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Hippocampal subregions and networks linked with antidepressant response to electroconvulsive therapy

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Abstract

Electroconvulsive therapy (ECT) has been repeatedly linked to hippocampal plasticity. However, it remains unclear what role hippocampal plasticity plays in the antidepressant response to ECT. This magnetic resonance imaging (MRI) study tracks changes in separate hippocampal subregions and hippocampal networks in patients with depression (n = 44, 23 female) to determine their relationship, if any, with improvement after ECT. Voxelwise analyses were restricted to the hippocampus, amygdala, and parahippocampal cortex, and applied separately for responders and nonresponders to ECT. In analyses of arterial spin-labeled (ASL) MRI, nonresponders exhibited increased cerebral blood flow (CBF) in bilateral anterior hippocampus, while responders showed CBF increases in right middle and left posterior hippocampus. In analyses of gray matter volume (GMV) using T1-weighted MRI, GMV increased throughout bilateral hippocampus and surrounding tissue in nonresponders, while responders showed increased GMV in right anterior hippocampus only. Using CBF loci as seed regions, BOLD-fMRI data from healthy controls (n = 36, 19 female) identified spatially separable neurofunctional networks comprised of different brain regions. In graph theory analyses of these networks, functional connectivity within a hippocampus-thalamus-striatum network decreased only in responders after two treatments and after index. In sum, our results suggest that the location of ECT-related plasticity within the hippocampus may differ according to antidepressant outcome, and that larger amounts of hippocampal plasticity may not be conducive to positive antidepressant response. More focused targeting of hippocampal subregions and/or circuits may be a way to improve ECT outcome.

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Fig. 1: Regional CBF increases in responders and nonresponders to ECT within the hippocampus and surrounding tissue.
Fig. 2: Regional GMV increases after ECT in responders and nonresponders.
Fig. 3: Leave-one-out (LOO) subsampling validates the location of CBF and GMV increases in responders (R) and nonresponders (NR) to ECT.
Fig. 4: Seed-based functional connectivity analyses of BOLD-fMRI data from nondepressed control volunteers established spatially separable functional networks associated with each hippocampal region exhibiting regional CBF change validated with LOO subsampling (Fig. 3).
Fig. 5: Posttreatment changes (delta) in MRI metrics were modestly correlated with changes in memory scores in some hippocampal subregions and networks.

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Acknowledgements

This work was supported by the NIH, including R01 MH092301 and U01 MH110008 to KLN and RE and K24 MH102743 to KLN, the Muriel Harris Chair in Geriatric Psychiatry to RE, as well as the Brian and Behavior Research Foundation, a NARSAD Young Investigator award to AML.

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Authors and Affiliations

  1. Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, University of California Los Angeles, Los Angeles, CA, 90095, USA

    Amber M. Leaver, Megha Vasavada, Antoni Kubicki, Benjamin Wade, Joana Loureiro, Shantanu H. Joshi, Roger P. Woods & Katherine L. Narr

  2. Department of Radiology, Northwestern University, Chicago, IL, 60611, USA

    Amber M. Leaver

  3. Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, 90095, USA

    Gerhard Hellemann, Roger P. Woods, Randall Espinoza & Katherine L. Narr

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  1. Amber M. Leaver
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Leaver, A.M., Vasavada, M., Kubicki, A. et al. Hippocampal subregions and networks linked with antidepressant response to electroconvulsive therapy. Mol Psychiatry 26, 4288–4299 (2021). https://doi.org/10.1038/s41380-020-0666-z

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