Brain state-dependent closed-loop modulation of paired associative stimulation controlled by sensorimotor desynchronization

Background: Pairing peripheral electrical stimulation (ES) and transcranial magnetic stimulation (TMS) increases corticospinal excitability when applied with a specific temporal pattern. When the two stimulation techniques are applied separately, motor imagery (MI)-related oscillatory modulation amplifies both ES-related cortical effects -sensorimotor event-related desynchronization (ERD) - and TMS-induced peripheral responses - motor-evoked potentials (MEP). However, the influence of brain self-regulation on the associative pairing of these stimulation techniques is still unclear.Objective: The aim of this pilot study was to investigate the effects of MI-related ERD during associative ES and TMS on subsequent corticospinal excitability. Method: The paired application of functional electrical stimulation (FES) of the extensor digitorum communis (EDC) muscle and subsequent single-pulse TMS (110% resting motor threshold) of the contralateral primary motor cortex was controlled by beta-band (16-22Hz) ERD during motor-imagery of finger extension and applied within a brain-machine interface environment in six healthy subjects. Neural correlates were probed by acquiring the stimulus-response curve (SRC) of both MEP peak-to-peak amplitude and area under the curve (AUC) before and after the intervention. Result: The application of approximately 150 pairs of associative FES and TMS resulted in a significant increase of MEP amplitudes and AUC, indicating that the induced increase of corticospinal excitability was mediated by the recruitment of additional neuronal pools. MEP increases were brain-state dependent and correlated with beta-band ERD, but not with the background EDC muscle activity; this finding was independent of the FES intensity applied.Conclusion: These results could be relevant for developing closed-loop therapeutic approaches such as the application of brain state-dependent, paired associative stimulation in the context of neurorehabilitation.