Localized estimation of event-related neural source activity from simultaneous MEG-EEG with a recurrent neural network.

Estimating intracranial current sources underlying the electromagnetic signals observed from extracranial sensors is a perennial challenge in non-invasive neuroimaging. Established solutions to this inverse problem treat time samples independently without considering the temporal dynamics of event-related brain processes. This paper describes current source estimation from simultaneously recorded magneto- and electro-encephalography (MEEG) using a recurrent neural network (RNN) that learns sequential relationships from neural data. The RNN was trained in two phases: (1) pre-training and (2) transfer learning with L1 regularization applied to the source estimation layer. Performance of using scaled labels derived from MEEG, magnetoencephalography (MEG), or electroencephalography (EEG) were compared, as were results from volumetric source space with free dipole orientation and surface source space with fixed dipole orientation. Exact low-resolution electromagnetic tomography (eLORETA) and mixed-norm L1/L2 (MxNE) source estimation methods were also applied to these data for comparison with the RNN method. The RNN approach outperformed other methods in terms of output signal-to-noise ratio, correlation and mean-squared error metrics evaluated against reference event-related field (ERF) and event-related potential (ERP) waveforms. Using MEEG labels with fixed-orientation surface sources produced the most consistent estimates. To estimate sources of ERF and ERP waveforms, the RNN generates temporal dynamics within its internal computational units, driven by sequential structure in neural data used as training labels. It thus provides a data-driven model of computational transformations from psychophysiological events into corresponding event-related neural signals, which is unique among MEEG source reconstruction solutions.

Lightweight and wearable magnetoencephalography system based on spatially-grid constrained coils and compact magnetically shielded room.

Magnetoencephalography based on optically pumped magnetometers can passively detect the ultra-weak brain magnetic field signals, which has significant clinical application prospects for the diagnosis and treatment of cerebral disorders. This paper proposes a brain magnetic signal measurement method on the basis of the active-passive coupling magnetic shielding strategy and helmet-mounted detection array, which has lower cost and comparable performance over the existing ones. We first utilized the spatially-grid constrained coils and biplanar coils with proportion-integration-differentiation controller with tracking differentiator to ensure a near-zero and stable magnetic field environment with large uniform region. Subsequently, we implemented the brain magnetic signal measurement with the subject randomly moving fingers through tapping a keyboard and with the condition of opening and closing the eyes. Effectively induced brain magnetic signals were detected at the motor functional area and occipital lobe area in the two experiments, respectively. The proposed method will contribute to the development of functional brain imaging.

Frontotemporal lobar degeneration changes neuronal beta-frequency dynamics during the mismatch negativity response.

The consequences of frontotemporal lobar degeneration include changes in prefrontal cortical neurophysiology, with abnormalities of neural dynamics reported in the beta frequency range (14-30 Hz) that correlate with functional severity. We examined beta dynamics in two clinical syndromes associated with frontotemporal lobar degeneration: the behavioral variant of frontotemporal dementia (bvFTD) and progressive supranuclear palsy (PSP). Whilst these two syndromes are partially convergent in cognitive effects, they differ in disease mechanisms such as molecular pathologies and prefrontal atrophy. Whether bvFTD and PSP also differ in neurophysiology remains to be fully investigated. We compared magnetoencephalography from 20 controls, 23 people with bvFTD and 21 people with PSP (Richardson's syndrome) during an auditory roving oddball paradigm. We measured changes in low and high total beta power responses (14-22 and 22-30 Hz respectively) over frontotemporal cortex in the period of the mismatch negativity response (100-250 ms post-stimulus). In controls, we found increased 14-22 Hz beta power following unexpected sensory events (i.e. increased deviant versus standard response), from right prefrontal cortex. Relative to controls, PSP reversed the mismatch response in this time-frequency window, reflecting reduced responses to the deviant stimuli (relative to standard stimuli). Abnormal beta at baseline in PSP could account for the reduced task-modulation of beta. Across bvFTD and PSP groups, the beta response to deviant stimuli (relative to standard stimuli) correlated with clinical severity, but not with atrophy of the prefrontal source region. These findings confirm the proposed importance of higher-order cortical regions, and their beta-power generators, in sensory change detection and context-updating during oddball paradigms. The physiological effects are proposed to result from changes in synaptic density, cortical neurotransmitters and subcortical connections, rather than merely atrophy. Beta-power changes may assist clinical stratification and provide intermediate outcomes for experimental medicine studies of novel therapeutic strategies.

