Frontiers in Aging Neuroscience最新文献

{"title":"Frontiers | Characterizing the clinical heterogeneity of early symptomatic Alzheimer’s disease: a data-driven machine learning approach","authors":"Xiwu Wang, Teng Ye, Deguo Jiang, Wenjun Zhou, Jie Zhang, for the Alzheimer’s Disease Neuroimaging Initiative","doi":"10.3389/fnagi.2024.1410544","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1410544","url":null,"abstract":"IntroductionAlzheimer’s disease (AD) is highly heterogeneous, with substantial individual variabilities in clinical progression and neurobiology. Amyloid deposition has been thought to drive cognitive decline and thus a major contributor to the variations in cognitive deterioration in AD. However, the clinical heterogeneity of patients with early symptomatic AD (mild cognitive impairment or mild dementia due to AD) already with evidence of amyloid abnormality in the brain is still unknown.MethodsParticipants with a baseline diagnosis of mild cognitive impairment or mild dementia, a positive amyloid-PET scan, and more than one follow-up Alzheimer’s Disease Assessment Scale-Cognitive Subscale-13 (ADAS-Cog-13) administration within a period of 5-year follow-up were selected from the Alzheimer’s Disease Neuroimaging Initiative database (n = 421; age = 73±7; years of education = 16 ± 3; percentage of female gender = 43%; distribution of APOE4 carriers = 68%). A non-parametric k-means longitudinal clustering analysis in the context of the ADAS-Cog-13 data was performed to identify cognitive subtypes.ResultsWe found a highly variable profile of cognitive decline among patients with early AD and identified 4 clusters characterized by distinct rates of cognitive progression. Among the groups there were significant differences in the magnitude of rates of changes in other cognitive and functional outcomes, clinical progression from mild cognitive impairment to dementia, and changes in markers presumed to reflect neurodegeneration and neuronal injury. A nomogram based on a simplified logistic regression model predicted steep cognitive trajectory with an AUC of 0.912 (95% CI: 0.88 – 0.94). Simulation of clinical trials suggested that the incorporation of the nomogram into enrichment strategies would reduce the required sample sizes from 926.8 (95% CI: 822.6 – 1057.5) to 400.9 (95% CI: 306.9 – 516.8).DiscussionOur findings show usefulness in the stratification of patients in early AD and may thus increase the chances of finding a treatment for future AD clinical trials.","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141935472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction: Corrigendum: 20-HETE inhibition by HET0016 decreases the blood-brain barrier permeability and brain edema after traumatic brain injury.","authors":"","doi":"10.3389/fnagi.2024.1469763","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1469763","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.3389/fnagi.2018.00239.].</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11318355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141972540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction: 20-HETE inhibition by HET0016 decreases the blood-brain barrier permeability and brain edema after traumatic brain injury.","authors":"","doi":"10.3389/fnagi.2024.1469759","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1469759","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.3389/fnagi.2018.00207.].</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11318277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of liver function markers and apolipoprotein E ε4 with pathogenesis and cognitive decline in Alzheimer’s disease","authors":"Sang-Won Han, Sang-Hwa Lee, Jong Ho Kim, Jae-Jun Lee, Young Ho Park, SangYun Kim, Kwangsik Nho, Jong-Hee Sohn","doi":"10.3389/fnagi.2024.1411466","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1411466","url":null,"abstract":"BackgroundAlzheimer’s disease (AD) is a complex neurodegenerative disorder influenced by various factors, including liver function, which may impact the clearance of amyloid-β (Aβ) in the brain. This study aimed to explore how the apolipoprotein E (<jats:italic>APOE</jats:italic>) ε4 allele affects the relationship of liver function markers with AD pathology and cognition.MethodsWe analyzed data from two independent cohorts, including 732 participants from the Hallym University Medical Center and 483 from the Alzheimer’s Disease Neuroimaging