Spectrotemporal cortical dynamics and semantic control during sentence completion.

OBJECTIVE: To investigate cortical oscillations during a sentence completion task (SC) using magnetoencephalography (MEG), focusing on the semantic control network (SCN), its leftward asymmetry, and the effects of semantic control load. METHODS: Twenty right-handed adults underwent MEG while performing SC, consisting of low cloze (LC: multiple responses) and high cloze (HC: single response) stimuli. Spectrotemporal power modulations as event-related synchronizations (ERS) and desynchronizations (ERD) were analyzed: first, at the whole-brain level; second, in key SCN regions, posterior middle/inferior temporal gyri (pMTG/ITG) and inferior frontal gyri (IFG), under different semantic control loads. RESULTS: Three cortical response patterns emerged: early (0-200 ms) theta-band occipital ERS; intermediate (200-700 ms) semantic network alpha/beta-band ERD; late (700-3000 ms) dorsal language stream alpha/beta/gamma-band ERD. Under high semantic control load (LC), pMTG/ITG showed prolonged left-sided engagement (ERD) and right-sided inhibition (ERS). Left IFG exhibited heightened late (2500-2550 ms) beta-band ERD with increased semantic control load (LC vs. HC). CONCLUSIONS: SC involves distinct cortical responses and depends on the left IFG and asymmetric engagement of the pMTG/ITG for semantic control. SIGNIFICANCE: Future use of SC in neuromagnetic preoperative language mapping and for understanding the pathophysiology of language disorders in neurological conditions.

A Novel, Robust, and Portable Platform for Magnetoencephalography using Optically Pumped Magnetometers.

Magnetoencephalography (MEG) measures brain function via assessment of magnetic fields generated by neural currents. Conventional MEG uses superconducting sensors, which place significant limitations on performance, practicality, and deployment; however, the field has been revolutionised in recent years by the introduction of optically-pumped-magnetometers (OPMs). OPMs enable measurement of the MEG signal without cryogenics, and consequently the conception of 'OPM-MEG' systems which ostensibly allow increased sensitivity and resolution, lifespan compliance, free subject movement, and lower cost. However, OPM-MEG remains in its infancy with limitations on both sensor and system design. Here, we report a new OPM-MEG design with miniaturised and integrated electronic control, a high level of portability, and improved sensor dynamic range (arguably the biggest limitation of existing instrumentation). We show that this system produces equivalent measures when compared to an established instrument; specifically, when measuring task-induced beta-band, gamma-band and evoked neuro-electrical responses, source localisations from the two systems were highly comparable and temporal correlation was >0.7 at the individual level and >0.9 for groups. Using an electromagnetic phantom, we demonstrate improved dynamic range by running the system in background fields up to 8 nT. We show that the system is effective in gathering data during free movement (including a sitting-to-standing paradigm) and that it is compatible with simultaneous electroencephalography (EEG - the clinical standard). Finally, we demonstrate portability by moving the system between two laboratories. Overall, our new system is shown to be a significant step forward for OPM-MEG technology and offers an attractive platform for next generation functional medical imaging.

Motor learning- and consolidation-related resting state fast and slow brain dynamics across wake and sleep.

Motor skills dynamically evolve during practice and after training. Using magnetoencephalography, we investigated the neural dynamics underpinning motor learning and its consolidation in relation to sleep during resting-state periods after the end of learning (boost window, within 30 min) and at delayed time scales (silent 4 h and next day 24 h windows) with intermediate daytime sleep or wakefulness. Resting-state neural dynamics were investigated at fast (sub-second) and slower (supra-second) timescales using Hidden Markov modelling (HMM) and functional connectivity (FC), respectively, and their relationship to motor performance. HMM results show that fast dynamic activities in a Temporal/Sensorimotor state network predict individual motor performance, suggesting a trait-like association between rapidly recurrent neural patterns and motor behaviour. Short, post-training task re-exposure modulated neural network characteristics during the boost but not the silent window. Re-exposure-related induction effects were observed on the next day, to a lesser extent than during the boost window. Daytime naps did not modulate memory consolidation at the behavioural and neural levels. These results emphasise the critical role of the transient boost window in motor learning and memory consolidation and provide further insights into the relationship between the multiscale neural dynamics of brain networks, motor learning, and consolidation.

Delayed effective connectivity characterizes the epileptogenic zone during stereo-EEG.

