Neural markers of reduced arousal and consciousness in mild cognitive impairment.

OBJECTIVES: People with Alzheimer's Disease (AD) experience changes in their level and content of consciousness, but there is little research on biomarkers of consciousness in pre-clinical AD and Mild Cognitive Impairment (MCI). This study investigated whether levels of consciousness are decreased in people with MCI. METHODS: A multi-site site magnetoencephalography (MEG) dataset, BIOFIND, comprising 83 people with MCI and 83 age matched controls, was analysed. Arousal (and drowsiness) was assessed by computing the theta-alpha ratio (TAR). The Lempel-Ziv algorithm (LZ) was used to quantify the information content of brain activity, with higher LZ values indicating greater complexity and potentially a higher level of consciousness. RESULTS: LZ was lower in the MCI group versus controls, indicating a reduced level of consciousness in MCI. TAR was higher in the MCI group versus controls, indicating a reduced level of arousal (i.e. increased drowsiness) in MCI. LZ was also found to be correlated with mini-mental state examination (MMSE) scores, suggesting an association between cognitive impairment and level of consciousness in people with MCI. CONCLUSIONS: A decline in consciousness and arousal can be seen in MCI. As cognitive impairment worsens, measured by MMSE scores, levels of consciousness and arousal decrease. These findings highlight how monitoring consciousness using biomarkers could help understand and manage impairments found at the preclinical stages of AD. Further research is needed to explore markers of consciousness between people who progress from MCI to dementia and those who do not, and in people with moderate and severe AD, to promote person-centred care.

Spatiotemporal dynamics of cortical somatosensory network in typically developing children.

Sense of touch is essential for our interactions with external objects and fine control of hand actions. Despite extensive research on human somatosensory processing, it is still elusive how involved brain regions interact as a dynamic network in processing tactile information. Few studies probed temporal dynamics of somatosensory information flow and reported inconsistent results. Here, we examined cortical somatosensory processing through magnetic source imaging and cortico-cortical coupling dynamics. We recorded magnetoencephalography signals from typically developing children during unilateral pneumatic stimulation. Neural activities underlying somatosensory evoked fields were mapped with dynamic statistical parametric mapping, assessed with spatiotemporal activation analysis, and modeled by Granger causality. Unilateral pneumatic stimulation evoked prominent and consistent activations in the contralateral primary and secondary somatosensory areas but weaker and less consistent activations in the ipsilateral primary and secondary somatosensory areas. Activations in the contralateral primary motor cortex and supramarginal gyrus were also consistently observed. Spatiotemporal activation and Granger causality analysis revealed initial serial information flow from contralateral primary to supramarginal gyrus, contralateral primary motor cortex, and contralateral secondary and later dynamic and parallel information flows between the consistently activated contralateral cortical areas. Our study reveals the spatiotemporal dynamics of cortical somatosensory processing in the normal developing brain.

Tracking the neurodevelopmental trajectory of beta band oscillations with optically pumped magnetometer-based magnetoencephalography.

Neural oscillations mediate the coordination of activity within and between brain networks, supporting cognition and behaviour. How these processes develop throughout childhood is not only an important neuroscientific question but could also shed light on the mechanisms underlying neurological and psychiatric disorders. However, measuring the neurodevelopmental trajectory of oscillations has been hampered by confounds from instrumentation. In this paper, we investigate the suitability of a disruptive new imaging platform - optically pumped magnetometer-based magnetoencephalography (OPM-MEG) - to study oscillations during brain development. We show how a unique 192-channel OPM-MEG device, which is adaptable to head size and robust to participant movement, can be used to collect high-fidelity electrophysiological data in individuals aged between 2 and 34 years. Data were collected during a somatosensory task, and we measured both stimulus-induced modulation of beta oscillations in sensory cortex, and whole-brain connectivity, showing that both modulate significantly with age. Moreover, we show that pan-spectral bursts of electrophysiological activity drive task-induced beta modulation, and that their probability of occurrence and spectral content change with age. Our results offer new insights into the developmental trajectory of beta oscillations and provide clear evidence that OPM-MEG is an ideal platform for studying electrophysiology in neurodevelopment.

