As the multi-center studies with resting-state functional magnetic resonance imaging (RS-fMRI) have been more and more applied to neuropsychiatric studies, both intra- and inter-scanner reliability of RS-fMRI are becoming increasingly important. The amplitude of low frequency fluctuation (ALFF), regional homogeneity (ReHo), and degree centrality (DC) are 3 main RS-fMRI metrics in a way of voxel-wise whole-brain (VWWB) analysis. Although the intra-scanner reliability (i.e., test-retest reliability) of these metrics has been widely investigated, few studies has investigated their inter-scanner reliability. In the current study, 21 healthy young subjects were enrolled and scanned with blood oxygenation level dependent (BOLD) RS-fMRI in 3 visits (V1 – V3), with V1 and V2 scanned on a GE MR750 scanner and V3 on a Siemens Prisma. RS-fMRI data were collected under two conditions, eyes open (EO) and eyes closed (EC), each lasting 8 minutes. We firstly evaluated the intra- and inter-scanner reliability of ALFF, ReHo, and DC. Secondly, we measured systematic difference between two scanning visits of the same scanner as well as between two scanners. Thirdly, to account for the potential difference of intra- and inter-scanner local magnetic field inhomogeneity, we measured the difference of relative BOLD signal intensity to the mean BOLD signal intensity of the whole brain between each pair of visits. Last, we used percent amplitude of fluctuation (PerAF) to correct the difference induced by relative BOLD signal intensity. The inter-scanner reliability was much worse than intra-scanner reliability; Among the VWWB metrics, DC showed the worst (both for intra-scanner and inter-scanner comparisons). PerAF showed similar intra-scanner reliability with ALFF and the best reliability among all the 4 metrics. PerAF reduced the influence of BOLD signal intensity and hence increase the inter-scanner reliability of ALFF. For multi-center studies, inter-scanner reliability should be taken into account.

Previous resting state functional magnetic resonance imaging (RS-fMRI) studies suggested that repetitive transcranial magnetic stimulation (rTMS) can modulate local activity in distant areas via functional connectivity (FC). A brain region has more than one connection with the superficial cortical areas. The current study proposed a multi-target focused rTMS protocol for indirectly stimulating a deep region, and to investigate 1) whether FC strength between stimulation targets (right middle frontal gyrus [rMFG] and right inferior parietal lobule [rIPL]) and effective region (dorsal anterior cingulate cortex [dACC]) can predict local activity changes of dACC and 2) whether multiple stimulation targets can focus on the dACC via FC. A total of 24 healthy participants received rTMS with two stimulation targets, both showing strong FC with the dACC. There were four rTMS conditions (>1 week apart, 10 Hz, 1800 pulses for each): rMFG-target, rIPL-target, Double-targets (900 pulses for each target), and Sham. The results failed to validate the multi-target focused rTMS hypothesis. But rMFG-target significantly decreased the local activity in the dACC. In addition, stronger dACC-rMFG FC was associated with a greater local activity change in the dACC. Future studies should use stronger FC to focus stimulation effects on the deep region.

Background:The dorsolateral prefrontal cortex (DLPFC) is the standard stimulation target for the repetitive transcranial magnetic stimulation (rTMS) treatment of major depression disorder (MDD). A retrospective study by Fox and colleagues found that a more negative resting-state functional magnetic resonance imaging (RS-fMRI) functional connectivity (FC) between left DLPFC and the subgenual anterior cingulate cortex (sgACC) in a large group of healthy participants is associated with a better curative effects of rTMS in MDD, suggesting that the sgACC may be an effective region.However, a recent meta-analysis on RS-fMRI studies found that the pregenual ACC (pgACC), rather than the sgACC, of MDD patients showed increased local activity. Methods: We used the stimulation coordinates in the left DLPFC analyzed by Fox et al. to perform RS-fMRI FC between the stimulation targets obtained from previous rTMS MDD studies and the potential effective regions (sgACC and pgACC, respectively) on the RS-fMRI data from 88 heathy participants. Results: (a) Both the pgACC and the sgACC were negatively connected to the left DLPFC; (b) both FCs of sgACC-DLPFC and pgACC-DLPFC were more negative in responders than in nonresponders; and (c) the associations between DLPFC-sgACC functional connectivity and clinical efficacy were clustered around the midline sgACC. Conclusions: Both the pgACC and the sgACC may be potential effective regions for rTMS on the left DLPFC for treatment of MDD. However, individualized ACC-DLPFC FC-based rTMS on depression should be performed in the future to test the pgACC or the sgACC as effective regions. K E Y W O R D S depression, functional connectivity, pregenual anterior cingulate cortex, repetitive transcranial magnetic stimulation, subgenual anterior cingulate cortex S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Jing Y, Zhao N, Deng X-P, et al.Pregenual or subgenual anterior cingulate cortex as potential effective region for brain stimulation of depression. Brain