Augmenting Plasticity Induction in Human Motor Cortex by Disinhibition Stimulation

Cereb Cortex. 2016 Jan;26(1):58-69. doi: 10.1093/cercor/bhu176. Epub 2014 Aug 6.


Cellular studies showed that disinhibition, evoked pharmacologically or by a suitably timed priming stimulus, can augment long-term plasticity (LTP) induction. We demonstrated previously that transcranial magnetic stimulation evokes a period of presumably GABA(B)ergic late cortical disinhibition (LCD) in human primary motor cortex (M1). Here, we hypothesized that, in keeping with cellular studies, LCD can augment LTP-like plasticity in humans. In Experiment 1, patterned repetitive TMS was applied to left M1, consisting of 6 trains (intertrain interval, 8 s) of 4 doublets (interpulse interval equal to individual peak I-wave facilitation, 1.3-1.5 ms) spaced by the individual peak LCD (interdoublet interval (IDI), 200-250 ms). This intervention (total of 48 pulses applied over ∼45 s) increased motor-evoked potential amplitude, a marker of corticospinal excitability, in a right hand muscle by 147% ± 4%. Control experiments showed that IDIs shorter or longer than LCD did not result in LTP-like plasticity. Experiment 2 indicated topographic specificity to the M1 hand region stimulated by TMS and duration of the LTP-like plasticity of 60 min. In conclusion, GABA(B)ergic LCD offers a powerful new approach for augmenting LTP-like plasticity induction in human cortex. We refer to this protocol as disinhibition stimulation (DIS).

Keywords: I-waves; LTP-like plasticity; late cortical disinhibition; motor cortex; transcranial magnetic stimulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Electric Stimulation / methods
  • Evoked Potentials, Motor / physiology*
  • Female
  • Hand / physiology*
  • Humans
  • Long-Term Potentiation / physiology
  • Male
  • Motor Cortex / physiology*
  • Muscle, Skeletal / physiology*
  • Neuronal Plasticity / physiology*
  • Transcranial Magnetic Stimulation / methods
  • Young Adult