Salvatore Falciglia, Laura Caffi, Claudio Baiata, Chiara Palmisano, Ioannis Ugo Isaias, Alberto Mazzoni
{"title":"Transformer-based long-term predictor of subthalamic beta activity in Parkinson’s disease","authors":"Salvatore Falciglia, Laura Caffi, Claudio Baiata, Chiara Palmisano, Ioannis Ugo Isaias, Alberto Mazzoni","doi":"10.1038/s41531-025-01011-1","DOIUrl":"https://doi.org/10.1038/s41531-025-01011-1","url":null,"abstract":"<p>Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a mainstay treatment for patients with Parkinson’s disease (PD). The adaptive DBS approach (aDBS) modulates stimulation, based on the power in the beta range ([12–30] Hz) of STN local field potentials, aiming to follow the patient’s clinical state. Control of aDBS relies on identifying the correct thresholds of pathological beta power. Currently, in-person reprogramming sessions, due to changes in beta power distribution over time, are needed to ensure clinical efficacy. Here we present LAURA, a Transformer-based framework predicting the nonlinear evolution of subthalamic beta power up to 6 days in advance, based on the analysis of chronic recordings. High prediction accuracy (>90%) was achieved in four PD patients with chronic DBS over months of recordings, independently of stimulation parameters. Our study paves the way for remote monitoring strategies and the implementation of new algorithms for personalized auto-tuning aDBS devices.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"109 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144612841","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}
Elijah Mak, Robert I Reid, Scott A Przybelski, Angela J Fought, Timothy G Lesnick, Christopher G Schwarz, Matthew L Senjem, Sheelakumari Raghavan, Prashanthi Vemuri, Clifford R Jack, Hoon Ki Min, Manoj K Jain, Toji Miyagawa, Leah K Forsberg, Julie A Fields, Rodolfo Savica, Jonathan Graff-Radford, David T Jones, Hugo Botha, Erik K St Louis, David S Knopman, Vijay K Ramanan, Dennis W Dickson, Neill R Graff-Radford, Gregory S Day, Tanis J Ferman, Ronald C Petersen, Val J Lowe, Bradley F Boeve, John T O'Brien, Kejal Kantarci
{"title":"Author Correction: Cortical microstructural abnormalities in dementia with Lewy bodies and their associations with Alzheimer's disease copathologies.","authors":"Elijah Mak, Robert I Reid, Scott A Przybelski, Angela J Fought, Timothy G Lesnick, Christopher G Schwarz, Matthew L Senjem, Sheelakumari Raghavan, Prashanthi Vemuri, Clifford R Jack, Hoon Ki Min, Manoj K Jain, Toji Miyagawa, Leah K Forsberg, Julie A Fields, Rodolfo Savica, Jonathan Graff-Radford, David T Jones, Hugo Botha, Erik K St Louis, David S Knopman, Vijay K Ramanan, Dennis W Dickson, Neill R Graff-Radford, Gregory S Day, Tanis J Ferman, Ronald C Petersen, Val J Lowe, Bradley F Boeve, John T O'Brien, Kejal Kantarci","doi":"10.1038/s41531-025-01068-y","DOIUrl":"https://doi.org/10.1038/s41531-025-01068-y","url":null,"abstract":"","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"11 1","pages":"209"},"PeriodicalIF":6.7,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144619724","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}
Liuzhenxiong Yu, Jinying Han, Xin Chen, Lili Hu, Mengqi Wang, Minhao Zhu, Jingjing Cheng, Pingping Liu, Lu Fang, Yaqiang Li, Junjun Wu, Xingyu Zhao, Jinmei Sun, Gong-Jun Ji, Kai Wang, Rong Ye, Panpan Hu
{"title":"Regional-specific structural and functional changes of posterior cerebellar vermis across different stages of Parkinson’s disease with gait dysfunction","authors":"Liuzhenxiong Yu, Jinying Han, Xin Chen, Lili Hu, Mengqi Wang, Minhao Zhu, Jingjing Cheng, Pingping Liu, Lu Fang, Yaqiang Li, Junjun Wu, Xingyu Zhao, Jinmei Sun, Gong-Jun Ji, Kai Wang, Rong Ye, Panpan Hu","doi":"10.1038/s41531-025-01065-1","DOIUrl":"https://doi.org/10.1038/s41531-025-01065-1","url":null,"abstract":"<p>Stage-specific roles of posterior cerebellar vermis (PV) subdivisions, the posterior superior vermis (PSV) and posterior inferior vermis (PIV), in Parkinson’s disease postural instability/gait difficulty (PD-PIGD) remain unclear. This retrospective, cross-sectional study investigated their volumetric and functional connectivity (FC) changes and clinical correlates across PD-PIGD stages. We analyzed 94 PD-PIGD patients (Hoehn & Yahr, HY1-4) and 46 healthy controls (HCs). Patient data were from outpatients and baseline assessments in two clinical trials (ClinicalTrials.gov: NCT02969941, reg. 2016-06-01; NCT05192759, reg. 2021-11-22). Compared with HCs, early-stage (HY1) patients showed enhanced PSV-left paracentral lobule (L_PCL) FC, alongside a trend toward increased PSV volume. This PSV-L_PCL FC correlated with better cognition function and gait performance, an association partly cognition-mediated. Our findings reveal a PSV-specific nonlinear pattern of structural and functional changes in PD-PIGD, distinct from PIV or other cerebellar subregions, potentially reflecting early compensatory mechanisms transitioning to later network dysfunction.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"61 2 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144611136","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}
