Direction of saccadic and smooth eye movements induced by electrical stimulation of the human frontal eye field: effect of orbital position

The present study reports on the direction of saccadic and smooth eye movements, which were induced electrically from the human dorsolateral frontal cortex including the human frontal eye field (FEF). The eye position prior to stimulation was varied in order to examine its effect on induced eye movement direction. The five patients of the study underwent invasive presurgical evaluation for pharmacoresistant epilepsy. The present data show that the direction of electrically induced eye movements was always contralateral and either horizontal or oblique upward if the eye started from the primary position. The elicited direction was changed if the eyes started from an eccentric position. The frequency of oblique eye movements was increased and oblique downward responses were induced, which were not observed if the eye started from the primary position. This was found for saccades and, especially, for smooth eye movements. Head movements, which were almost exclusively induced with saccades, did not depend on initial orbital position. Four conclusions can be drawn. Firstly, saccades and smooth eye movements induced from the human dorsolateral cortex including the human FEF have the same directional bias. Secondly, the frequent upward responses and the absence of downward responses induced from the primary position suggests either a more numerous or a more superficial representation of neurons that code for the former direction. Thirdly, at some sites the direction of saccades and smooth eye movements varies depending on the initial orbital position. Since these directional changes were observed without changes in eye-head coordination, our data suggest that stimulation of the FEF might evoke goal-directed saccades or interferes with a resettable saccade integrator. Fourthly, human studies that investigate eye movements induced from the lateral frontal cortex need to control eye position prior to stimulation

Electrical source imaging and connectivity analysis to localize the seizure-onset zone based on high-density ictal scalp EEG recordings

Functional connectivity analysis of ictal intracranial EEG (icEEG) recordings can help with seizure-onset zone (SOZ) localization in patients with focal epilepsy1. However, it would be of high clinical value to be able to localize the SOZ based on non-invasive ictal EEG recordings to better target or avoid icEEG and improve surgical outcome. In this work, we propose an approach to localize the SOZ based on non-invasive ictal high- density EEG (hd-EEG) recordings. We considered retrospective ictal hd-EEG recordings of two patients who were rendered seizure free after surgery. Furthermore, we simulated 1000 ictal hd-EEG epochs of 10s with an underlying network consisting of 3 randomly placed epileptic patches in the brain. EEG source imaging (ESI) was performed in CARTOOL using an individual head model (LSMAC) to calculate the forward model2. We considered dipoles uniformly distributed in the brain with a spacing of 5mm. LORETA3 was used as inverse solution method. Center dipoles of clusters with high activation were determined as dipoles for which there was no higher power in their neighborhood. The time-varying connectivity pattern between the time series of these dipoles was calculated using the integrated, full-frequency, and spectrum-weighted Adaptive Directed Transfer Function4. This was done in the frequency band containing the seizure information, 3-30Hz. The outdegree of each selected dipole was determined as the sum over time of all outgoing connections. Around the dipole with the highest outdegree, we determined a region of dipoles that had a power that was at least 90% of the power of the center dipole. This region was then considered as the SOZ. We were able to successfully localize the driver in the resected zone for both patients. For the simulation data, the results can be quantified: in 71% of the simulations, the localization error remained below 25mm. If the selection of the dipole would be solely based on the highest power, the error would be more than 82mm. ESI in combination with connectivity analysis can successfully localize the SOZ in non- invasive ictal hd-EEG recordings and outperforms localization based on power. This could have important clinical relevance for the presurgical evaluation in focal epilepsy. References: 1. van Mierlo, P et al. (2014) Prog Neurobiol. 121:19-35. 2. Brunet, D. et al. (2011) Comput. Intell. Neurosci. 2. 3. Pascal-Marqui, R.D., et al. (1994) Int. J. Psychophysiol. 18(1):49-65. 4. van Mierlo, P. et al. (2013) Epilepsia 54.8:1409-1418

Stimulating illusory own-body perceptions

'Out-of-body' experiences (OBEs) are curious, usually brief sensations in which a person's consciousness seems to become detached from the body and take up a remote viewing position. Here we describe the repeated induction of this experience by focal electrical stimulation of the brain's right angular gyrus in a patient who was undergoing evaluation for epilepsy treatment. Stimulation at this site also elicited illusory transformations of the patient's arm and legs (complex somatosensory responses) and whole-body displacements (vestibular responses), indicating that out-of-body experiences may reflect a failure by the brain to integrate complex somatosensory and vestibular information

