Organization of the epileptogenic zone and signal analysis at seizure onset in patients with drug-resistant epilepsy due to focal cortical dysplasia with mTOR pathway gene mutations-An SEEG study.

Epilepsy surgery in genetic drug-resistant epilepsy is a debated subject as more histological and molecular data are available. We retrospectively collected data from focal drug-resistant epilepsy patients that underwent stereoelectroencephalography (SEEG) invasive recordings. Patients with nonlesional brain imaging or in whom a first epilepsy surgery failed to control seizures were selected. We computed and displayed the intracranial ictal onset activity pattern on structural imaging. Patients underwent epilepsy gene panel testing, next generation sequencing-NGS. Of 113 patients, 13 underwent genetic testing, and in 6 patients, a mechanistic target of rapamycin pathway gene germline mutation (mTOR) was identified. Brain imaging was nonlesional except for one patient in whom two abnormalities suggestive of focal cortical dysplasia (FCD) were found. Patients underwent tailored brain surgery based on SEEG data, tissue analysis revealed FCD and postsurgical outcome was favorable. Our findings are similar to previous case series suggesting that epilepsy surgery can be a treatment option in patients with mTOR pathway mutation. In patients with mTOR pathway mutation, the postsurgical outcome is favorable if complete resection of the epileptogenic zone is performed. Electrophysiological seizure onset patterns in FCDs associated with mTOR pathway mutations display low-voltage fast activity as previously described.

Musicogenic seizures in temporal lobe epilepsy: Case reports based on ictal source localization analysis.

Musicogenic epilepsy is a rare form of reflex epilepsy in which seizures are provoked by music. Different musicogenic stimuli have been identified: pleasant/unpleasant music or specific musical patterns. Several etiologies have been uncovered, such as focal cortical dysplasia, autoimmune encephalitis, tumors, or unspecific gliosis. In this article, we report two patients with musicogenic seizures. The first patient was diagnosed with structural temporal lobe epilepsy. Her seizures were elicited by music that she liked. Interictal and ictal video-electroencephalography (video-EEG) and signal analysis using independent component analysis revealed the right temporal lobe seizure onset extending over the neocortical regions. The patient underwent right temporal lobectomy (including the amygdala, the head, and the body of the hippocampus) and faced an Engel IA outcome 3 years post-surgery. The second patient was diagnosed with autoimmune temporal lobe epilepsy (GAD-65 antibodies). Her seizures were triggered by contemporary hit radio songs without any personal emotional significance. Interictal and ictal video-electroencephalography (video-EEG) and independent component analysis highlighted the left temporal lobe seizure onset extending over the neocortical regions. Intravenous immunoglobulin therapy was initiated, and the patient became seizure-free at 1 year. In conclusion, musicogenic seizures may be elicited by various auditory stimuli, the presence or absence of an emotional component offering an additional clue for the underlying network pathophysiology. Furthermore, in such cases, the use of independent component analysis of the scalp EEG signals proves useful in revealing the location of the seizure generator, and our findings point toward the temporal lobe, both mesial and neocortical regions.

Motor and emotional facial features in parietal lobe seizures: an ictal functional connectivity study using SEEG

Objectives: Parietal lobe epilepsy is one of the rarest types and patients with this form of epilepsy report multiple subjective symptoms during ictal manifestation. Specific facial coupling of emotion and motor symptoms may take various forms, such as pouting and disgust or smiling. We aimed to highlight brain structures and the network involved during ictal grimacing in parietal lobe seizures. Methods: In this study, we report two patients with drug-resistant epilepsy, with seizure onset located in the inferior parietal lobule and a semiology characterized by ictal grimacing. Patients were explored with intracranial electrodes using the stereo-electroencephalographic method. Time-frequency and functional connectivity (a non-linear regression method based on the h² correlation coefficient) signal analyses were performed time-locked to ictal grimace. For both patients, using spectral analysis, we were able to confirm that the bipolar channels, localized at the level of the inferior parietal lobule, were involved in the seizure onset zone, exhibiting a high frequency discharge. Results: The first patient presented with ictal pouting and disgust and the second with smiling/laughter. Connectivity analysis highlighted two different networks responsible for seizure semiology, consisting of grimacing with different emotional expression. The inferior parietal lobule, connected mainly to the anterior insula, dorsal-lateral prefrontal cortex and frontal operculum were responsible for the typical grimace associated with disgust. Furthermore, the inferior parietal lobule, basal temporal structures, superior temporal gyrus, orbitofrontal cortex and temporal pole were involved in smiling and laughter. Significance: It is of great significance for epileptologists to know that the same seizure onset zone in the inferior parietal lobule can generate contrasting facial expressions, smiling/laughter and pouting/disgust, by engaging different epileptogenic networks; the temporo-basal-orbitofrontal and insulo-opercular networks, respectively.

