MEASURING BRAIN AND COGNITIVE CHANGES IN MEMORY SYSTEMS AFTER TARGETED MULTIDAY REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION OF HEALTHY YOUNG, HEALTHY OLD, AND AMNESTIC MILD COGNITIVE IMPAIRMENT PARTICIPANTS

Abstract

Healthy and pathological aging processes contribute to declines in memory abilities in older adults, and current treatments offer limited remediation. One novel approach — targeted non-invasive brain stimulation (NBS) of intrinsic memory networks — is reported to enhance memory abilities in healthy young adults by 20% (Wang et al., 2014). To test generalizability of this finding, we are administering a clinical trial (ClinicalTrials.gov #NCT03574207) which replicates previously-reported NBS approaches in healthy young adults, healthy older adults, and patients with amnestic mild cognitive impairment (aMCI). Enrollment is continuing during this interim update; target enrollment for healthy young, healthy old, and aMCI groups is N=16 each. Our approach replicates methods from Wang et al. (2014). Enrolled participants complete two interventions (two weeks apart) consisting of pre-stimulation brain and cognitive measurement, NBS (treatment or sham for five consecutive days), and post-stimulation brain and cognitive measurement. The one-week interventions are identically formatted except for NBS parameters. Pre-/post-stimulation, brain variables measured include structural and resting-state functional MRI data; cognitive variables measured include cognitive abilities (e.g., hippocampal-dependent memory). In both intervention formats, we apply repetitive transcranial magnetic stimulation (rTMS) using β-frequency pulse sequences which alternate 2-sec. 20 Hz stimulation with 28-sec. rest for 20 min; the stimulation location is constant (left lateral parietal cortex coactive with hippocampus). Stimulation intensity is tailored to each participant's resting motor threshold (RMT) and varies by condition: treatment condition, 100% RMT; sham condition, 10% RMT. Participants complete both conditions in a counterbalanced order. Participant condition assignment is currently blinded per our trial design, but we will discuss our design and preliminary findings. We anticipate observing changes in brain and cognitive measures related to stimulation condition. Changes in brain variables are anticipated to include differences in regional resting-state functional connectivity, while changes in cognitive variables are expected to be positive following treatment NBS (vs. sham). Our ongoing clinical trial measures changes in brain and cognitive variables associated with NBS of a functional brain network supporting memory processes. Our expected findings will elucidate the plasticity of intrinsic networks supporting memory — conditioned on age and cognitive status — in response to NBS.