[en] Fatigue is a very limiting condition in many activities of the daily living and is present in different neurological pathologies. Although the underlying mechanisms are not well understood, it is considered to have a great impact on the different functional capacities of the people who suffer from it. From a motor system perspective, fatigue is divided as central and peripheral. Central fatigue has been related to the inability to execute or maintain muscle force. Notwithstanding, there are many activities of the daily living, like rhythmic repetitive movements such as walking, typing, mouse-clicking, or movements in assembly lines, which can be executed with very low levels of muscle force and also induce fatigue, likely of central origin. For this reason, it seems paradoxical that central expressions of fatigue induced by repetitive movements have hardly been explored. This PhD Thesis presents results from three different studies. We used noninvasive brain stimulation techniques to characterize central expressions of fatigue induced by movements performed repeatedly. All studies enrolled young healthy participants. In the first study, we evaluated the effect of transcranial direct current stimulation on arm reaching movements, performed repeatedly as fast as possible in a reaction time protocol. In the sham stimulation session, we observed the development of fatigue with task progression, which was absent in the case of real stimulation sessions. Regretfully, the methodology used in this study did not permit us to understand physiological mechanism behind this observation. For the second and third studies, we used transcranial magnetic stimulation, stimulation at the level of the cervicomedullary junction (electric and magnetic) and percutaneous nerve stimulation to explore the central expressions of fatigue induced by repetitive movements. We compared its profile to the central manifestations of fatigue during isometric contractions, which is considered the \gold-standard" to study fatigue. These non-invasive brain stimulation techniques allowed us to identify central cortical circuits as the loci of fatigue produced during un-resisted repetitive movements. Excitability of spinal motoneurons was not impaired. This profile is different from observations during isometric maximal voluntary contractions of same duration, for which an evident impact on the excitability of the spinal motoneurons is present. Our results indicate that central expressions of fatigue induced by movements performed repeatedly are different from those generated during isometric contractions, despite a same task-duration and relative effort. Our results are relevant because they permit dissociating central circuits and structures responsible for different types of motor system fatigue. This is important due to the impact of fatigue on activities of the daily living in physiological and clinical conditions, in sports, or ergonomics. Also, these results allow a better understanding of putative approaches to treat motor system fatigue based on neuromodulation techniques, either in physiological as pathological conditions.

[gl] A fatiga é una condición que limita múltiples actividades da vida diaria e está presente en distintas patoloxías neurolóxicas. Maila non estar suficientemente definida, coñécese que afecta a distintos planos funcionais da persoa. Dende o punto de vista motor, a fatiga tense definido como fatiga central e periférica, e no caso da fatiga central a mesma ten sido clasicamente vencellada á diminución experimentada polas persoas na capacidade de facer forza muscular. Porén, existen nas actividades da vida diaria múltiples accións, como movementos repetitivos rítmicos executados ao camiñar, durante o uso de teclados e ratos, ou en cadeas de montaxe, que poden ser realizados con baixos niveis de forza, e malia elo ser susceptibles de xerar fatiga, posiblemente de tipo central. É por elo un paradoxo que as bases da fatiga central producida por movementos repetitivos apenas se teñan exploradas. Nesta tese doutoral presentamos os resultados de tres estudos nos que, mediante o uso de técnicas de estimulación cerebral non invasivas, ternos caracterizado as expresión centrais da fatiga producida por movementos realizados repetidamente. Todos os estudos foron levados a cabo en persoas novas sen patoloxías. No primeiro estudo avaliamos o efecto da estimulación con corrente directa nas características dos movementos de alcance realizados de maneira repetida á máxima velocidade nun protocolo de tempo de reacción. Durante a sesión de estimulación placebo observouse un desenrolo da fatiga co progreso da tarefa, que non se manifestou no caso das sesións de estimulación real. Desafortunadamente a metodoloxía utilizada neste primeiro estudo non permitiu explorar os posibles mecanismos fisiolóxicos que explicasen dita observación. No segundo e terceiro estudo utilizouse a estimulación magnética transcraneal, a estimulación á altura da decusación piramidal, e a estimulación eléctrica do nervio (aplicada de maneira percutánea) para explorar as expresións centrais da fatiga inducida durante movementos repetitivos. O perfil de dita fatiga comparouse co producido por contraccións isométricas, consideradas a referencia para o estudo da fatiga. Por medio do uso destas técnicas identificamos circuítos centrais de tipo cortical coma loci da fatiga producida durante movementos repetitivos non resistidos, sen que a excitabilidade das motoneuronas espiñais se comprometa. Este perfil é distinto da fatiga producida polas contracción isométricas máximas da mesma duración, que si impactan de maneira moi importante na excitabilidade da medula espiñal. Os nosos resultados indican, claramente, que as bases centrais da fatiga producida por movementos executados repetidamente son distintas da fatiga xerada por contraccións isométricas da mesma duración e esforzo relativo. Estes resultados son moi relevantes debido a que permiten disgregar estruturas e circuítos centrais responsables de distintos tipos de fatiga do sistema motor; elo é importante dado o impacto da fatiga nas actividades da vida diaria, tanto en poboación fisiolóxicas como clínicas, en actividades deportivas ou laborais. Permiten, asemade, planificar de maneira máis acaída as posibles estratexias de intervención mediante técnicas de modulación da excitabilidade do sistema nervioso central, as cales son potencialmente útiles para intervir en distintas expresión da fatiga motora, tanto en poboacións fisiolóxicas como patolóxicas.