Fornix Mediates Information Propagation in Brain Networks Following DLPFC-Targeted rTMS in Alzheimer's Disease: A Randomized Controlled Trial

Aims: Repetitive transcranial magnetic stimulation (rTMS) could improve the clinical manifestations in Alzheimer's disease (AD), but its impact on deep brain tissue related to memory remains unclear. This study explored whether rTMS targeting cortical gray matter could regulate the white matter (WM) and exert modulatory effects on the network through WM bundles. Methods: Seventy-three AD patients underwent 14-day rTMS over the left dorsolateral prefrontal cortex (44 real, 25 sham). Granger causality analysis assessed changes in effective connectivity (EC) between the fornix and whole-brain voxels. Furthermore, the effects of rTMS treatment on fiber tracking parameters were analyzed. Results: After rTMS therapy, patients with AD showed increased EC based on fornix in the real-stimulation group. Functional network projections indicated that these clusters belonged to the frontoparietal network, the somatomotor network, as well as three white matter networks. Additionally, increased EC associated with fornix exhibited lateralization on the right side. Diffusion tensor imaging results showed no significant differences after the 14-day rTMS treatment. Conclusion: In conclusion, a 14-day rTMS treatment in AD could regulate fornical function by increasing cortical-fornix EC, indicating neuroplasticity changes in response to therapy. Trial Registration: Chinese Clinical Trial Registry (https://www.chictr.org.cn/index.html; ChiCTR2200062564).