Effects of Repetitive Transcranial Magnetic Stimulation on Spike Pattern and Topography in Patients with Focal Epilepsy

Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive method for brain stimulation. Group-studies applying rTMS in epilepsy patients aiming to decrease epileptic spike- or seizure-frequency have led to inconsistent results. Here we studied whether therapeutic trains of rTMS have detectable effects on individual spike pattern and/or frequency in patients suffering from focal epilepsy. Five patients with focal epilepsy underwent one session of rTMS online with EEG using a 6Hz prime/1Hz rTMS protocol (real and sham). The EEG was recorded continuously throughout the stimulation, and the epileptic spikes recorded immediately before (baseline) and after stimulation (sham and real) were subjected to further analysis. Number of spikes, spike-strength and spike-topography were examined. In two of the five patients, real TMS led to significant changes when compared to baseline and sham (decrease in spike-count in one patient, change in topography of the after-discharge in the other patient). Spike-count and topography remained unchanged the remaining patients. Overall, our results do not indicate a consistent effect of rTMS stimulation on interictal spike discharges, but speak in favor of a rather weak and individually variable immediate effect of rTMS on focal epileptic activity. The individuation of most effective stimulation patterns will be decisive for the future role of rTMS in epilepsies and needs to be determined in larger studie

Neuropsychological outcome after extra-temporal epilepsy surgery

Background: The neuropsychological results of temporal lobe epilepsy surgery are well reported in the literature. The aim of this study was to analyse the neuropsychological outcome in a consecutive series of patients with extra-temporal epilepsy. Methods: We retrospectively analysed the data of patients operated between 1996 and 2008 for extra-temporal epilepsy. Standard neuropsychological tests were applied. We assessed the neuropsychological outcome after surgery and the correlation of the neuropsychological outcome with (1) side and localisation of surgery, (2) Engel scale for seizure outcome and (3) timing of surgery. Findings: Patients had a better neuropsychological outcome when undergoing non-frontal resection [χ2 (2) =6.66, p = 0.036]. Subjects who had undergone left or right resection showed no difference in outcome [χ2 (2) =0.533, p = 0.766]. The correlation between the Engel scale for seizure re-occurence and the neuropsychological scores showed only a tendency for better outcome (Spearman ρ = −0.437; p = 0.069). The global measure of change did not correlate significantly with delay of surgery (Spearman ρ = −0.163; p = 0.518). Conclusions: Resective epilepsy surgery improves neuropsychological status outcome in patients with extra-temporal epilepsy even if the patient did not become seizure free. The outcome is better for non-frontal localisatio

The predictive value of hypometabolism in focal epilepsy:a prospective study in surgical candidates

Purpose: FDG PET is an established tool in presurgical epilepsy evaluation, but it is most often used selectively in patients with discordant MRI and EEG results. Interpretation is complicated by the presence of remote or multiple areas of hypometabolism, which leads to doubt as to the true location of the seizure onset zone (SOZ) and might have implications for predicting the surgical outcome. In the current study, we determined the sensitivity and specificity of PET localization prospectively in a consecutive unselected cohort of patients with focal epilepsy undergoing in-depth presurgical evaluation. Methods: A total of 130 patients who underwent PET imaging between 2006 and 2015 matched our inclusion criteria, and of these, 86 were operated on (72% with a favourable surgical outcome, Engel class I). Areas of focal hypometabolism were identified using statistical parametric mapping and concordance with MRI, EEG and intracranial EEG was evaluated. In the surgically treated patients, postsurgical outcome was used as the gold standard for correctness of localization (minimum follow-up 12 months). Results: PET sensitivity and specificity were both 95% in 86 patients with temporal lobe epilepsy (TLE) and 80% and 95%, respectively, in 44 patients with extratemporal epilepsy (ETLE). Significant extratemporal hypometabolism was observed in 17 TLE patients (20%). Temporal hypometabolism was observed in eight ETLE patients (18%). Among the 86 surgically treated patients, 26 (30%) had hypometabolism extending beyond the SOZ. The presence of unilobar hypometabolism, included in the resection, was predictive of complete seizure control (p = 0.007), with an odds ratio of 5.4. Conclusion: Additional hypometabolic areas were found in one of five of this group of nonselected patients with focal epilepsy, including patients with “simple” lesional epilepsy, and this finding should prompt further in-depth evaluation of the correlation between EEG findings, semiology and PET. Hypometabolism confined to the epileptogenic zone as defined by EEG and MRI is associated with a favourable postoperative outcome in both TLE and ETLE patients.</p