The patient underwent a presurgical evaluation. At the time of the non-invasive presurgical evaluation, the patient was receiving carbamazepine (800 mg/day), levetiracetam (1000 mg/day), lacosamide (250 mg/day), and (on-demand) clobazam. Long-term video-electroencephalogram (EEG) revealed focal interictal epileptiform discharges over the left frontotemporal lobe (F3-C3 and T7-P7; see Fig. 1). We also observed diffuse and bilateral synchronous epileptiform discharges, with slight asymmetry of amplitude and/or onset in favor of the left side (Fig. 2). Electric Source Imaging (ESI) was localized in the left temporal pole for the focal discharges. We also recorded eight seizures. At seizure onset, the patient showed a face of disgust (Fig. 3) followed occasionally by a right-hand wiping and then bilateral nasolabial myoclonus. The patient had two seizures with bilateral tonic–clonic evolution in the context of medication reduction. One of them was preceded by right hemi-facial myoclonus and forced rotation of the head with the eyes toward the right. The EEG lateralization was less clear than during interictal activity (see the diffuse, bilateral spike-and-wave discharges at the onset of the second seizure, Fig. 4). However, in three seizures, a left-sided rhythmic activity was identified later during the seizure (Fig. 5). Brain 3T Magnetic Resonance Imaging (MRI) with a dedicated epilepsy protocol showed a discrete hippocampal asymmetry, with a smaller size on the left side, but without a clear sign of hippocampal sclerosis. Voxel-based morphometry and 7T MRI did not find a significant abnormality. FluoroDeoxyGlucose-Positron Emission Tomography ([18F]FDG-PET) showed a left cortical temporopolar hypometabolism and the maximal hyperperfusion on ictal Single Photon Emission Computed Tomography (SPECT) and subtraction analysis (Subtraction Ictal SPECT COregistered to MRI: SISCOM) was localized in the left cortical temporopolar region. Neuropsychological testing (performed 1 year before our evaluation) revealed a slight deficit for elaborate language and short-term verbal memory with no evolution. Psychiatric evaluation was unremarkable.

Left focal interictal discharge. Inversion of potential on F3-C3 and T7-P7 about 0.8 s after the blue vertical line (x). This sharp-wave indicates a generator in the left frontotemporal region. High- and low-pass filters: 0.5–200 Hz

Example of bilateral synchronous epileptiform discharges. In the middle of the page, bilateral synchronous epileptiform discharges are evident. Although there is no clear lateralization at onset, the inversion of potential polarity on P7 suggests a slight precession of the left temporal region over the contralateral side. See Fig. 7 for an example of a bilateral synchronous discharge recorded with intracranial electrodes. High- and low-pass filters: 1.6–200 Hz

Face of disgust at seizure onset. As seen on this screenshot, the patient systematically presented with a face of disgust at seizure onset. See Souirti et al. [1] to compare the patient’s facial expression with the typical ictal pouting triggered by cingulate seizures

Diffuse onset of the second recorded epileptic seizure. a Bilateral synchronous electrical onset of a seizure (deeg stands for “début EEG,” start of EEG seizure). b At 5.5 s after the electrical onset, the patient showed a “face of disgust,” again without clear lateralization on scalp EEG. Same scale as in the preceding panel. High-pass and low-pass filters: 1.6–200 Hz. c Same seizure onset using a common average reference mode. As seen, the amplitude is also symmetrical between the two hemispheres. High- and low-pass filters: 0.5–200 Hz

Left focalization during the epileptic seizure. Although this seizure started with a bilateral synchronous discharge (deeg stands for “début EEG”, start of EEG seizure), left lateralized discharges appeared later in the course of the seizure, as indicated by the red rectangle (inversion of potentials on C3 and T7). High- and low-pass filters: 1.2–200 Hz

At our multidisciplinary case review, we considered a left hemispheric, nonlesional epilepsy involving the medial left temporal lobe, cingulate cortex, and/or insula, with a global picture of a “temporal plus” epilepsy and the expression of disgust with some aspects of ictal pouting (“chapeau de gendarme”) described in similar cortical structures [1]. The occasional bilateral synchronous discharges suggested the involvement of a deep or midline structure. The clear localization toward the left of focal discharges, as well as the ictal discharges concentrated over the left hemisphere after seizure onset (see above and Fig. 5), the semiology before bilateral tonic–clonic evolution, and the results of PET and SPECT imaging and neuropsychological testing all indicated a left hemispheric onset. We proposed an invasive recording with stereotactic depth electrodes to investigate the suspected regions discussed above (temporal pole, amygdala, hippocampus [including lateral temporal contacts], superior posterior temporal gyrus, anterior, middle and posterior insula, anterior, middle and posterior cingulate, orbitofrontal, inferior frontal gyrus and supplementary motor area) including one contralateral region (anterior hippocampus). See Fig. 6 for an overview of the implantation scheme.

Implantation scheme for multisite, intracranial recording. Note that since all target brain regions are not located on the same geometric plane, it is not possible to show these targets on one single image. This figure thus intends to provide an idea of how many electrodes were implanted, and their relative position to each other. a,b From left to right: sagittal—sagittal—sagittal—coronal—sagittal plane of the implantation scheme. a Stereotaxic positions of intracranial electrodes: (color code = target) pink = anterior left cingulate; blue = middle left cingulate; white = posterior left cingulate; green = left superior temporal gyrus; purple = left amygdala; red = left anterior hippocampus; yellow = left posterior hippocampus. b Insular electrodes: red/green/blue = anterior/middle/posterior insular electrodes, respectively

During SEEG, the patient had more than 20 focal seizures. Seizures started in the lateral (i.e., cortical) left temporopolar region and, for some of them, with a simultaneous onset in the superior posterior temporal gyrus. Cortical mapping revealed that high-frequency stimulation of the superior temporal area was sufficient to elicit speech deficit already at low intensity (50 Hz, 4 mA, 2 s). Interictal epileptiform discharges occurred predominantly on left temporolateral contacts and less often left insular contacts; bursts of diffuse discharges were also recorded and showed a slightly earlier onset in the left temporal pole contacts (Fig. 7).

Bilateral, synchronous discharges on intracranial recordings. a All contacts recording three typical widespread synchronous discharges, corresponding to the bilateral discharges seen on scalp EEG. Scale: 200 µV, 1 s b Same epoch, focused on contacts showing most significant changes. On the third burst, the blue vertical line indicates a slightly earlier onset in contacts AG9, corresponding to the lateral temporal pole. Note that although the amplitude seems higher in the insular contacts (IAG1–5), assessing localization based on signal amplitude on bipolar montages is not reliable. Scale 500 µV, 1 s. High- and low-pass filters: 10–400 Hz