Volitional modulation and neurofeedback of sensorimotor oscillatory activity is currently being evaluated as a strategy to facilitate motor restoration following stroke. Knowledge on the interplay between this regional brain self-regulation, distributed network entrainment and handedness is, however, limited. In a randomized cross-over design, twenty-one healthy subjects (twelve right-handers [RH], nine left-handers [LH]) performed kinesthetic motor imagery of left (48 trials) and right finger extension (48 trials). A brain-machine interface turned event-related desynchronization in the beta frequency-band (16-22 Hz) during motor imagery into passive hand opening by a robotic orthosis. Thereby, every participant subsequently activated either the dominant (DH) or non-dominant hemisphere (NDH) to control contralateral hand opening. The task-related cortical networks were studied with electroencephalography. The magnitude of the induced oscillatory modulation range in the sensorimotor cortex was independent of both handedness (RH, LH) and hemispheric specialization (DH, NDH). However, the regional beta-band modulation was associated with different alpha-band networks in RH and LH: RH presented a stronger inter-hemispheric connectivity, while LH revealed a stronger intra-hemispheric interaction. Notably, these distinct network entrainments were independent of hemispheric specialization. In healthy subjects, sensorimotor beta-band activity can be robustly modulated by motor imagery and proprioceptive feedback in both hemispheres independent of handedness. However, right and left handers show different oscillatory entrainment of cortical alpha-band networks during neurofeedback. This finding may inform neurofeedback interventions in future to align them more precisely with the underlying physiology.

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