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.

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.

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.

From cryogenic to on-scalp magnetoencephalography for the evaluation of paediatric epilepsy.

Magnetoencephalography (MEG) is a neurophysiological technique based on the detection of brain magnetic fields. Whole-head MEG systems typically house a few hundred sensors requiring cryogenic cooling in a rigid one-size-fits-all (commonly adult-sized) helmet to keep a thermal insulation space. This leads to an increased brain-to-sensor distance in children, because of their smaller head circumference, and decreased signal-to-noise ratio. MEG allows detection and localization of interictal and ictal epileptiform discharges, and pathological high frequency oscillations, as a part of the presurgical assessment of children with refractory focal epilepsy, where electroencephalography is not contributive. MEG can also map the eloquent cortex before surgical resection. MEG also provides insights into the physiopathology of both generalized and focal epilepsy. On-scalp recordings based on cryogenic-free sensors have demonstrated their use in the field of childhood focal epilepsy and should become a reference technique for diagnosing epilepsy in the paediatric population. WHAT THIS PAPER ADDS: Magnetoencephalography (MEG) contributes to the diagnosis and understanding of paediatric epilepsy. On-scalp MEG recordings demonstrate some advantages over cryogenic MEG.

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.

Speech-derived haptic stimulation enhances speech recognition in a multi-talker background.

Speech understanding, while effortless in quiet conditions, is challenging in noisy environments. Previous studies have revealed that a feasible approach to supplement speech-in-noise (SiN) perception consists in presenting speech-derived signals as haptic input. In the current study, we investigated whether the presentation of a vibrotactile signal derived from the speech temporal envelope can improve SiN intelligibility in a multi-talker background for untrained, normal-hearing listeners. We also determined if vibrotactile sensitivity, evaluated using vibrotactile detection thresholds, modulates the extent of audio-tactile SiN improvement. In practice, we measured participants' speech recognition in a multi-talker noise without (audio-only) and with (audio-tactile) concurrent vibrotactile stimulation delivered in three schemes: to the left or right palm, or to both. Averaged across the three stimulation delivery schemes, the vibrotactile stimulation led to a significant improvement of 0.41 dB in SiN recognition when compared to the audio-only condition. Notably, there were no significant differences observed between the improvements in these delivery schemes. In addition, audio-tactile SiN benefit was significantly predicted by participants' vibrotactile threshold levels and unimodal (audio-only) SiN performance. The extent of the improvement afforded by speech-envelope-derived vibrotactile stimulation was in line with previously uncovered vibrotactile enhancements of SiN perception in untrained listeners with no known hearing impairment. Overall, these results highlight the potential of concurrent vibrotactile stimulation to improve SiN recognition, especially in individuals with poor SiN perception abilities, and tentatively more so with increasing tactile sensitivity. Moreover, they lend support to the multimodal accounts of speech perception and research on tactile speech aid devices.

Anodal Cerebellar Transcranial Direct Current Stimulation Reduces Motor and Cognitive Symptoms in Friedreich's Ataxia: A Randomized, Sham-Controlled Trial.

BACKGROUND: Friedreich Ataxia is the most common recessive ataxia with only one therapeutic drug approved solely in the United States. OBJECTIVE: The aim of this work was to investigate whether anodal cerebellar transcranial direct current stimulation (ctDCS) reduces ataxic and cognitive symptoms in individuals with Friedreich's ataxia (FRDA) and to assess the effects of ctDCS on the activity of the secondary somatosensory (SII) cortex. METHODS: We performed a single-blind, randomized, sham-controlled, crossover trial with anodal ctDCS (5 days/week for 1 week, 20 min/day, density current: 0.057 mA/cm2 ) in 24 patients with FRDA. Each patient underwent a clinical evaluation (Scale for the Assessment and Rating of Ataxia, composite cerebellar functional severity score, cerebellar cognitive affective syndrome scale) before and after anodal and sham ctDCS. Activity of the SII cortex contralateral to a tactile oddball stimulation of the right index finger was evaluated with brain functional magnetic resonance imaging at baseline and after anodal/sham ctDCS. RESULTS: Anodal ctDCS led to a significant improvement in the Scale for the Assessment and Rating of Ataxia (-6.5%) and in the cerebellar cognitive affective syndrome scale (+11%) compared with sham ctDCS. It also led to a significant reduction in functional magnetic resonance imaging signal at the SII cortex contralateral to tactile stimulation (-26%) compared with sham ctDCS. CONCLUSIONS: One week of treatment with anodal ctDCS reduces motor and cognitive symptoms in individuals with FRDA, likely by restoring the neocortical inhibition normally exerted by cerebellar structures. This study provides class I evidence that ctDCS stimulation is effective and safe in FRDA. © 2023 International Parkinson and Movement Disorder Society.

Diagnostic and therapeutic approaches in refractory insular epilepsy.

Due to heterogenous seizure semiology and poor contribution of scalp electroencephalography (EEG) signals, insular epilepsy requires use of the appropriate diagnostic tools for its diagnosis and characterization. The deep location of the insula also presents surgical challenges. The aim of this article is to review the current diagnostic and therapeutic tools and their contribution to the management of insular epilepsy. Magnetic resonance imaging (MRI), isotopic imaging, neurophysiological imaging, and genetic testing should be used and interpretated with caution. Isotopic imaging and scalp EEG have demonstrated a lower value in epilepsy from insular compared to temporal origin, which increases the interest of functional MRI and magnetoencephalography. Intracranial recording with stereo-electroencephalography (SEEG) is often required. The insular cortex, being highly connected and deeply located under highly functional areas, is difficult to reach, and its ablative surgery raises functional issues. Tailored resection based on SEEG or alternative curative treatments, such as radiofrequency thermocoagulation, laser interstitial thermal therapy, or stereotactic radiosurgery, have produced encouraging results. The management of insular epilepsy has benefited from major advances in the last years. Perspectives for diagnostic and therapeutic procedures will contribute to better management of this complex form of epilepsy.

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.

Atypical procedural learning skills in children with Developmental Coordination Disorder.

We investigated the procedural learning deficit hypothesis in Developmental Coordination Disorder (DCD) while controlling for global performance such as slower reaction times (RTs) and variability. Procedural (sequence) learning was assessed in 31 children with DCD and 31 age-matched typically developing (TD) children through a serial reaction time task (SRTT). Sequential and random trial conditions were intermixed within five training epochs. Two repeated measures ANOVAs were conducted on a Sequence-Specific Learning Index (SSLI) and a Global Performance Index (GPI, speed/accuracy measure) with Epoch (for SSLI and GPI) and Condition (for GPI) as within-subjects factors, and Group as between-subjects factor. Controlling for RTs differences through normalized RTs, revealed a global reduction of SSLI in children with DCD compared with TD peers suggesting reduced sequence learning skills in DCD. Still, a significant Group x Condition interaction observed on GPI indicated that children from both groups were able to discriminate between sequential and random trials. DCD presented reduced procedural learning skills after controlling for global performance. This finding highlights the importance of considering the general functioning of the child while assessing learning skills in patients.

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.