Reliable measurement of auditory-driven gamma synchrony with a single EEG electrode: a simultaneous EEG-MEG study.

OBJECTIVE: Auditory-driven gamma synchrony (GS) is linked to the function of a specific cortical circuit based on a parvalbumin+ and pyramidal neuron loop. This loop is impaired in neuropsychiatric conditions (i.e. schizophrenia, Alzheimer's disease, stroke etc.) and its relevance in clinical practice is increasingly being recognized. Auditory stimulation at a typical gamma frequency of 40Hz can be applied as a 'stress test' for efficient excitation/inhibition (E/I) of the entire cerebral cortex to provoke GS and record it with magnetoencephalography (MEG) or high-density electroencephalography (EEG). However, these two techniques are costly and not widely available. Therefore, we assessed whether a single EEG electrode is sufficient to provide an accurate estimate of the auditory-driven GS level of the entire cortical surface while expecting the highest correspondence in the auditory and somatosensory cortices. METHODS: We measured simultaneous EEG-MEG in 29 healthy subjects, utilizing 3 EEG electrodes (C4, F4, O2) and a full MEG setup. Recordings were performed during binaural exposure to auditory gamma stimulation and during silence. We compared GS measurement of each of the three EEG electrodes separately against full MEG mapping. Time-resolved phase locking value (PLVt) was computed between EEG signals and cortex reconstructed MEG signals. RESULTS: During auditory stimulation, but not at rest, EEG captures a significant amount of GS, especially from both auditory cortices and motor-premotor regions. This was especially true for frontal (C4) and central electrodes (F4). DISCUSSION AND CONCLUSIONS: While hd-EEG and MEG are necessary for accurate spatial mapping of GS at rest and during auditory stimulation, a single EEG channel is sufficient to detect the global level of GS. These results have great translational potential for mapping GS in standard clinical settings.

Magnetic Detection of Neural Activity by Nanocoil Transducers.

Electrophysiological recordings from brain cells are performed routinely using implanted electrodes, but they traditionally require a wired connection to the outside of the brain. A completely passive, wireless device that does not require on-board power for active transmission but that still facilitates remote detection could open the door for mass-scale direct recording of action potentials and transform the way we acquire brain signals. We present a nanofabricated coil that forms a neuroelectromagnetic junction, yielding a highly enhanced magnetic field transduction of electrophysiology. We show that this micrometer-scale device enables remote magnetic detection of neuronal fields from the center of the coil using room temperature superconducting quantum interference device (SQUID) microscopy. Further, time-locked stimulation in conjunction with magnetometry demonstrates thresholding behavior that affirms the viability of the technology for detection with no requirement for wires or on-board power. This strategy may permit unprecedented detection of electrophysiology using magnetoencephalography and magnetic resonance imaging.

EMG-projected MEG high-resolution source imaging of human motor execution: Brain-muscle coupling above movement frequencies.

Magnetoencephalography (MEG) is a non-invasive functional imaging technique for pre-surgical mapping. However, movement-related MEG functional mapping of primary motor cortex (M1) has been challenging in presurgical patients with brain lesions and sensorimotor dysfunction due to the large numbers of trials needed to obtain adequate signal to noise. Moreover, it is not fully understood how effective the brain communication is with the muscles at frequencies above the movement frequency and its harmonics. We developed a novel Electromyography (EMG)-projected MEG source imaging technique for localizing early-stage (-100 to 0 ms) M1 activity during ~l min recordings of left and right self-paced finger movements (~1 Hz). High-resolution MEG source images were obtained by projecting M1 activity towards the skin EMG signal without trial averaging. We studied delta (1-4 Hz), theta (4-7 Hz), alpha (8-12 Hz), beta (15-30 Hz), gamma (30-90 Hz), and upper-gamma (60-90 Hz) bands in 13 healthy participants (26 datasets) and three presurgical patients with sensorimotor dysfunction. In healthy participants, EMG-projected MEG accurately localized M1 with high accuracy in delta (100.0%), theta (100.0%), and beta (76.9%) bands, but not alpha (34.6%) or gamma/upper-gamma (0.0%) bands. Except for delta, all other frequency bands were above the movement frequency and its harmonics. In three presurgical patients, M1 activity in the affected hemisphere was also accurately localized, despite highly irregular EMG movement patterns in one patient. Altogether, our EMG-projected MEG imaging approach is highly accurate and feasible for M1 mapping in presurgical patients. The results also provide insight into movement-related brain-muscle coupling above the movement frequency and its harmonics.

