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DANDI:001888

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EEG recordings from a Grin2b+/- rat model of GRIN2B neurodevelopmental disorder: absence seizures and sleep-wake abnormalities

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Claims

From the paper Absence seizures and sleep-wake abnormalities in a rat model of GRIN2B neurodevelopmental disorder

Reproducing Hristova, Fasol et al. (2025) from dandiset 001888 24

Notebook reproduce_hristova_2025.ipynb

  • Not reproducedFigure 4B

    During NREM sleep Grin2b+/- rats have higher beta power than WT (two-way ANOVA genotype x band, interaction p = .038; Tukey beta p = .0008, other bands p >= .82).

    In NREM sleep, Grin2b+/− animals had statistically higher beta power in comparison to wild‐type rats

    Figure 4B

    What the paper reports

    • genotype x frequency interaction: two-way ANOVA, F = 2.64, df = 4, p = 0.038 (n = 9 wild-type and 14 Grin2b+/- rats)
    • beta band, genotype: Tukey post hoc test, p = 8 × 10⁻⁴ (n = 9 wild-type and 14 Grin2b+/- rats)

    NREM beta is lower in Het (difference -0.078 normalized, Tukey p = 1.0); interaction p = 0.90. Every variant with both WT (GRIN2B-132 either way, contiguous bands, SWD epochs from flags, slope rejection, cleaner S1 channel, stored spectra) has Het beta lower, by 0.0035 to 0.30. With GRIN2B-238 left out Het beta is higher in 7 of 12 variants, by 0.0032 to 0.147, with Tukey p >= 0.99 and interaction p >= 0.92.

    How the test differed from the paper’s method

    • As for fig4a-rem-spectrum; two WT rats.
  • Not reproducedFigure 4C

    During wake, spectral power is reduced in Grin2b+/- rats overall, without a difference in single bands (two-way ANOVA genotype x band, genotype p = .01, interaction p = .86).

    In the wake state, spectral power was significantly reduced in Grin2b+/− rats relative to ... littermates, although this reduction was not restricted to individual frequency bands

    Figure 4C

    What the paper reports

    • effect of genotype: two-way ANOVA, F = 6.84, df = 1, p = 0.01 (n = 9 wild-type and 14 Grin2b+/- rats)
    • genotype x frequency interaction: two-way ANOVA, F = .33, df = 4, p = 0.86 (n = 9 wild-type and 14 Grin2b+/- rats)

    Normalized wake power is higher in Het on average (+0.081; genotype F = 0.58, p = 0.45), and higher on average in every variant on the raw EEG with both WT (+0.0065 to +0.168). The stored spectra have Het lower on average (-0.027, p = 0.59; p = 0.0072 only with GRIN2B-132 counted as WT), as does the cleaner S1 channel without GRIN2B-238 (-0.0072, p = 0.93).

    How the test differed from the paper’s method

    • As for fig4a-rem-spectrum; two WT rats.
  • Partially reproducedFigure 2C, middle

    SWDs are longer on average in Grin2b+/- rats than in WT (two-sample t test, df = 22, T = -5.26, p = .00003).

    Furthermore, Grin2b+/− rats had a longer average SWD duration and total SWD duration than

    Figure 2C, middle

    What the paper reports

    • two-sample unpaired t test, df = 22, T = -5.26, p = 3 × 10⁻⁵ (n = 9 wild-type and 15 Grin2b+/- rats)

    Het mean SWD duration 4.54 s against 1.47 s in GRIN2B-240, the only WT rat with SWDs; t test p = 0.16 (df 13). With GRIN2B-132 (1.70 s) as WT p = 0.062; without GRIN2B-228 p = 0.090. A t test against a single WT value says little either way.

    How the test differed from the paper’s method

    • One WT rat has SWDs, so the WT group has one value.
  • Partially reproducedDiscussion, paragraph 2

    Over 24 h, Grin2b+/- rats spend on average 59.97 min in SWDs, while WT littermates average less than a minute.

    Over 24 h, Grin2b+/− mutants had on average of 59.97 min of SWDs, almost an entire hour of the day in an absence seizure. In contrast, wild‐type littermates had average totals of less than a minute.

    Discussion, paragraph 2

    The Het mean of 57.77 min per day (SEM 9.04, 14 rats) is within 59.97 +- 6.0. The WT mean is 1.37 min (0 and 2.75), not below 1 min. Without GRIN2B-228 the Het mean is 62.21, also within tolerance; without GRIN2B-238 the WT mean is 2.75. Counting the epochs SWD events overlap as 5 s each gives 110.57 min, and counting the epochs the scorer flags gives 60.2 min, so the paper's number fits both the event durations and the flags.

    How the test differed from the paper’s method

    • Two WT rats, where the paper has nine; the WT part rests on GRIN2B-240 alone.
  • Partially reproducedFigure 3G, right; Results, Sleep–wake abnormalities in Grin2b+/- rats, paragraph 2

    REM bouts are longer on average in Grin2b+/- rats than in WT (Wilcoxon rank-sum, W = 33, p = .043).

    Of interest, the average duration of REM sleep bouts was longer for Grin2b+/− animals

    Figure 3G, right; Results, Sleep–wake abnormalities in Grin2b+/- rats, paragraph 2

    What the paper reports

    • Wilcoxon rank-sum test, W = 33, p = 0.043 (n = 9 wild-type and 15 Grin2b+/- rats)

    Het REM bouts 71.9 s, WT 56.8 s; W = 2, p = 0.067. With GRIN2B-132 (95.5 s) as WT the difference is 2.2 s (p = 0.59). Without GRIN2B-228 p = 0.076; with bouts not split by SWD epochs p = 0.067.

    How the test differed from the paper’s method

    • Two WT rats; bout definition chosen here.
  • Partially reproducedFigure 3H, middle and right

    Grin2b+/- rats have fewer NREM bouts, which are longer, than WT (Wilcoxon rank-sum, bouts W = 29.5, p = .025; mean bout duration W = 26, p = .015).

