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1. Brain modulation after exergaming training in advanced forms of Parkinson’s disease: a randomized controlled study

Author: Anna Skrzatek, Dijana Nuic, Saoussen Cherif, Benoit Beranger, Cecile Gallea, Eric Bardinet, and Marie-Laure Welter
Subjects: Parkinson’s disease, Exergaming, Brain magnetic resonance imaging, Resting-state functional connectivity, Gait disorders, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Abstract Background Physical activity combined with virtual reality and exergaming has emerged as a new technique to improve engagement and provide clinical benefit for gait and balance disorders in people with Parkinson’s disease (PD). Objective To investigate the effects of a training protocol using a home-based exergaming system on brain volume and resting-state functional connectivity (rs-FC) in persons with PD. Methods A single blind randomized controlled trial was conducted in people with PD with gait and/or balance disorders. The experimental (active) group performed 18 training sessions at home by playing a custom-designed exergame with full body movements, standing in front of a RGB-D Kinect® motion sensor, while the control group played using the computer keyboard. Both groups received the same training program. Clinical scales, gait recordings, and brain MRI were performed before and after training. We assessed the effects of both training on both the grey matter volumes (GVM) and rs-FC, within and between groups. Results Twenty-three patients were enrolled and randomly assigned to either the active (n = 11) or control (n = 12) training groups. Comparing pre- to post-training, the active group showed significant improvements in gait and balance disorders, with decreased rs-FC between the sensorimotor, attentional and basal ganglia networks, but with an increase between the cerebellar and basal ganglia networks. In contrast, the control group showed no significant changes, and rs-FC significantly decreased in the mesolimbic and visuospatial cerebellar and basal ganglia networks. Post-training, the rs-FC was greater in the active relative to the control group between the basal ganglia, motor cortical and cerebellar areas, and bilaterally between the insula and the inferior temporal lobe. Conversely, rs FC was lower in the active relative to the control group between the pedunculopontine nucleus and cerebellar areas, between the temporal inferior lobes and the right thalamus, between the left putamen and dorsolateral prefrontal cortex, and within the default mode network. Conclusions Full-body movement training using a customized exergame induced brain rs-FC changes within the sensorimotor, attentional and cerebellar networks in people with PD. Further research is needed to comprehensively understand the neurophysiological effects of such training approaches. Trial registration ClinicalTrials.gov NCT03560089.
Published: 2024
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2. Effects of repetitive transcranial magnetic stimulation of the right inferior parietal lobe on the body image perception in anorexia nervosa: A pilot randomized controlled study

Author: Nathalie Chastan, Najate Achamrah, Olivier Etard, Clément Nathou, Marie‐Astrid Piquet, Sébastien Guillaume, Jérôme Attal, André Gillibert, Pierre Dechelotte, Olivier Guillin, and Marie‐Laure Welter
Subjects: anorexia nervosa, body image, repetitive transcranial magnetic stimulation, right inferior parietal lobe, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Introduction Restrictive anorexia nervosa (AN) is associated with distorted perception of body shape, previously linked to hypoactivity and reduced excitability of the right inferior parietal lobe (rIPL). Here, we investigated the impact of high‐frequency repetitive transcranial magnetic stimulation (HF rTMS) of the rIPL on body shape perception in patients with AN. Methods Seventeen patients with AN (median [Q1_Q3] age, 35 [27_39] years; disease duration, 12 [6_18] years) were randomly assigned to receive real or sham HF (10 Hz) rTMS of the rIPL over a period of 2 weeks, comprising 10 sessions. The primary outcome measure was the Body Shape Questionnaire (BSQ). Secondary outcomes included eating disorder symptoms, body mass index, mood, anxiety, and safety. Data collection were done at baseline, post‐rTMS, and at 2 weeks and 3 months post‐rTMS. Results Following both real and sham rTMS of the rIPL, no significant differences were observed in body shape perception or other parameters. Both real and sham rTMS interventions were deemed safe and well tolerated. Notably, serious adverse events were associated with the underlying eating and mood disorders, resulting in hospitalization for undernutrition (five patients) or suicidal attempts (two patients). Conclusion This pilot study does not support the use of rTMS of the rIPL as an effective method for improving body shape perception in individuals with the restrictive form of AN. Further research is warranted to comprehensively explore both the clinical and neurophysiological effects of HF rTMS in this population.
Published: 2024
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3. Brain dysfunction in gait disorders of Caribbean atypical Parkinsonism and progressive supranuclear palsy patients: A comparative study

Author: Marie-Laure Welter, Alexandre Vasseur, Regine Edragas, Hugo Chaumont, Fanny Pineau, Graziella Mangone, Claire Olivier, Isabelle Leber, Sophie Rivaud-Pechoux, Stéphane Lehericy, Cecile Gallea, Lydia Yahia-Cherif, and Annie Lannuzel
Subjects: Gait disorders, Progressive supranuclear palsy, Caribean atypical parkinsonism, Gait recordings, Magnetic resonance imaging, Computer applications to medicine. Medical informatics, R858-859.7, Neurology. Diseases of the nervous system, RC346-429
Abstract: Introduction: Gait disorders and falls occur early in progressive supranuclear palsy (PSP-RS) and Caribbean atypical parkinsonism (Caribbean AP). However, the link between these signs and brain lesions has never been explored in these patient populations. Here, we investigate and compare the imaging factors that relate to gait and balance disorders in Caribbean AP and PSP-RS patients. Methods: We assessed gait and balance using clinical scales and gait recordings in 16 Caribbean AP and 15 PSP-RS patients and 17 age-matched controls. We measured the grey and white matter brain volumes on 3 T brain MRI images. We performed a principal component analysis (PCA) including all the data to determine differences and similarities between groups, and explore the relationship between gait disorders and brain volumes. Results: Both Caribbean AP patients and PSP-RS have marked gait and balance disorders with similar severity. In both groups, gait and balance disorders were found to be most strongly related to structural changes in the lateral cerebellum, caudate nucleus, and fronto-parietal areas. In Caribbean AP patients, gait disorders were also related to additional changes in the cortex, including frontal, insular, temporal and cuneus lobes, whereas in PSP-RS patients, additional white matter changes involved the mesencephalon and parahippocampal gyrus. Conclusion: Gait and balance disorders in Caribbean AP patients are mainly related to dysfunction of cortical brain areas involved in visuo-sensorimotor processing and self-awareness, whereas these signs mainly result from premotor-brainstem-cerebellar network dysfunction in PSP-RS patients, brain areas involved in initiation and maintenance of locomotor pattern and postural adaptation.
Published: 2023
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4. High-frequency cerebellar tACS for managing essential tremor

Author: Jean-Charles Lamy, Claire Olivier, Zuzana Kosutzka, Angèle Van Hamme, Saoussen Cherif, Brian Lau, Marie Vidailhet, Carine Karachi, and Marie-Laure Welter
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Published: 2023
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5. Role of gastric motility in weight gain after subthalamic nucleus stimulation in Parkinson's disease

Author: Nathalie Chastan, Najate Achamrah, Stéphane Derrey, David Maltete, Moise Coeffier, Anne-Marie Leroi, Pierre Dechelotte, Marie-Laure Welter, and Guillaume Gourcerol
Subjects: Parkinson's disease, Deep brain stimulation, Subthalamic nucleus, Weight gain, Gastric motility, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Published: 2021
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6. Beta burst coupling across the motor circuit in Parkinson's disease

Author: Gerd Tinkhauser, Flavie Torrecillos, Yann Duclos, Huiling Tan, Alek Pogosyan, Petra Fischer, Romain Carron, Marie-Laure Welter, Carine Karachi, Wim Vandenberghe, Bart Nuttin, Tatiana Witjas, Jean Régis, Jean-Philippe Azulay, Alexandre Eusebio, and Peter Brown
Subjects: Parkinson's disease, Beta oscillations, Basal ganglia-cortical network, Beta bursts, Local field potentials, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Exaggerated activity in the beta band (13–35 Hz) is a hallmark of basal ganglia signals in patients with Parkinson's disease (PD). Beta activity however is not constantly elevated, but comes in bursts. In previous work we showed that the longer beta bursts are maintained, the more the oscillatory synchronisation within the subthalamic nucleus (STN) increases, which is posited to limit the information coding capacity of local circuits. Accordingly, a higher incidence of longer bursts correlates positively with clinical impairment, while the opposite is true for short, more physiological bursts. Here, we test the hypothesis that beta bursts not only indicate local synchronisation within the STN, but also phasic coupling across the motor network and hence entail an even greater restriction of information coding capacity in patients with PD. Local field potentials from the subthalamic nucleus and EEG over the motor cortex area were recorded in nine PD patients after temporary lead externalization after surgery for deep brain stimulation and overnight withdrawal of levodopa. Beta bursts were defined as periods exceeding the 75th percentile of signal amplitude and the coupling between bursts was considered using two distinct measurements, first the % overlapping (%OVL) as a feature of the amplitude coupling and secondly the phase synchrony index (PSI) to measure the phase coupling between regions. %OVL between STN and cortex and between the left and the right STN was higher than expected between the regions than if they had been independent. Similarly, PSI was higher during bursts as opposed to non-bursts periods. In addition, %OVL was greater for long compared to short bursts. Our results support the hypothesis that beta bursts involve long-range coupling between structures in the basal ganglia-cortical network. The impact of this is greater during long as opposed to short duration beta bursts. Accordingly, we posit that episodes of simultaneously elevated coupling across multiple structures in the basal ganglia-cortical circuit further limit information coding capacity and may have further impact upon motor impairment.
Published: 2018
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7. The feasibility and positive effects of a customised videogame rehabilitation programme for freezing of gait and falls in Parkinson’s disease patients: a pilot study

Author: Dijana Nuic, Maria Vinti, Carine Karachi, Pierre Foulon, Angèle Van Hamme, and Marie-Laure Welter
Subjects: Parkinson’s disease, Freezing of gait, Falls, Videogame, Rehabilitation, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Abstract Background Freezing of gait and falls represent a major burden in patients with advanced forms of Parkinson’s disease (PD). These axial motor signs are not fully alleviated by drug treatment or deep-brain stimulation. Recently, virtual reality has emerged as a rehabilitation option for these patients. In this pilot study, we aim to determine the feasibility and acceptability of rehabilitation with a customised videogame to treat gait and balance disorders in PD patients, and assess its effects on these disabling motor signs. Methods We developed a customised videogame displayed on a screen using the Kinect system. To play, the patient had to perform large amplitude and fast movements of all four limbs, pelvis and trunk, in response to visual and auditory cueing, to displace an avatar to collect coins and avoid obstacles to gain points. We tested ten patients with advanced forms of PD (median disease duration = 16.5 years) suffering from freezing of gait and/or falls (Hoehn&Yahr score ≥ 3) resistant to antiparkinsonian treatment and deep brain stimulation. Patients performed 18 training sessions during a 6–9 week period. We measured the feasibility and acceptability of our rehabilitation programme and its effects on parkinsonian disability, gait and balance disorders (with clinical scales and kinematics recordings), positive and negative affects, and quality of life, after the 9th and 18th training sessions and 3 months later. Results All patients completed the 18 training sessions with high feasibility, acceptability and satisfaction scores. After training, the freezing-of-gait questionnaire, gait-and-balance scale and axial score significantly decreased by 39, 38 and 41%, respectively, and the activity-balance confidence scale increased by 35%. Kinematic gait parameters also significantly improved with increased step length and gait velocity and decreased double-stance time. Three months after the final session, no significant change persisted except decreased axial score and increased step length and velocity. Conclusions This study suggests that rehabilitation with a customised videogame to treat gait and balance disorders is feasible, well accepted, and effective in parkinsonian patients. These data serve as preliminary evidence for further larger and controlled studies to propose this customised videogame rehabilitation programme at home. Trial registration ClinicalTrials.gov NCT02469350.
Published: 2018
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8. Deep brain activation patterns involved in virtual gait without and with a doorway: An fMRI study.

Author: Véronique Marchal, Jason Sellers, Mélanie Pélégrini-Issac, Cécile Galléa, Eric Bertasi, Romain Valabrègue, Brian Lau, Pierre Leboucher, Eric Bardinet, Marie-Laure Welter, and Carine Karachi
Subjects: Medicine, Science
Abstract: The human gait program involves many brain areas such as motor cortices, cerebellum, basal ganglia, brainstem, and spinal cord. The mesencephalic locomotor region (MLR), which contains the pedunculopontine (PPN) and cuneiform (CN) nuclei, is thought to be one of the key supraspinal gait generators. In daily life activities, gait primarily occurs in complex conditions, such as through narrow spaces, or while changing direction or performing motor or cognitive tasks. Here, we aim to explore the activity of these subcortical brain areas while walking through narrow spaces, using functional MRI in healthy volunteers and designing a virtual reality task mimicking walking down a hallway, without and with an open doorway to walk through. As a control, we used a virtual moving walkway in the same environment. Twenty healthy volunteers were scanned. Fifteen subjects were selected for second level analysis based on their ability to activate motor cortices. Using the contrast Gait versus Walkway, we found activated clusters in motor cortices, cerebellum, red nucleus, thalamus, and the left MLR including the CN and PPN. Using the contrast Gait with Doorway versus Walkway with Doorway, we found activated clusters in motor cortices, left putamen, left internal pallidum, left substantia nigra, right subthalamic area, and bilateral MLR involving the CN and PPN. Our results suggest that unobstructed gait involves a motor network including the PPN whereas gait through a narrow space requires the additional participation of basal ganglia and bilateral MLR, which may encode environmental cues to adapt locomotion.
Published: 2019
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9. Functional imaging correlates of akinesia in Parkinson's disease: Still open issues

Author: Charlotte Spay, Garance Meyer, Marie-Laure Welter, Brian Lau, Philippe Boulinguez, and Bénédicte Ballanger
Subjects: Computer applications to medicine. Medical informatics, R858-859.7, Neurology. Diseases of the nervous system, RC346-429
Abstract: Akinesia is a major manifestation of Parkinson's disease (PD) related to difficulties or failures of willed movement to occur. Akinesia is still poorly understood and is not fully alleviated by standard therapeutic strategies. One reason is that the area of the clinical concept has blurred boundaries referring to confounded motor symptoms. Here, we review neuroimaging studies which, by providing access to finer-grained mechanisms, have the potential to reveal the dysfunctional brain processes that account for akinesia. It comes out that no clear common denominator could be identified across studies that are too heterogeneous with respect to the clinical/theoretical concepts and methods used. Results reveal, however, that various abnormalities within but also outside the motor and dopaminergic pathways might be associated with akinesia in PD patients. Notably, numerous yet poorly reproducible neural correlates were found in different brain regions supporting executive control by means of resting-state or task-based studies. This includes for instance the dorsolateral prefrontal cortex, the inferior frontal cortex, the supplementary motor area, the medial prefrontal cortex, the anterior cingulate cortex or the precuneus. This observation raises the issue of the multidimensional nature of akinesia. Yet, other open issues should be considered conjointly to drive future investigations. Above all, a unified terminology is needed to allow appropriate association of behavioral symptoms with brain mechanisms across studies. We adhere to a use of the term akinesia restricted to dysfunctions of movement initiation, ranging from delayed response to freezing or even total abolition of movement. We also call for targeting more specific neural mechanisms of movement preparation and action triggering with more sophisticated behavioral designs/event-related neurofunctional analyses. More work is needed to provide reliable evidence, but answering these still open issues might open up new prospects, beyond dopaminergic therapy, for managing this disabling symptom. Keywords: Akinesia, Parkinson's disease, Neuroimaging, PET, fMRI
Published: 2019
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10. Tackling psychosocial maladjustment in Parkinson's disease patients following subthalamic deep-brain stimulation: A randomised clinical trial.

