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1. Use of quantitative tremor evaluation to enhance target selection during deep brain stimulation surgery for essential tremor

Author

Simone Hemm-Ode, Jean-Jacques Lemaire, Erik Schkommodau, Ashesh Shah, Jerome Coste, Institute for Medical and Analytical Technologies, School of Life Sciences (IMA), University of Applied Sciences and Arts Northwestern Switzerland (HES-SO), Service de Neurochirurgie [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), University of Applied Sciences and Arts Northwestern Switzerland (FHNW), German Society for Biomedical Engineering, Apport de l'accélérométrie à la stimulation cérébrale - 2011-A00774-37 - CHU de Clermont-Ferrand, Service de Neurochirurgie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, and SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)

Subjects
medicine.medical_specialty, Deep brain stimulation, Essential tremor, business.industry, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, medicine.medical_treatment, Thalamus, Biomedical Engineering, Stimulation, medicine.disease, nervous system diseases, deep brain stimulation, Physical medicine and rehabilitation, thalamus, Evaluation methods, medicine, accelerometry, Medicine, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business, Surgical treatment, essential tremor, Deep brain stimulation surgery
Abstract

Deep brain stimulation (DBS), an effective surgical treatment for Essential Tremor (ET), requires test stimulations in the thalamus to find the optimum site for permanent electrode implantation. During these test stimulations, the changes in tremor are only visually evaluated. This, along with other parameters, increases the subjectivity when comparing the efficacy of different thalamic nuclei. We developed a method to quantitatively evaluate tremor during the test stimulations of DBS surgery and applied to 6 ET patients undergoing this treatment. From the quantitative data collected, we identified effective stimulation amplitudes for every test stimulation position and compared it with the ones identified visually during the surgery. We also classified the data based on the thalamic nuclei in which the center of the stimulating contact was present during test stimulations. Results indicate that, to achieve the same reduction in tremor, on average, the stimulation amplitude identified by our method was 0.6 mA lower than those identified by visual evaluation. The comparison of the different thalamic nuclei showed that stimulations in the Ventro-oral and the Intermediolateral nuclei of the thalamus result in higher reduction in tremor for similar stimulation amplitudes as the frequently targeted Ventrointermediate nucleus. We conclude that our quantitative tremor evaluation method is more sensitive than the widely used visual evaluation. Using such quantitative methods will aid in identifying the optimum target structure for patients undergoing DBS.

Published
2015
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2. Intraoperative acceleration measurements to quantify improvement in tremor during deep brain stimulation surgery

Author

Jean-Jacques Lemaire, W. M. Michael Schüpbach, Claudio Pollo, Ethan Taub, Simone Hemm-Ode, Jerome Coste, Erik Schkommodau, Raphael Guzman, Ashesh Shah, Institute for Medical and Analytical Technologies, School of Life Sciences (IMA), University of Applied Sciences and Arts Northwestern Switzerland (FHNW), Thérapie guidée par l'image (TGI), Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Service de Neurochirurgie [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Departments of Neurosurgery and Biomedicine, University Hospital Basel [Basel], Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Department of Neurology, University Hospital, Bern-University of Bern, Department of Neurosurgery, University Hospital, Bern, This research was funded by the Swiss National Science Foundation and partly by the Germainede Staël program of the Swiss Academy of Engineering Sciences. The experimental procedures were approved by the respective Institutional Ethics Committee (Center1: 2011-A00774-37/AU905, Center 2: 2365—multicenter study together with the UniversityHospital in Basel), Apport de l'accélérométrie à la stimulation cérébrale - 2011-A00774-37 - CHU de Clermont-Ferrand, SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)-SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Service de Neurochirurgie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Coste, Jérôme

