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1. Results of a Randomized Clinical Trial of Speech after Early Neurostimulation in Parkinson's Disease

Author

Serge, Pinto, Adelheid, Nebel, Jörn, Rau, Robert, Espesser, Pauline, Maillochon, Oliver, Niebuhr, Paul, Krack, Tatiana, Witjas, Alain, Ghio, Marie-Charlotte, Cuartero, Lars, Timmermann, Alfons, Schnitzler, Helke, Hesekamp, Niklaus, Meier, Julia, Müllner, Thomas D, Hälbig, Bettina, Möller, Steffen, Paschen, Laura, Paschen, Jens, Volkmann, Michael T, Barbe, Gereon R, Fink, Johannes, Becker, Paul, Reker, Andrea A, Kühn, Gerd-Helge, Schneider, Valérie, Fraix, Eric, Seigneuret, Andrea, Kistner, Olivier, Rascol, Christine, Brefel-Courbon, Fabienne, Ory-Magne, Christian J, Hartmann, Lars, Wojtecki, Anne, Fradet, David, Maltête, Philippe, Damier, Séverine, Le Dily, Friederike, Sixel-Döring, Petra, Benecke, Daniel, Weiss, Tobias, Wächter, Marcus O, Pinsker, Jean, Régis, Stéphane, Thobois, Gustavo, Polo, Jean-Luc, Houeto, Andreas, Hartmann, Karina, Knudsen, Marie, Vidailhet, Michael, Schüpbach, Günther, Deuschl, Laboratoire Parole et Langage (LPL), and Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Neurology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), [SHS.LANGUE]Humanities and Social Sciences/Linguistics
Abstract

The EARLYSTIM trial demonstrated for Parkinson's disease patients with early motor complications that deep brain stimulation of the subthalamic nucleus (STN-DBS) and best medical treatment (BMT) was superior to BMT alone.This prospective, ancillary study on EARLYSTIM compared changes in blinded speech intelligibility assessment between STN-DBS and BMT over 2 years, and secondary outcomes included non-speech oral movements (maximum phonation time [MPT], oral diadochokinesis), physician- and patient-reported assessments.STN-DBS (n = 102) and BMT (n = 99) groups underwent assessments on/off medication at baseline and 24 months (in four conditions: on/off medication, ON/OFF stimulation-for STN-DBS). Words and sentences were randomly presented to blinded listeners, and speech intelligibility rate was measured. Statistical analyses compared changes between the STN-DBS and BMT groups from baseline to 24 months.Over the 2-year period, changes in speech intelligibility and MPT, as well as patient-reported outcomes, were not different between groups, either off or on medication or OFF or ON stimulation, but most outcomes showed a nonsignificant trend toward worsening in both groups. Change in oral diadochokinesis was significantly different between STN-DBS and BMT groups, on medication and OFF STN-DBS, with patients in the STN-DBS group performing slightly worse than patients under BMT only. A signal for clinical worsening with STN-DBS was found for the individual speech item of the Unified Parkinson's Disease Rating Scale, Part III.At this early stage of the patients' disease, STN-DBS did not result in a consistent deterioration in blinded speech intelligibility assessment and patient-reported communication, as observed in studies of advanced Parkinson's Disease. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Published
2022
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2. Emotional experience in patients with clinically isolated syndrome and early multiple sclerosis

Author

René M. Giess, Thomas D. Hälbig, Judith Bellmann-Strobl, Klemens Ruprecht, Friedemann Paul, Torsten Wüstenberg, and Hagen Kunte

Subjects
medicine.medical_specialty, Multiple Sclerosis, Emotions, emotion, MRI-Setting, emotional, Audiology, Neuropsychological Tests, Arousal, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, In patient, 030212 general & internal medicine, Valence (psychology), International Affective Picture System, emotional experience, Clinically isolated syndrome, medicine.diagnostic_test, business.industry, Multiple sclerosis, Neuropsychology, Magnetic resonance imaging, Recognition, Psychology, neuropsychological, medicine.disease, Magnetic Resonance Imaging, Neurology, sense organs, Neurology (clinical), Function and Dysfunction of the Nervous System, early Multiple sclerosis, business, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit, 030217 neurology & neurosurgery, MRI
Abstract

Background and purpose Evidence suggests that there are changes in the processing of emotional information (EP) in people with multiple sclerosis (MS). It is unclear which functional domains of EP are affected, whether these changes are secondary to other MS-related neuropsychological or psychiatric symptoms and if EP changes are present in early MS. The aim of the study was to investigate EP in patients with early MS (clinically isolated syndrome and early relapsing/remitting MS) and healthy controls (HCs). Methods A total of 29 patients without neuropsychological or psychiatric deficits and 29 matched HCs were presented with pictures from the International Affective Picture System with negative, positive or neutral content. Participants rated the induced emotion regarding valence and arousal using nine-level Likert scales. A speeded recognition test assessed memory for the emotional stimuli and for the emotional modulation of response time. A subgroup of participants was tested during a magnetic resonance imaging (MRI) session. Results Patients in the MRI subgroup rated the experience induced by pictures with positive or negative emotional content significantly more weakly than HCs. Further, these patients were significantly less aroused when watching the pictures from the International Affective Picture System. There were no effects in the non-MRI subgroup or effects on emotional memory or response times. Conclusions Emotional processing changes may be present in early MS in the form of flattened emotional experience on both the valence and arousal dimensions. These changes do not appear to be secondary to neuropsychological or psychiatric deficits. The fact that emotional flattening was only found in the MRI setting suggests that EP changes may be unmasked within stressful environments and points to the potential yet underestimated impact of the MRI setting on behavioral outcomes.

