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

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

Virtual MEG Helmet : Computer Simulation of an Approach to Neuromagnetic Field Sampling

Head movements during an MEG recording are commonly considered an obstacle. In this computer simulation study, we introduce an approach, the virtual MEG helmet (VMH), which employs the head movements for data quality improvement. With a VMH, a denser MEG helmet is constructed by adding new sensors corresponding to different head positions. Based on the Shannon's theory of communication, we calculated the total information as a figure of merit for comparing the actual 306-sensor Elekta Neuromag helmet to several types of the VMH. As source models, we used simulated randomly distributed source current (RDSC), simulated auditory and somatosensory evoked fields. Using the RDSC model with the simulation of 360 recorded events, the total information (bits/sample) was 989 for the most informative single head position and up to 1272 for the VMH (addition of 28.6%). Using simulated AEFs, the additional contribution of a VMH was 12.6% and using simulated SEF only 1.1%. For the distributed and bilateral sources, a VMH can provide a more informative sampling of the neuromagnetic field during the same recording time than measuring the MEG from one head position. VMH can, in some situations, improve source localization of the neuromagnetic fields related to the normal and pathological brain activity. This should be investigated further employing real MEG recordings.Peer reviewe

Exome sequencing reveals predominantly de novo variants in disorders with intellectual disability (ID) in the founder population of Finland

The genetics of autosomal recessive intellectual disability (ARID) has mainly been studied in consanguineous families, however, founder populations may also be of interest to study intellectual disability (ID) and the contribution of ARID. Here, we used a genotype-driven approach to study the genetic landscape of ID in the founder population of Finland. A total of 39 families with syndromic and non-syndromic ID were analyzed using exome sequencing, which revealed a variant in a known ID gene in 27 families. Notably, 75% of these variants in known ID genes were de novo or suspected de novo (64% autosomal dominant; 11% X-linked) and 25% were inherited (14% autosomal recessive; 7% X-linked; and 4% autosomal dominant). A dual molecular diagnosis was suggested in two families (5%). Via additional analysis and molecular testing, we identified three cases with an abnormal molecular karyotype, including chr21q22.12q22.2 uniparental disomy with a mosaic interstitial 2.7 Mb deletion covering DYRK1A and KCNJ6. Overall, a pathogenic or likely pathogenic variant was identified in 64% (25/39) of the families. Last, we report an alternate inheritance model for 3 known ID genes (UBA7, DDX47, DHX58) and discuss potential candidate genes for ID, including SYPL1 and ERGIC3 with homozygous founder variants and de novo variants in POLR2F and DNAH3. In summary, similar to other European populations, de novo variants were the most common variants underlying ID in the studied Finnish population, with limited contribution of ARID to ID etiology, though mainly driven by founder and potential founder variation in the latter case.Peer reviewe

SQUIDs in biomagnetism : A roadmap towards improved healthcare

This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 686865.Peer reviewedPublisher PD

Exome sequencing reveals predominantly de novo variants in disorders with intellectual disability (ID) in the founder population of Finland

The genetics of autosomal recessive intellectual disability (ARID) has mainly been studied in consanguineous families, however, founder populations may also be of interest to study intellectual disability (ID) and the contribution of ARID. Here, we used a genotype-driven approach to study the genetic landscape of ID in the founder population of Finland. A total of 39 families with syndromic and non-syndromic ID were analyzed using exome sequencing, which revealed a variant in a known ID gene in 27 families. Notably, 75% of these variants in known ID genes were de novo or suspected de novo (64% autosomal dominant; 11% X-linked) and 25% were inherited (14% autosomal recessive; 7% X-linked; and 4% autosomal dominant). A dual molecular diagnosis was suggested in two families (5%). Via additional analysis and molecular testing, we identified three cases with an abnormal molecular karyotype, including chr21q22.12q22.2 uniparental disomy with a mosaic interstitial 2.7 Mb deletion covering DYRK1A and KCNJ6. Overall, a pathogenic or likely pathogenic variant was identified in 64% (25/39) of the families. Last, we report an alternate inheritance model for 3 known ID genes (UBA7, DDX47, DHX58) and discuss potential candidate genes for ID, including SYPL1 and ERGIC3 with homozygous founder variants and de novo variants in POLR2F and DNAH3. In summary, similar to other European populations, de novo variants were the most common variants underlying ID in the studied Finnish population, with limited contribution of ARID to ID etiology, though mainly driven by founder and potential founder variation in the latter case

Neural correlates of late positivities associated with infrequent visual events and response errors

The P3 response has been one of the most extensively studied event-related potential (ERP) components. Still, the exact functional role and cortical basis of P3 has remained unsettled. To explore the cortical processes underlying the generation of late positivities, we recorded the activation evoked by frequent Go and infrequent NoGo stimuli and correct versus erroneous responses using combined magnetoencephalography (MEG) and ERP measurements during a visual Go/NoGo task. The stimulus-locked signals in the ERP channels revealed an enhanced negative N2 and a prominent late positive component (LPC) after the complex NoGo stimuli associated with successfully withheld responses. The response-locked ERP signals revealed error-related negativity (ERN) and positivity (Pe) after erroneous responses. The positive LPC and Pe components were coupled with functionally and temporally comparable MEG signals. This MEG activation detected during the positive components was localized bilaterally in the posterior temporal cortex. In the response-locked averages, the temporal activity was enhanced around 200 ms after a commission of an error. In the stimulus-locked averages, the activation was also enhanced after infrequent NoGo stimuli around 500 ms after stimulus onset and delayed about 80 ms for the initially miscategorized NoGo stimuli accompanied by erroneous response. The results suggest that the cortical correlates of Pe are not specifically related to commission of an error, but both the LPC and Pe components, and bilateral temporal cortices, are more generally involved in stimulus-driven attentional processing evoked by unexpected stimuli. The negative ERP components evoked by NoGo stimuli (N2) and erroneous responses (ERN) were found to be associated with partly non-overlapping neural sources.Peer reviewe

Current clinical magnetoencephalography practice across Europe : Are we closer to use MEG as an established clinical tool?

Purpose: This comprehensive survey aims at characterizing the current clinical use of magnetoencephalography (MEG) across European MEG centres. Methods: Forty-four MEG centres across Europe were contacted in May 2015 via personalized e-mail to contribute to survey. The web-based survey was available on-line for 1 month and the MEG centres that did not respond were further contacted to maximize participation. Results: Among the 57% of responders, 12 centres from 10 different countries reported to use MEG for clinical applications. A total of 524 MEG investigations were performed in 2014 for the pre-surgical evaluation of epilepsy, while in the same period 244 MEG investigations were performed for pre-surgical functional brain mapping. Seven MEG centres located in different European countries performed >50 MEG investigations for epilepsy mapping in 2014, both in children and adults. In those centres, time from patient preparation to MEG data reporting tends to be lower than those investigating a lower annual number of patients. Conclusion: This survey demonstrates that there is in Europe an increasing and widespread expertise in the field of clinical MEG. These findings should serve as a basis to harmonize clinical MEG procedures and promote the clinical added value of MEG across Europe. MEG should now be considered in Europe as a mature clinical neurophysiological technique that should be used routinely in two specific clinical indications, i.e, the pre-surgical evaluation of refractory focal epilepsy and functional brain mapping. (C) 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.Peer reviewe

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

Results of language studies.

<p>Results of language studies.</p