Subjects
medicine.medical_specialty, Movement disorders, Deep brain stimulation, Parkinson's disease, medicine.medical_treatment, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, 0206 medical engineering, Acceleration, Biomedical Engineering, 610 Medicine & health, 02 engineering and technology, Wrist, Neurosurgical Procedures, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Tremor, Medicine, Humans, Lead (electronics), Intraoperative monitoring, [SDV.IB] Life Sciences [q-bio]/Bioengineering, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Movement Disorders, Essential tremor, business.industry, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Brain, medicine.disease, 020601 biomedical engineering, Computer Science Applications, Electrodes, Implanted, nervous system diseases, medicine.anatomical_structure, Physical therapy, Parkinson’s disease, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Implant, medicine.symptom, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Deep brain stimulation (DBS) surgery is extensively used in the treatment of movement disorders. Nevertheless, methods to evaluate the clinical response during intraoperative stimulation tests to identify the optimal position for the implantation of the chronic DBS lead remain subjective. In this paper, we describe a new, versatile method for quantitative intraoperative evaluation of improvement in tremor with an acceleration sensor that is mounted on the patient's wrist during surgery. At each anatomical test position, the improvement in tremor compared to the initial tremor is estimated on the basis of extracted outcome measures. This method was tested on 15 tremor patients undergoing DBS surgery in two centers. Data from 359 stimulation tests were acquired. Our results suggest that accelerometric evaluation detects tremor changes more sensitively than subjective visual ratings. The effective stimulation current amplitudes identified from the quantitative data (1.1 ± 0.8 mA) are lower than those identified by visual evaluation (1.7 ± 0.8 mA) for similar improvement in tremor. Additionally, if these data had been used to choose the chronic implant position of the DBS lead, 15 of the 26 choices would have been different. These results show that our method of accelerometric evaluation can potentially improve DBS targeting.

Published
2017
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3. A novel assistive method for rigidity evaluation during deep brain stimulation surgery using acceleration sensors

Author

Erik Schkommodau, Jean-Jacques Lemaire, Philippe Derost, Ashesh Shah, Jerome Coste, Raphael Guzman, Ethan Taub, Simone Hemm, Institute for Medical and Analytical Technologies, School of Life Sciences (IMA), University of Applied Sciences and Arts Northwestern Switzerland (FHNW), Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Service de Neurochirurgie [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Departments of Neurosurgery and Biomedicine, University Hospital Basel [Basel], Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Service de Neurologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU de Clermont-Ferrand, Université Clermont Auvergne, Institut Pascal, Apport de l'accélérométrie à la stimulation cérébrale - 2011-A00774-37 - CHU de Clermont-Ferrand, Thérapie guidée par l'image (TGI), SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), This research was funded by the Swiss National Science Foundation as a part of the project205321_135285 and partly by the Germaine de Stael program of the Swiss Academy ofEngineering Sciences. We acknowledge and thank Prof. F. Durif, Dr. M. Ulla, and Dr. A.Marques of the Department of Neurology at the CHU Clermont-Ferrand, France, and Ms. BiancaRaffaelli and Prof. Dr. Peter Fuhr of the Department of Neurology at the University Hospital ofBasel, Switzerland, for performing the routine passive movements for rigidity evaluations.The clinical use of the afore-described data-recording system for the purpose of intraoperativeand postoperative symptom evaluation in the framework of this study was approved by theinstitutional review boards of the University Hospital in Clermont-Ferrand (France) and theUniversity Hospital of Basel (Switzerland)., CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)-SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Service de Neurochirurgie [CHU Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, and SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)

Subjects
medicine.medical_specialty, Deep brain stimulation, Movement disorders, Parkinson's disease, medicine.medical_treatment, fields of Forel, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Deep Brain Stimulation, Movement, 0206 medical engineering, Stimulation, Rigidity (psychology), 02 engineering and technology, Wrist, Accelerometer, Neurosurgical Procedures, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, medicine, Humans, Electrodes, functional neurosurgery, Aged, subthalamic nucleus, business.industry, Parkinson Disease, General Medicine, Middle Aged, medicine.disease, 020601 biomedical engineering, quantification, Muscle Rigidity, Subthalamic nucleus, medicine.anatomical_structure, rigidity, Physical therapy, acceleration sensor, intraoperative, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.IB]Life Sciences [q-bio]/Bioengineering, medicine.symptom, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

