Reduction of Hippocampal High-Frequency Activity in Wag/Rij Rats with a Genetic Predisposition to Absence Epilepsy
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals
2.2. Electrodes Implantation and Recording Procedure
2.3. Automatic Recognition of Hippocampal Oscillations
2.4. Temporal Dynamics of Hippocampal Oscillations
3. Results
3.1. Ripples
- First, the preictal period 2 min immediately prior to the onset of SWDs was analyzed (cluster analysis) in 1 min, 30 s and 15 s time windows (Figure 3a). K-means cluster analysis of ripple density was performed in all 297 SWDs, including 207 SWDs with ripples and 90 SWDs without ripples, during the analyzed 120-s interval. Three statistically different clusters were defined (ANOVA for all four intervals F2;294 = 417 ÷ 853, all p’s < 0.00001, Figure 3a). Two-factors repeated measures ANOVA for the factor ‘cluster’ was F2;294 = 1787, p < 0.0001; for the factor ‘period’ − F3;882 = 33.1, p < 0.0001; ‘cluster’*‘period’ interaction F6;882 = 27.7, p < 0.0001. The majority of cases fell into Cluster 3 (258 SWDs or 86.9% of all SWDs) and showed near-zero ripple density and differed from Cluster 1 and Cluster 2 (p < 0.0001, Bonferroni post-hoc tests, Figure 3a). Cluster 1 (14 SWDs or 4.7% from all SWDs) and Cluster 2 (25 SWDs or 8.4% from all SWDs) were characterized by significantly higher ripple density during the 120s interval than Cluster 3. Therefore, only 13.6% of SWDs were preceded by hippocampal ripples during a 2 min preictal period, and there were two significantly different clusters characterized by different preictal dynamics. Each cluster contained measures from different rats; therefore, clusters did not represent individual differences in ripple activity. Rather spike-wave seizures could represent at least three seizure types in reference to the involvement of hippocampal processes.
- Second, a 40 s period was analyzed (cluster analysis) with a 2 s bin size from −30 s before the onset of SWDs (0 s) to 10 s after the onset of SWDs (Figure 4). Using K-means cluster analysis in all 297 SWDs, we defined three statistically different clusters (ANOVA for all twelve intervals F2;294 = 10.7 ÷ 135.5, all p’s < 0.0001). Again, the majority of cases fell into Cluster 3 with near zero-ripple-density (268 SWDs or 88.5% of all SWDs). Cluster 1 (15 SWDs, 5.1%) and Cluster 2 (19 SWDs, 6.4%) showed higher ripple density and slightly different dynamics (Bonferroni post-hoc test p < 0.05, Figure 3b).
- Third, ripple density was analyzed in preictal, ictal/postictal periods with a 2 s bin size during the period −16 to 8 s around the SWD start time (i.e., a 24 s period, Figure 4). During this period, hippocampal ripples were found in 58.9% of SWD-containing periods (n = 175), and the remaining 41.1% of periods showed no ripples (n = 122). In the first group, hippocampal ripples during the 24-s period were distributed irregularly (Friedman ANOVA, χ2Friedman (df = 12) = 22.1, p = 0.036). The Bonferroni test indicated that ripple density did not differ from zero during two 2 s preictal periods −8 to −4 s, and immediately after SWDs onset 0 to 4 s (p < 0.05, Figure 5). Therefore, a significant reduction to nearly zero-ripple-density was found 4–8 s prior to SWDs onset and during the 4 s immediately after SWDs onset.
3.2. 50–70 Hz High-Frequency Oscillations
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Appendix A
Rat ID. | Total Duration of Recording, s | Total Number of SWDs (Number per h) | Synchronized State | Desynchronized State | ||||
---|---|---|---|---|---|---|---|---|
% From the Total Time | Ripple Density per s | HFO Density per s | % From the Total Time | Ripple Density per s | HFO Density per s | |||
G10 | 5436 | 91 (60.2) | 61 | 0.020 | 0.30 | 39 | 0.014 | 0.215 |
G8 | 5561 | 84 (54.4) | 35 | 0.286 | 0.373 | 65 | 0.240 | 0.355 |
12,152 | 26 (7.7) | 59 | 0.033 | 0.438 | 41 | 0.017 | 0.425 | |
G11 | 4548 | 17 (13.5) | 0 | 100 | 0.024 | 0.263 | ||
5158 | 79 (55.1) | 43 | 0.177 | 0.377 | 57 | 0.178 | 0.212 | |
G12 | 3571 | 0 | 21 | 0.008 | 0.643 | 79 | 0.012 | 0.406 |
3600 | 0 | 67 | 0.005 | 0.481 | 33 | 0.009 | 0.411 |
Rat ID. | Number of SWDs Analyzed | HFO Density per s | ||||
---|---|---|---|---|---|---|
Baseline | Preictal Period | Ictal Period (Start) | Ictal Period (End) | Postictal Periods | ||
−5 … 0 s before SWDsOnset | 0 … 5 s after SWDsOnset | 5 … 0 s before SWDsEnd | 0…+5 s after SWDsEnd | |||
G10 | 14 | 1.900 ± 1.324 | 1.357 ± 1.082 | 0.500 ± 0.855 | 1.571 ± 1.158 | 1.429 ± 1.342 |
G8 (5561 s) | 15 | 1.900 ± 1.100 | 1.067 ± 0.961 | 1.333 ± 1.047 | 1.267 ± 1.033 | 1.067 ± 0.704 |
G8 (12152 s) | 15 | 2.117 ± 1.451 | 1.133 ± 0.516 | 1.200 ± 1.014 | 1.200 ± 1.082 | 1.133 ± 0.743 |
G11 (4548 s) | 15 | 2.100 ± 1.311 | 1.533 ± 1.834 | 1.133 ± 1.060 | 1.200 ± 1.082 | 0.800 ± 0.676 |
G11 (5158 s) | 15 | 2.100 ± 1.311 | 1.333 ± 1.047 | 0.600 ± 1.056 | 0.933 ± 0.961 | 1.133 ± 0.743 |
Average | 2.023 ± 1.299 | 1.284 ± 0.899 | 0.959 ± 1.039 | 1.203 ± 1.054 | 1.108 ± 0.869 |
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Sitnikova, E.; Perevozniuk, D.; Rutskova, E.; Uzakov, S.; Korshunov, V.A. Reduction of Hippocampal High-Frequency Activity in Wag/Rij Rats with a Genetic Predisposition to Absence Epilepsy. Diagnostics 2022, 12, 2798. https://doi.org/10.3390/diagnostics12112798
Sitnikova E, Perevozniuk D, Rutskova E, Uzakov S, Korshunov VA. Reduction of Hippocampal High-Frequency Activity in Wag/Rij Rats with a Genetic Predisposition to Absence Epilepsy. Diagnostics. 2022; 12(11):2798. https://doi.org/10.3390/diagnostics12112798
Chicago/Turabian StyleSitnikova, Evgenia, Dmitrii Perevozniuk, Elizaveta Rutskova, Shukhrat Uzakov, and Viktor A. Korshunov. 2022. "Reduction of Hippocampal High-Frequency Activity in Wag/Rij Rats with a Genetic Predisposition to Absence Epilepsy" Diagnostics 12, no. 11: 2798. https://doi.org/10.3390/diagnostics12112798