Table 11.
Detailed results and statistical analyses related to stereotypies, repetitive behavior, perseveration, and cognitive flexibility
| Sterotypies in open field | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Genotype | Cohort | Genotype × cohort | Pairwise comparisons | ||||||||||||||
| Test | Data structure | WT | Het | KO | F | p value | Power | F | p value | Power | F | p value | Power | WT vs Het | WT vs KO | Het vs KO | |
| Grooming, time (s) | 2wANOVA | Nonnormal | 67.01 ± 7.01 | 62.6 ± 5.58 | 92.49 ± 10.45 | 4.929 | 0.011 | 0.784 | 22.806 | 0.000 | 0.997 | 2.530 | 0.090 | 0.484 | 0.883 | 0.023 | 0.006 |
| Grooming, number | 2wANOVA | Normal | 25.42 ± 1.51 | 22.26 ± 1.5 | 27.1 ± 1.93 | 2.000 | 0.146 | 0.394 | 1.402 | 0.242 | 0.213 | 1.745 | 0.185 | 0.349 | − | − | − |
| Jumping, time (s) | 2wANOVA | Nonnormal | 0.07 ± 0.05 | 0 ± 0 | 0.18 ± 0.1 | 1.666 | 0.199 | 0.335 | 0.033 | 0.857 | 0.054 | 1.149 | 0.325 | 0.242 | − | − | − |
| Jumping, number | 2wANOVA | Nonnormal | 0.36 ± 0.23 | 0 ± 0 | 0.42 ± 0.23 | 1.300 | 0.281 | 0.269 | 0.155 | 0.696 | 0.067 | 1.816 | 0.173 | 0.362 | − | − | − |
| Rotation, time (s) | 2wANOVA | Nonnormal | 0.39 ± 0.1 | 1.49 ± 0.81 | 4.21 ± 2.76 | 1.560 | 0.220 | 0.316 | 2.069 | 0.156 | 0.292 | 1.038 | 0.361 | 0.222 | − | − | − |
| Rotation, number | 2wANOVA | Nonnormal | 1.63 ± 0.39 | 2.21 ± 0.46 | 6.15 ± 1.82 | 5.883 | 0.005 | 0.856 | 3.301 | 0.075 | 0.430 | 3.022 | 0.057 | 0.561 | 0.920 | 0.010 | 0.028 |
| Twitching/shaking, time (s) | 2wANOVA | Nonnormal | 0.28 ± 0.07 | 0.69 ± 0.33 | 0.63 ± 0.1 | 1.089 | 0.344 | 0.231 | 0.540 | 0.466 | 0.111 | 0.879 | 0.422 | 0.193 | − | − | − |
| Twitching/shaking, number | 2wANOVA | Nonnormal | 1.73 ± 0.42 | 2.63 ± 0.88 | 3 ± 0.47 | 1.194 | 0.311 | 0.250 | 1.484 | 0.229 | 0.223 | 0.589 | 0.559 | 0.143 | − | − | − |
| Repetitive novel object contact task, object preference, time | |||||||||||||||||
| Object exploration, time (s) | Test | Data structure | F | p value | Power | WT vs Het | WT vs KO | Het vsKO | |||||||||
| - Object | rMeasures | Sph.viol | 10.533 | 0.000 | 0.999 | − | − | − | |||||||||
| - Object × gen. | rMeasures | Sph.viol | 2.150 | 0.069 | 0.753 | − | − | − | |||||||||
| - Genotype | rMeasures | Sph.viol | 7.964 | 0.001 | 0.943 | 0.956 | 0.014 | 0.006 | |||||||||
| - Cohort | rMeasures | Sph.viol | 24.654 | 0.000 | 0.998 | − | − | − | |||||||||
| - Object × gen. × coh. | rMeasures | Sph.viol | 0.366 | 0.859 | 0.152 | − | − | − | |||||||||
| - Gen. × coh. | rMeasures | Sph.viol | 0.647 | 0.528 | 0.152 | − | − | − | |||||||||
| Genotype | Cohort | Genotype × cohort | Pairwise comparisons | ||||||||||||||
| Object exploration | Test | Data structure | WT | Het | KO | F | p value | Power | F | p value | Power | F | p value | Power | WT vs Het | WT vs KO | Het vs KO |
| Dice, time (s) | 2wANOVA | Nonnormal | 16.51 ± 2.49 | 14.82 ± 1.66 | 12.14 ± 1.79 | 1.748 | 0.185 | 0.349 | 4.640 | 0.036 | 0.560 | 0.833 | 0.441 | 0.185 | − | − | − |
| Jack, time (s) | 2wANOVA | Nonnormal | 21.78 ± 3.18 | 27.99 ± 5.1 | 15.39 ± 2 | 4.078 | 0.023 | 0.697 | 14.158 | 0.000 | 0.958 | 0.500 | 0.610 | 0.127 | 0.311 | 0.443 | 0.025 |
| Lego, time (s) | 2wANOVA | Nonnormal | 24.91 ± 3.59 | 28.25 ± 2.94 | 14.97 ± 1.87 | 8.622 | 0.001 | 0.959 | 20.965 | 0.000 | 0.994 | 0.774 | 0.467 | 0.174 | 0.509 | 0.031 | 0.001 |
| Pin, time (s) | 2wANOVA | Nonnormal | 20.8 ± 4.3 | 13.72 ± 1.82 | 10.86 ± 1.7 | 3.199 | 0.050 | 0.585 | 4.532 | 0.038 | 0.550 | 0.057 | 0.944 | 0.058 | 0.244 | 0.067 | 0.755 |
