Electrical cortical stimulations modulate spike and post-spike slow-related high-frequency activities in human epileptic foci
Introduction
Epilepsy, a neurological disorder, is caused by abnormal electrical discharge due to excessive neuronal activity. Interictal epileptiform discharges (IEDs) are used to diagnose epilepsy and identify the localization of the seizure onset zone (SOZ) (de Curtis and Avanzini, 2001). Each IED usually consists of spikes (excitation) and post-spike slow waves (PSSs) (inhibition) (Blumenfeld, 2005, Serafini and Loeb, 2015). Wide-band electrocorticogram (ECoG) has enabled us to record high-frequency oscillations or activities (HFOs/HFAs). Epileptic HFOs, usually divided into ripple (R: 80–200 Hz) and fast ripple (FR: above 200 or 250 Hz) according to their frequencies, have been recently suggested as possible surrogate markers for epileptogenicity (Crepon et al., 2010, Jefferys et al., 2012). Interictal HFOs are more reliable markers for the SOZ compared with epileptic spikes (Jacobs et al., 2012, Jirsch et al., 2006) and are significantly associated with favorable seizure outcomes (Cho et al., 2014, Jacobs et al., 2010, Kerber et al., 2014). For instance, one study demonstrated significant spatial and temporal associations between IEDs and HFOs (Engel et al., 2009), and another study showed that IEDs with abnormal HFOs, particularly fast ripples (FRs, 250–500 Hz), had greater sensitivity in identifying the epileptogenic region than those without concomitant abnormal HFOs (Jacobs et al., 2008). Thus, HFOs have been extensively examined due to their specific significance for the SOZ. One study demonstrated that both visible HFOs and those with sharp spikes (HFAs) are strongly associated with the epileptogenic zone and are good surrogate markers for favorable surgical outcomes (Burnos et al., 2016). Notably, our previous study found that the HFA power of early cortico-cortical evoked potentials (CCEP) is significantly higher in the SOZ than in the non-SOZ (Kobayashi et al., 2017). These findings suggest that HFAs related to the sharp components reflect the epileptogenicity-related hyperexcitability.
Brain stimulation techniques, such as transcranial magnetic stimulation (TMS) (Kinoshita et al., 2005a, Tergau et al., 1999), transcranial direct/alternating current stimulation (tDCS/tACS) (Herrmann et al., 2013, Reato et al., 2013), and responsive neurostimulation system (RNS) (Ben-Menachem and Krauss, 2014, Morrell, 2011), have recently been employed to treat various neurological and psychiatric disorders. In addition, electrical cortical stimulation (ECS) is considered an adjunctive therapy for patients with contraindications for resection surgery. Accumulating studies demonstrated that ECS produces inhibitory effects, especially on the acquisition of epileptogenicity due to kindling in rodents (Lopez-Meraz et al., 2004), and that high frequency (50 Hz) ECS suppresses IEDs and beta band activities (10–32 Hz) (Kinoshita et al., 2005b), and low-frequency ECS inhibits IEDs and seizure frequency in humans (Koubeissi et al., 2013, Lim et al., 2016). However, the mechanisms by which ECS controls cortical excitability remain unclear.
We hypothesized that ECS inhibits interictal epileptic activities, as does the RNS, which can help decrease the frequency of debilitating ictal seizures (Bergey et al., 2015). Using IEDs, which are known as pathological expressions of the synchronization of neuronal assemblies, and spike-related HFAs as dynamic measures of abnormal cortical excitability, we investigated the effect of ECS on the epileptic focus in patients with intractable epilepsy.
Section snippets
Patients
A total of 9 consecutive patients with intractable focal epilepsy who had undergone invasive presurgical evaluation were recruited in this study. One patient was excluded owing to excessive motion artifacts on ECoG. Four (Patients 1–4) of the included 8 patients were partly described in a previous paper (Kinoshita et al., 2005b). Among the 8 patients, 5 exhibited neocortical epilepsy (NE), and 3 had mesial temporal lobe epilepsy (MTLE). Detailed patient information is summarized in Table 1.
The
Results
Table 3 summarizes the results for the five evaluation factors. The result for each factor is as follows.
Discussion
We examined the suppressive effects of 50-Hz ECS on IEDs. We found the following: (1) frequencies of IEDs and amplitudes of their spike components significantly decreased after SOZ stimulation; (2) the spike-related HFA power in FR and R bands significantly decreased in 4 and 3 patients, respectively; (3) the spike/PSS amplitude ratio decreased significantly in 2 and marginally in 1 out of 4 patients with clear PSSs; and (4) PSS-related low gamma activities increased in 3 patients. To the best
Conclusions
This study demonstrated the inhibitory effects of the 50-Hz stimulation at the SOZ. This stimulation reduced the number of IEDs, the amplitude of spike, and the power of spike-related HFAs and augmented the amplitude of PSS and PSS-related low gamma power. This study suggests that ECS potentially modulates cortical excitability, thereby reducing excitation and increasing inhibition, and the findings could help identify the optimal parameters for stimulation therapy in patients with epilepsy.
Declaration of Competing Interest
None of the authors have any conflicts of interest or potential financial interests to disclose. Department of Epilepsy, Movement Disorders and Physiology is the Industry-Academia Collaboration Courses, supported by Eisai Co., Ltd., Nihon Kohden Corporation, Otsuka Pharmaceutical Co., and UCB Japan Co., Ltd. We confirm that we have read the journal’s position on issues involving ethical publication and affirm that this report is consistent with those guidelines and all authors have approved the
Acknowledgements
This work was partly supported by the Japan Ministry of Education, Culture, Sports, Science and Technology (KAKENHI Grant Numbers: 15H05874, 15H05875, and 15K10361) and Japan Society for the Promotion of Science (KAKENHI Grant Numbers: 17K09798, 17K16120, 18H02709, 18K19514, and 26293209).
References (80)
- et al.
Decreased susceptibility to pentylenetetrazol-induced seizures after low-frequency transcranial magnetic stimulation in rats
Neurosci Lett
(2001) - et al.
GABAergic synchronization in the limbic system and its role in the generation of epileptiform activity
Prog Neurobiol
(2011) - et al.
The morphology of high frequency oscillations (HFO) does not improve delineating the epileptogenic zone
Clin Neurophysiol
(2016) - et al.
Emergence of semiology in epileptic seizures
Epilepsy Behav
(2014) - et al.
Value of ictal and interictal epileptiform discharges and high frequency oscillations for delineating the epileptogenic zone in patients with focal cortical dysplasia
Clin Neurophysiol
(2018) - et al.
Interictal spikes in focal epileptogenesis
Prog Neurobiol
(2001) - et al.
Parameters for direct cortical electrical stimulation in the human: histopathologic confirmation
Electroencephalogr Clin Neurophysiol
(1990) - et al.
Deep brain stimulation of the anterior nucleus of the thalamus: effects of electrical stimulation on pilocarpine-induced seizures and status epilepticus
Epilepsy Res
(2008) - et al.
Electrical high frequency stimulation of the caudate nucleus induces local GABA outflow in freely moving rats
J Neurosci Methods
(2007) - et al.
Electrical stimulation for cortical mapping reduces the density of high frequency oscillations
Epilepsy Res
(2014)