Initiative, each group consisting of individuals with and without the <jats:italic>APOE</jats:italic> ε4 allele. Cross-sectional analyses evaluated the associations of liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase, total bilirubin, and albumin) with AD diagnosis, amyloid positron emission tomography (PET) burden, and cerebrospinal fluid biomarkers for AD (Aβ42, total tau, and phosphorylated tau181) at baseline. Longitudinally, we investigated the associations between these liver enzymes and changes in cognitive performance over the course of a year. Logistic and linear regression models were used to analyze these associations and mediation analyses were conducted to assess whether age and amyloid PET burden mediated these associations.ResultsOnly in the <jats:italic>APOE</jats:italic> ε4 carrier group, a high AST to ALT ratio and low ALT levels were significantly associated with AD diagnosis, increased amyloid PET burden, and faster longitudinal decline in cognitive function in both cohorts. In particular, the AST to ALT ratio was associated with cerebrospinal fluid Aβ42 levels exclusively in the <jats:italic>APOE</jats:italic> ε4 carrier group in the Alzheimer’s Disease Neuroimaging Initiative cohort but not with phosphorylated tau<jats:sub>181</jats:sub> or total tau levels. Moreover, mediation analyses from both cohorts revealed that in the <jats:italic>APOE</jats:italic> ε4 carriers group, age did not mediate the associations between liver enzymes and AD diagnosis or amyloid PET burden. However, amyloid PET burden partially mediated the association between liver enzymes and AD diagnosis exclusively in the <jats:italic>APOE</jats:italic> ε4 carriers group.ConclusionThis study provides valuable insights into the significant association of the <jats:italic>APOE</jats:italic> ε4 allele with liver enzymes and their potential role in Aβ-related pathogenesis and cognition in AD. Further research is required to elucidate the underlying mechanisms and potential therapeutic implications of these findings.","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141772416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation of brain tissue volume loss with inflammatory biomarkers IL1β, P-tau, T-tau, and NLPR3 in the aging cognitively impaired population","authors":"Kyung Mi Lee, Sang Tae Kim, Yunan Tian, Sue Min Jung, Yunjung Chang, Hak Young Rhee, Soonchan Park, Chang-Woo Ryu, Woo-In Lee, Eui Jong Kim, Geon-Ho Jahng","doi":"10.3389/fnagi.2024.1388654","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1388654","url":null,"abstract":"BackgroundBlood inflammatory biomarkers have emerged as important tools for diagnosing, assessing treatment responses, and predicting neurodegenerative diseases. This study evaluated the associations between blood inflammatory biomarkers and brain tissue volume loss in elderly people.MethodsThis study included 111 participants (age 67.86 ± 8.29 years; 32 men and 79 women). A battery of the following blood inflammatory biomarkers was measured, including interleukin 1-beta (IL1β), NACHT, LRR, and PYD domains-containing protein 3 (NLRP3), monomer Aβ42 (mAβ), oligomeric Aβ42 (oAβ), miR155, neurite outgrowth inhibitor A (nogo-A), phosphorylated tau (P-tau), and total tau (T-tau). Three-dimensional T1-weight images (3D T1WI) of all participants were prospectively obtained and segmented into gray matter and white matter to measure the gray matter volume (GMV), white matter volume (WMV), and gray-white matter boundary tissue volume (gwBTV). The association between blood biomarkers and tissue volumes was assessed using voxel-based and region-of-interest analyses.ResultsGMV and gwBTV significantly decreased as the levels of IL1β and T-tau increased, while no significant association was found between the level of P-tau and the three brain tissue volumes. Three brain tissue volumes were negatively correlated with the levels of IL1β, P-tau, and T-tau in the hippocampus. Specifically, IL1β and T-tau levels showed a distinct negative association with the three brain tissue volume losses in the hippocampus. In addition, gwBTV was negatively associated with the level of NLRP3.ConclusionThe observed association between brain tissue volume loss and elevated levels of IL1β and T-tau suggests that these biomarkers in the blood may serve as potential biomarkers of cognitive impairment in elderly people. Thus, IL1β and T-tau could be used to assess disease severity and monitor treatment response after