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Motor facilitation during real-time movement imitation in Parkinson’s disease: a virtual reality study

  • Robles-García, Verónica
  • Arias, Pablo
  • Sanmartín, Gabriel
  • Espinosa, Nelson
  • Flores, Julián
  • Grieve, Kenneth
  • Cudeiro Mazaira, Francisco Javier
[Abstract] Background: Impaired temporal stability and poor motor unit recruitment are key impairments in Parkinsonian motor control during a whole spectrum of rhythmic movements, from simple finger tapping to gait. Therapies based on imitation can be designed for patients with motor impairments and virtual-reality (VR) offers a new perspective. Motor actions are known to depend upon the dopaminergic system, whose involvement in imitation is unknown. We sought to understand this role and the underlying possibilities for motor rehabilitation, by observing the execution of different motor-patterns during imitation in a VR environment in subjects with and without dopaminergic deficits. Methods: 10 OFF-dose idiopathic Parkinson’s Disease patients (PD), 9 age-matched and 9 young-subjects participated. Subjects performed finger-tapping at their “comfort” and “slow-comfort” rates, while immersed in VR presenting their “avatar” in 1st person perspective. Imitation was evaluated by asking subjects to replicate finger-tapping patterns different to their natural one. The finger-pattern presented matched their comfort and comfort-slow rates, but without a pause on the table (continuously moving). Results: Patients were able to adapt their finger-tapping correctly, showing that in comparison with the control groups, the dopaminergic deficiency of PD did not impair imitation. During imitation the magnitude of EMG increased and the temporal variability of movement decreased. Conclusions: PD-patients have unaltered ability to imitate instructed motor-patterns, suggesting that a fully-functional dopaminergic system is not essential for such imitation. It should be further investigated if imitation training over a period of time induces positive off-line motor adaptations with transfer to non-imitation tasks.
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Validity of the finger tapping test in Parkinson’s disease, elderly and young healthy subjects: is there a role for central fatigue?

  • Arias, Pablo
  • Robles-García, Verónica
  • Espinosa, Nelson
  • Corral Bergantiños, Yoanna
  • Cudeiro Mazaira, Francisco Javier
[Abstract] Objective: The main goal of this work is to evaluate the validity of the finger tapping test (FT) to detect alterations in rhythm formation. Methods: We use FT to study the alterations in motor rhythm in three different groups: Parkinson’s patients, elderly healthy controls, and young healthy control subjects (HY). The test was performed in COMFORT and FAST tapping modes and repeated on two different days. Results: For the variables analyzed (frequency and variability) both modes were repeatable in all groups. Also, intra-class correlation coefficients showed excellent levels of consistency between days. The test clearly differentiated the groups in both FAST and COMFORT modes. However, when fatigue was analyzed, a decrease in the tapping frequency was observed in HY during the FAST mode only. The amplitude of motor evoked potentials (MEPs) induced by transcranial magnetic stimulation (TMS) was early-potentiated but not delayed-depressed, both for COMFORT and FAST modes. This suggests that fatigue was not of cortico-spinal origin. Other forms of central fatigue are discussed. Conclusions: FT at FAST mode is not a valid test to detect differences in rhythm formation across the groups studied; fatigue is a confounding variable in some groups if the test is performed as fast as possible. Significance: COMFORT mode is recommended in protocols including the FT for evaluating rhythm formation.
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Antagonist muscle co-activation during straight walking and its relation to kinematics: Insight from young, elderly and Parkinson's disease

  • Arias, Pablo
  • Espinosa, Nelson
  • Robles-García, Verónica
  • Cao, Ricardo
  • Cudeiro Mazaira, Francisco Javier
[Abstract] Increased antagonist muscle co-activation of the lower limb during walking seems to be an adaptive process to the physiological changes of aging, in order to gain joint stability. In the healthy subjects this view seems to be reinforced by the fact that the co-activation index (CAI) increases when the gait is faster. The few reports on antagonist co-activation in Parkinson's disease (PD) patients indicate that they have larger co-activation than the healthy elderly, supporting the idea of the stabilization role of CAI during gait, as postural instability is a cardinal feature of PD. However it has also been reported that there is a reduction of the CAI when increasing velocity in PD or normal elderly. This questions the role of coactivation in stabilization during increased velocity. In this study we have analyzed the gait of healthy subjects (young and elderly), and PD patients (with and without freezing of gait, FOG) in order to better understand the relation between co-activation and gait kinematics, and to gain insight into the pathological changes associated with FOG in PD. We used Multiple Linear Regression models to study the relationship in shank muscles between CAI, velocity and cadence. Our results indicate that, for all groups of interest, the relationship between co-activation and the kinematics of gait is poor, due to the high degree of variability, questioning the explanatory value of the index.
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Time-averaged shallow water model: asymptotic derivation and numerical validation

