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What can neuroimaging of neuromodulation reveal about the basis of circuit therapies for psychiatry?

Abstract

Neuromodulation is increasingly becoming a therapeutic option for treatment resistant psychiatric disorders. These non-invasive and invasive therapies are still being refined but are clinically effective and, in some cases, provide sustained symptom reduction. Neuromodulation relies on changing activity within a specific brain region or circuit, but the precise mechanisms of action of these therapies, is unclear. Here we review work in both humans and animals that has provided insight into how therapies such as deep brain and transcranial magnetic stimulation alter neural activity across the brain. We focus on studies that have combined neuromodulation with neuroimaging such as PET and MRI as these measures provide detailed information about the distributed networks that are modulated and thus insight into both the mechanisms of action of neuromodulation but also potentially the basis of psychiatric disorders. Further we highlight work in nonhuman primates that has revealed how neuromodulation changes neural activity at different scales from single neuron activity to functional connectivity, providing key insight into how neuromodulation influences the brain. Ultimately, these studies highlight the value of combining neuromodulation with neuroimaging to reveal the mechanisms through which these treatments influence the brain, knowledge vital for refining targeted neuromodulation therapies for psychiatric disorders.

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Fig. 1: Cross talk between human and animal studies for the development of neuromodulation for psychiatric disorders.

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Acknowledgements

The authors would like to thank their funders and other members of the PR, BR, and HM labs for advice and encouragement.

Funding

SF, KSC, BR, HM, and PR are supported by the grant from Hope for Depression Research Foundation and the grant from The National Institute of Mental Health (NIMH) (R01MH132789). SF, AF, CE, BR, and PR are supported by grants from NIMH and the BRAIN initiative (R01MH110822 and RF1MH117040). BR is supported by grants from NIMH (R01MH111439) and NINDS (R01NS109498). AF is supported by Overseas Research Fellowship from Takeda Science Foundation and a Brain & Behavior Research Foundation Young Investigator grant (#28979).

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Fujimoto, S., Fujimoto, A., Elorette, C. et al. What can neuroimaging of neuromodulation reveal about the basis of circuit therapies for psychiatry?. Neuropsychopharmacol. (2024). https://doi.org/10.1038/s41386-024-01976-2

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