diagnosis in elderly people who are at risk of cognitive decline.","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141772420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research hotspots and frontiers of essential tremor from 2013 to 2023: a visualization analysis based on CiteSpace","authors":"Linlin Zhang, Shifang Cui, Xiaoming Xi, Hongyan Bi, Bin Huang","doi":"10.3389/fnagi.2024.1380851","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1380851","url":null,"abstract":"BackgroundET, one of the most prevalent neurological disorders, presents a significant challenge in terms of disability. Despite the growing focus on ET in recent years, comprehensive bibliometric analysis has been lacking.MethodsThis study delves into essential tremor research covering the period from 2013 to 2023, utilizing the Web of Science (WOS) database. Employing CiteSpace for quantitative analysis, it examines an array of metrics including annual publication trends, contributions from countries and institutions, authorship patterns, key terminologies, and patterns of reference co-citation. The primary objective is to use CiteSpace for a detailed visual exploration of the literature over the last decade, pinpointing the evolving landscape and key areas of focus in essential tremor research, and thus providing a foundation for future investigative endeavors.ResultsThere were 2,224 literary works included in all. The amount of published works has been steadily rising in recent years. Of them, the majority originate from the United States, Louis, Elan D. is the publisher of the most publications (161 articles), and Movement Disorders is the journal that receives the most citations. The key words contribution and co-cited literatures suggest that the main research hotspots in recent years are the physiological and pathological mechanism of essential tremor, the determination of optimal targets for deep brain stimulation (DBS) and surgery transcranial magnetic resonance-guided focused ultrasound (MRgFUS) in the surgical management of essential tremor and the innovative research of botulinum toxin administration method.","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141772417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lamivudine modulates the expression of neurological impairment-related genes and LINE-1 retrotransposons in brain tissues of a Down syndrome mouse model","authors":"Alessandra Borgognone, Maria Casadellà, María Martínez de Lagrán, Roger Paredes, Bonaventura Clotet, Mara Dierssen, Aleix Elizalde-Torrent","doi":"10.3389/fnagi.2024.1386944","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1386944","url":null,"abstract":"Elevated activity of retrotransposons is increasingly recognized to be implicated in a wide range of neurodegenerative and neurodevelopmental diseases, including Down syndrome (DS), which is the most common chromosomal condition causing intellectual disability globally. Previous research by our group has revealed that treatment with lamivudine, a reverse transcriptase inhibitor, improved neurobehavioral phenotypes and completely rescued hippocampal-dependent recognition memory in a DS mouse model, Ts65Dn. We hypothesized that retrotransposition rates would increase in the Ts65Dn mouse model, and lamivudine could block retrotransposons. We analyzed the differentially expressed long interspersed element-1 (LINE-1 or L1) mapping on MMU16 and 17, and showed for the first time that retrotransposition could be associated with Ts65Dn’s pathology, as misregulation of L1 was found in brain tissues associated with trisomy. In the cerebral cortex, 6 out of 26 upregulated L1s in trisomic treated mice were located in the telomeric region of MMU16 near <jats:italic>Ttc3</jats:italic>, <jats:italic>Kcnj6</jats:italic>, and <jats:italic>Dscam</jats:italic> genes. In the hippocampus, one upregulated L1 element in trisomic treated mice was located near the <jats:italic>Fgd4</jats:italic> gene on MMU16. Moreover, two downregulated L1s rescued after treatment with lamivudine were located in the intronic region of <jats:italic>Nrxn1</jats:italic> (MMU17) and <jats:italic>Snhg14</jats:italic> (MMU7), implicated in a variety of neurodegenerative disorders. To gain further insight into the mechanism of this improvement, we here analyzed the gene expression profile in the hippocampus and cerebral cortex of trisomic mice treated and no-treated with lamivudine compared to their wild-type littermates. We found