L. Phan, D. Miller, A. Gopinath, M. Lin, E. J. Miller, D. Guenther, S. Quintin, D. Borg, Z. Hasanpour-Segherlou, A. Newman, Z. Sorrentino, J. Seibold, B. Hoh, B. Giasson, H. Khoshbouei
{"title":"Parkinson’s paradox: alpha-synuclein’s selective strike on SNc dopamine neurons over VTA","authors":"L. Phan, D. Miller, A. Gopinath, M. Lin, E. J. Miller, D. Guenther, S. Quintin, D. Borg, Z. Hasanpour-Segherlou, A. Newman, Z. Sorrentino, J. Seibold, B. Hoh, B. Giasson, H. Khoshbouei","doi":"10.1038/s41531-025-01055-3","DOIUrl":"https://doi.org/10.1038/s41531-025-01055-3","url":null,"abstract":"<p>A central question in Parkinson’s disease (PD) and related synucleinopathies research is why dopamine neurons in the substantia nigra pars compacta (SNc) are more vulnerable than those in the ventral tegmental area (VTA). We investigated how α-synuclein affects neuronal activity before cell death using two mouse models: α-synuclein preformed fibril injections and AAV-mediated human α-synuclein expression. Four-weeks post-injection, histological analysis confirmed no significant neuronal loss in either structure, providing a temporal window to study neuronal activity before cell death. Electrophysiological recordings revealed region-specific vulnerability: SNc dopamine neurons exhibited significantly increased baseline firing rates while VTA neurons remained unaffected. SNc neurons showed impaired homeostatic firing regulation following hyperpolarization, while VTA neurons maintained normal recovery. Elevated α-synuclein also altered network stability in SNc dopamine neurons before cell death, while sparing VTA neurons. These findings reveal early functional differences that may explain the selective vulnerability of SNc dopamine neurons in PD.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"10 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144603087","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}
Nienke A. Timmermans, Roberta Terranova, Diogo C. Soriano, Hayriye Cagnan, Yordan P. Raykov, Ioan Gabriel Bucur, Bastiaan R. Bloem, Rick C. Helmich, Luc J. W. Evers
{"title":"A generalizable and open-source algorithm for real-life monitoring of tremor in Parkinson’s disease","authors":"Nienke A. Timmermans, Roberta Terranova, Diogo C. Soriano, Hayriye Cagnan, Yordan P. Raykov, Ioan Gabriel Bucur, Bastiaan R. Bloem, Rick C. Helmich, Luc J. W. Evers","doi":"10.1038/s41531-025-01056-2","DOIUrl":"https://doi.org/10.1038/s41531-025-01056-2","url":null,"abstract":"<p>Wearable sensors can objectively and continuously monitor daily-life tremor in Parkinson’s Disease (PD). We developed an open-source algorithm for real-life monitoring of PD tremor which achieves generalizable performance across different wrist-worn devices. We achieved this using a unique combination of two independent, complementary datasets. The first was a small, but extensively video-labeled gyroscope dataset collected during unscripted activities at home (<i>n</i> = 24 PD; <i>n</i> = 24 controls). We used this to train and validate a logistic regression tremor detector based on cepstral coefficients. The second was a large, unsupervised dataset (<i>n</i> = 517 PD; <i>n</i> = 50 controls, data collected for 2 weeks with a different device), used to externally validate the algorithm. Results show that our algorithm can reliably quantify real-life PD tremor (sensitivity of 0.61 (0.20) and specificity of 0.97 (0.05)). Weekly aggregated tremor time and power showed excellent test-retest reliability and moderate correlation to MDS-UPDRS rest tremor scores. This opens possibilities to support clinical trials and individual tremor management with wearable technology.