Dynamics of Epileptiform Discharges Induced by Transcranial Magnetic Stimulation in Genetic Generalized Epilepsy.

OBJECTIVE: In patients with Genetic Generalized Epilepsy (GGE), transcranial magnetic stimulation (TMS) can induce epileptiform discharges (EDs) of varying duration. We hypothesized that (a) the ED duration is determined by the dynamic states of critical network nodes (brain areas) at the early post-TMS period, and (b) brain connectivity changes before, during and after the ED, as well as within the ED. METHODS: EEG recordings from two GGE patients were analyzed. For hypothesis (a), the characteristics of the brain dynamics at the early ED stage are measured with univariate and multivariate EEG measures and the dependence of the ED duration on these measures is evaluated. For hypothesis (b), effective connectivity measures are combined with network indices so as to quantify the brain network characteristics and identify changes in brain connectivity. RESULTS: A number of measures combined with specific channels computed on the first EEG segment post-TMS correlate with the ED duration. In addition, brain connectivity is altered from pre-ED to ED and post-ED and statistically significant changes were also detected across stages within the ED. CONCLUSION: ED duration is not purely stochastic, but depends on the dynamics of the post-TMS brain state. The brain network dynamics is significantly altered in the course of EDs.

TMS combined with EEG in genetic generalized epilepsy: A phase II diagnostic accuracy study.

OBJECTIVES: (A) To develop a TMS-EEG stimulation and data analysis protocol in genetic generalized epilepsy (GGE). (B) To investigate the diagnostic accuracy of TMS-EEG in GGE. METHODS: Pilot experiments resulted in the development and optimization of a paired-pulse TMS-EEG protocol at rest, during hyperventilation (HV), and post-HV combined with multi-level data analysis. This protocol was applied in 11 controls (C) and 25 GGE patients (P), further dichotomized into responders to antiepileptic drugs (R, n=13) and non-responders (n-R, n=12).Features (n=57) extracted from TMS-EEG responses after multi-level analysis were given to a feature selection scheme and a Bayesian classifier, and the accuracy of assigning participants into the classes P-C and R-nR was computed. RESULTS: On the basis of the optimal feature subset, the cross-validated accuracy of TMS-EEG for the classification P-C was 0.86 at rest, 0.81 during HV and 0.92 at post-HV, whereas for R-nR the corresponding figures are 0.80, 0.78 and 0.65, respectively. Applying a fusion approach on all conditions resulted in an accuracy of 0.84 for the classification P-C and 0.76 for the classification R-nR. CONCLUSION: TMS-EEG can be used for diagnostic purposes and for assessing the response to antiepileptic drugs. SIGNIFICANCE: TMS-EEG holds significant diagnostic potential in GGE.

Transcranial Magnetic Stimulation Combined with EEG Reveals Covert States of Elevated Excitability in the Human Epileptic Brain.

BACKGROUND: Transcranial magnetic stimulation combined with electroencephalogram (TMS-EEG) can be used to explore the dynamical state of neuronal networks. In patients with epilepsy, TMS can induce epileptiform discharges (EDs) with a stochastic occurrence despite constant stimulation parameters. This observation raises the possibility that the pre-stimulation period contains multiple covert states of brain excitability some of which are associated with the generation of EDs. OBJECTIVE: To investigate whether the interictal period contains "high excitability" states that upon brain stimulation produce EDs and can be differentiated from "low excitability" states producing normal appearing TMS-EEG responses. METHODS: In a cohort of 25 patients with Genetic Generalized Epilepsies (GGE) we identified two subjects characterized by the intermittent development of TMS-induced EDs. The high-excitability in the pre-stimulation period was assessed using multiple measures of univariate time series analysis. Measures providing optimal discrimination were identified by feature selection techniques. The "high excitability" states emerged in multiple loci (indicating diffuse cortical hyperexcitability) and were clearly differentiated on the basis of 14 measures from "low excitability" states (accuracy = 0.7). CONCLUSION: In GGE, the interictal period contains multiple, quasi-stable covert states of excitability a class of which is associated with the generation of TMS-induced EDs. The relevance of these findings to theoretical models of ictogenesis is discussed.

Causality networks from multivariate time series and application to epilepsy.

Granger causality and variants of this concept allow the study of complex dynamical systems as networks constructed from multivariate time series. In this work, a large number of Granger causality measures used to form causality networks from multivariate time series are assessed. For this, realizations on high dimensional coupled dynamical systems are considered and the performance of the Granger causality measures is evaluated, seeking for the measures that form networks closest to the true network of the dynamical system. In particular, the comparison focuses on Granger causality measures that reduce the state space dimension when many variables are observed. Further, the linear and nonlinear Granger causality measures of dimension reduction are compared to a standard Granger causality measure on electroencephalographic (EEG) recordings containing episodes of epileptiform discharges.