A simple magnetoencephalographic auditory paradigm may aid in confirming left-hemispheric language dominance in epilepsy patients

Objective The intracarotid amobarbital procedure (IAP) is the current "gold standard" in the preoperative assessment of language lateralization in epilepsy surgery candidates. It is, however, invasive and has several limitations. Here we tested a simple noninvasive language lateralization test performed with magnetoencephalography (MEG). Methods We recorded auditory MEG responses to pairs of vowels and pure tones in 16 epilepsy surgery candidates who had undergone IAP. For each individual, we selected the pair of planar gradiometer sensors with the strongest N100m response to vowels in each hemisphere and -from the vector sum of signals of this gradiometer pair-calculated the vowel/tone amplitude ratio in the left (L) and right (R) hemisphere and, subsequently, the laterality index: LI = (L-R)/(L+R). In addition to the analysis using a single sensor pair, an alternative analysis was performed using averaged responses over 18 temporal sensor pairs in both hemispheres. Results The laterality index did not correlate significantly with the lateralization data obtained from the IAP. However, an MEG pattern of stronger responses to vowels than tones in the left hemisphere and stronger responses to tones than vowels in the right hemisphere was associated with left-hemispheric language dominance in the IAP in all the six patients who showed this pattern. This results in a specificity of 100% and a sensitivity of 67% of this MEG pattern in predicting left-hemispheric language dominance (p = 0.01, Fisher's exact test). In the analysis using averaged responses over temporal channels, one additional patient who was left-dominant in IAP showed this particular MEG pattern, increasing the sensitivity to 78% (p = 0.003). Significance This simple MEG paradigm shows promise in feasibly and noninvasively confirming left-hemispheric language dominance in epilepsy surgery candidates. It may aid in reducing the need for the IAP, if the results are confirmed in larger patient samples.Peer reviewe

Detrended fluctuation analysis in the presurgical evaluation of parietal lobe epilepsy patients

Objective: To examine the usability of long-range temporal correlations (LRTCs) in non-invasive localization of the epileptogenic zone (EZ) in refractory parietal lobe epilepsy (RPLE) patients. Methods: We analyzed 10 RPLE patients who had presurgical MEG and underwent epilepsy surgery. We quantified LRTCs with detrended fluctuation analysis (DFA) at four frequency bands for 200 cortical regions estimated using individual source models. We correlated individually the DFA maps to the distance from the resection area and from cortical locations of interictal epileptiform discharges (IEDs). Additionally, three clinical experts inspected the DFA maps to visually assess the most likely EZ locations. Results: The DFA maps correlated with the distance to resection area in patients with type II focal cortical dysplasia (FCD) (p < 0:05), but not in other etiologies. Similarly, the DFA maps correlated with the IED locations only in the FCD II patients. Visual analysis of the DFA maps showed high interobserver agreement and accuracy in FCD patients in assigning the affected hemisphere and lobe. Conclusions: Aberrant LRTCs correlate with the resection areas and IED locations. Significance: This methodological pilot study demonstrates the feasibility of approximating cortical LRTCs from MEG that may aid in the EZ localization and provide new non-invasive insight into the presurgical evaluation of epilepsy. (c) 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

Interictal magnetoencephalography in parietal lobe epilepsy – comparison of equivalent current dipole and beamformer (SAMepi) analysis

Objective To evaluate a novel analysis method (SAMepi) in the localization of interictal epileptiform magnetoencephalographic (MEG) activity in parietal lobe epilepsy (PLE) patients in comparison with equivalent current dipole (ECD) analysis. Methods We analyzed the preoperative interictal MEG of 17 operated PLE patients utilizing visual analysis and: (1) ECD with a spherical conductor model; (2) ECD with a boundary element method (BEM) conductor model; and (3) SAMepi - a kurtosis beamformer method. Localization results were compared between the three methods, to the location of the resection and to the clinical outcome. Results Fourteen patients had an epileptiform finding in the visual analysis; SAMepi detected spikes in 11 of them. A unifocal finding in both the ECD and in the SAMepi analysis was associated with a better chance of seizure-freedom (p=0.02). There was no significant difference in the distances from the unifocal MEG localizations to the nearest border of the resection between the different analysis methods. Conclusions Localizations of unifocal interictal spikes detected by SAMepi did not significantly differ from the conventional ECD localizations. Significance SAMepi - a novel semiautomatic analysis method - is useful in localizing interictal epileptiform MEG activity in the presurgical evaluation of parietal lobe epilepsy patients.Peer reviewe

Magnetoencephalographic Abnormalities in Creutzfeldt-Jakob Disease: A Case Report

Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative disease with no effective therapy available. We recorded spontaneous magnetoencephalography and auditory evoked fields (AEFs) from a male patient with a rapidly progressive memory disorder, ataxia and myoclonus. Post-mortem examination confirmed sporadic CJD. Sources of the abnormal slow wave activity were localized with a beamformer software. Sources of sharp transients and AEFs were modeled with equivalent current dipoles. The estimated sources of spontaneous activity abnormalities were more dominant in the left hemisphere, in line with left-dominant abnormalities in diffusion-weighted MRI. Sources of AEFs were found in both temporal lobes. Magnetoencephalography measurements on CJD patients are feasible, and provide efficient means for localizing abnormal cortical activity in CJD