Published
2019

3. Quality of life predicts outcome of deep brain stimulation in early Parkinson disease

Author

Stéphane Thobois, Marie Vidailhet, Stéphane Derrey, Andrea Kistner, Philippe Damier, Daniel Weiss, W.M. Michael Schuepbach, Günther Deuschl, Thomas D. Hälbig, Tobias Wächter, Andreas Kupsch, Michael T. Barbe, Jan Vesper, Carmen Schade-Brittinger, Christine Brefel-Courbon, G.R. Fink, Jean-Luc Houeto, Friederike Sixel-Döring, Alireza Gharabaghi, Jens Volkmann, Karina Knudsen, David Maltête, Andrea A. Kühn, Andrea Falk, Patrick Mertens, Gerd-H. Schneider, Lars Timmermann, Alfons Schnitzler, Eric Seigneuret, Fabienne Ory-Magne, Pascal Derkinderen, Patrick Chaynes, Tatiana Witjas, Joern Rau, Valérie Fraix, S. Paschen, J. Regis, Lisa Tonder, Lars Wojtecki, Marcus O. Pinsker, Paul Krack, Haidar S. Dafsari, Andreas Hartmann, Fanny Pineau, Laura Paschen, Claudia Trenkwalder, Yves Agid, Universität Bern [Bern] (UNIBE), 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)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), CIC AP-HP (pitie-Salpetriere)/inserm, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Medtronic [Minneapolis, MI, USA], Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], University of Geneva [Switzerland], Centre de coordination des essais cliniques, Philipps-University, Marburg, Allemagne., Centre d'investigation clinique Neurosciences [CHU Pitié Salpêtrière] (CIC Neurosciences), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), NeuroCure Clinical Research Center (NCRC), Charité University Medical Center, Charité (Campus Mitte), Berlin, Germany., Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Department of Neuroscience, Karolinska institutet, Stockholm, Sweden, Department of Neuroscience, Karolinska institutet, Department of Neurology, University Medical Center Schleswig-Holstein, Arnold-Heller-Street 3, Kiel 24105, Germany., Department of Neurology, Christian-Albrechts-University, Kiel, Germany., Christian-Albrechts-Universität zu Kiel (CAU), University of Cologne, Faculty of Medicine and University Hospital Cologne, Department of Neurology, Cologne, Germany., National Parkinson Foundation Centre of Excellence, King's College Hospital, London, UK., Department of Neurology, University of Cologne, Cologne, Germany., Department of Neurology, Movement Disorder and Neuromodulation Unit, Charité-Universitätsmedizin, Berlin, Germany., NeuroCure Clinical Research Center, Charité-Universitätsmedizin, Berlin, Germany., Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Neurology & Neurosurgery, Charite University Medicine Berlin, Campus Virchow Klinikum & Benjamin Franklin, Berlin, Germany., Centre Hospitalier Universitaire [Grenoble] (CHU), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), UM des troubles du mouvement, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Service d'Anatomie et Cytopathologie [Toulouse], Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'investigation clinique de Toulouse (CIC 1436), Department of Functional Neurosurgery and Stereotaxy, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany., Service de neurochirurgie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie [Rouen], Normandie Université (NU)-Normandie Université (NU), Clinique neurologique, Hôpital Laennec, Neuropathies du système nerveux entérique et pathologies digestives, implication des cellules gliales entériques, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Paracelsus-Elena-Klinik, Kassel, Germany., Department of Neurology, Philipps University Marburg, Germany., Paracelsus Elena Klinik, Centre for Parkinson's Disease & Movement Disorders, Department of Neurosurgery, University of Tuebingen, Center of Neurology, Hertie Institute for Clinical Brain Research, University of Tuebingen, University of Vermont [Burlington], Stereotactic and Functional Neurosurgery Service and Gamma Knife Unit CHU Timone Marseille, France., AP-HM, CHU Timone, Pole de Neurosciences Cliniques, Department of Neurology, Marseille, France., Service de Neurologie, Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service Public de Wallonie, Department of Nuclear Medicine and PET Centre Aarhus University Hospital, Institute of Clinical Medicine Aarhus University, Norrebrogade 44, Building 10, 8000, Aarhus C, Denmark., Somnomar, Sleep Research Institute, Service de neurologie [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neurologie et thérapeutique expérimentale, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR70-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), 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), Heinrich-Heine-Universität Düsseldorf [Düsseldorf], Département de Neurologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-IFR70-CHU Pitié-Salpêtrière [APHP], Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Toulouse, Service de Pharmacologie Médicale et Clinique, CHU Toulouse [Toulouse], University of Vermont College of Medicine [Burlington, VT, USA], Laboratoire de Neurosciences Cognitives [Marseille] (LNC), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR70-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Universität Bern [Bern], 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), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Charité Hospital, Humboldt Universität zu Berlin, and Service de neurochirurgie [Rouen]

Subjects
0301 basic medicine, medicine.medical_specialty, Parkinson's disease, Deep brain stimulation, medicine.medical_treatment, 610 Medicine & health, Disease, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Quality of life, Rating scale, law, Internal medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Clinical endpoint, Medicine, ddc:610, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], 10. No inequality, ComputingMilieux_MISCELLANEOUS, business.industry, medicine.disease, humanities, 3. Good health, nervous system diseases, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Subthalamic nucleus, 030104 developmental biology, Neurology (clinical), business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 030217 neurology & neurosurgery
Abstract

ObjectiveTo investigate predictors for improvement of disease-specific quality of life (QOL) after deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson disease (PD) with early motor complications.MethodsWe performed a secondary analysis of data from the previously published EARLYSTIM study, a prospective randomized trial comparing STN-DBS (n = 124) to best medical treatment (n = 127) after 2 years follow-up with disease-specific QOL (39-item Parkinson's Disease Questionnaire summary index [PDQ-39-SI]) as the primary endpoint. Linear regression analyses of the baseline characteristics age, disease duration, duration of motor complications, and disease severity measured at baseline with the Unified Parkinson’s Disease Rating Scale (UPDRS) (UPDRS-III “off” and “on” medications, UPDRS-IV) were conducted to determine predictors of change in PDQ-39-SI.ResultsPDQ-39-SI at baseline was correlated to the change in PDQ-39-SI after 24 months in both treatment groups (p < 0.05). The higher the baseline score (worse QOL) the larger the improvement in QOL after 24 months. No correlation was found for any of the other baseline characteristics analyzed in either treatment group.ConclusionImpaired QOL as subjectively evaluated by the patient is the most important predictor of benefit in patients with PD and early motor complications, fulfilling objective gold standard inclusion criteria for STN-DBS. Our results prompt systematically including evaluation of disease-specific QOL when selecting patients with PD for STN-DBS.Clinicaltrials.gov identifierNCT00354133.

