Frequency- and area-specific entrainment of intrinsic cortical oscillations by repetitive transcranial magnetic stimulation
Neural oscillations are ubiquitous throughout the cortex, but the frequency of oscillations differs from area to area. To elucidate the mechanistic architectures establishing various rhythmic activities, we tested whether spontaneous neural oscillations in different cortical modules can be entrained by direct perturbation with distinct frequencies of transcranial magnetic stimulation (TMS). While recording the electroencephalogram (EEG), we applied single-pulse TMS (sTMS) and repetitive TMS (rTMS) at 5, 11, and 23 Hz to motor or visual cortex. To assess entrainment, defined as phase locking of intrinsic oscillations to periodic external force , we examined local and global modulation of the phase-locking factor (PLF). sTMS triggered transient phase locking in a wide frequency band with distinct PLF peaks at 21 Hz in the motor cortex and 8 Hz in the visual cortex. With TMS pulse trains of 11 Hz over visual cortex and 23 Hz over motor cortex, phase locking was progressively enhanced at the stimulation frequency and lasted for a few cycles after the stimulation terminated. Moreover, such local entrainment propagated to other cortical regions, suggesting that rTMS entrained intrinsic neural oscillations locally and globally via network nodes. Because the entrainment was frequency-specific for each target site, these frequencies may correspond to the natural frequency of each cortical module and of the global networks. rTMS enables direct manipulation of the brain and is thus useful for investigating the causal roles of synchronous neural oscillations and synchrony in brain functions, and for the treatment of clinical symptoms associated with impaired oscillations and synchrony.\n\nSignificance StatementWe provide the first evidence for area- and frequency-specific entrainment by frequency-tuned repetitive transcranial magnetic stimulation (rTMS), and the propagation of this entrainment to other areas. Our results indicate that rTMS at the natural frequency of each cortical system is particularly effective for entraining oscillatory phase. Moreover, local entrainment led to global entrainment in functionally coupled areas. The ability to control brain rhythms in the intact human brain is highly beneficial for studying the causal roles of rhythmic activity in brain function. Moreover, this modulatory technique has the potential to treat patients with impaired rhythmic networks in disorders such as schizophrenia and stroke.