TY - JOUR
T1 - Spontaneous and TMS-related EEG changes as new biomarkers to measure anti-epileptic drug effects
AU - Biondi, Andrea
AU - Rocchi, L.
AU - Santoro, V.
AU - Rossini, P. G.
AU - Beatch, G. N.
AU - Richardson, M. P.
AU - Premoli, I.
N1 - Funding Information:
MPR is funded by MRC Programme Grant MR/K013998/1, EPSRC Centre for Predictive Modelling in Healthcare EP/N014391/1, and by the NIHR Biomedical Research Centre and South London and Maudsley NHS Foundation Trust and King’s College London. IP is partly funded by Xenon Pharmaceuticals Inc. This study represents independent research supported by the National Institute for Health Research (NIHR)-Well come King’s Clinical Research Facility and the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.
Funding Information:
MPR is funded by MRC Programme Grant MR/K013998/1, EPSRC Centre for Predictive Modelling in Healthcare EP/N014391/1, and by the NIHR Biomedical Research Centre and South London and Maudsley NHS Foundation Trust and King?s College London. IP is partly funded by Xenon Pharmaceuticals Inc. This study represents independent research supported by the National Institute for Health Research (NIHR)-Well come King?s Clinical Research Facility and the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King?s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/2/4
Y1 - 2022/2/4
N2 - Robust biomarkers for anti-epileptic drugs (AEDs) activity in the human brain are essential to increase the probability of successful drug development. The frequency analysis of electroencephalographic (EEG) activity, either spontaneous or evoked by transcranial magnetic stimulation (TMS-EEG) can provide cortical readouts for AEDs. However, a systematic evaluation of the effect of AEDs on spontaneous oscillations and TMS-related spectral perturbation (TRSP) has not yet been provided. We studied the effects of Lamotrigine, Levetiracetam, and of a novel potassium channel opener (XEN1101) in two groups of healthy volunteers. Levetiracetam suppressed TRSP theta, alpha and beta power, whereas Lamotrigine decreased delta and theta but increased the alpha power. Finally, XEN1101 decreased TRSP delta, theta, alpha and beta power. Resting-state EEG showed a decrease of theta band power after Lamotrigine intake. Levetiracetam increased theta, beta and gamma power, while XEN1101 produced an increase of delta, theta, beta and gamma power. Spontaneous and TMS-related cortical oscillations represent a powerful tool to characterize the effect of AEDs on in vivo brain activity. Spectral fingerprints of specific AEDs should be further investigated to provide robust and objective biomarkers of biological effect in human clinical trials.
AB - Robust biomarkers for anti-epileptic drugs (AEDs) activity in the human brain are essential to increase the probability of successful drug development. The frequency analysis of electroencephalographic (EEG) activity, either spontaneous or evoked by transcranial magnetic stimulation (TMS-EEG) can provide cortical readouts for AEDs. However, a systematic evaluation of the effect of AEDs on spontaneous oscillations and TMS-related spectral perturbation (TRSP) has not yet been provided. We studied the effects of Lamotrigine, Levetiracetam, and of a novel potassium channel opener (XEN1101) in two groups of healthy volunteers. Levetiracetam suppressed TRSP theta, alpha and beta power, whereas Lamotrigine decreased delta and theta but increased the alpha power. Finally, XEN1101 decreased TRSP delta, theta, alpha and beta power. Resting-state EEG showed a decrease of theta band power after Lamotrigine intake. Levetiracetam increased theta, beta and gamma power, while XEN1101 produced an increase of delta, theta, beta and gamma power. Spontaneous and TMS-related cortical oscillations represent a powerful tool to characterize the effect of AEDs on in vivo brain activity. Spectral fingerprints of specific AEDs should be further investigated to provide robust and objective biomarkers of biological effect in human clinical trials.
UR - http://www.scopus.com/inward/record.url?scp=85124173085&partnerID=8YFLogxK
U2 - 10.1038/s41598-022-05179-x
DO - 10.1038/s41598-022-05179-x
M3 - Article
C2 - 35121751
AN - SCOPUS:85124173085
SN - 2045-2322
VL - 12
SP - 1919
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 1919
ER -