| Object exploration, % | Test | Data structure | F | p value | Power | WT vs Het | WT vs KO | Het vsKO | |||||||||
| - Object | rMeasures | Sph.ass | 8.329 | 0.000 | 0.985 | − | − | − | |||||||||
| - Object × gen. | rMeasures | Sph.ass | 0.721 | 0.633 | 0.259 | − | − | − | |||||||||
| - Genotype | rMeasures | Sph.ass | 0.750 | 0.478 | 0.170 | − | − | − | |||||||||
| - Cohort | rMeasures | Sph.ass | 0.000 | 1.000 | 0.050 | − | − | − | |||||||||
| - Object × gen. × coh. | rMeasures | Sph.ass | 0.652 | 0.688 | 0.236 | − | − | − | |||||||||
| - Gen. × coh. | rMeasures | Sph.ass | 0.000 | 1.000 | 0.050 | − | − | − | |||||||||
| Genotype | Cohort | Genotype × cohort | Pairwise comparisons | ||||||||||||||
| Object exploration | Test | Data structure | WT | Het | KO | F | p value | Power | F | pvalue | Power | F | p value | Power | WT vs Het | WT vs KO | Het vsKO |
| Dice, time (%) | 2wANOVA | Nonnormal | 20.09 ± 1.78 | 19.13 ± 2.11 | 24.11 ± 3.72 | 1.259 | 0.293 | 0.261 | 4.635 | 0.036 | 0.560 | 1.179 | 0.316 | 0.246 | − | − | − |
| Jack, time (%) | 2wANOVA | Nonnormal | 26.86 ± 3.3 | 30.29 ± 3.61 | 28.38 ± 3.26 | 0.221 | 0.803 | 0.083 | 1.529 | 0.222 | 0.228 | 0.022 | 0.978 | 0.053 | − | − | − |
| Lego, time (%) | 2wANOVA | Normal | 29.85 ± 2.19 | 32.98 ± 2.28 | 27.98 ± 2.5 | 1.174 | 0.318 | 0.245 | 0.986 | 0.326 | 0.164 | 0.072 | 0.931 | 0.060 | − | − | − |
| Pin, time (%) | 2wANOVA | Nonnormal | 23.18 ± 3.02 | 17.57 ± 2.65 | 19.51 ± 2.32 | 0.701 | 0.501 | 0.161 | 0.186 | 0.669 | 0.071 | 1.684 | 0.196 | 0.337 | − | − | − |
| Object exploration ranked by preference | Test | Data structure | F | p value | Power | WT vs Het | WT vs KO | Het vsKO | |||||||||
| - Object | rMeasures | Sph.viol | 110.887 | 0.000 | 1.000 | − | − | − | |||||||||
| - Object × gen. | rMeasures | Sph.viol | 5.483 | 0.002 | 0.996 | − | − | − | |||||||||
| - Genotype | rMeasures | Sph.viol | 8.054 | 0.001 | 0.946 | 0.948 | 0.014 | 0.006 | |||||||||
| - Cohort | rMeasures | Sph.viol | 24.578 | 0.000 | 0.998 | − | − | − | |||||||||
| - Object × gen. × coh. | rMeasures | Sph.viol | 1.187 | 0.321 | 0.457 | − | − | − | |||||||||
| - Gen. × coh. | rMeasures | Sph.viol | 0.643 | 0.530 | 0.152 | − | − | − | |||||||||
| Genotype | Cohort | Genotype × cohort | Pairwise comparisons | ||||||||||||||
| Object exploration | Test | Data structure | WT | Het | KO | F | p value | Power | F | p value | Power | F | pvalue | Power | WT vs Het | WT vs KO | Het vs KO |
| Object #1, time (s) | 2wANOVA | Nonnormal | 31.83 ± 3.59 | 37.45 ± 4.09 | 20.53 ± 1.64 | 9.051 | 0.000 | 0.967 | 15.093 | 0.000 | 0.968 | 0.934 | 0.400 | 0.202 | 0.264 | 0.048 | 0.001 |
| Object #2, time (s) | 2wANOVA | Nonnormal | 24.5 ± 3.27 | 22.95 ± 2.14 | 15.23 ± 1.78 | 6.709 | 0.003 | 0.899 | 22.529 | 0.000 | 0.996 | 0.456 | 0.637 | 0.120 | 0.941 | 0.016 | 0.033 |
| Object #3, time (s) | 2wANOVA | Nonnormal | 15.68 ± 2.69 | 15.29 ± 1.56 | 10.48 ± 1.15 | 4.224 | 0.020 | 0.714 | 20.037 | 0.000 | 0.992 | 1.306 | 0.280 | 0.269 | 0.998 | 0.094 | 0.102 |
| Object #4, time (s) | 2wANOVA | Nonnormal | 12 ± 2.41 | 9.34 ± 0.96 | 7.12 ± 0.99 | 3.763 | 0.030 | 0.660 | 12.155 | 0.001 | 0.927 | 0.630 | 0.537 | 0.149 | 0.451 | 0.074 | 0.533 |
| Object exploration,ranked by preference | Test | Data structure | F | p value | Power | WT vs Het | WT vs KO | Het vsKO | |||||||||
| - Object | rMeasures | Sph.viol | 146.534 | 0.000 | 1.000 | − | − | − | |||||||||
