma activity (P7, p = 0.044; P8, p = 0.004). Therefore, increased gamma wave activity in FHP appears to be related to CVA decrease due to external force that was applied to the nervous system and cervical spine. [ABSTRACT FROM AUTHOR]

This narrative review examines the intricate psychophysiological interplay between cognitive functions and physical responses within military personnel engaged in combat. It elucidates the spectrum of responses elicited by symmetric and asymmetric warfare alongside specialised combat scenarios, including close-quarters and subterranean warfare. Central to this discourse is the emphasis on integrating training programs beyond physical conditioning to encompass psychological resilience and decision-making efficacy under duress. The exploration further ventures into applying advanced technologies such as virtual reality and wearable devices, highlighting their pivotal role in augmenting training outcomes and supporting soldier health. Through a detailed analysis of psychophysiological variations across different military branches of service, the narrative review advocates for bespoke training regimens and support frameworks tailored to address the unique exigencies of each service branch. Concluding observations stress the importance of evolving military training paradigms, advocating for adopting realistic, immersive training simulations that mirror the complexities of the contemporary battlefield. This synthesis aims to contribute to the ongoing discourse on optimising military training protocols and enhancing the operational readiness and well-being of armed forces personnel. This narrative review is essential for military psychologists, trainers, and policymakers, aiming to bridge the gap between theoretical knowledge and practical implementation in military training programs. [ABSTRACT FROM AUTHOR]

Oedema occurs when higher than normal amounts of solutes and water accumulate in tissues. In brain parenchymal tissue, vasogenic oedema arises from changes in blood–brain barrier permeability, e.g. in peritumoral oedema. Cytotoxic oedema arises from excess accumulation of solutes within cells, e.g. ischaemic oedema following stroke. This type of oedema is initiated when blood flow in the affected core region falls sufficiently to deprive brain cells of the ATP needed to maintain ion gradients. As a consequence, there is: depolarization of neurons; neural uptake of Na+ and Cl− and loss of K+; neuronal swelling; astrocytic uptake of Na+, K+ and anions; swelling of astrocytes; and reduction in ISF volume by fluid uptake into neurons and astrocytes. There is increased parenchymal solute content due to metabolic osmolyte production and solute influx from CSF and blood. The greatly increased [K+]isf triggers spreading depolarizations into the surrounding penumbra increasing metabolic load leading to increased size of the ischaemic core. Water enters the parenchyma primarily from blood, some passing into astrocyte endfeet via AQP4. In the medium term, e.g. after three hours, NaCl permeability and swelling rate increase with partial opening of tight junctions between blood–brain barrier endothelial cells and opening of SUR1-TPRM4 channels. Swelling is then driven by a Donnan-like effect. Longer term, there is gross failure of the blood–brain barrier. Oedema resolution is slower than its formation. Fluids without colloid, e.g. infused mock CSF, can be reabsorbed across the blood–brain barrier by a Starling-like mechanism whereas infused serum with its colloids must be removed by even slower extravascular means. Large scale oedema can increase intracranial pressure (ICP) sufficiently to cause fatal brain herniation. The potentially lethal increase in ICP can be avoided by craniectomy or by aspiration of the osmotically active infarcted region. However, the only satisfactory treatment resulting in retention of function is restoration of blood flow, providing this can be achieved relatively quickly. One important objective of current research is to find treatments that increase the time during which reperfusion is successful. Questions still to be resolved are discussed. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is neurodegenerative disease in middle-aged and elderly people with some pathological mechanisms including immune disorder, neuroinflammation, white matter injury and abnormal aggregation of alphasynuclein, etc. New research suggests that white matter injury may be important in the development of PD, but how inflammation, the immune system, and white matter damage interact to harm dopamine neurons is not yet understood. Therefore, it is particularly important to delve into the crosstalk between immune cells in the central and peripheral nervous system based on the study of white matter damage in PD. This crosstalk could not only exacerbate the pathological process of PD but may also reveal new therapeutic targets. By understanding how immune cells penetrate through the blood-brain barrier and activate inflammatory responses within the central nervous system, we can better grasp the impact of structural destruction of white matter in PD and explore how this process can be modulated to mitigate or combat disease progression. Microglia, astrocytes, oligodendrocytes and peripheral immune cells (especially T cells) play a central role in its pathological process where these immune cells produce and respond to pro-inflammatory cytokines such as tumor necrosis factor (TNF-α), interleukin-1β(IL-1β) and interleukin-6(IL-6), and white matter injury causes microglia to become pro-inflammatory and release inflammatory mediators, which attract more immune cells to the damaged area, increasing the inflammatory response. Moreover, white matter damage also causes dysfunction of blood-brain barrier, allows peripheral immune cells and inflammatory factors to invade the brain further, and enhances microglia activation forming a vicious circle that intensifies neuroinflammation. And these factors collectively promote the neuroinflammatory environment and neurodegeneration changes of PD. Overall, these findings not only deepen our understanding of the complexity of PD, but also provide new targets for the development of therapeutic strategies focused on inflammation and immune regulation mechanisms. In summary, this review provided the theoretical basis for clarifying the pathogenesis of PD, summarized the association between white matter damage and the immune cells in the central and peripheral nervous systems, and then emphasized their potential specific mechanisms of achieving crosstalk with further aggravating the pathological process of PD. [ABSTRACT FROM AUTHOR]