The investigation of dysregulated visual perceptual organization in adults with autism spectrum disorders with phase-amplitude coupling and directed connectivity.

Phase-amplitude coupling (PAC) has been used as a powerful tool to understand the mechanism underlying neural binding by investigating neural synchrony across different frequency bands. This study examined the possibility that dysregulated alpha-gamma modulation may be crucially involved in aberrant brain functioning in autism spectrum disorder (ASD). Magnetoencephalographic data were recorded from 13 adult participants with ASD and 16 controls. The time-coursed sources averaged over a primary visual area 1 and fusiform gyrus area were reconstructed with the minimum-norm estimate method. The alpha-gamma PAC was further calculated based on these sources. The statistical analysis was implemented based on the PAC and directed asymmetry index. The results showed the hyper-activity coupling for ASD at the no-face condition and revealed the importance of alpha-gamma phase modulation in detecting a face. Our data provides novel evidence for the role of the alpha-gamma PAC and suggests that the globe connectivity may be more critical during visual perception.

Eye movements track prioritized auditory features in selective attention to natural speech.

Over the last decades, cognitive neuroscience has identified a distributed set of brain regions that are critical for attention. Strong anatomical overlap with brain regions critical for oculomotor processes suggests a joint network for attention and eye movements. However, the role of this shared network in complex, naturalistic environments remains understudied. Here, we investigated eye movements in relation to (un)attended sentences of natural speech. Combining simultaneously recorded eye tracking and magnetoencephalographic data with temporal response functions, we show that gaze tracks attended speech, a phenomenon we termed ocular speech tracking. Ocular speech tracking even differentiates a target from a distractor in a multi-speaker context and is further related to intelligibility. Moreover, we provide evidence for its contribution to neural differences in speech processing, emphasizing the necessity to consider oculomotor activity in future research and in the interpretation of neural differences in auditory cognition.

Post-task responses following working memory and movement are driven by transient spectral bursts with similar characteristics.

The post-movement beta rebound has been studied extensively using magnetoencephalography (MEG) and is reliably modulated by various task parameters as well as illness. Our recent study showed that rebounds, which we generalise as "post-task responses" (PTRs), are a ubiquitous phenomenon in the brain, occurring across the cortex in theta, alpha, and beta bands. Currently, it is unknown whether PTRs following working memory are driven by transient bursts, which are moments of short-lived high amplitude activity, similar to those that drive the post-movement beta rebound. Here, we use three-state univariate hidden Markov models (HMMs), which can identify bursts without a priori knowledge of frequency content or response timings, to compare bursts that drive PTRs in working memory and visuomotor MEG datasets. Our results show that PTRs across working memory and visuomotor tasks are driven by pan-spectral transient bursts. These bursts have very similar spectral content variation over the cortex, correlating strongly between the two tasks in the alpha (R2 = .89) and beta (R2 = .53) bands. Bursts also have similar variation in duration over the cortex (e.g., long duration bursts occur in the motor cortex for both tasks), strongly correlating over cortical regions between tasks (R2 = .56), with a mean over all regions of around 300 ms in both datasets. Finally, we demonstrate the ability of HMMs to isolate signals of interest in MEG data, such that the HMM probability timecourse correlates more strongly with reaction times than frequency filtered power envelopes from the same brain regions. Overall, we show that induced PTRs across different tasks are driven by bursts with similar characteristics, which can be identified using HMMs. Given the similarity between bursts across tasks, we suggest that PTRs across the cortex may be driven by a common underlying neural phenomenon.

Heuristics in risky decision-making relate to preferential representation of information.

When making choices, individuals differ from one another, as well as from normativity, in how they weigh different types of information. One explanation for this relates to idiosyncratic preferences in what information individuals represent when evaluating choice options. Here, we test this explanation with a simple risky-decision making task, combined with magnetoencephalography (MEG). We examine the relationship between individual differences in behavioral markers of information weighting and neural representation of stimuli pertinent to incorporating that information. We find that the extent to which individuals (N = 19) behaviorally weight probability versus reward information is related to how preferentially they neurally represent stimuli most informative for making probability and reward comparisons. These results are further validated in an additional behavioral experiment (N = 88) that measures stimulus representation as the latency of perceptual detection following priming. Overall, the results suggest that differences in the information individuals consider during choice relate to their risk-taking tendencies.

s-TBN: A New Neural Decoding Model to Identify Stimulus Categories From Brain Activity Patterns.

