Browsing by Author "James, P"
Now showing 1 - 5 of 5
Results Per Page
Sort Options
Item Abnormal cerebellar processing of the neck proprioceptive information drives dysfunctions in cervical dystonia.(Sci Rep. 2018, 2018-02) Popa, T; Hubsch, C; James, P; Richard, A; Russo, M; Pradeep, S; Krishan, S; Roze, E; Meunier, S; Kishore, AThe cerebellum can influence the responsiveness of the primary motor cortex (M1) to undergo spike timing-dependent plastic changes through a complex mechanism involving multiple relays in the cerebello-thalamo-cortical pathway. Previous TMS studies showed that cerebellar cortex excitation can block the increase in M1 excitability induced by a paired-associative stimulation (PAS), while cerebellar cortex inhibition would enhance it. Since cerebellum is known to be affected in many types of dystonia, this bidirectional modulation was assessed in 22 patients with cervical dystonia and 23 healthy controls. Exactly opposite effects were found in patients: cerebellar inhibition suppressed the effects of PAS, while cerebellar excitation enhanced them. Another experiment comparing healthy subjects maintaining the head straight with subjects maintaining the head turned as the patients found that turning the head is enough to invert the cerebellar modulation of M1 plasticity. A third control experiment in healthy subjects showed that proprioceptive perturbation of the sterno-cleido-mastoid muscle had the same effects as turning the head. We discuss these finding in the light of the recent model of a mesencephalic head integrator. We also suggest that abnormal cerebellar processing of the neck proprioceptive information drives dysfunctions of the integrator in cervical dystonia.Item Age-related decline in the responsiveness of motor cortex to plastic forces reverses with levodopa or cerebellar stimulation(Neurobiology of aging, 2014-11) Kishore, A; Popa, T; James, P; Yahia-Cherif, L; Backer, F; Varughese, CL; Govind, P; Pradeep, S; Meunier, SThe plasticity of motor cortex is integral for motor memory and skills acquisition but it declines with aging. Forty healthy volunteers, across 6 decades, were tested to examine the (a) age-dependency of motor cortex responsiveness to plasticity induction, as measured from the response to paired associative stimulation (PAS) and the (b) effect of aging on the cerebellar modulation of motor cortex response to PAS. We examined if reduced dopaminergic transmission was involved in the age-related decline of response to PAS by retesting 10 of the older subjects after a single dose of levodopa. There was a substantial decline in the motor cortex response to PAS with aging, which was restored by levodopa in the older subjects. The cerebellar modulation of motor cortex response to PAS was less vulnerable to aging and a single session of cerebellar inhibition reinstated the cortical responsiveness in older subjects. Both levodopa and cerebellar inhibition can be tested for their ability to enhance motor skills acquisition and motor performance in the elderly