Imaging the effective networks associated with cortical function through intracranial high-frequency stimulation.

Direct electrical stimulation (DES) is considered to be the gold standard for mapping cortical function. A careful mapping of the eloquent cortex is key to successful resective or ablative surgeries, with a minimal postoperative deficit, for treatment of drug-resistant epilepsy. There is accumulating evidence suggesting that not only local, but also remote activations play an equally important role in evoking clinical effects. By introducing a new intracranial stimulation paradigm and signal analysis methodology allowing to disambiguate EEG responses from stimulation artifacts we highlight the spatial extent of the networks associated with clinical effects. Our study includes 26 patients that underwent stereoelectroencephalographic investigations for drug-resistant epilepsy, having 337 depth electrodes with 4,351 contacts sampling most brain structures. The routine high-frequency electrical stimulation protocol for eloquent cortex mapping was altered in a subtle way, by alternating the polarity of the biphasic pulses in a train, causing the splitting the spectral lines of the artifactual components, exposing the underlying tissue response. By performing a frequency-domain analysis of the EEG responses during DES we were able to capture remote activations and highlight the effect's network. By using standard intersubject averaging and a fine granularity HCP-MMP parcellation, we were able to create local and distant connectivity maps for 614 stimulations evoking specific clinical effects. The clinical value of such maps is not only for a better understanding of the extent of the effects' networks guiding the invasive exploration, but also for understanding the spatial patterns of seizure propagation given the timeline of the seizure semiology.

Network of autoscopic hallucinations elicited by intracerebral stimulations of periventricular nodular heterotopia: An SEEG study.

Periventricular nodular heterotopias (PVNH) are areas of neurons abnormally located in the white matter that might be involved in physiological cortical functions. Autoscopic hallucinations are changes in self-consciousness determined by a mismatch in integration of multiple sensory inputs. Our goal is to highlight the brain network involved in generation of autoscopic hallucination elicited by electrical stimulation of a PVNH in a drug resistant epilepsy patient. Our patient was explored using stereo-electroencephalography with electrodes covering the right posterior temporal PVNH and the adjacent cortex. Direct electrical high frequency stimulation of the PVNH elicited autoscopic hallucinations mainly involving the face and upper trunk. We then used multiple modalities to determine brain connectivity: single pulse electrical stimulation of the PVNH and stimulation-evoked potentials were used to highlight resting state effective connectivity. High-frequency stimulation using alternating polarity pulses enabled us to identify the network involved, time-locked to the clinical effect and to map symptom-related effective connectivity. Functional connectivity using a non-linear regression method was used to determine dependencies between different cortical regions following the stimulation. Finally, structural connectivity was highlighted using deterministic fiber tracking. Multi-modal connectivity analysis identified a network involving the PVNH, occipital and temporal neocortex, fusiform gyrus and parietal cortex.

Accuracy and Safety of Customized Stereotactic Fixtures for Stereoelectroencephalography in Pediatric Patients.

Stereoelectroencephalography (SEEG) in children with intractable epilepsy presents particular challenges. Their thin and partially ossified cranium, specifically in the temporal area, is prone to fracture while attaching stereotactic systems to the head or stabilizing the head in robot's field of action. Postponing SEEG in this special population of patients can have serious consequences, reducing their chances of becoming seizure-free and impacting their social and cognitive development. This study demonstrates the safety and accuracy offered by a frameless personalized 3D printed stereotactic implantation system for SEEG investigations in children under 4 years of age. SEEG was carried out in a 3-year-old patient with drug-resistant focal epilepsy, based on a right temporal-perisylvian epileptogenic zone hypothesis. Fifteen intracerebral electrodes were placed using a StarFix patient-customized stereotactic fixture. The median lateral entry point localization error of the electrodes was 0.90 mm, median lateral target point localization error was 1.86 mm, median target depth error was 0.83 mm, and median target point localization error was 1.96 mm. There were no perioperative complications. SEEG data led to a tailored right temporal-insular-opercular resection, with resulting seizure freedom (Engel IA). In conclusion, patient-customized stereotactic fixtures are a safe and accurate option for SEEG exploration in young children.

Cingulate cortex function and multi-modal connectivity mapped using intracranial stimulation.

