Plasma fatty acids reflect pain, disability, and psychological well-being in knee osteoarthritis in a longitudinal study with joint replacement surgery Anne-Mari Mustonen, Laura Säisänen, Lauri Karttunen, Amir Esrafilian, Petro Julkunen, Jusa Reijonen, Reijo Käkelä, Sanna P. Sihvo, Juho Kopra, Heikki Kröger, Jari Arokoski, Petteri Nieminen Scientific Reports, 2026 We investigated the associations of pro- and anti-inflammatory fatty acids (FAs) with cartilage degradation, functional limitations, pain, and psychological well-being in knee osteoarthritis (KOA). Fasting plasma samples were obtained from controls ( n = 12) and from end-stage KOA patients at baseline ( n = 13), and 3 months ( n = 11) and 12 months ( n = 9) after knee replacement surgery. FA composition in total lipids was analyzed with gas chromatography and mass spectrometry. Cartilage loss was determined by magnetic resonance imaging, and knee pain and disability by physical performance and quantitative sensory testing, neuromuscular examination, and several questionnaires. The associations between variables were tested with the univariate analysis of variance adjusted for age and body mass index. KOA was characterized with elevated baseline 16:1n-7 percentages, while the proportions of 24:0 decreased 12 months after surgery and those of 24:1n-9 decreased 3 and 12 months after surgery. Several FA variables, such as 20:3n-6, 20:4n-6, long-chain saturated FAs, and 24:1n-9, were associated with pain, stiffness, disability, pain self-efficacy, or mental health. Circulating FAs can predict KOA symptoms, independent of age and body adiposity, and provide promising targets to design novel pain treatments.
External clinical audits in clinical radiology in Finland Petro Julkunen, Nina Heinola, Taina Autti, Ritva Bly Radiation Protection Dosimetry, 2026 Clinical audits have been implemented in Finland to healthcare organizations over 20 years. We introduce the outcomes of fourth round external clinical audits on medical radiological procedures following the implementation of the EU Directive (Basic Safety Standards). We analyzed 31 external clinical audits on radiological practices in 2018–2022. The summarized strengths and recommendations from the audits were collected from the main auditing organization’s database. 306 recommendations were given, 18% related to definitions of responsibilities, 16% to internal procedural guidelines, 16% to personnel education, and 25% to quality assurance and utilization of self-assessments of radiological procedures. Private and small organizations received less recommendations than large and public operators. Moreover, 215 strengths were reported, focusing on the clarity of responsibilities (21%) and excellence in quality assurance (15%). Reaching and maintaining feasible radiological diagnostic accuracy by consideration of radiation safety requires continuous quality assurance and development facilitated, and monitored by clinical audits.
Increased motor cortex excitability in chronic complex regional pain syndrome Jukka Vanhanen, Janne Nordberg, Janika Paavola, Petro Julkunen, Miguel Munoz, Jyrki P. Mäkelä, Selja Vaalto, Erika Kirveskari, Satu Jääskeläinen Clinical Neurophysiology, 2026 OBJECTIVE: To characterize corticospinal excitability and cortical motor representation in complex regional pain syndrome (CRPS) type I and type II, addressing inconsistencies in prior research regarding these mechanisms. METHODS: Fifty-nine CRPS patients (44 type I and 15 type II) underwent TMS and paired-pulse TMS examinations to assess resting motor threshold (RMT), motor evoked potential (MEP) amplitude and latency, short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) bilaterally, alongside cortical representation areas of the hands at M1 cortex. Results were compared with 23 healthy subjects. RESULTS: CRPS patients had lower RMT, higher MEP amplitudes, and lower ICF than healthy subjects. The SICI in CRPS patients showed no interhemispheric differences and did not differ from healthy subjects. MEP latency was shorter to the affected than to the unaffected hand in CRPS type II. Higher pain intensity correlated with higher degree of intracortical facilitation bilaterally, and with smaller motor representation area of the unaffected hand. CONCLUSION: Findings of this study suggest increased motor cortical excitability in CRPS patients relative to healthy subjects, with no interhemispheric asymmetry of SICI or ICF observed in chronic CRPS. SIGNIFICANCE: These results provide a comprehensive view of intracortical inhibition, facilitation and corticospinal excitability in chronic CRPS.