  • Rodríguez Seijo, José Manuel
  • Taboada-Vázquez, Raquel
The objective of this paper is to derive, from the Navier-Stokes equations in a shallow domain,a new bidimensional shallow water model able to filter the high frequency oscillations that are produced, when the Reynolds number is increased, in turbulent ows. With this aim, the non- dimensional Navier-Stokes equations are time-averaged, and then asymptotic analysis techniques have been used as in our previous works. The small non-dimensional parameter considered, "e", is the quotient between the typical depth of the basin and the typical horizontal length of the domain; and it is studied what happens when "e" becomes small. Once the new model has been justified, by the method of asymptotic expansions, we perform some numerical experiments. The results of these experiments con rm that this new model is able to approximate analytical solutions of Navier-Stokes equations with more accuracy than classical shallow water models, when high frequency oscillations appear. To reach a given accuracy, the time step for the new model can be much larger (even four hundred times larger) than the time step required for the classical models.
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Discapacidade intelectual e avellentamento

  • Millán-Calenti, José Carlos
  • López-Rey, M.J.
  • Quintana, Jorge
  • Meleiro, Luis
[Resumo] Destacan os autores en termos xerais a pouca atención que os investigadores prestaron ó colectivo de poboación maior con deficiencia mental. Os esforzos na actualidade dos traballos de investigación sobre o envellecemento van encamiñados a “engadir vida ós anos, máis que engadir anos a vida”. O proceso de avellentamento dase nun seno familiar raras veces axeitado a esta circunstancia, e con carencias importantes nos sistemas de apoio. Pretendese que no futuro as persoas con discapacidade intelectual vivan máis anos e poidan gozar da súa ancianidade con maior dignidade e con maiores cotas de saúde e benestar. Na actualidade non existen en Galicia centros especializados para atender a estas persoas con discapacidade intelectual engadida o proceso de avellentamento. Por outra banda, os centros xeriatricos non poden acollelos ata que teñan os 60 anos, cando este colectivo xa presenta problemas de ancianidade arredor dos 45 anos. Asimesmo os centros xeriatricos non están deseñados para persoas con discapacidade. Polo tanto compre dar resposta a esta nova demanda de persoas que teñen unha esperanza de vida cada vez maior.
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A xerontoloxía, o envellecemento e a discapacidade intelectual

  • Meleiro, Luis
  • Quintana, Jorge
  • Vila, Marta
  • Marante Moar, Pilar
  • Lodeiro Fernández, Susana
  • Seijas-Ramos, Sonia
  • Millán-Calenti, José Carlos
[Resumo] Debido ao progresivo avellentamento da sociedade galega, cómpre reconsiderar os distintos termos e conceptos ao uso, así como establecer ~ un marco axeitado de intervención en que se teñan en conta os principios da xerontoloxía moderna, i.e. valoración integral, intervención axeitada e personalizada, así como coordinación dos recursos. Neste sentido e de acordo co incremento da lonxevidade das persoas con discapacidade inte lectual, cómpre ter en conta as súas propias características xa que aínda tendo as mesmas necesidades ca outros colectivos, o seu envellecemento morfo-funcional amósase de xeito prematuro.
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Virtual Reality as a Tool for Evaluation of Repetitive Rhythmic Movements in the Elderly and Parkinson’s Disease Patients

  • Arias, Pablo
  • Robles-García, Verónica
  • Sanmartín, Gabriel
  • Flores, Julián
  • Cudeiro Mazaira, Francisco Javier
[Abstract] This work presents an immersive Virtual Reality (VR) system to evaluate, and potentially treat, the alterations in rhythmic hand movements seen in Parkinson’s disease (PD) and the elderly (EC), by comparison with healthy young controls (YC). The system integrates the subjects into a VR environment by means of a Head Mounted Display, such that subjects perceive themselves in a virtual world consisting of a table within a room. In this experiment, subjects are presented in 1st person perspective, so that the avatar reproduces finger tapping movements performed by the subjects. The task, known as the finger tapping test (FT), was performed by all three subject groups, PD, EC and YC. FT was carried out by each subject on two different days (sessions), one week apart. In each FT session all subjects performed FT in the real world (FTREAL) and in the VR (FTVR); each mode was repeated three times in randomized order. During FT both the tapping frequency and the coefficient of variation of inter-tap interval were registered. FTVR was a valid test to detect differences in rhythm formation between the three groups. Intra-class correlation coefficients (ICC) and mean difference between days for FTVR (for each group) showed reliable results. Finally, the analysis of ICC and mean difference between FTVR vs FTREAL, for each variable and group, also showed high reliability. This shows that FT evaluation in VR environments is valid as real world alternative, as VR evaluation did not distort movement execution and detects alteration in rhythm formation. These results support the use of VR as a promising tool to study alterations and the control of movement in different subject groups in unusual environments, such as during fMRI or other imaging studies., Galicia. Consellería de Educación; 2007/000140-0
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Endocannabinoid CB1 receptors modulate visual output from the thalamus