Published
2019
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4. Behavioural outcomes of subthalamic stimulation and medical therapy versus medical therapy alone for Parkinson's disease with early motor complications (EARLYSTIM trial): secondary analysis of an open-label randomised trial

Author

Eugénie Lhommée, Lars Wojtecki, Virginie Czernecki, Karsten Witt, Franziska Maier, Lisa Tonder, Lars Timmermann, Thomas D Hälbig, Fanny Pineau, Franck Durif, Tatiana Witjas, Marcus Pinsker, Maximilian Mehdorn, Friederike Sixel-Döring, Andreas Kupsch, Rejko Krüger, Saskia Elben, Stephan Chabardès, Stéphane Thobois, Christine Brefel-Courbon, Fabienne Ory-Magne, Jean-Marie Regis, David Maltête, Anne Sauvaget, Jörn Rau, Alfons Schnitzler, Michael Schüpbach, Carmen Schade-Brittinger, Gunther Deuschl, Jean-Luc Houeto, Paul Krack, Velina Negovanska, Marie-Laure Welter, Jean-Christophe Corvol, Yves Agid, Soledad Navarro, Niklaus Meier, Andreas Hartmann, Helke Hesekamp, Philippe Cornu, Bettina Möller, Adelheid Nebel, Jan Raethjen, Karina Knudsen, Jens Volkmann, Daniela Falk, Steffen Paschen, Ingo Meister, Jens Kuhn, Kerstin Donner, Josef Kessler, Michael Barbe, Gereon Fink, Mohammad Maarouf, Andrea Kühn, Bianca Müller, Katharina Faust, Doreen Gruber, Gerd-H. Schneider, Eric Seigneuret, Pierre Pollak, Valerie Fraix, Andrea Kistner, Olivier Rascol, Christophe Arbus, Lola Danet, Patrick Chaynes, Stefan J. Groiss, Christian Hartmann, Martin Südmeyer, Mahnaz Partowinia-Peters, Jan Vesper, Severine Ledily, Philippe Damier, Sylvie Raoul, Claudia Trenkwalder, Wenke Richter-Dreske, Tobias Wächter, Daniel Weiss, Alexandro Eusebio, Jean Philippe Azulay, Gustavo Polo, Serge Pinto, Johannes Levin, Stephanie Dornier, Fredy Pene, Delphine Hourton, Mathieu Quintin, Cecile Hoffart-Jourdain, Helene Brocvielle, Kerstin Balthasar, Meryem Stein, Susanne Harnisch, Alexander Reuss, Behnaz Aminossadati, Christian Nasemann, Wolfgang Oertel, Benoit Bataille, Dieter Hellwig, Alireza Gharabaghi, Florian Amtage, Patrick Mertens, Manja Kloss, Bart Post, Hans Speelman, UM des troubles du mouvement, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Department of Neurology, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University Schleswig-Holstein, Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Laboratoire de Neurosciences Cognitives [Marseille] (LNC), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Christian-Albrechts-Universität zu Kiel (CAU), Department of Neurosurgery, Center of Neurology and Hertie-Institute for Clinical Brain Research, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, CHU Grenoble, Service de neurologie C [Hôpital Pierre Wertheimer - HCL], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (ISC-MJ), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre d'investigation clinique de Toulouse (CIC 1436), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Centre hospitalier universitaire de Nantes (CHU Nantes), Neurologie et thérapeutique expérimentale, IFR70-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Somnomar, Sleep Research Institute, Service de neurologie [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de neurologie, Centre de Traitement de la Peur de l'Avion, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), 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), Department of neurology, Inselspital Bern, 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)-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), Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Charité Hospital, Humboldt University Of Berlin, Centre Hospitalier Universitaire [Grenoble] (CHU), Neurosciences précliniques, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Pharmacologie Clinique [CHU Toulouse], Pôle Santé publique et médecine publique [CHU Toulouse], Service Anatomie et cytologie pathologiques [CHU Toulouse], Pôle Biologie [CHU Toulouse], Imagerie cérébrale et handicaps neurologiques (ICHN), Institut des sciences du cerveau de Toulouse. (ISCT), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Neurochirurgie [CHU Toulouse], Pôle Neurosciences [CHU Toulouse], Infineon Technologies AG [München], Institut National de la Recherche Agronomique (INRA), Clinique neurologique, Hôpital Laennec, Service de physiologie, CHU Pontchaillou [Rennes], Paracelsus Elena Klinik, Centre for Parkinson's Disease & Movement Disorders, Center of Neurology, Hertie Institute for Clinical Brain Research, University of Tuebingen, Hôpital de la Timone [CHU - APHM] (TIMONE), Service de neurochirurgie fonctionnelle, Hospices Civils de Lyon (HCL), Laboratoire Parole et Langage (LPL), Philipps Universität Marburg = Philipps University of Marburg, Department of Neurosurgery, University of Tuebingen, Département de l’étude du milieu naturel et agricole, Centre Wallon de Recherches Agronomiques (CRA-W), Heidelberg University, Department of Clinical Genetics, Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (CNC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Fédération des Maladies du Système Nerveux, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neuroradiologie [CHU Pitié-Salpêtrière], 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], Humboldt-Universität zu Berlin, Laboratoire de pharmacologie médicale et clinique, Service d'anatomie et cytologie pathologiques [Purpan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurochirurgie [Rangueil], CHU Toulouse [Toulouse]-Hôpital de Rangueil, Philipps Universität Marburg, Heinrich-Heine-Universität Düsseldorf [Düsseldorf], Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Département de Neurologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-IFR70-CHU Pitié-Salpêtrière [APHP], Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux - Clermont Auvergne (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), Eberhard Karls Universität Tübingen, Imagerie cérébrale et handicaps neurologiques, CIC Toulouse, Service d'Explorations Fonctionnelles Neurologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [APHP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), 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 [APHP], Friedrich-Schiller-Universität Jena, Humboldt Universität zu Berlin, Infineon Technologies AG [Neubiberg, Germany], Philipps Universität Marbug, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Adult, Male, medicine.medical_specialty, Parkinson's disease, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Deep Brain Stimulation, International Cooperation, Motor Activity, Severity of Illness Index, law.invention, Antiparkinson Agents, Cohort Studies, Levodopa, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Quality of life, law, Subthalamic Nucleus, Germany, Severity of illness, medicine, Humans, Apathy, ComputingMilieux_MISCELLANEOUS, Depression (differential diagnoses), Psychiatric Status Rating Scales, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, Beck Depression Inventory, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Parkinson Disease, Middle Aged, medicine.disease, ddc:616.8, 3. Good health, 030104 developmental biology, Physical therapy, Female, Neurology (clinical), France, medicine.symptom, business, 030217 neurology & neurosurgery, Cohort study
Abstract