Objective: We aimed to use the onset time of Alzheimer's disease (AD) as the reference time to longitudinally investigate the atrophic characteristics of brain structures prior to the onset of AD. Materials and methods: A total of 328 participants from the ADNI database with clear onset of AD and structural imaging data were included in our study. The time before the onset of AD (abbreviated as BAD) was calculated. We investigated the longitudinal brain changes in 97 regions using multivariate linear mixed effects regression models. Results: The average BAD was -28.15 months, with a range from -156 to 0 months. The 54 brain regions showed significant atrophy prior to the onset of AD, and these regions were mainly distributed in the frontal and temporal lobes. The parietal and occipital lobe exhibited relatively less atrophy than the other brain lobes. Sex, age, and magnetic field strength had greater direct impacts on structural indicators than APOE genotype and education. The analysis of interaction effects revealed that the APOE +4 mutation carriers exhibited more severe structural changes in specific brain regions as the BAD increased. However, sex, age, and education had minimal regulatory influence on the structural changes associated with BAD. Conclusion: Longitudinal analysis, with the onset time point of AD as the reference, can accurately describe the features of structural changes preceding the onset of AD and provide a comprehensive understanding of AD development. [ABSTRACT FROM AUTHOR]

Background: Abnormal neuronal synchrony is associated with several neurological disorders, including Parkinson's disease (PD), essential tremor, dystonia, and epilepsy. Coordinated reset (CR) stimulation was developed computationally to counteract abnormal neuronal synchrony. During CR stimulation, phase-shifted stimuli are delivered to multiple stimulation sites. Computational studies in plastic neural networks reported that CR stimulation drove the networks into an attractor of a stable desynchronized state by downregulating synaptic connections, which led to long-lasting desynchronization effects that outlasted stimulation. Later, corresponding long-lasting desynchronization and therapeutic effects were found in animal models of PD and PD patients. To date, it is unclear how spatially dependent synaptic connections, as typically observed in the brain, shape CR-induced synaptic downregulation and long-lasting effects. Methods: We performed numerical simulations of networks of leaky integrate-and-fire neurons with spike-timing-dependent plasticity and spatially dependent synaptic connections to study and further improve acute and long-term responses to CR stimulation. Results: The characteristic length scale of synaptic connections relative to the distance between stimulation sites plays a key role in CR parameter adjustment. In networks with short synaptic length scales, a substantial synaptic downregulation can be achieved by selecting appropriate stimulus-related parameters, such as the stimulus amplitude and shape, regardless of the employed spatiotemporal pattern of stimulus deliveries. Complex stimulus shapes can induce local connectivity patterns in the vicinity of the stimulation sites. In contrast, in networks with longer synaptic length scales, the spatiotemporal sequence of stimulus deliveries is of major importance for synaptic downregulation. In particular, rapid shuffling of the stimulus sequence is advantageous for synaptic downregulation. Conclusion: Our results suggest that CR stimulation parameters can be adjusted to synaptic connectivity to further improve the long-lasting effects. Furthermore, shuffling of CR sequences is advantageous for long-lasting desynchronization effects. Our work provides important hypotheses on CR parameter selection for future preclinical and clinical studies. [ABSTRACT FROM AUTHOR]

