Mechanisms of deafferentation-induced plasticity in human motor cortex.
Level 3 - non-randomized controlled study
Small within-subject physiological drug-challenge trial in healthy volunteers without reported randomization.
PubMed 9712668 · doi:10.1523/JNEUROSCI.18-17-07000.1998
What was done
In six healthy volunteers, investigators evaluated the neurochemical mechanisms of cortical plasticity by combining forearm ischemic nerve block (INB) with low-frequency repetitive transcranial magnetic stimulation (rTMS) applied to the deafferented motor cortex. Motor-evoked potential (MEP) size and intracortical inhibition (ICI) were recorded via single- and paired-pulse TMS in the biceps brachii muscle. Measurements were taken across drug-free control sessions, sleep deprivation (to control for non-specific sedative effects), and following single oral doses of lorazepam (2 mg, a GABA-A modulator), lamotrigine (300 mg, a voltage-gated Na+/Ca2+ channel blocker), or dextromethorphan (150 mg, an NMDA receptor antagonist).
What was found
In drug-free control sessions, INB combined with rTMS increased MEP amplitude and decreased ICI (lasting >60 min). Administration of either lorazepam or lamotrigine abolished both the MEP increase and the ICI reduction. Dextromethorphan suppressed the reduction in ICI but did not prevent the increase in MEP size. Sleep-deprived sessions produced changes similar to control conditions, confirming that sedation did not account for the pharmacological effects. Specific numerical values, effect sizes, and variance were not reported in the abstract.
Why it matters
This study provides mechanistic evidence in humans that rapid deafferentation-induced motor cortex excitability changes involve GABAergic disinhibition and ion channel dynamics, whereas prolonged reductions in intracortical inhibition depend on NMDA-mediated long-term potentiation-like mechanisms.
Limits
The sample size is very small (n = 6 healthy subjects), and the abstract does not report randomization, blinding, or exact numerical values with confidence intervals. Systemic oral administration of CNS-active drugs cannot completely exclude contributions from subcortical or spinal sites.
Cited by
- supports Rapid plasticity in sensory and motor maps occurs in part through the unmasking of pre-existing, latent neural connections rather than the immediate growth of new anatomical connections.