Distribution of effect sizes.

<p>(A) Distribution of effect sizes, calculated as % of control group freezing. Interventions were divided into memory-impairing (-48.6 ± 18.1%, n = 146), memory-enhancing (71.6 ± 53.2%, n = 53) or non-effective (-1.8 ± 26.2%, n = 211) for visualization purposes, according to the statistical significance of the comparison performed in the article. Additionally, the whole sample of experiments is shown in grey (-9.0 ± 47.5% [-13.6 to -4.4], n = 410). Values are expressed as mean ± SD [95% confidence interval]. Lines and whiskers in the inset express median and interquartile interval. (B) Distribution of normalized effect sizes, calculated as % of the group with the highest mean (i.e. control group for memory-impairing interventions, or treated group for memory-enhancing interventions).</p

Correlation between description of results and effect size/statistical power.

<p>Description scores refer to the mean score given by 14 neuroscience researchers who rated terms as “weak” (0), “neutral” (1) or “strong” (2) in the case of those describing significant differences, or as “similar” (0), “neutral” (1) or “trend” (2) in the case of those describing non-significant ones. (A) Correlation between normalized effect size and description score for significant results. r = -0.05, p = 0.48 (n = 195). (B) Correlation between statistical power and description score for significant results. r = 0.03, p = 0.73 (n = 155). (C) Correlation between normalized effect size and description score for non-significant results. r = 0.28, p = 0.0002* (n = 174). (D) Correlation between upper-bound estimate of statistical power and description score for non-significant results. r = 0.03, p = 0.74 (n = 146). Asterisk indicates significant result according to Holm-Sidak correction for 28 experiment-level correlations.</p

Correlations between effect size, variation and statistical power.

<p>(A) Correlation between normalized effect size and mean sample size. No correlation is found (r = 0.0007, p = 0.99; r = -0.26, p = 0.64 after adjustment), although sample size variation is limited. (B) Correlation between normalized effect size and coefficient of variation. Correlation of the whole sample of experiments yields r = 0.37, p<0.0001* (n = 336; r = 0.32, p<0.001 after adjustment for freezing levels). (C) Correlation between normalized effect size and statistical power based on upper-bound effect size of 45.6%. Correlation of the whole sample of experiments yields r = -0.12, p = 0.03 (r = 0.11, p = 0.84 after adjustment for freezing levels), but distribution is skewed due to a ceiling effect on power. (D) Correlation between normalized effect size and statistical power based on intermediate effect size of 37.2%; r = -0.16, p = 0.003* (r = -0.16, p = 0.48 after adjustment). (E) Correlation between normalized effect size and statistical power based on lower-bound effect size of 29.5%; r = -0.21, p<0.0001* (r = -0.1, p = 0.06 after adjustment). Asterisks indicate significant results according to Holm-Sidak correction for 28 experiment-level correlations.</p

Correlation between citations and percentage of significant experiments, effect size and statistical power.

<p>Citations were obtained for all articles on August 26^th, 2016. (A) Correlation between % of significant results per article and citations. r = -0.03, p = 0.75 (n = 121). (B) Correlation between mean normalized effect size of effective interventions and citations. r = 0.097, p = 0.34 (n = 98). (C) Correlation between mean statistical power (upper-bound estimate) and citations. r = -0.08, p = 0.40 (n = 104). (D) Correlation between study quality score and citations. r = 0.09, p = 0.31 (n = 121). According to Holm-Sidak correction for 8 article-level correlations, none is significant.</p

Study flow diagram.

<p>Our PubMed search yielded 400 results, of which 14 were excluded based on initial screening of titles and abstracts and 386 were selected for full-text analysis. This led to the inclusion of 122 articles, containing a total of 410 comparisons (i.e. individual experiments). The main reasons for exclusion are listed in the figure, in compliance with the PRISMA statement [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0196258#pone.0196258.ref021" target="_blank">21</a>].</p

Number of articles including quality assessment items.

<p>Number of articles including quality assessment items.</p

Effect sizes and coefficients of variation across different protocols, species and sexes.

<p>Colors indicate memory-enhancing (red), memory-impairing (blue) or non-effective (yellow) experiments, all of which are pooled for analysis. Lines and whiskers express median and interquartile interval. (A) Distribution of effect sizes across cued (n = 171) and contextual (n = 239) conditioning protocols. Student’s t test, p<0.0001*. (B) Coefficients of variation across cued (n = 145) and contextual (n = 191) conditioning protocols. Student’s t test, p = 0.001*. (C) Distribution of effect sizes across experiments using mice (n = 237) or rats (n = 173). Student’s t test, p = 0.76. (D) Coefficients of variation across experiments using mice (n = 193) or rats (n = 143). Student’s t test, p = 0.008. (E) Distribution of effect sizes across experiments using male (n = 277), female (n = 36) or both (n = 67) sexes. One-way ANOVA, p = 0.004*; Tukey’s post-hoc test, male vs. female p = 0.01, male vs. both p = 0.40, female vs. both p = 0.003. 30 experiments were excluded from this analysis for not stating the sex of animals. (F) Coefficients of variation across experiments using male (n = 233), female (n = 28) or both (n = 60) sexes. One-way ANOVA, p<0.0001*; Tukey’s test, male vs. female p = 0.85, male vs. both p<0.0001, female vs. both p = 0.0006. For coefficient of variation analyses, 74 experiments were excluded due to lack of information on sample size for individual groups. Asterisks indicate significant results according to Holm-Sidak correction for 14 experiment-level comparisons.</p

Clinical outcomes at baseline and post-treatment assessments (n = 8).

<p>Clinical outcomes at baseline and post-treatment assessments (n = 8).</p

Structure and content of intervention programme.

<p>Structure and content of intervention programme.</p

Significant effect of animal age category (A), d-galactose dose category (B), animal strain (C), and behavioural task (D) on the neurobehavioral score (NBS) measured using standardised mean differences (SMDs).

<p>Horizontal grey bars show the 95% CI of the global estimate of impairment in NBS and vertical error bars show 95% confidence interval (CI). The relative number of animals in each comparison has been presented using bar width.</p