| - Object × gen. | rMeasures | Sph.viol | 0.832 | 0.490 | 0.321 | − | − | − | |||||||||
| - Genotype | rMeasures | Sph.viol | 0.812 | 0.450 | 0.181 | − | − | − | |||||||||
| - Cohort | rMeasures | Sph.viol | 0.783 | 0.381 | 0.140 | − | − | − | |||||||||
| - Object × gen. × coh. | rMeasures | Sph.viol | 1.054 | 0.377 | 0.407 | − | − | − | |||||||||
| - Gen. × coh. | rMeasures | Sph.viol | 0.812 | 0.450 | 0.181 | − | − | − | |||||||||
| Genotype | Cohort | Genotype × cohort | Pairwise comparisons | ||||||||||||||
| Object exploration | Test | Data structure | WT | Het | KO | F | p value | Power | F | p value | Power | F | p value | Power | WT vs Het | WT vs KO | Het vs KO |
| Object #1, time (%) | 2wANOVA | Nonnormal | 39.5 ± 2.19 | 43 ± 1.71 | 40.58 ± 2.74 | 1.029 | 0.365 | 0.219 | 1.745 | 0.193 | 0.254 | 0.963 | 0.389 | 0.207 | − | − | − |
| Object #2, time (%) | 2wANOVA | Nonnormal | 28.98 ± 1.16 | 27.21 ± 1.2 | 27.58 ± 1.39 | 0.805 | 0.453 | 0.180 | 1.231 | 0.273 | 0.193 | 2.400 | 0.102 | 0.461 | − | − | − |
| Object #3, time (%) | 2wANOVA | Normal | 17.99 ± 1.18 | 18.73 ± 1.21 | 19.28 ± 1.12 | 0.093 | 0.911 | 0.063 | 0.228 | 0.635 | 0.076 | 0.347 | 0.709 | 0.102 | − | − | − |
| Object #4, time (s) | 2wANOVA | Normal | 13.51 ± 0.92 | 11.62 ± 0.99 | 12.54 ± 1.16 | 1.091 | 0.344 | 0.230 | 0.423 | 0.518 | 0.098 | 0.747 | 0.479 | 0.169 | − | − | − |
| Repetitive novel object contact task, object preference, number | |||||||||||||||||
| Object interactions, number | Test | Data structure | F | p value | Power | WT vs Het | WT vs KO | Het vsKO | |||||||||
| - Object | rMeasures | Sph.viol | 2.653 | 0.051 | 0.638 | − | − | − | |||||||||
| - Object × gen. | rMeasures | Sph.viol | 0.858 | 0.528 | 0.331 | − | − | − | |||||||||
| - Genotype | rMeasures | Sph.viol | 2.108 | 0.133 | 0.412 | − | − | − | |||||||||
| - Cohort | rMeasures | Sph.viol | 73.475 | 0.000 | 1.000 | − | − | − | |||||||||
| - Object × gen. × coh. | rMeasures | Sph.viol | 0.459 | 0.837 | 0.184 | − | − | − | |||||||||
| - Gen. × coh. | rMeasures | Sph.viol | 1.110 | 0.338 | 0.234 | − | − | − | |||||||||
| Genotype | Cohort | Genotype × cohort | Pairwise comparisons | ||||||||||||||
| Exploration numbers | Test | Data structure | WT | Het | KO | F | p value | Power | F | pvalue | Power | F | pvalue | Power | WT vs Het | WT vs KO | Het vsKO |
| Dice | 2wANOVA | Nonnormal | 20.17 ± 1.7 | 21.05 ± 1.39 | 20.76 ± 1.69 | 0.054 | 0.948 | 0.058 | 15.707 | 0.000 | 0.973 | 0.620 | 0.542 | 0.148 | − | − | − |
| Jack | 2wANOVA | Normal | 20.17 ± 2.46 | 23.42 ± 2.38 | 20.94 ± 1.95 | 1.196 | 0.311 | 0.249 | 72.111 | 0.000 | 1.000 | 1.200 | 0.310 | 0.250 | − | − | − |
| Lego | 2wANOVA | Normal | 23.94 ± 2.46 | 26.31 ± 1.71 | 20.82 ± 2 | 2.785 | 0.072 | 0.523 | 17.510 | 0.000 | 0.984 | 0.367 | 0.695 | 0.106 | 0.495 | 0.573 | 0.091 |
| Pin | 2wANOVA | Normal | 20.17 ± 2.46 | 23.42 ± 2.38 | 20.94 ± 1.95 | 1.196 | 0.311 | 0.249 | 72.111 | 0.000 | 1.000 | 1.200 | 0.310 | 0.250 | − | − | − |
| Object interaction % | Test | Data structure | F | p value | Power | WT vs Het | WT vs KO | Het vsKO | |||||||||
| - Object | rMeasures | Sph.viol | 4.812 | 0.022 | 0.897 | − | − | − | |||||||||
| - Object × gen. | rMeasures | Sph.viol | 0.363 | 0.762 | 0.151 | − | − | − | |||||||||
| - Genotype | rMeasures | Sph.viol | 0.328 | 0.722 | 0.099 | − | − | − | |||||||||
| - Cohort | rMeasures | Sph.viol | 7.375 | 0.009 | 0.758 | − | − | − | |||||||||
