Magnetoencephalography

This is a practical book on MEG that covers a wide range of topics. The book begins with a series of reviews on the use of MEG for clinical applications, the study of cognitive functions in various diseases, and one chapter focusing specifically on studies of memory with MEG. There are sections with chapters that describe source localization issues, the use of beamformers and dipole source methods, as well as phase-based analyses, and a step-by-step guide to using dipoles for epilepsy spike analyses. The book ends with a section describing new innovations in MEG systems, namely an on-line real-time MEG data acquisition system, novel applications for MEG research, and a proposal for a helium re-circulation system. With such breadth of topics, there will be a chapter that is of interest to every MEG researcher or clinician

On-scalp MEG using high-Tc SQUIDs: Measuring brain activity with superconducting magnetometers

This thesis describes work done towards realizing on-scalp magnetoencephalography (MEG) based on high critical temperature (high-Tc) superconducting quantum interference device (SQUID) sensors. MEG is a non-invasive neuroimaging modality that records the magnetic fields produced by neural currents with good spatial and high temporal resolution. However, state-of-the-art MEG is limited by the use of liquid helium-cooled sensors (T ~ 4 K). The amount of thermal insulation between the sensors and the subject\u27s head that is required to achieve the extreme temperature difference (~300 K), typically realized in the form of superinsulation foil and ~2 centimeters of vacuum, limits measurable signals. Replacing the sensors with high-Tc SQUIDs can mitigate this problem. High-Tc SQUIDs operate at much higher temperatures (90 K) allowing significant reduction of the stand-off distance (to ~1 mm). They can furthermore be cooled with liquid nitrogen (77 K), a cheaper, more sustainable alternative to the liquid helium used for cooling in conventional MEG systems.The work described in this thesis can be divided into three main areas: (I) simulation work for practical implementations of on-scalp systems, (II) development of a 7-channel high-Tc SQUID-based on-scalp MEG system, and (III) on-scalp MEG recordings.In the first part, spatial information density (SID), a metric to evaluate the performance of simulated MEG sensor arrays, is introduced and - along with total information capacity - used to compare the performance of various simulated full-head on-scalp MEG sensor arrays.\ua0Simulations demonstrate the potential of on-scalp MEG, with all on-scalp systems exhibiting higher information capacity than the state-of-the-art. SID further reveals more homogeneous sampling of the brain with flexible systems. A method for localizing magnetometers in on-scalp MEG systems is introduced and tested in simulations. The method uses small, magnetic dipole-like coils to determine the location and orientation of individual sensors, enabling straightforward co-registration in flexible on-scalp MEG systems. The effects of different uncertainties and errors on the accuracy of the method were quantified.In the second part, design, construction, and performance of a 7-channel on-scalp MEG system is described. The system houses seven densely-packed (2 mm edge-to-edge), head-aligned high-Tc SQUID magnetometers (9.2 mm x 8.6 mm) inside a single, liquid nitrogen-cooled cryostat. With a single filling, the system can be utilized for MEG recordings for >16 h with low noise levels (~0-130 fT). Using synchronized clocks and a direct injection feedback scheme, the system achieves low sensor crosstalk (<0.6%).\ua0In the third part, on-scalp MEG recordings with the 7-channel system as well as its predecessor, a single-channel system, are presented. The recordings are divided into proof-of-principle and benchmarking experiments. The former consist of well-studied, simple paradigms such as auditory evoked activity and visual alpha. Expected signal components were clearly seen in the on-scalp recordings. The benchmarking studies were done to compare and contrast on-scalp with state-of-the-art MEG. To this end, a number of experimental stimulus paradigms were recorded on human subjects with the high-Tc SQUID-based on-scalp systems as well as a state-of-the-art, commercial full-head MEG system. Results include the expected signal gains that are associated with recording on-scalp as well as new details of the neurophysiological signals. Using the previously described on-scalp MEG co-registration method enabled source localization with high agreement to the full-head recording (the distance between dipoles localized with the two systems was 4.2 mm)