that treatment with lamivudine rescued the expression of 24% of trisomic genes in the cortex (located on mouse chromosome (MMU) 16 and 17) and 15% in the hippocampus (located in the human chromosome 21 orthologous regions), with important DS candidate genes such as <jats:italic>App</jats:italic> and <jats:italic>Ets2</jats:italic>, rescued in both regions.","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141739739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The influence of eight cognitive training regimes upon cognitive screening tool performance in post-stroke survivors: a network meta-analysis","authors":"Liqin Zhou, Xiaofeng Huang, Jieyu Wang, Fengming Wang, Jihong Liu, Nanhai Liu","doi":"10.3389/fnagi.2024.1374546","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1374546","url":null,"abstract":"BackgroundTraditional meta-analysis offers only direct comparative evidence. The optimal cognitive training for poststroke cognitive impairment (PSCI) remains largely undetermined.ObjectivesThis study aims to assess and compare the effectiveness of selected cognitive training methods for PSCI patients and to identify and rank the most effective intervention programs.MethodsSearches were conducted in PubMed, Embase, Cochrane Library, Web of science, China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, and China Biomedical Database for randomized controlled trials up to September 30, 2023. Two researchers independently performed literature screening, data extraction, and quality assessment. Network meta-analysis was utilized to synthesize the main findings. The primary outcome focused on the intervention’s impact on subjective cognitive function, with secondary outcomes including effects on activities of daily living, motor function, and functional independence. This study is registered with PROSPERO (CRD42023463282).ResultsFifty eligible randomized controlled trials were identified, revealing eight distinct interventions. These interventions collectively demonstrate efficacy in enhancing cognition. Traditional cognitive training significantly improves overall cognitive function, daily living function, motor function, and functional independence. In Loewenstein Occupational Therapy Cognitive Assessment, Barthel Index, Fugl-Meyer Assessment, and Functional Independence Measure scales, a combination of computer-based and traditional cognitive training outperformed the conventional control group MD = 29.97 (95%CI: 16.3, 44.2), MD = 18.67 (95%CI: 9.78, 27.45), MD = 28.76 (95%CI: 5.46, 51.79) and MD = 42.2 (95%CI: 5.25, 78.99). In the MMSE scale, virtual reality cognitive training combined with traditional training was most effective MD = 8.01 (95%CI: 3.6, 12.4). On the MoCA scale, the combination of exercise and cognitive training showed superior results MD = 6.68 (95%CI: 2.55, 10.78). Only the combined computer-based and traditional cognitive training, as well as traditional cognitive training alone, significantly enhanced functional independence, with no notable differences in other pairwise interventions.ConclusionThe network meta-analysis suggests that augmenting traditional training with other modalities may enhance overall effectiveness. Specifically, interventions incorporating computer-based cognitive training appear to surpass other methods in improving cognition, daily living function, motor skills, and functional independence. The findings of this network meta-analysis provide evidence-based guidance for clinical decision-making.Systematic Review Registration<jats:ext-link>https://www.crd.york.ac.uk/PROSPERO/</jats:ext-link>, identifier in PROSPERO (CRD42023463282).","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141739738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection of freezing of gait in Parkinson's disease from foot-pressure sensing insoles using a temporal convolutional neural network","authors":"Jae-Min Park, Chang-Won Moon, Byung Chan Lee, Eungseok Oh, Juhyun Lee, Won-Jun Jang, Kang Hee Cho, Si-Hyeon Lee","doi":"10.3389/fnagi.2024.1437707","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1437707","url":null,"abstract":"BackgroundsFreezing of gait (FoG) is a common and debilitating symptom of Parkinson's disease (PD) that can lead to falls and reduced quality of life. Wearable sensors have been used to detect FoG, but current methods have limitations in accuracy and practicality. In this paper, we aimed to develop a deep learning model using pressure sensor