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"29 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144603090","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":"Theta-frequency subthalamic stimulation enhances conflict resolution in Parkinson’s disease patients with freezing of gait through frontal cortex modulation","authors":"Hutao Xie, Yutong Bai, Yutong Zhuang, Jiansong Huang, Delong Wu, Xin Zhang, Lin Shi, Hua Zhang, Jian Li, Jing Fu, Anchao Yang, Fangang Meng, Quan Zhang, Yin Jiang, Jianguo Zhang","doi":"10.1038/s41531-025-01067-z","DOIUrl":"https://doi.org/10.1038/s41531-025-01067-z","url":null,"abstract":"<p>Freezing of gait (FOG) in Parkinson’s disease (PD) is a debilitating motor symptom linked to executive dysfunction, particularly impaired conflict resolution. However, the underlying neural mechanisms and optimal treatment remain unclear. We assessed conflict resolution using a modified Flanker task in 90 PD patients (52 with FOG) and 37 healthy controls. PD-FOG patients exhibited significantly greater conflict costs than patients without FOG and healthy controls. Task-based fMRI revealed enhanced frontal cortical activation associated with conflict processing deficits in PD-FOG, positively correlating with FOG severity. In a subgroup of 18 PD-FOG patients undergoing fMRI during subthalamic nucleus deep brain stimulation (STN-DBS), theta-frequency (5 Hz) stimulation improved conflict resolution and increased frontal activation, whereas high-frequency (130 Hz) stimulation primarily activated motor regions without cognitive benefit. These findings indicate that frontal dysfunction contributed to the conflict resolution deficits in PD-FOG and support theta-frequency STN-DBS as a promising therapeutic approach for enhancing cognitive function.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"11 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144603088","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}
Mariëlle J. Stam, Bernadette C. M. van Wijk, Arthur W. G. Buijink, Dan Piña-Fuentes, Rob M. A. de Bie, Rick Schuurman, Martijn Beudel
{"title":"Long-term consistency of aperiodic and periodic physiomarkers in subthalamic local field potentials in Parkinson’s disease","authors":"Mariëlle J. Stam, Bernadette C. M. van Wijk, Arthur W. G. Buijink, Dan Piña-Fuentes, Rob M. A. de Bie, Rick Schuurman, Martijn Beudel","doi":"10.1038/s41531-025-01053-5","DOIUrl":"https://doi.org/10.1038/s41531-025-01053-5","url":null,"abstract":"<p>Beta oscillations (±13–35 Hz) and aperiodic spectral features extracted from local field potential (LFP) recordings have been identified as promising physiomarkers for adaptive deep brain stimulation (aDBS) in Parkinson’s disease. However, the long-term consistency of these signal features across behavioural and clinical conditions remains unclear. Bilateral subthalamic nucleus LFPs were recorded from twelve patients with an average inter-recording interval of 137 days, during rest, a finger-to-nose task and speech, with stimulation switched off and on. Intra-class correlation coefficients indicated moderate between-visit consistency for aperiodic offset and exponent but good to excellent consistency of beta peak power. Most aperiodic and power changes induced by task execution and stimulation were statistically comparable across visits. Results remained inconclusive regarding the properties of beta peaks exhibiting the strongest power suppression post-stimulation. Our findings support the potential of beta peak power as primary physiomarker for aDBS, with aperiodic components as possibly suitable supplementary markers.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"22 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144603089","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}
Michele De Sciscio,Robert V Bryant,Sarah Haylock-Jacobs,Alice S Day,William Pitchers,Robert Iansek,Samuel P Costello,Thomas E Kimber
{"title":"Faecal microbiota transplant in Parkinson's disease: pilot study to establish safety & tolerability.","authors":"Michele De Sciscio,Robert V Bryant,Sarah Haylock-Jacobs,Alice S Day,William Pitchers,Robert Iansek,Samuel P Costello,Thomas E Kimber","doi":"10.1038/s41531-025-01061-5","DOIUrl":"https://doi.org/10.1038/s41531-025-01061-5","url":null,"abstract":"Emerging evidence suggests gut microbiota differences in Parkinson's Disease (PD) may impact disease progression and treatment. Faecal Microbiota Transplantation (FMT) offers a potential therapeutic approach. We conducted an open-label pilot study to assess the safety, tolerability, and symptom impact of FMT in 12 patients with mild to moderate PD, administered via enema for 6 months. FMT was safe and well tolerated, causing only mild, transient gastrointestinal symptoms. While no significant motor symptom changes were observed, there was a trend toward reduced daily OFF time at 2 months. Whilst no sustained improvement in non-motor symptoms was found after 6 months, transient improvements in quality of life and non-motor scores were noted at 2 months; these gains regressed by study end. Overall, extended FMT therapy in PD appears safe and tolerable, with reduction in daily motor OFF time and self-reported non-motor symptoms that was not sustained throughout the 6-months of treatment.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"109 1","pages":"203"},"PeriodicalIF":8.7,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594225","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 Chen, Haobo Wang, Xiang Ye, Xingkai Hao, Fujie Yan, Jian Wu, Danyang Li, Yan Wang, Lizhou Xu