Author: Joao Flores Alves Dos Santos, Sophie Tezenas du Montcel, Marcella Gargiulo, Cecile Behar, Sébastien Montel, Thierry Hergueta, Soledad Navarro, Hayat Belaid, Pauline Cloitre, Carine Karachi, Luc Mallet, and Marie-Laure Welter
Subjects: Medicine, Science
Abstract: Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for the motor and non-motor signs of Parkinson's disease (PD), however, psychological disorders and social maladjustment have been reported in about one third of patients after STN-DBS. We propose here a perioperative psychoeducation programme to limit such social and familial disruption.Nineteen PD patients and carers were included in a randomised single blind study. Social adjustment scale (SAS) scores from patients and carers that received the psychoeducation programme (n = 9) were compared, both 1 and 2 years after surgery, with patients and carers with usual care (n = 10). Depression, anxiety, cognitive status, apathy, coping, parkinsonian disability, quality-of-life, carers' anxiety and burden were also analysed.Seventeen patients completed the study, 2 were excluded from the final analysis because of adverse events. At 1 year, 2/7 patients with psychoeducation and 8/10 with usual care had an aggravation in at least one domain of the SAS (p = .058). At 2 years, only 1 patient with psychoeducation suffered persistent aggravated social adjustment as compared to 8 patients with usual care (p = .015). At 1 year, anxiety, depression and instrumental coping ratings improved more in the psychoeducation than in the usual care group (p = .038, p = .050 and p = .050, respectively). No significant differences were found between groups for quality of life, cognitive status, apathy or motor disability.Our results suggest that a perioperative psychoeducation programme prevents social maladjustment in PD patients following STN-DBS and improves anxiety and depression compared to usual care. These preliminary data need to be confirmed in larger studies.
Published: 2017
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11. Cerebellar Transcranial Alternating Current Stimulation in Essential Tremor Patients with Thalamic Stimulation: A Proof-of-Concept Study

Author: Claire Olivier, Jean-Charles Lamy, Zuzana Kosutzka, Angèle Van Hamme, Saoussen Cherif, Brian Lau, Marie Vidailhet, Carine Karachi, and Marie-Laure Welter
Subjects: Pharmacology, Pharmacology (medical), Neurology (clinical)
Published: 2023
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12. Stimulation of the pedunculopontine and cuneiform nuclei for freezing of gait and falls in Parkinson disease: Cross-over single-blinded study and long-term follow-up

Author: Julie, Bourilhon, Yannick, Mullie, Claire, Olivier, Saoussen, Cherif, Hayat, Belaid, David, Grabli, Virginie, Czernecki, Carine, Karachi, and Marie-Laure, Welter
Subjects: Neurology, Deep Brain Stimulation, Pedunculopontine Tegmental Nucleus, Humans, Parkinson Disease, Single-Blind Method, Neurology (clinical), Geriatrics and Gerontology, Gait, Gait Disorders, Neurologic, Dihydroxyphenylalanine, Follow-Up Studies
Abstract: Deep brain stimulation (DBS) of the mesencephalic locomotor region, composed of the pedunculopontine (PPN) and cuneiform (CuN) nuclei, has been proposed to treat dopa-resistant gait and balance disorders in Parkinson's disease (PD). Here, we report the long-term effects of PPN- or CuN-DBS on these axial disorders.In 6 PD patients operated for mesencephalic locomotor region DBS and prospectively followed for more than 2 years, we assessed the effects of both PPN- and CuN-DBS (On-dopa) in a cross-over single-blind study by using clinical scales and recording gait parameters. Patients were also examined Off-DBS.More than 2 years after surgery, axial and Tinetti scores were significantly aggravated with both PPN- or CuN-DBS relative to before and one year after surgery. Gait recordings revealed an increased double-stance duration with both PPN- or CuN-DBS, higher swing phase duration with CuN-DBS and step width with PPN-DBS. With PPN- versus CuN-DBS, the step length, velocity and cadence were significantly higher; and the double-stance and turn durations significantly lower. Irrespective the target, we found no significant change in clinical scores Off-DBS compared to On-DBS. The duration of anticipatory postural adjustments as well as step length were lower with versus without PPN-DBS. We found no other significant changes in motor, cognitive or psychiatric scores, except an increased anxiety severity.In this long-term follow-up study with controlled assessments, PPN- or CuN-DBS did not improve dopa-resistant gait and balance disorders with a worsening of these axial motor signs with time, thus indicating no significant clinical effect.
Published: 2022
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13. Parkinson Disease and Subthalamic Nucleus Deep Brain Stimulation: Cognitive Effects in <scp> GBA </scp> Mutation Carriers

Author: Gian Pal, Graziella Mangone, Emily J. Hill, Bichun Ouyang, Yuanqing Liu, Vanessa Lythe, Debra Ehrlich, Rachel Saunders‐Pullman, Vicki Shanker, Susan Bressman, Roy N. Alcalay, Priscilla Garcia, Karen S. Marder, Jan Aasly, M. Maral Mouradian, Samantha Link, Marc Rosenbaum, Sharlet Anderson, Bryan Bernard, Robert Wilson, Glenn Stebbins, William C. Nichols, Marie‐Laure Welter, Sepehr Sani, Mitra Afshari, Leo Verhagen, Rob M.A. Bie, Tom Foltynie, Deborah Hall, Jean‐Christophe Corvol, Christopher G. Goetz, Neurology, ANS - Neurodegeneration, and APH - Aging & Later Life
Subjects: Male, Heterozygote, Databases, Factual, Deep Brain Stimulation, Parkinson Disease, Middle Aged, Neuropsychological Tests, Cognition, Neurology, Subthalamic Nucleus, Mutation, Glucosylceramidase, Humans, Female, Neurology (clinical), Aged
Abstract: Objective: This study was undertaken to compare the rate of change in cognition between glucocerebrosidase (GBA) mutation carriers and noncarriers with and without subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson disease. Methods: Clinical and genetic data from 12 datasets were examined. Global cognition was assessed using the Mattis Dementia Rating Scale (MDRS). Subjects were examined for mutations in GBA and categorized as GBA carriers with or without DBS (GBA+DBS+, GBA+DBS-), and noncarriers with or without DBS (GBA-DBS+, GBA-DBS-). GBA mutation carriers were subcategorized according to mutation severity (risk variant, mild, severe). Linear mixed modeling was used to compare rate of change in MDRS scores over time among the groups according to GBA and DBS status and then according to GBA severity and DBS status. Results: Data were available for 366 subjects (58 GBA+DBS+, 82 GBA+DBS-, 98 GBA-DBS+, and 128 GBA-DBS- subjects), who were longitudinally followed (range = 36–60 months after surgery). Using the MDRS, GBA+DBS+ subjects declined on average 2.02 points/yr more than GBA-DBS- subjects (95% confidence interval [CI] = −2.35 to −1.69), 1.71 points/yr more than GBA+DBS- subjects (95% CI = −2.14 to −1.28), and 1.49 points/yr more than GBA-DBS+ subjects (95% CI = −1.80 to −1.18). Interpretation: Although not randomized, this composite analysis suggests that the combined effects of GBA mutations and STN-DBS negatively impact cognition. We advise that DBS candidates be screened for GBA mutations as part of the presurgical decision-making process. We advise that GBA mutation carriers be counseled regarding potential risks associated with STN-DBS so that alternative options may be considered. ANN NEUROL 2022;91:424–435.
Published: 2022
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14. Personality Assessment with Temperament and Character Inventory in Parkinson's Disease

Author: Mathilde Boussac, Christophe Arbus, Olivier Colin, Chloé Laurencin, Alexandre Eusebio, Elodie Hainque, Jean Christophe Corvol, Nathalie Versace, Olivier Rascol, Vanessa Rousseau, Estelle Harroch, Fabienne Ory-Magne, Margherita Fabbri, Caroline Moreau, Anne-Sophie Rolland, Béchir Jarraya, David Maltête, Sophie Drapier, Ana-Raquel Marques, Nicolas Auzou, Thomas Wirth, Mylène Meyer, Bruno Giordana, Mélissa Tir, Tiphaine Rouaud, David Devos, Christine Brefel-Courbon, Pr Luc Defebvre, Dr Nicolas Carriere, Dr Guillaume Grolez, Dr Guillaume Baille, Dr Kreisler, Pr Jean-Pierre Pruvo, Pr Leclerc, Dr Renaud Lopes, Dr Romain Viard, Dr Gregory Kuchcinski, Mr Julien Dumont, Pr Kathy Dujardin, Mme M. Delliaux, Mrs M. Brion, Dr Gustavo Touzet, Pr Nicolas Reyns, Pr Arnaud Delval, Mrs Valerie Santraine, Mrs Marie Pleuvret, Mrs Nolwen Dautrevaux, Mr Victor Laugeais, Thavarak Ouk, Camille Potey, Celine Leclercq, Elise Gers, Jean-Christophe Corvol, null Marie-Vidailhet, Marie-Laure Welter, Lucette Lacomblez, David Grabli, Emmanuel Roze, Yulia Worbe, Cécile Delorme, Hana You, Jonas Ihle, Raquel Guimeraes-Costa, Florence Cormier-Dequaire, Aurélie Méneret, Andréas Hartmann, Louise-Laure Mariani, Stéphane Lehericy, Virginie Czernecki, Fanny Pineau, Frédérique Bozon, Camille Huiban, Eve Benchetrit, Carine Karachi, Soledad Navarro, Philippe Cornu, Arlette Welaratne, Carole Dongmo-Kenfack, Lise Mantisi, Nathalie Jarry, Sophie Aix, Carine Lefort, Dr Tiphaine Rouaud, Pr Philippe Damier, Pr Pascal Derkinderen, Dr Anne-Gaelle Corbille, Dr Elisabeth Calvier-Auffray, Mrs Laetitia Rocher, Mrs Anne-Laure Deruet, Dr Raoul Sylvie, Dr Roualdes Vincent, Mrs Le Dily Séverine, Dr Ana Marques, Dr Berangere Debilly, Pr Franck Durif, Dr Philippe Derost, Dr Charlotte Beal, Carine Chassain, Laure Delaby, Tiphaine Vidal, Pr Jean Jacques Lemaire, Isabelle Rieu, Elodie Durand, Pr Alexandre Eusebio, Pr Jean-Philippe Azulay, Dr Tatiana Witjas, Dr Frédérique Fluchère, Dr Stephan Grimaldi, Pr Nadine Girard, Marie Delfini, Dr Romain Carron, Pr Jean Regis, Dr Giorgio Spatola, Camille Magnaudet, Dr Ansquer Solène, Dr Benatru Isabelle, Dr Colin Olivier, Pr Houeto Jl, Pr Guillevin Remy, Mrs Fradet Anne, Mrs Anziza Manssouri, Mrs Blondeau Sophie, Dr Richard Philippe, Dr Cam Philippe, Dr Page Philippe, Pr Bataille Benoit, Mrs Rabois Emilie, Mrs Guillemain Annie, Dr Drapier Sophie, Dr Frédérique Leh, Dr Alexandre Bonnet, Pr Marc Vérin, Dr Jean-Christophe Ferré, Mr Jean François Houvenaghel, Pr Claire Haegelen, Mrs Francoise Kestens, Mrs Solenn Ory, Pr Pierre Burbaud, Dr Nathalie Damon-Perriere, Pr Wassilios Meissner, Pr Francois Tison, Dr Stéphanie Bannier, Dr Elsa Krim, Pr Dominique Guehl, Sandrine Molinier-Blossier, Morgan Ollivier, Marion Lacoste, Marie Bonnet, Pr Emmanuel Cuny, Dr Julien Engelhardt, Olivier Branchard, Clotilde Huet, Julie Blanchard, Pr Rascol Olivier, Dr Christine Brefel Courbon, Dr Fabienne Ory Magne, Dr Marion Simonetta Moreau, Pr Christophe Arbus, Pr Fabrice Bonneville, Dr Jean Albert Lotterie, Marion Sarrail, Charlotte Scotto d’Apollonia, Pr Patrick Chaynes, Pr François Caire, Pr David Maltete, Dr Romain Lefaucheur, Dr Damien Fetter, Dr Nicolas Magne, Mrs Sandrine Bioux, Mrs Maud Loubeyre, Mrs Evangéline Bliaux, Mrs Dorothée Pouliquen, Pr Stéphane Derrey, Mrs Linda Vernon, Dr Frédéric Ziegler, Mathieu Anheim, Ouhaid Lagha-Boukbiza, Christine Tranchant, Odile Gebus, Solveig Montaut, S. Kremer, Nadine Longato, Clélie Phillips, Jimmy Voirin, Marie des Neiges Santin, Dominique Chaussemy, Dr Amaury Mengin, Dr Caroline Giordana, Dr Claire Marsé, Lydiane Mondot, Robin Kardous, Bernadette Bailet, Héloise Joly, Denys Fontaine, Dr Aurélie Leplus, Amélie Faustini, Vanessa Ferrier, Pr Pierre Krystkowiak, Dr Mélissa Tir, Pr Jean-Marc Constans, Sandrine Wannepain, Audrey Seling, Dr Michel Lefranc, Stéphanie Blin, Béatrice Schuler, Pr Stephane Thobois, Dr Teodor Danaila, Dr Chloe Laurencin, Pr Yves Berthezene, Dr Roxana Ameli, Helene Klinger, Dr Gustavo Polo, Patrick Mertens, A. Nunes, Elise Metereau, Dr Lucie Hopes, Dr Solène Frismand, Dr Emmanuelle Schmitt, Mrs Mylène Meyer, Mrs Céline Dillier, Pr Sophie Colnat, Mrs Anne Chatelain, Dr Jean- Philippe Brandel, Dr Cécile Hubsch, Dr Patte Karsenti, Dr Marie Lebouteux, Dr Marc Ziegler, Dr Christine Delmaire, Dr Julien Savatowky, Mrs Juliette Vrillac, Mrs Claire Nakache, Dr Vincent D'Hardemare, Mr Lhaouas Belamri, Dr Valérie Mesnage, Dr Cécilia Bonnet, Dr Jarbas Correa Lino, Dr Camille Decrocq, Dr Anne Boulin, Mrs Inès Barre, Mrs Jordane Manouvrier, Dr Bérénice Gardel, Pr Béchir Jarraya, Mrs Catherine Ziz, Mrs Lydie Prette, Mr Hassen Douzane, David Gay, Robin Bonicel, Fouzia El Mountassir, Clara Fischer, Jean-François Mangin, Marie Chupin, Yann Cointepas, Bertrand Accart, Patrick Gelé, Florine Fievet, Matthieu Chabel, Virginie Derenaucourt, Loïc Facon, Yanick Tchantchou Njosse, Dominique Deplanque, Alain Duhamel, Lynda Djemmane, Florence Duflot, 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 Hospitalier de Brive-la-Gaillarde (CH Brive), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon, Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), CHU Marseille, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), 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), Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d’Excellence en Maladies Neurodégénératives (NeuroToul), CIC - Biotherapie - Toulouse, Institut National de la Santé et de la Recherche Médicale (INSERM), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille, Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Hôpital Foch [Suresnes], Neuroimagerie cognitive - Psychologie cognitive expérimentale (UNICOG-U992), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA), Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), CHU Bordeaux [Bordeaux], Les Hôpitaux Universitaires de Strasbourg (HUS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Amiens-Picardie, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), Centre hospitalier universitaire de Nantes (CHU Nantes), This work was supported by the France Parkinson charity and French Ministry of Health (PHRC national 2012). This is an ancillary study to Protocol ID: 2013-A00193-42, ClinicalTrials.gov: NCT02360683., Centre Hospitalier Brive-la-Gaillarde, and Hôpital P.P.-Riquet
Subjects: Personality Inventory, Temperament and character inventory, Parkinson's disease, Parkinson Disease, Personality Assessment, Antidepressive Agents, Neurology, Anti-Anxiety Agents, Fluctuating PD patients, Quality of Life, Humans, Neurology (clinical), Geriatrics and Gerontology, Temperament, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Personality
Abstract: International audience; INTRODUCTION: There is a growing interest in personality evaluation in Parkinson's disease (PD), following observations of specific temperaments in PD patients. Therefore, our objective was to evaluate personality dimensions from the Temperament and Character Inventory (TCI) in a cohort of fluctuating PD patients considered for deep brain stimulation. METHODS: Fluctuating PD patients from the PREDISTIM cohort were included. Description of TCI dimensions and comparison with a French normative cohort were performed. Pearson correlations between TCI dimensions and motor, behavioral and cognitive variables were investigated. Structural and internal consistency analysis of the TCI were further assessed. RESULTS: The 570 PD patients presented significant higher scores in Harm Avoidance, Reward Dependence, Persistence, Self-Directedness and Cooperativeness and significant lower scores in Self-Transcendence compared to the French normative cohort; only Novelty Seeking scores were not different. Harm Avoidance and Self-directedness scores were correlated with PDQ-39 total, HAMD, HAMA scores, and anxiolytic/antidepressant treatment. Novelty Seeking scores were correlated with impulsivity. Pearson correlations between TCI dimensions, principal component analysis of TCI sub-dimensions and Cronbach's alpha coefficients showed adequate psychometric proprieties. CONCLUSION: The TCI seems to be an adequate tool to evaluate personality dimensions in PD with good structural and internal consistencies. These fluctuating PD patients also have specific personality dimensions compared to normative French population. Moreover, Harm Avoidance and Self-Directedness scores are associated with anxio-depressive state or quality of life and, and Novelty Seeking scores with impulsivity.
Published: 2022
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15. N°197 – Can electrophysiological analysis of subthalamic nucleus oscillations uncover new biomarkers for freezing of gait in Parkinson[StQuote]s disease patients?

