Alzheimer’s disease (AD) is a common central neurodegenerative disease disorder characterized primarily by cognitive impairment and non-cognitive neuropsychiatric symptoms that significantly impact patients’ daily lives and behavioral functioning. The pathogenesis of AD remains unclear and current Western medicines treatment are purely symptomatic, with a singular pathway, limited efficacy, and substantial toxicity and side effects. In recent years, as research into AD has deepened, there has been a gradual increase in the exploration and application of medicinal plants for the treatment of AD. Numerous studies have shown that medicinal plants and their active ingredients can potentially mitigate AD by regulating various molecular mechanisms, including the production and aggregation of pathological proteins, oxidative stress, neuroinflammation, apoptosis, mitochondrial dysfunction, neurogenesis, neurotransmission, and the brain-gut microbiota axis. In this review, we analyzed the pathogenesis of AD and comprehensively summarized recent advancements in research on medicinal plants for the treatment of AD, along with their underlying mechanisms and clinical evidence. Ultimately, we aimed to provide a reference for further investigation into the specific mechanisms through which medicinal plants prevent and treat AD, as well as for the identification of efficacious active ingredients derived from medicinal plants.
Glioma is the most common malignancy in the central nervous system. Even with optimal therapies, glioblastoma (the most aggressive form of glioma) is incurable, with only 26.5% of patients having a 2-year survival rate. The present meta-analysis evaluated the association of magnetic resonance imaging (MRI)-derived parameters in glioma patients with progression-free survival (PFS) and overall survival. Eligible clinical articles on glioma patients included those that contained an evaluation of the association between MRI findings, PFS, and overall length of survival.
Review of the literature included the following databases: WHO International Clinical Trials Registry Platform; Google Scholar; Web of Science; PubMed; SIGLE; NYAM; Scopus; Randomized controlled trial (RCT); Virtual Health Library (VHL); Cochrane Collaboration; EMBASE; and Clinical Trials.
The current review included 20 studies, and covered 2097 patients with gliomas. There were 1310 patients with glioblastoma and 320 with astrocytoma. There were 161 patients with grade-2 gliomas and 111 patients with grade-3. Tumour necrosis, peritumoural oedema, and multiple lesions were associated with PFS, as well as tumour necrosis and peritumoural oedema with overall survival.
The present meta-analysis highlighted the ability of MRI to predict PFS and overall survival in patients with gliomas. This is crucial to identify patients at risk for poor survival outcomes and for individualising the treatment plan for such patients.
CRD42023489535, https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=489535.
Autism spectrum disorder (ASD) has been reported to confer an increased risk of natural premature death. Telomere erosion caused by oxidative stress is a common consequence in age-related diseases. However, whether telomere length (TL) and oxidative indicators are significantly changed in ASD patients compared with controls remains controversial. The aim of this study was to determine the associations of ASD with TL and oxidative indicators by performing a meta-analysis of all published evidence.
The PubMed and Embase databases were searched for articles published up to April, 2024. The effect size was expressed as standardized mean difference (SMD) and 95% confidence interval (CI) via Stata 15.0 software.
Thirty-nine studies were included. Pooled results showed that compared with controls, children and adolescents with ASD were associated with significantly shorter TL (SMD = –0.48; 95% CI = –0.66– –0.29; p < 0.001; particularly in males), lower total antioxidant capacity (TAC: SMD = –1.15; 95% CI = –2.01– –0.30; p = 0.008), and higher oxidative DNA (8-hydroxy-2′-deoxyguanosine, 8-OHdG: SMD = 0.63; 95% CI = 0.03–1.23; p = 0.039), lipid (hexanolyl-lysine, HEL: SMD = 0.37; 95% CI = 0.13–0.62; p = 0.003), and protein (3-nitrotyrosine, 3-NT: SMD = 0.86; 95% CI = 0.21–1.51; p = 0.01; dityrosine, DT: SMD = 0.66; 95% CI = 0.521–0.80; p < 0.01) damage. There were no significant differences between ASD and controls in 8-isoprostane and oxidative stress index after publication bias correction, and in N-formylkynurenine during overall meta-analysis.
