Adrian L. Asendorf, Elena Guerra, Verena Dzialas, Magdalena Banwinkler, Hendrik Theis, Niklas Hagemann, Kathrin Möllenhoff, Thilo van Eimeren, Merle C. Hoenig
{"title":"Physical activity and network attack tolerance preserve motor function in Parkinson’s disease: A pilot study","authors":"Adrian L. Asendorf, Elena Guerra, Verena Dzialas, Magdalena Banwinkler, Hendrik Theis, Niklas Hagemann, Kathrin Möllenhoff, Thilo van Eimeren, Merle C. Hoenig","doi":"10.1038/s41531-025-01033-9","DOIUrl":"https://doi.org/10.1038/s41531-025-01033-9","url":null,"abstract":"<p>We tested whether network resilience, quantified by network attack tolerance (NAT), is associated with dopamine terminal (DaT) integrity, motor function and lifestyle factors in Parkinson’s disease (PD). Data from 22 individuals with PD and 39 healthy controls included information on lifetime physical activity (PA), cognitive/motor performance, putaminal DaT integrity, and resting-state fMRI. NAT was assessed at global and subnetwork level by calculating global efficiency upon iterative node removal. Linear-mixed-effects models were used to test the effects of PA, education, and dopamine integrity on NAT. Next, the moderating effect of lifestyle factors on the association between NAT and motor function were assessed, controlling for DaT integrity. Greater putaminal DaT integrity was linked to higher somatomotor NAT. Higher global and somatomotor NAT supported motor function, especially in patients with moderate lifetime PA. These preliminary results indicate that lifestyle factors serve network-specific attack tolerance, thereby aiding maintenance of motor function in early-stage PD.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"7 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503536","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}
Simona Aresta, Petronilla Battista, Cinzia Palmirotta, Serena Tagliente, Gianvito Lagravinese, Paola Santacesaria, Allegra Benzini, Davide Mongelli, Brigida Minafra, Christian Lunetta, Adolfo M. García, Christian Salvatore
{"title":"Digital phenotyping of Parkinson’s disease via natural language processing","authors":"Simona Aresta, Petronilla Battista, Cinzia Palmirotta, Serena Tagliente, Gianvito Lagravinese, Paola Santacesaria, Allegra Benzini, Davide Mongelli, Brigida Minafra, Christian Lunetta, Adolfo M. García, Christian Salvatore","doi":"10.1038/s41531-025-01050-8","DOIUrl":"https://doi.org/10.1038/s41531-025-01050-8","url":null,"abstract":"<p>Frontostriatal degeneration in Parkinson’s disease (PD) is associated with language deficits, which can be identified using natural language processing, a remarkable tool for digital-phenotyping. Current evidence is mostly blind to the disorder’s cognitive phenotypes. We validated an AI-driven approach to capture digital language markers of PD with and without mild cognitive impairment (PD-MCI, PD-nMCI) relative to healthy controls (HCs). Analyzing the connected speech of participants, we extracted linguistic features with CLAN software. Classification was performed using SVM and RFE. Discrimination between PD and HCs reached an AUC of 77%, with even better results for subgroup analyses (AUC: 85% PD-nMCI vs. HCs; 83% PD-MCI vs. HCs; 75% PD-nMCI vs. PD-MCI). Key linguistic features included retracing, action verb, utterance error, and verbless-utterance ratios. Despite the small sample size, which may limit statistical power and generalizability, this study highlights the foundational potential of linguistic digital markers for early diagnosis and phenotyping of PD.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"644 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144341230","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}
Sissel Ida Schmidt, Justyna Okarmus, Daniel Aghaie Madsen, Julie Schmidt Hansen, Emil Gregersen, Hjalte Gram, Lucas S. Winkelmann, Anderson Souza Oliveira, Rachel Heon-Roberts, Brent J. Ryan, Kristine Freude, Morten Blaabjerg, Poul Henning Jensen, Morten Meyer