Background: Migraine is a neurological disease with a significant genetic component and is characterized by recurrent and prolonged episodes of headache. Previous epidemiological studies have reported a higher risk of dementia in migraine patients. Neuroimaging studies have also shown structural brain atrophy in regions that are common to migraine and dementia. However, these studies are observational and cannot establish causality. The present study aims to explore the genetic causal relationship between migraine and dementia, as well as the mediation roles of brain structural changes in this association using Mendelian randomization (MR). Methods: We collected the genome-wide association study (GWAS) summary statistics of migraine and its two subtypes, as well as four common types of dementia, including Alzheimer's disease (AD), vascular dementia, frontotemporal dementia, and Lewy body dementia. In addition, we collected the GWAS summary statistics of seven longitudinal brain measures that characterize brain structural alterations with age. Using these GWAS, we performed Two-sample MR analyses to investigate the causal effects of migraine and its two subtypes on dementia and brain structural changes. To explore the possible mediation of brain structural changes between migraine and dementia, we conducted a two-step MR mediation analysis. Results: The MR analysis demonstrated a significant association between genetically predicted migraine and an increased risk of AD (OR = 1.097, 95% CI = [1.040, 1.158], p = 7.03 × 10− 4). Moreover, migraine significantly accelerated annual atrophy of the total cortical surface area (-65.588 cm2 per year, 95% CI = [-103.112, -28.064], p = 6.13 × 10− 4) and thalamic volume (-9.507 cm3 per year, 95% CI = [-15.512, -3.502], p = 1.91 × 10− 3). The migraine without aura (MO) subtype increased the risk of AD (OR = 1.091, 95% CI = [1.059, 1.123], p = 6.95 × 10− 9) and accelerated annual atrophy of the total cortical surface area (-31.401 cm2 per year, 95% CI = [-43.990, -18.811], p = 1.02 × 10− 6). The two-step MR mediation analysis revealed that thalamic atrophy partly mediated the causal effect of migraine on AD, accounting for 28.2% of the total effect. Discussion: This comprehensive MR study provided genetic evidence for the causal effect of migraine on AD and identified longitudinal thalamic atrophy as a potential mediator in this association. These findings may inform brain intervention targets to prevent AD risk in migraine patients. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is a chronic neurodegenerative disease that affects the central nervous system, primarily the motor nervous system, and occurs most often in older adults. A large number of studies have shown that high intelligence leads to an increased risk of PD. However, whether there is a causal relationship between intelligence on PD has not yet been reported. Methods: In this study, Mendelian randomization (MR) analysis was performed with intelligence (ebi-a-GCST006250) and fluid intelligence score (ukb-b-5238) as exposure factors and PD (ieu-b-7) as an outcome, which the datasets were mined from the IEU OpenGWAS database. MR analysis was performed through 3 methods [MR Egger, weighted median, inverse variance weighted (IVW)], of which IVW was the primary method. In addition, the reliability of the results of the MR analysis was assessed via the heterogeneity test, the horizontal polytropy test, and Leave-One-Out (LOO). Finally, based on gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, the genes corresponding to intelligence and fluid intelligence score related to SNPs were enriched for functional features and pathways. Results: The results of MR analysis suggested that elevated intelligence indicators can increase the risk of PD [p = 0.015, Odd Ratio (OR) = 1.316]. Meanwhile, fluid intelligence score was causally associated with the PD (p = 0.035), which was a risk factor (OR = 1.142). The reliability of the results of MR analysis was demonstrated by sensitivity analysis. Finally, the results of GO enrichment analysis for 87 genes corresponding to intelligence related SNPs mainly included regulation of synapse organization, developmental cell growth, etc. These genes were enriched in the synaptic vessel cycle, polycomb expressive complex in KEGG. Similarly, 44 genes corresponding to SNPs associated with fluid intelligence score were used for enrichment analysis. Based on the GO database, these genes were mainly enriched in regulation of developmental growth, negative regulation of neuron projection development, etc. In KEGG, 44 genes corresponding to SNPs associated with fluid intelligence score were enriched in signaling pathways including Alzheimer's disease, the cellular senescence, etc. Conclusion: The causal relationships between intelligence and fluid intelligence scores, and PD were demonstrated through MR analysis, providing an important reference and evidence for the study of PD. [ABSTRACT FROM AUTHOR]

