Perisomatic Inhibition and Its Relation to Epilepsy and to Synchrony Generation in the Human Neocortex

Inhibitory neurons innervating the perisomatic region of cortical excitatory principal cells are known to control the emergence of several physiological and pathological synchronous events, including epileptic interictal spikes. In humans, little is known about their role in synchrony generation, although their changes in epilepsy have been thoroughly investigated. This paper demonstraits how parvalbumin (PV)- and type 1 cannabinoid receptor (CB1R)-positive perisomatic interneurons innervate pyramidal cell bodies, and their role in synchronous population events spontaneously emerging in the human epileptic and non-epileptic neocortex, in vitro. Quantitative electron microscopy showed that the overall, PV+ and CB1R+ somatic inhibitory inputs remained unchanged in focal cortical epilepsy. On the contrary, the size of PV-stained synapses increased, and their number decreased in epileptic samples, in synchrony generating regions. Pharmacology demonstrated—in conjunction with the electron microscopy—that although both perisomatic cell types participate, PV+ cells have stronger influence on the generation of population activity in epileptic samples. The somatic inhibitory input of neocortical pyramidal cells remained almost intact in epilepsy, but the larger and consequently more efficient somatic synapses might account for a higher synchrony in this neuron population. This, together with epileptic hyperexcitability, might make a cortical region predisposed to generate or participate in hypersynchronous events.

Theta and gamma hippocampal-neocortical oscillations during the episodic-like memory test: impairment in epileptogenic rats

Cortical oscillations in different frequency bands have been shown to be intimately involved in exploration of environment and cognition. Here, the local field potentials in the hippocampus, the medial prefrontal cortex (mPFC), and the medial entorhinal cortex (mEC) were recorded simultaneously in rats during the execution of the episodic-like memory task. The power of hippocampal theta (~4-10 Hz), slow gamma (~25-50 Hz), and fast gamma oscillations (~55-100 Hz) was analyzed in all structures examined. Particular attention was paid to the theta coherence between three mentioned structures. The modulation of the power of gamma rhythms by the phase of theta cycle during the execution of the episodic-like memory test by rats was also closely studied. Healthy rats and rats one month after kainate-induced status epilepticus (SE) were examined. Paroxysmal activity in the hippocampus (high amplitude interictal spikes), excessive excitability of animals, and the death of hippocampal and dentate granular cells in rats with kainate-evoked SE were observed, which indicated the development of seizure focus in the hippocampus (epileptogenesis). One month after SE, the rats exhibited a specific impairment of episodic memory for the what-where-when triad: unlike healthy rats, epileptogenic SE animals did not identify the objects during the test. This impairment was associated with the changes in the characteristics of theta and gamma rhythms and specific violation of theta coherence and theta/gamma coupling in these structures in comparison with the healthy animals. We believe that these disturbances in the cortical areas play a role in episodic memory dysfunction in kainate-treated animals. These findings can shed light on the mechanisms of cognitive deficit during epileptogenesis.

Beamforming seizures from the temporal lobe

Background: Surgical treatment of drug-resistant temporal lobe epilepsy (TLE) depends on proper identification of the seizure onset zone (SOZ), and differentiation of mesial, temporolimbic seizure onsets from temporal neocortical seizure onsets. Non-invasive source imaging using electroencephalography (EEG) and magnetoencephalography (MEG) can provide accurate information on interictal spike localization; however, EEG and MEG have low sensitivity for epileptiform activity restricted to deep temporolimbic structures. Moreover, in mesial temporal lobe epilepsy (MTLE), interictal spikes frequently arise in neocortical foci distant from the SOZ, rendering interictal spike localization potentially misleading for presurgical planning. Methods: In this study, we used two different beamformer techniques applied to the MEG signal of ictal events acquired during EEG-MEG recordings in six patients with TLE (three neocortical, three MTLE). The ictal source localization results were compared to the patients' ground truth SOZ localizations determined from intracranial EEG and/or clinical, neuroimaging and postsurgical outcome evidence. Results: Beamformer analysis proved to be highly accurate in all cases and able to reliably identify focal seizure onsets localized to mesial, temporolimbic structures. In three patients, interictal spikes were either absent, too complex for inverse dipole modeling, or localized to anterolateral temporal neocortex distant to a mesial temporal SOZ. Conclusions: This report demonstrates the suitability of MEG beamformer analysis of ictal events in TLE, which can supersede or complement the traditional analysis of interictal spikes. The method outlined is applicable to any type of epileptiform event, greatly expanding the information value of MEG and broadening its utility for presurgical recording in epilepsy.

