Priming Stimulation Enhances the Depressant Effect of Low-Frequency Repetitive Transcranial Magnetic Stimulation

Meenakshi B. Iyer, Nicole Schleper, Eric M. Wassermann

Research output: Contribution to journalArticlepeer-review

296 Scopus citations

Abstract

Low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) can depress the excitability of the cortex locally and has been proposed for the treatment of disorders such as schizophrenia and epilepsy. Some have speculated that the depressant effect is related to long-term depression (LTD) of cortical synapses. Because in vitro LTD can be enhanced by pretreatment of synapses with higher-frequency stimulation, we hypothesized that if rTMS depression had mechanisms in common with LTD, higher-frequency priming would increase it also. In 25 healthy volunteers in two experiments, we measured motor-evoked potentials (MEPs) from TMS of the motor cortex to define the baseline response. Subthreshold rTMS (6 Hz, fixed rate or frequency modulated) was used to prime the motor cortex, followed by suprathreshold 1 Hz stimulation for 10 min at just above the MEP threshold. Over the next 60 min, we recorded MEPs every 10 sec and found significant increases in the amount of cortical depression with both types of 6 Hz priming rTMS relative to sham. The MEP depression from 6 Hz-primed 1 Hz rTMS showed no evidence of decay after 60 min. Pretreatment with 6 Hz primes both 1 Hz rTMS depression and LTD. Although not conclusive evidence, this strengthens the case for overlapping mechanisms and suggests a potent new technique for enhancing low-frequency rTMS depression that may have experimental and clinical applications.

Original languageEnglish (US)
Pages (from-to)10867-10872
Number of pages6
JournalJournal of Neuroscience
Volume23
Issue number34
DOIs
StatePublished - Nov 26 2003

Keywords

  • Long-term depression
  • Motor cortex
  • Plasticity
  • Priming
  • Transcranial magnetic stimulation
  • Treatment

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