Although subthalamic stimulation is a recognised treatment for motor complications in Parkinson's disease, reports on behavioural outcomes are controversial, which represents a major challenge when counselling candidates for subthalamic stimulation. We aimed to assess changes in behaviour in patients with Parkinson's disease receiving combined treatment with subthalamic stimulation and medical therapy over a 2-year follow-up period as compared with the behavioural evolution under medical therapy alone.We did a parallel, open-label study (EARLYSTIM) at 17 surgical centres in France (n=8) and Germany (n=9). We recruited patients with Parkinson's disease who were disabled by early motor complications. Participants were randomly allocated (1:1) to either medical therapy alone or bilateral subthalamic stimulation plus medical therapy. The primary outcome was mean change in quality of life from baseline to 2 years. A secondary analysis was also done to assess behavioural outcomes. We used the Ardouin Scale of Behavior in Parkinson's Disease to assess changes in behaviour between baseline and 2-year follow-up. Apathy was also measured using the Starkstein Apathy Scale, and depression was assessed with the Beck Depression Inventory. The secondary analysis was done in all patients recruited. We used a generalised estimating equations (GEE) regression model for individual items and mixed model regression for subscores of the Ardouin scale and the apathy and depression scales. This trial is registered with ClinicalTrials.gov, number NCT00354133. The primary analysis has been reported elsewhere; this report presents the secondary analysis only.Between July, 2006, and November, 2009, 251 participants were recruited, of whom 127 were allocated medical therapy alone and 124 were assigned bilateral subthalamic stimulation plus medical therapy. At 2-year follow-up, the levodopa-equivalent dose was reduced by 39% (-363·3 mg/day [SE 41·8]) in individuals allocated bilateral subthalamic stimulation plus medical therapy and was increased by 21% (245·8 mg/day [40·4]) in those assigned medical therapy alone (p0·0001). Neuropsychiatric fluctuations decreased with bilateral subthalamic stimulation plus medical therapy during 2-year follow-up (mean change -0·65 points [SE 0·15]) and did not change with medical therapy alone (-0·02 points [0·15]); the between-group difference in change from baseline was significant (p=0·0028). At 2 years, the Ardouin scale subscore for hyperdopaminergic behavioural disorders had decreased with bilateral subthalamic stimulation plus medical therapy (mean change -1·26 points [SE 0·35]) and had increased with medical therapy alone (1·12 points [0·35]); the between-group difference was significant (p0·0001). Mean change from baseline at 2 years in the Ardouin scale subscore for hypodopaminergic behavioural disorders, the Starkstein Apathy Scale score, and the Beck Depression Inventory score did not differ between treatment groups. Antidepressants were stopped in 12 patients assigned bilateral subthalamic stimulation plus medical therapy versus four patients allocated medical therapy alone. Neuroleptics were started in nine patients assigned medical therapy alone versus one patient allocated bilateral subthalamic stimulation plus medical therapy. During the 2-year follow-up, two individuals assigned bilateral subthalamic stimulation plus medical therapy and one patient allocated medical therapy alone died by suicide.In a large cohort with Parkinson's disease and early motor complications, better overall behavioural outcomes were noted with bilateral subthalamic stimulation plus medical therapy compared with medical therapy alone. The presence of hyperdopaminergic behaviours and neuropsychiatric fluctuations can be judged additional arguments in favour of subthalamic stimulation if surgery is considered for disabling motor complications.German Federal Ministry of Education and Research, French Programme Hospitalier de Recherche Clinique National, and Medtronic.

Published
2017
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5. Levodopa inhibits habit-learning in Parkinson’s disease

Author

Ute A. Kopp, Andreas Kupsch, Thomas D. Hälbig, Peter Scherer, Doreen Gruber, and Hannah Fuhrer

Subjects
Adult, Male, Levodopa, medicine.medical_specialty, Neurology, Parkinson's disease, education, Pharmacology, Choice Behavior, Antiparkinson Agents, Dopamine, Humans, Medicine, In patient, Ecosystem, Biological Psychiatry, Aged, Learning Disabilities, business.industry, digestive, oral, and skin physiology, Dopaminergic, Association Learning, Parkinson Disease, Middle Aged, medicine.disease, nervous system diseases, Psychiatry and Mental health, Female, Neurology (clinical), Cues, business, medicine.drug
Abstract

Mixed dopaminergic medication, comprising dopamine agonists and levodopa, may affect habit-learning in patients with Parkinson’s disease (PD). However, the specific impact of levodopa on this effect is unknown. We assessed habit-learning in 20 non-demented PD-patients both with and without levodopa. We observed intact habit-learning in PD-patients OFF-medication. In contrast, the administration of 200 mg of levodopa impaired habit-learning. We conclude that potential deficits in habit-learning in PD may be attributed to the intake of levodopa.

Published
2013
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6. Reversal learning reveals cognitive deficits and altered prediction error encoding in the ventral striatum in Huntington's disease

Author

Florian Schlagenhauf, Lorenz Deserno, Patricia Panneck, Konstantin Prass, Josef Priller, Katharina Nickchen, Thomas D. Hälbig, Andreas Heinz, Maria del Mar Amador, Joachim Behr, Katharina Dehnicke, and Rebecca Boehme

Subjects
0301 basic medicine, physiopathology [Huntington Disease], Male, Huntingtin, physiopathology [Cognitive Dysfunction], diagnostic imaging [Cognitive Dysfunction], physiopathology [Ventral Striatum], physiopathology [Gray Matter], Striatum, Neuropsychological Tests, Functional Laterality, Cohort Studies, genetics [Huntington Disease], Behavioral Neuroscience, 0302 clinical medicine, ddc:150, Gray Matter, diagnostic imaging [Huntington Disease], Brain Mapping, medicine.diagnostic_test, Neuropsychology, Cognition, Middle Aged, Magnetic Resonance Imaging, diagnostic imaging [Ventral Striatum], Psychiatry and Mental health, Huntington Disease, medicine.anatomical_structure, Neurology, Disease Progression, Female, Psychology, Algorithms, Adult, Cognitive Neuroscience, Central nervous system, Reversal Learning, physiology [Reversal Learning], 03 medical and health sciences, Cellular and Molecular Neuroscience, Huntington's disease, medicine, Humans, Cognitive Dysfunction, Radiology, Nuclear Medicine and imaging, Computer Simulation, Ventral striatum, diagnostic imaging [Gray Matter], medicine.disease, 030104 developmental biology, Ventral Striatum, psychology [Huntington Disease], Neurology (clinical), Probability Learning, Functional magnetic resonance imaging, Neuroscience, 030217 neurology & neurosurgery
Abstract

Huntington's disease (HD) is an autosomal dominant neurodegenerative condition characterized by a triad of movement disorder, neuropsychiatric symptoms and cognitive deficits. The striatum is particularly vulnerable to the effects of mutant huntingtin, and cell loss can already be found in presymptomatic stages. Since the striatum is well known for its role in reinforcement learning, we hypothesized to find altered behavioral and neural responses in HD patients in a probabilistic reinforcement learning task performed during functional magnetic resonance imaging. We studied 24 HD patients without central nervous system (CNS)-active medication and 25 healthy controls. Twenty HD patients and 24 healthy controls were able to complete the task. Computational modeling was used to calculate prediction error values and estimate individual parameters. We observed that gray matter density and prediction error signals during the learning task were related to disease stage. HD patients in advanced disease stages appear to use a less complex strategy in the reversal learning task. In contrast, HD patients in early disease stages show intact encoding of learning signals in the degenerating left ventral striatum. This effect appears to be lost with disease progression.