OBJECTIVEDespite the widespread use of deep brain stimulation (DBS) for movement disorders such as Parkinson's disease (PD), the exact anatomical target responsible for the therapeutic effect is still a subject of research. Intraoperative stimulation tests by experts consist of performing passive movements of the patient's arm or wrist while the amplitude of the stimulation current is increased. At each position, the amplitude that best alleviates rigidity is identified. Intrarater and interrater variations due to the subjective and semiquantitative nature of such evaluations have been reported. The aim of the present study was to evaluate the use of an acceleration sensor attached to the evaluator's wrist to assess the change in rigidity, hypothesizing that such a change will alter the speed of the passive movements. Furthermore, the combined analysis of such quantitative results with anatomy would generate a more reproducible description of the most effective stimulation sites.METHODSTo test the reliability of the method, it was applied during postoperative follow-up examinations of 3 patients. To study the feasibility of intraoperative use, it was used during 9 bilateral DBS operations in patients suffering from PD. Changes in rigidity were calculated by extracting relevant outcome measures from the accelerometer data. These values were used to identify rigidity-suppressing stimulation current amplitudes, which were statistically compared with the amplitudes identified by the neurologist. Positions for the chronic DBS lead implantation that would have been chosen based on the acceleration data were compared with clinical choices. The data were also analyzed with respect to the anatomical location of the stimulating electrode.RESULTSOutcome measures extracted from the accelerometer data were reproducible for the same evaluator, thus providing a reliable assessment of rigidity changes during intraoperative stimulation tests. Of the 188 stimulation sites analyzed, the number of sites where rigidity-suppressing amplitudes were found increased from 144 to 170 when the accelerometer evaluations were considered. In general, rigidity release could be observed at significantly lower amplitudes with accelerometer evaluation (mean 0.9 ± 0.6 mA) than with subjective evaluation (mean 1.4 ± 0.6 mA) (p < 0.001). Of 14 choices for the implant location of the DBS lead, only 2 were the same for acceleration-based and subjective evaluations. The comparison across anatomical locations showed that stimulation in the fields of Forel ameliorates rigidity at similar amplitudes as stimulation in the subthalamic nucleus, but with fewer side effects.CONCLUSIONSThis article describes and validates a new assistive method for assessing rigidity with acceleration sensors during intraoperative stimulation tests in DBS procedures. The initial results indicate that the proposed method may be a clinically useful aid for optimal DBS lead placement as well as a new tool in the ongoing scientific search for the optimal DBS target for PD.

Published
2016
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4. A method to quantitatively evaluate changes in tremor during deep brain stimulation surgery

Author

Jerome Coste, Simone Hemm-Ode, Jean-Jacques Lemaire, Erik Schkommodau, Ashesh Shah, Institute for Medical and Analytical Technologies, School of Life Sciences (IMA), University of Applied Sciences and Arts Northwestern Switzerland (FHNW), Service de Neurochirurgie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Image Guided Clinical Neurosciences and Connectomics (IGCNC), Université d'Auvergne - Clermont-Ferrand I (UdA), Apport de l'accélérométrie à la stimulation cérébrale - 2011-A00774-37 - CHU de Clermont-Ferrand, Service de Neurochirurgie [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], and CHU Clermont-Ferrand

Subjects
medicine.medical_specialty, Deep brain stimulation, medicine.medical_treatment, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, 0206 medical engineering, Symptomatic treatment, Acceleration, Trajectory, Stimulation, 02 engineering and technology, Electromyography, Wrist, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Satellite broadcasting, Medicine, medicine.diagnostic_test, business.industry, Neurophysiology, 020601 biomedical engineering, medicine.anatomical_structure, Brain stimulation, Feature extraction, Surgery, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Accelerometers, business, 030217 neurology & neurosurgery, Deep brain stimulation surgery
Abstract

International audience; Deep Brain Stimulation (DBS) surgery is used increasingly as a symptomatic treatment for patients with movement related neuro-degenerative disorders. However, the method of intraoperative symptom evaluation is subjective. This paper proposes a method to quantitatively evaluate tremor by measuring the acceleration of the patient's wrist during the surgery. The results of applying the method to 2 patients suggest that the acceleration measurements are very sensitive to the change in the tremor and that they can be used to identify clinically effective stimulation amplitudes. By collecting acceleration data from DBS surgeries for many patients, we hope to add more knowledge to the mechanisms of deep brain stimulation.