TL, 8-OHdG, TAC, HEL, 3-NT, and DT represent potential biomarkers for prediction of ASD in children and adolescents.
Resting state networks (RSNs) of the brain are characterized as correlated spontaneous time-varying fluctuations in the absence of goal-directed tasks. These networks can be local or large-scale spanning the brain. The study of the spatiotemporal properties of such networks has helped understand the brain’s fundamental functional organization under healthy and diseased states. As we age, these spatiotemporal properties change. Moreover, RSNs exhibit neural plasticity to compensate for the loss of cognitive functions. This narrative review aims to summarize current knowledge from functional magnetic resonance imaging (fMRI) studies on age-related alterations in RSNs. Underlying mechanisms influencing such changes are discussed. Methodological challenges and future directions are also addressed. By providing an overview of the current state of knowledge in this field, this review aims to guide future research endeavors aimed at promoting healthy brain aging and developing effective interventions for age-related cognitive impairment and neurodegenerative diseases.
The complicated neurological syndrome known as multiple sclerosis (MS) is typified by demyelination, inflammation, and neurodegeneration in the central nervous system (CNS). Managing this crippling illness requires an understanding of the complex interactions between neurophysiological systems, diagnostic techniques, and therapeutic methods. A complex series of processes, including immunological dysregulation, inflammation, and neurodegeneration, are involved in the pathogenesis of MS. Gene predisposition, autoreactive T cells, B cells, and cytokines are essential participants in the development of the disease. Demyelination interferes with the ability of the CNS to transmit signals, which can cause a variety of neurological symptoms, including impaired motor function, sensory deficiencies, and cognitive decline. Developing tailored therapeutics requires understanding the underlying processes guiding the course of the disease. Neuroimaging, laboratory testing, and clinical examination are all necessary for an accurate MS diagnosis. Evoked potentials and cerebrospinal fluid studies assist in verifying the diagnosis, but magnetic resonance imaging (MRI) is essential for identifying distinctive lesions in the CNS. Novel biomarkers have the potential to increase diagnostic precision and forecast prognosis. The goals of MS treatment options are to control symptoms, lower disease activity, and enhance quality of life. To stop relapses and reduce the course of the disease, disease-modifying treatments (DMTs) target several components of the immune response. DMTs that are now on the market include interferons, glatiramer acetate, monoclonal antibodies, and oral immunomodulators; each has a unique mode of action and safety profile. Symptomatic treatments improve patients' general well-being by addressing specific symptoms, including pain, sphincter disorders, fatigue, and spasticity. Novel treatment targets, neuroprotective tactics, and personalized medicine techniques will be the main focus of MS research in the future. Improving long-term outcomes for MS patients and optimizing disease treatment may be possible by utilizing immunology, genetics, and neuroimaging developments. This study concludes by highlighting the complexity of multiple MS, including its changing therapeutic landscape, diagnostic problems, and neurophysiological foundations. A thorough grasp of these elements is essential to improving our capacity to identify, manage, and eventually overcome this intricate neurological condition.
Mitochondria are organelles of eukaryotic cells delimited by two membranes and cristae that consume oxygen to produce adenosine triphosphate (ATP), and are involved in the synthesis of vital metabolites, calcium homeostasis, and cell death mechanisms. Strikingly, normal mitochondria function as an integration center between multiple conditions that determine neural cell homeostasis, whereas lesions that lead to mitochondrial dysfunction can desynchronize cellular functions, thus contributing to the pathophysiology of traumatic brain injury (TBI). In addition, TBI leads to impaired coupling of the mitochondrial electron transport system with oxidative phosphorylation that provides most of the energy needed to maintain vital functions, ionic homeostasis, and membrane potentials. Furthermore, mitochondrial metabolism produces signaling molecules such as reactive oxygen species (ROS), regulating calcium levels and controlling the expression profile of intrinsic pro-apoptotic effectors influenced by TBI. Hence, the set of these functions is widely referred to as ‘mitochondrial function’, although the complexity of the relationship between such components limits such a definition. In this review, we present mitochondria as a therapeutic target, focus on TBI, and discuss aspects of mitochondrial structure and function.