individuals.Item Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015(LANCET) Wang, HD; Naghavi, M; Allen, C; Barber, RM; Bhutta, ZA; Carter, A; Casey, DC; Charlson, FJ; Chen, AZ; Coates, MM; Coggeshall, M; Dandona, L; Dicker, DJ; Erskine, HE; Ferrari, AJ; Fitzmaurice, C; Foreman, K; Forouzanfar, MH; Fraser, MS; Pullman, N; Gething, PW; Goldberg, EM; Graetz, N; Haagsma, JA; Hay, SI; Huynh, C; Johnson, C; Kassebaum, NJ; Kinfu, Y; Kulikoff, XR; Kutz, M; Kyu, HH; Larson, HJ; Leung, J; Liang, XF; Lim, SS; Lind, M; Lozano, R; Marquez, N; Mensah, GA; Mikesell, J; Mokdad, AH; Mooney, MD; Nguyen, G; Nsoesie, E; Pigott, DM; Pinho, C; Roth, GA; Salomon, JA; Sandar, L; Silpakit, N; Sligar, A; Sorensen, RJD; Stanaway, J; Steiner, C; Teeple, S; Thomas, BA; Troeger, C; VanderZanden, A; Vollset, SE; Wanga, V; Whiteford, HA; Wolock, T; Zoeckler, L; Abate, KH; Abbafati, C; Abbas, KM; Abd-Allah, F; Abera, SF; Abreu, DMX; Abu-Raddad, LJ; Abyu, GY; Achoki, T; Adelekan, AL; Ademi, Z; Adou, AK; Adsuar, JC; Afanvi, KA; Afshin, A; Agardh, EE; Agarwal, A; Agrawal, A; Kiadaliri, AA; Ajala, ON; Akanda, AS; Akinyemi, RO; Akinyemiju, TF; Akseer, N; Al Lami, FH; Alabed, S; Al-Aly, Z; Alam, K; Alam, NKM; Alasfoor, D; Aldhahri, SF; Aldridge, RW; Alegretti, MA; Aleman, AV; Alemu, ZA; Alexander, LT; Alhabib, S; Ali, R; Alkerwi, A; Alla, F; Allebeck, P; Al-Raddadi, R; Alsharif, U; Altirkawi, KA; Martin, EA; Alvis-Guzman, N; Amare, AT; Amegah, AK; Ameh, EA; Amini, H; Ammar, W; Amrock, SM; Andersen, HH; Anderson, B; Anderson, GM; Antonio, CAT; Aregay, AF; Arnlov, J; Arsenijevic, VSA; Al Artaman; Asayesh, H; Asghar, RJ; Atique, S; Avokpaho, EFGA; Awasthi, A; Azzopardi, P; Bacha, U; Badawi, A; Bahit, MC; Balakrishnan, K; Banerjee, A; Barac, A; Barker-Collo, SL; Barnighausen, T; Barregard, L; Barrero, LH; Basu, A; Basu, S; Bayou, YT; Bazargan-Hejazi, S; Beardsley, J; Bedi, N; Beghi, E; Belay, HA; Bell, B; Bell, ML; Bello, AK; Bennett, DA; Bensenor, IM; Berhane, A; Bernabe, E; Betsu, BD; Beyene, AS; Bhala, N; Bhalla, A; Biadgilign, S; Bikbov, B; Bin Abdulhak, AA; Biroscak, BJ; Biryukov, S; Bjertness, E; Blore, JD; Blosser, CD; Bohensky, MA; Borschmann, R; Bose, D; Bourne, RRA; Brainin, M; Brayne, CEG; Brazinova, A; Breitborde, NJK; Brenner, H; Brewer, JD; Brown, A; Brown, J; Brugha, TS; Buckle, GC; Butt, ZA; Calabria, B; Campos-Novato, IR; Campuzano, JC; Carapetis, JR; Cardenas, R; Carpenter, D; Carrero, JJ; Castaneda-Oquela, CA; Rivas, JC; Catala-Lopez, F; Cavalleri, F; Cercy, K; Cerda, J; Chen, WQ; Chew, A; Chiang, PPC; Chibalabala, M; Chibueze, CE; Chimed-Ochir, O; Chisumpa, VH; Choi, JYJ; Chowdhury, R; Christensen, H; Christopher, DJ; Ciobanu, LG; Cirillo, M; Cohen, AJ; Colistro, V; Colomar, M; Colquhoun, SM; Cooper, C; Cooper, LT; Cortinovis, M; Cowie, BC; Crump, JA; Damsere-Derry, J; Danawi, H; Dandona, R; Daoud, F; Darby, SC; Dargan, PI; das Neves, J; Davey, G; Davis, AC; Davitoiu, DV; de Castro, EF; de Jager, P; De Leo, D; Degenhardt, L; Dellavalle, RP; Deribe, K; Deribew, A; Dharmaratne, SD; Dhillon, PK; Diaz-Torne, C; Ding, EL; dos Santos, KPB; Dossou, E; Driscoll, TR; Duan, LL; Dubey, M; Bartholow, B; Ellenbogen, RG; Lycke, C; Elyazar, I; Endries, AY; Ermakov, SP; Eshrati, B; Esteghamati, A; Estep, K; Faghmous, IDA; Fahimi, S; Jose, E; Farid, TA; Farinha, CSES; Faro, A; Farvid, MS; Farzadfar, F; Feigin, VL; Fereshtehnejad, SM; Fernandes, JG; Fernandes, JC; Fischer, F; Fitchett, JRA; Flaxman, A; Foigt, N; Fowkes, FGR; Franca, EB; Franklin, RC; Friedman, J; Frostad, J; Hirst, T; Futran, ND; Gall, SL; Gambashidze, K; Gamkrelidze, A; Ganguly, P; Gankpe, FG; Gebre, T; Gebrehiwot, TT; Gebremedhin, AT; Gebru, AA; Geleijnse, JM; Gessner, BD; Ghoshal, AG; Gibney, KB; Gillum, RF; Gilmour, S; Giref, AZ; Giroud, M; Gishu, MD; Giussani, G; Glaser, E; Godwin, WW; Gomez-Dantes, H; Gona