Author: Mathieu Yèche, Katia Lehongre, Saoussen Cherif, David Maltête, Stéphane Derrey, Dorian Bannier, Déborah Ziri, Brian Lau, Carine Karachi, and Marie-Laure Welter
Subjects: Neurology, Physiology (medical), Neurology (clinical), Sensory Systems
Published: 2023
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16. Repetitive transcranial magnetic stimulation for patients with functional paralysis: a randomized controlled study

Author: Nathalie Chastan, Olivier Etard, Dominique Parain, Priscille Gerardin, Gaël Fouldrin, Philippe Derambure, Céline Tard, André Gillibert, Clément Nathou, Arnaud Delval, Marie‐Laure Welter, Olivier Guillin, Mobilités : Vieillissement, Pathologie, Santé (COMETE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), GIP Cyceron (Cyceron), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Normandie Université (NU), Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille, Centre Esquirol [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre expert inter-régional de coordination de la maladie de Parkinson [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Etard, olivier, Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: Adult, clinical trials, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Headache, Motor Cortex, [SDV.NEU.PC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, controlled, Treatment Outcome, Neurology, Double-Blind Method, randomized, transcranial magnetic stimulation, Humans, Paralysis, Female, Neurology (clinical), functional motor signs, [SDV.NEU.SC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences
Abstract: International audience; Background and purpose: Repetitive transcranial magnetic stimulation (rTMS) has been proposed to treat functional neurological disorders. Here, the aim was to assess the efficacy of rTMS to treat functional paralysis in a controlled randomized trial.Methods: Patients received two sessions of active or sham 0.25 Hz rTMS (60 stimuli each), with a 1-day interval, applied over the motor cortex contralateral to the paralysis. The primary outcome was the number of patients with an increase in motor score between baseline and after the second rTMS session, rated by two investigators blinded to the treatment allocation. Secondary outcomes were changes in global and fine motor scores between groups after rTMS, and the occurrence of adverse events.Results: Sixty-two patients (46 female; mean [SD] age, 35.2 [13.9] years) were enrolled and randomized. Thirteen out of 32 (41%) and 11/30 (37%) patients had increased motor strength after active or sham rTMS, respectively (p = 0.80). Changes in both global and fine motor scores after rTMS relative to baseline were also not significantly different between treatment groups (median difference in the global motor score 0.62 [0.83] and 0.37 [0.61], and in the fine motor scores 0.12 [0.18] and 0.08 [0.11], in active and sham rTMS groups, respectively; p = 0.14). Six serious adverse events, consisting of three cephalalgia in the active group and two cephalalgia and one asthenia in the sham group, were observed.Conclusions: Two sessions of sham or active low frequency rTMS were effective to improve functional paralysis, suggesting a placebo effect of this non-invasive brain stimulation technique.
Published: 2022
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17. Structural connectivity predicts clinical outcomes of deep brain stimulation for Tourette syndrome

Author: Marwan Hariz, Daria Nesterovich Anderson, Juan Carlos Baldermann, Jens Kuhn, Daniel Huys, Kara A. Johnson, Albert F.G. Leentjens, Kelly D. Foote, Jill L. Ostrem, Aysegul Gunduz, Michael S. Okun, Michael H. Pourfar, Marie-Laure Welter, Ludvic Zrinzo, Christopher R. Butson, Thomas Foltynie, Gordon Duffley, Alon Y. Mogilner, Leonardo Almeida, Veerle Visser-Vandewalle, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Psychiatrie & Neuropsychologie, and MUMC+: MA Med Staf Spec Psychiatrie (9)
Subjects: Adult, Male, Cingulate cortex, Tic disorder, Deep brain stimulation, Tics, Deep Brain Stimulation, medicine.medical_treatment, MODELS, severity, tractography, Tourette syndrome, DOUBLE-BLIND, BASAL GANGLIA, thalamic-stimulation, neuronal-activity, Image Interpretation, Computer-Assisted, medicine, Humans, Prefrontal cortex, Retrospective Studies, business.industry, cortico-striato-thalamo-cortical networks, NETWORK ACTIVITY, tics, tic suppression, Brain, obsessive-compulsive behaviour, Original Articles, Middle Aged, medicine.disease, modulation, Diffusion Tensor Imaging, Treatment Outcome, neuromodulation, Female, Orbitofrontal cortex, Neurology (clinical), Nerve Net, business, Neuroscience, Tourette Syndrome, Tractography
Abstract: Deep brain stimulation may be an effective therapy for select cases of severe, treatment-refractory Tourette syndrome; however, patient responses are variable, and there are no reliable methods to predict clinical outcomes. The objectives of this retrospective study were to identify the stimulation-dependent structural networks associated with improvements in tics and comorbid obsessive-compulsive behaviour, compare the networks across surgical targets, and determine if connectivity could be used to predict clinical outcomes. Volumes of tissue activated for a large multisite cohort of patients (n = 66) implanted bilaterally in globus pallidus internus (n = 34) or centromedial thalamus (n = 32) were used to generate probabilistic tractography to form a normative structural connectome. The tractography maps were used to identify networks that were correlated with improvement in tics or comorbid obsessive-compulsive behaviour and to predict clinical outcomes across the cohort. The correlated networks were then used to generate ‘reverse’ tractography to parcellate the total volume of stimulation across all patients to identify local regions to target or avoid. The results showed that for globus pallidus internus, connectivity to limbic networks, associative networks, caudate, thalamus, and cerebellum was positively correlated with improvement in tics; the model predicted clinical improvement scores (P = 0.003) and was robust to cross-validation. Regions near the anteromedial pallidum exhibited higher connectivity to the positively correlated networks than posteroventral pallidum, and volume of tissue activated overlap with this map was significantly correlated with tic improvement (P 0.23). For obsessive-compulsive behaviour, both targets showed that connectivity to the prefrontal cortex, orbitofrontal cortex, and cingulate cortex was positively correlated with improvement; however, only the centromedial thalamus maps predicted clinical outcomes across the cohort (P = 0.034), but the model was not robust to cross-validation. Collectively, the results demonstrate that the structural connectivity of the site of stimulation are likely important for mediating symptom improvement, and the networks involved in tic improvement may differ across surgical targets. These networks provide important insight on potential mechanisms and could be used to guide lead placement and stimulation parameter selection, as well as refine targets for neuromodulation therapies for Tourette syndrome.
Published: 2020
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18. 'Le regard des autres': the experience of walking in social environments as a person with Parkinson's disease

Author: Ross Parry, Olivier Buttelli, Narjis Sellam, Jacques Riff, Marie Vidailhet, Marie-Laure Welter, and Elodie Lalo
Subjects: Public Health, Environmental and Occupational Health, General Medicine, General Chemistry, Applied Psychology
Abstract: To examine the experience of people with Parkinson's disease when walking in different social situations, and improve understanding of how this affects participation in meaningful activity.A convenience sample of fourteen people with Parkinson's disease and a history of gait dysfunction was recruited. In-depth interviews and direct observations were conducted in the participants' home environments. Specific examples from community mobility were reviewed using first person interviewing techniques with the support of video footage. Interview transcripts were analyzed using an interpretive phenomenological approach to derive key themes.The feeling of 'being looked at' (Further to the functional aspects of mobility, gait is important for maintaining self-image in people with Parkinson's disease. Affective gaze interactions have significant consequences upon participation restriction. These findings underscore the interest of activities which strengthen self-image and validate movement diversity in PD rehabilitation.
Published: 2022

19. Pedunculopontine and Cuneiform Nuclei Deep Brain Stimulation for Severe Gait and Balance Disorders in Parkinson's Disease: Interim Results from a Randomized Double-Blind Clinical Trial

Author: Hana You, Yannick Mullie, Claire Olivier, Sara Fernandez-Vidal, Eric Bardinet, Brian Lau, Carine Karachi, Fernando Pérez-García, Julie Bourilhon, Hayat Belaid, Virginie Czernecki, Chantal François, Antoine Collomb-Clerc, David Grabli, and Marie-Laure Welter
Subjects: medicine.medical_specialty, Deep brain stimulation, Parkinson's disease, medicine.medical_treatment, Deep Brain Stimulation, Mesencephalic locomotor region, behavioral disciplines and activities, Cellular and Molecular Neuroscience, Physical medicine and rehabilitation, medicine, Pedunculopontine Tegmental Nucleus, Humans, Gait, Cuneiform, Gait Disorders, Neurologic, business.industry, Balance disorders, Parkinson Disease, medicine.disease, nervous system diseases, Dihydroxyphenylalanine, Clinical trial, surgical procedures, operative, nervous system, Quartile, Neurology (clinical), business, therapeutics
Abstract: Background: Dopa-resistant freezing of gait (FOG) and falls represent the dominant motor disabilities in advanced Parkinson’s disease (PD). Objective: We investigate the effects of deep brain stimulation (DBS) of the mesencephalic locomotor region (MLR), comprised of the pedunculopontine (PPN) and cuneiform (CuN) nuclei, for treating gait and balance disorders, in a randomized double-blind cross-over trial. Methods: Six PD patients with dopa-resistant FOG and/or falls were operated for MLR-DBS. Patients received three DBS conditions, PPN, CuN, or Sham, in a randomized order for 2-months each, followed by an open-label phase. The primary outcome was the change in anteroposterior anticipatory-postural-adjustments (APAs) during gait initiation on a force platform Results: The anteroposterior APAs were not significantly different between the DBS conditions (median displacement [1st–3rd quartile] of 3.07 [3.12–4.62] cm with sham-DBS, 1.95 [2.29–3.85] cm with PPN-DBS and 2.78 [1.66–4.04] cm with CuN-DBS; p = 0.25). Step length and velocity were significantly higher with CuN-DBS vs. both sham-DBS and PPN-DBS. Conversely, step length and velocity were lower with PPN-DBS vs. sham-DBS, with greater double stance and gait initiation durations. One year after surgery, step length was significantly lower with PPN-DBS vs. inclusion. We did not find any significant change in clinical scales between DBS conditions or one year after surgery. Conclusion: Two months of PPN-DBS or CuN-DBS does not effectively improve clinically dopa-resistant gait and balance disorders in PD patients.
Published: 2021

20. Nucleus Basalis of Meynert Stimulation for Lewy Body Dementia: A Phase I Randomized Clinical Trial

Author: Julie Bourilhon, Olivier Godefroy, Luc Defebvre, Didier Hannequin, Romain Lefaucheur, Stéphane Derrey, Stéphane Thobois, Pierre Vera, Jean-Luc Houeto, Kathy Dujardin, André Gillibert, David Wallon, Teodor Danaila, Olivier Martinaud, Pierre Krystkowiak, Marie-Laure Welter, Mathieu Chastan, David Maltête, Equipe Quantification en Imagerie Fonctionnelle (QuantIF-LITIS), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), and Normandie Université (NU)
Subjects: Male, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Deep Brain Stimulation, MESH: Mental Recall, Stimulation, Neuropsychological Tests, Nucleus basalis, law.invention, Lingual gyrus, 0302 clinical medicine, Postoperative Complications, Randomized controlled trial, MESH: Fluorodeoxyglucose F18, law, MESH: Postoperative Complications, MESH: Double-Blind Method, 030212 general & internal medicine, MESH: Treatment Outcome, MESH: Aged, MESH: Middle Aged, Cross-Over Studies, Brain, MESH: Neuropsychological Tests, Middle Aged, MESH: Positron-Emission Tomography, surgical procedures, operative, Implantable Neurostimulators, Treatment Outcome, Anesthesia, Basal Nucleus of Meynert, MESH: Basal Nucleus of Meynert, therapeutics, MESH: Radiopharmaceuticals, Lewy Body Disease, Deep brain stimulation, MESH: Sleep, MESH: Prosthesis Implantation, behavioral disciplines and activities, MESH: Cross-Over Studies, Article, Prosthesis Implantation, MESH: Brain, 03 medical and health sciences, Double-Blind Method, Fluorodeoxyglucose F18, medicine, Dementia, Humans, MESH: Lewy Body Disease, Aged, MESH: Humans, Lewy body, business.industry, medicine.disease, MESH: Male, MESH: Implantable Neurostimulators, nervous system diseases, nervous system, Positron-Emission Tomography, Mental Recall, Neurology (clinical), MESH: Deep Brain Stimulation, Radiopharmaceuticals, business, Sleep, 030217 neurology & neurosurgery, Stroop effect
Abstract: ObjectivesNucleus basalis of Meynert deep brain stimulation (NBM-DBS) has been proposed for patients with dementia. Here, we aim to assess the safety and effects of NBM-DBS in patients with Lewy body dementia (LBD), in a randomized, double-blind, crossover clinical trial.MethodsSix patients with mild to moderate LBD (mean [SD] age, 62.2 [7.8] years) were included, operated on for bilateral NBM-DBS, and assigned to receive either active or sham NBM-DBS followed by the opposite condition for 3 months. The primary outcome was the difference in the total free recalls of the Free and Cued Selective Reminding Test (FCSRT) between active and sham NBM-DBS. Secondary outcomes were assessments of the safety and effects of NBM-DBS on cognition, motor disability, sleep, and PET imaging.ResultsThere was no significant difference in the FCSRT score with active vs sham NBM-DBS. The surgical procedures were well tolerated in all patients, but we observed significant decreases in Stroop and Benton scores after electrode implantation. We observed no significant difference in other scales between active and sham NBM-DBS. With active NBM-DBS relative to baseline, phonemic fluency and motor disability significantly decreased. Lastly, the superior lingual gyrus metabolic activity significantly increased with active NBM-DBS.ConclusionsNBM-DBS does not appear to be totally safe for patients with LBD with no evidence of cognitive benefit.ClinicalTrials.gov IdentifierNCT01340001.Classification of EvidenceThis study provides Class II evidence that, for patients with LBD operated on for bilateral NBM-DBS, active NBM-DBS stimulation compared to sham stimulation did not significantly change selective recall scores.
Published: 2021
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21. Emotions Modulate Subthalamic Nucleus Activity: New Evidence in Obsessive-Compulsive Disorder and Parkinson’s Disease Patients

