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

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.