    Nonetheless, Grin2b+/− rats demonstrated abnormal NREM distributions when compared to ... littermates, as they had statistically fewer NREM bouts, which where longer in average duration

    Figure 3H, middle and right

    What the paper reports

    • number of NREM bouts: Wilcoxon rank-sum test, W = 29.5, p = 0.025 (n = 9 wild-type and 15 Grin2b+/- rats)
    • average NREM bout duration: Wilcoxon rank-sum test, W = 26, p = 0.015 (n = 9 wild-type and 15 Grin2b+/- rats)

    Mean NREM bout duration Het 127.1 s, WT 92.3 s, W = 0, p = 0.017. Number of NREM bouts Het 218.5, WT 273.0 per day, W = 25, p = 0.10. With the scorer's flags, the stored scores or bouts not split by SWD epochs both parts have p < 0.05 (bouts p = 0.032). Without GRIN2B-228 bouts p = 0.11, duration p = 0.019.

    How the test differed from the paper’s method

    • Two WT rats; bout definition chosen here.
  • Partially reproducedFigure 3I, left; Results, Sleep–wake abnormalities in Grin2b+/- rats, paragraph 4

    Grin2b+/- rats spend less total time awake over 24 h than WT (Welch t test, df = 10.25, T = 2.26, p = .047).

    When compared to wild‐type littermates, the total minutes awake was significantly reduced in Grin2b+/− rats

    Figure 3I, left; Results, Sleep–wake abnormalities in Grin2b+/- rats, paragraph 4

    What the paper reports

    • Welch's two-sample unpaired t test, df = 10.25, T = 2.26, p = 0.047 (n = 9 wild-type and 15 Grin2b+/- rats)

    Het 834.1 min awake per day, WT 944.9, difference -110.8 min; Welch p = 0.35. With the scorer's flags -68.1 min (p = 0.49), with only the SWD time removed -65.5 min (p = 0.50), with the stored scores -10.8 min (p = 0.89), so most of the difference is SWD time removed from wake. Without GRIN2B-228 -121.2 min (p = 0.33).

    How the test differed from the paper’s method

    • Two WT rats; SWD epochs are the epochs SWD events overlap.
  • Partially reproducedFigure 3I, middle and right

    Grin2b+/- rats have more wake bouts of shorter duration than WT (Wilcoxon rank-sum, W = 18, p = .0035; Welch t test on mean bout duration, df = 8.91, T = 2.97, p = .016).

    When compared to wild‐type littermates, the total minutes awake was significantly reduced in Grin2b+/− rats, with mutants having more wake bouts of shorter duration

    Figure 3I, middle and right

    What the paper reports

    • number of wake bouts: Wilcoxon rank-sum test, W = 18, p = 0.0035 (n = 9 wild-type and 15 Grin2b+/- rats)
    • average wake bout duration: Welch's two-sample unpaired t test, df = 8.91, T = 2.97, p = 0.016 (n = 9 wild-type and 15 Grin2b+/- rats)

    Het 559.4 wake bouts per day against WT 294.5 (W = 2, p = 0.067); mean wake bout 100.6 s against 206.2 s (Welch p = 0.31). With the stored scores, where SWD epochs count as wake, both reverse (190.8 against 241.0 bouts, p = 0.017; 304.2 against 239.2 s), and they reverse with bouts not split by SWD epochs too (186.3 against 241.0 bouts, p = 0.017; 275.4 against 237.7 s). The outcome rests on SWD epochs ending wake bouts, which follows the Methods' exclusion of SWD times but builds part of the difference in. Without GRIN2B-228 the bout count has p = 0.019.

    How the test differed from the paper’s method

    • Two WT rats; bout definition chosen here; SWD epochs end wake bouts.
  • Partially reproducedFigure 5A; Results, Brain state abnormalities in Grin2b+/- rats are not correlated with absence seizure activity, paragraph 1

    Over both genotypes, SWDs occur mostly in wake (94.8%), then NREM (4.4%), and rarely in REM sleep (0.5%).

    Collectively for both genotypes, we observed that SWDs predominantly occurred during wake (94.8%), followed by NREM (4.4%) and scarcely during REM sleep (.5%)

    Figure 5A; Results, Brain state abnormalities in Grin2b+/- rats are not correlated with absence seizure activity, paragraph 1

    Reading (a) gives wake 94.18%, NREM 5.55%, REM 0.27% over 16 rats with SWDs; wake is within tolerance and the order holds, NREM and REM are not. Reading (b) 92.87, 6.81, 0.32; (c) 91.17, 8.64, 0.19; (d) 89.27, 10.50, 0.23. Readings (c) and (d) follow the Supplementary Methods' rule. No reading puts all three within tolerance. Without GRIN2B-228 the values move by at most 0.6 percentage points.

    How the test differed from the paper’s method

    • The paper's text allows four readings of how the percentages are formed; all are shown.
    • Two of the paper's nine WT rats; GRIN2B-132 is included.
  • Partially reproducedFigure 5C; Results, Brain state abnormalities in Grin2b+/- rats are not correlated with absence seizure activity, paragraph 1

    All Grin2b+/- rats have SWDs that start at wake-NREM transitions, against 3 of 9 WT rats (Fisher's exact test, p = .00062).

    all Grin2b+/− rats had SWDs initiating at wake‐NREM transitions, whereas this was the case for only a small fraction of ... littermates (33.33%, 3/9 rats)

    Figure 5C; Results, Brain state abnormalities in Grin2b+/- rats are not correlated with absence seizure activity, paragraph 1

    What the paper reports

    • Fishers exact test, p = 6.2 × 10⁻⁴ (n = 9 wild-type and 15 Grin2b+/- rats)

    13 of 14 Het rats have at least one SWD at a wake-NREM transition, 0 of 2 WT; Fisher p = 0.025. GRIN2B-228 (2 SWDs in two days, none after NREM) has none. The claim's statement that all Het have such SWDs does not hold for GRIN2B-228; it may not be one of the paper's rats. Without GRIN2B-228 13 of 13 Het count (Fisher p = 0.0095), which would meet the criterion; the outcome is judged on all 16 rats.

    How the test differed from the paper’s method

    • The definition of a wake-NREM transition (a wake epoch followed by an NREM epoch within the six epochs before the SWD) was chosen here.
  • Partially reproducedFigure 5D-F

    In Grin2b+/- rats, total SWD duration is not correlated with total REM or NREM time, the number of REM, NREM or wake bouts, or the mean REM, NREM or wake bout duration (Pearson, all p >= .066).