Protocol for motor and language mapping by navigated TMS in patients and healthy volunteers; workshop report

Navigated transcranial magnetic stimulation (nTMS) is increasingly used for preoperative mapping of motor function, and clinical evidence for its benefit for brain tumor patients is accumulating. In respect to language mapping with repetitive nTMS, literature reports have yielded variable results, and it is currently not routinely performed for presurgical language localization. The aim of this project is to define a common protocol for nTMS motor and language mapping to standardize its neurosurgical application and increase its clinical value. The nTMS workshop group, consisting of highly experienced nTMS users with experience of more than 1500 preoperative nTMS examinations, met in Helsinki in January 2016 for thorough discussions of current evidence and personal experiences with the goal to recommend a standardized protocol for neurosurgical applications. nTMS motor mapping is a reliable and clinically validated tool to identify functional areas belonging to both normal and lesioned primary motor cortex. In contrast, this is less clear for language-eloquent cortical areas identified by nTMS. The user group agreed on a core protocol, which enables comparison of results between centers and has an excellent safety profile. Recommendations for nTMS motor and language mapping protocols and their optimal clinical integration are presented here. At present, the expert panel recommends nTMS motor mapping in routine neurosurgical practice, as it has a sufficient level of evidence supporting its reliability. The panel recommends that nTMS language mapping be used in the framework of clinical studies to continue refinement of its protocol and increase reliability.Peer reviewe

Magnetoencephalography in the preoperative assessment of epilepsy surgery candidates