Deficits in emotion recognition have been shown to be closely related to social-cognitive functioning in schizophrenic. This study aimed to investigate the event-related potential (ERP) characteristics of social perception in schizophrenia patients and to explore the neural mechanisms underlying these abnormal cognitive processes related to social perception.
Participants included 33 schizophrenia patients and 35 healthy controls (HCs). All participants underwent electroencephalogram recording while completing the Emotion Intensity Recognition Task (EIRT). Behavioral data and ERP components were analyzed using repeated measures analysis of variance.
Schizophrenia patients had longer reaction times (RTs) to sad faces compared with disgusted faces, and had lower accuracy than the HCs. Additionally, schizophrenia patients had lower accuracy than the HCs for disgusted faces, surprised faces, angry faces, and fearful faces. Late Positive Potential (LPP) mean amplitudes of the HCs were larger than the schizophrenia patients for sad faces in the frontal lobe and central lobe. For happy faces, the HCs elicited larger LPP mean amplitudes than schizophrenia patients in the frontal lobe and central lobe. For surprised faces, the LPP mean amplitudes were higher in the HCs in the central lobe and parietal lobe than in schizophrenia patients. The HCs exhibited larger LPP mean amplitudes for angry faces in the frontal lobe, central lobe, and parietal lobe than in schizophrenia patients. For fearful faces, the HCs elicited a larger LPP mean amplitude than schizophrenia patients in the frontal lobe, central lobe, and parietal lobe.
Schizophrenia patients present impaired social perception, and the observed ERP patterns provide valuable insights into the neural mechanisms underlying the EIRT results, highlighting the differences between HCs and schizophrenia patients. These findings underscore the potential of the EIRT as a biomarker for cognitive and emotional dysregulation in schizophrenia.
No: ChiCTR2300078149. Registered 29 November, 2023; https://www.chictr.org.cn/showproj.html?proj=211510.
The effects of remimazolam (Re) in combination with andrographolide (AP) on learning, memory, and motor abilities in rats following cardiopulmonary bypass (CPB) surgery were studied.
We hypothesized that the combination of Re and AP could improve postoperative cognitive dysfunction (POCD) in rats after CPB by modulating nervous system inflammation. Cognitive function was assessed using the Morris Water Maze test, and the concentrations of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) in serum were measured by enzyme-linked immunosorbent assay (ELISA). Apoptosis was evaluated using western blotting and the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining assay.
The results indicated that both Re and AP independently improved cognitive function in rats after CPB and inhibited the secretion of inflammatory factors and apoptosis in hippocampal tissues. Combined administration of Re and AP enhanced the alleviation of POCD compared with monotherapy. The adenosine monophosphate-activated protein kinase/silent information regulator of transcription 1 (AMPK/SIRT1) signaling pathway was activated by the combination of Re and AP.
Collectively, the combination of Re and AP treatment significantly improves POCD in rats after CPB through activation of the AMPK/SIRT1 signaling pathway.
To study the use of a dementia screening tool in our clinic cohort of adults with Down syndrome.
A retrospective chart review of patients with Down syndrome was conducted to follow the use of the Adaptive Behaviour Dementia Questionnaire (ABDQ) in a dementia screening protocol. The ABDQ results for patients aged 40 years and older at a Down syndrome specialty clinic program were assessed. Based on caregiver feedback, an ABDQ with modified instructions was piloted and the impact assessed.
As part of our clinic’s initiative to implement a new clinical protocol to screen for dementia, the ABDQ was completed by 47 caregivers of adults with Down syndrome, aged 39 years and above, from December, 2021 to April, 2023. Based on clinical impressions at the same timepoint, the ABDQ had a sensitivity of 0%, specificity of 97.4%, positive predictive value of 0%, and negative predictive value of 80.4%. Nine patients were deemed to have mild cognitive impairment and/or dementia by clinical impressions, but they did not identify as positive on the ABDQ. The Down syndrome clinic team modified the ABDQ in an effort to provide clearer language and increased sensitivity. The modified ABDQ showed a sensitivity of 0%, specificity of 93.8%, positive predictive value of 0% and negative predictive value of 75%.
Neither the original ABDQ nor a modified version adequately identified patients with cognitive impairment and/or dementia within the Down syndrome clinical program. The inability to replicate findings from the initial ABDQ validation may be due to differences in setting and format.