OBJECTIVE: Single-pulse electrical stimulations (SPES) can elicit normal and abnormal responses that might characterize the epileptogenic zone, including spikes, high-frequency oscillations and cortico-cortical evoked potentials (CCEPs). In this study, we investigate their association with the epileptogenic zone during stereoelectroencephalography (SEEG) in 28 patients with refractory focal epilepsy. METHODS: Characteristics of CCEPs (distance-corrected or -uncorrected latency, amplitude and the connectivity index) and the occurrence of spikes and ripples were assessed. Responses within the epileptogenic zone and within the non-involved zone were compared using receiver operating characteristics curves and analysis of variance (ANOVA) either in all patients, patients with well-delineated epileptogenic zone, and patients older than 15 years old. RESULTS: We found an increase in distance-corrected CCEPs latency after stimulation within the epileptogenic zone (area under the curve = 0.71, 0.72, 0.70, ANOVA significant after false discovery rate correction). CONCLUSIONS: The increased distance-corrected CCEPs latency suggests that neuronal propagation velocity is altered within the epileptogenic network. This association might reflect effective connectivity changes at cortico-cortical or cortico-subcortico-cortical levels. Other responses were not associated with the epileptogenic zone, including the CCEPs amplitude, the connectivity index, the occurrences of induced ripples and spikes. The discrepancy with previous descriptions may be explained by different spatial brain sampling between subdural and depth electrodes. SIGNIFICANCE: Increased distance-corrected CCEPs latency, indicating delayed effective connectivity, characterizes the epileptogenic zone. This marker could be used to help tailor surgical resection limits after SEEG.

Subclinical epileptiform activity in the Alzheimer continuum: association with disease, cognition and detection method.

BACKGROUND: Epileptic seizures are an established comorbidity of Alzheimer's disease (AD). Subclinical epileptiform activity (SEA) as detected by 24-h electroencephalography (EEG) or magneto-encephalography (MEG) has been reported in temporal regions of clinically diagnosed AD patients. Although epileptic activity in AD probably arises in the mesial temporal lobe, electrical activity within this region might not propagate to EEG scalp electrodes and could remain undetected by standard EEG. However, SEA might lead to faster cognitive decline in AD. AIMS: 1. To estimate the prevalence of SEA and interictal epileptic discharges (IEDs) in a well-defined cohort of participants belonging to the AD continuum, including preclinical AD subjects, as compared with cognitively healthy controls. 2. To evaluate whether long-term-EEG (LTM-EEG), high-density-EEG (hd-EEG) or MEG is superior to detect SEA in AD. 3. To characterise AD patients with SEA based on clinical, neuropsychological and neuroimaging parameters. METHODS: Subjects (n = 49) belonging to the AD continuum were diagnosed according to the 2011 NIA-AA research criteria, with a high likelihood of underlying AD pathophysiology. Healthy volunteers (n = 24) scored normal on neuropsychological testing and were amyloid negative. None of the participants experienced a seizure before. Subjects underwent LTM-EEG and/or 50-min MEG and/or 50-min hd-EEG to detect IEDs. RESULTS: We found an increased prevalence of SEA in AD subjects (31%) as compared to controls (8%) (p = 0.041; Fisher's exact test), with increasing prevalence over the disease course (50% in dementia, 27% in MCI and 25% in preclinical AD). Although MEG (25%) did not withhold a higher prevalence of SEA in AD as compared to LTM-EEG (19%) and hd-EEG (19%), MEG was significantly superior to detect spikes per 50 min (p = 0.002; Kruskall-Wallis test). AD patients with SEA scored worse on the RBANS visuospatial and attention subset (p = 0.009 and p = 0.05, respectively; Mann-Whitney U test) and had higher left frontal, (left) temporal and (left and right) entorhinal cortex volumes than those without. CONCLUSION: We confirmed that SEA is increased in the AD continuum as compared to controls, with increasing prevalence with AD disease stage. In AD patients, SEA is associated with more severe visuospatial and attention deficits and with increased left frontal, (left) temporal and entorhinal cortex volumes. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04131491. 12/02/2020.

Functional connectivity of sensorimotor network is enhanced in spastic diplegic cerebral palsy: A multimodal study using fMRI and MEG.

