Tractography-guided hippocampal theta burst stimulation to improve memory performance and increase hippocampal connectivity in mild cognitive impairment

Abstract

Abstract A personalized, image-guided theta-burst stimulation (TBS) protocol was developed for individuals with mild cognitive impairment (MCI). MCI is a transitional stage between normal aging and Alzheimer's disease (AD). There is a need for interventions to alleviate the deterioration of memory. Targeting the hippocampus, which still exhibits plasticity at the stage of MCI, may be an effective strategy to enhance memory functions. By using white matter tractography maps as a guide, we were able to effectively relay the modulation effects of the superficial TBS to the hippocampus. Nine right-handed older adults (aged 65 to 74 years old) classified as MCI based on the Uniform Data Set version 3 (UDS3) neuropsychological battery participated in our study. Diffusion-weighted images were acquired for each participant at baseline to determine the optimal superficial stimulation site. White matter tractography of the left hippocampus was generated using MRtrix. In this cross-over design, participants were exposed to each of these conditions twice: excitatory intermittent TBS (iTBS), inhibitory continuous TBS (cTBS), and sham stimulation. A minimum of 5 days separates each TBS session to avoid potential carry-over effects. Outcome measures including resting-state fMRI and the Face-Name associative memory test (FNAME) were acquired immediately before and after each TBS session. Excitatory iTBS significantly improved associative memory and increased resting-state functional connectivity along the inferior longitudinal fasciculus (ILF) to the hippocampus compared to the sham TBS. Individuals who had a greater increase in functional connectivity between subfields of the hippocampus (i.e., CA1 and hippocampal fissures) and the superficial stimulation site following active TBS had greater memory enhancement (p < 0.05). New insights are provided about TBS propagation along the ILF from the surface stimulation site to the hippocampus. This tractography-guided TBS may be a useful strategy to guide the design of future TBS protocols to treat MCI. Keywords: Transcranial magnetic stimulation, Tractography, Mild Cognitive Impairment, Memory