Clinical utility and prospective of TMS–EEG: Updated review from an international expert group Ulf Ziemann, Yang Bai, Fiona M. Baumer, Mikkel M. Beck, Paolo Belardinelli, Daniele Belvisi, Stephan Bender, Til Ole Bergmann, Marta Bortoletto, Silvia Casarotto, Elias Casula, Arthur R. Chaves, Daniel Ciampi de Andrade, Antonella Conte, Zafiris J. Daskalakis, Faranak Farzan, Fabio Ferrarelli, Paul B. Fitzgerald, Pedro C. Gordon, Christian Grefkes, Sylvain Harquel, Julio C. Hernandez-Pavon, Aron T. Hill, Kate E. Hoy, Friedhelm C. Hummel, Petro Julkunen, Elisa Kallioniemi, Corey J. Keller, Vasilios K. Kimiskidis, Melissa Kirkovski, Giacomo Koch, Giorgio Leodori, Pantelis Lioumis, Sara Määttä, Inbal Maidan, Marcello Massimini, Annerose Mengel, Johanna Metsomaa, Carlo Miniussi, Tuomas P. Mutanen, Yoshihiro Noda, Recep A. Ozdemir, Estelle Raffin, Lorenzo Rocchi, Nigel C. Rogasch, Mario Rosanova, Emiliano Santarnecchi, Simone Sarasso, Siobhan M. Schabrun, Mouhsin M. Shafi, Hartwig R. Siebner, Else A. Tolner, Leo Tomasevic, Sara Tremblay, Caroline Tscherpel, Domenica Veniero, Viviana Versace, Daphne Voineskos, Steve Vucic, Abraham Zangen, Christoph Zrenner, Risto J. Ilmoniemi Clinical Neurophysiology, 2026 Transcranial magnetic stimulation (TMS) is a non-invasive technique to stimulate the brain, while electroencephalography (EEG) is a non-invasive technique to record its electrical activity. Their combined use (TMS-EEG) has been established only relatively recently, after successful development of TMS-compatible EEG amplifiers. TMS-EEG offers the unparalleled opportunity to directly perturb the brain with TMS and simultaneously record its response with EEG. This allows inferences on causal input-output relationships, therefore going critically beyond purely observational techniques, such as resting-state EEG or functional MRI, in the study of brain dynamics. This consensus review updates the work of Tremblay and coworkers [Clin Neurophysiol 2019; 130: 802-844]. Since then, substantial advances have been made in understanding contamination of TMS-EEG signals by physiological and non-physiological artifacts, as well as in developing strategies to avoid or control them. In parallel, new insights have emerged regarding the physiological mechanisms underlying TMS-EEG responses and their diagnostic and prognostic utility in a broad range of psychiatric and neurological disorders. As such, TMS-EEG is rapidly shaping a dynamic new field in clinical neurophysiology and neuroscience. This review provides a critical and comprehensive synthesis of current knowledge, including practical guidance for implementing TMS-EEG in the clinical setting.
An open-source JavaScript clinical neurophysiology library for education and clinical research Sampsa Lohi, Petro Julkunen, Reetta Kälviäinen, Esa Mervaala Clinical Neurophysiology Practice, 2026 Objective: We present 'Epicurrents', an open-source JavaScript library for processing and displaying neurophysiological signal data in a web browser. Methods: The library follows a modular architecture to enable support for multiple clinical neurophysiology modalities. It supports open standards such as the European Data Format (EDF) and Digital Imaging and Communications in Medicine (DICOM), with optional Python and Open Neural Network Exchange (ONNX) integrations for scientific signal processing. The application presented in this article is platform agnostic, requires no installation, and is usable both online and offline as a progressive web application. Results: The library has been tested in real-world educational and research projects and is used by the European Academy of Neurology for hands-on EEG-education in their congresses. While JavaScript's memory management poses limitations for processing large recordings, architectural workarounds such as shared memory buffers and asynchronous processing have resulted in improved performance. Conclusions: The application presented here is not intended nor certified for clinical diagnostics, but its accessibility and extensibility make it a promising tool for neurophysiology education and research. Significance: Epicurrents is the first modular JavaScript library for clinical neurophysiology education and illustrates how web technologies can also enhance collaborative scientific research in the field of clinical neurophysiology.