| - Object × gen. × coh. | rMeasures | Sph.viol | 0.560 | 0.627 | 0.220 | − | − | − | |||||||||
| - Gen. × coh. | rMeasures | Sph.viol | 0.328 | 0.722 | 0.099 | − | − | − | |||||||||
| Genotype | Cohort | Genotype × cohort | Pairwise comparisons | ||||||||||||||
| Object interaction number | Test | Datastructure | WT | Het | KO | F | p value | Power | F | pvalue | Power | F | pvalue | Power | WT vs Het | WT vs KO | Het vsKO |
| Dice | 2wANOVA | Normal | 24.87 ± 1.44 | 23.13 ± 1.27 | 25.81 ± 1.7 | 1.119 | 0.335 | 0.235 | 10.075 | 0.003 | 0.875 | 0.297 | 0.745 | 0.094 | − | − | − |
| Jack | 2wANOVA | Normal | 23.14 ± 1.35 | 24.09 ± 1.09 | 24.69 ± 0.91 | 0.164 | 0.849 | 0.074 | 11.956 | 0.001 | 0.923 | 0.546 | 0.583 | 0.135 | − | − | − |
| Lego | 2wANOVA | Nonnormal | 28.84 ± 2 | 28.66 ± 1.57 | 24.78 ± 1.41 | 1.507 | 0.232 | 0.305 | 2.901 | 0.095 | 0.386 | 1.286 | 0.286 | 0.265 | − | − | − |
| Pin | 2wANOVA | Nonnormal | 33.55 ± 7.69 | 32.7 ± 6.64 | 30.85 ± 4.83 | 0.235 | 0.792 | 0.085 | 10.476 | 0.002 | 0.887 | 0.467 | 0.630 | 0.122 | − | − | − |
| Object interaction number, object ranked by preference | Test | Data structure | F | p value | Power | WT vs Het | WT vs KO | Het vsKO | |||||||||
| - Object | rMeasures | Sph.viol | 74.224 | 0.000 | 1.000 | − | − | − | |||||||||
| - Object × gen. | rMeasures | Sph.viol | 0.867 | 0.499 | 0.335 | − | − | − | |||||||||
| - Genotype | rMeasures | Sph.viol | 2.228 | 0.119 | 0.432 | − | − | − | |||||||||
| - Cohort | rMeasures | Sph.viol | 72.229 | 0.000 | 1.000 | − | − | − | |||||||||
| - Object × gen. × coh. | rMeasures | Sph.viol | 0.653 | 0.649 | 0.254 | − | − | − | |||||||||
| - Gen. × coh. | rMeasures | Sph.viol | 1.142 | 0.328 | 0.239 | − | − | − | |||||||||
| Genotype | Cohort | Genotype × cohort | Pairwise comparisons | ||||||||||||||
| Object interaction number | Test | Data structure | WT | Het | KO | F | p value | Power | F | pvalue | Power | F | p value | Power | WT vs Het | WT vs KO | Het vsKO |
| Object #1 | 2wANOVA | Normal | 26.88 ± 2.3 | 29.15 ± 1.88 | 25.58 ± 1.75 | 1.682 | 0.197 | 0.337 | 30.522 | 0.000 | 1.000 | 0.173 | 0.842 | 0.075 | − | − | − |
| Object #2 | 2wANOVA | Nonnormal | 23.23 ± 2.05 | 25.15 ± 2.07 | 21.64 ± 1.85 | 2.474 | 0.095 | 0.473 | 59.810 | 0.000 | 1.000 | 0.752 | 0.477 | 0.170 | 0.421 | 0.829 | 0.167 |
| Object #3 | 2wANOVA | Nonnormal | 17.94 ± 2.12 | 21.94 ± 1.92 | 18.88 ± 1.7 | 2.307 | 0.110 | 0.446 | 66.844 | 0.000 | 1.000 | 1.460 | 0.242 | 0.297 | − | − | − |
| Object #4 | 2wANOVA | Nonnormal | 16.41 ± 1.91 | 17.94 ± 1.34 | 16.94 ± 1.62 | 0.441 | 0.646 | 0.118 | 54.987 | 0.000 | 1.000 | 2.377 | 0.104 | 0.457 | − | − | − |
| Object interaction %, object ranked by preference | Test | Data structure | F | p value | Power | WT vs Het | WT vs KO | Het vs KO | |||||||||
| - Object | rMeasures | Sph.viol | 86.885 | 0.000 | 1.000 | − | − | − | |||||||||
| - Object × gen. | rMeasures | Sph.viol | 0.745 | 0.578 | 0.288 | − | − | − | |||||||||
| - Genotype | rMeasures | Sph.viol | 1.010 | 0.411 | 0.207 | − | − | − | |||||||||
| - Cohort | rMeasures | Sph.viol | 0.960 | 0.390 | 0.163 | − | − | − | |||||||||
| - Object × gen. × coh. | rMeasures | Sph.viol | 0.979 | 0.327 | 0.390 | − | − | − | |||||||||
| - Gen. × coh. | rMeasures | Sph.viol | 0.960 | 0.390 | 0.207 | − | − | − | |||||||||
| Genotype | Cohort | Genotype × cohort | Pairwise comparisons | ||||||||||||||