{"title":"Formation of seeding-competent α-synuclein aggregates in parkin-deficient iPSC-derived human neurons","authors":"Sissel Ida Schmidt, Justyna Okarmus, Daniel Aghaie Madsen, Julie Schmidt Hansen, Emil Gregersen, Hjalte Gram, Lucas S. Winkelmann, Anderson Souza Oliveira, Rachel Heon-Roberts, Brent J. Ryan, Kristine Freude, Morten Blaabjerg, Poul Henning Jensen, Morten Meyer","doi":"10.1038/s41531-025-01038-4","DOIUrl":"https://doi.org/10.1038/s41531-025-01038-4","url":null,"abstract":"<p>Loss-of-function mutations in <i>PARK2</i> (parkin) cause early-onset familial Parkinson’s disease (PD) and may also contribute to sporadic PD. While Lewy bodies, enriched in aggregated phosphorylated α-synuclein (α-Syn), are typical in PD, their presence in <i>PARK2</i>-mediated PD remains debated. Using human isogenic <i>PARK2</i><sup>−/−</sup> induced pluripotent stem cell-derived neurons, we investigated α-Syn pathology under parkin deficiency. <i>PARK2</i><sup>−/−</sup> neurons showed elevated intracellular aggregated and total α-Syn levels, increased α-Syn release, and higher levels of aggregation-inducing α-Syn seeds. These neurons also displayed more pSer129 α-Syn<sup>+</sup> inclusions, which were further enhanced by α-Syn preformed fibril (PFF) exposure. Moreover, we identified synaptic loss in the <i>PARK2</i><sup><i>−/−</i></sup> neurons, exacerbated by PFF treatment, and dysregulated Ca<sup>2+</sup> homeostasis consistent with enhanced activity of the smooth endoplasmic reticulum Ca<sup>2+</sup>-ATPase (SERCA). Our data provide an important contribution to the debate on the role of α-Syn in the pathology of <i>PARK2</i>-related PD and challenge the view of <i>PARK2</i>-related PD as a non-synucleinopathy.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"59 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144335016","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}
Jason Langley, Kristy S. Hwang, Daniel E. Huddleston, Xiaoping P. Hu
{"title":"Nigral volume loss in prodromal, early, and moderate Parkinson’s disease","authors":"Jason Langley, Kristy S. Hwang, Daniel E. Huddleston, Xiaoping P. Hu","doi":"10.1038/s41531-025-00976-3","DOIUrl":"https://doi.org/10.1038/s41531-025-00976-3","url":null,"abstract":"<p>The loss of melanized neurons in the substantia nigra pars compacta (SNc) is a hallmark pathology in Parkinson’s disease (PD). Melanized neurons in SNc can be visualized in vivo using magnetization transfer (MT) effects. Nigral volume was extracted in data acquired with a MT-prepared gradient echo sequence in 50 controls, 90 non-manifest carriers (46 LRRK2 and 44 GBA1 nonmanifest carriers), 217 prodromal hyposmic participants, 76 participants with rapid eye movement sleep behavior disorder (RBD), 194 de novo PD patients and 26 moderate PD patients from the Parkinson’s Progressive Markers Initiative. No difference in nigral volume was seen between controls and LRRK2 and GBA1 non-manifest carriers (<i>F</i> = 0.732; <i>P</i> = 0.483). A significant main effect in group was observed between controls, prodromal hyposmic participants, RBD participants, and overt PD patients (<i>F</i> = 9.882; <i>P</i> < 10<sup>−3</sup>). This study shows that nigral depigmentation can be robustly detected in prodromal and overt PD populations.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"105 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337532","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}
Marianna Capecci, Nicolò Baldini, Elisa Andrenelli, Alice Lambertucci, Paola Bisoglio, Martina Grugnetti, Hibel Margherita, Maria Gabriella Ceravolo
