Neuromagnetic activation and oscillatory dynamics of stimulus-locked processing during naturalistic viewing.

Naturalistic stimuli such as watching a movie while in the scanner provide an ecologically valid paradigm that has the potential of extracting valuable information on how the brain processes complex stimuli in realistic visual and auditory contexts. Naturalistic viewing is also easier to conduct with challenging participant groups including patients and children. Given the high temporal resolution of MEG, in the present study, we demonstrate how a short movie clip can be used to map distinguishable activation and connectivity dynamics underlying the processing of specific classes of visual stimuli such as face and hand manipulations, as well as contrasting activation dynamics for auditory words and non-words. MEG data were collected from 22 healthy volunteers (6 females, 3 left handed, mean age - 27.7 â€‹± â€‹5.28 years) during the presentation of naturalistic audiovisual stimuli. The MEG data were split into trials with the onset of the stimuli belonging to classes of interest (words, non-words, faces, hand manipulations). Based on the components of the averaged sensor ERFs time-locked to the visual and auditory stimulus onset, four and three time-windows, respectively, were defined to explore brain activation dynamics. Pseudo-Z, defined as the ratio of the source-projected time-locked power to the projected noise power for each vertex, was computed and used as a proxy of time-locked brain activation. Statistical testing using the mean-centered Partial Least Squares analysis indicated periods where a given visual or auditory stimuli had higher activation. Based on peak pseudo-Z differences between the visual conditions, time-frequency resolved analyses were performed to assess beta band desynchronization in motor-related areas, and inter-trial phase synchronization between face processing areas. Our results provide the first evidence that activation and connectivity dynamics in canonical brain regions associated with the processing of particular classes of visual and auditory stimuli can be reliably mapped using MEG during presentation of naturalistic stimuli. Given the strength of MEG for brain mapping in temporal and frequency domains, the use of naturalistic stimuli may open new techniques in analyzing brain dynamics during ecologically valid sensation and perception.

Cognitive loading via mental arithmetic modulates effects of blink-related oscillations on precuneus and ventral attention network regions.

Blink-related oscillations (BROs) have been linked with environmental monitoring processes associated with blinking, with cortical activations in the bilateral precuneus. Although BROs have been described under resting and passive fixation conditions, little is known about their characteristics under cognitive loading. To address this, we investigated BRO effects during both mental arithmetic (MA) and passive fixation (PF) tasks using magnetoencephalography (n =20), while maintaining the same sensory environment in both tasks. Our results confirmed the presence of BRO effects in both MA and PF tasks, with similar characteristics including blink-related increase in global field power and blink-related activation of the bilateral precuneus. In addition, cognitive loading due to MA also modulated BRO effects by decreasing BRO-induced cortical activations in key brain regions including the bilateral anterior precuneus. Interestingly, blinking during MA-but not PF-activated regions of the ventral attention network (i.e., right supramarginal gyrus and inferior frontal gyrus), suggesting possible recruitment of these areas for blink processing under cognitive loading conditions. Time-frequency analysis revealed a consistent pattern of BRO-related effects in the precuneus in both tasks, but with task-related functional segregation within the anterior and posterior subregions. Based on these findings, we postulate a potential neurocognitive mechanism for blink processing in the precuneus. This study is the first investigation of BRO effects under cognitive loading, and our results provide compelling new evidence for the important cognitive implications of blink-related processing in the human brain.

Multimodal characterization of the semantic N400 response within a rapid evaluation brain vital sign framework.

BACKGROUND: For nearly four decades, the N400 has been an important brainwave marker of semantic processing. It can be recorded non-invasively from the scalp using electrical and/or magnetic sensors, but largely within the restricted domain of research laboratories specialized to run specific N400 experiments. However, there is increasing evidence of significant clinical utility for the N400 in neurological evaluation, particularly at the individual level. To enable clinical applications, we recently reported a rapid evaluation framework known as "brain vital signs" that successfully incorporated the N400 response as one of the core components for cognitive function evaluation. The current study characterized the rapidly evoked N400 response to demonstrate that it shares consistent features with traditional N400 responses acquired in research laboratory settings-thereby enabling its translation into brain vital signs applications. METHODS: Data were collected from 17 healthy individuals using magnetoencephalography (MEG) and electroencephalography (EEG), with analysis of sensor-level effects as well as evaluation of brain sources. Individual-level N400 responses were classified using machine learning to determine the percentage of participants in whom the response was successfully detected. RESULTS: The N400 response was observed in both M/EEG modalities showing significant differences to incongruent versus congruent condition in the expected time range (p < 0.05). Also as expected, N400-related brain activity was observed in the temporal and inferior frontal cortical regions, with typical left-hemispheric asymmetry. Classification robustly confirmed the N400 effect at the individual level with high accuracy (89%), sensitivity (0.88) and specificity (0.90). CONCLUSION: The brain vital sign N400 characteristics were highly consistent with features of the previously reported N400 responses acquired using traditional laboratory-based experiments. These results provide important evidence supporting clinical translation of the rapidly acquired N400 response as a potential tool for assessments of higher cognitive functions.