  • Dasilva, Miguel A.
  • Grieve, Kenneth
  • Cudeiro Mazaira, Francisco Javier
  • Rivadulla, Casto
[Abstract] Rationale Endocannabinoids have emerged as a modulatory brain system affecting different types of synapses, broadly distributed throughout the CNS, which explain the diverse psychophysical effects observed following activation of the endocannabinoid system. Objectives and methods The present study aimed to characterize the effect of CB1-mediated activity in the visual thalamus. In vivo single-unit extracellular recordings were performed in anaesthetized adult pigmented rats, measuring visual and spontaneous activity, combined with application of CB1 receptor agonists (anandamide, 2-AG, and O2545) and one antagonist, AM251. Results CB1 receptors activation revealed two cellular populations, with excitatory effects on ∼28% of cells and inhibitory in ∼72%, actions which were blocked by the antagonist AM251. The agonist action significantly altered both spontaneous and visual activity, shifting the signal-tonoise ratio (S/N), with accompanying changes in the variability within the visual response. Increased responses by agonist application were accompanied by a decrease in S/N and an increase in variability, while those cells inhibited by the agonist showed an increase in S/N and a decrease in variability. There was no obvious correlation between the two effects and any other response property suggesting a more general role in modulating all information passing from LGN to cortex. Conclusions Our data support a role for CB1 at the level of the thalamus acting as a dynamic modulator of visual information being sent to the cortex, apparently maintaining the salience of the signal within upper and lower boundaries. This may account for some of the behavioral effects of cannabis., Ministerio de Ciencia e Innovación; BFU2009-08169, Xunta de Galicia; 2007/000140-0
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Transcranial static magnetic field stimulation of the human motor cortex

  • Oliviero, Antonio
  • Mordillo-Mateos, Laura
  • Arias, Pablo
  • Panyavin, Ivan
  • Foffani, Guglielmo
  • Aguilar, Juan
[Abstract] The aim of the present study was to investigate in healthy humans the possibility of a non-invasive modulation of motor cortex excitability by the application of static magnetic fields through the scalp. Static magnetic fields were obtained by using cylindrical NdFeB magnets. We performed four sets of experiments. In Experiment 1, we recorded motor potentials evoked by single-pulse transcranial magnetic stimulation (TMS) of the motor cortex before and after 10min of transcranial static magnetic field stimulation (tSMS) in conscious subjects. We observed an average reduction of motor cortex excitability of up to 25%, as revealed by TMS, which lasted for severalminutes after the end of tSMS, andwas dose dependent (intensity of the magnetic field) but not polarity dependent. In Experiment 2, we confirmed the reduction of motor cortex excitability induced by tSMS using a double-blind sham-controlled design. In Experiment 3, we investigated the duration of tSMS that was necessary to modulate motor cortex excitability. We found that 10 min of tSMS (compared to 1min and 5 min) were necessary to induce significant effects. In Experiment 4, we used transcranial electric stimulation (TES) to establish that the tSMS-induced reduction ofmotor cortex excitability was not due to corticospinal axon and/or spinal excitability, but specifically involved intracortical networks. These results suggest that tSMS using small static magnets may be a promising tool to modulate cerebral excitability in a non-invasive, painless, and reversible way.
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Cortical plasticity and motor learning : variability in response to non-invasive brain stimulation and its relation with motor learning = Plasticidad cerebral y aprendizaje: variabilidad inter-e intra-individual en la respuesta a la estimulación cerebral no invasiva y su relación con el aprendizaje motor