{"title":"Impact of an intensive outpatient rehabilitation on non-motor patients’ reported outcomes in PD: the INTENSO study","authors":"Marianna Capecci, Nicolò Baldini, Elisa Andrenelli, Alice Lambertucci, Paola Bisoglio, Martina Grugnetti, Hibel Margherita, Maria Gabriella Ceravolo","doi":"10.1038/s41531-025-01035-7","DOIUrl":"https://doi.org/10.1038/s41531-025-01035-7","url":null,"abstract":"<p>Non-motor symptoms in Parkinson’s disease (PD) can reduce quality of life and increase disability. This historical cohort study investigated how rehabilitation intensity influences non-motor symptoms. The primary outcomes were changes in non-motor symptoms in the short and medium term. Secondary outcomes were changes in disability burden, motor symptom severity, and freezing of gait after treatment. Measurements were taken before (T0) and after treatment (T1) and 6 ± 1 months after T1 (T2). According to total training duration, 24 patients with PD were assigned to High-Intensity Training group (HIT, 1800 min) and 24 to Low-Intensity Training (LIT, less than 900 minutes). At T1, only the HIT group showed clinically significant improvements in non-motor symptoms, which were maintained at T2. In contrast, the LIT group experienced worsening disability at follow-up. Multivariate analysis revealed training intensity and baseline disability as predictors of improvement. These findings support the benefits of high intensity exercise in PD management.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"608 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144335013","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}
{"title":"A novel fusion architecture for detecting Parkinson’s Disease using semi-supervised speech embeddings","authors":"Tariq Adnan, Abdelrahman Abdelkader, Zipei Liu, Ekram Hossain, Sooyong Park, Md Saiful Islam, Ehsan Hoque","doi":"10.1038/s41531-025-00956-7","DOIUrl":"https://doi.org/10.1038/s41531-025-00956-7","url":null,"abstract":"We introduce a framework for screening Parkinson’s disease (PD) using English pangram utterances. Our dataset includes 1306 participants (392 with PD) from both home and clinical settings, covering diverse demographics (53.2% female). We used deep learning embeddings from Wav2Vec 2.0, WavLM, and ImageBind to capture speech dynamics indicative of PD. Our novel fusion model for PD classification aligns different speech embeddings into a cohesive feature space, outperforming baseline alternatives. In a stratified randomized split, the model achieved an AUROC of 88.9% and an accuracy of 85.7%. Statistical bias analysis showed equitable performance across sex, ethnicity, and age subgroups, with robustness across various disease durations and PD stages. Detailed error analysis revealed higher misclassification rates in specific age ranges for males and females, aligning with clinical insights. External testing yielded AUROCs of 82.1% and 78.4% on two clinical datasets, and an AUROC of 77.4% on an unseen general spontaneous English speech dataset, demonstrating versatility in natural speech analysis and potential for global accessibility and health equity.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"13 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144328967","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}
Jessica Chedid, Yan Li, Adahir Labrador-Garrido, Dad Abu-Bonsrah, Chiara Pavan, Tyra Fraser, Dmitry Ovchinnikov, Melanie Zhong, Ryan Davis, Dario Strbenac, Jennifer A. Johnston, Lachlan H. Thompson, Deniz Kirik, Clare L. Parish, Glenda M. Halliday, Carolyn M. Sue, Gautam Wali, Nicolas Dzamko
{"title":"Dopamine and cortical neurons with different Parkinsonian mutations show variation in lysosomal and mitochondrial dysfunction","authors":"Jessica Chedid, Yan Li, Adahir Labrador-Garrido, Dad Abu-Bonsrah, Chiara Pavan, Tyra Fraser, Dmitry Ovchinnikov, Melanie Zhong, Ryan Davis, Dario Strbenac, Jennifer A. Johnston, Lachlan H. Thompson, Deniz Kirik, Clare L. Parish, Glenda M. Halliday, Carolyn M. Sue, Gautam Wali, Nicolas Dzamko","doi":"10.1038/s41531-025-01048-2","DOIUrl":"https://doi.org/10.1038/s41531-025-01048-2","url":null,"abstract":"<p>Mutations causing Parkinson’s disease (PD) give diverse pathological phenotypes whose cellular correlates remain to be determined. Those with <i>PRKN</i> mutations have significantly earlier selective vulnerability of dopamine neurons, those with <i>SNCA</i> mutations have increased alpha-synuclein deposition, while those with <i>LRRK2</i> mutations have additional deposition of tau. Yet all three mutation types