An integrated full-head OPM-MEG system based on 128 zero-field sensors.

Compact optically-pumped magnetometers (OPMs) are now commercially available with noise floors reaching 10 fT/Hz1/2. However, to be used effectively for magnetoencephalography (MEG), dense arrays of these sensors are required to operate as an integrated turn-key system. In this study, we present the HEDscan, a 128-sensor OPM MEG system by FieldLine Medical, and evaluate its sensor performance with regard to bandwidth, linearity, and crosstalk. We report results from cross-validation studies with conventional cryogenic MEG, the Magnes 3,600 WH Biomagnetometer by 4-D Neuroimaging. Our results show high signal amplitudes captured by the OPM-MEG system during a standard auditory paradigm, where short tones at 1000 Hz were presented to the left ear of six healthy adult volunteers. We validate these findings through an event-related beamformer analysis, which is in line with existing literature results.

Developmental Differences in Neuromagnetic Cortical Activation and Phase Synchrony Elicited by Scenes with Faces during Movie Watching.

The neural underpinnings of humans' ability to process faces and how it changes over typical development have been extensively studied using paradigms where face stimuli are oversimplified, isolated, and decontextualized. The prevalence of this approach, however, has resulted in limited knowledge of face processing in ecologically valid situations, in which faces are accompanied by contextual information at multiple time scales. In the present study, we use a naturalistic movie paradigm to investigate how neuromagnetic activation and phase synchronization elicited by faces from movie scenes in humans differ between children and adults. We used MEG data from 22 adults (6 females, 3 left handed; mean age, 27.7 ± 5.28 years) and 20 children (7 females, 1 left handed; mean age, 9.5 ± 1.52 years) collected during movie viewing. We investigated neuromagnetic time-locked activation and phase synchronization elicited by movie scenes containing faces in contrast to other movie scenes. Statistical differences between groups were tested using a multivariate data-driven approach. Our results revealed lower face-elicited activation and theta/alpha phase synchrony between 120 and 330 ms in children compared with adults. Reduced connectivity in children was observed between the primary visual areas as well as their connections with higher-order frontal and parietal cortical areas. This is the first study to map neuromagnetic developmental changes in face processing in a time-locked manner using a naturalistic movie paradigm. It supports and extends the existing evidence of core face-processing network maturation accompanied by the development of an extended system of higher-order cortical areas engaged in face processing.

Accessing knowledge of the 'here and now': a new technique for capturing electromagnetic markers of orientation processing.

OBJECTIVE: The ability to orient with respect to the current context (e.g. current time or location) is crucial for daily functioning, and is used to measure overall cognitive health across many frontline clinical assessments. However, these tests are often hampered by their reliance on verbal probes (e.g. 'What city are we in?') in evaluating orientation. Objective, physiology-based measures of orientation processing are needed, but no such measures are currently in existence. We report the initial development of potential brainwave-based markers of orientation processing as characterized using electroencephlography (EEG) and magnetoencephalography (MEG). APPROACH: An auditory stimulus sequence embedded with words corresponding to orientation-relevant (i.e. related to the 'here and now') and orientation-irrelevant (i.e. unrelated to the current context) conditions was used to elicit orientation processing responses. EEG/MEG data, in concert with clinical assessments, were collected from 29 healthy adults. Analysis at sensor and source levels identified and characterized neural signals related to orientation processing. MAIN RESULTS: Orientation-irrelevant stimuli elicited increased negative amplitude in EEG-derived event-related potential (ERP) waveforms during the 390-570 ms window (p < 0.05), with cortical activations across the left frontal, temporal, and parietal regions. These effects are consistent with the well-known N400 response to semantic incongruence. In contrast, ERP responses to orientation-relevant stimuli exhibited increased positive amplitude during the same interval (p < 0.05), with activations across the bilateral temporal and parietal regions. Importantly, these differential responses were robust at the individual level, with machine-learning classification showing high accuracy (89%), sensitivity (0.88) and specificity (0.90). SIGNIFICANCE: This is the first demonstration of a neurotechnology platform that elicits, captures, and evaluates electrophysiological markers of orientation processing. We demonstrate neural responses to orientation stimuli that are validated across EEG and MEG modalities and robust at the individual level. The extraction of physiology-based markers through this technique may enable improved objective brain functional evaluation in clinical applications.

Spontaneous Blinks Activate the Precuneus: Characterizing Blink-Related Oscillations Using Magnetoencephalography.

