Title : The multi-networks connectivity at baseline predicts the clinical efficacy of left angular gyrus-navigated rTMS in Alzheimer’s disease: a sham-controlled study
Neuro-navigated repetitive transcranial magnetic stimulation (rTMS) is effective in alleviating cognitive symptoms in patients with Alzheimer’s disease (AD). However, the strategy for target determination and the mechanisms for cognitive improvement remain unclear. We tested the efficacy of rTMS and explored the effect of rTMS-induced cortical plasticity on network modification and their predictive value for treatment response.
One hundred-thirteen elderly subjects were recruited in this study, including both cross-sectional (n = 79) and longitudinal experiments (the rTMS group: n = 24; the sham group: n = 10). The cross-sectional experiment explored the precise intervention target based on the cortical-hippocampal network. The longitudinal experiment investigated the clinical efficacy of neuro-navigated rTMS treatment over a four-week period and explored its underlying neural mechanism using seed-based and network-based analysis. Finally, we applied connectome-based predictive modelling (CPM) to predict the rTMS response using these functional features at baseline.
We found that rTMS at a targeted site of the left angular gyrus (MNI: -45, -67, 38) significantly induced cognitive improvement in memory and language function (p < 0.001). The underlying mechanism of improved cognition involved regulation of the restrictive relationships between default mode network (DMN) subsystems and among the large-scale functional networks associated with the DMN. Furthermore, CPM analysis indicated that the connectivity patterns of DMN subsystems (r = 0.52, p = 0.01) or large-scale networks (r = 0.85, p = 0.001) at baseline significantly predicted the rTMS therapeutic effect.
These findings provide direct evidence that neuro-navigated rTMS targeting the left angular gyrus holds tremendous promise in elucidating the neural underpinnings of cognitive deficits in AD patients. Importantly, dynamic regulation of the intra- and inter-DMN at baseline may represent a potential predictor for favourable rTMS treatment response in patients with cognitive impairment.