Voxeloc: A time-saving graphical user interface for localizing and visualizing stereo-EEG electrodes.

BACKGROUND: Thanks to its unrivalled spatial and temporal resolutions and signal-to-noise ratio, intracranial EEG (iEEG) is becoming a valuable tool in neuroscience research. To attribute functional properties to cortical tissue, it is paramount to be able to determine precisely the localization of each electrode with respect to a patient's brain anatomy. Several software packages or pipelines offer the possibility to localize manually or semi-automatically iEEG electrodes. However, their reliability and ease of use may leave to be desired. NEW METHOD: Voxeloc (voxel electrode locator) is a Matlab-based graphical user interface to localize and visualize stereo-EEG electrodes. Voxeloc adopts a semi-automated approach to determine the coordinates of each electrode contact, the user only needing to indicate the deep-most contact of each electrode shaft and another point more proximally. RESULTS: With a deliberately streamlined functionality and intuitive graphical user interface, the main advantages of Voxeloc are ease of use and inter-user reliability. Additionally, oblique slices along the shaft of each electrode can be generated to facilitate the precise localization of each contact. Voxeloc is open-source software and is compatible with the open iEEG-BIDS (Brain Imaging Data Structure) format. COMPARISON WITH EXISTING METHODS: Localizing full patients' iEEG implants was faster using Voxeloc than two comparable software packages, and the inter-user agreement was better. CONCLUSIONS: Voxeloc offers an easy-to-use and reliable tool to localize and visualize stereo-EEG electrodes. This will contribute to democratizing neuroscience research using iEEG.

Implantation and reimplantation of intracranial EEG electrodes in patients considering epilepsy surgery.

In patients with drug-resistant epilepsy who are considering surgery, intracranial EEG (iEEG) helps delineate the putative epileptogenic zone. In a minority of patients, iEEG fails to identify seizure onsets. In such cases, it might be worthwhile to reimplant more iEEG electrodes. The consequences of such a strategy for the patient are unknown. We matched 12 patients in whom the initially implanted iEEG electrodes did not delineate the seizure onset zone precisely enough to offer resective surgery, and in whom additional iEEG electrodes were implanted during the same inpatient stay, to controls who did not undergo reimplantation. Seven cases and eight controls proceeded to resective surgery. No intracranial infection occurred. One control suffered an intracranial hemorrhage. Three cases and two controls suffered from a post-operative neurological or neuropsychological deficit. We found no difference in post-operative seizure control between cases and controls. Compared to an ILAE score of 5 (ie, stable seizure frequency in the absence of resective surgery), cases showed significant improvement. Reimplantation of iEEG electrodes can offer the possibility of resective epilepsy surgery to patients in whom the initial iEEG investigation was inconclusive, without compromising on the risk of complications or seizure control.

Blinded study: prospectively defined high-frequency oscillations predict seizure outcome in individual patients.

Interictal high-frequency oscillations are discussed as biomarkers for epileptogenic brain tissue that should be resected in epilepsy surgery to achieve seizure freedom. The prospective classification of tissue sampled by individual electrode contacts remains a challenge. We have developed an automated, prospective definition of clinically relevant high-frequency oscillations in intracranial EEG from Montreal and tested it in recordings from Zurich. We here validated the algorithm on intracranial EEG that was recorded in an independent epilepsy centre so that the analysis was blinded to seizure outcome. We selected consecutive patients who underwent resective epilepsy surgery in Geneva with post-surgical follow-up > 12 months. We analysed long-term recordings during sleep that we segmented into intervals of 5 min. High-frequency oscillations were defined in the ripple (80-250 Hz) and the fast ripple (250-500 Hz) frequency bands. Contacts with the highest rate of ripples co-occurring with fast ripples designated the relevant area. As a validity criterion, we calculated the test-retest reliability of the high-frequency oscillations area between the 5 min intervals (dwell time ≥50%). If the area was not fully resected and the patient suffered from recurrent seizures, this was classified as a true positive prediction. We included recordings from 16 patients (median age 32 years, range 18-53 years) with stereotactic depth electrodes and/or with subdural electrode grids (median follow-up 27 months, range 12-55 months). For each patient, we included several 5 min intervals (median 17 intervals). The relevant area had high test-retest reliability across intervals (median dwell time 95%). In two patients, the test-retest reliability was too low (dwell time < 50%) so that outcome prediction was not possible. The area was fully included in the resected volume in 2/4 patients who achieved post-operative seizure freedom (specificity 50%) and was not fully included in 9/10 patients with recurrent seizures (sensitivity 90%), leading to an accuracy of 79%. An additional exploratory analysis suggested that high-frequency oscillations were associated with interictal epileptic discharges only in channels within the relevant area and not associated in channels outside the area. We thereby validated the automated procedure to delineate the clinically relevant area in each individual patient of an independently recorded dataset and achieved the same good accuracy as in our previous studies. The reproducibility of our results across datasets is promising for a multicentre study to test the clinical application of high-frequency oscillations to guide epilepsy surgery.

Electric source imaging for presurgical epilepsy evaluation: current status and future prospects.