Observation, execution, and imitation of target actions based on mirror neuron network (MNN) have become common physiotherapy strategies. Electrical stimulation (ES) is a common intervention to improve muscle strength and motor control in rehabilitation treatments. It is possible to enhance MNN’s activation by combining motor execution (ME) and motor imitation (MI) with ES simultaneously. This study aims to reveal whether ES could impact cortical activation during ME and MI.
We recruited healthy individuals and assigned them randomly to the control group (CG) or experiment group (EG). Participants in EG performed ME and MI tasks with ES, while participants in CG performed the same two tasks with sham ES. We utilized functional near-infrared spectroscopy (fNIRS) to detect brain activation of MNN during ME and MI with and without ES, a randomized block design experiment paradigm was designed. Descriptive analysis of oxy-hemoglobin (HbO) and deoxy-hemoglobin (HbR) were used to show the hemoglobin (Hb) concentration changes after different event onsets in both CG and EG, a linear mixed-effects model (LMM) of HbO data was employed to analyze the effect of ES on the activation of MNN.
A total of 102 healthy adults were recruited and 72 participants’ data were analysed in the final report. The block averaged Hb data showed that HbO concentration increased and HbR concentration decreased in most MNN regions during ME and MI in both groups. The LMM results showed that ES can significantly improve the activation of inferior frontal gyrus, middle frontal gyrus, and precentral gyrus during MI, the supplementary motor area, inferior parietal lobule, and superior temporal gyri showed increased activation, but without statistical significance. Although the results did not reach statistical significance during ME, ES still showed positive effects on increased overall activations.
In this study, we present potential novel rehabilitation approaches that combines MNN strategies and low-frequency ES to enhance cortical activation. Our results revealed that ES has potential to increase activation of most MNN brain areas, providing evidence for related rehabilitative interventions and device development.
This study was registered on the China Clinical Trial Registration Center (identifier: ChiCTR2200064082, registered 26, September 2022, https://www.chictr.org.cn/showproj.html?proj=178285).
White matter (WM) is a principal component of the human brain, forming the structural basis for neural transmission between cortico-cortical and subcortical structures. The impairment of WM integrity is closely associated with the aging process, manifesting as the reorganization of brain networks based on graph theoretical analysis of complex networks and increased volume of white matter hyperintensities (WMHs) in imaging studies.
This study investigated changes in the robustness of WM brain networks during aging and assessed their correlation with WMHs. We constructed WM brain networks for 159 volunteers from a community sample dataset using diffusion tensor imaging (DTI). We then calculated the robustness of these networks by simulating neurodegeneration based on network attack analysis, and studied the correlations between WM network robustness, age, and the proportion of WMHs.
The analysis revealed a moderate, negative correlation between WM network robustness and age, and a weak and negative correlation between WM network robustness and the proportion of WMHs.
These findings suggest that WM pathologies are associated with aging and offer new insights into the imaging characteristics of the aging brain.
Recent studies suggest that the anterior limb of the internal capsule may be an area of convergence for multiple compulsion loops. In this study, the role of different dopaminergic compulsion loops in the mechanism of obsessive-compulsive disorder (OCD) was investigated by selectively damaging dopaminergic neurons or fibers in the corresponding targets with 6-hydroxydopamine (6-OHDA) and depicting the anatomical map of various compulsion loops located in the anterior limb of the internal capsule.
A total of 52 male Sprague Dawley (SD) rats were exposed to either saline (1 mL/kg, NS group, n = 6) or quinpirole (QNP, dopamine D2-agonist, 0.5 mg/kg, n = 46) twice weekly for 5 weeks. After each injection, the rats were placed on an open field to analyze aspects of their behaviour, including the number of home base visits (NOH), average time between each home base visit (ATBO), and total distance travelled (TDM). After model setup, 46 QNP rats were divided randomly into five groups: 6-OHDA anterior limb of internal capsule (AC) stereotactic injection group (QNP+AC group, n = 10), 6-OHDA mediodorsal thalamic nucleus (MD) stereotactic injection group (QNP+MD group, n = 10), 6-OHDA nucleus accumbens (NAC) stereotactic injection group (QNP+NAC group, n = 10), saline stereotactic injection group (QNP+NS-S group, n = 10), and non-surgical group (QNP+Non-S group, n = 6). In the NS group, rats simultaneously received a 6-OHDA stereotactic injection (NS+6-OHDA-S group, n = 6: AC2, MD2, NAC2). All QNP-treated rats were then continued to be given QNP twice a week for 4 weeks, and their behaviour was observed after each infusion. After 4 weeks, immunofluorescence staining was used to monitor the distribution of dopamine neurons and nerve fibers in different areas of the intervention nerve loops, and quantitative analysis was performed.
