Fig. 5: CL stimulation prevents epilepsy progression and memory deterioration.

a, LFP traces from hippocampus and corresponding mPFC spectrograms for sample kindled-only, sham and CL rat. Scale bar, 1 s. b, IEDmPFC occurrence across kindling (left) and quantified at late kindling (right); ANOVA with Bonferroni–Holm correction, P = 2.93 × 10−6, F = 25.47; kindled-only/sham, P = 0.3287; CL/kindled-only; P = 2.64 × 10−6; CL/sham, P = 0.0049; kindled-only n = 39 sessions, 10 rats; sham n = 32 sessions, 7 rats; CL n = 48 sessions, 11 rats. *P < 0.05. c, mPFC epileptogenicity over kindling (left; Mann–Kendall tau; CL, n = 11 rats, P = 0.3; sham, n = 7 rats, P = 8.43 × 10−8; kindled-only, n = 10 rats, P = 8.42 × 10−8). Progression of epileptogenicity over kindling days for kindled-only and sham rats (right; linear mixed-effects model; CL, P = 0.188; sham, P = 0.001; kindled-only, P = 3.51 × 10−26). Box center = coefficient estimate, box boundaries = 5, 95% CI. *P < 0.05. d, Kaplan–Meier curve of progression from focal to bilateral convulsive seizures (kindled-only; n = 10 rats; sham, n = 7 rats; CL, n = 11 rats; log-rank test: kindled-only/sham, P = 1.25 × 10−2; kindled-only/CL, P = 2.42 × 10−3; sham/CL, P = 2.25 × 10−2). e, Examples of exploration path (dashed lines) with reward locations (blue circle, nonretrieved reward; open circle, retrieved reward) for the first three trials of the memory test in late kindling for sample kindled-only and CL rats. f, Memory performance over kindling for kindled-only (n = 4 rats), sham (n = 4 rats) and CL (n = 6 rats): ANOVA with Bonferroni–Holm correction: F = 19.76; kindled-only/sham: baseline (P = 0.77, n = 12/12 sessions), early (P = 0.90, n = 8/8 sessions) and late (P = 0.77, n = 12/12 sessions); sham/CL: baseline (P = 0.98, n = 12/17 sessions), early (P = 0.064, n = 8/11 sessions) and late (P = 4.15 × 10−12, n = 12/17 sessions); kindled-only/CL: baseline (P = 0.77, n = 12/17 sessions), early (P = 0.047, n = 8/11 sessions) and late (P = 7.85 × 10−13, n = 12/17 sessions). *P < 0.05. Data are presented as mean ± s.e.m. unless otherwise noted.