A reusable benchmark of brain-age prediction from M/EEG resting-state signals

Population-level modeling can define quantitative measures of individual aging by applying machine learning to large volumes of brain images. These measures of brain age, obtained from the general population, helped characterize disease severity in neurological populations, improving estimates of diagnosis or prognosis. Magnetoencephalography (MEG) and Electroencephalography (EEG) have the potential to further generalize this approach towards prevention and public health by enabling assessments of brain health at large scales in socioeconomically diverse environments. However, more research is needed to define methods that can handle the complexity and diversity of M/EEG signals across diverse real-world contexts. To catalyse this effort, here we propose reusable benchmarks of competing machine learning approaches for brain age modeling. We benchmarked popular classical machine learning pipelines and deep learning architectures previously used for pathology decoding or brain age estimation in 4 international M/EEG cohorts from diverse countries and cultural contexts, including recordings from more than 2500 participants. Our benchmarks were built on top of the M/EEG adaptations of the BIDS standard, providing tools that can be applied with minimal modification on any M/EEG dataset provided in the BIDS format. Our results suggest that, regardless of whether classical machine learning or deep learning was used, the highest performance was reached by pipelines and architectures involving spatially aware representations of the M/EEG signals, leading to R^2 scores between 0.60-0.71. Hand-crafted features paired with random forest regression provided robust benchmarks even in situations in which other approaches failed. Taken together, this set of benchmarks, accompanied by open-source software and high-level Python scripts, can serve as a starting point and quantitative reference for future efforts at developing M/EEG-based measures of brain aging. The generality of the approach renders this benchmark reusable for other related objectives such as modeling specific cognitive variables or clinical endpoints

Neural mechanisms of foreign language phoneme acquisition in early adulthood : MEG study