Neural decoding is still a challenging and a hot topic in neurocomputing science. Recently, many studies have shown that brain network patterns containing rich spatiotemporal structural information represent the brain's activation information under external stimuli. In the traditional method, brain network features are directly obtained using the standard machine learning method and provide to a classifier, subsequently decoding external stimuli. However, this method cannot effectively extract the multidimensional structural information hidden in the brain network. Furthermore, studies on tensors have show that the tensor decomposition model can fully mine unique spatiotemporal structural characteristics of a spatiotemporal structure in data with a multidimensional structure. This research proposed a stimulus-constrained Tensor Brain Network (s-TBN) model that involves the tensor decomposition and stimulus category-constraint information. The model was verified on real neuroimaging data obtained via magnetoencephalograph and functional mangetic resonance imaging). Experimental results show that the s-TBN model achieve accuracy matrices of greater than 11.06% and 18.46% on the accuracy matrix compared with other methods on two modal datasets. These results prove the superiority of extracting discriminative characteristics using the STN model, especially for decoding object stimuli with semantic information.

A user-friendly visual brain-computer interface based on high-frequency steady-state visual evoked fields recorded by OPM-MEG.

Objective. Magnetoencephalography (MEG) shares a comparable time resolution with electroencephalography. However, MEG excels in spatial resolution, enabling it to capture even the subtlest and weakest brain signals for brain-computer interfaces (BCIs). Leveraging MEG's capabilities, specifically with optically pumped magnetometers (OPM-MEG), proves to be a promising avenue for advancing MEG-BCIs, owing to its exceptional sensitivity and portability. This study harnesses the power of high-frequency steady-state visual evoked fields (SSVEFs) to build an MEG-BCI system that is flickering-imperceptible, user-friendly, and highly accurate.Approach.We have constructed a nine-command BCI that operates on high-frequency SSVEF (58-62 Hz with a 0.5 Hz interval) stimulation. We achieved this by placing the light source inside and outside the magnetic shielding room, ensuring compliance with non-magnetic and visual stimulus presentation requirements. Five participants took part in offline experiments, during which we collected six-channel multi-dimensional MEG signals along both the vertical (Z-axis) and tangential (Y-axis) components. Our approach leveraged the ensemble task-related component analysis algorithm for SSVEF identification and system performance evaluation.Main Results.The offline average accuracy of our proposed system reached an impressive 92.98% when considering multi-dimensional conjoint analysis using data from both theZandYaxes. Our method achieved a theoretical average information transfer rate (ITR) of 58.36 bits min-1with a data length of 0.7 s, and the highest individual ITR reached an impressive 63.75 bits min-1.Significance.This study marks the first exploration of high-frequency SSVEF-BCI based on OPM-MEG. These results underscore the potential and feasibility of MEG in detecting subtle brain signals, offering both theoretical insights and practical value in advancing the development and application of MEG in BCI systems.

Measuring Human Auditory Evoked Fields with a Flexible Multi-Channel OPM-Based MEG System.

BACKGROUND: Magnetoencephalography (MEG) is a non-invasive imaging technique for directly measuring the external magnetic field generated from synchronously activated pyramidal neurons in the brain. The optically pumped magnetometer (OPM) is known for its less expensive, non-cryogenic, movable and user-friendly custom-design provides the potential for a change in functional neuroimaging based on MEG. METHODS: An array of OPMs covering the opposite sides of a subject's head is placed inside a magnetically shielded room (MSR) and responses evoked from the auditory cortices are measured. RESULTS: High signal-to-noise ratio auditory evoked response fields (AEFs) were detected by a wearable OPM-MEG system in a MSR, for which a flexible helmet was specially designed to minimize the sensor-to-head distance, along with a set of bi-planar coils developed for background field and gradient nulling. Neuronal current sources activated in AEF experiments were localized and the auditory cortices showed the highest activities. Performance of the hybrid optically pumped magnetometer-magnetoencephalography/electroencephalography (OPM-MEG/EEG) system was also assessed. CONCLUSIONS: The multi-channel OPM-MEG system performs well in a custom built MSR equipped with bi-planar coils and detects human AEFs with a flexible helmet. Moreover, the similarities and differences of auditory evoked potentials (AEPs) and AEFs are discussed, while the operation of OPM-MEG sensors in conjunction with EEG electrodes provides an encouraging combination for the exploration of hybrid OPM-MEG/EEG systems.