, P; Goodridge, A; Gopalani, SV; Gosselin, RA; Gotay, CC; Goto, A; Gouda, HN; Greaves, F; Gugnani, HC; Gupta, R; Gupta, R; Gupta, V; Gutierrez, RA; Hafezi-Nejad, N; Haile, D; Hailu, AD; Hailu, GB; Halasa, YA; Hamadeh, RR; Hamidi, S; Hancock, J; Handal, AJ; Hankey, GJ; Hao, YT; Harb, HL; Harikrishnan, S; Haro, JM; Havmoeller, R; Heckbert, SR; Heredia-Pi, IB; Heydarpour, P; Hilderink, HBM; Hoek, HW; Hogg, RS; Horino, M; Horita, N; Hosgood, HD; Hotez, PJ; Hoy, DG; Hsairi, M; Htet, AS; Htike, MMT; Hu, GQ; Huang, C; Huang, H; Huiart, L; Husseini, A; Huybrechts, I; Huynh, G; Iburg, KM; Innos, K; Inoue, M; Iyer, VJ; Jacobs, TA; Jacobsen, KH; Jahanmehr, N; Jakovljevic, MB; James, P; Javanbakht, M; Jayaraman, SP; Jayatilleke, AU; Jeemon, P; Jensen, PN; Jha, V; Jiang, G; Jiang, Y; Jibat, T; Jimenez-Corona, A; Jonas, JB; Joshi, TK; Kabir, Z; Karnak, R; Kan, HD; Kant, S; Karch, A; Karema, CK; Karimkhani, C; Karletsos, D; Karthikeyan, G; Kasaeian, A; Katibeh, M; Kaul, A; Kawakami, N; Kayibanda, JF; Keiyoro, PN; Kemmer, L; Kemp, AH; Kengne, AP; Keren, A; Kereselidze, M; Kesavachandran, CN; Khader, YS; Khalil, IA; Khan, AR; Khan, EA; Khang, YH; Khera, S; Khoja, TAM; Kieling, C; Kim, D; Kim, YJ; Kissela, BM; Kissoon, N; Knibbs, LD; Knudsen, AK; Kokubo, Y; Kolte, D; Kopec, JA; Kosen, S; Koul, PA; Koyanagi, A; Krog, NH; Defo, BK; Bicer, BK; Kudom, AA; Kuipers, EJ; Kulkarni, VS; Kumar, GA; Kwan, GF; Lal, A; Lal, DK; Lalloo, R; Lam, H; Lam, JO; Langan, SM; Lansingh, VC; Larsson, A; Laryea, DO; Latif, AA; Lawrynowicz, AEB; Leigh, J; Levi, M; Li, Y; Lindsay, MP; Lipshultz, SE; Liu, PY; Liu, S; Liu, Y; Lo, LT; Logroscino, G; Lotufo, PA; Lucas, RM; Lunevicius, R; Lyons, RA; Ma, S; Machado, VMP; Mackay, MT; MacLachlan, JH; El Razek, HMA; El Razek, MMA; Majdan, M; Majeed, A; Malekzadeh, R; Manamo, WAA; Mandisarisa, J; Mangalam, S; Mapoma, CC; Marcenes, W; Margolis, DJ; Martin, GR; Martinez-Raga, J; Marzan, MB; Masiye, F; -Jones, AJM; Massano, J; Matzopoulos, R; Mayosi, BM; McGarvey, ST; McGrath, JJ; Mckee, M; McMahon, BJ; Meaney, PA; Mehari, A; Mehndiratta, MM; Mena-Rodriguez, F; Mekonnen, AB; Melaku, YA; Memiah, P; Memish, ZA; Mendoza, W; Meretoja, A; Meretoja, TJ; Mhimbira, FA; Micha, R; Miller, TR; Mirarefin, M; Misganaw, A; Mock, CN; Mohammad, KA; Mohammadi, A; Mohammed, S; Mohan, V; Mola, GLD; Monasta, L; Hernandez, JCM; Montero, P; Montico, M; Montine, TJ; Moradi-Lakeh, M; Morawska, L; Morgan, K; Mori, R; Mozaffarian, D; Mueller, U; Murthy, GVS; Murthy, S; Musa, KI; Nachega, JB; Nagel, G; Naidoo, KS; Naik, N; Naldi, L; Nangia, V; Nash, D; Nejjari, C; Neupane, S; Newton, CR; Newton, JN; Ng, M; Ngalesoni, FN; Ngirabega, JD; Le Nguyen, Q; Nisar, MI; Pete, PMN; Nomura, M; Norheim, OF; Norman, PE; Norrving, B; Nyakarahuka, L; Ogbo, FA; Ohkubo, T; Ojelabi, FA; Olivares, PR; Olusanya, BO; Olusanya, JO; Opio, JN; Oren, E; Ortiz, A; Osman, M; Ota, E; Ozdemir, R; Pa, M; Pandian, JD; Pant, PR; Papachristou, C; Park, EK; Park, JH; Parry, CD; Parsaeian, M; Caicedo, AJP; Patten, SB; Patton, GC; Paul, VK; Pearce, N; Pedro, JM; Stokic, LP; Pereira, DM; Perico, N; Pesudovs, K; Petzold, M; Phillips, MR; Piel, FB; Pillay, JD; Plass, D; Platts-Mills, JA; Polinder, S; Pope, CA; Popova, S; Poulton, RG; Pourmalek, F; Prabhakaran, D; Qorbani, M; Quame-Amaglo, J; Quistberg, DA; Rafay, A; Rahimi, K; Rahimi-Movaghar, V; Rahman, M; Rahman, MHU; Rahman, SU; Rai, RK; Rajavi, Z; Rajsic, S; Raju, M; Rakovac, I; Rana, SM; Ranabhat, CL; Rangaswamy, T; Rao, P; Rao, SR; Refaat, AH; Rehm, J; Reitsma, MB; Remuzzi, G; Resnikofff, S; Ribeiro, AL; Ricci, S; Blancas, MJR; Roberts, B; Roca, A; Rojas-Rueda, D; Ronfani, L; Roshandel, G; Rothenbacher, D; Roy, A; Roy, NK; Ruhago, GM; Sagar, R; Saha, S; Sahathevan, R; Saleh, MM; Sanabria, JR; Sanchez-Nino, MD; Sanchez-Riera, L; Santos, IS; Sarmiento-Suarez, R; Sartorius, B; Satpathy, M; Savic, M; Sawhney, M; Schaub, MP; Schmidt, MI; Schneider, IJC; Schottker, B; Schutte, AE; Schwebel, DC; Seedat, S; Sepanlou, SG; Servan-Mori, EE; Shackelford, KA; Shaddick, G; Shaheen, A; Shahraz, S; Shaikh, MA; Shakh-Nazarova, M; Sharma, R; She, J; Sheikhbahaei, S; Shen, JB; Shen, ZY; Shepard, DS; Sheth, KN; Shetty, BP; Shi, PL; Shibuya, K; Shin, MJ; Shiri, R; Shiue, I; Shrime, MG; Sigfusdottir, ID; Silberberg, DH; Silva, DAS; Silveira, DGA; Silverberg, JI; Simard, EP; Singh, A; Singh, GM; Singh, JA; Singh, OP; Singh, PK; Singh, V; Soneji, S; Soreide, K; Soriano, JB; Sposato, LA; Sreeramareddy, CT; Stathopoulou, V; Stein, DJ; Stein, MB; Stranges, S; Stroumpoulis, K; Sunguya, BF; Sur, P; Swaminathan, S; Sykes, BL; Szoeke, CEI; Tabares-Seisdedos, R; Tabb, KM; Takahashi, K; Takala, JS; Talongwa, RT; Tandon, N; Tavakkoli, M; Taye, B; Taylor, HR; Ao, BJT; Tedla, BA; Tefera, WM; Ten Have, M; Terkawi, AS; Tesfay, FH; Tessema, GA; Thomson, AJ; Thorne-Lyman, AL; Thrift, AG; Thurston, GD; Tillmann, T; Tirschwell, DL; Tonelli, M; Topor-Madry, R; Topouzis, F; Nx, JAT; Traebert, J; Tran, BX; Truelsen, T; Trujillo, U; Tura, AK; Tuzcu, EM; Uchendu, US; Ukwaja, KN; Undurraga, EA; Uthman, OA; Van Dingenen, R; Van Donkelaar, A; Vasankari, T; Vasconcelos, AMN; Venketasubramanian, N; Vidavalur, R; Vijayakumar, L; Villalpando, S; Violante, FS; Vlassov, VV; Wagner, JA; Wagner, GR; Wallin, MT; Wang, LH; Watkins, DA; Weichenthal, S; Weiderpass, E; Weintraub, RG; Werdecker, A; Westerman, R; White, RA; Wijeratne, T; Wilkinson, JD; Williams, HC; Wiysonge, CS; Woldeyohannes, SM; Wolfe, CDA; Won, SH; Wong, JQ; Woolf, AD; Xavier, D; Xiao, QY; Xu, GL; Yakob, B; Yalew, AZ; Yan, LL; Yano, YC; Yaseri, M; Ye, P; Yebyo, HG; Yip, P; Yirsaw, BD; Yonemoto, N; Yonga, G; Younis, MZ; Yu, SC; Zaidi, Z; Zaki, MES; Zannad, F; Zavala, DE; Zeeb, H; Zeleke, BM; Zhang, H; Zodpey, S; Zonies, D; Zuhlke, LJ; Vos, T; Lopez, AD; Murray, CJLBackground Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures. Methods We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Findings Globally, life expectancy from birth increased from 61.7 years (95% uncertainty interval 61.4-61.9) in 1980 to 71.8 years (71.5-72.2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11.3 years (3.7-17.4), to 62.6 years (56.5-70.2). Total deaths increased by 4.1% (2.6-5.6) from 2005 to 2015, rising to 55.8 million (54.9 million to 56.6 million) in 2015, but age-standardised death rates fell by 17.0% (15.8-18.1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14.1% (12.6-16.0) to 39.8 million (39.2 million to 40.5 million) in 2015, whereas age-standardised rates decreased by 13.1% (11.9-14.3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42.1%, 39.1-44.6), malaria (43.1%, 34.7-51.8), neonatal preterm birth complications (29.8%, 24.8-34.9), and maternal disorders (29.1%, 19.3-37.1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death. Interpretation At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems. Copyright (C) The Author(s). Published by Elsevier Ltd.Item Motor cortex plasticity can indicate vulnerability to motor fluctuation and high L-DOPA need in drug-naïve Parkinson's disease.