Author: Luc Mallet, Anne Buot, Sara Fernandez-Vidal, Brian Lau, Carine Karachi, Marie-Laure Welter, Hayat Belaid, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and 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)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Obsessive-Compulsive Disorder, Levodopa, medicine.medical_specialty, Deep brain stimulation, Parkinson's disease, Deep Brain Stimulation, Cognitive Neuroscience, medicine.medical_treatment, Emotions, Stimulus (physiology), Audiology, behavioral disciplines and activities, 050105 experimental psychology, 03 medical and health sciences, 0302 clinical medicine, Subthalamic Nucleus, mental disorders, Basal ganglia, medicine, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, Valence (psychology), Biological Psychiatry, ComputingMilieux_MISCELLANEOUS, business.industry, 05 social sciences, Parkinson Disease, medicine.disease, nervous system diseases, Subthalamic nucleus, Electrophysiology, nervous system, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Background Subthalamic nucleus (STN) deep brain stimulation alleviates obsessive-compulsive disorder (OCD) symptoms, suggesting that this basal ganglia structure may play a key role in integrating limbic and motor information. We explored the modulation of STN neural activity by visual emotional information under different motor demands. Methods We compared STN local field potentials acquired in 7 patients with OCD and 15 patients with Parkinson’s disease off and on levodopa while patients categorized pictures as unpleasant, pleasant, or neutral and pressed a button for 1 of these 3 categories depending on the instruction. Results During image presentation, theta power increased for unpleasant compared with neutral images in both patients with OCD and patients with Parkinson’s disease. Only in patients with OCD was theta power also increased in pleasant compared with neutral trials. During the button press in patients with OCD, no modification of STN activity was seen on average, but theta power increased when the image triggering the motor response was unpleasant. Conversely, in patients with Parkinson’s disease, a beta decrease was observed during the button press unrelated to the valence of the stimulus. Finally, in patients with OCD, a significant positive relationship was observed between the amplitude of the emotionally related theta response and symptom severity (measured using the Yale-Brown Obsessive Compulsive Scale). Conclusions We highlighted modulations of STN theta band activity related to emotions that were specific to OCD and correlated with OCD symptom severity. STN theta-induced activity might therefore underlie dysfunction of the limbic STN and its related network leading to OCD pathophysiology.
Published: 2020
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22. A Causal Role for the Pedunculopontine Nucleus in Human Instrumental Learning

Author: Anne Buot, David Grabli, Carine Karachi, Marie-Laure Welter, Stefano Palminteri, Mathias Pessiglione, Vasilisa Skvortsova, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Neurosciences Cognitives & Computationnelles (LNC2), Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Max Planck UCL Centre for Computational Psychiatry and Ageing Research, London, Service de Neurochirurgie [CHU Pitié-Salpêtrière], 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), HAL-SU, Gestionnaire, 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), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, computational modeling, Male, reinforcement learning, Deep brain stimulation, dopamine Parkinson disease, deep-brain stimulation, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Deep Brain Stimulation, Dopamine, Local field potential, Biology, local field potentials, General Biochemistry, Genetics and Molecular Biology, decision making, Midbrain, 03 medical and health sciences, reward prediction error, 0302 clinical medicine, Reward, medicine, Pedunculopontine Tegmental Nucleus, Reinforcement learning, Humans, Pedunculopontine nucleus, Aged, low-frequency oscillations, Mechanism (biology), Dopaminergic, pedunculopontine nucleus, Parkinson Disease, Middle Aged, [SDV] Life Sciences [q-bio], 030104 developmental biology, Conditioning, Operant, Female, General Agricultural and Biological Sciences, Neuroscience, 030217 neurology & neurosurgery, psychological phenomena and processes, medicine.drug
Abstract: International audience; A critical mechanism for maximizing reward is instrumental learning. In standard instrumental learning models, action values are updated on the basis of reward prediction errors (RPEs), defined as the discrepancy between expectations and outcomes. A wealth of evidence across species and experimental techniques has established that RPEs are signaled by midbrain dopamine neurons. However, the way dopamine neurons receive information about reward outcomes remains poorly understood. Recent animal studies suggest that the pedunculopontine nucleus (PPN), a small brainstem structure considered as a locomotor center, is sensitive to reward and sends excitatory projection to dopaminergic nuclei. Here, we examined the hypothesis that the PPN could contribute to reward learning in humans. To this aim, we leveraged a clinical protocol that assessed the therapeutic impact of PPN deep-brain stimulation (DBS) in three patients with Parkinson disease. PPN local field potentials (LFPs), recorded while patients performed an instrumental learning task, showed a specific response to reward outcomes in a low-frequency (alpha-beta) band. Moreover, PPN DBS selectively improved learning from rewards but not from punishments, a pattern that is typically observed following dopaminergic treatment. Computational analyses indicated that the effect of PPN DBS on instrumental learning was best captured by an increase in subjective reward sensitivity. Taken together, these results support a causal role for PPN-mediated reward signals in human instrumental learning.
Published: 2020
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23. Le Hasard et le Possible, Alim Louis Benabid, Odile Jacob, 2021, 256 pages, 23,90 €

Author: Marie-Laure Welter
Published: 2022
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24. Normal and pathological neuronal distribution of the human mesencephalic locomotor region

Author: Sylvie Dumas, Anne-Sophie Rolland, Brian Lau, Chantal François, Fernando Pérez-García, Antoine Colomb‐Clerc, Carine Karachi, Sophie B. Sébille, Marie-Laure Welter, Sara Fernandez Vidal, Eric Bardinet, and Matthieu Faillot
Subjects: 0301 basic medicine, Deep brain stimulation, Parkinson's disease, Deep Brain Stimulation, medicine.medical_treatment, Biology, Progressive supranuclear palsy, 03 medical and health sciences, Glutamatergic, 0302 clinical medicine, Mesencephalon, Image Processing, Computer-Assisted, Pedunculopontine Tegmental Nucleus, medicine, Humans, Pedunculopontine nucleus, Neurons, Denervation, Parkinson Disease, medicine.disease, 030104 developmental biology, Neurology, GABAergic, Cholinergic, Supranuclear Palsy, Progressive, Neurology (clinical), Neuroscience, 030217 neurology & neurosurgery, Brain Stem
Abstract: Background Deep brain stimulation of the pedunculopontine nucleus has been performed to treat dopamine-resistant gait and balance disorders in patients with degenerative diseases. The outcomes, however, are variable, which may be the result of the lack of a well-defined anatomical target. Objectives The objectives of this study were to identify the main neuronal populations of the pedunculopontine and the cuneiform nuclei that compose the human mesencephalic locomotor region and to compare their 3-dimensional distribution with those found in patients with Parkinson's disease and progressive supranuclear palsy. Methods We used high-field MRI, immunohistochemistry, and in situ hybridization to characterize the distribution of the different cell types, and we developed software to merge all data within a common 3-dimensional space. Results We found that cholinergic, GABAergic, and glutamatergic neurons comprised the main cell types of the mesencephalic locomotor region, with the peak densities of cholinergic and GABAergic neurons similarly located within the rostral pedunculopontine nucleus. Cholinergic and noncholinergic neuronal losses were homogeneous in the mesencephalic locomotor region of patients, with the peak density of remaining neurons at the same location as in controls. The degree of denervation of the pedunculopontine nucleus was highest in patients with progressive supranuclear palsy, followed by Parkinson's disease patients with falls. Conclusions The peak density of cholinergic and GABAergic neurons was located similarly within the rostral pedunculopontine nucleus not only in controls but also in pathological cases. The neuronal loss was homogeneously distributed and highest in the pedunculopontine nucleus of patients with falls, which suggests a potential pathophysiological link. © 2018 International Parkinson and Movement Disorder Society.
Published: 2018
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25. Long‐term GPi‐DBS improves motor features in myoclonus‐dystonia and enhances social adjustment

Author: François Viallet, David Grabli, Elodie Hainque, Marjan Jahanshahi, Cecilia Bonnet, Sophie Rivaud-Péchoux, Stephen Tisch, Soledad Navarro, Zuzana Kosutzka, Carine Karachi, Marta Ruiz, Emmanuel Roze, Marie-Laure Welter, and Marie Vidailhet
Subjects: Adult, Male, 0301 basic medicine, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, Deep brain stimulation, Adolescent, Deep Brain Stimulation, medicine.medical_treatment, Motor Disorders, Time, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Rating scale, Humans, Medicine, Disabled Persons, Aged, Dystonia, business.industry, Middle Aged, medicine.disease, Abnormal involuntary movement, nervous system diseases, Treatment Outcome, 030104 developmental biology, Mood, Neurology, Dystonic Disorders, Physical therapy, Female, Neurology (clinical), Abnormal Involuntary Movement Scale, medicine.symptom, business, Social Adjustment, Myoclonus, 030217 neurology & neurosurgery
Abstract: Background Good short-term results of pallidal deep brain stimulation have been reported in myoclonus-dystonia. Efficacy and safety in the long term remain to be established. In addition, the actual impact of DBS treatment on social inclusion is unknown. The objective of this study was to assess the long-term clinical outcome, quality of life, and social adjustment of GPi-DBS in patients with e-sarcoglycan (DYT11)-positive myoclonus-dystonia. Methods Consecutive myoclonus-dystonia patients with e-sarcoglycan mutations who underwent GPi-DBS were evaluated at least 5 years postoperatively. Motor symptoms were assessed using the Burke-Fahn-Marsden Dystonia Rating Scale including the Disability Scale, a composite score combining the rest and action parts of the Unified Myoclonus Rating Scale and modified Abnormal Involuntary Movement Scale. Standardized video-protocols were assessed by a blinded and external movement disorder specialist. Social adjustment, cognition, and mood were evaluated. Results Nine patients (5 women) with long-term GPi-DBS (8.7 ± 3.1 years) were included. There was significant improvement in the composite myoclonus score (94.1% ± 4% improvement; P = 0.008). Dystonia severity was also markedly improved (71.4% ± 28.33% improvement; P = 0.008) as well as motor disability (88.3% ± 20% improvement; P = 0.008) and abnormal involuntary movement score (71.1% ± 15.0% improvement; P = 0.008). No patients experienced postoperative speech or gait problems or any permanent adverse effects. Eight of the 9 patients had fully enhanced social adjustment and personal achievement, with little or no mood or behavioral disorders. Conclusions GPi-DBS seems to be a safe and efficacious treatment for medically refractory ɛ-sarcoglycan myoclonus-dystonia, with sustained motor benefit, good quality of life, and social adjustment in long-term follow-up. © 2018 International Parkinson and Movement Disorder Society.
Published: 2018
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26. 'The whole perimeter is difficult': Parkinson’s disease and the conscious experience of walking in everyday environments

Author: Jacques Riff, Ross Parry, Elodie Lalo, Olivier Buttelli, Marie Vidailhet, Narjis Sellam, Marie-Laure Welter, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), 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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut des Systèmes Intelligents et de Robotique (ISIR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire pluridisciplinaire de recherche en ingénierie des systèmes, mécanique et énergétique (PRISME), Université d'Orléans (UO)-Institut National des Sciences Appliquées - Centre Val de Loire (INSA CVL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), Université d'Orléans (UO), Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Neuro-Imagerie de Recherche (CENIR), Hôpital Charles Nicolle [Rouen], 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)-Centre National de la Recherche Scientifique (CNRS), 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), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, Interview, medicine.medical_treatment, media_common.quotation_subject, Parkinsonian gait, Poison control, Walking, gait, 050105 experimental psychology, Disability Evaluation, 03 medical and health sciences, 0302 clinical medicine, Perception, Activities of Daily Living, ecological, medicine, Humans, 0501 psychology and cognitive sciences, Mobility Limitation, valence, Valence (psychology), Qualitative Research, Aged, media_common, Rehabilitation, phenomenological analysis, Interpretative phenomenological analysis, 05 social sciences, Neurological Rehabilitation, Parkinson Disease, Middle Aged, Gaze, Self Concept, qualitative, Parkinson’s disease, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, Gait Analysis, Psychology, environment, 030217 neurology & neurosurgery, Cognitive psychology
Abstract: Purpose: This study sought to characterize the way patients with Parkinson’s disease consciously perceive and respond to their surroundings while walking in everyday situations. Method: A qualitative research program designed around an ecological data collection protocol was employed. A convenience sample of 14 patients with a diagnosis of Parkinson’s disease and a history of gait difficulties were recruited. Details regarding patients’ subjective experience of walking in everyday environments were obtained using first person interviewing techniques with the support of video footage from their daily-life activity. Interview transcripts were analyzed using an interpretive phenomenological approach in order to derive key themes. Results: The sense of proximity and the way in which an individual perceived themselves with respect to their surroundings appeared central to the way patients organized their locomotor behavior. Further to this, the patient relationship to different features and obstacles appeared conditioned by prior experiences in those circumstances. Patients described managing gait difficulties by consciously regulating their walking trajectory and gaze with respect to their environment. Conclusion: Perceptual challenges, visual flow and the dynamic valence of features in the patient’s surroundings may have important effects upon the gait stability of patients with Parkinson’s disease and warrant further attention in planning rehabilitation interventions.Implications for rehabilitationWalking abilities of patients with Parkinson’s disease should be conceptualized in terms of perceptuomotor coupling to a given environment.The functional significance of a patient’s environment is dynamic and might be seen to vary in accordance with their physical capacities.Valency, or the subjective relationship between a patient and their surrounds, appears to be an important component of the “fit” between a person and their environment.Novel rehabilitation strategies for the management of parkinsonian gait disturbances might seek to integrate psychological, sensorimotor and environmental elements in order to have individually tailored, ecologically valid home assessment and community rehabilitation programs. Walking abilities of patients with Parkinson’s disease should be conceptualized in terms of perceptuomotor coupling to a given environment. The functional significance of a patient’s environment is dynamic and might be seen to vary in accordance with their physical capacities. Valency, or the subjective relationship between a patient and their surrounds, appears to be an important component of the “fit” between a person and their environment. Novel rehabilitation strategies for the management of parkinsonian gait disturbances might seek to integrate psychological, sensorimotor and environmental elements in order to have individually tailored, ecologically valid home assessment and community rehabilitation programs.
Published: 2018
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27. Long-term effects of anterior pallidal deep brain stimulation for tourette's syndrome

Author: Solène Ansquer, Andreas Hartmann, Yulia Worbe, Luc Mallet, Jean-Luc Houeto, Mamadou Hassimiou Diallo, Stéphane Thobois, Carine Karachi, Tiphaine Rouaud, Marie-Laure Welter, Denys Fontaine, Emmanuel Cuny, and Sophie Tezenas du Montcel
Subjects: Internal globus pallidus, Deep brain stimulation, Neurology, Tics, business.industry, Tourette's syndrome, medicine.medical_treatment, Medicine, Neurology (clinical), business, medicine.disease, Neuroscience, Term (time)
Published: 2019
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28. Anterior pallidal deep brain stimulation for Tourette's syndrome: a randomised, double-blind, controlled trial