  • López Alonso, Virginia
[Resumen]El cerebro humano es plástico, tiene la capacidad de producir cambios en su estructura y función. Los mecanismos principales que explican dichos cambios a nivel sináptico son la potenciación a largo plazo (LTP) y la depresión a largo plazo (LTD). Ambos mecanismos pueden ser inducidos mediante la práctica (procesos de aprendizaje), pero también pueden ser inducidos de manera artificial a través de estimulación eléctrica tanto en la corteza cerebral como en el hipocampo. En las últimas décadas se han desarrollado numerosas técnicas que permiten estimular la corteza cerebral humana de manera segura y no invasiva. La estimulación magnética transcraneal (TMS) y la estimulación transcraneal por corriente directa (tDCS) son las dos técnicas más utilizadas. Numerosos estudios han demostrado que ambas técnicas inducen cambios en la excitabilidad cortical y, por ende, en la plasticidad (compartiendo propiedades con el LTP y el LTD inducido en preparaciones corticales). Estos cambios en la excitabilidad cortical se han utilizado para justificar el uso de estas técnicas tanto en la mejora de los procesos rehabilitadores de diferentes poblaciones de pacientes como en la potenciación del aprendizaje en sujetos sanos. Sin embargo, hay una gran controversia en cuanto al efecto de estas técnicas a nivel individual, ya que en los últimos años se han publicado artículos en los que se observa que algunos sujetos no responden como es esperado a la estimulación. Al ser estas técnicas de estimulación relativamente nuevas, existen todavía varias cuestiones que no han sido resueltas completamente. En el presente trabajo tratamos de abordar las siguientes: 1) La gran variabilidad inter-individual que parece existir en la respuesta a las diferentes técnicas de estimulación. 2) La fiabilidad intra-sujeto de las técnicas de estimulación. 3) La relación entre plasticidad cortical y la capacidad de aprendizaje motor En este trabajo demostramos que, efectivamente, existen diferentes patrones de respuesta a cada uno de los protocolos de facilitación testados. Un grupo de sujetos responde como se espera (incrementando la excitabilidad cortical), mientras que otro grupo de sujetos no muestra la respuesta esperada. Además, el que una persona responda a un protocolo no es indicativo de que vaya a responder a otro. En segundo lugar, los resultados nos han mostrado que hay una fiabilidad intra-sujeto moderada durante la media hora siguiente a la estimulación transcraneal. Y en tercer lugar, nuestros datos no muestran relación entre la plasticidad inducida en el área motora con estimulación transcraneal y la capacidad de aprendizaje motor. Sin embargo, hemos encontrado una relación entre el patrón de respuesta a la estimulación y el tiempo de reacción. Nuestros resultados muestran que el grupo de sujetos que responde como se espera a determinados protocolos de estimulación, tienen un tiempo de reacción menor que aquellos del grupo que no responde como es esperado. Por lo tanto, debido a la gran variabilidad inter-individual en la respuesta a la estimulación transcraneal no invasiva, junto con la gran cantidad de protocolos de estimulación y de tareas de aprendizaje motor existentes, parece necesario contemplar todos estos aspectos a la hora de diseñar programas en los que se utilicen estas técnicas. Es decir, es importante saber qué protocolo y/o qué tarea de aprendizaje es más adecuada para según qué tipo de terapia y según qué tipo de sujeto. Además, parece que la fiabilidad intra-sujeto de las técnicas de estimulación es aceptable, por lo que una vez comprobada la eficacia de una técnica en un sujeto, podemos esperar que sucesivas sesiones muestren similares efectos. Futuros estudios deben ser realizados para seguir concretando los protocolos y parámetros óptimos para cada intervención en la que se utilicen técnicas de estimulación transcraneal no invasiva., [Abstract]Human brain is plastic, i.e. it has the ability to make changes in its structure and function. The key mechanisms involved in these changes at the synaptic level are the long-term potentiation (LTP) and the long-term depression (LTD). LTP and LTD have been induced by practice (learning processes) or artificially through electrical stimulation in cortical and hippocampal slices. In the last decades, several techniques have been developed to stimulate the awake human cerebral cortex safely and non-invasively. The two commonly used stimulation techniques are transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) produce changes in cortical excitability, with several properties in common with LTP/LTD in cortical slices. These changes in cortical excitability have been used to justify the utilization of these techniques both in rehabilitative processes of different patients populations and in the potentiation of learning in healthy subjects. However, there is controversy regarding effects on small groups of subjects and whether the effects of these techniques are effective or safe for the individual. In the last years some studies suggest that some subjects do not respond as expected to the stimulation. As these techniques are very recent, there are some questions that remain still unresolved. In the present work we wanted to address the following: 1) The huge inter-individual variability in response to the different noninvasive brain stimulation techniques. 2) The intra-subject reliability of the non-invasive brain stimulation techniques. 