data from wearable insoles to accurately detect FoG in PD patients.MethodsWe recruited 14 PD patients and collected data from multiple trials of a standardized walking test using the Pedar insole system. We proposed temporal convolutional neural network (TCNN) and applied rigorous data filtering and selective participant inclusion criteria to ensure the integrity of the dataset. We mapped the sensor data to a structured matrix and normalized it for input into our TCNN. We used a train-test split to evaluate the performance of the model.ResultsWe found that TCNN model achieved the highest accuracy, precision, sensitivity, specificity, and F1 score for FoG detection compared to other models. The TCNN model also showed good performance in detecting FoG episodes, even in various types of sensor noise situations.ConclusionsWe demonstrated the potential of using wearable pressure sensors and machine learning models for FoG detection in PD patients. The TCNN model showed promising results and could be used in future studies to develop a real-time FoG detection system to improve PD patients' safety and quality of life. Additionally, our noise impact analysis identifies critical sensor locations, suggesting potential for reducing sensor numbers.","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141739740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frontiers | Matching supplementary motor area-primary motor cortex paired transcranial magnetic stimulation improves motor dysfunction in Parkinson’s disease: a single-center, double-blind randomized controlled clinical trial protocol","authors":"Xiaoshun Tang, Zhexue Huang, Guangyue Zhu, Haoyuan Liang, Hui Sun, Yu Zhang, Yalin Tan, Minglong Cui, Haiyan Gong, Xijin Wang, Yu-Hui Chen","doi":"10.3389/fnagi.2024.1422535","DOIUrl":"https://doi.org/10.3389/fnagi.2024.1422535","url":null,"abstract":"BackgroundNon-invasive neuroregulation techniques have been demonstrated to improve certain motor symptoms in Parkinson’s disease (PD). However, the currently employed regulatory techniques primarily concentrate on stimulating single target points, neglecting the functional regulation of networks and circuits. The supplementary motor area (SMA) has a significant value in motor control, and its functionality is often impaired in patients with PD. The matching SMA-primary motor cortex (M1) paired transcranial magnetic stimulation (TMS) treatment protocol, which benefits patients by modulating the sequential and functional connections between the SMA and M1, was elucidated in this study.MethodsThis was a single-center, double-blind, randomized controlled clinical trial. We recruited 78 subjects and allocated them in a 1:1 ratio by stratified randomization into the paired stimulation (n = 39) and conventional stimulation groups (n = 39). Each patient underwent 3 weeks of matching SMA-M1 paired TMS or sham-paired stimulation. The subjects were evaluated before treatment initiation, 3 weeks into the intervention, and 3 months after the cessation of therapy. The primary outcome measure in this study was the Unified Parkinson’s Disease Rating Scale III, and the secondary outcome measures included non-motor functional assessment, quality of life (Parkinson’s Disease Questionnaire-39), and objective assessments (electromyography and functional near-infrared spectroscopy).DiscussionClinical protocols aimed at single targets using non-invasive neuroregulation techniques often improve only one function. Emphasizing the circuit and network regulation in PD is important for enhancing the effectiveness of TMS rehabilitation. Pairing the regulation of cortical circuits may be a potential treatment method for PD. As a crucial node in motor control, the SMA has direct fiber connections with basal ganglia circuits and complex fiber connections with M1, which are responsible for motor execution. SMA regulation may indirectly regulate the function of basal ganglia circuits. Therefore, the developed cortical pairing stimulation pattern can reshape the control of information flow from the SMA to M1. The novel neuroregulation model designed for this study is based on the circuit mechanisms of PD and previous research results, with a scientific foundation and the potential to be a means of neuroregulation for PD.Clinical trial registration: ClinicalTrials.gov, identifier [ChiCTR2400083325].","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141867615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}