Effects of continuous versus intermittent theta-burst TMS on fMRI connectivity.

Transcranial magnetic stimulation is a noninvasive technique that can be used to evoke distributed network-level effects. Previous work demonstrated that the Hippocampal-Cortical Network responds preferably (i.e., greater memory improvement and increases in hippocampal-network connectivity) to continuous theta-burst stimulation protocol relative to intermittent theta-burst and to 20-Hz rTMS. Here, these data were further analyzed to characterize effects of continuous versus intermittent theta-burst stimulation on network-level connectivity measures - as well as local connectedness - via resting-state fMRI. In contrast to theories that propose continuous and intermittent theta-burst cause local inhibitory versus excitatory effects, respectively, both protocols caused local decreases in fMRI connectivity around the stimulated parietal site. While iTBS caused decreases in connectivity across the hippocampal-cortical network, cTBS caused increases and decreases in connectivity across the network. cTBS had no effect on the parietal-cortical network, whereas iTBS caused decreases in the right parietal cortex (contralateral hemisphere to the stimulation target). These findings suggest that continuous theta-burst may have entrained the endogenous hippocampal-cortical network, whereas the intermittent train was unable to maintain entrainment that may have yielded the long-lasting effects measured in this study (i.e., within 20-min post-stimulation). Furthermore, these effects were specific to the hippocampal-cortical network, which has a putative endogenous functionally-relevant theta rhythm, and not to the parietal network. These results add to the growing body of evidence that suggests effects of theta-burst stimulation are not fully characterized by excitatory/inhibitory theories. Further work is required to understand local and network-level effects of noninvasive stimulation.