Combined endogenous and exogenous disinhibition of intracortical circuits augments plasticity induction in the human motor cortex

Lukas Ziegler; Robin Schulte; Alireza Gharabaghi

doi:10.1016/j.brs.2019.03.009

Combined endogenous and exogenous disinhibition of intracortical circuits augments plasticity induction in the human motor cortex

Brain Stimul. 2019 Jul-Aug;12(4):1027-1040. doi: 10.1016/j.brs.2019.03.009. Epub 2019 Mar 12.

Authors

Lukas Ziegler¹, Robin Schulte¹, Alireza Gharabaghi²

Affiliations

¹ Division of Functional and Restorative Neurosurgery, Tuebingen NeuroCampus, Eberhard Karls University Tuebingen, Tuebingen, Germany.
² Division of Functional and Restorative Neurosurgery, Tuebingen NeuroCampus, Eberhard Karls University Tuebingen, Tuebingen, Germany. Electronic address: alireza.gharabaghi@uni-tuebingen.de.

PMID: 30894281
DOI: 10.1016/j.brs.2019.03.009

Abstract

Background: Motor imagery (MI) engages cortical areas in the human brain similar to motor practice. Corticospinal excitability (CSE) is facilitated during but not after MI practice. We hypothesized that lasting CSE changes could be achieved by associatively pairing this endogenous modulation with exogenous stimulation of the same intracortical circuits.

Methods: We combined MI with a disinhibition protocol (DIS) targeting intracortical circuits by paired-pulse repetitive transcranial magnetic stimulation in one main and three subsequent experiments. The follow-up experiments were applied to increase effects, e.g., by individualizing inter-stimulus intervals, adding neuromuscular stimulation and expanding the intervention period. CSE was captured during (online) and after (offline) the interventions via input-output changes and cortical maps of motor evoked potentials. A total of 35 healthy subjects (mean age 26.1 ± 2.6 years, 20 females) participated in this study.

Results: A short intervention (48 stimuli within ∼90s) increased CSE. This plasticity developed rapidly, was associative (with MI_on, but not MI_off or REST) and persisted beyond the intervention period. Follow-up experiments revealed the relevance of individualizing inter-stimulus intervals and of consistent inter-burst periods for online and offline effects, respectively. Expanding this combined MI/DIS intervention to 480 stimuli amplified the sustainability of CSE changes. When concurrent neuromuscular electrical stimulation was applied, the plasticity induction was cancelled.

Conclusions: This novel associative stimulation protocol augmented plasticity induction in the human motor cortex within a remarkably short period of time and in the absence of active movements. The combination of endogenous and exogenous disinhibition of intracortical circuits may provide a therapeutic backdoor when active movements are no longer possible, e.g., for hand paralysis after stroke.

Keywords: Disinhibition; Electrical stimulation; Motor cortex; Motor evoked potentials; Motor imagery; Transcranial magnetic stimulation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Evoked Potentials, Motor / physiology*
Female
Follow-Up Studies
Hand / physiology
Humans
Imagery, Psychotherapy / methods*
Male
Motor Cortex / diagnostic imaging
Motor Cortex / physiology*
Movement / physiology
Nerve Net / diagnostic imaging
Nerve Net / physiology*
Neural Inhibition / physiology*
Neuronal Plasticity / physiology
Transcranial Magnetic Stimulation / methods*
Young Adult