    Quantification revealed total SWD duration is negatively correlated with total time awake ... and is uncorrelated to all other sleep measurements

    Figure 5D-F

    What the paper reports

    • total time in REM: Pearson correlation, T = -.055, df = 13, R = -.015, p = 0.96 (n = 15 Grin2b+/- rats)
    • total time in NREM: Pearson correlation, T = -1.47, df = 13, R = -.13, p = 0.65 (n = 15 Grin2b+/- rats)
    • number of REM bouts: Pearson correlation, T = .704, df = 13, R = -.19, p = 0.49 (n = 15 Grin2b+/- rats)
    • number of NREM bouts: Pearson correlation, T = 2.006, df = 13, R = .49, p = 0.066 (n = 15 Grin2b+/- rats)
    • number of wake bouts: Pearson correlation, T = .61, df = 13, R = .17, p = 0.55 (n = 15 Grin2b+/- rats)
    • average REM bout duration: Pearson correlation, T = .61, df = 13, R = .17, p = 0.55 (n = 15 Grin2b+/- rats)
    • average NREM bout duration: Pearson correlation, T = -1.44, df = 13, R = -.37, p = 0.17 (n = 15 Grin2b+/- rats)
    • average wake bout duration: Pearson correlation, T = -.93, df = 13, R = -.25, p = 0.37 (n = 15 Grin2b+/- rats)

    Two of the eight measures correlate with total SWD time, the number of wake bouts (R = 0.54, p = 0.046) and mean wake bout duration (R = -0.58, p = 0.028); the other six have p from 0.16 to 0.96. With the scorer's flags the same two correlate (R = 0.82, -0.72); with the stored scores, with bouts not split by SWD epochs or without GRIN2B-228 none does. The paper gives R = 0.17 and -0.25 for these two.

    How the test differed from the paper’s method

    • 14 Het; the criterion grades eight tests (none significant reproduced, one or two partial).
  • ReproducedFigure 2B

    Grin2b+/- rats have more SWDs than WT across the 24-h day; hour of day has no effect and does not interact with genotype (linear mixed model, genotype F = 55.36, p < .00001; hour p = .16; interaction p = .49).

    Hour of the day had no effect on the number of seizures between the two genotypes, and Grin2b+/− rats had significantly more seizures overall when compared to wild‐type littermates

    Figure 2B

    What the paper reports

    • effect of genotype: linear mixed model, F = 55.36, df = 1, p < 10⁻⁵ (n = 9 wild-type and 15 Grin2b+/- rats)
    • effect of hour: linear mixed model, F = 1.29, df = 23, p = 0.16 (n = 9 wild-type and 15 Grin2b+/- rats)
    • hour x genotype interaction: linear mixed model, F = .97, df = 23, p = 0.49 (n = 9 wild-type and 15 Grin2b+/- rats)

    Split-plot ANOVA on SWDs per ZT hour, genotype F = 11.45, p = 0.0045 (Het higher), hour p = 0.069, interaction p = 0.9998. Het hourly means 19.2 to 37.8, WT 0 to 8.2. With GRIN2B-132 as WT or Het the genotype effect holds (p = 0.0011, 0.013) and hour reaches p = 0.041. Without GRIN2B-228, GRIN2B-238 or both, genotype p = 0.0001, 0.048 and 0.0036, hour p 0.070 to 0.074. A fitted random-intercept model (MixedLM) gives the same genotype and interaction statistics. The paper's genotype F is 55.36 with 9 WT; here there are 2.

    How the test differed from the paper’s method

    • Two WT rats, where the paper has nine.
    • The random-intercept mixed model is tested as a split-plot ANOVA.
  • ReproducedFigure 2C, left

    Grin2b+/- rats have more SWDs over 24 h than WT (Wilcoxon rank-sum, W = 4.5, p = .0002).

    The above reflected a statistically significant increase in the total number of SWDs over the full 24 h in Grin2b+/− rats when compared to wild‐type

    Figure 2C, left

    What the paper reports

    • Wilcoxon rank-sum test, W = 4.5, p = 2 × 10⁻⁴ (n = 9 wild-type and 15 Grin2b+/- rats)

    Het 690.6 SWDs per day, WT 56.3 (GRIN2B-238 none, GRIN2B-240 112.5); W = 1, p = 0.047. GRIN2B-240 ranks above one Het, GRIN2B-228, which has 1 SWD per day. With GRIN2B-132 as WT p = 0.020, as Het p = 0.062. Without GRIN2B-228 p = 0.034 (W = 0); with GRIN2B-238 left out one WT remains and p = 0.20.

    How the test differed from the paper’s method

    • Two WT rats, where the paper has nine.
  • ReproducedFigure 2C, right

    The total time in SWDs over 24 h is higher in Grin2b+/- rats than in WT (Wilcoxon rank-sum, W = 5.5, p = .0002).

    Furthermore, Grin2b+/− rats had a longer average SWD duration and total SWD duration than

    Figure 2C, right

    What the paper reports

    • Wilcoxon rank-sum test, W = 5.5, p = 2 × 10⁻⁴ (n = 9 wild-type and 15 Grin2b+/- rats)

    Het 57.77 min per day, WT 1.37 min; W = 1, p = 0.033. With GRIN2B-132 as WT p = 0.012, as Het p = 0.029. Without GRIN2B-228 p = 0.019; with GRIN2B-238 left out one WT remains and p = 0.27.

    How the test differed from the paper’s method

    • Two WT rats, where the paper has nine.
  • ReproducedFigure S5A; Results, Absence seizures in Grin2b+/- rats, paragraph 2

    The number of SWDs does not differ between the light and dark phases, and Grin2b+/- rats have more SWDs than WT in both (linear mixed model, genotype p < .00001, phase p = .28, interaction p = .53).

