Beynel L, Davis SW, Crowell CA, Hilbig SA, Lim W, Nguyen D, Palmer H, Brito A, Peterchev AV, Luber B, Lisanby SH, Cabeza R, and Appelbaum LG
Working memory is the ability to perform mental operations on information that is stored in a flexible, limited capacity buffer. The ability to manipulate information in working memory is central to many aspects of human cognition, but also declines with healthy aging. Given the profound importance of such working memory manipulation abilities, there is a concerted effort towards developing approaches to improve them. The current study tested the capacity to enhance working memory manipulation with online repetitive transcranial magnetic stimulation in healthy young and older adults. Online high frequency (5Hz) repetitive transcranial magnetic stimulation was applied over the left dorsolateral prefrontal cortex to test the hypothesis that active repetitive transcranial magnetic stimulation would lead to significant improvements in memory recall accuracy compared to sham stimulation, and that these effects would be most pronounced in working memory manipulation conditions with the highest cognitive demand in both young and older adults. Repetitive transcranial magnetic stimulation was applied while participants were performing a delayed response alphabetization task with three individually-titrated levels of difficulty. The left dorsolateral prefrontal cortex was identified by combining electric field modeling to individualized functional magnetic resonance imaging activation maps and was targeted during the experiment using stereotactic neuronavigation with real-time robotic guidance, allowing optimal coil placement during the stimulation. As no accuracy differences were found between young and older adults, the results from both groups were collapsed. Subsequent analyses revealed that active stimulation significantly increased accuracy relative to sham stimulation, but only for the hardest condition. These results point towards further investigation of repetitive transcranial magnetic stimulation for memory enhancement focusing on high difficulty conditions as those most likely to exhibit benefits., Competing Interests: A. V. Peterchev is inventor on patents and patent applications and, in the past 5 years, has received travel support as well as patent royalties from Rogue Research; research and travel support, consulting fees, as well as equipment loan from Tal Medical; research and patent application support from Magstim; as well as equipment loans from MagVenture, all related to TMS technology, but not directly related to the presented work. Please find below the name and numbers for these patents. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Patents & patent applications (*Licensed and commercialized by Rogue Research since 2011): Peterchev, A. V. System for inducing electric field pulses in a body organ. US 7753836 B2.* (2010). Peterchev, A. V. System for inducing electric field pulses in a body organ. US 7946973 B2.* (2011). Peterchev, A. V. System for inducing electric field pulses in a body organ. EP 2026871 B1.* (2011). Peterchev, A. V. Systems and methods for inducing electric field pulses in a body organ. US 8545378 B2.* (2013). Peterchev, A. V. Systems for inducing electric field pulses in a body organ. EP 2432547 B1.* (2014). Peterchev, A. V., Lisanby, S. H., and Deng, Z.-D. Methods, apparatus, and systems for magnetic stimulation. US 8801589 B2. (2014). Goetz, S. M., Murphy, D. L. K., Peterchev, A. V. Magnetic Neurostimulation with Reduced Acoustic Emission. Application US20150367141A1 (2015). Goetz, S. M., Murphy, D. L. K., Peterchev, A. V. Apparatus and method for low-noise magnetic neurostimulation. Application DE102014008820A1. (2015). Peterchev, A. V. Systems for inducing electric field pulses in a body organ. US 9345901 B2.* (2016). Peterchev, A. V., Lisanby, S. H., and Deng, Z.-D. Methods, apparatus, and systems for magnetic stimulation. US 9295853 B2. (2016). Peterchev, A. V., Lisanby, S. H., and Deng, Z.-D. Methods, apparatus, and systems for magnetic stimulation. EP 2321007 B1. (2016). Goetz, S. M., Murphy, D. L. K., Peterchev, A. V. Device and method for low-noise magnetic neurostimulation. Application US20170189710A1. (2017).