Abstract
The development of technologies to protect or enhance memory in older people is an enduring goal of translational medicine. Here we describe repetitive (4-day) transcranial alternating current stimulation (tACS) protocols for the selective, sustainable enhancement of auditory–verbal working memory and long-term memory in 65–88-year-old people. Modulation of synchronous low-frequency, but not high-frequency, activity in parietal cortex preferentially improved working memory on day 3 and day 4 and 1 month after intervention, whereas modulation of synchronous high-frequency, but not low-frequency, activity in prefrontal cortex preferentially improved long-term memory on days 2–4 and 1 month after intervention. The rate of memory improvements over 4 days predicted the size of memory benefits 1 month later. Individuals with lower baseline cognitive function experienced larger, more enduring memory improvements. Our findings demonstrate that the plasticity of the aging brain can be selectively and sustainably exploited using repetitive and highly focalized neuromodulation grounded in spatiospectral parameters of memory-specific cortical circuitry.
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Data availability
The data used for analysis in this study are freely and permanently available on Open Science Framework (https://osf.io/g4wcq/).
Code availability
No custom codes were used for the experiment or the primary analyses.
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Acknowledgements
This work was supported by grants from the National Institutes of Health (R01-AG063775 and R01-MH114877) and a generous gift from an individual philanthropist awarded to R.M.G.R. We thank C. Willing and B. Lahner for assistance with data collection and X. (P.) Cheng and the anonymous reviewers for their thoughtful feedback on the manuscript.
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Conceptualization: R.M.G.R. and S.G.; data acquisition: R.M.G.R. and V.V.; data analysis and interpretation: R.M.G.R., S.G., W.W., V.V. and C.T.G.; writing—original draft: S.G. and W.W.; writing—review and editing: R.M.G.R., S.G., W.W., V.V. and C.T.G.; funding acquisition: R.M.G.R.; supervision: R.M.G.R.
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Extended data
Extended Data Fig. 1 Differences in memory performance according to biological sex in the DLPFC gamma group in Experiment 1.
Exploratory analyses examining the impact of biological sex showed a significant interaction effect of serial position x group x biological sex (F6.1,164.7 = 6.139, p = 7 × 10−6, ηp2 = 0.185) in Experiment 1 (N = 20 in the DLPFC gamma group, N = 20 in the IPL theta group, and N = 20 in the sham group). Follow-up analyses showed that the serial position x biological sex interaction was significant in the DLPFC gamma group (F2.4,43.2 = 19.160, p = 2.86 × 10−7, ηp2 = 0.516) but not in the IPL theta and sham groups (Fs < 1.754, ps > 0.173). Independent samples t-tests were performed to compare the memory performance for a given serial position on a given day between males and females in the DLPFC gamma group. Better primacy performance was observed among males in the DLPFC gamma group than females on day 2 (t18 = 2.619, p = 0.017, d = 1.177), day 3 (t18 = 2.288, p = 0.034, d = 1.028), day 4 (t18 = 3.151, p = 0.006, d = 1.416), and 1 month (t13.4 = 2.477, p = 0.027, d = 1.029) timepoints. Other trends observed were improved performance in males on day 2 of neuromodulation, evident in the middle 1 (t18 = 2.490, p = 0.023, d = 1.119) and the middle 3 (t18 = 2.136, p = 0.047, d = 0.960) clusters, and better performance among females at the offline timepoint 1 month after intervention in the middle 2 (t18 = −2.226, p = 0.039, d = −1.001) and recency (t18 = −2.448, p = 0.025, d = −1.1) clusters. However, none of these effects survived correction for multiple comparisons (Bonferroni correction; pcutoff = 0.0017). Data are represented as mean values +/− S.E.M. across participants.
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Grover, S., Wen, W., Viswanathan, V. et al. Long-lasting, dissociable improvements in working memory and long-term memory in older adults with repetitive neuromodulation. Nat Neurosci 25, 1237–1246 (2022). https://doi.org/10.1038/s41593-022-01132-3
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DOI: https://doi.org/10.1038/s41593-022-01132-3
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