Pub Date : 2026-01-30DOI: 10.1038/s41531-026-01271-5
Sarah Jaehwa Park,Barış Erhan Özdinç,Kathryn Grace Coker,Dana M Walsh,Devon J Fox,Samantha Evans,Joshua Farahnik,Kelly Moffat,Margaret Boomgaarden,Laurie K Mischley
Previous studies suggest there are distinct gut microbial and functional variations in patients with Parkinson's disease (PwPD) that may reveal potential microbiome signatures or biomarkers to aid in early detection of the disease. In this case-control study, we used whole genome sequencing to compare the stool samples of 55 PwPD to 42 healthy controls (HC) from a public database (BioProject Accession PRJEB39223). For bacterial phyla, we observed a greater relative abundance in Firmicutes and Actinobacteria among PwPD, while that of Bacteroidetes was lower. For phages, PwPD had a greater relative abundance of Siphoviridae, Tectiviridae, and Podoviridae, while Microviridae was lower. Moreover, we described 10 functional pathways that most significantly differed between PwPD and HC (all P < 0.0001). In conclusion, significant differences were observed in gut bacteria, phages, and functional pathways between PwPD and HC that both support and conflict with previous case-control studies and warrant further validation.
{"title":"Metagenomics indicates an interplay of the microbiome and functional pathways in Parkinson's disease.","authors":"Sarah Jaehwa Park,Barış Erhan Özdinç,Kathryn Grace Coker,Dana M Walsh,Devon J Fox,Samantha Evans,Joshua Farahnik,Kelly Moffat,Margaret Boomgaarden,Laurie K Mischley","doi":"10.1038/s41531-026-01271-5","DOIUrl":"https://doi.org/10.1038/s41531-026-01271-5","url":null,"abstract":"Previous studies suggest there are distinct gut microbial and functional variations in patients with Parkinson's disease (PwPD) that may reveal potential microbiome signatures or biomarkers to aid in early detection of the disease. In this case-control study, we used whole genome sequencing to compare the stool samples of 55 PwPD to 42 healthy controls (HC) from a public database (BioProject Accession PRJEB39223). For bacterial phyla, we observed a greater relative abundance in Firmicutes and Actinobacteria among PwPD, while that of Bacteroidetes was lower. For phages, PwPD had a greater relative abundance of Siphoviridae, Tectiviridae, and Podoviridae, while Microviridae was lower. Moreover, we described 10 functional pathways that most significantly differed between PwPD and HC (all P < 0.0001). In conclusion, significant differences were observed in gut bacteria, phages, and functional pathways between PwPD and HC that both support and conflict with previous case-control studies and warrant further validation.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"282 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146088920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-29DOI: 10.1038/s41531-025-01243-1
G Issabekov,B Al-Fatly,M Mousavi,J Roediger,R Köhler,J Habets,A L de Almeida Marcelino,M S Tuncer,P Krause,M Astalosch,D Kübler-Weller,C Spies,P Spindler,K Faust,P Truckenmueller,G H Schneider,A A Kühn,L A Steiner
Propofol is widely used for general anesthesia (GA) during deep brain stimulation (DBS) surgery targeting the subthalamic nucleus (STN) in Parkinson's disease (PD), yet its effects on intraoperative spatial navigation, critical for electrode placement, remain contentious. We performed multimodal analysis on 583 microelectrode recordings (MER) from PD patients undergoing DBS surgery under local anesthesia (LA) and GA. Deep sedation interfered with the identification of the dorsal STN border, and propofol dosages >4 mg/kg/h resulted in deeper final electrodes. While firing rate (FR) and burst index (BI) differed between LA and GA, only BI distinguished imaging-defined STN and correlated negatively with the proximity to the DBS sweetspot across conditions. Thus, propofol-based GA complicates navigation in DBS surgery, but MER remain informative if propofol levels are carefully controlled. BI emerges as a potential biomarker when MER are "polluted" by high levels of propofol, offering critical feedback during DBS surgery under GA.