Aberrant high-beta band functional connectivity during reward processing in melancholic major depressive disorder: An MEG study.

OBJECTIVE: To identify the spatial-temporal pattern variation of whole-brain functional connectivity (FC) during reward processing in melancholic major depressive disorder (MDD) patients, and to determine the clinical correlates of connectomic differences. METHODS: 61 MDD patients and 32 healthy controls were enrolled into the study. During magnetoencephalography (MEG) scanning, all participants completed the facial emotion recognition task. The MDD patients were further divided into two groups: melancholic (n = 31) and non-melancholic (n = 30), based on the Mini International Neuropsychiatric Interview (M.I.N.I.) assessment. Melancholic symptoms were examined by using the 6-item melancholia subscale from the Hamilton Depression Rating Scale (HAM-D6). The whole-brain orthogonalized power envelope connections in the high-beta band (20-35 Hz) were constructed in each period after the happy emotional stimuli (0-200 ms, 100-300 ms, 200-400 ms, 300-500 ms, and 400-600 ms). Then, the network-based statistic (NBS) was used to determine the specific abnormal connection patterns in melancholic MDD patients. RESULTS: The NBS identified a sub-network difference at the mid-late period (300-500 ms) in response to happy faces among the three groups (corrected P = 0.035). Then, the post hoc and correlation analyses found five FCs were decreased in melancholic MDD patients and were related to HAM-D6 score, including FCs of left fusiform gyrus-right orbital inferior frontal gyrus (r = -0.52, P < 0.001), left fusiform gyrus-left amygdala (r = -0.26, P = 0.049), left posterior cingulate gyrus-right precuneus (r = -0.32, P = 0.025), left precuneus-right precuneus (r = -0.27, P = 0.049), and left precuneus-left inferior occipital gyrus (r = -0.32, P = 0.025). CONCLUSION: In response to happy faces, melancholic MDD patients demonstrated a disrupted functional connective pattern (20-35 Hz, 300-500 ms), which involved brain regions in visual information processing and the limbic system. The aberrant functional connective pattern in reward processing might be a biomarker of melancholic MDD.

Resting-state functional connectivity involved in tactile orientation processing.

BACKGROUND: Grating orientation discrimination (GOD) is commonly used to assess somatosensory spatial processing. It allows discrimination between parallel and orthogonal orientations of tactile stimuli applied to the fingertip. Despite its widespread application, the underlying mechanisms of GOD, particularly the role of cortico-cortical interactions and local brain activity in this process, remain elusive. Therefore, we aimed to investigate how a specific cortico-cortical network and inhibitory circuits within the primary somatosensory cortex (S1) and secondary somatosensory cortex (S2) contribute to GOD. METHODS: In total, 51 healthy young adults were included in our study. We recorded resting-state magnetoencephalography (MEG) and somatosensory-evoked magnetic field (SEF) in participants with open eyes. We converted the data into a source space based on individual structural magnetic resonance imaging. Next, we estimated S1- and S2-seed resting-state functional connectivity (rs-FC) at the alpha and beta bands through resting-state MEG using the amplitude envelope correlation method across the entire brain (i.e., S1/S2-seeds × 15,000 vertices × two frequencies). We assessed the inhibitory response in the S1 and S2 from SEFs using a paired-pulse paradigm. We automatically measured the GOD task in parallel and orthogonal orientations to the index finger, applying various groove widths with a custom-made device. RESULTS: We observed a specific association between the GOD threshold (all P < 0.048) and the alpha rs-FC in the S1-superior parietal lobule and S1-adjacent to the parieto-occipital sulcus (i.e., lower rs-FC values corresponded to higher performance). In contrast, no association was observed between the local responses and the threshold. DISCUSSION: The results of this study underpin the significance of specific cortico-cortical networks in recognizing variations in tactile stimuli.

Semi-analytic three-shell forward calculation for magnetoencephalography.