Author: Marie-Laure Welter, Jean-Luc Houeto, Stéphane Thobois, Benoit Bataille, Marc Guenot, Yulia Worbe, Andreas Hartmann, Virginie Czernecki, Eric Bardinet, Jerome Yelnik, Sophie Tezenas du Montcel, Yves Agid, Marie Vidailhet, Philippe Cornu, Audrey Tanguy, Solène Ansquer, Nematollah Jaafari, Emmanuel Poulet, Giulia Serra, Pierre Burbaud, Emmanuel Cuny, Bruno Aouizerate, Pierre Pollak, Stephan Chabardes, Mircea Polosan, Michel Borg, Denys Fontaine, Bruno Giordana, Sylvie Raoul, Tiphaine Rouaud, Anne Sauvaget, Isabelle Jalenques, Carine Karachi, Luc Mallet, M.L. Welter, E. Cuny, P. Derkinderen, D. Fontaine, J.L. Houeto, I. Jalenques, L. Mallet, P. Pollak, S. Thobois, A. Bissery, H. Oya, E. Bardinet, J. Yelnik, A. Buot, V. Czernecki, S. Tezenas du Montcel, A. Tanguy, M. Hajji, C. Karachi, A. Hartmann, Y. Agid, Y. Worbe, D. Dormont, M. Vidailhet, P. Cornu, B. Aouizerate, P. Burbaud, F. Durif, C. Fauchon, F. Rondepierre, P. Derost, M. Aya Kombo, M. Polosan, S. Chabardès, A. Krainik, P. Krack, B. Piallat, M. Guenot, E. Poulet, H. Klinger, G. Serra, E. Broussolle, T. Rouaud, A. Sauvaget, P. Damier, S Raoul, M. Borg, B. Giordana, M.-N. Magnie-Mauro, N. Jaafari, B. Bataille, S. Ansquer, I. Benatru, A. Fradet, E. Dugast, A. Ouerdani, E. Rabois, M. Quintin, S. Palfi, Krack, Paul, Pollak, Pierre, Service de Neuroradiologie [CHU Pitié-Salpêtrière], 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), 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), Service de Neurologie, Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de neurologie [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de neurochirurgie fonctionnelle [Hôpital Pierre Wertheimer - HCL], 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service des Maladies du Système Nerveux [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Neuro-Imagerie de Recherche (CENIR), 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), Neurologie et thérapeutique expérimentale, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR70-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de neurologie [Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Ecole de Technologie Supérieure [Montréal] (ETS), Immunologie antivirale systémique et cérébrale, Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie et physiopathologie de la signalisation cellulaire (PPSC), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux]-Centre National de la Recherche Scientifique (CNRS), Hôpital Charles Perrens, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Psychiatrie, CHU Grenoble, Centre Hospitalier Universitaire [Grenoble] (CHU), Laboratoire de Psychologie et NeuroCognition (LPNC ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital Pasteur [Nice] (CHU), Service de neurologie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Centre Mémoire de Ressources et de Recherche [CHU Clermont-Ferrand] (CMRR), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, 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), Service de neurologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Hôpital de La Milétrie, Service de Biostatistiques [Lyon], Hospices Civils de Lyon (HCL), Department of Neurosurgery, Carver College of Medicine [Iowa City], University of Iowa [Iowa City]-University of Iowa [Iowa City], Service de Neurologie [CHU Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, UM des troubles du mouvement, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Neurosciences précliniques, Clinique neurologique, Hôpital Laennec, inconnu, Inconnu, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service d'Explorations Fonctionnelles Neurologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Neurosurgery, Centre de Référence National 'Syndrome Gilles de la Tourette', Pôle des Maladies du Système Nerveux, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique des Hôpitaux de Paris, 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], Station Expérimentale des Procédés Pilotes en Environnement (STEPPE), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM), ANTE-INSERM U836, équipe 11, Fonctions cérébrales et neuromodulation, Clinique de psychiatrie, CHU Grenoble-CHU Grenoble, Réseau d'Etude des Gliomes, REG, Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux - Clermont Auvergne (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), Service de Neurochirurgie [CHU Pitié-Salpêtrière], 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), Transduction du Signal et Plasticite Dans Le Systeme Nerveux, Gaz de France Suez (GDF Suez), CHU Pitié-Salpêtrière [APHP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), 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), Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR70-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux]-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier Charles Perrens [Bordeaux], [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université de Rennes (UR), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Pôle des Maladies du Système Nerveux [CHU Pitié-Salpêtrière] (Pôle MSN), 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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), 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), Service de neurologie [CHU Saint-Antoine], 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], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), 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), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Laboratoire de Psychologie et NeuroCognition (LPNC), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre Mémoire de Ressources et de Recherche [CHU de Clermont-Ferrand], Service de neurologie, and Hôpital Gabriel Montpied
Subjects: Adult, Male, medicine.medical_specialty, Movement disorders, Deep brain stimulation, Deep Brain Stimulation, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Stimulation, Globus Pallidus, Severity of Illness Index, law.invention, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Randomized controlled trial, law, Outcome Assessment, Health Care, Severity of illness, medicine, Clinical endpoint, Humans, Treatment Failure, Young adult, Adverse effect, ComputingMilieux_MISCELLANEOUS, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, musculoskeletal, neural, and ocular physiology, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Middle Aged, nervous system diseases, ddc:616.8, 030227 psychiatry, 3. Good health, Surgery, surgical procedures, operative, nervous system, Anesthesia, Female, Neurology (clinical), medicine.symptom, business, therapeutics, 030217 neurology & neurosurgery, Tourette Syndrome
Abstract: Summary Background Deep brain stimulation (DBS) has been proposed to treat patients with severe Tourette's syndrome, and open-label trials and two small double-blind trials have tested DBS of the posterior and the anterior internal globus pallidus (aGPi). We aimed to specifically assess the efficacy of aGPi DBS for severe Tourette's syndrome. Methods In this randomised, double-blind, controlled trial, we recruited patients aged 18–60 years with severe and medically refractory Tourette's syndrome from eight hospitals specialised in movement disorders in France. Enrolled patients received surgery to implant bilateral electrodes for aGPi DBS; 3 months later they were randomly assigned (1:1 ratio with a block size of eight; computer-generated pairwise randomisation according to order of enrolment) to receive either active or sham stimulation for the subsequent 3 months in a double-blind fashion. All patients then received open-label active stimulation for the subsequent 6 months. Patients and clinicians assessing outcomes were masked to treatment allocation; an unmasked clinician was responsible for stimulation parameter programming, with intensity set below the side-effect threshold. The primary endpoint was difference in Yale Global Tic Severity Scale (YGTSS) score between the beginning and end of the 3 month double-blind period, as assessed with a Mann-Whitney-Wilcoxon test in all randomly allocated patients who received active or sham stimulation during the double-blind period. We assessed safety in all patients who were enrolled and received surgery for aGPi DBS. This trial is registered with ClinicalTrials.gov, number NCT00478842. Findings Between Dec 6, 2007, and Dec 13, 2012, we enrolled 19 patients. We randomly assigned 17 (89%) patients, with 16 completing blinded assessments (seven [44%] in the active stimulation group and nine [56%] in the sham stimulation group). We noted no significant difference in YGTSS score change between the beginning and the end of the 3 month double-blind period between groups (active group median YGTSS score 68·5 [IQR 34·0 to 83·5] at the beginning and 62·5 [51·5 to 72·0] at the end, median change 1·1% [IQR −23·9 to 38·1]; sham group 73·0 [69·0 to 79·0] and 79·0 [59·0 to 81·5], median change 0·0% [–10·6 to 4·8]; p=0·39). 15 serious adverse events (three in patients who withdrew before stimulation and six each in the active and sham stimulation groups) occurred in 13 patients (three who withdrew before randomisation, four in the active group, and six in the sham group), with infections in DBS hardware in four patients (two who withdrew before randomisation, one in the sham stimulation group, and one in the active stimulation group). Other serious adverse events included one electrode misplacement (active stimulation group), one episode of depressive signs (active stimulation group), and three episodes of increased tic severity and anxiety (two in the sham stimulation group and one in the active stimulation group). Interpretation 3 months of aGPi DBS is insufficient to decrease tic severity for patients with Tourette's syndrome. Future research is needed to investigate the efficacy of aGPi DBS for patients over longer periods with optimal stimulation parameters and to identify potential predictors of the therapeutic response. Funding French Ministry of Health.
Published: 2017
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29. Gait analysis using optimality criteria imputed from human data

Author: Adina M. Panchea, Philippe Fraisse, Nacim Ramdani, Olivier Buttelli, Sylvain Miossec, Angèle Van Hamme, Marie-Laure Welter, Laboratoire pluridisciplinaire de recherche en ingénierie des systèmes, mécanique et énergétique (PRISME), Université d'Orléans (UO)-Institut National des Sciences Appliquées - Centre Val de Loire (INSA CVL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), Interactive Digital Humans (IDH), Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier (LIRMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre d'investigation clinique Neurosciences [CHU Pitié Salpêtrière] (CIC Neurosciences), 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), Service de neurologie 1 [CHU Pitié-Salpétrière], 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), ANR-12-TECS-0020,ECOTECH,Technologie innovante pour caractériser les pertes d'équilibre en contexte écologique de vie : application à la maladie de Parkinson(2012), Ramdani, Nacim, Technologie pour la santé et l'autonomie - Technologie innovante pour caractériser les pertes d'équilibre en contexte écologique de vie : application à la maladie de Parkinson - - ECOTECH2012 - ANR-12-TECS-0020 - TecSan - VALID, Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), 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), Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-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), Service de Neurologie [CHU Pitié-Salpêtrière], and IFR70-CHU Pitié-Salpêtrière [AP-HP]
Subjects: 0209 industrial biotechnology, Computer science, Process (engineering), Human walking control, 02 engineering and technology, computer.software_genre, [SPI.AUTO]Engineering Sciences [physics]/Automatic, Modeling for control optimization, 020901 industrial engineering & automation, Gait (human), [SPI.MECA.BIOM] Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], 0202 electrical engineering, electronic engineering, information engineering, Inverse optimal control, business.industry, [SPI.MECA.BIOM]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], Pattern recognition, Optimal control, Gait, Identification (information), Task (computing), Model predictive control, [SPI.AUTO] Engineering Sciences [physics]/Automatic, Optimal control theory, Control and Systems Engineering, Gait analysis, Trajectory and Path Planning, Identification and control methods, 020201 artificial intelligence & image processing, Data mining, Artificial intelligence, business, computer, Humanoid robot
Abstract: International audience; This study proposes an efficient and automatic tool to understand and analyze the human natural and fast gait tasks. First, the gait tasks are modeled as a nonlinear optimal control problem along with a nonlinear model predictive control, usually used in the humanoid robots control. Second, under the assumption that the walking motions are the result of an optimization process, the identification of plausible optimality criteria weight values is achieved with an inverse optimal control (IOC) approach. Our IOC walking scheme is performed on ten subjects with ten trials for each gait task considered. Results show that the variability observed in the experimental data are exhibited by our proposed scheme. Finally, an easy distinguish can be made between the gait tasks only by checking out the exhibited criteria weight values.
Published: 2017
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30. Pedunculopontine network dysfunction in Parkinson's disease with postural control and sleep disorders

Author: Smaranda Leu-Semenescu, Marie-Laure Welter, Marie Vidailhet, Pierre Berroir, Chantal François, Cyril Poupon, Emmanuel Roze, Stéphane Lehéricy, Claire Ewenczyk, David Grabli, Cecile Gallea, Sara Fernandez-Vidal, Bertrand Degos, Habib Benali, Lydia Yahia-Cherif, Romain Valabregue, Eric Bardinet, Eric Bertasi, and Isabelle Arnulf
Subjects: 0301 basic medicine, Sleep disorder, medicine.medical_specialty, Parkinson's disease, Supplementary motor area, Rapid eye movement sleep, medicine.disease, Sleep in non-human animals, Arousal, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, Physical medicine and rehabilitation, Neurology, medicine, Physical therapy, Neurology (clinical), Psychology, 030217 neurology & neurosurgery, Anterior cingulate cortex, Pedunculopontine nucleus
Abstract: Background The objective of this study was to investigate pedunculopontine nucleus network dysfunctions that mediate impaired postural control and sleep disorder in Parkinson's disease. Methods We examined (1) Parkinson's disease patients with impaired postural control and rapid eye movement sleep behavior disorder (further abbreviated as sleep disorder), (2) Parkinson's disease patients with sleep disorder only, (3) Parkinson's disease patients with neither impaired postural control nor sleep disorder, and (4) healthy volunteers. We assessed postural control with clinical scores and biomechanical recordings during gait initiation. Participants had video polysomnography, daytime sleepiness self-evaluation, and resting-state functional MRIs. Results Patients with impaired postural control and sleep disorder had longer duration of anticipatory postural adjustments during gait initiation and decreased functional connectivity between the pedunculopontine nucleus and the supplementary motor area in the locomotor network that correlated negatively with the duration of anticipatory postural adjustments. Both groups of patients with sleep disorder had decreased functional connectivity between the pedunculopontine nucleus and the anterior cingulate cortex in the arousal network that correlated with daytime sleepiness. The degree of dysfunction in the arousal network was related to the degree of connectivity in the locomotor network in all patients with sleep disorder, but not in patients without sleep disorder or healthy volunteers. Conclusions These results shed light on the functional neuroanatomy of pedunculopontine nucleus networks supporting the clinical manifestation and the interdependence between sleep and postural control impairments in Parkinson's disease. © 2016 International Parkinson and Movement Disorder Society
Published: 2017
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31. 'De-novo' consultation: Evaluation of an outpatient's clinic dedicated to early diagnosis of parkinsonian syndromes

Author: Andreas Hartmann, Cécile Hubsch, David Grabli, Louise-Laure Mariani, Pauline Dodet, Jean-Christophe Corvol, Marie Vidailhet, Yulia Worbe, S. Aix, J. Ruggeri, Florence Cormier, A. M. Bonnet, Emmanuel Roze, Marie-Laure Welter, Bertrand Degos, Lucette Lacomblez, Service de Neuroradiologie [CHU Pitié-Salpêtrière], 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 expert inter-régional de coordination de la maladie de Parkinson [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), 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], Service de neuropédiatrie et maladies métaboliques [CHU Robert-Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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 HAL-UPMC, Gestionnaire
Subjects: Adult, Male, Pediatrics, medicine.medical_specialty, Parkinson's disease, Referral, Disease, Ambulatory Care Facilities, Parkinsonian syndrome, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Parkinsonian Disorders, Outpatients, medicine, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Expert center, Young adult, Medical diagnosis, Disease management (health), Referral and Consultation, Aged, Retrospective Studies, Aged, 80 and over, business.industry, Retrospective cohort study, Middle Aged, Early diagnosis, medicine.disease, 3. Good health, Patient care management, Neurology, 030220 oncology & carcinogenesis, Physical therapy, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], France, Neurology (clinical), Differential diagnosis, business, 030217 neurology & neurosurgery
Abstract: International audience; In the absence of specific clinical signs, imaging or biomarkers, the differential diagnosis of degenerative parkinsonian syndromes may be difficult at early stages of the disease. To reduce the risk of misdiagnosis or delayed diagnosis and referral to multiple medical centers at disease onset, easier access to expert centers should be available. To improve the initial care of parkinsonian patients, the Parkinson's disease Expert Center (PEC) at Pitié-Salpêtrière Academic Hospital has set up a specific outpatients clinic with short waiting times dedicated to the diagnosis of early Parkinson's disease and related disorders.MethodsThe PEC setup first identifies requests for diagnostic confirmation of parkinsonian syndromes, then specific outpatients clinic visits are scheduled weekly, with examinations carried out by neurologists at the PEC on a rotating schedule. Data from the first year of the new procedure were analyzed retrospectively through self-administered questionnaires sent to patients seen during this period. The main outcomes were to confirm the ability to keep to short delays for patients’ examinations and to assess patients’ satisfaction with the setup.ResultsBoth study outcomes were achieved. The creation of an outpatients clinic dedicated to the early diagnosis of parkinsonian syndromes allowed shorter delays before the first examination of 5 weeks instead of several months. Keeping to the weekly schedule and limited time taken for each visit was also achieved. Following this initial outpatients visit, diagnosis of a parkinsonian syndrome was clinically confirmed or further specified in 80% of cases. A survey of patients’ satisfaction showed a rate of over 91% in terms of the timing and course of clinical examinations at our PEC.Discussion/ConclusionThis study of our quality-improvement program for Parkinson's disease management has shown that specific consultations with shorter waiting times aiming to allow early specialized assessment of parkinsonian syndromes is beneficial for patients and reduces the risk of delayed diagnoses.
Published: 2017
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32. Deep brain activation patterns involved in virtual gait without and with a doorway: An fMRI study

