Post-study caffeine administration enhances memory consolidation in humans

Journal name:
Nature Neuroscience
Volume:
17,
Pages:
201–203
Year published:
DOI:
doi:10.1038/nn.3623
Received
Accepted
Published online
Corrected online
Corrected online

It is currently not known whether caffeine has an enhancing effect on long-term memory in humans. We used post-study caffeine administration to test its effect on memory consolidation using a behavioral discrimination task. Caffeine enhanced performance 24 h after administration according to an inverted U-shaped dose-response curve; this effect was specific to consolidation and not retrieval. We conclude that caffeine enhanced consolidation of long-term memories in humans.

At a glance

Figures

  1. Caffeine enhances discrimination performance 24 h after study.
    Figure 1: Caffeine enhances discrimination performance 24 h after study.

    (a) Outline of study design. After arrival of screened subjects, a baseline salivary sample was collected. Then the encoding task was administered. This was an incidental indoor-outdoor judgment task (stimuli every 2,500 ms, with an interstimulus interval (ISI) of 500 ms). After encoding, subjects were administered either 200 mg caffeine or placebo pills. After 1 h and 3 h, additional saliva samples were collected. Subjects returned 24 h later for testing. Before a recognition test, a final saliva sample was collected. Recognition was tested using an old-similar-new judgment task (stimuli every 2,500 ms with a 500-ms ISI) using targets, foils and similar lures that are particularly sensitive to hippocampal pattern separation. (b) Lure discrimination by subjects (i.e., whether subjects had a higher propensity to call lure items 'similar' rather than 'old') (t42 = 1.79, one-tailed P = 0.04). *P < 0.05, one-tailed. (c,d) Target hit rates (c) and foil rejection rates (d) (t42 = 0.59, one-tailed P = 0.27 and t42 = 0.15, one-tailed P = 0.44 between groups that received caffeine and placebo, for data in c and d, respectively). Error bars, ±s.e.m.; n = 20 subjects (caffeine) and n = 24 subjects (placebo).

  2. Impact of caffeine on consolidation and variable dose effects.
    Figure 2: Impact of caffeine on consolidation and variable dose effects.

    (a) LDI in subjects administered placebo or caffeine immediately after the study session (immediate), or caffeine 24 h after the study session (delayed). LDI in immediate caffeine group was enhanced compared to placebo (t71 = 2.0, two-tailed P = 0.0049). LDI in the delayed group was no different from placebo (t55 = 0.63, P = 0.53). (b) Analysis by item similarity showed a significant main effect of similarity (F2,88 = 12.87, P = 0.001) as well as a main effect of caffeine (F1,42 = 4.07, P = 0.05). (c) Discrimination as a function of indicated caffeine dose (200 mg caffeine compared to placebo, t71 = 2.0, two-tailed P = 0.049 and compared to 100 mg caffeine, t48 = 2.19, two-tailed P = 0.033). Discrimination at 200 mg and 300 mg caffeine doses compared to placebo and 100 mg caffeine combined, t96 = 2.77, two-tailed P = 0.007. (d) Rebinned subject performance based on change in the amount of caffeine from baseline divided into quartiles (no change, low change, medium change and high change) showing evidence for an inverted U-shaped dose-response curve. The quadratic curve fit (R2 = 0.81) was significantly better than the linear fit (R2 = 0.45) for discrimination as a function of caffeine change (F = 29.5, P = 0.001). Error bars, ±s.e.m.*P< 0.05.

  3. Representative high-performance liquid chromatography (HPLC) trace.
    Supplementary Fig. 1: Representative high-performance liquid chromatography (HPLC) trace.

    Trace shows distinct peaks for caffeine, paraxanthine and benzotriazole. Units are in milli Absorbance Units (mAU) at 280 nm.

  4. Caffeine absorption and metabolism.
    Supplementary Fig. 2: Caffeine absorption and metabolism.

    Group averages of the sum of caffeine and paraxanthine concentrations (μg/ml) from HPLC. Both the caffeine and placebo group had negligible amounts of caffeine and paraxanthine in saliva at baseline. The caffeine group had a significant increase in caffeine and paraxanthine concentrations at 1 hour and 3 hours, then declined to baseline at 24 hours. The placebo group had no such increase in caffeine or paraxanthine. Error bars are + 1 s.e.m.

Change history

Corrected online 17 January 2014
In the version of this article initially published, in the first sentence in the Online Methods, the s.d. of the age of the subjects was missing and the number of female subjects was given as 280. The s.d. is 2 years and the number of female subjects is 80. The error has been corrected in the HTML and PDF versions of the article.
Corrected online 30 October 2014
In the version of this article initially published, there were errors in the reporting of statistics. In the Figure 1b legend, the asterisked P value was given in the HTML version as *P = 0.05 and in the PDF version as *P < 0.05. It should read *P < 0.05, one-tailed. In the Figure 2a legend, the degrees of freedom for the immediate caffeine group were given as 42 and the P value as 0.05; the correct values are 71 and 0.049, respectively. In the Figure 2b legend and the fifth paragraph of the main text, the P value for the main effect of caffeine was given as 0.001; the correct value is 0.05. The errors have been corrected in the HTML and PDF versions of the article.

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Author information

Affiliations

  1. Department of Psychological and Brain Sciences, Johns Hopkins University, Baltimore, Maryland, USA.

    • Daniel Borota,
    • Elizabeth Murray,
    • Allen Chang,
    • Joseph M Watabe,
    • Maria Ly &
    • Michael A Yassa
  2. Department of Chemistry, Johns Hopkins University, Baltimore, Maryland, USA.

    • Gizem Keceli &
    • John P Toscano
  3. Department of Neurobiology and Behavior, University of California, Irvine, California, USA.

    • Michael A Yassa

Contributions

D.B., J.P.T. and M.A.Y. designed the study. D.B., E.M., G.K., A.C., J.M.W. and M.L. conducted the experiments. D.B. and M.A.Y. wrote the manuscript with input from all authors.

Competing financial interests

The authors declare no competing financial interests.

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Supplementary information

Supplementary Figures

  1. Supplementary Figure 1: Representative high-performance liquid chromatography (HPLC) trace. (38 KB)

    Trace shows distinct peaks for caffeine, paraxanthine and benzotriazole. Units are in milli Absorbance Units (mAU) at 280 nm.

  2. Supplementary Figure 2: Caffeine absorption and metabolism. (52 KB)

    Group averages of the sum of caffeine and paraxanthine concentrations (μg/ml) from HPLC. Both the caffeine and placebo group had negligible amounts of caffeine and paraxanthine in saliva at baseline. The caffeine group had a significant increase in caffeine and paraxanthine concentrations at 1 hour and 3 hours, then declined to baseline at 24 hours. The placebo group had no such increase in caffeine or paraxanthine. Error bars are + 1 s.e.m.

PDF files

  1. Supplementary Text and Figures (217 KB)

    Supplementary Figures 1–2 and Supplementary Table 1

Additional data