    Number of SWD events during the light and dark phases did not differ significantly but were increased significantly in Grin2b+/− rats

    Figure S5A; Results, Absence seizures in Grin2b+/- rats, paragraph 2

    What the paper reports

    • effect of genotype: linear mixed model, F = 55.36, df = 1, p < 10⁻⁵ (n = 9 wild-type and 15 Grin2b+/- rats)
    • effect of phase: linear mixed model, F = 1.23, df = 1, p = 0.28 (n = 9 wild-type and 15 Grin2b+/- rats)
    • phase x genotype interaction: linear mixed model, F = .41, df = 1, p = 0.53 (n = 9 wild-type and 15 Grin2b+/- rats)

    Phase F = 1.19, p = 0.29; genotype F = 11.45, p = 0.0045; interaction p = 0.86. Het 316.7 SWDs in the light and 373.9 in the dark, WT 12.5 and 43.8. Within Het, light minus dark median -79.8 (signed-rank p = 0.19). Without GRIN2B-228, GRIN2B-238 or both, phase p = 0.30 and genotype p = 0.0001, 0.048 and 0.0036.

    How the test differed from the paper’s method

    • Two WT rats; the mixed model is tested as a split-plot ANOVA.
  • ReproducedFigure S8B

    Sex does not affect the number, mean duration or total duration of SWDs (two-way ANOVA sex x genotype, sex p = .74, .99 and .99).

    Grin2b+/− rats had a statistically greater number of SWDs, with longer average and total durations than Grin2b+/+ rats, and these differences were not influenced by the animals’ sex

    Figure S8B

    What the paper reports

    • effect of sex on SWD number: two-way analysis of variance, F = .12, df = 1, p = 0.74 (n = 3 male and 6 female wild-type, 8 male and 7 female Grin2b+/- rats)
    • effect of sex on SWD average duration: two-way ANOVA, F = .0002, df = 1, p = 0.99 (n = 3 male and 6 female wild-type, 8 male and 7 female Grin2b+/- rats)
    • effect of sex on total SWD duration: two-way ANOVA, F = .0001, df = 1, p = 0.99 (n = 3 male and 6 female wild-type, 8 male and 7 female Grin2b+/- rats)

    Sex term p = 0.29, 0.94 and 0.78 for number, mean duration and total duration. Within Het, females 763.3 SWDs per day against 617.9 in males (t test p = 0.31), 4.59 against 4.50 s, 60.3 against 55.2 min. Without GRIN2B-228, GRIN2B-238 or both the sex terms have p from 0.31 to 0.94.

    How the test differed from the paper’s method

    • The ANOVA has no sex by genotype interaction, as both WT are female; the paper's model has one.
  • ReproducedFigure 2D; Results, Absence seizures in Grin2b+/- rats, paragraph 3

    The EEG spectrum during SWDs has a clear peak in the theta range with a harmonic, in both genotypes.

    In SWD epoch averages we found a clear peak in the theta frequency range with a secondary harmonic in both genotypes

    Figure 2D; Results, Absence seizures in Grin2b+/- rats, paragraph 3

    All 15 rats with at least 5 usable SWD epochs in the raw windows (13 Het, the WT GRIN2B-240 and GRIN2B-132) have a peak at 7.0 to 8.0 Hz and another at 14.0 to 16.0 Hz. The stored spectra show peaks near the same frequencies (7.4 to 8.2 and 14.4 to 16.2 Hz). GRIN2B-240 has 18 usable SWD epochs.

    How the test differed from the paper’s method

    • Spectra from about 4.8 h of raw EEG per rat (one 24-min chunk at six ZT hours of each day), on the SWD-detection channel, with a 2-s Welch segment chosen here.
    • The peak rule (local maximum with prominence 0.1 in log10 power, harmonic within 1 Hz of twice the peak) was chosen here; the paper describes the peak by eye.
  • ReproducedFigure 3D

    Grin2b+/- rats have less REM sleep per hour than WT across the day, and the reduction is not specific to certain hours (linear mixed model, genotype F = 9.98, p = .0045; hour x genotype p = .53).

    Grin2b+/− rats had overall significantly less REM sleep compared to wild‐type littermates, and this reduction was not specific to certain hours of the day

    Figure 3D

    What the paper reports

    • effect of genotype: linear mixed model, F = 9.98, df = 1, p = 0.0045 (n = 9 wild-type and 15 Grin2b+/- rats)
    • hour x genotype interaction: linear mixed model, F = .95, df = 23, p = 0.53 (n = 9 wild-type and 15 Grin2b+/- rats)

    Genotype F = 4.69, p = 0.048 (Het lower); interaction p = 0.096. At the threshold; with GRIN2B-132 as WT p = 0.19, as Het p = 0.038 (interaction p = 0.071); with the scorer's flags or the stored scores p = 0.049 and 0.050. Without GRIN2B-228 genotype p = 0.060; without GRIN2B-238 or both genotype p = 0.019 and 0.025 but the interaction has p = 0.0001 and 0.00005. The outcome holds with all 16 rats and with GRIN2B-132 counted as Het, and not without GRIN2B-228 or GRIN2B-238. A fitted mixed model (MixedLM) gives genotype Wald p = 0.030 and interaction p = 0.086.

    How the test differed from the paper’s method

    • Two WT rats; the mixed model is tested as a split-plot ANOVA.
    • SWD epochs are the epochs SWD events overlap; the lab's scorer uses its per-epoch flags.
  • ReproducedFigure 3G, left

    Grin2b+/- rats spend less total time in REM sleep over 24 h than WT (two-sample t test, df = 22, T = 3.16, p = .0045).

    Similarly, Grin2b+/− rats spent less total time in REM sleep than wild‐type littermate controls when total minutes per animal were analyzed

    Figure 3G, left

    What the paper reports

    • two-sample unpaired t test, df = 22, T = 3.16, p = 0.0045 (n = 9 wild-type and 15 Grin2b+/- rats)

    Het 44.8 min of REM per day, WT 69.7 (54.3 and 85.2); t = 2.16, df 14, p = 0.048. With GRIN2B-132 as WT p = 0.19, as Het p = 0.038; SWD-epoch variants p = 0.049 and 0.050, and 0.049 with only the SWD time removed. Without GRIN2B-228 p = 0.060; without GRIN2B-238 p = 0.019.

    How the test differed from the paper’s method

    • Two WT rats, where the paper has nine.
  • ReproducedFigure 3G, middle

    Grin2b+/- rats have fewer REM bouts than WT (two-sample t test, df = 22, T = 3.94, p = .00069).