Author: Carine Karachi, Brian Lau, Mélanie Pélégrini-Issac, Romain Valabregue, Jason Sellers, Cecile Gallea, Pierre Leboucher, Marie-Laure Welter, Véronique Marchal, Eric Bertasi, Eric Bardinet, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), 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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de Neuro-Imagerie de Recherche (CENIR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Plateforme PRISME [Paris], 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)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Service de neurophysiologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de Neurochirurgie [CHU Pitié-Salpêtrière], 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), Research was funded by the 'Investissements d’Avenir' (investing in the future) program ANR-10-IAIHU-06. This work was supported by a grant from the 'Régie Autonome des Transports Parisiens' (RATP) and the grant ANR 'Technologie de la Santé' [N˚ ANR-GUI-AAP-05 ECOTECH]. The contribution of JS was supported by an ATIP-Avenir grant to BL from the Mairie de Paris., 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), Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris] (CENIR), 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], and Bodescot, Myriam
Subjects: Male, Cerebellum, Physiology, Red nucleus, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Deep Brain Stimulation, medicine.medical_treatment, Walking, Basal Ganglia, Diagnostic Radiology, 0302 clinical medicine, Gait (human), Thalamus, Functional Magnetic Resonance Imaging, Basal ganglia, Medicine and Health Sciences, Image Processing, Computer-Assisted, Gait, Cerebral Cortex, Brain Mapping, Multidisciplinary, Radiology and Imaging, 05 social sciences, Brain, Magnetic Resonance Imaging, medicine.anatomical_structure, Medicine, Female, Brainstem, Anatomy, Gait Analysis, Psychology, Locomotion, Research Article, Adult, Deep brain stimulation, Imaging Techniques, Science, Neuroimaging, Research and Analysis Methods, 050105 experimental psychology, Young Adult, 03 medical and health sciences, Diagnostic Medicine, medicine, Humans, 0501 psychology and cognitive sciences, Biological Locomotion, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Biology and Life Sciences, Spinal cord, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Caudate Nucleus, Neuroscience, human activities, 030217 neurology & neurosurgery
Abstract: International audience; The human gait program involves many brain areas such as motor cortices, cerebellum, basal ganglia, brainstem, and spinal cord. The mesencephalic locomotor region (MLR), which contains the pedunculopontine (PPN) and cuneiform (CN) nuclei, is thought to be one of the key supraspinal gait generators. In daily life activities, gait primarily occurs in complex conditions, such as through narrow spaces, or while changing direction or performing motor or cognitive tasks. Here, we aim to explore the activity of these subcortical brain areas while walking through narrow spaces, using functional MRI in healthy volunteers and designing a virtual reality task mimicking walking down a hallway, without and with an open doorway to walk through. As a control, we used a virtual moving walkway in the same environment. Twenty healthy volunteers were scanned. Fifteen subjects were selected for second level analysis based on their ability to activate motor cortices. Using the contrast Gait versus Walkway, we found activated clusters in motor cortices, cerebellum, red nucleus, thalamus, and the left MLR including the CN and PPN. Using the contrast Gait with Doorway versus Walkway with Doorway, we found activated clusters in motor cortices, left putamen, left internal pallidum, left substantia nigra, right subthalamic area, and bilateral MLR involving the CN and PPN. Our results suggest that unobstructed gait involves a motor network including the PPN whereas gait through a narrow space requires the additional participation of basal ganglia and bilateral MLR, which may encode environmental cues to adapt locomotion.
Published: 2019
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33. Cover Image

Author: Guillaume Costentin, Stéphane Derrey, Emmanuel Gérardin, Yohann Cruypeninck, Thibaut Pressat‐Laffouilhere, Youssef Anouar, David Wallon, Floriane Le Goff, Marie‐Laure Welter, and David Maltête
Subjects: Neurology, Radiological and Ultrasound Technology, Radiology, Nuclear Medicine and imaging, Neurology (clinical), Anatomy, Cover Image
Abstract: [Image: see text] COVER ILLUSTRATION 3D reconstruction and axial slices of one subject's brain in MNI 152 space. Tracts involved in verbal fluency which are disrupted along the trajectories of electrodes implanted for subthalamic deep brain stimulation in Parkinson's disease are represented. Blue on 3D reconstruction : Superior Longitudinal Tract, orange : Inferior Longitudinal Tract, green : Arcuate Fasciculus, light blue on axial slice : Anterior Thalamic Radiation and violet : Fronto‐striatal Tract.
Published: 2019
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34. White matter tracts lesions and decline of verbal fluency after deep brain stimulation in Parkinson's disease

Author: David Wallon, Floriane Le Goff, Youssef Anouar, Stéphane Derrey, Guillaume Costentin, Yohann Cruypeninck, Marie-Laure Welter, David Maltête, Emmanuel Gerardin, Thibaut Pressat-Laffouilhere, Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Service de neurochirurgie [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), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Service d'imagerie médicale [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Unité de biostatistiques [CHU Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Différenciation et communication neuronale et neuroendocrine (DC2N), and Service de neurophysiologie [Rouen]
Subjects: Adult, Male, Parkinson's disease, Deep brain stimulation, medicine.medical_treatment, Deep Brain Stimulation, Neuroimaging, 050105 experimental psychology, Lesion, White matter, 03 medical and health sciences, 0302 clinical medicine, Subthalamic Nucleus, Neural Pathways, medicine, Verbal fluency test, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, Cognitive Dysfunction, Inferior longitudinal fasciculus, Research Articles, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Radiological and Ultrasound Technology, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, 05 social sciences, Superior longitudinal fasciculus, Parkinson Disease, Anatomy, Middle Aged, medicine.disease, Magnetic Resonance Imaging, White Matter, Electrodes, Implanted, Subthalamic nucleus, medicine.anatomical_structure, Neurology, nervous system, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: Decline of verbal fluency (VF) performance is one of the most systematically reported neuropsychological adverse effects after subthalamic nucleus deep brain stimulation (STN-DBS). It has been suggested that this worsening of VF may be related to a microlesion due to the electrode trajectories. We describe the disruption of surrounding white matter tracts following electrode implantation in Parkinson's disease (PD) patients with STN-DBS and assess whether damage of fiber pathways is associated with VF impairment after surgery. We retrospectively analyzed 48 PD patients undergoing bilateral STN DBS. The lesion mask along the electrode trajectory transformed into the MNI 152 coordinate system, was compared with white matter tract atlas in Tractotron software, which provides a probability and proportion of fibers disconnection. Combining tract- and atlas-based analysis reveals that the trajectory of the electrodes intersected successively with the frontal aslant tract, anterior segment of arcuate tract, the long segment of arcuate tract, the inferior longitudinal fasciculus, the superior longitudinal fasciculus, the anterior thalamic radiation, and the fronto striatal tract. We found no association between the proportion fiber disconnection and the severity of VF impairment 6 months after surgery. Our findings demonstrated that microstructural injury associated with electrode trajectories involved white matter bundles implicated in VF networks.
Published: 2019
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35. Long-term effects of anterior pallidal deep brain stimulation for Tourette's syndrome

Author: Marie-Laure, Welter, Jean-Luc, Houeto, Yulia, Worbe, Mamadou Hassimiou, Diallo, Andreas, Hartmann, Sophie, Tezenas du Montcel, Solène, Ansquer, Stéphane, Thobois, Denys, Fontaine, Tiphaine, Rouaud, Emmanuel, Cuny, Carine, Karachi, Luc, Mallet, and Mallet, Luc
Subjects: Adult, Male, Deep Brain Stimulation, Tourette's syndrome, Middle Aged, Globus Pallidus, Internal globus pallidus, Young Adult, ddc:616.89, Treatment Outcome, Deep brain stimulation, Tics, Humans, Female, Tourette Syndrome
Published: 2019

36. Axial symptoms predict mortality in patients with Parkinson disease with subthalamic stimulation

Author: Giulia Serra, Philippe Cornu, David Grabli, Marie-Laure Welter, Michael Schuepbach, Yves Agid, Carine Karachi, Niklaus Meier, Virginie Czernecki, Soledad Navarro, Brian Lau, Marie Vidailhet, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurophysiologie [CHU Pitié-Salpêtrière], 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), Gestionnaire, Hal Sorbonne Université, 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), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, medicine.medical_specialty, Levodopa, Deep Brain Stimulation, 610 Medicine & health, Disease, Article, Antiparkinson Agents, Disability Evaluation, 03 medical and health sciences, 0302 clinical medicine, Subthalamic Nucleus, Dopamine, Internal medicine, Humans, Medicine, In patient, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Longitudinal Studies, 030212 general & internal medicine, Axial symptoms, business.industry, Hazard ratio, Dopaminergic, Parkinson Disease, Middle Aged, Prognosis, 3. Good health, nervous system diseases, surgical procedures, operative, nervous system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Subthalamic stimulation, Disease Progression, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), business, 030217 neurology & neurosurgery, Follow-Up Studies, medicine.drug
Abstract: ObjectiveTo characterize how disease progression is associated with mortality in a large cohort of patients with Parkinson disease (PD) with long-term follow-up after subthalamic nucleus deep brain stimulation (STN-DBS).MethodsMotor and cognitive disabilities were assessed before and 1, 2, 5, and 10 years after STN-DBS in 143 consecutive patients with PD. We measured motor symptoms “off” and “on” levodopa and STN-DBS and recorded causes of death. We used linear mixed models to characterize symptom progression, including interactions between treatment conditions and time to determine how treatments changed efficacy. We used joint models to link symptom progression to mortality.ResultsMedian observation time was 12 years after surgery, during which akinesia, rigidity, and axial symptoms worsened, with mean increases of 8.8 (SD 6.5), 1.8 (3.1), and 5.4 (4.1) points from year 1–10 after surgery (“on” dopamine/“on” STN-DBS), respectively. Responses to dopaminergic medication and STN-DBS were attenuated with time, but remained effective for all except axial symptoms, for which both treatments and their combination were predicted to be ineffective 20 years after surgery. Cognitive status significantly declined. Forty-one patients died, with a median time to death of 9 years after surgery. The current level of axial disability was the only symptom that significantly predicted death (hazard ratio 4.30 [SE 1.50] per unit of square-root transformed axial score).ConclusionsWe quantified long-term symptom progression and attenuation of dopaminergic medication and STN-DBS treatment efficacy in patients with PD and linked symptom progression to mortality. Axial disability significantly predicts individual risk of death after surgery, which may be useful for planning therapeutic strategies in PD.
Published: 2019
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37. Computational Dissection of Dopamine Motor and Motivational Functions in Humans

Author: Bertrand Degos, Raphaël Le Bouc, Lionel Rigoux, Marie Vidailhet, Jean Daunizeau, Liane Schmidt, Marie-Laure Welter, and Mathias Pessiglione
Subjects: Male, 0301 basic medicine, Economic decision making, Parkinson's disease, Dopamine Agents, Hypokinesia, Disease, Choice Behavior, Models, Biological, 03 medical and health sciences, 0302 clinical medicine, Reward, Reward sensitivity, Dopamine, medicine, Humans, Computer Simulation, Apathy, Motivation, General Neuroscience, Dopaminergic, Motor control, Bayes Theorem, Parkinson Disease, Articles, Middle Aged, medicine.disease, 030104 developmental biology, Female, medicine.symptom, Psychology, Neuroscience, 030217 neurology & neurosurgery, medicine.drug
Abstract: Motor dysfunction (e.g., bradykinesia) and motivational deficit (i.e., apathy) are hallmarks of Parkinson9s disease (PD). Yet, it remains unclear whether these two symptoms arise from a same dopaminergic dysfunction. Here, we develop a computational model that articulates motor control to economic decision theory, to dissect the motor and motivational functions of dopamine in humans. This model can capture different aspects of the behavior: choice (which action is selected) and vigor (action speed and intensity). It was used to characterize the behavior of 24 PD patients, tested both when medicated and unmedicated, in two behavioral tasks: an incentive motivation task that involved producing a physical effort, knowing that it would be multiplied by reward level to calculate the payoff, and a binary choice task that involved choosing between high reward/high effort and low reward/low effort options. Model-free analyses in both tasks showed the same two effects when comparing unmedicated patients to medicated patients: dopamine depletion (1) decreased the amount of effort that patients were willing to produce for a given reward and (2) slowed down the production of this effort, regardless of reward level. Model-based analyses captured these effects with two independent parameters, namely reward sensitivity and motor activation rate. These two parameters were respectively predictive of medication effects on clinical measures of apathy and motor dysfunction. More generally, we suggest that such computational phenotyping might help characterizing deficits and refining treatments in neuropsychiatric disorders. SIGNIFICANCE STATEMENT Many neurological conditions are characterized by motor and motivational deficits, which both result in reduced behavior. It remains extremely difficult to disentangle whether these patients are simply unable or do not want to produce a behavior. Here, we propose a model-based analysis of the behavior produced in tasks that involve trading physical efforts for monetary rewards, to quantify parameters that capture motor dynamics as well as sensitivity to reward, effort, and fatigue. Applied to Parkinson9s disease, this computational analysis revealed two independent effects of dopamine enhancers, which predicted clinical improvement in motor and motivational deficits. Such computational profiling might provide a useful explanatory level, between neural dysfunction and clinical manifestations, for characterizing neuropsychiatric disorders and personalizing treatments.
Published: 2016
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38. Extrapyramidal deficits in ALS: a combined biomechanical and neuroimaging study

Author: Eya Mseddi, Vincent Meininger, Eric Bardinet, Pierre-François Pradat, Gaëlle Bruneteau, Daniel Delgadillo, Marie-Laure Welter, Maryse Feron, Nadine Le Forestier, Malek Abidi, Maria del Mar Amador, Annabelle Couillandre, Rabab Debs, Nicolas Termoz, Lucette Lacomblez, Giovanni de Marco, Peter Bede, François Salachas, Giorgia Querin, Mélanie Pélégrini-Issac, Timothée Lenglet, Centre de Recherche sur le Sport et le Mouvement (CeRSM), Université Paris Nanterre (UPN), Centre de Neuro-Imagerie de Recherche (CENIR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de neurologie 2 [CHU Pitié-Salpêtrière], Service des Maladies du Système Nerveux [CHU Pitié-Salpêtrière], Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), 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), Service de neurologie 1 [CHU Pitié-Salpétrière], Fédération des Maladies du Système Nerveux, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut d'imagerie neurofonctionnelle (IIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure des Télécommunications (ENST)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-École des hautes études en sciences sociales (EHESS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris-Sud - Paris 11 (UP11)-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), Pôle des Maladies du Système Nerveux [CHU Pitié-Salpêtrière] (Pôle MSN), 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), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École des hautes études en sciences sociales (EHESS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Ecole Nationale Supérieure des Télécommunications (ENST)-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)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (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), 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), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Laboratoire d'Imagerie Biomédicale [Paris] (LIB)
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, Neurology, Context (language use), Neuroimaging, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Magnetic resonance imaging, Basal ganglia, medicine, Cerebellar Degeneration, Humans, Prospective Studies, Amyotrophic lateral sclerosis, Gray Matter, myotrophic lateral sclerosis, Postural Balance, Postural instability, Gait Disorders, Neurologic, Gait impairment, Aged, business.industry, Amyotrophic Lateral Sclerosis, Middle Aged, medicine.disease, Gait, Biomechanical Phenomena, 030104 developmental biology, Gait analysis, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: International audience; Introduction Extrapyramidal deficits are poorly characterised in amyotrophic lateral sclerosis (ALS) despite their contribu-tion to functional disability, increased fall risk and their quality-of-life implications. Given the concomitant pyramidal and cerebellar degeneration in ALS, the clinical assessment of extrapyramidal features is particularly challenging.Objective The comprehensive characterisation of postural instability in ALS using standardised clinical assessments, gait analyses and computational neuroimaging tools in a prospective study design.Methods Parameters of gait initiation in the anticipatory postural adjustment phase (APA) and execution phase (EP) were evaluated in ALS patients with and without postural instability and healthy controls. Clinical and gait analysis parameters were interpreted in the context of brain imaging findings.Results ALS patients with postural instability exhibit impaired gait initiation with an altered APA phase, poor dynamic postural control and significantly decreased braking index. Consistent with their clinical profile, “unsteady” ALS patients have reduced caudate and brain stem volumes compared to “steady” ALS patients.Interpretation Our findings highlight that the ALS functional rating scale (ALSFRS-r) does not account for extrapyramidal deficits, which are major contributors to gait impairment in a subset of ALS patients. Basal ganglia degeneration in ALS does not only contribute to cognitive and behavioural deficits, but also adds to the heterogeneity of motor disability
Published: 2018
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39. Clinical and anatomical predictors for freezing of gait and falls after subthalamic deep brain stimulation in Parkinson's disease patients