{"title":"The graded effect of propofol in electrophysiology-guided navigation during deep brain stimulation surgery.","authors":"G Issabekov,B Al-Fatly,M Mousavi,J Roediger,R Köhler,J Habets,A L de Almeida Marcelino,M S Tuncer,P Krause,M Astalosch,D Kübler-Weller,C Spies,P Spindler,K Faust,P Truckenmueller,G H Schneider,A A Kühn,L A Steiner","doi":"10.1038/s41531-025-01243-1","DOIUrl":"https://doi.org/10.1038/s41531-025-01243-1","url":null,"abstract":"Propofol is widely used for general anesthesia (GA) during deep brain stimulation (DBS) surgery targeting the subthalamic nucleus (STN) in Parkinson's disease (PD), yet its effects on intraoperative spatial navigation, critical for electrode placement, remain contentious. We performed multimodal analysis on 583 microelectrode recordings (MER) from PD patients undergoing DBS surgery under local anesthesia (LA) and GA. Deep sedation interfered with the identification of the dorsal STN border, and propofol dosages >4 mg/kg/h resulted in deeper final electrodes. While firing rate (FR) and burst index (BI) differed between LA and GA, only BI distinguished imaging-defined STN and correlated negatively with the proximity to the DBS sweetspot across conditions. Thus, propofol-based GA complicates navigation in DBS surgery, but MER remain informative if propofol levels are carefully controlled. BI emerges as a potential biomarker when MER are \"polluted\" by high levels of propofol, offering critical feedback during DBS surgery under GA.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"82 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Neuronal mitochondria display distinct morphologies across compartments, with dendritic mitochondria being elongated and axonal ones shorter, and their morphologies are dynamically changed via fusion and fission machineries. Mitochondrial structural abnormalities are common in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, yet systematic evaluation of therapeutic targets remains limited. Here, we tested key mitochondrial shape regulators, mitofusin 1/2 for fusion and Mff/Fis1 for fission, in an α-synucleinopathy model. Using MitoVis, a deep learning-based neuronal mitochondrial image analysis tool, we achieved rapid, compartment-specific analysis of mitochondrial morphologies. Among all interventions, Fis1 knockdown most effectively protected mitochondrial structure to control levels without inducing over-elongation of axonal mitochondria, which was linked to abnormal Ca2+ dynamics. While all manipulations preserved dendritic spine loss, Fis1 optimally maintained axonal mitochondrial function. These findings demonstrate a high-throughput screening approach for mitochondrial regulators and highlight Fis1 as a promising preventive/therapeutic target. Our results support targeting mitochondrial morphology as a viable strategy for treating α-synucleinopathy and potentially other mitochondria-related neurodegenerative diseases.
{"title":"Systematic evaluation of mitochondrial morphology regulators for amelioration of neuronal α-synucleinopathy.","authors":"Su Yeon Kim,JunYoung Choi,Dong Cheol Jang,Pa Reum Lee,Gyu-Sang Hong,Jinkuk Kim,Won-Ki Jeong,Kihoon Han,Seok-Kyu Kwon","doi":"10.1038/s41531-026-01277-z","DOIUrl":"https://doi.org/10.1038/s41531-026-01277-z","url":null,"abstract":"Neuronal mitochondria display distinct morphologies across compartments, with dendritic mitochondria being elongated and axonal ones shorter, and their morphologies are dynamically changed via fusion and fission machineries. Mitochondrial structural abnormalities are common in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, yet systematic evaluation of therapeutic targets remains limited. Here, we tested key mitochondrial shape regulators, mitofusin 1/2 for fusion and Mff/Fis1 for fission, in an α-synucleinopathy model. Using MitoVis, a deep learning-based neuronal mitochondrial image analysis tool, we achieved rapid, compartment-specific analysis of mitochondrial morphologies. Among all interventions, Fis1 knockdown most effectively protected mitochondrial structure to control levels without inducing over-elongation of axonal mitochondria, which was linked to abnormal Ca2+ dynamics. While all manipulations preserved dendritic spine loss, Fis1 optimally maintained axonal mitochondrial function. These findings demonstrate a high-throughput screening approach for mitochondrial regulators and highlight Fis1 as a promising preventive/therapeutic target. Our results support targeting mitochondrial morphology as a viable strategy for treating α-synucleinopathy and potentially other mitochondria-related neurodegenerative diseases.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"4 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-27DOI: 10.1038/s41531-025-01236-0
Joshua D Elford,Elise J Heesbeen,Nienke A van der Plaats,Johan Garssen,Aletta D Kraneveld,Lucianne Groenink,Paula Perez Pardo
The gut microbiome is believed to play an important role in the development and onset of Parkinson's disease (PD). While human studies report differences in gut microbiota between PD individuals and healthy controls, it is unclear whether preclinical animal models show similar patterns. We performed a systematic review and Bayesian regularised meta-analysis of preclinical PD studies that assessed both motor function and gut microbiota. Motor deficits were consistently observed across models, but gut bacterial diversity (α-diversity) and changes in key taxa (e.g. Akkermansia, Lactobacillus, Bifidobacterium) were inconsistent and poorly aligned with human data. In contrast, short-chain fatty acids (SCFAs) showed more reproducible changes and greater translatability to human findings. Chronic toxin-based models demonstrated the highest reproducibility. Overall, gut microbiota composition in animal PD models lacks consistency and human relevance, whereas SCFAs may offer a more reliable outcome. Finally, our study makes possible recommendations for reporting to improve future studies.