Spontaneous blinking occurs 15-20 times per minute. Although blinking has often been associated with its physiological role of corneal lubrication, there is now increasing behavioral evidence suggesting that blinks are also modulated by cognitive processes such as attention and information processing. Recent low-density electroencephalography (EEG) studies have reported so-called blink-related oscillations (BROs) associated with spontaneous blinking at rest. Delta-band (0.5-4 Hz) BROs are thought to originate from the precuneus region involved in environmental monitoring and awareness, with potential clinical utility in evaluation of disorders of consciousness. However, the neural mechanisms of BROs have not been elucidated. Using magnetoencephalography (MEG), we characterized delta-band BROs in 36 healthy individuals while controlling for background brain activity. Results showed that, compared to pre-blink baseline, delta-band BROs resulted in increased global field power (p < 0.001) and time-frequency spectral power (p < 0.05) at the sensor level, peaking at ~250 ms post-blink maximum. Source localization showed that spontaneous blinks activated the bilateral precuneus (p < 0.05 FWE), and source activity within the precuneus was also consistent with sensor-space results. Crucially, these effects were only observed in the blink condition and were absent in the control condition, demonstrating that results were due to spontaneous blinks rather than as part of the inherent brain activity. The current study represents the first MEG examination of BROs. Our findings suggest that spontaneous blinks activate the precuneus regions consistent with environmental monitoring and awareness, and provide important neuroimaging support for the cognitive role of spontaneous blinks.

Non-magnetic compliant finger sensor for continuous fine motor movement detection.

A non-magnetic MEG compatible device has been developed that provides continuous force and velocity information. Combined with MEG, this device may find utility in characterizing brain regions associated with force and velocity relative to individual digits or movement pattern. 15 healthy right-handed participants were given visual cues to perform random finger movements on the prototype finger sensor for 21 s and then rest for 21 s (7 times). Respective finger flexion data were obtained, during 151-channel MEG brain scanning, by feeding the signal from finger sensor into four input Analog to Digital Converter (ADC) channels in the MEG hardware. The source activity was reconstructed in beta band using a Linearly Constrained Minimum Variance (LCMV) beamformer in the beta band. The ADC channels were used as regressors for a continuous time General Linear Model (GLM) and a Region of Interest (ROI) was identified to examine activity. MEG analysis showed bilateral activation in the primary motor cortex region. Because individual digits could be isolated in the ADC data, somatotopy of the fingers were observed consistent with the homunculus except pinky finger. The total span was calculated to be 5.5662 mm. The study confirms that the finger sensor is magnetically compatible with MEG measurements and may potentially provide a means to study complex sensorimotor functions. Improved isolation of individual digit information along with the use of machine learning algorithms can help retrieve more accurate results.

Syntactic computations in the language network: characterizing dynamic network properties using representational similarity analysis.

The core human capacity of syntactic analysis involves a left hemisphere network involving left inferior frontal gyrus (LIFG) and posterior middle temporal gyrus (LMTG) and the anatomical connections between them. Here we use magnetoencephalography (MEG) to determine the spatio-temporal properties of syntactic computations in this network. Listeners heard spoken sentences containing a local syntactic ambiguity (e.g., "… landing planes …"), at the offset of which they heard a disambiguating verb and decided whether it was an acceptable/unacceptable continuation of the sentence. We charted the time-course of processing and resolving syntactic ambiguity by measuring MEG responses from the onset of each word in the ambiguous phrase and the disambiguating word. We used representational similarity analysis (RSA) to characterize syntactic information represented in the LIFG and left posterior middle temporal gyrus (LpMTG) over time and to investigate their relationship to each other. Testing a variety of lexico-syntactic and ambiguity models against the MEG data, our results suggest early lexico-syntactic responses in the LpMTG and later effects of ambiguity in the LIFG, pointing to a clear differentiation in the functional roles of these two regions. Our results suggest the LpMTG represents and transmits lexical information to the LIFG, which responds to and resolves the ambiguity.

Neonatal pain-related stress, functional cortical activity and visual-perceptual abilities in school-age children born at extremely low gestational age.

Children born very prematurely (< or =32 weeks) often exhibit visual-perceptual difficulties at school-age, even in the absence of major neurological impairment. The alterations in functional brain activity that give rise to such problems, as well as the relationship between adverse neonatal experience and neurodevelopment, remain poorly understood. Repeated procedural pain-related stress during neonatal intensive care has been proposed to contribute to altered neurocognitive development in these children. Due to critical periods in the development of thalamocortical systems, the immature brain of infants born at extremely low gestational age (ELGA; < or =28 weeks) may have heightened vulnerability to neonatal pain. In a cohort of school-age children followed since birth we assessed relations between functional brain activity measured using magnetoencephalogragy (MEG), visual-perceptual abilities and cumulative neonatal pain. We demonstrated alterations in the spectral structure of spontaneous cortical oscillatory activity in ELGA children at school-age. Cumulative neonatal pain-related stress was associated with changes in background cortical rhythmicity in these children, and these alterations in spontaneous brain oscillations were negatively correlated with visual-perceptual abilities at school-age, and were not driven by potentially confounding neonatal variables. These findings provide the first evidence linking neonatal pain-related stress, the development of functional brain activity, and school-age cognitive outcome in these vulnerable children.