    It is likely that this reduction was due to fewer REM sleep bouts in Grin2b+/− animals

    Figure 3G, middle

    What the paper reports

    • two-sample unpaired t test, df = 22, T = 3.94, p = 6.9 × 10⁻⁴ (n = 9 wild-type and 15 Grin2b+/- rats)

    Het 37.9 REM bouts per day, WT 74.0; t = 4.12, df 14, p = 0.0010. Both WT have more bouts than every Het. With GRIN2B-132 as WT p = 0.068. Without GRIN2B-228, GRIN2B-238 or both p <= 0.0017; with bouts not split by SWD epochs p = 0.0007.

    How the test differed from the paper’s method

    • Two WT rats; the bout definition (runs of one state, ended by SWD epochs) was chosen here.
  • ReproducedFigure 3H, left

    Total NREM sleep over 24 h does not differ between genotypes (two-sample t test, df = 22, T = -.09, p = .93).

    Similarly, there was no difference between Grin2b+/− and ... rats in the total amount of time spent in NREM sleep over the full 24 h

    Figure 3H, left

    What the paper reports

    • two-sample unpaired t test, df = 22, T = -.09, p = 0.93 (n = 9 wild-type and 15 Grin2b+/- rats)

    Het 450.5 min, WT 419.3 min, difference 31.2 min; t = -1.29, p = 0.22. With GRIN2B-132 as WT the difference is 48.4 min, p = 0.035. Without GRIN2B-238 the Het have 17.6 min less (p = 0.54); with only the SWD time removed p = 0.19. With two WT the test has little power to find a difference.

    How the test differed from the paper’s method

    • Two WT rats, where the paper has nine.
  • ReproducedFigure 4A

    EEG spectral power during REM sleep does not differ between genotypes (two-way ANOVA genotype x band, genotype p = .14, interaction p = .69).

    No statistically significant differences were found between Grin2b+/− and ... rats during REM sleep

    Figure 4A

    What the paper reports

    • effect of genotype: two-way analysis of variance, F = 2.25, df = 1, p = 0.14 (n = 9 wild-type and 14 Grin2b+/- rats)
    • genotype x frequency interaction: two-way analysis of variance, F = .57, df = 4, p = 0.69 (n = 9 wild-type and 14 Grin2b+/- rats)

    Normalized REM band power, genotype F = 3.30, p = 0.073; interaction p = 0.998; Het lower by 0.19 on average. Contiguous bands give genotype p = 0.034, SWD epochs from flags p < 0.0001, the stored spectra p = 0.17, the cleaner S1 channel p = 0.067; the slope rejection removes no epoch. Without GRIN2B-228 p = 0.094, without GRIN2B-238 p = 0.19. The windows cover a median of 5 to 10% of each state's epochs (1.1% of GRIN2B-129's REM). With two WT the test has little power, and the band ANOVA treats an animal's five bands as separate observations, as the paper's does.

    How the test differed from the paper’s method

    • Spectra from about 4.8 h of raw EEG per rat on the SWD-detection channel; the paper used one representative channel and all epochs.
    • Band limits (delta 1-4, theta 4-8, sigma 10-15, beta 15-30, gamma 30-48 Hz) and the Welch segment are not given in the paper. The spectral-slope rejection, read here as a slope below -5 of log10 power against log10 frequency or power at 1 Hz above 500 mV^2/Hz, removes no epoch.
    • The paper chose the S1 channel with fewer artefacts by eye; that choice is not in the dandiset. The main channel is S1_Tr_R, and the per-animal channel with fewer artefact epochs is a variant.
  • ReproducedResults, Brain state abnormalities in Grin2b+/- rats are not correlated with absence seizure activity, paragraph 1; Figure S5B

    In Grin2b+/- rats 24.2% of SWDs occur during the wake-NREM transition, similar to the 22.39% of the WT rats that have such SWDs (two-sample t test, p = .74).

    24.2% of SWDS in Grin2b+/− rats occurred during the wake‐NREM transitional period, which was similar to the 22.39% observed in

    Results, Brain state abnormalities in Grin2b+/- rats are not correlated with absence seizure activity, paragraph 1; Figure S5B

    What the paper reports

    • two-sample unpaired t test, df = 16, T = -.34, p = 0.74 (n = 3 wild-type and 15 Grin2b+/- rats)

    Reading (i), the share of NREM-initiated SWDs that are transitional, with an SWD initiated in NREM when any of the six epochs before it is NREM (the Supplementary Methods), gives 22.93% (SEM 1.97, 13 Het), within 24.2 +- 2.42. Reading (ii), the share of all SWDs, gives 2.23%. With NREM taken from the epoch before the SWD, the rule of the first criterion, reading (i) gives 36.31%. Leaving out GRIN2B-228 does not change reading (i). The claim's WT part is not tested, as no WT rat has transitional SWDs, so the WT value and the t test were not computed.

    How the test differed from the paper’s method

    • The denominator is not stated; two readings are shown.
    • The criterion's NREM rule was corrected after verification round 1, once the analysis had been seen, to the six-epoch rule the Supplementary Methods state; the first rule gave 36.31%.
    • The transition definition (a wake epoch followed by an NREM epoch within the six epochs before the SWD) was chosen here.
  • ReproducedFigure 5F, left

    In Grin2b+/- rats, total SWD duration is negatively correlated with total time awake (Pearson, R = -.51, p = .048).

    Quantification revealed total SWD duration is negatively correlated with total time awake

    Figure 5F, left

    What the paper reports

    • Pearson correlation, T = -2.16, df = 13, R = -.51, p = 0.048 (n = 15 Grin2b+/- rats)

    R = -0.81, p = 0.0005 over 14 Het (-0.82 with GRIN2B-132, -0.73 without GRIN2B-228). With the scorer's flags R = -0.75; with the stored scores R = -0.06 (p = 0.83); with only the SWD time removed from wake R = -0.74 (p = 0.0024). The correlation arises from SWD time being taken out of wake. In Het the SWD epochs removed total 110.6 min per day against 57.8 min of SWD time.

    How the test differed from the paper’s method

    • 14 Het, where the paper has 15.

Not tested in a notebook 10

10 data missing from the dataset
  • BlockedFigure 2E· Data missing from the dataset

    Delta power during SWDs is higher in Grin2b+/- rats than in WT (two-way ANOVA genotype x band, interaction p = .015; Tukey delta p = .039).

