Depression core network-based individualized targeting for transcranial magnetic stimulation

Tuukka T Raij; Emma Komulainen; Dogu Baran Aydogan; Siina Pamilo; Erkki Isometsä; Tommi Raij

doi:10.1016/j.brs.2023.03.005

Depression core network-based individualized targeting for transcranial magnetic stimulation

Brain Stimul. 2023 Mar-Apr;16(2):619-627. doi: 10.1016/j.brs.2023.03.005. Epub 2023 Mar 15.

Authors

Tuukka T Raij¹, Emma Komulainen², Dogu Baran Aydogan³, Siina Pamilo⁴, Erkki Isometsä⁵, Tommi Raij⁶

Affiliations

¹ Department of Psychiatry, University of Helsinki and Helsinki University Hospital, P.O. Box 590, FI-00029, HUS, Helsinki, Finland; Department of Neuroscience and Biomedical Engineering, and Advanced Magnetic Imaging Center, Aalto NeuroImaging, Aalto University School of Science, P.O Box 13000, FI-00076, AALTO, Espoo, Finland. Electronic address: tuukka.raij@hus.fi.
² Department of Psychiatry, University of Helsinki and Helsinki University Hospital, P.O. Box 590, FI-00029, HUS, Helsinki, Finland. Electronic address: emma.komulainen@hus.fi.
³ Department of Neuroscience and Biomedical Engineering, and Advanced Magnetic Imaging Center, Aalto NeuroImaging, Aalto University School of Science, P.O Box 13000, FI-00076, AALTO, Espoo, Finland; A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland. Electronic address: baran.aydogan@uef.fi.
⁴ Department of Neuroscience and Biomedical Engineering, and Advanced Magnetic Imaging Center, Aalto NeuroImaging, Aalto University School of Science, P.O Box 13000, FI-00076, AALTO, Espoo, Finland. Electronic address: siina.pamilo@aalto.fi.
⁵ Department of Psychiatry, University of Helsinki and Helsinki University Hospital, P.O. Box 590, FI-00029, HUS, Helsinki, Finland. Electronic address: erkki.isometsa@helsinki.fi.
⁶ Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA; Department of Radiology, Harvard Medical School, Boston, MA, USA. Electronic address: raij@nmr.mgh.harvard.edu.

Abstract

Background: Transcranial magnetic stimulation (TMS) of the dorsolateral prefrontal cortex (DLPFC) is an established treatment for major depressive disorder (MDD). Recent attempts to improve TMS efficacy by individually targeting DLPFC subregions that are functionally connected to the subgenual anterior cingulate cortex (sgACC) appear promising. However, sgACC covers only a small subset of core MDD-related areas. Further, fMRI connectivity of sgACC is poorly repeatable within subjects.

Methods: Based on an fMRI database analysis, we first constructed a novel core network model (CNM), capturing voxelwise emotion regulation- and MDD-related DLPFC connectivity. Then, in a sample of 15 healthy subjects and 29 MDD patients, we assessed (i) within-subject repeatability of the DLPFC connectivity patterns computed from time segments of varying lengths of individual-level fMRI data and (ii) association of MDD severity with the individual DLPFC connectivity strengths. We extracted group-level connectivity strengths in CNM from individual DLPFC coordinates stimulated with neuronavigated TMS in a separate sample of 25 MDD patients. These connectivity strengths were then correlated with individual TMS efficacy.

Results: Compared with sgACC connectivity, CNM increased intraindividual repeatability 5-fold. DLPFC connectivity strength from CNM was associated with MDD severity and TMS efficacy. While the locations of CNM-based individual TMS targets remained constant within individuals, they varied considerably between individuals.

Conclusions: CNM increased repeatability of functional targeting to a clinically feasible level. The observed association of MDD severity and TMS efficacy with DLPFC connectivity supports the validity of the CNM. The interindividual differences in target locations motivate future individualized clinical trials leveraging the CNM.

Keywords: Emotion regulation; Functional magnetic resonance imaging; Major depressive disorder; Targeting; Transcranial magnetic stimulation.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Depression
Depressive Disorder, Major* / diagnostic imaging
Depressive Disorder, Major* / therapy
Humans
Magnetic Resonance Imaging
Prefrontal Cortex / physiology
Transcranial Magnetic Stimulation*

Grants and funding

R01 NS126337/NS/NINDS NIH HHS/United States