Published
2013
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5. Using acceleration to quantify symptoms during deep brain stimulation surgery

Author

Jerome Coste, Erik Schkommodau, Jean-Jacques Lemaire, Simone Hemm-Ode, Ashesh Shah, Institute for Medical and Analytical Technologies, School of Life Sciences (IMA), University of Applied Sciences and Arts Northwestern Switzerland (FHNW), Service de Neurochirurgie [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Image Guided Clinical Neurosciences and Connectomics (IGCNC), Université d'Auvergne - Clermont-Ferrand I (UdA), This research has been supported by the Swiss National Science Foundation (SNSF), Clermont-Ferrand University Hospital and the School of Life Sciences., German Society for Biomedical Engineering, Apport de l'accélérométrie à la stimulation cérébrale - 2011-A00774-37 - CHU de Clermont-Ferrand, Service de Neurochirurgie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], and CHU Clermont-Ferrand-CHU Clermont-Ferrand

Subjects
medicine.medical_specialty, Deep brain stimulation, General interest, medicine.medical_treatment, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, 0206 medical engineering, Biomedical Engineering, Stimulation, acceleration measurements, 02 engineering and technology, 03 medical and health sciences, [SPI]Engineering Sciences [physics], 0302 clinical medicine, Physical medicine and rehabilitation, Medicine, business.industry, movement related disorders, 020601 biomedical engineering, deep brain stimulation, Physical therapy, tremor quantification, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Neurosurgery, business, 030217 neurology & neurosurgery, Deep brain stimulation surgery
Abstract

The use of Deep Brain Stimulation (DBS) surgery is increasing as a treatment for movement related disorders. One of the important areas of improvement is the target selection procedure. To do so we measured the acceleration of tremor by sensors in 6 patients during their DBS surgeries to evaluate the changes quantitatively. The post operative data analysis revealed that acceleration measurements are very sensitive to the changes in tremor and that they can be used to identify clinically effective stimulation amplitudes. With the aim to increase objectivity in symptom evaluation we intend to introduce real time analysis so as to provide more information to the neurosurgeon to aid him in his target selection during the surgery. © 2013 by Walter de Gruyter.

Published
2013
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6. Quantitative rigidity evaluation during deep brain stimulation surgery - a preliminary study

Author

Jerome Coste, Dagmar Gmünder, Simone Hemm-Ode, Jean-Jacques Lemaire, Ashesh Shah, Ulla Miguel, Institute for Medical and Analytical Technologies, School of Life Sciences (IMA), University of Applied Sciences and Arts Northwestern Switzerland (FHNW), Service de Neurologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Service de Neurochirurgie [CHU Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Image Guided Clinical Neurosciences and Connectomics (IGCNC), Université d'Auvergne - Clermont-Ferrand I (UdA), Fond National Suisse de la recherche scientifique, programme franco-suisse «Germaine de Staël», University of Applied Sciences and Arts Northwestern Switzerland, CHU de Clermont-Ferrand., German Society for Biomedical Engineering, Apport de l'accélérométrie à la stimulation cérébrale - 2011-A00774-37 - CHU de Clermont-Ferrand, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], Service de Neurochirurgie [Clermont-Ferrand], and CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand]

Subjects
medicine.medical_specialty, Deep brain stimulation, medicine.medical_treatment, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, 0206 medical engineering, Biomedical Engineering, Clinical state, Stimulation, 02 engineering and technology, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Wrist, Accelerometer, Clinical study, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Medicine, business.industry, 020601 biomedical engineering, Surgery, nervous system diseases, medicine.anatomical_structure, [SDV.IB]Life Sciences [q-bio]/Bioengineering, business, 030217 neurology & neurosurgery, Deep brain stimulation surgery
Abstract

Introduction Deep brain stimulation (DBS) is a common neurosurgical procedure for relieving movement related disorders such as Parkinson’s disease. DBS extends uncertainties associated with suboptimal target selection. Our aim was to evaluate the feasibility to objectively assess clinical effects obtained during intraoperative test stimulation based on acceleration measurements of the neurologist’s wrist. Methods One patient referred for bilateral DBS-implantation for the treatment of Parkinson’s disease was included in the study. A 3-axis accelerometer was fixed on the neurologist's wrist during intraoperative test stimulation. While the intensity of electric current used for stimulation was increased , the neurologist continuously moved the patient's wrist to determine the moment of and the amplitude at rigidity release ("stimulation threshold"). For each test stimulation position, differrent mathematical features were determined and statistically compared a) for the time period before re aching the stimulation threshold that had been identified by the neurologist and b) after reaching the threshold. We then visually identified the stimulation thresholds that would have been chosen based on the acceleration signal alone and compared them to the ones subjectively identified by the neurologist. Results A statistical significant change in rigidity (p

Published
2012
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