Abstract
Traditional non-invasive imaging methods describe statistical associations of functional co-activation over time. They cannot easily establish hierarchies in communication as done in non-human animals using invasive methods. Here, we interleaved functional MRI (fMRI) recordings with non-invasive transcranial magnetic stimulation (TMS) to map causal communication between the frontal cortex and subcortical target structures including the subgenual anterior cingulate cortex (sgACC) and the amygdala. Seed-based correlation maps from each participant’s resting fMRI scan determined individual stimulation sites with high temporal correlation to targets for the subsequent TMS/fMRI session(s). The resulting TMS/fMRI images were transformed to quantile responses, so that regions of high-/low-quantile response corresponded to the areas of the brain with the most positive/negative evoked response relative to the global brain response. We then modeled the average quantile response for a given region (e.g., structure or network) to determine whether TMS was effective in the relative engagement of the downstream targets. Both the sgACC and amygdala were differentially influenced by TMS. Furthermore, we found that the sgACC distributed brain network was modulated in response to fMRI-guided TMS. The amygdala, but not its distributed network, also responded to TMS. Our findings suggest that individual targeting and brain response measurements reflect causal circuit mapping to the sgACC and amygdala in humans. These results set the stage to further map circuits in the brain and link circuit pathway integrity to clinical intervention outcomes, especially when the intervention targets specific pathways and networks as is possible with TMS.
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Data availability
Data are available from the first author upon request and following a data use agreement.
Code availability
Code for analysis is already available in online repositories as described in the text.
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Acknowledgments
We thank Dr. Yvette Sheline for contributions to this project including equipment, scan time, and personnel. We also thank Yordan Todorov of Magventure, Inc. for TMS device support and contributing customized equipment for hardware control.
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This work was supported by the National Institutes of Health NIH R01 MH111886 (DJO) and NIH RF1 MH116920 (DJO). The funder had no role in study design; collection and analysis of data; in writing the report; or in the decision to submit the article for publication.
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Oathes, D.J., Zimmerman, J.P., Duprat, R. et al. Resting fMRI-guided TMS results in subcortical and brain network modulation indexed by interleaved TMS/fMRI. Exp Brain Res 239, 1165–1178 (2021). https://doi.org/10.1007/s00221-021-06036-5
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DOI: https://doi.org/10.1007/s00221-021-06036-5