Tämän tutkimuksen tavoitteena on selvittää omaan äidinkieleen kuulumattomien foneemikontrastien oppimisen mekanismeja nuorilla aikuisilla neurofysiologisten ja behavioraalisten menetelmien avulla. Perinteisesti kielen foneettisen avaruuden omaksumisen on ajateltu tapahtuvan ensisijaisesti varhaislapsuuden kielellisten herkkyyskausien aikana, jonka jälkeen uusien foneemien oppiminen on haastavaa. Myöhemmät tutkimukset ovat kuitenkin osoittaneet, että vieraiden foneemien omaksuminen on mahdollista myös aikuisiällä. Uusien foneemikategorioiden muodostuminen vaatii aivoissa solutason plastisia muutoksia. Aivojen kykyä erotella läheisesti toisiaan muistuttavia foneemikategorioita kielenprosessoinnin varhaisella tasolla on tutkittu neurofysiologisin menetelmin esimerkiksi tapahtumasidonnaisen poikkeavuusnegatiivisuusvasteen (eng. mismatch negativity, MMN) avulla. MMN-vaste, tai sen magneettinen vastine MMNm, syntyy seurauksena muutoksiin sensorisessa havaintoympäristössä. Tutkimuksissa lyhyenkin auditiivisen harjoittelujakson on havaittu vahvistavan aivojen kykyä erotella läheisesti toisiaan muistuttavia vieraita foneemeja ja voimistavan MMN- ja MMNm-vasteita. Tässä tutkimuksessa vieraan kielen foneettisen oppimisen neuraalista perustaa ja oppimisen aiheuttamia plastisia muutoksia aivoissa tutkittiin magnetoenkefalografialla (MEG) neuromagneettisten tapahtumasidonnaisten vasteiden (erityisesti MMNm) avulla. Tutkimuksessa mitattiin 20 suomalaista koehenkilöä, joiden tehtävänä oli oppia erottelemaan akustisesti toisiaan läheisesti muistuttavia venäjän kielen frikatiiveja Ш /ʂ/ ja Щ /ɕ(ː)/. Erottelukykyä mitattiin ensin behavioraalisella tehtävällä, jossa koehenkilöille toistettiin nauhoitettuja venäjänkielisiä epäsanaminimipareja, jossa sanan ensimmäistä foneemia varioitiin. Koehenkilöiden tehtävänä oli vastata, kuulivatko he sanoissa eroa. Samoja kuuloärsykkeitä toistettiin koehenkilöille sen jälkeen passiivisessa MEG-tehtävässä, jossa testattiin aivojen kykyä havaita ero ärsykkeissä ilman, että niihin kiinnitetään huomiota (koehenkilöt katselivat samalla äänetöntä elokuvaa). Mittauksen jälkeen koehenkilöt harjoittelivat foneemien erottelua kotona noin viikon ajan tietokoneavusteisen oppimispelin avulla, jonka jälkeen heidät mitattiin uudelleen. MEG-signaalien lähdemallinnusta varten koehenkilöiden aivoista otettiin myös rakenteelliset magneettikuvat. Tutkittavien foneemien behavioraalinen erottelukyky oli selvästi tuttuja kontrollifoneemeita heikompaa. Erottelukyky vaikutti paranevan harjoittelun seurauksena hieman, mutta ero ei ollut tilastollisesti merkitsevä. Hypoteesien vastaisesti tilastollisesti merkitseviä MMNm-vasteita ei löydetty ennen eikä jälkeen harjoittelun, eikä muissakaan auditorisissa MEG-vasteissa tai niiden neuraalisten lähdevirtojen voimakkuuksissa tai jakaumassa ollut tilastollisesti merkitsevää eroa mittauskertojen välillä. Yksilölliset erot oppimisessa olivat kuitenkin suuria. Koehenkilöillä, joilla behavioraalinen erottelukyky parani harjoittelun myötä, oli silmämääräisesti havaittavissa hypoteesien mukaista vahvistumista auditorisissa vasteissa. Vaikka efekti oli erittäin pieni eikä tilastollisesti merkitsevä, vastaavaa ei havaittu epäoppijoilla eikä kontrollitilanteessa. Tässä tutkimuksessa ei kyetty replikoimaan aiempien tutkimusten tuloksia foneemien omaksumisesta aikuisiällä. Vaikka on todennäköistä, että tietyt metodologiset heikkoudet (mm. vähäinen ärsykkeiden määrä MEG-tehtävässä, haastavat ärsykkeet) vaikuttivat tulosten merkitsevyyteen, voidaan tämän tutkimuksen valossa aiempien tutkimustulosten yleistettävyyttä kyseenalaistaa.The aim of this study is to examine the learning mechanisms and acquisition of non-native phoneme contrasts in young adults using neurophysiological and behavioral methods. According to the traditional view, acquiring novel phonemes after the sensitive periods in the early childhood is very difficult. However, later findings have shown that foreign phoneme contrasts can be learned at a later age, too. Acquiring new phonemic categories requires neuroplastic changes in the brain. Neurophysiological studies have examined the brain’s ability to differentiate between closely related phonemic categories at the early stage of spoken language processing by measuring, for example, event-related mismatch negativity responses (MMN). MMN, or its magnetic equivalent MMNm, is elicited when the brain registers a difference in a repetitive sensory stimulus. Studies have shown that even a moderate amount of auditory training with closely related foreign phonemes improves the brain’s ability to discriminate between them resulting in enhanced MMN or MMNm responses. In this experiment the neural mechanisms of foreign language phoneme acquisition and the learning-related neuroplastic changes were studied using magnetoencephalography (MEG) and neuromagnetic evoked responses (MMNm in particular). 20 Finnish subjects were measured in the experiment. Their task was to learn to differentiate between acoustically closely related Russian fricatives Ш /ʂ/ and Щ /ɕ(ː)/. The subjects’ differentiation skills were first tested in a behavioral task where Russian pseudoword minimal pairs were presented to them auditorily. The first phoneme in the word pairs was varied and the subjects had to report whether they heard a difference between the words or not. The same stimuli were then presented in a passive MEG task where the brain’s change detection responses were tested in an unattended situation as the subjects were watching a silent film. After the measurement the subjects practiced the phonemes at home for approximately one week by playing a learning game by computer. After training they were measured again. Structural magnetic resonance images of the subjects’ brain were also measured for MEG source localization purposes. Behavioral discrimination ability of the experimental phonemes was considerably worse than with familiar control phonemes. The discrimination skills seemed to improve by training, but the difference was not statistically significant. Contrary to the hypotheses, statistically significant MMNm responses were not found before or after training. No significant differences were found in other auditory MEG responses or their neural source current distributions between the measurements either. However, individual differences in learning were sizeable. For the subjects who improved their performance in the behavioral task a modest training-related boost in the auditory responses supporting the hypotheses could be observed. Although very small and statistically insignificant, the effect was opposite for control stimuli and did not exist in the non-learner group suggesting some sort of change in neural processing in the learner group. This study was not able to replicate the findings from various previous studies on phoneme acquisition in adulthood. Although it is likely that certain methodological limitations (e.g. small number of stimulus repetitions, challenging stimuli) affected the significance of the results, based on this study the generalizability of some of the previous findings can be called into question

It’s All About Context: Investigating the Effects of Consonant and Vowel Environment on Vowel-Evoked Envelope Following Responses