Compulsive behaviour declined gradually in the QNP+AC and QNP+NAC groups 3 and 4 weeks after surgery, with the QNP+AC group decreasing more rapidly. The QNP+MD group had decreased by 3 weeks after surgery but increased to almost the same level as pre-surgery at 4 weeks post-surgery. Postoperative fluorescence staining and quantitative analysis suggested the number of dopamine (DA) neurons or nerve fibers in the corresponding target area of the 6-OHDA injection were significantly reduced compared with the QNP+Non-S group.
6-OHDA selectively damages the targets of dopaminergic neurons or nerve fibers within the OCD loop, which somewhat alleviates compulsive behaviours. The results suggest that the AC might be the best target for therapeutic interventions for OCD.
Volume alterations in the parietal subregion have received less attention in Alzheimer’s disease (AD), and their role in predicting conversion of mild cognitive impairment (MCI) to AD and cognitively normal (CN) to MCI remains unclear. In this study, we aimed to assess the volumetric variation of the parietal subregion at different cognitive stages in AD and to determine the role of parietal subregions in CN and MCI conversion.
We included 662 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database, including 228 CN, 221 early MCI (EMCI), 112 late MCI (LMCI), and 101 AD participants. We measured the volume of the parietal subregion based on the Human Brainnetome Atlas (BNA-246) using voxel-based morphometry among individuals at various stages of AD and the progressive and stable individuals in CN and MCI. We then calculated the area under the curve (AUC) of the receiver operating characteristic (ROC) curve to test the ability of parietal subregions to discriminate between different cognitive groups. The Cox proportional hazard model was constructed to determine which specific parietal subregions, alone or in combination, could be used to predict progression from MCI to AD and CN to MCI. Finally, we examined the relationship between the cognitive scores and parietal subregion volume in the diagnostic groups.
The left inferior parietal lobule (IPL)_6_5 (rostroventral area 39) showed the best ability to discriminate between patients with AD and those with CN (AUC = 0.688). The model consisting of the left IPL_6_4 (caudal area 40) and bilateral IPL_6_5 showed the best combination for predicting the CN progression to MCI. The left IPL_6_1 (caudal area 39) showed the best predictive power in predicting the progression of MCI to AD. Certain subregions of the volume correlated with cognitive scales.
Subregions of the angular gyrus are essential in the early onset and subsequent development of AD, and early detection of the volume of these regions may be useful in identifying the tendency to develop the disease and its treatment.
In neuroscience, Ca2+ imaging is a prevalent technique used to infer neuronal electrical activity, often relying on optical signals recorded at low sampling rates (3 to 30 Hz) across multiple neurons simultaneously. This study investigated whether increasing the sampling rate preserves critical information that may be missed at slower acquisition speeds.
Primary neuronal cultures were prepared from the cortex of newborn pups. Neurons were loaded with Oregon Green BAPTA-1 AM (OGB1-AM) fluorescent indicator. Spontaneous neuronal activity was recorded at low (14 Hz) and high (500 Hz) sampling rates, and the same neurons (n = 269) were analyzed under both conditions. We compared optical signal amplitude, duration, and frequency.