| Object interaction % | Test | Data structure | WT | Het | KO | F | p value | Power | F | p value | Power | F | p value | Power | WT vs Het | WT vs KO | Het vs KO |
| Object #1 | 2wANOVA | Nonnormal | 32.55 ± 1.41 | 31.48 ± 1.02 | 31.19 ± 0.99 | 0.066 | 0.936 | 0.059 | 11.328 | 0.002 | 0.910 | 0.966 | 0.388 | 0.208 | − | − | − |
| Object #2 | 2wANOVA | Normal | 28.09 ± 0.86 | 26.68 ± 0.74 | 25.78 ± 0.8 | 1.433 | 0.249 | 0.292 | 0.009 | 0.926 | 0.051 | 0.256 | 0.775 | 0.088 | − | − | − |
| Object #3 | 2wANOVA | Nonnormal | 20.49 ± 0.83 | 22.71 ± 0.81 | 22.52 ± 0.79 | 1.538 | 0.225 | 0.311 | 9.140 | 0.004 | 0.842 | 2.049 | 0.140 | 0.402 | − | − | − |
| Object #4 | 2wANOVA | Normal | 18.85 ± 0.7 | 19.11 ± 0.83 | 20.08 ± 0.64 | 0.454 | 0.638 | 0.120 | 2.559 | 0.116 | 0.348 | 0.975 | 0.385 | 0.210 | − | − | − |
| Repetitive novel object contact task, pattern of object investigation | |||||||||||||||||
| Genotype | Cohort | Genotype × cohort | Pairwise comparisons | ||||||||||||||
| Three-object sequences | Test | Data structure | WT | Het | KO | F | p value | Power | F | p value | Power | F | p value | Power | WT vs Het | WT vs KO | Het vs KO |
| Total number of 3-object choices | 2wANOVA | Normal | 56.11 ± 3.2 | 53.57 ± 4.82 | 53.11 ± 3.29 | 0.077 | 0.926 | 0.061 | 12.053 | 0.001 | 0.925 | 0.573 | 0.567 | 0.140 | − | − | − |
| Number of different 3-object sequences | 2wANOVA | Normal | 26.5 ± 0.57 | 25.36 ± 1.21 | 25.47 ± 0.93 | 0.405 | 0.669 | 0.112 | 7.502 | 0.009 | 0.765 | 0.830 | 0.442 | 0.184 | − | − | − |
| Number of repetition of top preferred sequence | 2wANOVA | Nonnormal | 4.88 ± 0.4 | 4.78 ± 0.37 | 4.64 ± 0.29 | 0.012 | 0.988 | 0.052 | 10.796 | 0.002 | 0.896 | 0.052 | 0.950 | 0.057 | − | − | − |
| Number of repetition of 2nd preferred sequence | 2wANOVA | Nonnormal | 4.27 ± 0.27 | 4.15 ± 0.33 | 4.05 ± 0.26 | 0.017 | 0.983 | 0.052 | 8.748 | 0.005 | 0.826 | 0.312 | 0.733 | 0.097 | − | − | − |
| Number of repetition of 3rd preferred sequence | 2wANOVA | Nonnormal | 3.83 ± 0.23 | 3.68 ± 0.3 | 3.7 ± 0.25 | 0.042 | 0.959 | 0.056 | 6.542 | 0.014 | 0.708 | 0.303 | 0.740 | 0.095 | − | − | − |
| Number of repetition of top 3 preferred sequences | 2wANOVA | Normal | 13 ± 0.87 | 12.63 ± 0.98 | 12.41 ± 0.78 | 0.008 | 0.992 | 0.051 | 9.545 | 0.003 | 0.857 | 0.146 | 0.865 | 0.071 | − | − | − |
| % top preferred sequence choice | 2wANOVA | Nonnormal | 8.57 ± 0.32 | 9.41 ± 0.61 | 8.75 ± 0.19 | 1.324 | 0.276 | 0.272 | 0.000 | 0.994 | 0.050 | 1.436 | 0.248 | 0.293 | − | − | − |
| % top 2 preferred sequence choice | 2wANOVA | Nonnormal | 16.22 ± 0.52 | 17.48 ± 1.01 | 16.43 ± 0.32 | 1.179 | 0.316 | 0.246 | 0.143 | 0.707 | 0.066 | 1.543 | 0.224 | 0.312 | − | − | − |
| % top 3 preferred sequence choice | 2wANOVA | Nonnormal | 23.14 ± 0.71 | 24.69 ± 1.43 | 23.44 ± 0.51 | 0.837 | 0.439 | 0.185 | 0.564 | 0.456 | 0.114 | 1.040 | 0.361 | 0.221 | − | − | − |
| Genotype | Cohort | Genotype × cohort | Pairwise comparisons | ||||||||||||||
| Four-object sequences | Test | Data structure | WT | Het | KO | F | p value | Power | F | p value | Power | F | p value | Power | WT vs Het | WT vs KO | Het vs KO |
| Total number of 4-object choices | 2wANOVA | Normal | 55.55 ± 3.26 | 53.26 ± 4.79 | 52.58 ± 3.24 | 0.067 | 0.935 | 0.060 | 10.400 | 0.002 | 0.885 | 0.528 | 0.593 | 0.132 | − | − | − |
| Number of different 4-object sequences | 2wANOVA | Normal | 40.77 ± 1.59 | 39.63 ± 2.78 | 39 ± 2.03 | 0.097 | 0.908 | 0.064 | 9.857 | 0.003 | 0.868 | 0.895 | 0.415 | 0.195 | − | − | − |