Introduction: Electric source imaging (ESI) refers to the estimation of the cerebral sources of electric signals recorded at the head surface using electroencephalography (EEG). Thanks to the availability of EEG systems with high numbers of electrodes and to progress in software to analyze the signals they collect, ESI can be applied to epilepsy-related pathological EEG signals like interictal spikes and seizures.Areas covered: In this narrative review, we discuss selected original research articles on the use of ESI in epilepsy patients considered for surgery. Epilepsy-related activity can be localized accurately using ESI, as established by comparison to the gold standards of intracranial EEG and seizure control following epilepsy surgery. The information brought by ESI complements successfully that of other techniques like magnetic resonance imaging and positron-emission tomography, and is clinically relevant to patient management.Expert opinion: EEG is a readily available technique to measure brain activity in real time. Given its accuracy and usefulness, ESI should become part of the routine practice of clinical neurophysiology laboratories and epilepsy centers in the presurgical management of epilepsy patients.

The rough sound of salience enhances aversion through neural synchronisation.

Being able to produce sounds that capture attention and elicit rapid reactions is the prime goal of communication. One strategy, exploited by alarm signals, consists in emitting fast but perceptible amplitude modulations in the roughness range (30-150 Hz). Here, we investigate the perceptual and neural mechanisms underlying aversion to such temporally salient sounds. By measuring subjective aversion to repetitive acoustic transients, we identify a nonlinear pattern of aversion restricted to the roughness range. Using human intracranial recordings, we show that rough sounds do not merely affect local auditory processes but instead synchronise large-scale, supramodal, salience-related networks in a steady-state, sustained manner. Rough sounds synchronise activity throughout superior temporal regions, subcortical and cortical limbic areas, and the frontal cortex, a network classically involved in aversion processing. This pattern correlates with subjective aversion in all these regions, consistent with the hypothesis that roughness enhances auditory aversion through spreading of neural synchronisation.

Human amygdala response to unisensory and multisensory emotion input: No evidence for superadditivity from intracranial recordings.

The amygdala is crucially implicated in processing emotional information from various sensory modalities. However, there is dearth of knowledge concerning the integration and relative time-course of its responses across different channels, i.e., for auditory, visual, and audiovisual input. Functional neuroimaging data in humans point to a possible role of this region in the multimodal integration of emotional signals, but direct evidence for anatomical and temporal overlap of unisensory and multisensory-evoked responses in amygdala is still lacking. We recorded event-related potentials (ERPs) and oscillatory activity from 9 amygdalae using intracranial electroencephalography (iEEG) in patients prior to epilepsy surgery, and compared electrophysiological responses to fearful, happy, or neutral stimuli presented either in voices alone, faces alone, or voices and faces simultaneously delivered. Results showed differential amygdala responses to fearful stimuli, in comparison to neutral, reaching significance 100-200 ms post-onset for auditory, visual and audiovisual stimuli. At later latencies, ∼400 ms post-onset, amygdala response to audiovisual information was also amplified in comparison to auditory or visual stimuli alone. Importantly, however, we found no evidence for either super- or subadditivity effects in any of the bimodal responses. These results suggest, first, that emotion processing in amygdala occurs at globally similar early stages of perceptual processing for auditory, visual, and audiovisual inputs; second, that overall larger responses to multisensory information occur at later stages only; and third, that the underlying mechanisms of this multisensory gain may reflect a purely additive response to concomitant visual and auditory inputs. Our findings provide novel insights on emotion processing across the sensory pathways, and their convergence within the limbic system.

Electroencephalography, magnetoencephalography and source localization: their value in epilepsy.

PURPOSE OF REVIEW: Source localization of cerebral activity using electroencephalography (EEG) or magnetoencephalography (MEG) can reveal noninvasively the generators of the abnormal signals recorded in epilepsy, such as interictal epileptic discharges (IEDs) and seizures. Here, we review recent progress showcasing the usefulness of these techniques in treating patients with drug-resistant epilepsy. RECENT FINDINGS: The source localization of IEDs by high-density EEG and MEG has now been proved in large patient cohorts to be accurate and clinically relevant, with positive and negative predictive values rivaling those of structural MRI. Localizing seizure onsets is an emerging technique that seems to perform similarly well to the localization of interictal spikes, although there remain questions regarding the processing of signals for reliable results. The localization of somatosensory cortex using EEG/MEG is well established. The localization of language cortex is less reliable, although progress has been made regarding hemispheric lateralization. Source localization is also able to reveal how epilepsy alters the dynamics of neuronal activity in the large-scale networks that underlie cerebral function. SUMMARY: Given the high performance of EEG/MEG source localization, these tools should find a place similar to that of established techniques like MRI in the assessment of patients for epilepsy surgery.

Surgical Training for the Implantation of Neocortical Microelectrode Arrays Using a Formaldehyde-fixed Human Cadaver Model.