{"title":"Gardenia-derived extracellular vesicles exert therapeutic effects on dopaminergic neuron apoptosis-mediated Parkinson’s disease","authors":"Wen Chen, Haobo Wang, Xiang Ye, Xingkai Hao, Fujie Yan, Jian Wu, Danyang Li, Yan Wang, Lizhou Xu","doi":"10.1038/s41531-025-01044-6","DOIUrl":"https://doi.org/10.1038/s41531-025-01044-6","url":null,"abstract":"<p>Plant-derived extracellular vesicles (EVs) show health benefits. <i>Gardenia jasminoides</i> Ellis, known for its neuroprotective properties, lacks therapeutic investigation on gardenia-derived extracellular vesicles (GDEVs). This study investigated the value of GDEVs in Parkinson’s disease (PD) using rotenone (Rot)-induced Parkinsonism models in dopaminergic PC12 neuron cells and <i>Caenorhabditis elegans</i>. PD features apoptosis in dopaminergic neurons, while GDEVs alleviate PD by mitigating mitochondrial-mediated apoptosis. Specifically, GDEVs improve Rot-induced mitochondrial dysfunction to reduce cytochrome C release and apoptosis. Consequently, GDEVs reduce the risk of PD by lowering α-synuclein levels and regulating dopamine release. RNA sequencing and subsequent studies showed that GDEVs reduce p38 MAPK and p53 phosphorylation levels, and increase the Bcl-2/Bax ratio to prevent apoptosis in PC12 cells. In <i>Caenorhabditis elegans</i>, we verified that GDEVs reduce PD progression by increasing dopaminergic neurons using BZ555 mutants, and enhance dopamine release and motility. This study highlights the therapeutic potential of GDEVs in preventing neurodegenerative diseases.</p><figure></figure>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"19 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144547424","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}
Ruwani S. Wijeyekoon, Marta Camacho, David Bäckström, Lars Forsgren, Rachael A. Lawson, Alison J. Yarnall, Angus D. Macleod, Carl E. Counsell, Ole-Bjørn Tysnes, Guido Alves, Jodi Maple-Grødem, Roger A. Barker, Caroline H. Williams-Gray
{"title":"Beta-adrenoceptor drugs and progression to Parkinson’s disease milestones in a large pooled incident cohort","authors":"Ruwani S. Wijeyekoon, Marta Camacho, David Bäckström, Lars Forsgren, Rachael A. Lawson, Alison J. Yarnall, Angus D. Macleod, Carl E. Counsell, Ole-Bjørn Tysnes, Guido Alves, Jodi Maple-Grødem, Roger A. Barker, Caroline H. Williams-Gray","doi":"10.1038/s41531-025-01014-y","DOIUrl":"https://doi.org/10.1038/s41531-025-01014-y","url":null,"abstract":"<p>Beta-adrenoceptor-blockers and agonists have been associated with an increased and decreased risk of Parkinson’s disease (PD), respectively. We aimed to investigate whether these medications are linked to clinical heterogeneity and progression in PD. Longitudinal data from the Parkinson’s Incident Cohorts Collaboration (<i>n</i> = 1107) were analysed. Baseline clinical status and progression to Hoehn & Yahr stage 3 (H&Y3) or dementia were compared in beta-blocker or beta-agonist users versus non-users of each drug. Baseline motor and cognitive variables were similar in beta-blocker users (<i>n</i> = 195) versus non-users and beta-agonist users (<i>n</i> = 68) versus non-users, following adjustment for relevant confounders. Beta-blocker users (<i>n</i> = 156) progressed faster to H&Y3 (<i>p</i> = 0.002), accounting for relevant confounders (Hazard Ratio (HR) = 1.538; <i>p</i> = 0.011), while beta-agonist users (<i>n</i> = 54) progressed similarly to non-users. Neither drug was associated with progression to dementia. These findings support the possibility that beta-adrenoceptor drugs may have potential in modifying aspects of PD progression. Further investigation is essential to identify any causative component in the relationship.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"5 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144547386","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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