    Quantification of average power in commonly used frequency bands during SWDs, showing an increased delta power in Grin2b+/− rats

    Figure 2E

    What the paper reports

    • genotype x frequency interaction: two-way analysis of variance, F = 3.27, df = 4, p = 0.015 (n = 6 wild-type and 14 Grin2b+/- rats)
    • delta band, genotype: Tukey post hoc test, p = 0.039 (n = 6 wild-type and 14 Grin2b+/- rats)

    Only one WT rat (GRIN2B-240) has SWDs; GRIN2B-238 has none in either day, and the paper's other seven WT rats are not in the dandiset. The claim's rule needs at least two animals per genotype (also other, too few animals). A search of the archive for GRIN2B, Gonzalez-Sulser and the paper's DOI finds only this dandiset. As an illustration only, with GRIN2B-132 (no genotype) counted as WT, Het SWD delta power is lower than WT (-0.34, Tukey p = 1.0), against the paper's direction.

  • BlockedFigure 5A· Data missing from the dataset

    Compared with WT, Grin2b+/- rats have a higher share of SWDs in NREM and a lower share in wake (two-way ANOVA genotype x state, interaction p = .00008; Tukey NREM p = .0011, wake p = .0022).

    Compared to wild‐type littermates, Grin2b+/− rats have fewer SWDs in wake and more SWDs in NREM

    Figure 5A

    What the paper reports

    • genotype x state interaction: two-way analysis of variance, F = 10.94, df = 2, p = 8 × 10⁻⁵ (n = 9 wild-type and 15 Grin2b+/- rats)
    • NREM, genotype: Tukey post hoc test, p = 0.0011 (n = 9 wild-type and 15 Grin2b+/- rats)
    • wake, genotype: Tukey post hoc test, p = 0.0022 (n = 9 wild-type and 15 Grin2b+/- rats)

    Only one WT rat has SWDs (GRIN2B-240, 0% of its SWDs after NREM), and the paper's other seven WT rats are not in the dandiset, so the per-state comparison between genotypes cannot be tested under the claim's rule of two animals per group (also other, too few animals). As an illustration only, with GRIN2B-132 (no genotype) counted as WT, 6.30% of Het SWDs follow NREM against 0.23% in the two WT (interaction p = 0.013, Tukey NREM p = 0.29).

  • BlockedFigure 1C; Figure S2C· Data missing from the dataset

    GluN2B protein is reduced by about 50% in somatosensory cortex and hippocampus of Grin2b+/- rats (homogenate t test p = .000104; synaptosome Wilcoxon p = .00094).

    Glun2B protein levels in homogenates and synaptosome fractions were reduced by ~50% in adult heterozygous knockout ... rats compared to wild‐types

    Figure 1C; Figure S2C

    What the paper reports

    • somatosensory cortex homogenate (Figure 1C): two-sample unpaired t test, df = 14, T = -5.34, p = 10⁻⁴ (n = 8 wild-type and 8 Grin2b+/- rats)
    • somatosensory cortex synaptosome (Figure 1C): Wilcoxon rank-sum test, W = 64, p = 9.4 × 10⁻⁴ (n = 8 wild-type and 8 Grin2b+/- rats)
    • hippocampus homogenate (Figure S2C): two-sample unpaired t test, df = 14, T = -897, p < 10⁻⁵ (n = 8 wild-type and 8 Grin2b+/- rats)
    • hippocampus synaptosome (Figure S2C): two-sample unpaired t test, df = 14, T = -3.89, p = 0.0016 (n = 8 wild-type and 8 Grin2b+/- rats)

    The western blot quantification is not in the dandiset, which holds only EEG/EMG files, and the paper's data statement says raw data are available on request.

  • BlockedFigure 1D-F; Figure S2D-F· Data missing from the dataset

    GluN2A, GluR1 and PSD95 expression are unchanged in Grin2b+/- rats.

    The expression of GluN2A, GluR1, and PSD95 synaptic proteins in Grin2b+/− rats was unaffected in the somatosensory cortex (Figure 1D–F) and the hippocampus (Figure S2D–F).

    Figure 1D-F; Figure S2D-F

    What the paper reports

    • GluN2A, cortex homogenate: two-sample unpaired t test, df = 14, T = -.14, p = 0.89
    • GluN2A, cortex synaptosome: two-sample unpaired t test, df = 14, T = -1.52, p = 0.15
    • GluR1, cortex homogenate: two-sample unpaired t test, df = 14, T = -.98, p = 0.35
    • GluR1, cortex synaptosome: Wilcoxon rank-sum test, W = 28, p = 0.71
    • PSD95, cortex homogenate: two-sample unpaired t test, df = 14, T = -.35, p = 0.73
    • PSD95, cortex synaptosome: two-sample unpaired t test, df = 14, T = .59, p = 0.56
    • GluN2A, hippocampus homogenate: two-sample unpaired t test, df = 14, T = -.16, p = 0.88
    • GluN2A, hippocampus synaptosome: two-sample unpaired t test, df = 14, T = .48, p = 0.64
    • GluR1, hippocampus homogenate: two-sample unpaired t test, df = 14, T = -1.57, p = 0.14
    • GluR1, hippocampus synaptosome: two-sample unpaired t test, df = 14, T = -.44, p = 0.67
    • PSD95, hippocampus homogenate: two-sample unpaired t test, df = 14, T = .049, p = 0.96
    • PSD95, hippocampus synaptosome: Wilcoxon rank-sum test, W = 28, p = 0.71

    Western blot data not in the dandiset (see fig1c-glun2b-reduced).

  • BlockedResults, Normal physical and motor development in Grin2b+/- rats, paragraph 1; Figure S4· Data missing from the dataset

    Grin2b+/- rats survive, grow and develop motor reflexes like WT littermates (survival 48% and 52%; body weight, righting reflex and negative geotaxis do not differ).