are implicated in mitochondrial and/or lysosomal dysfunction. To compare cellular dysfunctions associated with these different pathological phenotypes, an unbiased high-content imaging platform was developed to assess both lysosomal and mitochondrial dysfunction, along with alpha-synuclein and tau protein deposition using induced pluripotent stem cell (iPSC) derived cortical and ventral midbrain neurons. Different PD mutations caused cell type specific dysfunctions, likely to impact on both selective neuronal vulnerability and the pathologies observed in PD. Comparison of dopamine neurons identified that both lysosomal and mitochondrial dysfunction were predominant with <i>PRKN</i> lof mutations, whereas <i>SNCA</i> A53T and <i>LRRK2</i> R1441G mutations had increased tau deposition. In contrast, cortical neurons with <i>SNCA</i> and <i>LRRK2</i> mutations both had mitochondrial and autophagy impairments without protein deposition, with <i>LRRK2</i> cells additionally showing decreased glucocerebrosidase activity and increased alpha-synuclein phosphorylation.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"32 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144334895","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}
Alexandra Vaiana, Jonathan Behr, Ryan Birol, Cornelis Blauwendraat, Bradford Casey, Kushan Chowdhury, Martin Citron, Joshua Crapser, Victoria Dardov, Fiona Ducotterd, Sonya Dumanis, John Dunlop, Michelle Durborow, Brian Fiske, Jessica Golden, Jonas Hannestad, Wendy Hung, Jennifer Kemp, Robin Kleiman, Adam Knight, Andrew Koemeter-Cox, Bruce Leuchter, Bejamin A. Logsdon, Rita Marreiros, Julie E. Miller, Amanda Mitchell, Pooja Mukherjee, Grace Navarro, Matthew R. Nelson, Karoly Nikolich, Tom Otis, Nicole Polinski, Shima Rastegar-Pouyani, Alastair D. Reith, Ekemini Riley, Lee Rubin, Mina Ryten, Jessica Sadick, Tina Schwabe, Todd Sherer, Sarah Silvergleid, Andrew Singleton, Lara St. Clair, Jan Stoehr, David J. Stone, Julianna Sullivan, Nicole Tanenbaum, Elisa Tinelli, Kate Trimble, Yifei Wang, Stacie Weninger, Nicolás Wiggenhauser, Stephen Wood, Darryle Schoepp, Virginie Buggia-Prevot, Shalini Padmanabhan, Gaia Skibinski
{"title":"A community-led initiative to de-risk and advance Parkinson’s disease therapeutic targets","authors":"Alexandra Vaiana, Jonathan Behr, Ryan Birol, Cornelis Blauwendraat, Bradford Casey, Kushan Chowdhury, Martin Citron, Joshua Crapser, Victoria Dardov, Fiona Ducotterd, Sonya Dumanis, John Dunlop, Michelle Durborow, Brian Fiske, Jessica Golden, Jonas Hannestad, Wendy Hung, Jennifer Kemp, Robin Kleiman, Adam Knight, Andrew Koemeter-Cox, Bruce Leuchter, Bejamin A. Logsdon, Rita Marreiros, Julie E. Miller, Amanda Mitchell, Pooja Mukherjee, Grace Navarro, Matthew R. Nelson, Karoly Nikolich, Tom Otis, Nicole Polinski, Shima Rastegar-Pouyani, Alastair D. Reith, Ekemini Riley, Lee Rubin, Mina Ryten, Jessica Sadick, Tina Schwabe, Todd Sherer, Sarah Silvergleid, Andrew Singleton, Lara St. Clair, Jan Stoehr, David J. Stone, Julianna Sullivan, Nicole Tanenbaum, Elisa Tinelli, Kate Trimble, Yifei Wang, Stacie Weninger, Nicolás Wiggenhauser, Stephen Wood, Darryle Schoepp, Virginie Buggia-Prevot, Shalini Padmanabhan, Gaia Skibinski","doi":"10.1038/s41531-025-01039-3","DOIUrl":"https://doi.org/10.1038/s41531-025-01039-3","url":null,"abstract":"<p>Identifying effective therapeutic targets for Parkinson’s disease (PD) is challenging, with no current disease-modifying therapies available. To address this, The Michael J. Fox Foundation for Parkinson’s Research launched the Targets to Therapies (T2T) initiative, uniting experts to prioritize and validate promising targets. T2T aims to develop validation strategies, create comprehensive target data profiles, and build tools to support drug development, ultimately accelerating the discovery of new therapies for PD patients.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"38 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144335022","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}