The envelope following response (EFR) has proven useful for studying brainstem speech processing. Previous work, however, demonstrates that its amplitude varies across stimuli. This thesis investigates whether this variation is attributable to the consonant or vowel context of the stimulus, or some interaction of the two. Experiment 1 evoked EFRs in 30 participants using seven English vowels embedded in four CVC environments. A strong effect of vowel and a minor effect of consonant on EFR amplitude were found. In Experiment 2, 64 listeners heard four different tokens of one of four possible English vowels (16 participants/vowel), embedded in the same CVC environments as before. A significant three-way interaction between vowel, vowel trial, and consonant was found, indicating that the EFR is highly sensitive to subtle acoustic differences in stimuli. To effectively utilize the EFR in research, future studies should carefully explore the mechanisms driving these complex context effects

Methodological and clinical aspects of ictal and interictal MEG

During the last years magnetoencephalography (MEG), has become an important part of the pre-surgical epilepsy workup. Interictal activity is usually recorded. Nevertheless, the technological advances now enable ictal MEG recordings as well. The records of 26 pharmaco-resistant focal epilepsy patients, who underwent ictal MEG and epilepsy surgery, were reviewed. In 12 patients prediction of ictal onset zone (IOZ) localization by ictal and interictal MEG was compared with ictal intracranial EEG (icEEG). On the lobar surface level the sensitivity of ictal MEG in IOZ location was 0.71 and the specificity 0.73. The sensitivity of the interictal MEG was 0.40 and specificity 0.77. The records of 34 operated epilepsy patients with focal cortical dysplasia (FCD) were retrospectively evaluated. The resected proportion of the source cluster related to interictal MEG was evaluated in respect to postoperative seizure outcome. 17 out of 34 patients with FCD (50%) achieved seizure freedom. The seizure outcome was similar in patients with MR-invisible and MR-visible FCD. With MEG source clusters and favorable seizure outcome (Engel class I and II) the proportion of the cluster volume resection was 49% - significantly higher (p=0.02) than with MEG clusters but unfavorable outcome (5.5% of cluster volume resection). Median nerve somatosensory evoked MEG responses were processed by movement compensation based on signal space separation (MC-SSS) and on spatio-temporal signal space separation (MC-tSSS). MEG was recorded in standard and deviant head positions. With up to 5 cm head displacement, MC-SSS decreased the mean localization error from 3.97 to 2.13 cm, but increased noise of planar gradiometers from 3.4 to 5.3 fT/cm. MC-tSSS reduced noise from 3.4 to 2.8 fT/cm and reduced the mean localization error from 3.91 to 0.89 cm. The MEG data containing speech-related artifacts and data containing alpha rhythm were processed by tSSS with different correlation limits. The speech artifact was progressively suppressed with the decreasing tSSS correlation limit. The optimal artifact suppression was achieved at correlation of 0.8. The randomly distributed source current (RDCS), and auditory and somatosensory evoked fields (AEFs and SEFs) were simulated. The information was calculated employing Shannon's theory of communication for a standard 306-sensor MEG device and for a virtual MEG helmet (VMH), which was constructed based on simulated MEG measurements in different head positions. With the simulation of 360 recorded events using RDCS model the maximum Shannon's number was 989 for single head position in standard MEG array and 1272 in VMH (28.6% additional information). With AEFs the additional contribution of VMH was 12.6% and with SEFs only 1.1%. To conclude, ictal MEG predicts IOZ location with higher sensitivity than interictal MEG. Resection of larger proportion of the MEG source cluster in patients with FCD is associated with a better seizure outcome, however, complete resection of MEG source cluster is often not required for achievement of favorable seizure outcome. The seizure outcome is similar in patients having MR-positive and MR-negative FCD. MC-tSSS decreases the source localization error to less than 1 cm, when the head is displaced up to 5 cm; however, it is reasonable to limit use of movement compensation for no more than 3-cm head displacement to keep the head inside sensor helmet. The optimization of the tSSS correlation limit to about 0.8 can improve the artifact suppression in MEG without substantial change of brain signals. MEG recording of the same brain activity in different head positions with subsequent construction of VMH can improve the information content of the data.Magnetoenkefalografia (MEG) on menetelmä, jolla mitataan aivojen tuottamia heikkoja magneettikenttiä. Yksi menetelmän tärkeimmistä kliinisistä käyttö-tarkoituksista on paikantaa epilepsiapesäkkeitä aivoissa. Tämä on tärkeää epilepsiakirurgian suunnittelussa. Potilaan liikkeet mittauksen aikana ovat aiheuttaneet epätarkkuutta pesäkkeiden paikannukseen ja häiriösignaaleja mittauksiin. Ongelma on ollut erityisen korostunut lasten mittauksissa ja epileptisten kohtausten rekisteröinneissä. Useimmissa potilaissa MEG-paikannus onkin perustunut kohtausten välisten epileptiformisten aivosähköilmiöiden paikannukseen. Pitkät MEG-rekisteröinnit ovat myös olleet haastavia koska yhteistyökykyisten potilaidenkin on vaikea olla liikkumatta pitkiä aikoja. Viime vuosien tekninen kehitys on mahdollistanut MEG-mittaukset myös pään liikkeiden aikana. Myös aivosignaalien ja kehossa olevien magneettisten materiaalien (esim hammaspaikat, sydämen tahdistimet tai aivostimulaattorit) aiheuttamien magneettisten häiriöiden erottaminen on nykyisin toteutettavissa. Tämä kehitys on mahdollistanut MEG-mittaukset potilailla, joilla aiemmin ei ollut mahdollisuutta hyötyä MEG-paikannuksista ja myös MEG-mittaukset epileptisten kohtausten aikana. Tärkeä osa väitöskirjaa on epilepsiakohtausten aikaisten MEG-mittausten kliinisen hyödyn arviointi. Tulokset osoittavat, että kohtauksenaikaiset MEG-mittaukset paikantavat herkemmin epilepsiakohtauksen lähdealueen aivoissa kuin kohtausten välisten epilepsiailmiöiden lähdepaikannus. Lähdealueiden paikannus on yhtä tarkka sekä aivokuoren pinnalla että 4 cm syvyydessä aivouurteissa. Pää ei kuitenkaan saisi liikkua 3 cm enempää MEG-mittauksen aikana, ja menetelmän herkkyys paranee oilennaisesti magneettikenttien matemaattiseen mallinnukseen perustuvalla magneettisten liikehäiriöiden poistolla. Väitöskirja tutkii lisäksi aivokuoren rakennemuutosten (paikallinen aivokuoridysplasia) aiheuttaman epilepsian kohtausten välisiä MEG-mittauksia. Päinvastoin kuin aiemmin on väitetty, ei aina ole tarpeen poistaa koko epileptisia lähdealueita sisältävää aivojen aluetta hyvän leikkaustuloksen saamiseksi. Väitöskirja esittelee myös laskennallisen MEG-anturiston määritysmenetelmän , joka lisää MEG-mittausten informaatiosisältöä huomioimalla pään liikkeet tulosten analyysissä

