PT  - JOURNAL ARTICLE
AU  - Dominic Kraus
AU  - Georgios Naros
AU  - Robert Guggenberger
AU  - Maria Teresa Leão
AU  - Ulf Ziemann
AU  - Alireza Gharabaghi
TI  - Recruitment of additional corticospinal pathways in the human brain with state-dependent paired associative stimulation
AID  - 10.1523/JNEUROSCI.2893-17.2017
DP  - 2018 Jan 15
TA  - The Journal of Neuroscience
PG  - 2893-17
4099  - http://www.jneurosci.org/content/early/2018/01/15/JNEUROSCI.2893-17.2017.short
4100  - http://www.jneurosci.org/content/early/2018/01/15/JNEUROSCI.2893-17.2017.full
AB  - Standard brain stimulation protocols modify human motor cortex excitability by modulating the gain of the activated corticospinal pathways. However, the restoration of motor function following lesions of the corticospinal tract requires also the recruitment of additional neurons to increase the net corticospinal output. For this purpose, we investigated a novel protocol based on brain state-dependent paired associative stimulation.Motor imagery (MI)-related electroencephalography was recorded in healthy males and females for brain state-dependent control of both cortical and peripheral stimulation in a brain-machine interface environment. State-dependency was investigated with concurrent, delayed and independent stimulation relative to the MI task. Specifically, sensorimotor event-related desynchronization (ERD) in the β-band (16-22 Hz) triggered peripheral stimulation through passive hand opening by a robotic orthosis and transcranial magnetic stimulation (TMS) to the respective cortical motor representation, either synchronously or subsequently. These MI-related paradigms were compared to paired cortical and peripheral input applied independent of the brain state. Cortical stimulation resulted in a significant increase in corticospinal excitability only when applied brain state-dependently and synchronously to peripheral input. These gains were resistant to a depotentiation task, revealed a nonlinear evolution of plasticity, and were mediated via the recruitment of additional corticospinal neurons rather than via synchronization of neuronal firing.Recruitment of additional corticospinal pathways may be achieved when cortical and peripheral inputs are applied concurrently, and during β-ERD. These findings resemble a gating mechanism and are potentially important for developing closed-loop brain stimulation for the treatment of hand paralysis following lesions of the corticospinal tract.SIGNIFICANCE STATEMENTThe activity state of the motor system influences the excitability of corticospinal pathways to external input. State-dependent interventions harness this property to increase the connectivity between motor cortex and muscles. These stimulation protocols modulate the gain of the activated pathways, but not the overall corticospinal recruitment.In this study, a brain-machine interface paired peripheral stimulation through passive hand opening with transcranial magnetic stimulation to the respective cortical motor representation during volitional beta-band desynchronization. Cortical stimulation resulted in the recruitment of additional corticospinal pathways, but only when applied brain state-dependently and synchronously to peripheral input. These effects resemble a gating mechanism and may be important for the restoration of motor function following lesions of the corticospinal tract.