OBJECTIVE: To assess the effects to functional connectivity (FC) caused by lesions related to spastic diplegic cerebral palsy (CP) in children and adolescents using multiple imaging modalities. METHODS: We used resting state magnetoencephalography (MEG) envelope signals in alpha, beta and gamma ranges and resting state functional magnetic resonance imaging (fMRI) signals to quantify FC between selected sensorimotor regions of interest (ROIs) in 11 adolescents with spastic diplegic cerebral palsy and 24 typically developing controls. Motor performance of the hands was quantified with gross motor, fine motor and kinesthesia tests. RESULTS: In fMRI, participants with CP showed enhanced FC within posterior parietal regions; in MEG, they showed enhanced interhemispheric FC between sensorimotor regions and posterior parietal regions both in alpha and lower beta bands. There was a correlation between the kinesthesia score and fronto-parietal connectivity in the control population. CONCLUSIONS: CP is associated with enhanced FC in sensorimotor network. This difference is not correlated with hand coordination performance. The effect of the lesion is likely not fully captured by temporal correlation of ROI signals. SIGNIFICANCE: Brain lesions can show as increased temporal correlation of activity between remote brain areas. We suggest this effect is likely separate from typical physiological correlates of functional connectivity.

Towards the automated detection of interictal epileptiform discharges with magnetoencephalography.

BACKGROUND: The analysis of clinical magnetoencephalography (MEG) in patients with epilepsy traditionally relies on visual identification of interictal epileptiform discharges (IEDs), which is time consuming and dependent on subjective criteria. NEW METHOD: Here, we explore the ability of Independent Components Analysis (ICA) and Hidden Markov Modeling (HMM) to automatically detect and localize IEDs. We tested our pipelines on resting-state MEG recordings from 10 school-aged children with (multi)focal epilepsy. RESULTS: In focal epilepsy patients, both pipelines successfully detected visually identified IEDs, but also revealed unidentified low-amplitude IEDs. Success was more mitigated in patients with multifocal epilepsy, as our automated pipeline missed IED activity associated with some foci-an issue that could be alleviated by post-hoc manual selection of epileptiform ICs or HMM states. COMPARISON WITH EXISTING METHODS: We compared our results with visual IED detection by an experienced clinical magnetoencephalographer, getting heightened sensitivity and requiring minimal input from clinical practitioners. CONCLUSIONS: IED detection based on ICA or HMM represents an efficient way to identify IED localization and timing. The development of these automatic IED detection algorithms provide a step forward in clinical MEG practice by decreasing the duration of MEG analysis and enhancing its sensitivity.

Tri-axial rubidium and helium optically pumped magnetometers for on-scalp magnetoencephalography recording of interictal epileptiform discharges: a case study.

Cryogenic magnetoencephalography (MEG) enhances the presurgical assessment of refractory focal epilepsy (RFE). Optically pumped magnetometers (OPMs) are cryogen-free sensors that enable on-scalp MEG recordings. Here, we investigate the application of tri-axial OPMs [87Rb (Rb-OPM) and 4He gas (He-OPM)] for the detection of interictal epileptiform discharges (IEDs). IEDs were recorded simultaneously with 4 tri-axial Rb- and 4 tri-axial He-OPMs in a child with RFE. IEDs were identified visually, isolated from magnetic background noise using independent component analysis (ICA) and were studied following their optimal magnetic field orientation thanks to virtual sensors. Most IEDs (>1,000) were detectable by both He- and Rb-OPM recordings. IEDs were isolated by ICA and the resulting magnetic field oriented mostly tangential to the scalp in Rb-OPMs and radial in He-OPMs. Likely due to differences in sensor locations, the IED amplitude was higher with Rb-OPMs. This case study shows comparable ability of Rb-OPMs and He-OPMs to detect IEDs and the substantial benefits of triaxial OPMs to detect IEDs from different sensor locations. Tri-axial OPMs allow to maximize spatial brain sampling for IEDs detection with a limited number of sensors.

Functional identification of language-responsive channels in individual participants in MEG investigations.

Making meaningful inferences about the functional architecture of the language system requires the ability to refer to the same neural units across individuals and studies. Traditional brain imaging approaches align and average brains together in a common space. However, lateral frontal and temporal cortex, where the language system resides, is characterized by high structural and functional inter-individual variability. This variability reduces the sensitivity and functional resolution of group-averaging analyses. This problem is compounded by the fact that language areas often lay in close proximity to regions of other large-scale networks with different functional profiles. A solution inspired by other fields of cognitive neuroscience (e.g., vision) is to identify language areas functionally in each individual brain using a 'localizer' task (e.g., a language comprehension task). This approach has proven productive in fMRI, yielding a number of discoveries about the language system, and has been successfully extended to intracranial recording investigations. Here, we apply this approach to MEG. Across two experiments (one in Dutch speakers, n=19; one in English speakers, n=23), we examined neural responses to the processing of sentences and a control condition (nonword sequences). We demonstrated that the neural response to language is spatially consistent at the individual level. The language-responsive sensors of interest were, as expected, less responsive to the nonwords condition. Clear inter-individual differences were present in the topography of the neural response to language, leading to greater sensitivity when the data were analyzed at the individual level compared to the group level. Thus, as in fMRI, functional localization yields benefits in MEG and thus opens the door to probing fine-grained distinctions in space and time in future MEG investigations of language processing.