Author: Eric Bardinet, Brian Lau, Florence Cormier-Dequaire, Soledad Navarro, Hayat Belaid, Marie-Laure Welter, Marie Vidailhet, S. Fernandez-Vidal, David Grabli, Carine Karachi, 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), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), 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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de neurophysiologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)
Subjects: 0301 basic medicine, Adult, Male, medicine.medical_specialty, Parkinson's disease, Deep brain stimulation, genetic structures, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Deep Brain Stimulation, Dopamine, Grey matter, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Atrophy, Subthalamic Nucleus, medicine, Humans, Effects of sleep deprivation on cognitive performance, Gait, Gait Disorders, Neurologic, Aged, business.industry, Putamen, Parkinson Disease, Middle Aged, medicine.disease, nervous system diseases, 3. Good health, Subthalamic nucleus, surgical procedures, operative, 030104 developmental biology, medicine.anatomical_structure, nervous system, Neurology, Accidental Falls, Female, Neurology (clinical), Geriatrics and Gerontology, business, therapeutics, 030217 neurology & neurosurgery
Abstract: Introduction Freezing of gait (FOG) and falls are the most disabling motor symptoms in Parkinson's disease (PD) patients. The effects of subthalamic deep-brain-stimulation (STN-DBS) on FOG and falls are still a matter of controversy, and factors contributing to their outcome have yet to be defined. Methods We examined the relationship between FOG and falls after STN-DBS and preoperative clinical features, MRI voxel-based-morphometry (VBM) analysis and statistical mapping of electrode locations. Results 331 patients (age at surgery = 57.7 ± 8.4 years; disease duration = 12.5 ± 5 years) were included in the final analysis, with VBM analysis in 151 patients. After surgery, FOG was aggravated in 93 patients and falls in 75 patients. After surgery, FOG severity was related to its level before surgery without dopaminergic treatment, the dopaminergic treatment dosage and severity of motor fluctuations after surgery; and falls severity to lower postoperative cognitive performance. VBM analyses revealed that, relative to other patient groups, patients with FOG worsening had putamen grey matter density decrease, and fallers patients a left postcentral gyrus atrophy. The best effects of STN-DBS on FOG and falls were associated with the location of contacts within the STN, but no specific location related to aggravation. Conclusions FOG and falls are reduced after STN-DBS in about 1/3 of patients, with the best effects obtained for electrodes located within the STN. Clinicians should be aware that, after STN-DBS, FOG severity is related to preoperative FOG severity whatever its dopa-sensitivity; and falls to lower postoperative cognitive performance; and atrophy of cortico-subcortical brain areas.
Published: 2018
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40. Does Bilateral Deep Brain Stimulation of the Subthalamic Nucleus Modify Ano-Rectal Motility in Parkinson's Disease? Results of a Randomized Cross-Over Study

Author: David Maltête, Guillaume Gourcerol, Stéphane Derrey, Marie-Laure Welter, Anne Marie Leroi, Nathalie Chastan, Service de physiologie digestive, urinaire, respiratoire et de l'exercice [CHU Rouen], Hôpital Charles Nicolle [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)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Service de neurologie [Rouen], CHU Rouen, Service de neurophysiologie [Rouen], Mobilités : Vieillissement, Pathologie, Santé (COMETE), Université de Caen Normandie (UNICAEN), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), 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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neurochirurgie [CHU Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Caen Normandie (UNICAEN), and 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)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, medicine.medical_specialty, Constipation, Deep brain stimulation, Parkinson's disease, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Deep Brain Stimulation, Urology, [SHS.PSY]Humanities and Social Sciences/Psychology, Anal Canal, Proof of Concept Study, Dyssynergia, 03 medical and health sciences, 0302 clinical medicine, Subthalamic Nucleus, medicine, Humans, ComputingMilieux_MISCELLANEOUS, Aged, Cross-Over Studies, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, Rectum, Parkinson Disease, General Medicine, Middle Aged, medicine.disease, Crossover study, nervous system diseases, Subthalamic nucleus, surgical procedures, operative, Anesthesiology and Pain Medicine, nervous system, Neurology, Reflex, Defecation, Female, Neurology (clinical), medicine.symptom, business, Gastrointestinal Motility, therapeutics, 030217 neurology & neurosurgery
Abstract: Background Ano-rectal motility impairment is often observed during Parkinson's disease (PD), generating symptoms as constipation and/or incontinence with impaired quality of life. Subthalamic nuclei (STN) deep brain stimulation (DBS) improves motor symptoms of PD, but its effects on anorectal motility are unknown. This study aimed to assess the effects of STN-DBS on the anorectal motility in PD patients, in a randomized cross-over study. Methods Sixteen PD patients with bilateral STN-DBS for at least 6 months were included. The anal resting pressure, duration and maximal amplitude of squeeze effort, recto-anal inhibitory reflex, maximal tolerable rectal volume, and anal pressure during defecation effort were measured and compared after STN-DBS was switched OFF and then ON for 2 hours, or vice-versa, in a randomized order. Key results STN-DBS increased maximal amplitude of anal squeezing pressure (OFF: 85.7 ± 14.5 vs ON: 108.4 ± 21.0 cmH2 O; P = 0.02), with no significant difference in the duration (P = 0.10). No other significant difference was found between stimulation conditions (OFF vs ON) for anal resting pressure (OFF: 72.5 ± 8.6 cmH2 O vs ON: 71.7 ± 9.0 cmH2 O; P = 0.24), recto-anal inhibitory reflex, maximal tolerable rectal volume (OFF: 231 ± 24 mL vs ON: 241 ± 26 mL; P = 0.68), or anal pressure during defecation effort with a similar rate of ano-rectal dyssynergia (7/16 and 8/16 with and without STN-DBS, respectively). No order effect (ON-OFF vs OFF-ON) was observed. Conclusion and inferences STN-DBS increased anal squeezing pressure, but did not modify anorectal dyssynergia in PD patients, This study demonstrated the involvement of STN in the voluntary control of anorectal motility in PD patients.
Published: 2018
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41. Post mortem high resolution diffusion MRI for large specimen imaging at 11.7 T with 3D segmented echo-planar imaging

Author: Sophie B. Sébille, Eric Bardinet, Mathieu Santin, Anne-Sophie Rolland, and Marie-Laure Welter
Subjects: 0301 basic medicine, Male, Computer science, Noise reduction, High resolution, Contrast Media, Signal-To-Noise Ratio, 03 medical and health sciences, 0302 clinical medicine, Imaging, Three-Dimensional, Animals, Diffusion Tractography, Diffusion (business), Image resolution, Large specimen, Echo-Planar Imaging, General Neuroscience, Brain, Image Enhancement, Macaca fascicularis, 030104 developmental biology, Diffusion Magnetic Resonance Imaging, Autopsy, 030217 neurology & neurosurgery, Biomedical engineering, Diffusion MRI, Tractography
Abstract: Background: Diffusion weighted imaging (DWI) is the only in vivo technique allowing for the mapping of tissue fiber architecture. Post mortem DWI is an increasingly popular method, since longer acquisition times (compared to in vivo) allow higher spatial and angular resolutions to be achieved. However, DWI protocols must be adapted to post mortem tissue (e.g., tuning acquisition parameters to account for changes in T1/T2). New method: In this work, we developed a framework to obtain high quality diffusion weighted images on post mortem large samples by using a combination of fast imaging with 3D diffusion-weighted segmented EPI (3D-DW seg-EPI), Gadolinium soaking and data denoising. Analyses including tractography were used to check the quality of the acquired data, including a comparison with 3D-DW SE acquisitions. Comparison with existing method: Effects on diffusion data of each of the components of the framework were tested: 3D-DW seg-EPI versus 3D-DW SE EPI; with and without data denoising; with and without Gd-soaking. Conclusions: Our study demonstrated the feasibility of analysing anatomical connectivity using diffusion imaging of a post mortem macaque brain with a 3D-DW seg-EPI sequence acquired at ultra-high field. The combination of high angular and spatial resolution DWI with Gd-soaking and denoising provided data allowing us to perform diffusion tractography with results very similar to those obtained with a 3D-DW SE acquisition (with shorter acquisition times: 222 h versus 37 h for 3D-DW seg-EPI).
Published: 2018

42. The feasibility and positive effects of a customised videogame rehabilitation programme for freezing of gait and falls in Parkinson’s disease patients: a pilot study

Author: Angèle Van Hamme, Dijana Nuic, Marie-Laure Welter, Pierre Foulon, Carine Karachi, and Maria Vinti
Subjects: Male, 030506 rehabilitation, medicine.medical_specialty, Deep brain stimulation, Parkinson's disease, Neurology, medicine.medical_treatment, Videogame, Poison control, Health Informatics, Pilot Projects, lcsh:RC321-571, 03 medical and health sciences, 0302 clinical medicine, Gait (human), Physical medicine and rehabilitation, Quality of life, medicine, Humans, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Postural Balance, Gait Disorders, Neurologic, Aged, Rehabilitation, Freezing of gait, business.industry, Research, Parkinson Disease, Middle Aged, medicine.disease, Trunk, Exercise Therapy, Video Games, Parkinson’s disease, Feasibility Studies, Falls, Accidental Falls, Female, 0305 other medical science, business, 030217 neurology & neurosurgery
Abstract: Background Freezing of gait and falls represent a major burden in patients with advanced forms of Parkinson’s disease (PD). These axial motor signs are not fully alleviated by drug treatment or deep-brain stimulation. Recently, virtual reality has emerged as a rehabilitation option for these patients. In this pilot study, we aim to determine the feasibility and acceptability of rehabilitation with a customised videogame to treat gait and balance disorders in PD patients, and assess its effects on these disabling motor signs. Methods We developed a customised videogame displayed on a screen using the Kinect system. To play, the patient had to perform large amplitude and fast movements of all four limbs, pelvis and trunk, in response to visual and auditory cueing, to displace an avatar to collect coins and avoid obstacles to gain points. We tested ten patients with advanced forms of PD (median disease duration = 16.5 years) suffering from freezing of gait and/or falls (Hoehn&Yahr score ≥ 3) resistant to antiparkinsonian treatment and deep brain stimulation. Patients performed 18 training sessions during a 6–9 week period. We measured the feasibility and acceptability of our rehabilitation programme and its effects on parkinsonian disability, gait and balance disorders (with clinical scales and kinematics recordings), positive and negative affects, and quality of life, after the 9th and 18th training sessions and 3 months later. Results All patients completed the 18 training sessions with high feasibility, acceptability and satisfaction scores. After training, the freezing-of-gait questionnaire, gait-and-balance scale and axial score significantly decreased by 39, 38 and 41%, respectively, and the activity-balance confidence scale increased by 35%. Kinematic gait parameters also significantly improved with increased step length and gait velocity and decreased double-stance time. Three months after the final session, no significant change persisted except decreased axial score and increased step length and velocity. Conclusions This study suggests that rehabilitation with a customised videogame to treat gait and balance disorders is feasible, well accepted, and effective in parkinsonian patients. These data serve as preliminary evidence for further larger and controlled studies to propose this customised videogame rehabilitation programme at home. Trial registration ClinicalTrials.gov NCT02469350.
Published: 2018

43. Efficacy and Safety of Deep Brain Stimulation in Tourette Syndrome: The International Tourette Syndrome Deep Brain Stimulation Public Database and Registry

Author: James F. Leckman, Sarah Elizabeth Zauber, Linda Ackermans, J. L. Houeto, Wei Hu, Zoltan Mari, Eileen M. Joyce, Fangang Meng, Terry Coyne, Michael S. Okun, Andres M. Lozano, Suketu M. Khandhar, Veerle Visser-Vandewalle, Alon Y. Mogilner, Harrison C. Walker, Erin H. Monari, Marie-Laure Welter, Michael H. Pourfar, Zinovia Kefalopoulou, Takanobu Kaido, Daniel Huys, Man Auyeung, Ludvic Zrinzo, Kelly D. Foote, Joohi Jimenez-Shahed, Aysegul Gunduz, Peter A. Silburn, Jian-Guo Zhang, Bryan T. Klassen, Jens Kuhn, Benjamin L. Walter, Elena Moro, Jill L. Ostrem, Domenico Servello, Daniel Martinez-Ramirez, Luc Mallet, Kyle Rizer, Barbara Changizi, Marwan Hariz, Carine Karachi, Yasin Temel, Mauro Porta, William S. Anderson, Juan Carlos Baldermann, Lauren E. Schrock, Robert E. Gross, Wissam Deeb, Thomas Foltynie, Irene A. Malaty, MUMC+: MA Med Staf Spec Neurochirurgie (9), RS: MHeNs - R3 - Neuroscience, and Neurochirurgie
Subjects: 0301 basic medicine, Male, Pediatrics, Neurology, Databases, Factual, Deep Brain Stimulation, medicine.medical_treatment, International Cooperation, Tourette syndrome, Severity of Illness Index, RECOMMENDATIONS, Cohort Studies, ddc:616.89, 0302 clinical medicine, Tourette Syndrome/therapy, Thalamus, PARKINSONS-DISEASE, Medicine, Single-Blind Method, Registries, Young adult, Globus Pallidus/physiology, Original Investigation, Middle Aged, surgical procedures, operative, Treatment Outcome, Female, therapeutics, Cohort study, Thalamus/physiology, Adult, medicine.medical_specialty, Deep brain stimulation, Adolescent, MEDLINE, Globus Pallidus, behavioral disciplines and activities, 03 medical and health sciences, Databases, Young Adult, Deep Brain Stimulation/methods, Severity of illness, Factual/statistics & numerical data, Humans, ddc:613, business.industry, medicine.disease, nervous system diseases, Institutional repository, 030104 developmental biology, nervous system, Neurology (clinical), business, 030217 neurology & neurosurgery, Tourette Syndrome
Abstract: IMPORTANCE Collective evidence has strongly suggested that deep brain stimulation (DBS) is a promising therapy for Tourette syndrome. OBJECTIVE To assess the efficacy and safety of DBS in a multinational cohort of patients with Tourette syndrome. DESIGN, SETTING, AND PARTICIPANTS The prospective International Deep Brain Stimulation Database and Registry included 185 patients with medically refractory Tourette syndrome who underwent DBS implantation from January 1, 2012, to December 31, 2016, at 31 institutions in 10 countries worldwide. EXPOSURES Patients with medically refractory symptoms received DBS implantation in the centromedian thalamic region (93 of 163 [57.1%]), the anterior globus pallidus internus (41 of 163 [25.2%]), the posterior globus pallidus internus (25 of 163 [15.3%]), and the anterior limb of the internal capsule (4 of 163 [2.5%]). MAINOUTCOMES AND MEASURES Scores on the Yale Global Tic Severity Scale and adverse events. RESULTS The International Deep Brain Stimulation Database and Registry enrolled 185 patients (of 171 with available data, 37 females and 134 males; mean [SD] age at surgery, 29.1 [10.8] years [range, 13-58 years]). Symptoms of obsessive-compulsive disorder were present in 97 of 151 patients (64.2%) and 32 of 148 (21.6%) had a history of self-injurious behavior. The mean (SD) total Yale Global Tic Severity Scale score improved from 75.01 (18.36) at baseline to 41.19 (20.00) at 1 year after DBS implantation (P
Published: 2018

