Repetitive transcranial magnetic stimulation elicits rate-dependent brain network responses in non-human primates

Brain Stimul. 2013 Sep;6(5):777-87. doi: 10.1016/j.brs.2013.03.002. Epub 2013 Mar 21.


Background: Transcranial magnetic stimulation (TMS) has the potential to treat brain disorders by tonically modulating firing patterns in disease-specific neural circuits. The selection of treatment parameters for clinical repetitive transcranial magnetic stimulation (rTMS) trials has not been rule based, likely contributing to the variability of observed outcomes.

Objective: To utilize our newly developed baboon (Papio hamadryas anubis) model of rTMS during position-emission tomography (PET) to quantify the brain's rate-response functions in the motor system during rTMS.

Methods: We delivered image-guided, suprathreshold rTMS at 3 Hz, 5 Hz, 10 Hz, 15 Hz and rest (in separate randomized sessions) to the primary motor cortex (M1) of the lightly anesthetized baboon during PET imaging; we also administered a (reversible) paralytic to eliminate any somatosensory feedback due to rTMS-induced muscle contractions. Each rTMS/PET session was analyzed using normalized cerebral blood flow (CBF) measurements; statistical parametric images and the resulting areas of significance underwent post-hoc analysis to determine any rate-specific rTMS effects throughout the motor network.

Results: The motor system's rate-response curves were unimodal and system wide--with all nodes in the network showing highly similar rate response functions--and an optimal network stimulation frequency of 5 Hz.

Conclusion(s): These findings suggest that non-invasive brain stimulation may be more efficiently delivered at (system-specific) optimal frequencies throughout the targeted network and that functional imaging in non-human primates is a promising strategy for identifying the optimal treatment parameters for TMS clinical trials in specific brain regions and/or networks.

Keywords: Animal models; Motor cortex; Network; PET; Rate; TMS.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cerebrovascular Circulation / physiology
  • Motor Cortex / blood supply
  • Motor Cortex / diagnostic imaging*
  • Motor Cortex / physiology*
  • Papio
  • Positron-Emission Tomography*
  • Transcranial Magnetic Stimulation*