Exploring the limits of MEG spatial resolution with multipolar expansions.

The advent of scalp magnetoencephalography (MEG) based on optically pumped magnetometers (OPMs) may represent a step change in the field of human electrophysiology. Compared to cryogenic MEG based on superconducting quantum interference devices (SQUIDs, placed 2-4 cm above scalp), scalp MEG promises significantly higher spatial resolution imaging but it also comes with numerous challenges regarding how to optimally design OPM arrays. In this context, we sought to provide a systematic description of MEG spatial resolution as a function of the number of sensors (allowing comparison of low- vs. high-density MEG), sensor-to-brain distance (cryogenic SQUIDs vs. scalp OPM), sensor type (magnetometers vs. gradiometers; single- vs. multi-component sensors), and signal-to-noise ratio. To that aim, we present an analytical theory based on MEG multipolar expansions that enables, once supplemented with experimental input and simulations, quantitative assessment of the limits of MEG spatial resolution in terms of two qualitatively distinct regimes. In the regime of asymptotically high-density MEG, we provide a mathematically rigorous description of how magnetic field smoothness constraints spatial resolution to a slow, logarithmic divergence. In the opposite regime of low-density MEG, it is sensor density that constraints spatial resolution to a faster increase following a square-root law. The transition between these two regimes controls how MEG spatial resolution saturates as sensors approach sources of neural activity. This two-regime model of MEG spatial resolution integrates known observations (e.g., the difficulty of improving spatial resolution by increasing sensor density, the gain brought by moving sensors on scalp, or the usefulness of multi-component sensors) and gathers them under a unifying theoretical framework that highlights the underlying physics and reveals properties inaccessible to simulations. We propose that this framework may find useful applications to benchmark the design of future OPM-based scalp MEG systems.

Cortical tracking of lexical speech units in a multi-talker background is immature in school-aged children.

Children have more difficulty perceiving speech in noise than adults. Whether this difficulty relates to an immature processing of prosodic or linguistic elements of the attended speech is still unclear. To address the impact of noise on linguistic processing per se, we assessed how babble noise impacts the cortical tracking of intelligible speech devoid of prosody in school-aged children and adults. Twenty adults and twenty children (7-9 years) listened to synthesized French monosyllabic words presented at 2.5 Hz, either randomly or in 4-word hierarchical structures wherein 2 words formed a phrase at 1.25 Hz, and 2 phrases formed a sentence at 0.625 Hz, with or without babble noise. Neuromagnetic responses to words, phrases and sentences were identified and source-localized. Children and adults displayed significant cortical tracking of words in all conditions, and of phrases and sentences only when words formed meaningful sentences. In children compared with adults, the cortical tracking was lower for all linguistic units in conditions without noise. In the presence of noise, the cortical tracking was similarly reduced for sentence units in both groups, but remained stable for phrase units. Critically, when there was noise, adults increased the cortical tracking of monosyllabic words in the inferior frontal gyri and supratemporal auditory cortices but children did not. This study demonstrates that the difficulties of school-aged children in understanding speech in a multi-talker background might be partly due to an immature tracking of lexical but not supra-lexical linguistic units.

Neurodevelopmental oscillatory basis of speech processing in noise.

Humans' extraordinary ability to understand speech in noise relies on multiple processes that develop with age. Using magnetoencephalography (MEG), we characterize the underlying neuromaturational basis by quantifying how cortical oscillations in 144 participants (aged 5-27 years) track phrasal and syllabic structures in connected speech mixed with different types of noise. While the extraction of prosodic cues from clear speech was stable during development, its maintenance in a multi-talker background matured rapidly up to age 9 and was associated with speech comprehension. Furthermore, while the extraction of subtler information provided by syllables matured at age 9, its maintenance in noisy backgrounds progressively matured until adulthood. Altogether, these results highlight distinct behaviorally relevant maturational trajectories for the neuronal signatures of speech perception. In accordance with grain-size proposals, neuromaturational milestones are reached increasingly late for linguistic units of decreasing size, with further delays incurred by noise.

On-Scalp Optically Pumped Magnetometers versus Cryogenic Magnetoencephalography for Diagnostic Evaluation of Epilepsy in School-aged Children.