Published
2017
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7. Differential role of dopamine in emotional attention and memory: Evidence from Parkinson's disease

Author

Pasquale G. Frisina, Stephanie Assuras, Andrei Voustianiouk, Joan C. Borod, Judy Creighton, Winona Tse, Jean-Michel Gracies, C. Warren Olanow, and Thomas D. Hälbig

Subjects
Parkinson's disease, Emotional blunting, Dopaminergic, medicine.disease, Arousal, Neurology, Dopamine, Negativity bias, Basal ganglia, medicine, Neurology (clinical), Valence (psychology), Psychology, Neuroscience, medicine.drug
Abstract

Consistent with the hypothesis that dopamine is implicated in the processing of salient stimuli relevant to the modification of various behavioral responses, Parkinson's disease is associated with emotional blunting. To address the hypothesis that emotional attention and memory are modulated by dopaminergic neurotransmission in Parkinson's disease, we assessed 15 nondemented patients with Parkinson's disease while on and off dopaminergic medication and 15 age-matched healthy controls. Visual stimuli were presented, and recognition was used to assess emotional memory. Response latency was used as a measure of emotional attention modulation. Stimuli were varied based on valence (pleasant, neutral, and unpleasant) and arousal (high and low) dimensions. Controls had significantly better memory for positive than negative stimuli, whereas patients with Parkinson's disease tested off medication had significantly better memory for negative than positive items. This negativity bias was lost when they were tested while on dopaminergic medication. Reaction times in patients with Parkinson's disease off medication were longer than in healthy controls and, paradoxically, were even longer when on medication. Further, although both healthy controls and patients with Parkinson's disease in the "off" state had arousal-induced prolongation of reaction time, this effect was not seen in patients with Parkinson's disease on medication. These data indicate that dopaminergic neurotransmission is implicated in emotional memory and attention and suggest that dopamine mediates emotional memory via the valence dimension and emotional attention via arousal. Furthermore, our findings suggest that emotional changes in Parkinson's disease result from the effects of both the disease process and dopaminergic treatment.

Published
2011
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8. Emotional processing affects movement speed

Author

Pasquale G. Frisina, Andrei Voustianiouk, Winona Tse, Joan C. Borod, C. Warren Olanow, Thomas D. Hälbig, and Jean-Michel Gracies

Subjects
Male, Movement, Emotions, Emotional processing, Developmental psychology, Arousal, Mental Processes, Reaction Time, Humans, Valence (psychology), Practical implications, Biological Psychiatry, Neurorehabilitation, Aged, Electromyography, Emotional stimuli, Cognition, Middle Aged, Psychiatry and Mental health, Neurology, Female, Neurology (clinical), Psychology, Photic Stimulation, Psychomotor Performance, Cognitive psychology
Abstract

Emotions can affect various aspects of human behavior. The impact of emotions on behavior is traditionally thought to occur at central, cognitive and motor preparation stages. Using EMG to measure the effects of emotion on movement, we found that emotional stimuli differing in valence and arousal elicited highly specific effects on peripheral movement time. This result has conceptual implications for the emotion-motion link and potentially practical implications for neurorehabilitation and professional environments where fast motor reactions are critical.

Published
2011
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9. The Effects of Withdrawal of Dopaminergic Medication in Nursing Home Patients With Advanced Parkinsonism

Author

William C. Koller, Leslie S. Libow, Thomas D. Hälbig, Jean-Michel Gracies, Gerson T. Lesser, Lisa Liang, Chaim Tarshish, Richard R. Neufeld, Pasquale G. Frisina, and Winona Tse

Subjects
Male, medicine.medical_specialty, Dopamine Agents, Population, Severity of Illness Index, law.invention, Levodopa, Drug withdrawal, Double-Blind Method, Randomized controlled trial, Quality of life, law, Severity of illness, Humans, Medicine, Dementia, education, General Nursing, Aged, Aged, 80 and over, Polypharmacy, education.field_of_study, business.industry, Health Policy, Parkinsonism, Parkinson Disease, General Medicine, medicine.disease, Nursing Homes, Substance Withdrawal Syndrome, Physical therapy, Female, New York City, Geriatrics and Gerontology, business
Abstract

Objective To determine the effects of dopaminergic medication withdrawal in an elderly, demented and minimally ambulatory nursing home population with parkinsonism in New York City. Methods In our double-blind, randomized study, 11 patients (7 males, 4 females) were randomized into 2 groups: one group underwent levodopa medication withdrawal (experimental group) and the other group continued on their levodopa (control group). Patients were evaluated weekly over the course of a month with a neurologic examination and a series of assessment tools, including the motor UPDRS (Unified Parkinson's disease rating scale), Hoehn and Yahr staging scale, the Mini-Mental State Examination (MMSE) and the Nursing Assistant Behavioral Detection Form. Setting An academic nursing home in New York City. Results The patients had a mean age of 82.00 ± 10.14 years, with a mean MMSE score of 9.50 ± 6.60 out of 30.00 maximum. The control and experimental groups did not differ significantly with respect to age ( P = .52), dementia severity ( P = .35), nor severity of PD symptoms as measured by the UPDRS ( P = .22) and Hoehn and Yahr staging ( P = .65). Overall, no significant changes were observed between the control and experimental groups in cognitive, behavioral, and motor function across each time period. Of interest, 2 of the drug withdrawal patients showed modest improvements in cognitive function as measured by the MMSE. Conclusion Our findings suggest that in patients with advanced parkinsonism and dementia, dopaminergic medication withdrawal may be a feasible way to reduce polypharmacy and potential medication-related side effects, with a minimal risk of worsening motor deterioration. Therefore, our findings may have potential implications for a medication intervention that could prevent potential deleterious side effects and improve health-related quality of life in this frail population.

