Persistent enhancement of hippocampal network connectivity by parietal rTMS is reproducible

Abstract Wang et al. (Science, 2014: 345, p. 1054) found that that five daily sessions of repetitive transcranial magnetic stimulation (rTMS) of the posterior parietal cortex (PPC) significantly increased functional connectivity (FC) in a network centered on the hippocampus, and caused a correlated increase in memory performance in humans. However, this finding has not been reproduced independently and the requirement for five sessions has not been validated. We aimed to reproduce the imaging results of this experiment, focusing on hippocampal FC changes and using fewer days of rTMS. We measured resting state FC before and after three (N = 9) or four (N = 6) consecutive daily PPC rTMS sessions, using similar delivery parameter settings as Wang et al. Eight subjects received three days of rTMS delivered to the vertex as a control. We employed whole-brain and hypothesis-based statistical approaches to test for hippocampal FC changes. Additionally, we calculated FC in 17 brain networks to determine whether the topographic pattern of FC change was similar between studies. We did not include behavioral testing in this study. PPC, but not vertex, rTMS caused significant changes in hippocampal FC to the same regions as in the previous study. Brain-wide changes in hippocampal FC significantly exceeded changes in global connectedness, indicating that the effect of PPC rTMS was specific to the hippocampal network. Baseline hippocampal FC measured before receiving stimulation predicted the degree of rTMS-induced hippocampal FC increase, as was the case in the previous study. These findings reproduce the imaging findings of Wang et al. and show that FC enhancement can occur after only 3-4 sessions of PPC rTMS. Significance Statement One of the most striking recent findings in the area of neuromodulation is that of Wang et al. (Science, 2014: 345, p. 1054), who reported that posterior parietal cortex (PPC) stimulation increased functional connectivity in a network related to declarative memory and centered on the hippocampus, a result with great potential experimental and clinical utility. We used a similar paradigm, with shorter treatment duration and reproduced the effects on connectivity, including specificity for the hippocampal network and dependence on the magnitude of baseline hippocampal connectivity. These results confirm and extend the initial finding and validate the technical approach.