{"title":"Gut bacteria composition in animal models of Parkinson's disease: a systematic review and meta-analysis.","authors":"Joshua D Elford,Elise J Heesbeen,Nienke A van der Plaats,Johan Garssen,Aletta D Kraneveld,Lucianne Groenink,Paula Perez Pardo","doi":"10.1038/s41531-025-01236-0","DOIUrl":"https://doi.org/10.1038/s41531-025-01236-0","url":null,"abstract":"The gut microbiome is believed to play an important role in the development and onset of Parkinson's disease (PD). While human studies report differences in gut microbiota between PD individuals and healthy controls, it is unclear whether preclinical animal models show similar patterns. We performed a systematic review and Bayesian regularised meta-analysis of preclinical PD studies that assessed both motor function and gut microbiota. Motor deficits were consistently observed across models, but gut bacterial diversity (α-diversity) and changes in key taxa (e.g. Akkermansia, Lactobacillus, Bifidobacterium) were inconsistent and poorly aligned with human data. In contrast, short-chain fatty acids (SCFAs) showed more reproducible changes and greater translatability to human findings. Chronic toxin-based models demonstrated the highest reproducibility. Overall, gut microbiota composition in animal PD models lacks consistency and human relevance, whereas SCFAs may offer a more reliable outcome. Finally, our study makes possible recommendations for reporting to improve future studies.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"51 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-24DOI: 10.1038/s41531-026-01272-4
Lu Lin,Jin Li,Si Zhu,Zhiling Zhang,Zhigang Li,Pingyi Xu,Wenyuan Guo
With the intensification of global plastic pollution, the potential threats posed by micro- and nanoplastics (MPs/NPs) to human health have become a major concern. MPs/NPs enter the organism through ingestion, inhalation, and skin contact, subsequently accumulating in multiple organs-particularly the brain. Increasing experimental and epidemiological evidence implicates MPs/NPs in the development of Parkinson's disease (PD). Preclinical research models indicate that MPs/NPs may accelerate both the initiation and progression of PD by facilitating α-synuclein misfolding and aggregation, triggering neuroinflammatory cascades, elevating oxidative stress, and impairing mitochondrial function. To further investigate the causal role of MPs/NPs in PD, upcoming studies should emphasize well-designed, large-scale prospective cohorts to assess individual exposure to plastic-related pollutants, elucidate the pathways of MPs/NPs into the central nervous system, establish safety thresholds for their neurotoxicity, explore the correlation between exposure levels and central nervous system accumulation, clarify the temporal relationship between MPs/NPs accumulation and PD pathology and symptom onset, and identify the neuropathological mechanisms triggered by relevant concentrations of MPs/NPs. Such data will be instrumental in informing preventive and potentially interventional strategies, while offering actionable insights into the interaction between MPs/NPs and PD.
{"title":"Micro-nanoplastics and Parkinson's disease: evidence and perspectives.","authors":"Lu Lin,Jin Li,Si Zhu,Zhiling Zhang,Zhigang Li,Pingyi Xu,Wenyuan Guo","doi":"10.1038/s41531-026-01272-4","DOIUrl":"https://doi.org/10.1038/s41531-026-01272-4","url":null,"abstract":"With the intensification of global plastic pollution, the potential threats posed by micro- and nanoplastics (MPs/NPs) to human health have become a major concern. MPs/NPs enter the organism through ingestion, inhalation, and skin contact, subsequently accumulating in multiple organs-particularly the brain. Increasing experimental and epidemiological evidence implicates MPs/NPs in the development of Parkinson's disease (PD). Preclinical research models indicate that MPs/NPs may accelerate both the initiation and progression of PD by facilitating α-synuclein misfolding and aggregation, triggering neuroinflammatory cascades, elevating oxidative stress, and impairing mitochondrial function. To further investigate the causal role of MPs/NPs in PD, upcoming studies should emphasize well-designed, large-scale prospective cohorts to assess individual exposure to plastic-related pollutants, elucidate the pathways of MPs/NPs into the central nervous system, establish safety thresholds for their neurotoxicity, explore the correlation between exposure levels and central nervous system accumulation, clarify the temporal relationship between MPs/NPs accumulation and PD pathology and symptom onset, and identify the neuropathological mechanisms triggered by relevant concentrations of MPs/NPs. Such data will be instrumental in informing preventive and potentially interventional strategies, while offering actionable insights into the interaction between MPs/NPs and PD.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"142 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146042467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This exploratory, single-group, open-label study investigated 17 patients with Parkinson’s disease (PD) using a pre-post design. Motor and non-motor outcomes were assessed through clinical scales, biochemical and genetic analyses, and machine learning models (Gradient Boosting Machines, Random Forests). After treatment with a neurotrophic peptide mixture, improvements were observed in daily activity (16%), cognition (11%), depression (10% reduction), and reactive anxiety (23% reduction). Biological changes included a 45% increase in platelet δ-granules, higher mitochondrial counts, elevated gene expression (notably BDNF in women, p = 0.046), and modulation of oxidative stress markers (17% reduction in TBARS, 30% increase in GSH). Machine learning identified BDNF and PINK1 expression, along with MOCA and MMSE scores, as key predictors of UPDRS improvement. These findings suggest that neurotrophic peptide therapy may influence clinical, structural, and molecular domains in PD. Larger, controlled trials are warranted to confirm therapeutic potential and clarify associations with cognitive and neurotrophic parameters.
这项探索性、单组、开放标签研究采用前后设计调查了17例帕金森病（PD）患者。通过临床量表、生化和遗传分析以及机器学习模型（梯度增强机、随机森林）评估运动和非运动结果。在使用神经营养肽混合物治疗后，观察到日常活动（16%），认知（11%），抑郁（减少10%）和反应性焦虑（减少23%）的改善。生物学变化包括血小板δ-颗粒增加45%，线粒体计数增加，基因表达升高（特别是女性BDNF， p = 0.046），氧化应激标志物调节（TBARS减少17%，GSH增加30%）。机器学习识别出BDNF和PINK1表达，以及MOCA和MMSE评分，作为UPDRS改善的关键预测因素。这些发现提示神经肽治疗可能影响帕金森病的临床、结构和分子领域。有必要进行更大规模的对照试验，以确认治疗潜力，并澄清与认知和神经营养参数的关联。
{"title":"Evaluation of the neurotrophic peptide mixture in pathogenetic therapy of patients with Parkinson’s disease","authors":"Dmytro Krasnienkov, Iryna Karaban, Nina Karasevych, Nataliia Melnyk, Sergiy Kryzhanovskyi, Kateryna Rozova, Olga Gonchar, Iryna Mankovska, Sofiia Smovzh, Kostiantyn Midlovets, Olexiy Barsukov, Oksana Zabuha, Tetiana Papurina","doi":"10.1038/s41531-026-01270-6","DOIUrl":"https://doi.org/10.1038/s41531-026-01270-6","url":null,"abstract":"This exploratory, single-group, open-label study investigated 17 patients with Parkinson’s disease (PD) using a pre-post design. Motor and non-motor outcomes were assessed through clinical scales, biochemical and genetic analyses, and machine learning models (Gradient Boosting Machines, Random Forests). After treatment with a neurotrophic peptide mixture, improvements were observed in daily activity (16%), cognition (11%), depression (10% reduction), and reactive anxiety (23% reduction). Biological changes included a 45% increase in platelet δ-granules, higher mitochondrial counts, elevated gene expression (notably BDNF in women, p = 0.046), and modulation of oxidative stress markers (17% reduction in TBARS, 30% increase in GSH). Machine learning identified BDNF and PINK1 expression, along with MOCA and MMSE scores, as key predictors of UPDRS improvement. These findings suggest that neurotrophic peptide therapy may influence clinical, structural, and molecular domains in PD. Larger, controlled trials are warranted to confirm therapeutic potential and clarify associations with cognitive and neurotrophic parameters.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"68 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146032868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-23DOI: 10.1038/s41531-026-01259-1
Assaf Benesh, Roy N Alcalay, Anat Mirelman, Ron Shamir
Parkinson's disease (PD) is a highly heterogeneous condition with symptoms spanning motor and non-motor domains. Clinical scales like the Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS) are standard in clinical trials where disease progression is monitored. They rely on summing item values, assuming uniform item importance and score increments. Here, we propose a novel data-driven approach to optimize weights for such scales-so that total scores better reflect the underlying disease severity. In a retrospective observational analysis of longitudinal cohort data from the Parkinson's Progression Markers Initiative (PPMI), our methods identified which items (and value increments) most strongly indicate PD progression, down-weighting or excluding less informative items. The learned weights substantially improve the monotonic relationship between total scores and clinical progression. We validated our weights using both held-out PPMI data and an independent dataset (BeaT-PD), demonstrating their robustness. Applying such weights in clinical trials may increase power and reduce the required sample size1.
