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]. Studies have shown that the left DLPFC targets with better antidepressant efficacy were more negatively correlated with the subgenual cingulate cortex (sgACC), suggesting rTMS efficacy might be improved via functional connectivity (FC)-guided targeting [
]. Some studies have proposed that the personalized DLPFC targets, defined as the individual maximal sgACC-DLPFC functional connectivity, may bring a better efficacy than the group-average DLPFC target [
]. However, whether rTMS with personalized DLPFC targets has the therapeutic advantage over the group-average target for depression remains unclear in the lack of direct comparisons between antidepressant outcomes from these two targeting methods.
Two retrospective studies provided an alternative way to examine the therapeutic potential of personalized DLFPC targets relative to other targeting methods [
] and personalized DLPFC targets, they found a better antidepressant outcome with a closer distance to the personalized target, suggesting the therapeutic potential of personalized DLPFC targets relative to the two conventional targeting methods. In our MDD patients who received rTMS previously over the group-average DLPFC site, we followed the same logic to investigate the therapeutic potential of personalized DLPFC targets relative to the group-average target. We hypothesized that closer proximity between group-average and personalized targets would be associated with better antidepressant outcomes.
The present study recruited 18 MDD outpatients between January 2018 and March 2021 at Shanghai Mental health Center (SHMC). The institutional ethical board of SMHC approved the protocol (2017–43), and all participants provided written consent before study entry. They all received 10-Hz rTMS treatment every weekday, amounting to 20 sessions. A common precise DLPFC target (Montreal Neurological Space coordinates: −42, 44, 30) was used with a group-average maximal sgACC-DLPFC connectivity [
]. The target was localized using individual structural MRI data guided by the Localite Neuronavigation System (NDI, Canada). All patients completed the Montgomery-Asberg Depression Rating Scale (MADRS) assessments, structural magnetic resonance imaging (MRI), and resting-state functional MRI acquisitions before and after 20-session rTMS treatment. MRI data were collected from a 3.0 T Siemens Verio MRI scanner (MRB17, Siemens AG, Erlangen, Germany) in SMHC (detailed parameters in supplementary materials). Functional connectivity was computed between each voxel within the left DLFPC and a sgACC-based seed map which substituted sgACC to improve the signal-to-noise ratio [
]. The personalized DLPFC target was identified by the sphere's center with a radius of 9 mm with a maximum of negative FC values. The Euclidean distance between group-average DLPFC target and personalized DLPFC targets was calculated, while the correlation of the distance and percentage improvement in MARDS score by rTMS was examined.
Of 18 MDD patients, 11 (61%) were female, the mean (SD) age was 31 (6) years old. The mean (SD) percentage of improvements in MARDS score was 75% (20%). Closer proximity between the group-average and personalized targets was significantly correlated with better MADRS improvements (R = −0.554; P = 0.017) (Fig. 1A). According to the fitted line, the mean percentage of improvement in MARDS score would be 89% if all depressive patients received rTMS over personalized targets (Fig. 1A). Compared to the actual group-average target, target site personalization further took a 14% increase in MADRS improvements theoretically. The response rate was 100% (n = 14 of 14) for patients when the distance to the group-average target was closer than 29 mm. The response rate was 25% (n = 1 of 4) for the remaining patients whose personalized targets were far away from the group-average target (Fig. 1B).
In general, MDD patients showed better antidepressant improvements when the actual group-average target was closer to the personalized target. Our results suggested that target site personalization indicates a degree of potential therapeutic benefits for MDD even over the group-average target. Limitations of the present study include the retrospective evaluation and moderate sample size.
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
This work was supported by National Nature Science Foundation of China ( 81871050 , 81971251 ); Natural Science Foundation of Shanghai ( 17ZR1424700 , 21ZR1481500 ); Key Projects of Shanghai Clinical Research Center ( CRC2018ZD01 , CRC2019ZD02 ); Shanghai Clinical Research Center for Mental Health ( 19MC1911100 ); Project of the Key Discipline Construction , Shanghai 3-Year Public Health Action Plan ( GWV-10.1-XK18 ). Yingying Tang is funded by Shanghai Municipal Education Commission— Gaofeng Clinical Medicine Grant Support ( 20191836 ).
Appendix A. Supplementary data
The following is the Supplementary data to this article: