Different stimulation targets of rTMS modulate specific triple-network and hippocampal-cortex functional connectivity

Background

Repetitive transcranial magnetic stimulation (rTMS) is widely applied to treat Alzheimer's disease (AD). Various treatment targets are currently being explored in clinical research. However, target diversity can result in considerable heterogeneity.

Objective

This study aimed to investigate whether different rTMS targets can enhance cognitive domains by modulating functional connectivity (FC) of the hippocampus (HIP) and triple network, which comprises the salience network (SN), central executive network (CEN), and default mode network (DMN).

Methods

We enrolled 63 patients with AD, of whom 48 and 15 underwent rTMS targeting the left dorsolateral prefrontal cortex (dlPFC) and the bilateral angular gyrus (ANG), respectively. We examined the network-level FC differences within the triple-network before and after treatment. Additionally, we utilized HIP as a seed for voxel-level analysis. We compared the similarities and differences in the effects of dlPFC and ANG rTMS.

Results

rTMS targeting the dlPFC primarily influenced the FC of the CEN, whereas rTMS targeting the ANG primarily influenced the SN and DMN. Moreover, the right temporal lobe within the DMN exhibited reduced FC with the left HIP following both therapies. The results of least absolute shrinkage and selection operator (LASSO) analysis indicated that hippocampal-cortex FC played a dominant role in the therapeutic effect. The observed FC changes significantly correlated with improvements in multiple cognitive scales.

Conclusion

rTMS targeting different regions affected the FC of specific networks. Both stimulation targets modulate the FC of hippocampal-cortex to influence therapeutic outcomes. Classification of patients based on damaged networks can further inform subsequent treatment strategies.