Proteomics Analysis Reveals Serum Biomarkers Reflecting Joint Pain and Physical Limitations in Knee Osteoarthritis Before and After Joint Replacement Surgery Anne-Mari Mustonen, Janne Tampio, Kristiina M. Huttunen, Petro Julkunen, Laura Säisänen, Lauri Karttunen, Jusa Reijonen, Amir Esrafilian, Tiina Kuningas, Atul Kumar, Heikki Kröger, Petteri Nieminen Cartilage, 2026 Objective Osteoarthritis (OA) is an age-related musculoskeletal disorder lacking effective disease-modifying therapies and early diagnostic biomarkers. This study aimed to identify serum proteins that could indicate the occurrence of knee OA (KOA) and correlate with patients’ pain and functional impairment. Design/Methods Fasting serum samples were collected from controls (n = 8) and patients with end-stage KOA at baseline (n = 8) and 12 months after total knee arthroplasty (n = 8). Proteomics analysis was conducted with liquid chromatography–mass spectrometry, followed by univariate and multivariate statistics and pathway analyses by MetaboAnalyst and STRING. Partial correlations were calculated with R, adjusted for sex, age, and body mass index, using a linear regression model. Results 151 proteins were upregulated and 5 proteins downregulated in baseline KOA compared to control. These proteins were linked to the complement system, immune response, coagulation, inflammatory response, calcium homeostasis, and extracellular matrix remodeling. Of these, complement factor I showed strong biomarker potential. Several proteins emerged as statistically significant predictors of cartilage loss, pain sensitivity, physical function, and corticospinal excitability. Systemic alterations persisted 12 months after surgery. Conclusion Serum proteins may serve as biomarkers of KOA, reflecting disease-related immune, inflammatory, and tissue-remodeling processes that persist after joint replacement.
Accuracy assessment of a cochlear implant imaging tool using clinical computed tomography images Stephan Geiger, Matti Iso-Mustajärvi, Tim Nauwelaers, Petro Julkunen, Pia Linder, Aarno Dietz Scientific Reports, 2025 In today's clinical routine, imaging tools are increasingly used for cochlear implant surgical planning and assessment. However, low resolution and artifacts of computer tomography (CT) images often prevent a reliable assessment of the cochlea geometry, as well as introduced trauma from the surgery. This study evaluated the reliability of a cochlear implant imaging tool for evaluation of clinical CT scans. 20 sets of clinical pre- and postoperative CT images, implanted with Advanced Bionics SlimJ and Mid-Scala electrode arrays, were analyzed using fusion imaging, manual measurements, and the imaging tool. The compared outcomes included cochlea diameter and width, angular insertion depth, and electrode scalar location. Cochlea diameter (A) and width (B) demonstrated excellent and good inter-rater agreement between the imaging tool and manual measurements, respectively, while angular insertion depth and electrode scalar location showed excellent agreement. The imaging tool achieved an overall high accuracy of 96.9%, with a sensitivity of 83.0% and specificity of 98.3% for assessing the electrode scalar location. The imaging tool exhibited high accuracy and good to excellent agreement with other established assessment methods for clinical CTs. With its strong usability and fast evaluations, this evidence supports the tool's reliable use in clinical practice.