| Number of repetition of top preferred sequence | 2wANOVA | Nonnormal | 3.05 ± 0.2 | 3.1 ± 0.2 | 3.41 ± 0.17 | 1.297 | 0.283 | 0.267 | 4.144 | 0.047 | 0.514 | 0.050 | 0.951 | 0.057 | − | − | − |
| Number of repetition of 2nd preferred sequence | 2wANOVA | Nonnormal | 2.83 ± 0.2 | 2.84 ± 0.2 | 2.76 ± 0.18 | 0.034 | 0.967 | 0.055 | 4.324 | 0.043 | 0.531 | 1.214 | 0.306 | 0.253 | − | − | − |
| Number of repetition of 3rd preferred sequence | 2wANOVA | Nonnormal | 2.44 ± 0.16 | 2.47 ± 0.19 | 2.23 ± 0.13 | 0.468 | 0.629 | 0.122 | 4.499 | 0.039 | 0.547 | 1.063 | 0.353 | 0.225 | − | − | − |
| Number of repetition of top 3 preferred sequences | 2wANOVA | Nonnormal | 8.33 ± 0.53 | 8.42 ± 0.55 | 8.41 ± 0.42 | 0.087 | 0.916 | 0.063 | 5.267 | 0.026 | 0.614 | 0.634 | 0.535 | 0.150 | − | − | − |
| % top preferred sequence choice | 2wANOVA | Nonnormal | 5.58 ± 0.3 | 6.31 ± 0.47 | 6.66 ± 0.27 | 2.187 | 0.123 | 0.425 | 2.759 | 0.103 | 0.370 | 1.056 | 0.356 | 0.224 | − | − | − |
| % top 2 preferred sequence choice | 2wANOVA | Nonnormal | 10.7 ± 0.44 | 11.99 ± 0.77 | 12.09 ± 0.51 | 1.734 | 0.187 | 0.346 | 2.734 | 0.105 | 0.367 | 1.166 | 0.320 | 0.244 | − | − | − |
| % top 3 preferred sequence choice | 2wANOVA | Nonnormal | 15.14 ± 0.54 | 16.93 ± 1.02 | 16.43 ± 0.67 | 1.557 | 0.221 | 0.314 | 3.181 | 0.081 | 0.416 | 1.237 | 0.299 | 0.257 | − | − | − |
| Barnes maze initial training - distance | |||||||||||||||||
| Distance | Test | Data structure | F | p value | Power | WT vs Het | WT vs KO | Het vsKO | |||||||||
| - Day | rMeasures | Sph.ass | 13.695 | 0.000 | 1.000 | − | − | − | |||||||||
| - Day × gen. | rMeasures | Sph.ass | 2.062 | 0.062 | 0.684 | − | − | − | |||||||||
| - Genotype | rMeasures | Sph.ass | 2.663 | 0.080 | 0.503 | 0.659 | 0.145 | 0.515 | |||||||||
| - Cohort | rMeasures | Sph.ass | 11.841 | 0.001 | 0.920 | − | − | − | |||||||||
| - Day × gen. × coh. | rMeasures | Sph.ass | 1.173 | 0.324 | 0.416 | − | − | − | |||||||||
| - Gen. × coh. | rMeasures | Sph.ass | 1.114 | 0.337 | 0.234 | − | − | − | |||||||||
| Genotype | Cohort | Genotype × cohort | Pairwise comparisons | ||||||||||||||
| Individual days | Test | Data structure | WT | Het | KO | F | p value | Power | F | p value | Power | F | pvalue | Power | WT vsHet | WT vsKO | Het vs KO |
| Day 1 | 2wANOVA | Normal | 501.24 ± 48.28 | 485.42 ± 47.71 | 484.49 ± 53.07 | 0.003 | 0.997 | 0.050 | 4.283 | 0.044 | 0.526 | 0.084 | 0.919 | 0.062 | − | − | − |
| Day 2 | 2wANOVA | Normal | 427.6 ± 43.5 | 468.59 ± 40.26 | 504.18 ± 47.17 | 1.234 | 0.301 | 0.256 | 9.205 | 0.004 | 0.844 | 1.918 | 0.158 | 0.378 | − | − | − |
| Day 3 | 2wANOVA | Normal | 292.36 ± 29.11 | 340.26 ± 31.24 | 485.74 ± 41.16 | 11.293 | 0.000 | 0.989 | 6.902 | 0.012 | 0.730 | 3.082 | 0.055 | 0.567 | 0.496 | 0.000 | 0.005 |
| Day 4 | 2wANOVA | Normal | 311.01 ± 34.75 | 370.86 ± 29.61 | 367.31 ± 42.11 | 1.479 | 0.239 | 0.300 | 5.449 | 0.024 | 0.628 | 0.666 | 0.519 | 0.155 | − | − | − |
| Barnes maze reversal - distance | |||||||||||||||||
| Distance | Test | Data structure | F | p value | Power | WT vs Het | WT vs KO | Het vs KO | |||||||||
| - Day effect | rMeasures | Sph.ass | 26.455 | 0.000 | 1.000 | − | − | − | |||||||||
| - Day × gen. | rMeasures | Sph.ass | 2.612 | 0.023 | 0.824 | − | − | − | |||||||||
| - Genotype | rMeasures | Sph.ass | 1.811 | 0.175 | 0.359 | − | − | − | |||||||||
| - Cohort | rMeasures | Sph.ass | 1.924 | 0.172 | 0.274 | − | − | − | |||||||||