In previous studies, the magnetic lead field theorem in the quasi-static approximation was derived and used for the development of a method for the forward problem of MEG. It was applied and tested on a single-shell model of the human head and the question whether one shell is adequate enough for the calculation of the magnetic field is the main reason for this study. This forward method is based on the fundamental concept that one can calculate the lead field for MEG by decomposing it into two parts: the lead field of an arbitrary volume conductor that is already known and the gradient of basis functions that have to be harmonic, here derived from spherical harmonics. The problem then is reduced to evaluating the coefficients found in the basis functions. In this research we aim to improve the accuracy of the forward model, hence improving the localization accuracy in inverse methods by introducing a more detailed realistic head model. We here generalize the algorithm developed for a single-shell volume conductor to a three-shell volume conductor representing the brain, the skull and the skin with homogenous and isotropic conductivities in realistic ratios. The expansion to three shells could be tested as the three-shell algorithm is approaching the single-shell with high accuracy in special cases where three-shell solutions can also be calculated using a single-shell solution, especially for higher levels of expansion. The deviation in the calculation of the lead field is also evaluated when using three shells with realistic conductivities. The magnetic field turned out to differ to an important measurable extend in particular for deeper sources, making the three-shell algorithm substantially more accurate for these dipole locations.

Language experience shapes predictive coding of rhythmic sound sequences.

Perceptual systems heavily rely on prior knowledge and predictions to make sense of the environment. Predictions can originate from multiple sources of information, including contextual short-term priors, based on isolated temporal situations, and context-independent long-term priors, arising from extended exposure to statistical regularities. While the effects of short-term predictions on auditory perception have been well-documented, how long-term predictions shape early auditory processing is poorly understood. To address this, we recorded magnetoencephalography data from native speakers of two languages with different word orders (Spanish: functor-initial vs Basque: functor-final) listening to simple sequences of binary sounds alternating in duration with occasional omissions. We hypothesized that, together with contextual transition probabilities, the auditory system uses the characteristic prosodic cues (duration) associated with the native language's word order as an internal model to generate long-term predictions about incoming non-linguistic sounds. Consistent with our hypothesis, we found that the amplitude of the mismatch negativity elicited by sound omissions varied orthogonally depending on the speaker's linguistic background and was most pronounced in the left auditory cortex. Importantly, listening to binary sounds alternating in pitch instead of duration did not yield group differences, confirming that the above results were driven by the hypothesized long-term 'duration' prior. These findings show that experience with a given language can shape a fundamental aspect of human perception - the neural processing of rhythmic sounds - and provides direct evidence for a long-term predictive coding system in the auditory cortex that uses auditory schemes learned over a lifetime to process incoming sound sequences.

Associations between neuromelanin depletion and cortical rhythmic activity in Parkinson's disease.

Parkinson's disease (PD) is marked by the death of neuromelanin-rich dopaminergic and noradrenergic cells in the substantia nigra (SN) and the locus coeruleus (LC), respectively, resulting in motor and cognitive impairments. While SN dopamine dysfunction has clear neurophysiological effects, the association of reduced LC norepinephrine signaling with brain activity in PD remains to be established. We used neuromelanin-sensitive T1-weighted MRI (NPD = 58; NHC = 27) and task-free magnetoencephalography (NPD = 58; NHC = 65) to identify neuropathophysiological factors related to the degeneration of the LC and SN in patients with PD. We found pathological increases in rhythmic alpha (8-12 Hz) activity in patients with decreased LC neuromelanin, with a stronger association in patients with worse attentional impairments. This negative alpha-LC neuromelanin relationship is strongest in fronto-motor cortices, where alpha activity is inversely related to attention scores. Using neurochemical colocalization analyses with normative atlases of neurotransmitter transporters, we also show that this effect is more pronounced in regions with high densities of norepinephrine transporters. These observations support a noradrenergic association between LC integrity and alpha band activity. Our data also show that rhythmic beta (15-29 Hz) activity in the left somato-motor cortex decreases with lower levels of SN neuromelanin; the same regions where beta activity reflects axial motor symptoms. Together, our findings clarify the association of well-documented alterations of rhythmic neurophysiology in PD with cortical and subcortical neurochemical systems. Specifically, attention-related alpha activity is related to dysfunction of the noradrenergic system, and beta activity with relevance to motor impairments reflects dopaminergic dysfunction.

Association between resting-state neurovascular coupling and neural signals as revealed by a combined fMRI and magnetoencephalography (MEG) study in humans.