Frontal Functional Network Disruption Associated with Amyotrophic Lateral Sclerosis: An fNIRS-Based Minimum Spanning Tree Analysis

Recent evidence increasingly associates network disruption in brain organization with multiple neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), a rare terminal disease. However, the comparability of brain network characteristics across different studies remains a challenge for conventional graph theoretical methods. One suggested method to address this issue is minimum spanning tree (MST) analysis, which provides a less biased comparison. Here, we assessed the novel application of MST network analysis to hemodynamic responses recorded by functional near-infrared spectroscopy (fNIRS) neuroimaging modality, during an activity-based paradigm to investigate hypothetical disruptions in frontal functional brain network topology as a marker of the executive dysfunction, one of the most prevalent cognitive deficit reported across ALS studies. We analyzed data recorded from nine participants with ALS and ten age-matched healthy controls by first estimating functional connectivity, using phase-locking value (PLV) analysis, and then constructing the corresponding individual and group MSTs. Our results showed significant between-group differences in several MST topological properties, including leaf fraction, maximum degree, diameter, eccentricity, and degree divergence. We further observed a global shift toward more centralized frontal network organizations in the ALS group, interpreted as a more random or dysregulated network in this cohort. Moreover, the similarity analysis demonstrated marginally significantly increased overlap in the individual MSTs from the control group, implying a reference network with lower topological variation in the healthy cohort. Our nodal analysis characterized the main local hubs in healthy controls as distributed more evenly over the frontal cortex, with slightly higher occurrence in the left prefrontal cortex (PFC), while in the ALS group, the most frequent hubs were asymmetrical, observed primarily in the right prefrontal cortex. Furthermore, it was demonstrated that the global PLV (gPLV) synchronization metric is associated with disease progression, and a few topological properties, including leaf fraction and tree hierarchy, are linked to disease duration. These results suggest that dysregulation, centralization, and asymmetry of the hemodynamic-based frontal functional network during activity are potential neuro-topological markers of ALS pathogenesis. Our findings can possibly support new bedside assessments of the functional status of ALS’ brain network and could hypothetically extend to applications in other neurodegenerative diseases