Epilepsy is a neurological disease characterized by disturbances in the electric activity of the brain. Up to a third of epilepsy patients have an inadequate response to anti-epileptic medication. In these patients, the possibility of surgical treatment, that is, the surgical removal of the epileptogenic brain tissue, should be considered. Some patient subgroups, such as those with no potential epileptogenic lesion in the magnetic resonance imaging (MRI) of the brain, so called MRI-negative patients, are particularly challenging and typically require comprehensive noninvasive and invasive presurgical investigations. Magnetoencephalography (MEG) is a noninvasive method in which the magnetic fields generated by the cortical post-synaptic currents are recorded. The generators of the MEG signal are thought to be the same as the generators of the electroencephalographic (EEG) signal. However, the two methods differ in their sensitivity to source currents in different orientation and depth. Therefore, the two methods are complementary. One of the studies of this thesis examined the utility of MEG in patients whose epilepsy is caused by a focal cortical dysplasia (FCD). FCDs are highly epileptogenic malformations of cortical development, and often result in epilepsy that is refractory to anti-epileptic medication. They may often be invisible in the brain MRI, requiring extensive presurgical evaluation. In this study, we found that a more complete removal of the MEG interictal spike source cluster locations was associated with better surgical outcome. Additionally, the concordance between the interictal MEG spike localizations and the epileptogenic zone estimated by an intracranial recording was considered good in most of the MRI-negative patients, who were of a special interest in this study. The second study investigated the use of MEG as a tool to assess language lateralization in epilepsy patients. We introduced a simple auditory paradigm that had previously been shown to elicit differently lateralized MEG responses in healthy right-handed vs. left-handed subjects suggesting a potential value in studying language lateralization. We compared the lateralization results of MEG to the results of the intracarotid amobarbital procedure (IAP), also known as the Wada test. Although the lateralization results of MEG did not show a significant correlation to the IAP lateralization results, we discovered an MEG response pattern that was only present in patients with left hemisphere dominant IAP results. This pattern was seen in 67% to 78% of the patients with left dominant IAP results depending on the MEG analysis method utilized. In the third study of this thesis, we examined the utility of a novel kurtosis beamformer analysis method, SAMepi, in patients with parietal lobe epilepsy to localize the sources of interictal epileptiform activity. Parietal lobe epilepsies are rare in epilepsy surgery series, which may partially be explained by the difficulty of localizing the epileptogenic zone in this patient group. SAMepi is a semi-automatic analysis method, that would significantly reduce the workload and the subjective decision-making compared to the current clinical practice. We found that SAMepi analysis provided localization results that in most patients were similar to the results of the current clinical standard, that is, the equivalent current dipole (ECD) analysis. However, its sensitivity in detecting epileptiform discharges was somewhat lower than that of the current practice of visually reviewing the MEG signals. In this thesis, we have aimed to develop the utility of MEG in challenging epilepsy surgery patient groups, and to introduce a novel language paradigm as well as a novel semi-automatic analysis method for interictal spike localization. Although MEG already is quite an established tool in the presurgical evaluations of epilepsy surgery candidates in many epilepsy surgery centers, the continuous development of the method is crucial to maximize its diagnostic yield and to justify its higher cost compared to more conventional neurophysiological techniques, such as EEG.Epilepsia on neurologinen sairaus, jossa aivojen poikkeava sähköinen toiminta aiheuttaa oireita, jotka tyypillisesti esiintyvät kohtauksittain. Noin kolmasosalla epilepsiaa sairastavista potilaista epilepsialääkityksellä ei saavuteta kohtauksettomuutta. Silloin on tärkeää selvittää, onko epilepsian kirurginen hoito mahdollista. Erityisen laajoja kajoamattomia ja kajoavia tutkimuksia tarvitaan epilepsiakirurgian suunnittelussa niillä potilailla, joilla pään magneettikuvantamisessa (MRI) ei löydy epilepsian aiheuttajaksi sopivaa rakennemuutosta. Magnetoenkefalografiassa (MEG) aivojen sähköisen toiminnan tuottamia hyvin heikkoja magneettikenttiä mitataan pään ulkopuolelta kajoamattomasti. Tämän väitöskirjatyön tarkoituksena oli tutkia ja kehittää MEG:n käyttöä osana epilepsiakirurgiaa edeltäviä tutkimuksia. Yhdessä osatyössä tutkimme MEG:n käyttöä epilepsiakirurgiapotilailla, joiden epilepsian syynä oli paikallinen aivokuoren kehityshäiriö (engl. focal cortical dysplasia, FCD). FCD aiheuttaa varsin usein lääkehoidolle vastaamattoman epilepsian ja erityisesti pienet FCD:t jäävät melko usein näkymättä pään magneettikuvantamisessa (ns. MRI-negatiiviset potilaat). Tutkimuksen tulokset viittaavat siihen, että täydellisempi MEG:n kohtaustenvälisten piikkien lähdealueen poisto on yhteydessä parempaan leikkaustulokseen. Lisäksi totesimme, että suurimmalla osalla MRI-negatiivisista potilaista MEG:n paikannustulokset olivat yhteneviä kallonsisäisten elektroenkefalografia (EEG) -rekisteröintien avulla määritetyn epileptogeenisen, eli epilepsiaa aiheuttavan, alueen kanssa. Toisessa osatyössä tutkimme yksinkertaisen kuuloärsyketehtävän toimivuutta kielellisten toimintojen lateralisaation määrittämisessä. Vertasimme MEG:n tuloksia kajoavan ns. Wada-tutkimuksen tuloksiin. Totesimme tietynlaisten MEG-vasteiden esiintyvän vain niillä potilailla, joilla Wada-tutkimuksen tulokset viittasivat vasemman aivopuoliskon kielidominanssiin. Tosin tämä MEG-löydös todettiin vain osalla (67% tai 78% analyysimenetelmästä riippuen) näistä potilaista. Kolmannessa osatyössä tutkimme MEG:n käyttöä kohtaustenvälisten epileptiformisten ilmiöiden paikannuksessa päälaenlohkon epilepsiaa sairastavilla potilailla. Nykyisen kliinisessa käytössä olevan standardimenetelmän eli ns. virtadipolianalyysin lisäksi analysoimme MEG-tulokset käyttäen uutta puoliautomaattista keilanmuodostukseen (engl. beamforming) perustuvaa paikannusmenetelmää. Totesimme, että uuden menetelmän tuottamat paikannustulokset olivat suurimmalta osin samankaltaisia kuin nykyisen standardimenetelmän tuottamat tulokset. Epileptiformisten ilmiöiden toteamisessa uusi menetelmä ei kuitenkaan ollut aivan yhtä herkkä kuin perinteinen MEG-signaalien manuaaliseen tarkistamiseen perustuva analyysi. Tämän väitöskirjatyön tavoitteena on ollut kehittää MEG:n käyttöä haastavien potilasryhmien epilepsiakirurgia-arvioissa. MEG on vakiinnuttanut asemansa osana epilepsiakirurgiaa edeltäviä tutkimuksia monissa epilepsiakirurgiakeskuksissa, mutta sen jatkuva kehittäminen on välttämätöntä siitä saatavan hyödyn lisäämiseksi erityisesti huomioiden MEG-tutkimusten korkea hinta ja rajallinen saatavuus verrattuna EEG-tutkimuksiin

Example dataset for the Helsinki VideoMEG project

<p>The files contain an example of magnetoencephalographic, video, and audio data from an epilepsy patient recorded with the Helsinki VideoMEG Project (https://github.com/andreyzhd/VideoMEG) system.</p> <p>The patient's seizures manifested themselves as a loss of muscle tone in the right arm. Therefore, seizures could not be observed in the normal MEG setup where the patient is either seated or lying with the arms supported. To facilitate seizure detection, the patient was instructed to keep the hands raised during the recording. However, the patient was able to maintain this posture only for short periods, and had his arms resting on chair supports during most of the recording. For more details, see patient 6 in http://dx.doi.org/10.1016/j.eplepsyres.2013.02.017</p

Averaged MEG responses of the patients showing the “left hemisphere language dominant MEG pattern”.

<p>Normalized response amplitudes, with the peak amplitude of the stronger N100m response set to the value of one (response to the vowel stimuli in the left hemisphere and response to the tone stimuli in the right hemisphere). The vertical bar marks the 95% confidence interval of the response amplitude. A: Single sensor analysis, B: Regional analysis.</p

Results of language studies.

<p>Results of language studies.</p

Clinical details of the patients.

<p>Clinical details of the patients.</p