The Blood Oxygenation Level-Dependent (BOLD) activation reflects hemodynamic events mediated by neurovascular coupling. During task performance, the BOLD hemodynamic response in a relevant area is mainly driven by the high levels of synaptic activity (reflected in local field potentials, LFP) but, in contrast, during a task-free, resting state, the contribution to BOLD of such neural events is small, as expected by the comparatively (to the task state) low level of neural events. Concomitant recording of BOLD and LFP at rest in animal experiments has estimated the neural contribution to BOLD to ~10%. Such experiments have not been performed in humans. As an approximation, we recorded (in the same subject, N = 57 healthy participants) at a task-free, resting state the BOLD signal and, in a different session, the magnetoencephalographic (MEG) signal, which reflects purely neural (synaptic) events. We then calculated the turnover of these signals by computing the successive moment-to-moment difference in the BOLD and MEG time series and retaining the median of the absolute value of the differenced series (TBOLD and TMEG, respectively). A linear regression of normalized TBOLD vs. TMEG revealed that ~30% of TMEG contributes to TBOLD, accounting for 11.3% of the latter's variance. This percentage estimate is close to the ~10% estimate above obtained by direct recordings in animal experiments.

Relationships between peak alpha frequency, age, and autistic traits in young children with and without autism spectrum disorder.

Background: Atypical peak alpha frequency (PAF) has been reported in children with autism spectrum disorder (ASD); however, the relationships between PAF, age, and autistic traits remain unclear. This study was conducted to investigate and compare the resting-state PAF of young children with ASD and their typically developing (TD) peers using magnetoencephalography (MEG). Methods: Nineteen children with ASD and 24 TD children, aged 5-7 years, underwent MEG under resting-state conditions. The PAFs in ten brain regions were calculated, and the associations between these findings, age, and autistic traits, measured using the Social Responsiveness Scale (SRS), were examined. Results: There were no significant differences in PAF between the children with ASD and the TD children. However, a unique positive association between age and PAF in the cingulate region was observed in the ASD group, suggesting the potential importance of the cingulate regions as a neurophysiological mechanism underlying distinct developmental trajectory of ASD. Furthermore, a higher PAF in the right temporal region was associated with higher SRS scores in TD children, highlighting the potential role of alpha oscillations in social information processing. Conclusions: This study emphasizes the importance of regional specificity and developmental factors when investigating neurophysiological markers of ASD. The distinct age-related PAF patterns in the cingulate regions of children with ASD and the association between right temporal PAF and autistic traits in TD children provide novel insights into the neurobiological underpinnings of ASD. These findings pave the way for future research on the functional implications of these neurophysiological patterns and their potential as biomarkers of ASD across the lifespan.

Minimum spanning tree analysis of unimpaired individuals at risk of Alzheimer's disease.

Identifying early and non-invasive biomarkers to detect individuals in the earliest stages of the Alzheimer's disease continuum is crucial. As a result, electrophysiology and plasma biomarkers are emerging as great candidates in this pursuit due to their low invasiveness. This is the first magnetoencephalography study to assess the relationship between minimum spanning tree parameters, an alternative to overcome the comparability and thresholding problem issues characteristic of conventional brain network analyses, and plasma phosphorylated tau231 levels in unimpaired individuals, with different risk levels of Alzheimer's disease. Seventy-six individuals with available magnetoencephalography recordings and phosphorylated tau231 plasma determination were included. The minimum spanning tree for the theta, alpha and beta bands for each subject was obtained, and the leaf fraction, tree hierarchy and diameter were calculated. To study the relationship between these topological parameters and phosphorylated tau231, we performed correlation analyses, for the whole sample and considering the two risk sub-groups separately. Increasing concentrations of phosphorylated tau231 were associated with greater leaf fraction and tree hierarchy values, along with lower diameter values, for the alpha and theta frequency bands. These results emerged for the whole sample and the higher risk group, but not for the lower risk group. Our results indicate that the network topology of cognitively unimpaired individuals with elevated plasma phosphorylated tau231 levels, a marker of Alzheimer's disease pathology and amyloid-ß accumulation, is already altered, shifting towards a more integrated network increasing its vulnerability and hub-dependency, mostly in the alpha band. This is indicated by increases in leaf fraction and tree hierarchy, along with reductions in diameter. These results match the initial trajectory proposed by theoretical models of disease progression and network disruption and suggest that changes in brain function and organization begin early on.

Comparison between EEG and MEG of static and dynamic resting-state networks.