Hyaluronic Acid and Large Extracellular Vesicles (EVs) in Synovial Fluid and Plasma of Patients With End-Stage Arthritis: Positive Association of EVs to Joint Pain Anne-Mari Mustonen, Janne Capra, Sanna Oikari, Laura Säisänen, Lauri Karttunen, Petro Julkunen, Petri Lehenkari, Antti Joukainen, Antti Jaroma, Tommi Paakkonen, Tommi Kääriäinen, Heikki Kröger, Petteri Nieminen Cartilage, 2025 Objective Hyaluronic acid (HA) in synovial fluid (SF) contributes to boundary lubrication with altered levels in osteoarthritis (OA) and rheumatoid arthritis (RA). SF extracellular vesicles (EVs) may participate in arthritis by affecting inflammation and cartilage degradation. It remains unknown whether HA and EVs display joint-specific alterations in arthritic SFs. Design We investigated the numbers and characteristics of HA-particles and large EVs in SF from knees and shoulders of 8 OA and 8 RA patients and 8 trauma controls, and in plasma from 10 healthy controls and 11 knee OA patients. The plasma and SF HA concentrations were determined with a sandwich-type enzyme-linked sorbent assay, and EVs and HA-particles were characterized from plasma and unprocessed and centrifuged SFs with confocal microscopy. The data were compared according to diagnosis, location, and preanalytical processing. Results The main findings were: (1) OA and RA SFs can be distinguished from trauma joints based on the distinctive profiles of HA-particles and large EVs, (2) there are differences in the SF HA and EV characteristics between shoulder and knee joints that could reflect their dissimilar mobility, weight-bearing, and shock absorption properties, (3) EV counts in SF and plasma can positively associate with pain parameters independent of age and body adiposity, and (4) low-speed centrifugation causes alterations in the features of HA-particles and EVs, complicating their examination in the original state. Conclusions Arthritis and anatomical location can affect the characteristics of HA-particles and large EVs that may have potential as biomarkers and effectors in joint degradation and pain.
Pain and functional limitations in knee osteoarthritis are reflected in the fatty acid composition of plasma extracellular vesicles Anne-Mari Mustonen, Petro Julkunen, Laura Säisänen, Lauri Karttunen, Amir Esrafilian, Jusa Reijonen, Sylvain Tollis, Reijo Käkelä, Sanna P. Sihvo, Nina Höglund, Tytti Niemelä, Anna Mykkänen, Jussi Mäki, Heikki Kröger, Jari Arokoski, Petteri Nieminen Biochimica Et Biophysica Acta Molecular and Cell Biology of Lipids, 2025 This study investigated relationships between fatty acid (FA) profiles of extracellular vesicles (EVs) and cartilage degradation, functional limitations, pain, and psychological well-being in knee osteoarthritis (KOA). Fasting plasma was collected from controls (n = 10), end-stage KOA patients at baseline (n = 12) and at 3 and 12 months (n = 11 and 9) after joint replacement surgery, and from KOA synovial fluid (SF) at baseline (n = 10). EVs were isolated with the exoEasy Maxi Kit or size-exclusion chromatography, and EV FAs were analyzed with gas chromatography-mass spectrometry. Articular cartilage loss was determined by magnetic resonance imaging, and knee pain and function were assessed through questionnaires and physiatric and neuromuscular examinations. The associations of these data with EV FA proportions were tested with the univariate analysis of variance adjusted for age and body adiposity. Higher proportions of 16:1n-7, 18:1n-7, and total monounsaturated FAs in plasma EVs were associated with less severe KOA symptoms, while higher 24:1n-9, total saturated FAs, and ratios of arachidonic acid to long-chain n-3 polyunsaturated FAs (PUFAs) were linked to KOA pain, independent of age and body adiposity. In SF EVs, higher product/precursor ratios of n-6 PUFAs were associated with increased joint stiffness, and higher total dimethyl acetals were linked to physical disability. EV FAs emerged as significant indicators of knee pain and function. The results can be utilized to discover novel biomarkers for KOA and may have implications for targeted prevention and treatment of KOA symptoms by using EVs with a specific FA cargo.