{"title":"Optimizing Parkinson's disease progression scales using computational methods.","authors":"Assaf Benesh, Roy N Alcalay, Anat Mirelman, Ron Shamir","doi":"10.1038/s41531-026-01259-1","DOIUrl":"https://doi.org/10.1038/s41531-026-01259-1","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a highly heterogeneous condition with symptoms spanning motor and non-motor domains. Clinical scales like the Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS) are standard in clinical trials where disease progression is monitored. They rely on summing item values, assuming uniform item importance and score increments. Here, we propose a novel data-driven approach to optimize weights for such scales-so that total scores better reflect the underlying disease severity. In a retrospective observational analysis of longitudinal cohort data from the Parkinson's Progression Markers Initiative (PPMI), our methods identified which items (and value increments) most strongly indicate PD progression, down-weighting or excluding less informative items. The learned weights substantially improve the monotonic relationship between total scores and clinical progression. We validated our weights using both held-out PPMI data and an independent dataset (BeaT-PD), demonstrating their robustness. Applying such weights in clinical trials may increase power and reduce the required sample size<sup>1</sup>.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146041194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Optimal subthalamic nucleus deep-brain stimulation (STN-DBS) for Parkinson's disease reduces motor symptoms without stimulating adjacent structures and causing side-effects. Fine-tuning STN-DBS using clinical evaluation is time-consuming and often requires multiple follow-ups. Electrophysiological recordings may enhance STN-DBS device programming for clinicians by providing objective evidence of neural pathway activation. This literature review critically evaluates evoked potentials as biomarkers of optimal STN-DBS and assesses potential integration into the device programming toolkit.
{"title":"Clinical utility of evoked potentials for programming subthalamic deep brain stimulation in Parkinsons disease.","authors":"Blake Hale,Anna Latorre,Lorenzo Rocchi,John Rothwell,Patricia Limousin","doi":"10.1038/s41531-026-01274-2","DOIUrl":"https://doi.org/10.1038/s41531-026-01274-2","url":null,"abstract":"Optimal subthalamic nucleus deep-brain stimulation (STN-DBS) for Parkinson's disease reduces motor symptoms without stimulating adjacent structures and causing side-effects. Fine-tuning STN-DBS using clinical evaluation is time-consuming and often requires multiple follow-ups. Electrophysiological recordings may enhance STN-DBS device programming for clinicians by providing objective evidence of neural pathway activation. This literature review critically evaluates evoked potentials as biomarkers of optimal STN-DBS and assesses potential integration into the device programming toolkit.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"17 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-22DOI: 10.1038/s41531-026-01264-4
Kara A Johnson,Patricia B Coutinho,Lauren E Kenney,Joshua K Wong,Justin D Hilliard,Kelly D Foote,Dawn Bowers,Gregory M Pontone,Coralie de Hemptinne
Depression is increasingly recognized as a prevalent source of disability in individuals with Parkinson's disease (PD), but its pathophysiology is not well understood. Neural activity in the basal ganglia, particularly the subthalamic nucleus, has been linked to depression in PD, but the role of the pallidum remains unclear. This retrospective study aimed to correlate preoperative depression symptoms with intraoperative resting-state neural activity recorded from the pallidum in N = 50 patients who underwent deep-brain stimulation (DBS) implantation surgery. Patients with clinically elevated depression symptoms exhibited elevated beta (13-30 Hz) power compared to patients without depression. Beta power, particularly high beta (20-30 Hz) power, was also associated with depression symptom severity, even when controlling for other demographic, clinical, pharmacological, and neurophysiological variables. These results suggest pallidal beta power as a potential biomarker of depression in PD and set the stage for tailoring DBS therapy to improve psychiatric symptoms in PD.