The characterisation of resting-state networks (RSNs) using neuroimaging techniques has significantly contributed to our understanding of the organisation of brain activity. Prior work has demonstrated the electrophysiological basis of RSNs and their dynamic nature, revealing transient activations of brain networks with millisecond timescales. While previous research has confirmed the comparability of RSNs identified by electroencephalography (EEG) to those identified by magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI), most studies have utilised static analysis techniques, ignoring the dynamic nature of brain activity. Often, these studies use high-density EEG systems, which limit their applicability in clinical settings. Addressing these gaps, our research studies RSNs using medium-density EEG systems (61 sensors), comparing both static and dynamic brain network features to those obtained from a high-density MEG system (306 sensors). We assess the qualitative and quantitative comparability of EEG-derived RSNs to those from MEG, including their ability to capture age-related effects, and explore the reproducibility of dynamic RSNs within and across the modalities. Our findings suggest that both MEG and EEG offer comparable static and dynamic network descriptions, albeit with MEG offering some increased sensitivity and reproducibility. Such RSNs and their comparability across the two modalities remained consistent qualitatively but not quantitatively when the data were reconstructed without subject-specific structural MRI images.

Alpha oscillations during visual selective attention are aberrant in youth and adults with cerebral palsy.

Our understanding of the neurobiology underlying cognitive dysfunction in persons with cerebral palsy is very limited, especially in the neurocognitive domain of visual selective attention. This investigation utilized magnetoencephalography and an Eriksen arrow-based flanker task to quantify the dynamics underlying selective attention in a cohort of youth and adults with cerebral palsy (n = 31; age range = 9 to 47 yr) and neurotypical controls (n = 38; age range = 11 to 49 yr). The magnetoencephalography data were transformed into the time-frequency domain to identify neural oscillatory responses and imaged using a beamforming approach. The behavioral results indicated that all participants exhibited a flanker effect (greater response time for the incongruent compared to congruent condition) and that individuals with cerebral palsy were slower and less accurate during task performance. We computed interference maps to focus on the attentional component and found aberrant alpha (8 to 14 Hz) oscillations in the right primary visual cortices in the group with cerebral palsy. Alpha and theta (4 to 7 Hz) oscillations were also seen in the left and right insula, and these oscillations varied with age across all participants. Overall, persons with cerebral palsy exhibit deficiencies in the cortical dynamics serving visual selective attention, but these aberrations do not appear to be uniquely affected by age.

Resting-state electroencephalography and magnetoencephalography in migraine-a systematic review and meta-analysis.

Magnetoencephalography/electroencephalography (M/EEG) can provide insights into migraine pathophysiology and help develop clinically valuable biomarkers. To integrate and summarize the existing evidence on changes in brain function in migraine, we performed a systematic review and meta-analysis (PROSPERO CRD42021272622) of resting-state M/EEG findings in migraine. We included 27 studies after searching MEDLINE, Web of Science Core Collection, and EMBASE. Risk of bias was assessed using a modified Newcastle-Ottawa Scale. Semi-quantitative analysis was conducted by vote counting, and meta-analyses of M/EEG differences between people with migraine and healthy participants were performed using random-effects models. In people with migraine during the interictal phase, meta-analysis revealed higher power of brain activity at theta frequencies (3-8 Hz) than in healthy participants. Furthermore, we found evidence for lower alpha and beta connectivity in people with migraine in the interictal phase. No associations between M/EEG features and disease severity were observed. Moreover, some evidence for higher delta and beta power in the premonitory compared to the interictal phase was found. Strongest risk of bias of included studies arose from a lack of controlling for comorbidities and non-automatized or non-blinded M/EEG assessments. These findings can guide future M/EEG studies on migraine pathophysiology and brain-based biomarkers, which should consider comorbidities and aim for standardized, collaborative approaches.

Optimizing magnetometers arrays and analysis pipelines for multivariate pattern analysis.