Spatiotemporal brain hierarchies of auditory memory recognition and predictive coding.

Our brain is constantly extracting, predicting, and recognising key spatiotemporal features of the physical world in order to survive. While neural processing of visuospatial patterns has been extensively studied, the hierarchical brain mechanisms underlying conscious recognition of auditory sequences and the associated prediction errors remain elusive. Using magnetoencephalography (MEG), we describe the brain functioning of 83 participants during recognition of previously memorised musical sequences and systematic variations. The results show feedforward connections originating from auditory cortices, and extending to the hippocampus, anterior cingulate gyrus, and medial cingulate gyrus. Simultaneously, we observe backward connections operating in the opposite direction. Throughout the sequences, the hippocampus and cingulate gyrus maintain the same hierarchical level, except for the final tone, where the cingulate gyrus assumes the top position within the hierarchy. The evoked responses of memorised sequences and variations engage the same hierarchical brain network but systematically differ in terms of temporal dynamics, strength, and polarity. Furthermore, induced-response analysis shows that alpha and beta power is stronger for the variations, while gamma power is enhanced for the memorised sequences. This study expands on the predictive coding theory by providing quantitative evidence of hierarchical brain mechanisms during conscious memory and predictive processing of auditory sequences.

Neural correlates of retrospective memory confidence during face-name associative learning.

The ability to accurately assess one's own memory performance during learning is essential for adaptive behavior, but the brain mechanisms underlying this metamemory function are not well understood. We investigated the neural correlates of memory accuracy and retrospective memory confidence in a face-name associative learning task using magnetoencephalography in healthy young adults (n = 32). We found that high retrospective confidence was associated with stronger occipital event-related fields during encoding and widespread event-related fields during retrieval compared to low confidence. On the other hand, memory accuracy was linked to medial temporal activities during both encoding and retrieval, but only in low-confidence trials. A decrease in oscillatory power at alpha/beta bands in the parietal regions during retrieval was associated with higher memory confidence. In addition, representational similarity analysis at the single-trial level revealed distributed but differentiable neural activities associated with memory accuracy and confidence during both encoding and retrieval. In summary, our study unveiled distinct neural activity patterns related to memory confidence and accuracy during associative learning and underscored the crucial role of parietal regions in metamemory.

Hierarchical syntax model of music predicts theta power during music listening.

Linguistic research showed that the depth of syntactic embedding is reflected in brain theta power. Here, we test whether this also extends to non-linguistic stimuli, specifically music. We used a hierarchical model of musical syntax to continuously quantify two types of expert-annotated harmonic dependencies throughout a piece of Western classical music: prolongation and preparation. Prolongations can roughly be understood as a musical analogue to linguistic coordination between constituents that share the same function (e.g., 'pizza' and 'pasta' in 'I ate pizza and pasta'). Preparation refers to the dependency between two harmonies whereby the first implies a resolution towards the second (e.g., dominant towards tonic; similar to how the adjective implies the presence of a noun in 'I like spicy … '). Source reconstructed MEG data of sixty-five participants listening to the musical piece was then analysed. We used Bayesian Mixed Effects models to predict theta envelope in the brain, using the number of open prolongation and preparation dependencies as predictors whilst controlling for audio envelope. We observed that prolongation and preparation both carry independent and distinguishable predictive value for theta band fluctuation in key linguistic areas such as the Angular, Superior Temporal, and Heschl's Gyri, or their right-lateralised homologues, with preparation showing additional predictive value for areas associated with the reward system and prediction. Musical expertise further mediated these effects in language-related brain areas. Results show that predictions of precisely formalised music-theoretical models are reflected in the brain activity of listeners which furthers our understanding of the perception and cognition of musical structure.

The neural representation of an auditory spatial cue in the primate cortex.