{"title":"Pallidal beta power is associated with depression in Parkinson's disease.","authors":"Kara A Johnson,Patricia B Coutinho,Lauren E Kenney,Joshua K Wong,Justin D Hilliard,Kelly D Foote,Dawn Bowers,Gregory M Pontone,Coralie de Hemptinne","doi":"10.1038/s41531-026-01264-4","DOIUrl":"https://doi.org/10.1038/s41531-026-01264-4","url":null,"abstract":"Depression is increasingly recognized as a prevalent source of disability in individuals with Parkinson's disease (PD), but its pathophysiology is not well understood. Neural activity in the basal ganglia, particularly the subthalamic nucleus, has been linked to depression in PD, but the role of the pallidum remains unclear. This retrospective study aimed to correlate preoperative depression symptoms with intraoperative resting-state neural activity recorded from the pallidum in N = 50 patients who underwent deep-brain stimulation (DBS) implantation surgery. Patients with clinically elevated depression symptoms exhibited elevated beta (13-30 Hz) power compared to patients without depression. Beta power, particularly high beta (20-30 Hz) power, was also associated with depression symptom severity, even when controlling for other demographic, clinical, pharmacological, and neurophysiological variables. These results suggest pallidal beta power as a potential biomarker of depression in PD and set the stage for tailoring DBS therapy to improve psychiatric symptoms in PD.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"52 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Parkinson's disease (PD) is a neurodegenerative disorder with complex motor and non-motor symptoms. This network meta-analysis evaluated the combined effects of medication and 20 rehabilitation therapies on motor function, neuro-psychiatric health, and quality of life in 8202 PD patients across 186 randomized controlled trials. Traditional Chinese Rehabilitation Therapy (TCRT), Exoskeleton-Assisted Rehabilitation Therapy (EART), Hydrotherapy Rehabilitation Therapy (HRT), and Conventional Kinesitherapy (CKT) significantly improved balance, while Mind-Body Exercise Therapy (MBET) and Non-Invasive Brain Stimulation Therapy (NIBST) enhanced overall motor capacity and reduced freezing of gait (FOG). Resistance Training Rehabilitation Therapy (RTRT) and Non-Invasive Brain Stimulation Therapy (NIBST) improved cognitive function, and Mind-Body Exercise Therapy (MBET) alleviated negative mood. Upper Limb Rehabilitation Therapy (ULRT) and Resistance Training Rehabilitation Therapy (RTRT) showed notable quality-of-life benefits. However, confidence in outcomes was often low due to risk of bias and imprecision. Meta-regression indicated that intervention duration was negatively correlated with cognitive gains. These findings highlight the need for precise, integrated rehabilitation strategies targeting specific symptoms to optimize PD management. Future research should explore individualized, mechanism-driven approaches to advance precision rehabilitation.
{"title":"Comparative effects of medication combined with twenty rehabilitation therapies: core outcomes in 8202 parkinson's patients.","authors":"Haojie Li,Xinyu Lin,Rui Huang,Shangjun Huang,Xie Wu","doi":"10.1038/s41531-026-01266-2","DOIUrl":"https://doi.org/10.1038/s41531-026-01266-2","url":null,"abstract":"Parkinson's disease (PD) is a neurodegenerative disorder with complex motor and non-motor symptoms. This network meta-analysis evaluated the combined effects of medication and 20 rehabilitation therapies on motor function, neuro-psychiatric health, and quality of life in 8202 PD patients across 186 randomized controlled trials. Traditional Chinese Rehabilitation Therapy (TCRT), Exoskeleton-Assisted Rehabilitation Therapy (EART), Hydrotherapy Rehabilitation Therapy (HRT), and Conventional Kinesitherapy (CKT) significantly improved balance, while Mind-Body Exercise Therapy (MBET) and Non-Invasive Brain Stimulation Therapy (NIBST) enhanced overall motor capacity and reduced freezing of gait (FOG). Resistance Training Rehabilitation Therapy (RTRT) and Non-Invasive Brain Stimulation Therapy (NIBST) improved cognitive function, and Mind-Body Exercise Therapy (MBET) alleviated negative mood. Upper Limb Rehabilitation Therapy (ULRT) and Resistance Training Rehabilitation Therapy (RTRT) showed notable quality-of-life benefits. However, confidence in outcomes was often low due to risk of bias and imprecision. Meta-regression indicated that intervention duration was negatively correlated with cognitive gains. These findings highlight the need for precise, integrated rehabilitation strategies targeting specific symptoms to optimize PD management. Future research should explore individualized, mechanism-driven approaches to advance precision rehabilitation.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"32 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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