The cingulate cortex is part of the limbic system. Its function and connectivity are organized in a rostro-caudal and ventral-dorsal manner which was addressed by various other studies using rather coarse cortical parcellations. In this study, we aim at describing its function and connectivity using invasive recordings from patients explored for focal drug-resistant epilepsy. We included patients that underwent stereo-electroencephalographic recordings using intracranial electrodes in the University Emergency Hospital Bucharest between 2012 and 2019. We reviewed all high frequency stimulations (50 â€‹Hz) performed for functional mapping of the cingulate cortex. We used two methods to characterize brain connectivity. Effective connectivity was inferred based on the analysis of cortico-cortical potentials (CCEPs) evoked by single pulse electrical stimulation (SPES) (15 â€‹s inter-pulse interval). Functional connectivity was estimated using the non-linear regression method applied to 60 â€‹s spontaneous electrical brain signal intervals. The effective (stimulation-evoked) and functional (non-evoked) connectivity analyses highlight brain networks in a different way. While non-evoked connectivity evidences areas having related activity, often in close proximity to each other, evoked connectivity highlights spatially extended networks. To highlight in a comprehensive way the cingulate cortex's network, we have performed a bi-modal connectivity analysis that combines the resting-state broadband h2 non-linear correlation with cortico-cortical evoked potentials. We co-registered the patient's anatomy with the fsaverage FreeSurfer template to perform the automatic labeling based on HCP-MMP parcellation. At a group level, connectivity was estimated by averaging responses over stimulated/recorded or recorded sites in each pair of parcels. Finally, for multiple regions that evoked a clinical response during high frequency stimulation, we combined the connectivity of individual pairs using maximum intensity projection. Connectivity was assessed by applying SPES on 2094 contact pairs and recording CCEPs on 3580 contacts out of 8582 contacts of 660 electrodes implanted in 47 patients. Clinical responses elicited by high frequency stimulations in 107 sites (pairs of contacts) located in the cingulate cortex were divided in 10 groups: affective, motor behavior, motor elementary, versive, speech, vestibular, autonomic, somatosensory, visual and changes in body perception. Anterior cingulate cortex was shown to be connected to the mesial temporal, orbitofrontal and prefrontal cortex. In the middle cingulate cortex, we located affective, motor behavior in the anterior region, and elementary motor and somatosensory in the posterior part. This region is connected to the prefrontal, premotor and primary motor network. Finally, the posterior cingulate was shown to be connected with the visual areas, mesial and lateral parietal and temporal cortex.

Sleep modulates effective connectivity: A study using intracranial stimulation and recording.

OBJECTIVE: Sleep is an active process with an important role in memory. Epilepsy patients often display a disturbed sleep architecture, with consequences on cognition. We aimed to investigate the effect of sleep on cortical networks' organization. METHODS: We analyzed cortico-cortical evoked responses elicited by single pulse electrical stimulation (SPES) using intracranial depth electrodes in 25 patients with drug-resistant focal epilepsy explored using stereo-EEG. We applied the SPES protocol during wakefulness and NREM - N2 sleep. We analyzed 31,710 significant responses elicited by 799 stimulations covering most brain structures, epileptogenic or non-epileptogenic. We analyzed effective connectivity between structures using a graph-theory approach. RESULTS: Sleep increases excitability in the brain, regardless of epileptogenicity. Local and distant connections are differently modulated by sleep, depending on the tissue epileptogenicity. In non-epileptogenic areas, frontal lobe connectivity is enhanced during sleep. There is increased connectivity between the hippocampus and temporal neocortex, while perisylvian structures are disconnected from the temporal lobe. In epileptogenic areas, we found a clear interhemispheric difference, with decreased connectivity in the right hemisphere during sleep. CONCLUSIONS: Sleep modulates brain excitability and reconfigures functional brain networks, depending on tissue epileptogenicity. SIGNIFICANCE: We found specific patterns of information flow during sleep in physiologic and pathologic structures, with possible implications for cognition.

Illusory own body perceptions mapped in the cingulate cortex-An intracranial stimulation study.

Body awareness is the result of sensory integration in the posterior parietal cortex; however, other brain structures are part of this process. Our goal is to determine how the cingulate cortex is involved in the representation of our body. We retrospectively selected patients with drug-resistant epilepsy, explored by stereo-electroencephalography, that had the cingulate cortex sampled outside the epileptogenic zone. The clinical effects of high-frequency electrical stimulation were reviewed and only those sites that elicited changes related to body perception were included. Connectivity of the cingulate cortex and other cortical structures was assessed using the h2 coefficient, following a nonlinear regression analysis of the broadband EEG signal. Poststimulation changes in connectivity were compared between two sets of stimulations eliciting or not eliciting symptoms related to body awareness (interest and control groups). We included 17 stimulations from 12 patients that reported different types of body perception changes such as sensation of being pushed toward right/left/up, one limb becoming heavier/lighter, illusory sensation of movement, sensation of pressure, sensation of floating or detachment of one hemi-body. High-frequency stimulation in the cingulate cortex (1 anterior, 15 middle, 1 posterior part) elicits body perception changes, associated with a decreased connectivity of the dominant posterior insula and increased coupling between other structures, located particularly in the nondominant hemisphere.