Bridging the gap to clinical use: A systematic review on TMS–EEG test-retest reliability Giacomo Bertazzoli, Elisa Dognini, Peter J. Fried, Carlo Miniussi, Petro Julkunen, Marta Bortoletto Clinical Neurophysiology, 2025 BACKGROUND: Transcranial magnetic stimulation (TMS) combined with electroencephalography (EEG) can provide insight on cortical excitability and brain circuits. TMS-evoked potentials (TEPs) are phase-locked waveforms reflecting neural activity, with potential applications in psychiatry and neurology. However, the reliability of TEPs remains underexplored, hindering clinical standardization. This systematic review evaluates TEP reliability, focusing on commonly used measures and assessments. METHODS: A systematic review was conducted on PubMed for studies from 2002 to October 10, 2024, using keywords combining TMS, EEG, and reliability terms. Systematic reviews and non-English articles were excluded. RESULTS: Eighteen studies met inclusion criteria, mostly assessing young, healthy populations. Late TEP components demonstrated high relative reliability, while early components exhibited lower reliability and variability across sessions. Analytical methods like the intraclass and concordance correlation coefficients, and Pearson's correlations consistently favored late TEPs. DISCUSSION: Late TEPs exhibit higher reliability, while early components require further research. TMS artifacts complicate interpretation, in both late and early responses. Formal reliability assessments, standardized protocols, and diverse populations are essential for advancing TEP reliability for clinical application. CONCLUSIONS: A more comprehensive reliability assessments is needed before the implementation of clinical applications.
X-ray scatter in projection radiography Satu Ylimaula, Lasse Räsänen, Miia Hurskainen, Arttu Peuna, Petro Julkunen, Miika Tapio Nieminen, Matti Hanni Radiation Protection Dosimetry, 2024
TMS combined with EEG: Recommendations and open issues for data collection and analysis Julio C. Hernandez-Pavon, Domenica Veniero, Til Ole Bergmann, Paolo Belardinelli, Marta Bortoletto, Silvia Casarotto, Elias P. Casula, Faranak Farzan, Matteo Fecchio, Petro Julkunen, Elisa Kallioniemi, Pantelis Lioumis, Johanna Metsomaa, Carlo Miniussi, Tuomas P. Mutanen, Lorenzo Rocchi, Nigel C. Rogasch, Mouhsin M. Shafi, Hartwig R. Siebner, Gregor Thut, Christoph Zrenner, Ulf Ziemann, Risto J. Ilmoniemi Brain Stimulation, 2023
Short- and long-interval intracortical inhibition in EPM1 is related to genotype Katri Silvennoinen, Laura Säisänen, Jelena Hyppönen, Saara M. Rissanen, Pasi A. Karjalainen, Sasha D'Ambrosio, Diego Jimenez‐Jimenez, Sara Zagaglia, John C. Rothwell, Simona Balestrini, Sanjay M. Sisodiya, Petro Julkunen, Esa Mervaala, Reetta Kälviäinen Epilepsia, 2023
Reproducibility in TMS–EEG studies: A call for data sharing, standard procedures and effective experimental control Paolo Belardinelli, Mana Biabani, Daniel M. Blumberger, Marta Bortoletto, Silvia Casarotto, Olivier David, Debora Desideri, Amit Etkin, Fabio Ferrarelli, Paul B. Fitzgerald, Alex Fornito, Pedro C. Gordon, Olivia Gosseries, Sylvain Harquel, Petro Julkunen, Corey J. Keller, Vasilios K. Kimiskidis, Pantelis Lioumis, Carlo Miniussi, Mario Rosanova, Simone Rossi, Simone Sarasso, Wei Wu, Christoph Zrenner, Zafiris J. Daskalakis, Nigel C. Rogasch, Marcello Massimini, Ulf Ziemann, Risto J. Ilmoniemi Brain Stimulation, 2019
Parallel input makes the brain run faster Tommi Raij, Jari Karhu, Dubravko Kičić, Pantelis Lioumis, Petro Julkunen, Fa-Hsuan Lin, Jyrki Ahveninen, Risto J. Ilmoniemi, Jyrki P. Mäkelä, Matti Hämäläinen, Bruce R. Rosen, John W. Belliveau Neuroimage, 2008