| - Day × gen. × coh. | rMeasures | Sph.ass | 3.192 | 0.007 | 0.902 | − | − | − | |||||||||
| - Genotype × cohort effect | rMeasures | Sph.ass | 0.290 | 0.750 | 0.093 | − | − | − | |||||||||
| Genotype | Cohort | Genotype × cohort | Pairwise comparisons | ||||||||||||||
| Individual days | Test | Data structure | WT | Het | KO | F | p value | Power | F | pvalue | Power | F | p value | Power | WT vs Het | WT vs KO | Het vsKO |
| Day 1 | 2wANOVA | Nonnormal | 420.93 ± 37.75 | 437.03 ± 37.86 | 591.59 ± 38.48 | 5.592 | 0.007 | 0.834 | 0.793 | 0.378 | 0.141 | 1.475 | 0.239 | 0.299 | 0.948 | 0.009 | 0.018 |
| Day 2 | 2wANOVA | Normal | 336.81 ± 35.36 | 413.64 ± 32.4 | 390.91 ± 45 | 1.285 | 0.286 | 0.265 | 0.374 | 0.544 | 0.092 | 2.525 | 0.091 | 0.481 | − | − | − |
| Day 3 | 2wANOVA | Normal | 357.93 ± 35.96 | 421.04 ± 44.36 | 395.85 ± 48.06 | 0.666 | 0.519 | 0.155 | 3.371 | 0.073 | 0.436 | 0.116 | 0.890 | 0.067 | − | − | − |
| Day 4 | 2wANOVA | Normal | 288.54 ± 39.85 | 288.65 ± 37.41 | 337.24 ± 38.59 | 0.965 | 0.389 | 0.207 | 8.849 | 0.005 | 0.829 | 1.373 | 0.264 | 0.281 | − | − | − |
| Barnes maze initial training probe test | |||||||||||||||||
| Genotype | Quadrant pairwise comparisons | ||||||||||||||||
| All animals | Test | Data structure | F | p value | Power | T vs L | T vs R | T vs O | L vsR | L vs O | R vs O | ||||||
| - Quadrant | rMeasures | Sph.viol | 296.653 | 0.000 | 1.000 | 0.000 | 0.000 | 0.000 | 0.555 | 0.201 | 0.628 | ||||||
| - Cohort | rMeasures | Sph.viol | 10.200 | 0.002 | 1.000 | ||||||||||||
| - Quadrant × coh. | rMeasures | Sph.viol | 11.435 | 0.000 | 0.983 | ||||||||||||
| WT | Test | Data structure | F | p value | Power | T vs L | T vs R | T vs O | L vs R | L vs O | R vs O | ||||||
| - Quadrant | rMeasures | Sph.viol | 58.318 | 0.000 | 1.000 | 0.000 | 0.000 | 0.000 | 0.057 | 0.168 | 0.335 | ||||||
| - Cohort | rMeasures | Sph.viol | 9.373 | 0.007 | 0.820 | ||||||||||||
| - Quadrant × coh. | rMeasures | Sph.viol | 4.241 | 0.010 | 0.831 | ||||||||||||
| Het | Test | Data structure | F | p value | Power | T vs L | T vs R | T vs O | L vsR | L vsO | R vs O | ||||||
| - Quadrant | rMeasures | Sph.viol | 107.980 | 0.000 | 1.000 | 0.000 | 0.000 | 0.000 | 0.205 | 0.895 | 0.278 | ||||||
| - Cohort | rMeasures | Sph.viol | 65.390 | 0.000 | 1.000 | ||||||||||||
| - Quadrant × coh. | rMeasures | Sph.viol | 5.366 | 0.003 | 0.915 | ||||||||||||
| KO | Test | Data structure | F | p value | Power | T vsL | T vsR | T vsO | L vsR | L vs O | R vs O | ||||||
| - Quadrant | rMeasures | Sph.viol | 378.546 | 0.000 | 1.000 | 0.000 | 0.000 | 0.000 | 0.832 | 0.278 | 0.341 | ||||||
| - Cohort | rMeasures | Sph.viol | 890.226 | 0.000 | 1.000 | ||||||||||||
| - Quadrant × coh. | rMeasures | Sph.viol | 1.683 | 0.186 | 0.406 | ||||||||||||
| Genotype | Cohort | Genotype × cohort | Pairwise comparisons | ||||||||||||||
| Probe test quadrants | Test | Data structure | WT | Het | KO | F | p value | Power | F | p value | Power | F | p value | Power | WT vsHet | WT vsKO | Het vsKO |
| Target | 2wANOVA | Nonnormal | 107.29 ± 7.96 | 125.68 ± 7.96 | 142.87 ± 4.53 | 5.342 | 0.008 | 0.816 | 12.144 | 0.001 | 0.927 | 0.935 | 0.400 | 0.202 | 0.112 | 0.001 | 0.173 |
| Left | 2wANOVA | Nonnormal | 28.57 ± 4.6 | 14.87 ± 2.32 | 11.37 ± 2.49 | 7.081 | 0.002 | 0.914 | 4.207 | 0.046 | 0.519 | 0.660 | 0.522 | 0.154 | 0.010 | 0.002 | 0.740 |
| Right | 2wANOVA | Nonnormal | 16.92 ± 3.86 | 20.57 ± 4.93 | 12.28 ± 2.15 | 1.097 | 0.342 | 0.231 | 7.056 | 0.011 | 0.739 | 1.048 | 0.359 | 0.222 | 0.763 | 0.678 | 0.290 |
