Interhemispheric Functional Connectivity of Sensorimotor Cortex Predicts Responsiveness of Transcranial Magnetic Stimulation in Older Adults

Background: Theta burst stimulation (TBS) holds promise for the induction of brain plasticity. However, the effects of TBS are highly variable across individual participants, and perhaps more so in older adults. Although it’s well established that non-invasive brain stimulation, including TBS, affects not only the stimulated region but also remote areas, how brain connectivity is modulated by TBS in older adults and whether baseline connectivity mediates the TBS effect remain unclear. The purpose of the study is to identify baseline network properties of sensorimotor system that may contribute to inter-individual variability of TBS response. Methods 19 right-handed older adults underwent one excitatory intermittent TBS (iTBS) session over left primary motor cortex (M1). We acquired both motor-evoked potentials (MEPs) at 13 single-pulse stimulation intensities and resting state fMRI data immediately before and after the iTBS session. We tested whether baseline measures including active motor threshold (aMT), input-output curve parameters and interhemispheric functional connectivity (ihFC) would predict individual response pattern. Results: iTBS significantly enhanced MEPs and functional connectivity in bilateral M1, somatosensory cortex and supplementary motor area. We found that participants with a lower aMT featured a relatively lower ihFC among motor cortices at baseline. Furthermore, our study showed that the relatively lower ihFC before iTBS session was associated with a greater enhancement in MEPs. Conclusion: Age-related reduction in hemispheric asymmetry has been frequently reported. In agreement with previous studies, older adults may recruit bilateral sensorimotor networks to maintain functionality, and thus exhibit a higher level of baseline ihFC. Similarly, the higher level of baseline ihFC might serve as a compensatory mechanism for the decreased sensitivity to single-pulse stimulation as indicated by a higher aMT. In summary, our findings suggest that older adults with lower aMT as well as lower ihFC might be able to elicit iTBS induced plasticity more effectively. Keywords: Theta burst stimulation, Cortical excitability, Interhemispheric connectivity, Inter-individual variability