Published
2008
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10. Dopaminergic modulation of emotional memory in Parkinson’s disease

Author

Andreas Kupsch, Franziska Wodarz, Ute A. Kopp, Jean-Michel Gracies, Georg Ebersbach, Joan C. Borod, and Thomas D. Hälbig

Subjects
Male, medicine.medical_specialty, Neurology, Parkinson's disease, Visual perception, Dopamine, Dopamine Agents, Emotions, Affect (psychology), Synaptic Transmission, Antiparkinson Agents, Memory, Basal ganglia, medicine, Humans, Biological Psychiatry, Aged, business.industry, Dopaminergic, Parkinson Disease, Middle Aged, medicine.disease, Psychiatry and Mental health, Mental Recall, Female, Neurology (clinical), business, Neuroscience, Photic Stimulation, Psychomotor Performance, medicine.drug
Abstract

The aim of this study was to assess the effect of dopaminergic treatment on emotional memory in patients with Parkinson's disease (PD). We tested memory for emotional and neutral visual stimuli in ten non-demented PD patients on and off dopaminergic medication. Patients recalled significantly more emotional items during the off- than on-medication testing session. In contrast, treatment condition did not affect memory for neutral items. These findings demonstrate that emotional memory deficits observed in PD may result from dopaminergic treatment and suggest an involvement of dopaminergic neurotransmission in emotional processing.

Published
2008
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11. Prevalence of movement disorders in an elderly nursing home population

Author

Chaim Tarshish, W. C. Koller, Judith Frank, Gerson Lesser, Susan Dolan, Winona Tse, Leslie S. Libow, Jean-Michel Gracies, C. Warren Olanow, Richard R. Neufeld, and Thomas D. Hälbig

Subjects
Male, Aging, Pediatrics, medicine.medical_specialty, Health (social science), Movement disorders, Essential Tremor, Prevalence, Severity of Illness Index, Nursing home population, medicine, Humans, Medical diagnosis, Aged, 80 and over, Dystonia, Movement Disorders, Essential tremor, business.industry, Parkinsonism, Parkinson Disease, medicine.disease, Nursing Homes, nervous system diseases, Cross-Sectional Studies, Physical therapy, Female, New York City, Geriatrics and Gerontology, medicine.symptom, business, Gerontology, Myoclonus
Abstract

We studied the prevalence of movement disorders in a large nursing home population (397 patients, mean age 86 years) in New York City. Patients were first evaluated by specially trained research coordinators and final clinical diagnoses were confirmed by a movement disorder specialist. A movement disorder was identified in 21% of patients (83/397). The most frequent movement disorders were essential tremor (ET) (8.8%) and parkinsonism (7.1%). Only half of those admitted with a diagnosis of parkinsonism were confirmed in their diagnosis by the movement disorder specialists. Three percent of patients exhibited drug-induced tremor, 1.3% had dystonia, 0.5% had myoclonus and 0.3% had generalized dyskinesias. Overall, our findings underline the high frequency of movement disorders in a nursing home population. The discrepancy between our findings and the prevalence rates for parkinsonism reported on the initial transfer diagnosis emphasizes the difficulty of accurate diagnosis of movement disorders and in particular parkinsonism.

Published
2008
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12. Clinical usefulness of the Parkinson's disease sleep scale

Author

C. Warren Olanow, Winona Tse, Jean-Michel Gracies, Thomas D. Hälbig, Sonia V. Tolgyesi, Yi-Ming Liu, W. C. Koller, and Gabriele M. Barthlen

Subjects
Male, Sleep Wake Disorders, medicine.medical_specialty, Parkinson's disease, Excessive daytime sleepiness, Polysomnography, Physical medicine and rehabilitation, Surveys and Questionnaires, Insomnia, Humans, Medicine, Aged, Aged, 80 and over, Sleep disorder, Sleep disorder specialist, medicine.diagnostic_test, business.industry, Epworth Sleepiness Scale, Sleep apnea, Parkinson Disease, Middle Aged, medicine.disease, Neurology, Physical therapy, Female, Neurology (clinical), Geriatrics and Gerontology, medicine.symptom, business
Abstract

Objective To test the usefulness of the Parkinson's disease sleep scale (PDSS) in identifying sleep disorders in the clinical practice setting. Methods Sixty-two PD patients were evaluated with the PDSS and the Epworth sleepiness scale (ESS). A cut-off of less than five for each PDSS item as an indicator of substantial sleep disturbance was chosen. If the ESS was equal to or greater than eight, patients were referred to a sleep disorder specialist and possible polysomnography. Results The mean total PDSS score was 104.7±21.5,which correlated with the mean Hoehn and Yahr score (1.9±0.9) as well as the mean ESS score (9.7±4.7). A significant correlation was also found between the ESS score and several items of the PDSS. Conclusions The PDSS was useful in identifying sleep disturbances which were not previously diagnosed, such as sleep maintenance insomnia and excessive daytime sleepiness. Problems with the PDSS include ambiguities of some questions, lack of quantification and an inability to identify specific sleep disturbances such as sleep apnea.

Published
2005
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13. Neuroprotective agents in Parkinson's disease: clinical evidence and caveats

Author

Winona Tse, Thomas D. Hälbig, and C. Warren Olanow

Subjects
Clinical Trials as Topic, Parkinson's disease, business.industry, Treatment outcome, MEDLINE, Brain, Parkinson Disease, Bioinformatics, medicine.disease, Neuroprotection, Antiparkinson Agents, Neuroprotective Agents, Treatment Outcome, Pharmacotherapy, Clinical evidence, Humans, Medicine, Drug Therapy, Combination, Neurology (clinical), business, Neuroscience
Published
2004
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14. Effects of levodopa on cognitive functioning in moderate-to-severe Parkinson?s disease (MSPD)

Author

M. F. Brin, Chris Morrison, Joan C. Borod, C. W. Olanow, and Thomas D. Hälbig

Subjects
Male, Levodopa, medicine.medical_specialty, Pediatrics, Neurology, Parkinson's disease, Deep Brain Stimulation, Disease, Neuropsychological Tests, Antiparkinson Agents, Cognition, medicine, Humans, Cognitive skill, Psychiatry, Biological Psychiatry, Depression (differential diagnoses), Aged, Neuropsychology, Parkinson Disease, Middle Aged, medicine.disease, Psychiatry and Mental health, Female, Neurology (clinical), Psychology, Psychomotor Performance, medicine.drug
Abstract

Although improved cognition has been reported in patients with mild Parkinson's disease (PD) following the administration of levodopa, mixed results have been found in moderately-to-severely affected PD patients (MSPD), particularly in studies conducted since 1980. In the present study, 16 MSPD patients were tested on separate days, once following overnight levodopa withdrawal and once while optimally treated. A battery of neuropsychological tests that assess a range of cognitive functions (i.e., attention, language, visuospatial, memory, and executive), as well as a measure of depression, were used. Although patients performed better on a measure of confrontation naming in the untreated than in the treated condition, there were no significant differences for any of the other cognitive variables or for the depression scale variable. Thus, these data suggest that there are generally no adverse or beneficial effects of levodopa therapy on cognition in MSPD patients.

