Abstract
BACKGROUND: Transcranial magnetic stimulation (TMS) is a promising non-pharmacological intervention for treatment of mild cognitive impairment (MCI) and early Alzheimer's disease (AD). Yet, we know little about precisely where stimulation would be ideal to improve cognitive function. OBJECTIVE: To examine the network functional connectivity (fc) characteristics of prefrontal and parietal stimulation sites, given that these sites have led to improved cognitive function in TMS studies involving MCI-AD and unimpaired participants. METHODS: Resting-state functional MRI data were acquired from 32 MCI participants at the baseline visit of an ongoing TMS trial and used to compute connectivity with prefrontal and parietal stimulation locations, selected on the basis of previous TMS studies. The TMS seed maps were examined for extent of spatial overlap with eight canonical networks. After identifying the network most likely to be targeted by TMS, we applied strategies that may provide purer targeting. Finally, we examined network connectivity in relation to participants' behavioral characteristics because of the potential for TMS treatment to be personalized. RESULTS: The prefrontal TMS seed map overlapped primarily with the salience network. The prefrontal site is also notable for its anti-correlated connectivity with the AD-vulnerable posterior cingulate cortex (PCC). The parietal TMS seed map showed the expected strong positive connectivity with the PCC and other default network regions. Nonetheless, this particular parietal site may simultaneously modulate the fronto-parietal network. Strategies to improve network targeting and to personalize TMS are reported as secondary findings. CONCLUSION: These results can be applied to network-targeted brain stimulation for MCI and early AD treatment. Greater precision and personalization of TMS offer the promise of achieving better outcomes for individuals with MCI or mild AD dementia.