    Following weaning, survival rates were determined to be 48% for Grin2b+/− rats and 52% for ... Taken together, these findings indicate that Grin2b haploinsufficiency does not impair physical development or gross motor function

    Results, Normal physical and motor development in Grin2b+/- rats, paragraph 1; Figure S4

    What the paper reports

    • pup body weight, effect of genotype (Figure S4A): linear mixed model, F = 2.78, df = 1, p = 0.12 (n = 5 wild-type and 8 Grin2b+/- pups)
    • adult body weight, effect of genotype (Figure S4B): linear mixed model, F = .0056, df = 1, p = 0.94 (n = 47 wild-type and 49 Grin2b+/- rats)
    • righting reflex, effect of genotype (Figure S4C): linear mixed model, F = .29, df = 1, p = 0.6 (n = 12 wild-type and 18 Grin2b+/- pups)
    • negative geotaxis (Figure S4D): Wilcoxon rank-sum test, W = 87, p = 0.37 (n = 12 wild-type and 18 Grin2b+/- pups)

    Survival, body weight, righting reflex and negative geotaxis measures are not in the dandiset or any public archive the paper names.

  • BlockedSupplementary Methods; Table S1; Figure S1· Data missing from the dataset

    The automated sleep scorer agrees with visual scoring on 90.8% of epochs (Cohen's kappa 0.83).

    Overall agreement between the scoring methods is 90.8%. The kappa coefficient was .83

    Supplementary Methods; Table S1; Figure S1

    The visual scores of the 4-h validation periods are not in the dandiset; the files hold only the automated scores.

  • BlockedFigure 6B· Data missing from the dataset

    Systemic ethosuximide reduces the number of SWDs relative to saline and memantine in both genotypes (linear mixed model, treatment p = .0049; ethosuximide-saline p = .0081).

    systemic ethosuximide resulted in significantly fewer SWDs than memantine and saline

    Figure 6B

    What the paper reports

    • effect of treatment: linear mixed model, F = 6.48, df = 2, p = 0.0049 (n = 5 wild-type and 12 Grin2b+/- rats)
    • ethosuximide against saline: Tukey post hoc test, p = 0.0081 (n = 5 wild-type and 12 Grin2b+/- rats)
    • ethosuximide against memantine: Tukey post hoc test, p = 0.015 (n = 5 wild-type and 12 Grin2b+/- rats)

    The pharmacology recordings (2-channel EEG of 17 rats over baseline, treatment and washout days) are not in the dandiset, whose 17 files are 73 to 99 h recordings with the 14-channel grid, each holding two 24-h baseline windows. No other dandiset for this paper was found.

  • BlockedFigure 6C· Data missing from the dataset

    Systemic ethosuximide and memantine reduce the mean SWD duration in Grin2b+/- rats but not in WT (treatment x genotype p = .044).

    Both ethosuximide and memantine, however, reduced the average duration of SWDs in Grin2b +/− but not

    Figure 6C

    What the paper reports

    • treatment x genotype interaction: linear mixed model, F = 3.34, df = 2, p = 0.044 (n = 5 wild-type and 12 Grin2b+/- rats)
    • Grin2b+/- ethosuximide against saline: Tukey post hoc test, p < 10⁻⁴
    • Grin2b+/- memantine against saline: Tukey post hoc test, p = 9 × 10⁻⁴
    • wild-type ethosuximide against saline: Tukey post hoc test, p = 0.88
    • wild-type memantine against saline: Tukey post hoc test, p = 0.99

    Pharmacology recordings not in the dandiset (see fig6b-systemic-etx-number).

  • BlockedFigure 6D· Data missing from the dataset

    Systemic ethosuximide reduces the total SWD duration in both genotypes (treatment p = .0011; ethosuximide-saline p = .0005).

    The combined effect of less SWDs with lower duration with ethosuximide likely resulted in ethosuximide, but not memantine, reducing total seizure durations in both rat groups

    Figure 6D

    What the paper reports

    • effect of treatment: linear mixed model, F = 9.44, df = 2, p = 0.0011 (n = 5 wild-type and 12 Grin2b+/- rats)
    • ethosuximide against saline: Tukey post hoc test, p = 5 × 10⁻⁴ (n = 5 wild-type and 12 Grin2b+/- rats)

    Pharmacology recordings not in the dandiset (see fig6b-systemic-etx-number).

  • BlockedFigure 7C· Data missing from the dataset

    Infusion of ethosuximide or memantine into the reticular thalamic nucleus reduces the number and total duration of SWDs in Grin2b+/- rats but not their mean duration.

    Infusion of ethosuximide and memantine into the nRT of Grin2b+/− animals led to a significant decrease in the amount of SWDs compared to saline ... ethosuximide and memantine had no effect on reducing average SWD durations of seizures that did occur ... resulted in decreased total seizure durations in Grin2b+/− rats

    Figure 7C

    What the paper reports

    • number of SWDs, effect of treatment: linear mixed model, F = 31.35, df = 2, p = 6.7 × 10⁻⁴ (n = 4 Grin2b+/- rats)
    • number of SWDs, ethosuximide against saline: Tukey post hoc test, p = 0.0016 (n = 4 Grin2b+/- rats)
    • number of SWDs, memantine against saline: Tukey post hoc test, p = 9 × 10⁻⁴ (n = 4 Grin2b+/- rats)
    • average SWD duration, effect of treatment: linear mixed model, F = 1.41, df = 2, p = 0.32 (n = 4 Grin2b+/- rats)
    • total SWD duration, effect of treatment: linear mixed model, F = 31.87, df = 2, p = 6.4 × 10⁻⁴ (n = 4 Grin2b+/- rats)
    • total SWD duration, ethosuximide against saline: Tukey post hoc test, p = 0.0016 (n = 4 Grin2b+/- rats)
    • total SWD duration, memantine against saline: Tukey post hoc test, p = 8 × 10⁻⁴ (n = 4 Grin2b+/- rats)

    The intrathalamic infusion recordings of 4 Grin2b+/- rats are not in the dandiset.

Findings about the data

What attempts found about the dataset itself, for its owner and the archive.