44. Beta burst coupling across the motor circuit in Parkinson's disease

Author: Marie-Laure Welter, Yann Duclos, Jean Régis, Petra Fischer, Romain Carron, Alexandre Eusebio, Wim Vandenberghe, Tatiana Witjas, Flavie Torrecillos, Jean-Philippe Azulay, Alek Pogosyan, Huiling Tan, Peter Brown, Carine Karachi, Bart Nuttin, and Gerd Tinkhauser
Subjects: Male, 0301 basic medicine, medicine.medical_treatment, Parkinson's disease, Local field potential, Electroencephalography, Basal Ganglia, 0302 clinical medicine, BASAL GANGLIA, Basal ganglia, Basal ganglia-cortical network, Beta bursts, Beta Rhythm, 610 Medicine & health, Beta oscillations, Physics, GLOBUS-PALLIDUS, Local field potentials, medicine.diagnostic_test, Motor Cortex, Parkinson Disease, Middle Aged, LOCAL-FIELD POTENTIALS, Subthalamic nucleus, medicine.anatomical_structure, Neurology, SYNCHRONIZATION, MONKEYS, Female, Life Sciences & Biomedicine, Motor cortex, DEEP BRAIN-STIMULATION, Deep brain stimulation, Article, lcsh:RC321-571, 03 medical and health sciences, MOVEMENT, Subthalamic Nucleus, medicine, Humans, OSCILLATORY ACTIVITY, Beta (finance), lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Aged, HUMAN SUBTHALAMIC NUCLEUS, Science & Technology, Neurosciences, 030104 developmental biology, Neurosciences & Neurology, Nerve Net, SENSORIMOTOR CORTEX, Neuroscience, 030217 neurology & neurosurgery
Abstract: Exaggerated activity in the beta band (13-35 Hz) is a hallmark of basal ganglia signals in patients with Parkinson's disease (PD). Beta activity however is not constantly elevated, but comes in bursts. In previous work we showed that the longer beta bursts are maintained, the more the oscillatory synchronisation within the subthalamic nucleus (STN) increases, which is posited to limit the information coding capacity of local circuits. Accordingly, a higher incidence of longer bursts correlates positively with clinical impairment, while the opposite is true for short, more physiological bursts. Here, we test the hypothesis that beta bursts not only indicate local synchronisation within the STN, but also phasic coupling across the motor network and hence entail an even greater restriction of information coding capacity in patients with PD. Local field potentials from the subthalamic nucleus and EEG over the motor cortex area were recorded in nine PD patients after temporary lead externalization after surgery for deep brain stimulation and overnight withdrawal of levodopa. Beta bursts were defined as periods exceeding the 75th percentile of signal amplitude and the coupling between bursts was considered using two distinct measurements, first the % overlapping (%OVL) as a feature of the amplitude coupling and secondly the phase synchrony index (PSI) to measure the phase coupling between regions. %OVL between STN and cortex and between the left and the right STN was higher than expected between the regions than if they had been independent. Similarly, PSI was higher during bursts as opposed to non-bursts periods. In addition, %OVL was greater for long compared to short bursts. Our results support the hypothesis that beta bursts involve long-range coupling between structures in the basal ganglia-cortical network. The impact of this is greater during long as opposed to short duration beta bursts. Accordingly, we posit that episodes of simultaneously elevated coupling across multiple structures in the basal ganglia-cortical circuit further limit information coding capacity and may have further impact upon motor impairment. ispartof: NEUROBIOLOGY OF DISEASE vol:117 pages:217-225 ispartof: location:United States status: published
Published: 2018
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45. Rôle du contrôle inhibiteur dans les troubles de l’initiation de la marche chez les patients avec maladie de Parkinson

Author: Marie-Laure Welter, Déborah Ziri, Nathalie George, Laurent Hugueville, Claire Olivier, Carine Karachi, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and 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)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, [SCCO.NEUR]Cognitive science/Neuroscience, 05 social sciences, General Medicine, 050105 experimental psychology, 03 medical and health sciences, 0302 clinical medicine, Neurology, Physiology (medical), [SCCO.PSYC]Cognitive science/Psychology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 0501 psychology and cognitive sciences, Neurology (clinical), ComputingMilieux_MISCELLANEOUS, 030217 neurology & neurosurgery
Abstract: Introduction Les troubles de l’initiation du pas, en particulier le freezing de la marche, sont frequents chez les patients avec maladie de Parkinson. Une exageration des processus inhibiteurs mis en jeu lors de contextes incertains participerait a la survenue de ce trouble. Les reseaux neuronaux impliques et leur dysfonctionnement au cours de la maladie de Parkinson restent toutefois mal connus. L’objectif est alors d’etudier l’activite cerebrale cortico-subthalamique lors de l’inhibition de l’action pendant l’initiation du pas chez des sujets sains et des patients parkinsoniens. Materiel et methodes L’activite cerebrale des sujets sains et des patients avec MPI candidats a la stimulation cerebrale profonde du NST (SCP-NST) est enregistree par EEG haut champ lors de l’initiation du pas pendant une tâche modifiee de Go/NoGo. Sur une plateforme de force, permettant de mesurer les temps de reaction et les performances locomotrices et posturales, le sujet initie la marche en fonction d’un indice visuel soit systematiquement (Go certain) soit dependamment de la couleur de l’indice (Go incertain). Chez les patients, l’activite du NST par potentiels de champ locaux est enregistree, ainsi que les effets du traitement dopaminergique et de la SCP-NST. Resultats Actuellement, 3 sujets sains et 3 patients operes de SCP-NST montrent une augmentation du temps de reaction lors des essais de Go incertain vs Go certain et des modifications des activites theta-alpha precedant l’initiation du pas chez les volontaires sains. Chez les patients, le temps de reaction est reduit apres traitement dopaminergique et avec la SCP-NST, en comparaison de la condition sans traitement. Discussion/conclusion Ces donnees preliminaires sont en accord avec l’hypothese de processus d’inhibition proactive, precedant l’initiation du pas, impliquant potentiellement le NST dans la levee de l’inhibition motrice.
Published: 2019
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46. Deep brain stimulation of the internal pallidum in Huntington’s disease patients: clinical outcome and neuronal firing patterns

Author: Jérôme Yelnik, Marie-Laure Welter, Brian Lau, Cécile Delorme, Carine Karachi, Alister Rogers, David Grabli, Alexandra Durr, Hélène Francisque, and Sara Fernandez Vidal
Subjects: Adult, Male, 0301 basic medicine, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, Neurology, Deep brain stimulation, Deep Brain Stimulation, medicine.medical_treatment, Motor Activity, Globus Pallidus, 03 medical and health sciences, Dysarthria, 0302 clinical medicine, Huntington's disease, mental disorders, medicine, Humans, Adverse effect, Chorea, Middle Aged, medicine.disease, humanities, nervous system diseases, Huntington Disease, Treatment Outcome, 030104 developmental biology, Globus pallidus, nervous system, Tolerability, Anesthesia, Physical therapy, Female, Neurology (clinical), medicine.symptom, Psychology, 030217 neurology & neurosurgery
Abstract: Deep brain stimulation (DBS) of the internal globus pallidus (GPi) could treat chorea in Huntington's disease patients. The objectives of this study were to evaluate the efficacy of GPi-DBS to reduce abnormal movements of three patients with Huntington's disease and assess tolerability. Three non-demented patients with severe pharmacoresistant chorea underwent bilateral GPi-DBS and were followed for 30, 24, and 12 months, respectively. Primary outcome measure was the change of the chorea and total motor scores of the Unified Huntington's Disease Rating Scale between pre- and last postoperative assessments. Secondary outcome measures were motor changes between ventral versus dorsal and between on- and off- GPi-DBS. GPi neuronal activities were analyzed and compared to those obtained in patients with Parkinson's disease. No adverse effects occurred. Chorea decreased in all patients (13, 67 and 29%) postoperatively. Total motor score decreased in patient 2 (19.6%) and moderately increased in patients 1 and 3 (17.5 and 1.7%), due to increased bradykinesia and dysarthria. Ventral was superior to dorsal GPi-DBS to control chorea. Total motor score increased dramatically off-stimulation compared to ventral GPi-DBS (70, 63 and 19%). Cognitive and psychic functions were overall unchanged. Lower mean rate and less frequent bursting activity were found in Huntington's disease compared to Parkinson's disease patients. Ventral GPi-DBS sustainably reduced chorea, but worsened bradykinesia and dysarthria. Based on these results and previous published reports, we propose to select non-demented HD patients with severe chorea, and a short disease evolution as the best candidates for GPi-DBS.
Published: 2015
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47. Pallidal activity in myoclonus dystonia correlates with motor signs

Author: Alister Rogers, Yohann Brun, Bernard Pidoux, Eric Bardinet, Carine Karachi, Marie-Laure Welter, Soledad Navarro, Marie Vidailhet, Emmanuel Roze, David Grabli, Nicolas Jodoin, Philippe Cornu, Jérôme Yelnik, and S. Fernandez-Vidal
Subjects: Dystonia, congenital, hereditary, and neonatal diseases and abnormalities, Deep brain stimulation, business.industry, medicine.medical_treatment, education, Myoclonic Jerk, Gene mutation, medicine.disease, nervous system diseases, Bursting, Globus pallidus, Neurology, mental disorders, otorhinolaryngologic diseases, Medicine, Premovement neuronal activity, Neurology (clinical), medicine.symptom, business, Neuroscience, Myoclonus
Abstract: Background Myoclonus–dystonia related to epsilon-sarcoglycan gene mutations is characterized by myoclonic jerks and mild to moderate dystonia. The role of basal ganglia dysfunction in the pathogenesis is unknown. Methods Pallidal neuronal activity was recorded in six myoclonus–dystonia and six primary generalized dystonia patients operated on for internal globus pallidus deep brain stimulation. Results In myoclonus–dystonia patients compared with primary-dystonia patients, internal pallidum neurons showed higher burst frequency, lower mean burst, and pause durations. External pallidum neurons showed higher mean pause frequency. Oscillatory activity was present in 33% and 35% of internal pallidum neurons in myoclonus–dystonia and primary-dystonia patients, respectively, predominantly in the theta frequency band (3-8 Hz). In myoclonus–dystonia patients with more severe myoclonus, internal pallidum neurons exhibited a higher bursting activity with high intraburst frequency and lower oscillatory activity frequency. Conclusions Myoclonus–dystonia appears to be related to specific changes in internal pallidum activity, leading to disruption in striato-pallido-thalamo-cortical circuits. © 2015 International Parkinson and Movement Disorder Society
Published: 2015
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48. 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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49. Contribution of the supplementary motor area and the cerebellum to the anticipatory postural adjustments and execution phases of human gait initiation

Author: Aliénor Richard, Sabine Meunier, Marie-Laure Welter, Xavier Drevelle, Jean-Louis Golmard, Angèle Van Hamme, 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), Département de Biostatistique, Santé Publique et Information Médicale [CHU Pitié-Salpêtrière] (BIOSPIM ), 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 d'investigation clinique Neurosciences [CHU Pitié Salpêtrière] (CIC Neurosciences), Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), 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], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], HAL UPMC, Gestionnaire, Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Adult, Male, Cerebellum, CTBS, Stimulation, gait initiation, 050105 experimental psychology, 03 medical and health sciences, Executive Function, Young Adult, 0302 clinical medicine, supplementary motor area, medicine, Humans, 0501 psychology and cognitive sciences, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Muscle, Skeletal, anticipatory postural adjustments, Gait, Postural Balance, Soleus muscle, Supplementary motor area, Electromyography, General Neuroscience, 05 social sciences, Motor Cortex, SMA, Transcranial Magnetic Stimulation, Biomechanical Phenomena, Phase duration, medicine.anatomical_structure, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, Brainstem, Psychology, Neuroscience, 030217 neurology & neurosurgery, Muscle Contraction
Abstract: International audience; Several brain structures including the brainstem, the cerebellum and the frontal cortico-basal ganglia network, with the primary and premotor areas have been shown to participate in the functional organization of gait initiation and postural control in humans, but their respective roles remain poorly understood. The aim of this study was to better understand the role of the supplementary motor area (SMA) and posterior cerebellum in the gait initiation process. Gait initiation parameters were recorded in 22 controls both before and after continuous theta burst transcranial stimulation (cTBS) of the SMA and cerebellum, and were compared to sham stimulation, using a randomized double-blind design study. The two phases of gait initiation process were analyzed: anticipatory postural adjustments (APAs) and execution, with recordings of soleus and tibialis anterior muscles. Functional inhibition of the SMA led to a shortened APA phase duration with advanced and increased muscle activity; during execution, it also advanced muscle co-activation and decreased the duration of stance soleus activity. Cerebellar functional inhibition did not influence the APA phase duration and amplitude but increased muscle co-activation, it decreased execution duration and showed a trend to increase velocity, with increased swing soleus muscle duration and activity. The results suggest that the SMA contributes to both the timing and amplitude of the APAs with no influence on step execution and the posterior cerebellum in the coupling between the APAs and execution phases and leg muscle activity pattern during gait initiation.
Published: 2017
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50. Rééducation par les serious games des troubles de la marche et de l’équilibre chez les patients avec maladie de Parkinson : étude randomisée contrôlée à domicile

Author: Marie-Laure Welter, Pierre Foulon, Dijana Nuic, Claire Olivier, Nienke M. de Vries, Bastiaan R. Bloem, Sjors C.F. van de Weijer, and Saoussen Cherif
Subjects: Neurology, Physiology (medical), Neurology (clinical), General Medicine
Abstract: Introduction La maladie de Parkinson (MPI) est une maladie neurodegenerative entrainant des troubles de la marche et de l’equilibre associes a des chutes, peu ou pas ameliores par le traitement medicamenteux. L’objectif de ce programme de recherche est de tester l’efficacite d’un programme de reeducation a domicile utilisant le jeu video « Toap Run » chez 50 patients avec MPI dans une etude controlee randomisee. Materiel et methodes Cinquante patients avec MPI souffrant de troubles de la marche et/ou de l’equilibre non ameliores par le traitement antiparkinsonien seront randomises en 2 groupes : – traitement actif avec 18 seances de reeducation par le jeu video a raison de 2–3 seances/semaine a l’aide d’un systeme Kinect, le sujet faisant deplacer un avatar dans le jeu en fonction des mouvements effectues ; – traitement non actif avec 18 seances de jeu realises avec un clavier d’ordinateur. Une evaluation clinique et neurophysiologique centree sur les troubles de la marche et de l’equilibre est realisee avant la 1re et apres la derniere seance d’entrainement. Le critere d’evaluation principal est le changement du temps de passation du Stand-Walk-Sit-Test (SWST). Resultats Seize patients ont ete inclus a ce jour (âge : 68,3 ± 5,7 ans ; duree d’evolution : 9,9 ± 5,4 ans), dont 8 dans chaque groupe. Le temps de passation de SWST a diminue de 1,8 s dans le groupe traite et de 0,45 s dans le groupe controle. Discussion/conclusion Les donnees preliminaires de cette etude clinique en cours suggerent que ce programme de reeducation par le jeu video « Toap Run » permet une amelioration du temps de marche chez les patients avec MPI.
Published: 2019
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