Paired Associated Stimulation (PAS) protocol has been used to enhance motor cortico-spinal pathway excitability. We explored the consequences of using PAS protocol synchronized with a dynamic task that causes fatigue in the main muscle responsible for the task execution, Abductor Pollicis Brevis (APB). Results showed an excitability depression in APB and an enhancement in the control muscle, Abductor Digiti Minimi (ADM). This suggests that ADM became the target of synaptic plasticity processes, as a consequence of APB fatigue. We conclude that fatigue can modulate the directionality of plastic changes and therefore, the target muscle.