Imaging the Extent and Location of Spatiotemporally Distributed Epileptiform Sources from MEG Measurements

Non-invasive MEG/EEG source imaging provides valuable information about the epileptogenic brain areas which can be used to aid presurgical planning in focal epilepsy patients suffering from drug-resistant seizures. However, the source extent estimation for electrophysiological source imaging remains to be a challenge and is usually largely dependent on subjective choice. Our recently developed algorithm, fast spatiotemporal iteratively reweighted edge sparsity minimization (FAST-IRES) strategy, has been shown to objectively estimate extended sources from EEG recording, while it has not been applied to MEG recordings. In this work, through extensive numerical experiments and real data analysis in a group of focal drug-resistant epilepsy patients interictal spikes, we demonstrated the ability of FAST-IRES algorithm to image the location and extent of underlying epilepsy sources from MEG measurements. Our results indicate the merits of FAST-IRES in imaging the location and extent of epilepsy sources for pre-surgical evaluation from MEG measurements.

The Onset of Interictal Spike-Related Ripples Facilitates Detection of the Epileptogenic Zone

Objective: Accurate estimation of the epileptogenic zone (EZ) is essential for favorable outcomes in epilepsy surgery. Conventional ictal electrocorticography (ECoG) onset is generally used to detect the EZ but is insufficient in achieving seizure-free outcomes. By contrast, high-frequency oscillations (HFOs) could be useful markers of the EZ. Hence, we aimed to detect the EZ using interictal spikes and investigated whether the onset area of interictal spike-related HFOs was within the EZ.Methods: The EZ is considered to be included in the resection area among patients with seizure-free outcomes after surgery. Using a complex demodulation technique, we developed a method to determine the onset channels of interictal spike-related ripples (HFOs of 80–200 Hz) and investigated whether they are within the resection area.Results: We retrospectively examined 12 serial patients who achieved seizure-free status after focal resection surgery. Using the method that we developed, we determined the onset channels of interictal spike-related ripples and found that for all 12 patients, they were among the resection channels. The onset frequencies of ripples were in the range of 80–150 Hz. However, the ictal onset channels (evaluated based on ictal ECoG patterns) and ripple onset channels coincided in only 3 of 12 patients.Conclusions: Determining the onset area of interictal spike-related ripples could facilitate EZ estimation. This simple method that utilizes interictal ECoG may aid in preoperative evaluation and improve epilepsy surgery outcomes.

Magnetoencephalography STOUT Method Adapted to Radiofrequency Thermocoagulation for MR-Negative Insular Epilepsy: A Case Report

Epilepsy is one of the most challenging neurologic diseases confronted by human society. Approximately 30–40% of the worldwide epilepsy patients are diagnosed with drug-resistant epilepsy and require pre-surgery evaluation. Magnetoencephalography (MEG) is a unique technology that provides optimal spatial-temporal resolution and has become a powerful non-invasive imaging modality that can localize the interictal spikes and guide the implantation of intracranial electrodes. Currently, the most widely used MEG source estimation method for clinical applications is equivalent current dipoles (ECD). However, ECD has difficulties in precisely locating deep sources such as insular lobe. In contrast to ECD, another MEG source estimation method named spatio-temporal unifying tomography (STOUT) with spatial sparsity has particular advantages in locating deep sources. In this case study, we recruited a 5 year-old female patient with insular lobe epilepsy and her seizure recurred in 1 year after receiving the radiofrequency thermocoagulation (RF-TC) therapy. The STOUT method was adopted to locate deep sources for identifying the epileptic foci in epilepsy evaluation. MEG STOUT method strongly supported a stereo-electroencephalographic (SEEG)-guided RF-TC operation, and the patient reported a satisfactory therapeutic effect. This case raises the possibility that STOUT method can be used particularly for the localization of deep sources, and successfully conducted RF-TC under the guidance of MEG STOUT results.