| Opposite | 2wANOVA | Nonnormal | 22.28 ± 4.49 | 14.37 ± 3.47 | 9.2 ± 2.09 | 2.438 | 0.099 | 0.466 | 10.443 | 0.002 | 0.886 | 1.149 | 0.326 | 0.240 | 0.199 | 0.024 | 0.526 |
| Barnes maze reversal probe test | |||||||||||||||||
| Genotype | Quadrant pairwise comparisons | ||||||||||||||||
| All animals | Test | Data structure | F | p value | Power | T vs L | T vsR | T vs O | L vsR | L vs O | R vs O | ||||||
| - Quadrant | rMeasures | Sph.viol | 50.865 | 0.000 | 1.000 | 0.000 | 0.000 | 0.000 | 0.242 | 0.000 | 0.000 | ||||||
| - Cohort | rMeasures | Sph.viol | 24.530 | 0.000 | 0.998 | ||||||||||||
| - Quadrant × coh. | rMeasures | Sph.viol | 4.443 | 0.005 | 0.870 | ||||||||||||
| WT | Test | Data structure | F | p value | Power | T vsL | T vsR | T vsO | L vs R | L vs O | R vs O | ||||||
| - Quadrant | rMeasures | Sph.viol | 32.279 | 0.000 | 1.000 | 0.000 | 0.000 | 0.000 | 0.005 | 0.024 | 0.003 | ||||||
| - Cohort | rMeasures | Sph.viol | 159.377 | 0.000 | 1.000 | ||||||||||||
| - Quadrant × coh. | rMeasures | Sph.viol | 0.007 | 0.956 | 0.051 | ||||||||||||
| Het | Test | Data structure | F | p value | Power | T vs L | T vs R | T vs O | L vsR | L vs O | R vs O | ||||||
| - Quadrant | rMeasures | Sph.viol | 28.198 | 0.000 | 1.000 | 0.000 | 0.000 | 0.001 | 0.235 | 0.001 | 0.086 | ||||||
| - Cohort | rMeasures | Sph.viol | 6.412 | 0.021 | 0.666 | ||||||||||||
| - Quadrant × coh. | rMeasures | Sph.viol | 10.315 | 0.000 | 0.998 | ||||||||||||
| KO | Test | Data structure | F | p value | Power | T vsL | T vs R | T vs O | L vs R | L vs O | R vs O | ||||||
| - Quadrant | rMeasures | Sph.viol | 12.026 | 0.000 | 0.999 | 0.000 | 0.010 | 0.646 | 0.070 | 0.000 | 0.000 | ||||||
| - Cohort | rMeasures | Sph.viol | 397.250 | 0.000 | 1.000 | ||||||||||||
| - Quadrant × coh. | rMeasures | Sph.viol | 2.273 | 0.095 | 0.531 | ||||||||||||
| Genotype | Cohort | Genotype × cohort | Pairwise comparisons | ||||||||||||||
| Probe test quadrants | Test | Data structure | WT | Het | KO | F | p value | Power | F | p value | Power | F | pvalue | Power | WT vs Het | WT vs KO | Het vsKO |
| Target | 2wANOVA | Nonnormal | 115.33 ± 11.27 | 105.35 ± 12.55 | 67.82 ± 11.65 | 5.430 | 0.008 | 0.822 | 8.183 | 0.006 | 0.800 | 3.469 | 0.040 | 0.621 | 0.773 | 0.010 | 0.046 |
| Left | 2wANOVA | Nonnormal | 18.44 ± 3.76 | 8.03 ± 2.15 | 9.68 ± 2.79 | 3.343 | 0.044 | 0.604 | 2.079 | 0.156 | 0.292 | 0.172 | 0.842 | 0.075 | 0.039 | 0.123 | 0.923 |
| Right | 2wANOVA | Nonnormal | 9.8 ± 2.46 | 18.48 ± 7.8 | 23.17 ± 5.32 | 1.367 | 0.265 | 0.280 | 1.873 | 0.178 | 0.268 | 2.980 | 0.061 | 0.551 | 0.489 | 0.229 | 0.826 |
| Opposite | 2wANOVA | Nonnormal | 32.67 ± 6.87 | 42.82 ± 10 | 75.15 ± 10.65 | 6.632 | 0.003 | 0.894 | 7.210 | 0.010 | 0.748 | 2.097 | 0.134 | 0.409 | 0.662 | 0.004 | 0.030 |
WT, wild-type mice; Het, heterozygous mice; KO, homozygous knock-out mice. Group values are reported as mean ± SEM. Bold font indicates significant results (p < 0.05). Individual results and statistical analyses for cohorts 1 and 2 are available in Extended Data Table 11-1. 2wANOVA: 2-way ANOVA, rMeasures: repeated measures, Norm: normal, No-norm: non-normal, Sph.ass: sphericity assumed, Sph.viol: sphericity violated, gen: genotype, coh: cohort. 2wANOVA: 2-way ANOVA, rMeasures: repeated measures, Sph.ass: sphericity assumed, Sph.viol: sphericity violated, gen: genotype, coh: cohort.