BACKGROUND: Multivariate pattern analysis (MVPA) has proven an excellent tool in cognitive neuroscience. It also holds a strong promise when applied to optically-pumped magnetometer-based magnetoencephalography. NEW METHOD: To optimize OPM-MEG systems for MVPA experiments this study examines data from a conventional MEG magnetometer array, focusing on appropriate noise reduction techniques for magnetometers. We determined the least required number of sensors needed for robust MVPA for image categorization experiments. RESULTS: We found that the use of signal space separation (SSS) without a proper regularization significantly lowered the classification accuracy considering a sub-array of 102 magnetometers or a sub-array of 204 gradiometers. We also found that classification accuracy did not improve when going beyond 30 sensors irrespective of whether SSS has been applied. COMPARISON WITH EXISTING METHODS: The power spectra of data filtered with SSS has a substantially higher noise floor that data cleaned with SSP or HFC. Consequently, MVPA decoding results obtained from the SSS-filtered data are significantly lower compared to all other methods employed. CONCLUSIONS: When designing MEG system based on SQUID magnetometers optimized for multivariate analysis for image categorization experiments, about 30 magnetometers are sufficient. We advise against applying SSS filters without a proper regularization to data from MEG and OPM systems prior to performing MVPA as this method, albeit reducing low-frequency external noise contributions, also introduces an increase in broadband noise. We recommend employing noise reduction techniques that either decrease or maintain the noise floor of the data like signal-space projection, homogeneous field correction and gradient noise reduction.

The Functional Connectome and Long-Term Symptom Presentation Associated With Mild Traumatic Brain Injury and Blast Exposure in Combat Veterans.

Mild traumatic brain injury (TBI) sustained in a deployment environment (deployment TBI) can be associated with increased severity of long-term symptom presentation, despite the general expectation of full recovery from a single mild TBI. The heterogeneity in the effects of deployment TBI on the brain can be difficult for a case-control design to capture. The functional connectome of the brain is an approach robust to heterogeneity that allows global measurement of effects using a common set of outcomes. The present study evaluates how differences in the functional connectome relate to remote symptom presentation following combat deployment and determines if deployment TBI, blast exposure, or post-traumatic stress disorder (PTSD) are associated with these neurological differences. Participants included 181 Iraq and Afghanistan combat-exposed Veterans, approximately 9.4 years since deployment. Structured clinical interviews provided diagnoses and characterizations of TBI, blast exposure, and PTSD. Self-report measures provided characterization of long-term symptoms (psychiatric, behavioral health, and quality of life). Resting-state magnetoencephalography was used to characterize the functional connectome of the brain individually for each participant. Linear regression identified factors contributing to symptom presentation including relevant covariates, connectome metrics, deployment TBI, blast exposure PTSD, and conditional relationships. Results identified unique contributions of aspects of the connectome to symptom presentation. Furthermore, several conditional relationships were identified, demonstrating that the connectome was related to outcomes in the presence of only deployment-related TBI (including blast-related TBI, primary blast TBI, and blast exposure). No conditional relationships were identified for PTSD; however, the main effect of PTSD on symptom presentation was significant for all models. These results demonstrate that the connectome captures aspects of brain function relevant to long-term symptom presentation, highlighting that deployment-related TBI influences symptom outcomes through a neurological pathway. These findings demonstrate that changes in the functional connectome associated with deployment-related TBI are relevant to symptom presentation over a decade past the injury event, providing a clear demonstration of a brain-based mechanism of influence.

MEG Microstates: An Investigation of Underlying Brain Sources and Potential Neurophysiological Processes.

Microstates are transient scalp configurations of brain activity measured by electroencephalography (EEG). The application of microstate analysis in magnetoencephalography (MEG) data remains challenging. In one MEG dataset (N = 113), we aimed to identify MEG microstates at rest, explore their brain sources, and relate them to changes in brain activity during open-eyes (ROE) or closed-eyes resting state (RCE) and an auditory Mismatch Negativity (MMN) task. In another dataset of simultaneously recorded EEG-MEG data (N = 21), we investigated the association between MEG and EEG microstates. Six MEG microstates (mMS) provided the best clustering of resting-state activity, each linked to different brain sources: mMS 1-2: left/right occipito-parietal; mMS 3: fronto-temporal; mMS 4: centro-medial; mMS 5-6: left/right fronto-parietal. Increases in occipital alpha power in RCE relative to ROE correlated with greater mMS 1-2 time coverage (τbs < 0.20, ps > .002), while the lateralization of deviance detection in MMN was associated with mMS 5-6 time coverage (τbs < 0.16, ps > .012). No temporal correlation was found between EEG and MEG microstates (ps > .05), despite some overlap in brain sources and global explained variance between mMS 2-3 and EEG microstates B-C (rs > 0.60, ps < .002). Hence, the MEG signal can be decomposed into microstates, but mMS brain activity clustering captures phenomena different from EEG microstates. Source reconstruction and task-related modulations link mMS to large-scale networks and localized activities. Thus, mMSs offer insights into brain dynamics and task-specific processes, complementing EEG microstates in studying physiological and dysfunctional brain activity.