Long-lasting enhancements of memory and hippocampal-cortical functional connectivity following multiple-day targeted noninvasive stimulation.

Noninvasive stimulation can alter the function of brain networks, although the duration of neuroplastic changes are uncertain and likely vary for different networks and stimulation parameters. We have previously shown that multiple-day repetitive transcranial magnetic stimulation can influence targeted hippocampal-cortical networks, producing increased functional MRI connectivity of these networks and concomitant improvements in memory that outlast stimulation by ∼24 h. Here, we present new analyses showing that multiple-day targeted stimulation of hippocampal-cortical networks produces even longer-lasting enhancement. The ability to learn novel, arbitrary face-word pairings improved over five consecutive daily stimulation sessions, and this improvement remained robust at follow-up testing performed an average of 15 days later. Furthermore, stimulation increased functional MRI connectivity of the targeted portion of the hippocampus with distributed regions of the posterior hippocampal-cortical network, and these changes in connectivity remained robust at follow-up testing. Neuroplastic changes of hippocampal-cortical networks caused by multiple-day noninvasive stimulation therefore persist for extended periods. These findings have implications for the design of multiple-day stimulation experiments and for the development of stimulation-based interventions for memory disorders.