Investigating Catamenial Epilepsy in Humans using EEG and Visually Induced Gamma Oscillations
Poster No:
1762
Submission Type:
Abstract Submission
Authors:
Malak Alshakhouri1, Suresh Muthukumaraswamy2, Khalid Hamandi3, Peter Bergin4, Cynthia Sharpe5, Rachael Sumner1
Institutions:
1The University of Auckland, Auckland, Auckland, 2University of Auckland, Auckland, Auckland, 3Cardiff University, Cardiff, Cardiff, 4Neurology, Auckland Hospital, Auckland, Auckland, 5Paediatric Neurology, Starship Children’s Health, Auckland, Auckland
First Author:
Co-Author(s):
Introduction:
Around 40% of females with epilepsy (FE) experience recurring seizure exacerbations during certain phases of the menstrual cycle, a condition termed catamenial epilepsy that is often treatment resistant (Alshakhouri et al., 2024). The most common pattern is perimenstrual catamenial epilepsy (PCE), exemplified by a two-fold increase in seizure frequency around menstruation (Herzog et al., 2004). The current leading hypothesis suggests PCE could be a withdrawal symptom caused by rapid decline of allopregnanolone (ALLO) premenstrually, following prolonged exposure during the luteal phase (Reddy, 2016). ALLO, a metabolite of progesterone, enhances the major inhibitory system of the brain via gamma-aminobutyric acid receptors (GABAARs). Our goal is to investigate changes in ALLO-mediated GABAergic inhibition across the menstrual cycle using an established visual gamma and electroencephalography (EEG) paradigm.
Methods:
This study used a within-subject, repeated-measures, counterbalanced, observational design. Twenty-five FE with uncontrolled seizers and 25 healthy controls (HC) attended 3 sessions timed to their perimenstrual (day -3 to +2), mid-follicular (day 5 to 8), and mid-luteal (day -5 to -9) cycle phases, with day 1 being first day of menstrual bleeding. Blood samples were taken to confirm ovulation and to assess the levels of progesterone, oestradiol and ALLO. At each visit, participants performed a simple visual task to induce gamma oscillations, consisting of 4 blocks of 84 trials, where a black and white annular grating is presented on a screen at 90% contrast, subtending 16° visual angle. EEG was obtained using a 64-channel actiCAP system. Data was pre-processed using Fieldtrip in MATLAB. A linearly constrained minimum variance beamformer was applied with a broad 30-90hz filter. The result was projected into the Montreal Neurological Institute coordinate system. The coordinate contributing the peak gamma power intensity was used to construct a virtual sensor, representing peak gamma frequency across power.
Results:
Initial analysis of 16 HC EEG datasets revealed a significant effect of menstrual cycle phase on visually induced peak gamma frequency (F(2,15) = 5.023, p = 0.021). Visually induced peak gamma frequency in the follicular phase was 4.8 Hz lower than the luteal phase (t(16)= -3.24, p= 0.005) and 3.8 Hz lower than the perimenstrual phase (t(16)= -2.24, p= 0.039). There was no significant difference between the perimenstrual phase and the luteal phase (t(16) = 0.696, p = 0.50). Interestingly, there was no significant changes in gamma frequency over the menstrual cycle in the EC (n = 20).
All participants in both cohorts exhibited shifts in plasma concentration of progesterone and oestradiol across the menstrual cycle that are indicative of ovulation (Figure 1). However, there was no significant correlation between shifts in hormone concentrations and gamma frequency in either cohorts.
All participants in both cohorts exhibited shifts in plasma concentration of progesterone and oestradiol across the menstrual cycle that are indicative of ovulation (Figure 1). However, there was no significant correlation between shifts in hormone concentrations and gamma frequency in either cohorts.
·Figure 1. Mean plasma hormone levels for each study session for (A) healthy and (B) epilepsy cohorts. Abbreviations: FOL = mid-follicular, LUT = mid-luteal, PERI = perimenstrual.
Conclusions:
The HC findings replicate our previous findings (Sumner et al., 2018), where peak gamma frequency was around 5 Hz higher during the luteal phase than the follicular phase, and extend this to consider the perimenstrual phase. Given that the perimenstrual phase is characterised by lower hormones than the mid-luteal phase, it is interesting that gamma frequency remains high. The lack of correlations between hormones and changes in gamma frequency suggests that changes in gamma frequency are not mediated by absolute hormone concentrations, but by other temporal dynamics such as receptor expression. Gamma frequency has been correlated with GABAAR density (Kujala et al., 2015). This aligns with our HC findings as GABAAR density increases post-ovulation during the luteal phase and increases further in the perimenstrual phase upon ALLO withdrawal. The lack of change in gamma frequency in FE may indicate GABAAR dysregulation, a masking effect of GABA agonist epilepsy drugs, or a combination of both.
Modeling and Analysis Methods:
EEG/MEG Modeling and Analysis 2
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Transmitter Receptors 1
Transmitter Systems
Physiology, Metabolism and Neurotransmission:
Pharmacology and Neurotransmission
Keywords:
Electroencephaolography (EEG)
Epilepsy
Neurotransmitter
RECEPTORS
1|2Indicates the priority used for review
Abstract Information
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Herzog, A. G., Harden, C. L., Liporace, J., Pennell, P., Schomer, D. L., Sperling, M., Fowler, K., Nikolov, B., Shuman, S., & Newman, M. (2004). Frequency of catamenial seizure exacerbation in women with localization-related epilepsy. Ann Neurol, 56(3), 431-434. https://doi.org/10.1002/ana.20214
Kujala, J., Jung, J., Bouvard, S., Lecaignard, F., Lothe, A., Bouet, R., Ciumas, C., Ryvlin, P., & Jerbi, K. (2015). Gamma oscillations in V1 are correlated with GABAA receptor density: A multi-modal MEG and Flumazenil-PET study. Scientific Reports, 5(1), 16347. https://doi.org/10.1038/srep16347
Reddy, D. S. (2016). Catamenial Epilepsy: Discovery of an Extrasynaptic Molecular Mechanism for Targeted Therapy. Front Cell Neurosci, 10, 101. https://doi.org/10.3389/fncel.2016.00101
Sumner, R. L., McMilllan, R. L., Shaw, A. D., Singh, K. D., Sundram, F., & Muthukumaraswamy, S. D. (2018). Peak visual gamma frequency is modified across the healthy menstrual cycle. Human Brain Mapping. https://doi.org/10.1002/hbm.24069