(Parkinsonism Relat Disord., 2016-12) Kishore, A; James, P; Krishnan, S; Yahia-Cherif, L; Meunier, S; Popa, TIntroduction: Motor cortex plasticity is reported to be decreased in Parkinson's disease in studies which pooled patients in various stages of the disease. Whether the early decrease in plasticity is related to the motor signs or is linked to the future development of motor complications of treatment is unclear. The aim of the study was to test if motor cortex plasticity and its cerebellar modulation are impaired in treatment-naïve Parkinson's disease, are related to the motor signs of the disease and predict occurrence of motor complications of treatment. Methods: Twenty-nine denovo patients with Parkinson's disease were longitudinally assessed for motor complications for four years. Using transcranial magnetic stimulation, the plasticity of the motor cortex and its cerebellar modulation were measured (response to paired-associative stimulation alone or preceded by 2 active cerebellar stimulation protocols), both in the untreated state and after a single dose of L-DOPA. Twenty-six matched, healthy volunteers were tested, only without L-DOPA. Results: Patients and healthy controls had similar proportions of responders and non-responders to plasticity induction. In the untreated state, the more efficient was the cerebellar modulation of motor cortex plasticity, the lower were the bradykinesia and rigidity scores. The extent of the individual plastic response to paired associative stimulation could indicate a vulnerability to develop early motor fluctuation but not dyskinesia. Conclusions: Measuring motor cortex plasticity in denovo Parkinson's disease could be a neurophysiological parameter that may help identify patients with greater propensity for early motor fluctuations.Item Severity of Writer's Cramp is Related to Faulty Motor Preparation(Cereb Cortex, 2017-09) Kishore, A; Popa, T; James, P; Krishnan, S; Robert, S; Meunier, SWe characterized, in 37 writer's cramp (WC) patients and 14 healthy volunteers (HV), the buildup of motor representations contralateral ("intended") and ispsilateral ("unintended") to the movement to be produced and the excitability changes in left primary motor cortex during the early reaction time (RT) of a pre-cued reaching movement to pick up a pen with either hand to write. We also tested the excitability of interhemispheric pathways from right dorsal premotor and motor cortices to left motor cortex. During early RT (1) the motor cortex excitability of unintended muscle representations did not decrease in patients as in HV and (2) the connection from the contralateral dorsal premotor cortex to the "intended" motor representation did not function in patients. In HV, the efficiency of intracortical GABA-ergic circuits at rest predicted the degree of excitability changes in the intended motor representation in the early RT. This was not true in patients who had lower efficiency of GABA-ergic circuits. Interestingly, the more severe was the writing impairment, the higher was the level of excitability in the intended and unintended motor representations. It demonstrates, for the first time, that abnormal motor preparation influences the severity of the writing impairment in WC patients.