This protocol describes a procedure to assist surgeons in training for the implantation of microelectrode arrays into the neocortex of the human brain. Recent technological progress has enabled the fabrication of microelectrode arrays that allow recording the activity of multiple individual neurons in the neocortex of the human brain. These arrays have the potential to bring unique insight onto the neuronal correlates of cerebral function in health and disease. Furthermore, the identification and decoding of volitional neuronal activity opens the possibility to establish brain-computer interfaces, and thus might help restore lost neurological functions. The implantation of neocortical microelectrode arrays is an invasive procedure requiring a supra-centimetric craniotomy and the exposure of the cortical surface; thus, the procedure must be performed by an adequately trained neurosurgeon. In order to provide an opportunity for surgical training, we designed a procedure based on a human cadaver model. The use of a formaldehyde-fixed human cadaver bypasses the practical, ethical and financial difficulties of surgical practice on animals (especially non-human primates) while preserving the macroscopic structure of the head, skull, meninges and cerebral surface and allowing realistic, operating room-like positioning and instrumentation. Furthermore, the use of a human cadaver is closer to clinical daily practice than any non-human model. The major drawbacks of the cadaveric simulation are the absence of cerebral pulsation and of blood and cerebrospinal fluid circulation. We suggest that a formaldehyde-fixed human cadaver model is an adequate, practical and cost-effective approach to ensure proper surgical training before implanting microelectrode arrays in the living human neocortex.

Mapping epileptic activity: sources or networks for the clinicians?

Epileptic seizures of focal origin are classically considered to arise from a focal epileptogenic zone and then spread to other brain regions. This is a key concept for semiological electro-clinical correlations, localization of relevant structural lesions, and selection of patients for epilepsy surgery. Recent development in neuro-imaging and electro-physiology and combinations, thereof, have been validated as contributory tools for focus localization. In parallel, these techniques have revealed that widespread networks of brain regions, rather than a single epileptogenic region, are implicated in focal epileptic activity. Sophisticated multimodal imaging and analysis strategies of brain connectivity patterns have been developed to characterize the spatio-temporal relationships within these networks by combining the strength of both techniques to optimize spatial and temporal resolution with whole-brain coverage and directional connectivity. In this paper, we review the potential clinical contribution of these functional mapping techniques as well as invasive electrophysiology in human beings and animal models for characterizing network connectivity.

Head model and electrical source imaging: a study of 38 epileptic patients.

Electrical source imaging (ESI) aims at reconstructing the electrical brain activity from scalp EEG. When applied to interictal epileptiform discharges (IEDs), this technique is of great use for identifying the irritative zone in focal epilepsies. Inaccuracies in the modeling of electro-magnetic field propagation in the head (forward model) may strongly influence ESI and lead to mislocalization of IED generators. However, a systematic study on the influence of the selected head model on the localization precision of IED in a large number of patients with known focus localization has not yet been performed. We here present such a performance evaluation of different head models in a dataset of 38 epileptic patients who have undergone high-density scalp EEG, intracranial EEG and, for the majority, subsequent surgery. We compared ESI accuracy resulting from three head models: a Locally Spherical Model with Anatomical Constraints (LSMAC), a Boundary Element Model (BEM) and a Finite Element Model (FEM). All of them were computed from the individual MRI of the patient and ESI was performed on averaged IED. We found that all head models provided very similar source locations. In patients having a positive post-operative outcome, at least 74% of the source maxima were within the resection. The median distance from the source maximum to the nearest intracranial electrode showing IED was 13.2, 15.6 and 15.6 mm for LSMAC, BEM and FEM, respectively. The study demonstrates that in clinical applications, the use of highly sophisticated and difficult to implement head models is not a crucial factor for an accurate ESI.

Electric source imaging of interictal activity accurately localises the seizure onset zone.

OBJECTIVE: It remains controversial whether interictal spikes are a surrogate of the seizure onset zone (SOZ). Electric source imaging (ESI) is an increasingly validated non-invasive approach for localising the epileptogenic focus in patients with drug-resistant epilepsy undergoing evaluation for surgery, using high-density scalp EEG and advanced source localisation algorithms that include the patient's own MRI. Here we investigate whether localisation of interictal spikes by ESI provides valuable information on the SOZ. METHODS: In 38 patients with focal epilepsy who later underwent intracranial EEG monitoring, we performed ESI of interictal spikes recorded with 128-256-channel EEG. We measured the distance between the ESI maximum and the nearest intracranial electrodes in the SOZ and irritative zone (IZ, the source of interictal spikes). The resection of the region harbouring the ESI maximum was correlated to surgical outcome. RESULTS: The median distance from the ESI maximum to the nearest electrode involved in the SOZ was 17 mm (IQR 8-27). The IZ and SOZ colocalised in most patients (median distance 0 mm, IQR 0-14), supporting the notion that localising interictal spikes is a valid surrogate for the SOZ. There was no difference in accuracy among patients with temporal or extratemporal epilepsy. In the 32 patients who underwent resective surgery, including the ESI maximum in the resection correlated with favourable outcome (p=0.03). CONCLUSIONS: Localisation of interictal spikes provides an excellent estimate of the SOZ in the majority of patients. ESI should be taken into account for the management of patients undergoing intracranial recordings.