Published
2004
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15. Subthalamic stimulation differentially modulates declarative and nondeclarative memory

Author

Thomas Trottenberg, Thomas D. Hälbig, Peter Scherer, Guy Arnold, Doreen Gruber, Andreas Kupsch, Gerd-Helge Schneider, and Ute A. Kopp

Subjects
Male, Basal Ganglia, Temporal lobe, Stereotaxic Techniques, Cognition, Memory, Subthalamic Nucleus, Basal ganglia, Reaction Time, Humans, Aged, Brain Mapping, Long-term memory, General Neuroscience, Memoria, Parkinson Disease, Middle Aged, Magnetic Resonance Imaging, Electric Stimulation, nervous system diseases, Neuroanatomy of memory, Subthalamic nucleus, surgical procedures, operative, nervous system, Brain stimulation, Female, Memory consolidation, Psychology, Microelectrodes, therapeutics, Neuroscience, Psychomotor Performance
Abstract

Declarative memory has been reported to rely on the medial temporal lobe system, whereas non-declarative memory depends on basal ganglia structures. We investigated the functional role of the subthalamic nucleus (STN), a structure closely connected with the basal ganglia for both types of memory. Via deep brain high frequency stimulation (DBS) we manipulated neural activity of the STN in humans. We found that DBS-STN differentially modulated memory performance: declarative memory was impaired, whereas non-declarative memory was improved in the presence of STN-DBS indicating a specific role of the STN in the activation of memory systems.

Published
2004
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16. Effects of dopaminergic and subthalamic stimulation on musical performance

Author

Eric Bardinet, Michael Schüpbach, Jérôme Yelnik, Eckart Altenmüller, Floris T. van Vugt, Thomas D. Hälbig, Neurologie et thérapeutique expérimentale, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR70-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Neurology, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), 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), Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris] (CENIR), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière (NEMESIS-CRICM), 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)-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), CIC AP-HP (pitie-Salpetriere)/inserm, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR70-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de Neuro-Imagerie de Recherche (CENIR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)

Subjects
Adult, Male, Parkinson's disease, Deep brain stimulation, Indoles, medicine.medical_treatment, Deep Brain Stimulation, Movement, Dopamine Agents, 610 Medicine & health, Stimulation, Metronome, behavioral disciplines and activities, law.invention, Levodopa, 03 medical and health sciences, 0302 clinical medicine, law, Subthalamic Nucleus, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Biological Psychiatry, 030304 developmental biology, 0303 health sciences, Dopaminergic, Auditory Perceptual Disorders, Motor control, Parkinson Disease, medicine.disease, nervous system diseases, Psychiatry and Mental health, Subthalamic nucleus, surgical procedures, operative, Neurology, nervous system, Brain stimulation, Time Perception, Neurology (clinical), Psychology, Neuroscience, therapeutics, 030217 neurology & neurosurgery, Music, Psychomotor Performance
Abstract

International audience; Although subthalamic-deep brain stimulation (STN-DBS) is an efficient treatment for Parkinson's disease (PD), its effects on fine motor functions are not clear. We present the case of a professional violinist with PD treated with STN-DBS. DBS improved musical articulation, intonation and emotional expression and worsened timing relative to a timekeeper (metronome). The same effects were found for dopaminergic treatment. These results suggest that STN-DBS, mimicking the effects of dopaminergic stimulation, improves fine-tuned motor behaviour whilst impairing timing precision.

Published
2013
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17. Preserved emotional modulation of motor response time despite psychomotor slowing in young-old adults

Author

Andrei Voustianiouk, Jean-Michel Gracies, Horacio Kaufmann, Stephanie Assuras, Joan C. Borod, C. Warren Olanow, Nancy S. Foldi, Judy Creighton, Winona Tse, and Thomas D. Hälbig

Subjects
Psychomotor learning, Adult, Male, Aging, General Neuroscience, Emotions, Emotional stimuli, Cognition, General Medicine, Emotional processing, Middle Aged, Developmental psychology, Arousal, Emotional modulation, Young Adult, Behavioral response, Reaction Time, Humans, Female, Valence (psychology), Psychology, Photic Stimulation, Aged
Abstract

Whereas aging affects cognitive and psychomotor processes negatively, the impact of aging on emotional processing is less clear. Using an “old–new” binary decision task, we ascertained the modulation of response latencies after presentation of neutral and emotional pictures in “young” (M = 27.1 years) and “young-old” adults with a mean age below 60 (M = 57.7 years). Stimuli varied on valence (pleasant, neutral, and unpleasant) and arousal (high and low) dimensions. Young-old adults had significantly longer reaction times. However, young and young-old adults showed the exact same pattern of response time modulation by emotional stimuli: Response latencies were longer for high-arousal than for low-arousal pictures and longer for negative than for positive or neutral stimuli. This result suggests that the specific effects of implicitly processed emotional valence and arousal information on behavioral response time are preserved in young-old adults despite significant age-related psychomotor decline.