3) The relationship between cortical plasticity and motor learning capacity. In this work we demonstrated first, that there are different patterns of response to each of the facilitative non-invasive brain stimulation protocols tested. There is a group of subjects that respond as expected (i.e. increasing cortical excitability), whilst there is another group of subject who do not show this expected response. Furthermore, an expected response to one protocol, do not imply such response to another protocol. Second, our results show a fair intra-subject reliability in response to noninvasive brain stimulation during the half-hour post-stimulation (tested with tDCS). And third, we observe no correlation between the plasticity induced in the motor cortex by non-invasive brain stimulation and the motor learning capacity. However, we found a relationship between the pattern of response to some non-invasive brain stimulation protocols and the reaction time, i.e. the group of subjects who respond as expected to the stimulation is faster than those subjects in the group with a non-expected response. Therefore, due to the huge inter-individual variability in response to noninvasive brain stimulation, and the large amount of stimulation protocols and motor learning task, it seems very important to take into account all of this for the design of programs involving stimulation. So, is important to know which protocol and/or motor task are more suitable depending on the therapy and depending on the subject. Furthermore, as the intra-individual reliability of stimulation seems to be fair, once a technique is successfully probe in a subject, is expected similar success in successive sessions. Future studies are needed to further establish the optimal protocols and parameters for each intervention in which non-invasive brain stimulation is involved, [Resumo] O cerebro humano é plástico, ten a capacidade de producir modificacións na súa estructura e na súa función. Os principais mecanismos que explican estas modificacións a nivel sináptico son a potenciación a longo prazo (LTP) e a depresión a longo prazo (LTD). Ambos mecanismos poden ser inducidos mediante a práctica (procesos de aprendizaxe), mais tamén poden ser inducidos de maneira artificial a través de estimulación eléctrica tanto na corteza cerebral coma no hipocampo. Nas últimas décadas véñense desenvolvendo numerosas técnicas que permiten estimular o córtex humano de maneira segura e non invasiva. A estimulación magnética transcraniana (TMS) e máis a estimulación transcraniana por corrente directa (tDCS) son as dúas técnicas máis empregadas. Numerosos estudios demostraron que ámbalas dúas técnicas inducen modificacións na excitabilidade cortical e, polo tanto, na plasticidade (compartindo propiedades co LTP e mailo LTD inducido en preparacións corticais). Estas modificacións na excitabilidade cortical utilízanse para xustificar o uso destas técnicas tanto nos procesos rehabilitadores de diferentes poboacións de doentes coma na potenciación do aprendizaxe en suxeitos saudables. Porén, existe unha grande controversia en relación ó efecto destas técnicas a nivel individual, xa que nos últimos anos publicáronse artigos nos que se observa que algúns suxeitos non responden como é de esperar á estimulación. Debido a que estas técnicas son relativamente novas, aínda existen varias cuestións sen resposta. No presente traballo preténdense abordar as seguintes: 1) A grande variabilidade inter-individual que parece existir na resposta ás diferentes técnicas de estimulación. 2) A fiabilidade intra-suxeito das técnicas de estimulación. 3) A relación entre plasticidade cortical e a capacidade de aprendizaxe motora. Neste traballo demostramos que, efectivamente, existen diferentes padróns de resposta a cada un dos protocolos de facilitación testados. Un grupo de suxeitos responde como é de esperar (incrementando a excitabilidade cortical), namentres que outro grupo de suxeitos non amosa a resposta esperada. Ademais, que unha persoa responda a un protocolo non é indicativo de que responda a outro. En segundo lugar, os resultados amosaron unha fiabilidade intra-suxeito moderada durante a media hora seguinte á estimulación transcraniana. E, en terceiro lugar, os nosos datos non amosan relación entre a plasticidade inducida na zona con estimulación transcraniana e a capacidade de aprendizaxe motora. Porén, encontramos unha relación entre o padrón de resposta á estimulación transcraniana e o tempo de reacción. Os nosos resultados amosan que o grupo de suxeitos que responde como é de esperar a determinados protocolos de estimulación, teñen un tempo de reacción menor que aqueles do grupo que non responde como é de esperar. Por tanto, debido á grande variabilidade inter-individual na resposta á estimulación transcraniana non invasiva, xunto coa grande cantidade de protocolo de estimulación e de tarefas de aprendizaxe motora existentes, semella necesario contemplar todos estes aspectos á hora de deseñar programas nos que se empreguen estas técnicas. É dicir, é importante saber o protocolos e/ou a tarefa de aprendizaxe máis adecuada para segundo o tipo de terapia e segundo o tipo de suxeito. Ademáis, semella que a fiabilidade intrasuxeito das técnicas de estimulación é aceptable, por tanto, unha vez comprobada a eficacia dunha técnica nun suxeito, é de esperar que sucesivas sesións amosen efectos similares. Futuros estudios deben ser realizados para seguir concretando os protocolos e parámetros óptimos para cada intervención na que sexan empregadas as técnicas de estimulación transcraniana non invasiva.
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