Although recurring Ca2+ transients appeared visually similar at 14 Hz and 500 Hz, quantitative analysis revealed significantly faster rise times and shorter durations (half-widths) at the higher sampling rate. Small-amplitude Ca2+ transients, undetectable at 14 Hz, became evident at 500 Hz, particularly in the neuropil (putative dendrites and axons), but not in nearby cell bodies. Large Ca2+ transients exhibited greater amplitudes and faster temporal dynamics in dendrites compared with somas, potentially due to the higher surface-to-volume ratio of dendrites. In neurons bulk-loaded with OGB1-AM, cell nucleus-mediated signal distortions were observed in every neuron examined (n = 57). Specifically, two regions of interest (ROIs) on different segments of the same cell body displayed significantly different signal amplitudes and durations due to dye accumulation in the nucleus.
Our findings reveal that Ca2+ signal undersampling leads to three types of information loss: (1) distortion of rise times and durations for large-amplitude transients, (2) failure to detect small-amplitude transients in cell bodies, and (3) omission of small-amplitude transients in the neuropil.
The significance of tactile stimulation in human social development and personal interaction is well documented; however, the underlying cerebral processes remain under-researched. This study employed functional magnetic resonance imaging (fMRI) to investigate the neural correlates of social touch processing, with a particular focus on the functional connectivity associated with the aftereffects of touch.
A total of 27 experimental subjects were recruited for the study, all of whom underwent a 5-minute calf and foot massage prior to undergoing resting-state fMRI. Additionally, 11 healthy controls participated solely in the resting-state fMRI recording. A functional connectivity network analysis was conducted to examine the alterations in connections between different brain regions following massage.
The findings indicated the involvement of discrete neural networks in the processing of social touch, with notable discrepancies in functional connectivity observed between the experimental and control groups. The study revealed that the control group exhibited a higher degree of connectivity within a subnetwork comprising 25 connections and 23 nodes than the experimental group following the massage intervention. The experimental group showed hypoactivation in this subnetwork following the massage. The left anterior pulvinar thalamus and the right pregenual anterior cingulate cortex, which serve as the key hubs within this subnetwork, exhibited higher clustering and increased node strength in the control group. Relatively small and unequal sample sizes are the limitations of the study that may affect the generalizability of the results.
These findings elucidate the neural underpinnings of tactile experiences and their potential impact on behavior and emotional state. Gaining insight into these mechanisms could inform therapeutic approaches that utilize touch to mitigate stress and enhance mental health. From a practical standpoint, our results have significant implications for the development of sensory stimulation strategies for patients with prolonged disorders of consciousness, sensory loss, autism spectrum disorders, or limited access to tactile interaction in their upper extremities.
Sports fatigue in soccer athletes has been shown to decrease neural activity, impairing cognitive function and negatively affecting motor performance. Transcranial direct current stimulation (tDCS) can alter cortical excitability, augment synaptic plasticity, and enhance cognitive function. However, its potential to ameliorate cognitive impairment during sports fatigue remains largely unexplored. This study investigated the effect of dual-site tDCS targeting the dorsolateral prefrontal cortex (DLPFC) or primary motor cortex (M1) on attention, decision-making, and working memory in elite soccer athletes during sports fatigue.
Sports fatigue was induced in 23 (non-goalkeeper) elite soccer athletes, who then participated in three counterbalanced intervention sessions: dual-site tDCS over the M1, dual-site tDCS over the DLPFC, and sham tDCS. Following tDCS, participants completed the Stroop, Iowa Gambling, and 2-back tasks.
We found a significant improvement in Stroop task accuracy following dual-site anodal tDCS over the M1 compared with the sham intervention in the incongruent condition (p = 0.036). Net scores in the Iowa Gambling task during blocks 4 (p = 0.019) and 5 (p = 0.014) significantly decreased under dual-site tDCS targeting the DLPFC compared with the sham intervention. No differences in 2-back task performance were observed between sessions (all p > 0.05).
We conclude that dual-site anodal tDCS applied to the M1 enhanced attention performance while tDCS targeting the DLPFC increased risk propensity in a decision-making task during sports fatigue in elite soccer athletes. However, dual-site anodal tDCS targeting either the M1 or DLPFC did not significantly influence working memory performance during sports fatigue in this population. These preliminary findings suggest that dual-site tDCS targeting the M1 has beneficial effects on attention performance, potentially informing future research on sports fatigue in athletes.
No: NCT06594978. Registered 09 September, 2024; https://clinicaltrials.gov/search?cond=NCT06594978.