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ObjectiveTo test whether targeting hippocampal-cortical brain networks with high-frequency transcranial magnetic stimulation in older adults influences behavioral and neural measures characteristic of age-related memory impairment.MethodsFifteen adults aged 64 to 80 years (mean = 72 years) completed a single-blind, sham-controlled experiment. Stimulation targets in parietal cortex were determined based on fMRI connectivity with the hippocampus. Recollection and recognition memory were assessed after 5 consecutive daily sessions of full-intensity stimulation vs low-intensity sham stimulation using a within-subjects crossover design. Neural correlates of recollection and recognition memory formation were obtained via fMRI, measured within the targeted hippocampal-cortical network vs a control frontal-parietal network. These outcomes were measured approximately 24 hours after the final stimulation session.ResultsRecollection was specifically impaired in older adults compared to a young-adult control sample at baseline. Relative to sham, stimulation improved recollection to a greater extent than recognition. Stimulation increased recollection fMRI signals throughout the hippocampal-cortical network, including at the targeted location of the hippocampus. Effects of stimulation on fMRI recollection signals were greater than those for recognition and were greater in the targeted network compared to the control network.ConclusionsAge-related recollection impairments were causally related to hippocampal-cortical network function in older adults. Stimulation selectively modified neural and behavioral hallmarks of age-related memory impairment, indicating effective engagement of memory intervention targets in older adults.

Introduction The distributed cortical network of the human hippocampus is important for episodic memory. In a previous experiment, noninvasive stimulation of the hippocampal‐cortical network applied for five consecutive days improved paired‐associate learning measured after the stimulation regimen via cued recall (Wang et al., Science, 2014, 345, 1054). This finding has not yet been directly replicated. Furthermore, evidence for long‐lasting effects of stimulation on paired‐associate learning was obtained by analyzing relatively small subsamples (Wang & Voss, Hippocampus, 2015, 25, 877) and requires further evaluation. Methods Sixteen healthy young adults participated in this replication study using the same experimental design as the original study. Participants received 1 week of active stimulation and 1 week of sham stimulation, with memory assessments occurring at the beginning (pre) and end (post) of each week. Assessments included the paired‐associate task used in the original study, as well as a long‐term episodic memory retention task in order to test the hypothesis that increased paired‐associate learning could come at the cost of accelerated long‐term forgetting. Change in memory scores was evaluated within (pre vs. post) and across (active vs. sham) weeks. Results Similar to Wang et al., paired‐associate learning was significantly improved after 1 week of active stimulation but not after 1 week of sham stimulation. We found no evidence that stimulation increased long‐term forgetting for either week. Conclusion These findings confirm the beneficial effects of stimulation on episodic memory that were reported previously and indicate that stimulation‐related gains in new learning ability do not come at the price of accelerated long‐term forgetting.

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