Wen-Xiang Duan,Wei-Ye Xie,Chen Ying,Wang Fen,Xiao-Yu Cheng,Cheng-Jie Mao,Jun-Yi Liu,Chun-Feng Liu
{"title":"Butyrate improves abnormal sleep architecture in a Parkinson's disease mouse model via BDNF/TrkB signaling.","authors":"Wen-Xiang Duan,Wei-Ye Xie,Chen Ying,Wang Fen,Xiao-Yu Cheng,Cheng-Jie Mao,Jun-Yi Liu,Chun-Feng Liu","doi":"10.1038/s41531-025-01029-5","DOIUrl":"https://doi.org/10.1038/s41531-025-01029-5","url":null,"abstract":"Sleep disturbances are among the most prevalent non-motor symptoms of Parkinson's disease (PD), yet their underlying mechanisms remain inadequately understood. Emerging evidence has emphasized a strong association between gut health and sleep stability, with notable early alterations in microbial composition and short-chain fatty acid (SCFA) levels observed during the progression of PD. Consequently, targeting the gut as a therapeutic strategy for sleep disturbances in PD has become a focus of our research. In this study, we demonstrated that a subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model exhibited a marked reduction in daytime sleep alongside an increase in nighttime sleep. Microbial sequencing and SCFA profiling revealed a significant decline in butyrate levels and the abundance of butyrate-producing bacteria. Correlation analysis indicated a significant positive correlation between butyrate levels and the duration of daytime non-rapid eye movement (NREM) sleep. Furthermore, supplementation with butyrate effectively restored normal sleep architecture in MPTP-induced PD mice. Further mechanistic studies revealed that this effect is mediated through the BDNF-TrkB pathway. These findings suggest that direct or indirect supplementation with butyrate may be a potential therapeutic approach for improving sleep disorders in PD patients.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"16 1","pages":"175"},"PeriodicalIF":8.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144328585","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}
Hamid Fekri Azgomi, Kenneth H. Louie, Jessica E. Bath, Kara N. Presbrey, Jannine P. Balakid, Jacob H. Marks, Thomas A. Wozny, Nicholas B. Galifianakis, Marta San Luciano, Simon Little, Philip A. Starr, Doris D. Wang
{"title":"Modeling and optimizing deep brain stimulation to enhance gait in Parkinson’s disease: personalized treatment with neurophysiological insights","authors":"Hamid Fekri Azgomi, Kenneth H. Louie, Jessica E. Bath, Kara N. Presbrey, Jannine P. Balakid, Jacob H. Marks, Thomas A. Wozny, Nicholas B. Galifianakis, Marta San Luciano, Simon Little, Philip A. Starr, Doris D. Wang","doi":"10.1038/s41531-025-00990-5","DOIUrl":"https://doi.org/10.1038/s41531-025-00990-5","url":null,"abstract":"<p>The effects of deep brain stimulation (DBS) on gait in Parkinson’s disease (PD) are variable due to challenges in gait assessment and limited understanding of stimulation parameters’ impacts on neural activity. We developed a data-driven approach to identify optimal DBS parameters to improve gait and uncover neurophysiological signatures of gait enhancement. Field potentials from the globus pallidus (GP) and motor cortex were recorded in three patients with PD (PwP) using implanted bidirectional neural stimulators during overground walking. We developed a Walking Performance Index (WPI) to assess gait metrics. DBS parameters were systematically varied to study their impacts on gait and neural dynamics. We were able to predict and identify personalized DBS settings that improved the WPI using a Gaussian Process Regressor. Improved walking correlated with reduced pallidal beta power during key gait phases. These findings, along with identified person-specific neural spectral biomarkers, underscore the importance of personalized, data-driven interventions for gait enhancement in PwP. ClinicalTrials.gov registration: NCT-03582891.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"38 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144312198","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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