Objectives: People with Alzheimer's Disease (AD) experience changes in their level and content of consciousness, but there is little research on biomarkers of consciousness in pre‐clinical AD and Mild Cognitive Impairment (MCI). This study investigated whether levels of consciousness are decreased in people with MCI. Methods: A multi‐site site magnetoencephalography (MEG) dataset, BIOFIND, comprising 83 people with MCI and 83 age matched controls, was analysed. Arousal (and drowsiness) was assessed by computing the theta‐alpha ratio (TAR). The Lempel‐Ziv algorithm (LZ) was used to quantify the information content of brain activity, with higher LZ values indicating greater complexity and potentially a higher level of consciousness. Results: LZ was lower in the MCI group versus controls, indicating a reduced level of consciousness in MCI. TAR was higher in the MCI group versus controls, indicating a reduced level of arousal (i.e. increased drowsiness) in MCI. LZ was also found to be correlated with mini‐mental state examination (MMSE) scores, suggesting an association between cognitive impairment and level of consciousness in people with MCI. Conclusions: A decline in consciousness and arousal can be seen in MCI. As cognitive impairment worsens, measured by MMSE scores, levels of consciousness and arousal decrease. These findings highlight how monitoring consciousness using biomarkers could help understand and manage impairments found at the preclinical stages of AD. Further research is needed to explore markers of consciousness between people who progress from MCI to dementia and those who do not, and in people with moderate and severe AD, to promote person‐centred care. Key points: Consciousness and Arousal in MCI: This study found that patients with Mild Cognitive Impairment (MCI) show reduced neural complexity and arousal levels, as measured by LZsum and theta‐alpha ratio (TAR), respectively. These reductions correlate with the severity of cognitive impairment.Correlation with Cognitive Tests: There is a significant correlation between the LZsum and TAR biomarkers and the Mini‐Mental State Examination (MMSE) scores, both overall and within the MCI group, indicating that these neural markers can reflect the extent of cognitive decline.Potential Early Indicators: The biomarkers used in the study not only showed a significant difference between MCI patients from controls, but are also sensitive to the degree of cognitive impairment, supporting their use in monitoring the early stages of dementia and suggesting that disruptions in consciousness may begin in preclinical stages.Implications for Management and Support: The findings underscore the importance of understanding subtle changes in arousal and awareness in MCI for patient‐cantered care. Such insights could help develop interventions to improve the daily functioning and quality of life of patients with MCI and Alzheimer's disease (AD), particularly as these changes in consciousness can affect decision‐making capacity, caregiver stress, and overall relationship quality. [ABSTRACT FROM AUTHOR]

Purpose: This study examined children's ability to perceive speech from multiple locations on the horizontal plane. Children with hearing loss were compared to normal-hearing peers while using amplification with and without advanced noise management. Method: Participants were 21 children with normal hearing (9-15 years) and 12 children with moderate symmetrical hearing loss (11-15 years). Word recognition, nonword detection, and word recall were assessed. Stimuli were presented randomly from multiple discrete locations in multitalker noise. Children with hearing loss were fit with devices having separate omnidirectional and noise management programs. The noise management feature is designed to preserve audibility in noise by rapidly analyzing input from all locations and reducing the noise management when speech is detected from locations around the hearing aid user. Results: Significant effects of left/right and front/back lateralization occurred as well as effects of hearing loss and hearing aid noise management. Children with normal hearing experienced a left-side advantage for word recognition and a right-side advantage for nonword detection. Children with hearing loss demonstrated poorer performance overall on all tasks with better word recognition from the back, and word recall from the right, in the omnidirectional condition. With noise management, performance improved from the front compared to the back for all three tasks and from the right for word recognition and word recall. Conclusions: The shape of children's local speech intelligibility on the horizontal plane is not omnidirectional. It is task dependent and shaped further by hearing loss and hearing aid signal processing. Front/back shifts in children with hearing loss are consistent with the behavior of hearing aid noise management, while the right-side biases observed in both groups are consistent with the effects of specialized speech processing in the left hemisphere of the brain. [ABSTRACT FROM AUTHOR]