Site-specific effects of online rTMS during a working memory task in healthy older adults.

Abstract

The process of manipulating information within working memory (WM) is central to many cognitive functions, but also declines rapidly in old age. Given the importance of WM manipulation for maintaining healthy cognition, improving this process could markedly enhance health-span in older adults. The current pre-registered study tested the potential of online repetitive transcranial magnetic stimulation (rTMS) to enhance WM manipulation in healthy elderly adults. Online 5Hz rTMS was applied over the left lateral parietal cortex of 15 subjects to test the hypothesis that active rTMS would significantly improve performance compared to sham stimulation, and that these effects would be most pronounced in conditions with the highest cognitive demand. rTMS was applied while participants performed a delayed-response alphabetization task with two individually-titrated levels of difficulty. Sham stimulation was applied using an electrical sham coil that produced similar clicking sounds and somatosensory sensation as active stimulation but induced negligible effects on the brain. A stimulation site in left lateral parietal cortex was identified from fMRI activation maps and was targeted using individualized electric field modeling, stereotactic neuronavigation, and real-time robotic positioning, allowing optimal coil placement during the stimulation. Contrary to the a priori hypothesis, active rTMS significantly decreased accuracy relative to sham, and only in the hardest difficulty level. These results, therefore, demonstrate engagement of cortical WM processing, but not the anticipated facilitation, and provide a prescription for future studies that may attempt to enhance memory through application of different stimulation parameters.\n\nHighlightsO_LIThis study is one of the first attempts to enhance WM manipulation with online rTMS\nC_LIO_LIOnline 5Hz rTMS and sham were applied over the left parietal cortex of older adults\nC_LIO_LIIndividualized fMRI and electric field modeling were used to optimize targeting\nC_LIO_LIContrary to expectations, rTMS disrupted working memory manipulation abilities\nC_LIO_LIThis demonstrates that parietal cortex is involved in WM and modifiable with rTMS\nC_LI