Published
2011

19. Differential role of dopamine in emotional attention and memory: evidence from Parkinson's disease

Author

Thomas D, Hälbig, Stephanie, Assuras, Judy, Creighton, Joan C, Borod, Winona, Tse, Pasquale G, Frisina, Andrei, Voustianiouk, Jean-Michel, Gracies, and C Warren, Olanow

Subjects
Male, Analysis of Variance, Dopamine Agents, Emotions, Parkinson Disease, Recognition, Psychology, Middle Aged, Neuropsychological Tests, Case-Control Studies, Reaction Time, Humans, Attention, Female, Photic Stimulation, Aged
Abstract

Consistent with the hypothesis that dopamine is implicated in the processing of salient stimuli relevant to the modification of various behavioral responses, Parkinson's disease is associated with emotional blunting. To address the hypothesis that emotional attention and memory are modulated by dopaminergic neurotransmission in Parkinson's disease, we assessed 15 nondemented patients with Parkinson's disease while on and off dopaminergic medication and 15 age-matched healthy controls. Visual stimuli were presented, and recognition was used to assess emotional memory. Response latency was used as a measure of emotional attention modulation. Stimuli were varied based on valence (pleasant, neutral, and unpleasant) and arousal (high and low) dimensions. Controls had significantly better memory for positive than negative stimuli, whereas patients with Parkinson's disease tested off medication had significantly better memory for negative than positive items. This negativity bias was lost when they were tested while on dopaminergic medication. Reaction times in patients with Parkinson's disease off medication were longer than in healthy controls and, paradoxically, were even longer when on medication. Further, although both healthy controls and patients with Parkinson's disease in the "off" state had arousal-induced prolongation of reaction time, this effect was not seen in patients with Parkinson's disease on medication. These data indicate that dopaminergic neurotransmission is implicated in emotional memory and attention and suggest that dopamine mediates emotional memory via the valence dimension and emotional attention via arousal. Furthermore, our findings suggest that emotional changes in Parkinson's disease result from the effects of both the disease process and dopaminergic treatment.

Published
2010

20. Skin picking in Parkinson's disease: a behavioral side-effect of dopaminergic treatment?

Author

Winona Tse and Thomas D. Hälbig

Subjects
Male, medicine.medical_specialty, Parkinson's disease, Side effect, business.industry, General Neuroscience, Dopaminergic, Dopamine Agents, Parkinson Disease, General Medicine, Middle Aged, medicine.disease, Dermatology, Levodopa, Psychiatry and Mental health, Neurology, Medicine, Humans, Skin-picking, Neurology (clinical), business, Self-Injurious Behavior
Published
2010

21. Levodopa

Author

Thomas D, Hälbig and William C, Koller

Published
2008

23. The pattern of cognitive-functional decline in elderly essential tremor patients: an exploratory-comparative study with Parkinson's and Alzheimer's disease patients

Author

Pasquale G. Frisina, Winona Tse, Thomas D. Hälbig, and Leslie S. Libow

Subjects
Male, medicine.medical_specialty, Movement disorders, Essential Tremor, Neurological disorder, Disease, Neuropsychological Tests, Disability Evaluation, Physical medicine and rehabilitation, Orientation (mental), Rating scale, Alzheimer Disease, Activities of Daily Living, Medicine, Humans, Cognitive impairment, General Nursing, Aged, Aged, 80 and over, Essential tremor, business.industry, Health Policy, Cognition, Parkinson Disease, General Medicine, medicine.disease, Long-Term Care, Female, Geriatrics and Gerontology, medicine.symptom, business, Cognition Disorders
Abstract

Objective Essential tremor (ET) is a neurological disorder that produces motor, cognitive, and functional disability. However, there has been no investigation linking cognitive impairment with functional disability in ET. Therefore, we examine the similarities and differences between ET, Alzheimer's disease (AD), and Parkinson's disease (PD) in terms of the linkage between cognitive and functional impairment. Design Thirty-four ET, 26 PD, and 31 AD subjects were tested for cognition (Mini-Mental State Examination [MMSE]), motor disability (United Parkinson's Disease Rating Scale part III [UPDRS-III]), and functional disability (Minimum Data Set-Activities of Daily Living Section [MDS-ADL]). Results As expected, in PD and AD subjects, MDS-ADL scores significantly correlated with UPDRS-III and MMSE scores. The ET subjects showed a different pattern of functional disability with MDS-ADL scores significantly correlating only with MMSE scores, and with the orientation MMSE modalities. Conclusions Our findings highlight the need to be more cognizant of the nonmotor aspects of ET, which in some patients may be more functionally disabling than the motor features themselves.

Published
2008

24. Emotional processing in Parkinson's disease: a reaction time study

Author

C. Warren Olanow, Joan C. Borod, Jean-Michel Gracies, Stephanie Assuras, Horacio Kaufmann, Andrei Voustianiouk, K. Fung, Winona Tse, Donald J. Weisz, Thomas D. Hälbig, and J. Barry

Subjects
Parkinson's disease, medicine, Neurology (clinical), Emotional processing, medicine.disease, Psychology, Neuroscience
Published
2007
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25. Processing of temporal duration information in working memory after frontodorsal tumour excisions

Author

Thomas D Hälbig, Angela D. Friederici, Claudius Gall, D. Yves von Cramon, and U. D. Schmid

Subjects
Adult, Male, medicine.medical_specialty, Cognitive Neuroscience, Experimental and Cognitive Psychology, Audiology, Neuropsychological Tests, Spatial memory, Functional Laterality, Task (project management), Perceptual Disorders, Postoperative Complications, Arts and Humanities (miscellaneous), Developmental and Educational Psychology, medicine, Humans, Recognition memory, Memory Disorders, Working memory, Brain Neoplasms, Cognitive disorder, Recognition, Psychology, Time perception, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Frontal Lobe, Neuropsychology and Physiological Psychology, Frontal lobe, Space Perception, Time Perception, Female, Psychology, Cognitive psychology
Abstract

This study aimed to test the hypothesis that impairments of temporal duration processing after frontal lobe lesions reflect deficits in executive monitoring functions rather than a domain-specific deficit in the maintenance of duration information in working memory. Patients with frontodorsal lesions, clinical controls with post-central lesions, and healthy controls performed recognition and classification tasks, which should allow for testing maintenance and monitoring functions, respectively. Results showed mild non-selective impairments of the frontal patients on both temporal and spatial recognition tasks, but a marked selective degradation on temporal classification while performance on spatial classification was unimpaired. This suggests that maintenance of duration information in working memory after frontal lesions is basically preserved but that, depending on executive task characteristics, there is a specific deficit in the strategic organization of this type of information.

Published
2002

26. 3.226 The frequency and magnitude of impulse control deficits in Parkinson's disease patients with deep brain stimulation of the subthalamic nucleus

Author

Winona Tse, B. R. Baker, C. W. Olanow, E. Hollander, Michele Tagliati, Heather M Shapiro, Thomas D. Hälbig, Pasquale G. Frisina, and W. C. Koller

Subjects
Deep brain stimulation, Parkinson's disease, business.industry, medicine.medical_treatment, medicine.disease, Impulse control, Subthalamic nucleus, Neurology, Magnitude (astronomy), Medicine, Neurology (clinical), Geriatrics and Gerontology, business, Neuroscience
Published
2007
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