Background Magnetoencephalography (MEG) is an established method used to detect and localize focal interictal epileptiform discharges (IEDs). Current MEG systems house hundreds of cryogenic sensors in a rigid, one-size-fits-all helmet, which results in several limitations, particularly in children. Purpose To determine if on-scalp MEG based on optically pumped magnetometers (OPMs) alleviates the main limitations of cryogenic MEG. Materials and Methods In this prospective single-center study conducted in a tertiary university teaching hospital, participants underwent cryogenic (102 magnetometers, 204 planar gradiometers) and on-scalp (32 OPMs) MEG. The two modalities for the detection and localization of IEDs were compared. The t test was used to compare IED amplitude and signal-to-noise ratio (SNR). Distributed source modeling was performed on OPM-based and cryogenic MEG data. Results Five children (median age, 9.4 years [range, 5-11 years]; four girls) with self-limited idiopathic (n = 3) or refractory (n = 2) focal epilepsy were included. IEDs were identified in all five children with comparable sensor topographies for both MEG devices. IED amplitudes were 2.3 (7.2 of 3.1) to 4.6 (3.2 of 0.7) times higher (P < .001) with on-scalp MEG, and the SNR was 27% (16.7 of 13.2) to 60% (12.8 of 8.0) higher (P value range: .001-.009) with on-scalp MEG in all but one participant (P = .93), whose head movements created pronounced motion artifacts. The neural source of averaged IEDs was located at approximately 5 mm (n = 3) or higher (8.3 mm, n = 1; 15.6 mm, n = 1) between on-scalp and cryogenic MEG. Conclusion Despite the limited number of sensors and scalp coverage, on-scalp magnetoencephalography (MEG) based on optically pumped magnetometers helped detect interictal epileptiform discharges in school-aged children with epilepsy with a higher amplitude, higher signal-to-noise ratio, and similar localization value compared with conventional cryogenic MEG. Online supplemental material is available for this article. © RSNA, 2022 See also the editorial by Widjaja in this issue.

Resting state fast brain dynamics predict interindividual variability in motor performance.

Motor learning features rapid enhancement during practice then offline post-practice gains with the reorganization of related brain networks. We hypothesised that fast transient, sub-second variations in magnetoencephalographic (MEG) network activity during the resting-state (RS) reflect early learning-related plasticity mechanisms and/or interindividual motor variability in performance. MEG RS activity was recorded before and 20 min after motor learning. Hidden Markov modelling (HMM) of MEG power envelope signals highlighted 8 recurrent topographical states. For two states, motor performance levels were associated with HMM temporal parameters both in pre- and post-learning resting-state sessions. However, no association emerged with offline changes in performance. These results suggest a trait-like relationship between spontaneous transient neural dynamics at rest and interindividual variations in motor abilities. On the other hand, transient RS dynamics seem not to be state-dependent, i.e., modulated by learning experience and reflect neural plasticity, at least on the short timescale.

The role of reading experience in atypical cortical tracking of speech and speech-in-noise in dyslexia.

Dyslexia is a frequent developmental disorder in which reading acquisition is delayed and that is usually associated with difficulties understanding speech in noise. At the neuronal level, children with dyslexia were reported to display abnormal cortical tracking of speech (CTS) at phrasal rate. Here, we aimed to determine if abnormal tracking relates to reduced reading experience, and if it is modulated by the severity of dyslexia or the presence of acoustic noise. We included 26 school-age children with dyslexia, 26 age-matched controls and 26 reading-level matched controls. All were native French speakers. Children's brain activity was recorded with magnetoencephalography while they listened to continuous speech in noiseless and multiple noise conditions. CTS values were compared between groups, conditions and hemispheres, and also within groups, between children with mild and severe dyslexia. Syllabic CTS was significantly reduced in the right superior temporal gyrus in children with dyslexia compared with controls matched for age but not for reading level. Severe dyslexia was characterized by lower rapid automatized naming (RAN) abilities compared with mild dyslexia, and phrasal CTS lateralized to the right hemisphere in children with mild dyslexia and all control groups but not in children with severe dyslexia. Finally, an alteration in phrasal CTS was uncovered in children with dyslexia compared with age-matched controls in babble noise conditions but not in other less challenging listening conditions (non-speech noise or noiseless conditions); no such effect was seen in comparison with reading-level matched controls. Overall, our results confirmed the finding of altered neuronal basis of speech perception in noiseless and babble noise conditions in dyslexia compared with age-matched peers. However, the absence of alteration in comparison with reading-level matched controls demonstrates that such alterations are associated with reduced reading level, suggesting they are merely driven by reduced reading experience rather than a cause of dyslexia. Finally, our result of altered hemispheric lateralization of phrasal CTS in relation with altered RAN abilities in severe dyslexia is in line with a temporal sampling deficit of speech at phrasal rate in dyslexia.