  • Data missingThe dandiset holds 2 of the paper's 9 analysed wild type rats (14 or 15 of its 15 Grin2b+/-), so genotype comparisons rest on two WT, one of which has no SWDs. The pharmacology and intrathalamic infusion recordings (Figures 6, 7, S11, S12), western blots (Figures 1, S2, S3), development measures (Figure S4) and the visual scoring used to validate the scorer (Table S1) are not in it. The paper says raw data are available on request.
  • Description missingGRIN2B-132 has no genotype and sex U, so it cannot be placed in either group. The conversion repository marks both as still to be confirmed by the lab.
  • Selection not documentedThe paper analysed 15 Grin2b+/- and 9 WT rats and excluded 4 and 9 descendants of one founder. The dandiset does not say which of its rats the paper analysed, and holds a Grin2b+/- rat (GRIN2B-228) with 1 SWD per day, unlike the paper's statement that all Grin2b+/- rats had SWDs at wake-NREM transitions.
  • Metadata errorThe sleep_states description gives code 4 for SWD epochs, but no file holds code 4; the stored scores are the scorer's output before SWD epochs are set, so SWD epochs are scored as wake, NREM or REM.
  • Metadata errorswd_epoch_counts is described as the number of SWD events per 5-s epoch but holds the scorer's flags (6 for an SWD epoch, 4 otherwise). The flagged epochs cover a median of 51% (0 to 73%) of the epochs SWD events overlap, mostly the last epoch of each SWD, and only about a tenth of SWD onsets fall in a flagged epoch.
  • Metadata errorIn seizure_totals_by_zt the per-hour SWD counts are in spike_wave_discharge, while number_of_seizure_events and Day hold the day's total in the first row and 0 elsewhere; the description itself marks the columns as unconfirmed.
  • Metadata errorsleep_state_power_spectra is described as a baseline-corrected PSD normalized to the average over states, with units to be confirmed. The lab's scorer writes the mean log10 multitaper amplitude referenced to each frequency's 5th percentile over the day, which is what the values (0 to about 1.6) fit; the paper's Welch spectra are not in the dandiset.
  • File format errorThe raw EEG and EMG are stored as unsigned 12-bit codes with offset 0, so every channel reads about +8 mV of DC in volts. Signal loss is written as 32767 on all channels at once, and some files hold other values outside 0 to 4095; neither is described. In the windows read, 21 to 73% of 5-s epochs per rat contain such samples (73% for GRIN2B-238).
  • Metadata errorThe dandiset's assets summary counts 16 files and 16 subjects, while the draft holds 17 NWB files of 17 rats.
  • Published code disagreesThe Methods exclude SWD times from the sleep states, while the lab's scorer replaces only the flagged epochs, which cover about half of the epochs SWD events overlap. The paper's wake results depend on this; with the stored scores (SWD epochs as wake) the wake bout differences reverse and the correlation of SWD time with wake time disappears.
  • Paper inconsistentIn the Figure 5 legend, NREM time gives T = -1.47 with R = -0.13 and df = 13, which implies T = -0.47; REM bouts give T = 0.704 with R = -0.19, of opposite sign; and REM bout duration and wake bouts have identical statistics (T = 0.61, R = 0.17, p = 0.55). The Figure 5A ANOVA gives genotype F = 1 with p = 0.98, which do not match for df = 1.
  • Paper inconsistentThe Figure 3 legend says no net differences between genotypes were observed for wake, while reporting a genotype effect on hourly wake time of F = 7.14, p = 0.014, and the Results say Grin2b+/- rats spent less time awake.
  • Description missingThe Supplementary Methods chose, by eye and per animal, the S1 EEG channel (left or right) and the EMG channel with fewer artefacts for sleep scoring; the dandiset does not record which channels were used.
  • Methods not availableThe paper does not give its frequency band limits, Welch segment length, bout definition or the rule for wake-NREM transitions, and neither linked repository holds the statistics or figure code.

Notebooks

Every registered entry that uses this dataset. An entry can hold several notebooks, and can use more than one dataset.

Reproduction Absence seizures and sleep in Grin2b+/- rats (Hristova, Fasol et al. 2025)

Tests the EEG findings of Hristova, Fasol et al. (2025) on dandiset 001888, which holds the 24-h wireless EEG and EMG recordings, sleep scores and SWD events of 14 Grin2b+/- rats, 2 wild type rats and one rat without genotype. It compares SWD number, duration and timing, sleep-wake amounts and bouts, state spectra computed from the raw EEG, the state in which SWDs start, and the correlation of SWD time with sleep measures. The western blots, development measures, visual scoring and pharmacology recordings of the paper are not in the dandiset. All files

Verification

  • Round 1
    2026-10-19    Agreed with 34 of 34 outcomes. Independent agent run by CatalystNeuro (same harness, separate context, did not write the notebook). Reviewed: Round 1. The first executed notebook with the conclusion cells and the summary removed, the helper module and the claims file, with the paper and its Supplementary Methods. The verifier had no attempt record and took its counts from the claims file. It gave its own outcome for each claim; all 34 agree with the record as it stood then. It checked the blocked claims against the archive's file list and metadata.
  • Round 2
    2026-10-19    Agreed with 34 of 34 outcomes. Independent agent run by CatalystNeuro (same harness, separate context, did not write the notebook). Reviewed: Round 2. The full executed notebook after the round-1 revision, with its conclusions and summary, the helper module, the claims file, the attempt record and the README, with the paper and its Supplementary Methods. The verifier agreed with all 34 outcomes, including the change of figs5b-transition-percent to reproduced, and found all round-1 points resolved. It found sentences the outputs did not support. The disc-het-swd-minutes conclusion said the paper's 59.97 min does not match the scorer's flags; cell 32 now prints the flagged epochs as 60.2 min, and the conclusion says the figure fits both. The fig4c range now ends at +0.168. The fig3d conclusion now says the outcome also holds with GRIN2B-132 counted as Het. The summary now names fig5def-no-other-correlations among the claims that would change without GRIN2B-228, and the fig3d interaction without GRIN2B-238. The README run time and the description of the recordings (73 to 99 h, each with two 24-h baseline windows) are corrected, as is the same description in the fig6b note and the claims-file comment. No outcome changed, and none is proposed to change.

Method differences

How the tests differed from the paper’s method or data, and the claims each applies to.

Provenance

Attempt record
001888-hristova-2025-01
Paper
Absence seizures and sleep-wake abnormalities in a rat model of GRIN2B neurodevelopmental disorder
Date
2026-10-19
Made by
An agent, run by CatalystNeuro
Dataset
DANDI:001888
Version
draft
Run on
GitHub Actions
Harness
Claude Code (GitHub Actions)
Model
claude-opus-5-5
Protocol
pilot-7

Transcripts of the agent runs

Each run’s prompt, messages and tool calls, with long output cut and the text of the paper left out, and its final report.

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