Modulation of practice-dependent plasticity in human motor cortex

Brain. 2001 Jun;124(Pt 6):1171-81. doi: 10.1093/brain/124.6.1171.


Motor practice may lead to expansion of trained representations in the motor cortex, but it is unknown whether this practice-dependent plasticity can be purposefully enhanced or depressed. Evidence, mainly based on animal experiments, indicates that the activity of GABA-related cortical inhibition is important in controlling the extent to which plasticity may occur. We tested the role of GABA in modulating practice-dependent plasticity in the human motor cortex. A decrease in GABA-related cortical inhibition was achieved by ischaemic nerve block (INB) in the hand by deafferentation/deefferentation and an increase was achieved by administration of the GABA(A) receptor agonist lorazepam. In Experiment 1, healthy subjects performed motor practice (MP), consisting of repeated ballistic contractions of the biceps muscle in the absence (MP alone) or presence of INB (MP+INB). Changes in the biceps motor cortex representation were assessed by transcranial magnetic stimulation (TMS). MP+INB resulted in a dramatic increase in the size of the motor evoked potential (MEP) and in paired-pulse excitability compared with mild or no changes in the MP-alone and INB-alone conditions. In Experiment 2, this dramatic increase in biceps representation induced by MP+INB was replicated when subjects were pretreated with placebo, but this increase was prevented or even switched to a decrease when subjects were pretreated with lorazepam. These findings indicate that a decrease in GABA-related inhibition facilitates practice-dependent plasticity in the human motor cortex, whereas an increase depresses it. In Experiment 3, practice-dependent plasticity (assessed by TMS, as in the first two experiments) was also tested at the behavioural level. The dramatic increase in biceps MEP size induced by MP+INB was paralleled by an increase in peak acceleration of the fastest elbow flexion movements. Similarly, the lack of change in MEP size in the MP-alone condition was paralleled by a lack of change in peak acceleration. We propose that changes in GABA activity may be instrumented to modulate plasticity purposefully; for instance, to enhance plastic change and recovery of function after a lesion in neurological patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomechanical Phenomena
  • Electric Stimulation
  • Electromyography
  • Evoked Potentials, Motor / drug effects
  • Evoked Potentials, Motor / physiology
  • GABA Modulators / administration & dosage
  • GABA Modulators / adverse effects
  • GABA-A Receptor Agonists
  • Humans
  • Lorazepam / administration & dosage
  • Lorazepam / adverse effects
  • Magnetics
  • Motor Cortex / cytology
  • Motor Cortex / drug effects
  • Motor Cortex / metabolism*
  • Motor Skills / drug effects
  • Motor Skills / physiology*
  • Movement / drug effects
  • Movement / physiology
  • Muscle, Skeletal / innervation
  • Muscle, Skeletal / physiology
  • Nerve Block / adverse effects
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology*
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Physical Fitness / physiology*
  • Receptors, GABA-A / metabolism
  • gamma-Aminobutyric Acid / metabolism*


  • GABA Modulators
  • GABA-A Receptor Agonists
  • Receptors, GABA-A
  • gamma-Aminobutyric Acid
  • Lorazepam