Humans make use of small differences in the timing of sounds at the two ears-interaural time differences (ITDs)-to locate their sources. Despite extensive investigation, however, the neural representation of ITDs in the human brain is contentious, particularly the range of ITDs explicitly represented by dedicated neural detectors. Here, using magneto- and electro-encephalography (MEG and EEG), we demonstrate evidence of a sparse neural representation of ITDs in the human cortex. The magnitude of cortical activity to sounds presented via insert earphones oscillated as a function of increasing ITD-within and beyond auditory cortical regions-and listeners rated the perceptual quality of these sounds according to the same oscillating pattern. This pattern was accurately described by a population of model neurons with preferred ITDs constrained to the narrow, sound-frequency-dependent range evident in other mammalian species. When scaled for head size, the distribution of ITD detectors in the human cortex is remarkably like that recorded in vivo from the cortex of rhesus monkeys, another large primate that uses ITDs for source localization. The data solve a long-standing issue concerning the neural representation of ITDs in humans and suggest a representation that scales for head size and sound frequency in an optimal manner.

Negation mitigates rather than inverts the neural representations of adjectives.

Combinatoric linguistic operations underpin human language processes, but how meaning is composed and refined in the mind of the reader is not well understood. We address this puzzle by exploiting the ubiquitous function of negation. We track the online effects of negation ("not") and intensifiers ("really") on the representation of scalar adjectives (e.g., "good") in parametrically designed behavioral and neurophysiological (MEG) experiments. The behavioral data show that participants first interpret negated adjectives as affirmative and later modify their interpretation towards, but never exactly as, the opposite meaning. Decoding analyses of neural activity further reveal significant above chance decoding accuracy for negated adjectives within 600 ms from adjective onset, suggesting that negation does not invert the representation of adjectives (i.e., "not bad" represented as "good"); furthermore, decoding accuracy for negated adjectives is found to be significantly lower than that for affirmative adjectives. Overall, these results suggest that negation mitigates rather than inverts the neural representations of adjectives. This putative suppression mechanism of negation is supported by increased synchronization of beta-band neural activity in sensorimotor areas. The analysis of negation provides a steppingstone to understand how the human brain represents changes of meaning over time.

Reactivation strength during cued recall is modulated by graph distance within cognitive maps.

Declarative memory retrieval is thought to involve reinstatement of neuronal activity patterns elicited and encoded during a prior learning episode. Furthermore, it is suggested that two mechanisms operate during reinstatement, dependent on task demands: individual memory items can be reactivated simultaneously as a clustered occurrence or, alternatively, replayed sequentially as temporally separate instances. In the current study, participants learned associations between images that were embedded in a directed graph network and retained this information over a brief 8 min consolidation period. During a subsequent cued recall session, participants retrieved the learned information while undergoing magnetoencephalographic recording. Using a trained stimulus decoder, we found evidence for clustered reactivation of learned material. Reactivation strength of individual items during clustered reactivation decreased as a function of increasing graph distance, an ordering present solely for successful retrieval but not for retrieval failure. In line with previous research, we found evidence that sequential replay was dependent on retrieval performance and was most evident in low performers. The results provide evidence for distinct performance-dependent retrieval mechanisms, with graded clustered reactivation emerging as a plausible mechanism to search within abstract cognitive maps.

Neural representations of perspectival shapes and attentional effects: Evidence from fMRI and MEG.

Does the human brain represent perspectival shapes, i.e., viewpoint-dependent object shapes, especially in relatively higher-level visual areas such as the lateral occipital cortex? What is the temporal profile of the appearance and disappearance of neural representations of perspectival shapes? And how does attention influence these neural representations? To answer these questions, we employed functional magnetic resonance imaging (fMRI), magnetoencephalography (MEG), and multivariate decoding techniques to investigate spatiotemporal neural representations of perspectival shapes. Participants viewed rotated objects along with the corresponding objective shapes and perspectival shapes (i.e., rotated round, round, and oval) while we measured their brain activities. Our results revealed that shape classifiers trained on the basic shapes (i.e., round and oval) consistently identified neural representations in the lateral occipital cortex corresponding to the perspectival shapes of the viewed objects regardless of attentional manipulations. Additionally, this classification tendency toward the perspectival shapes emerged approximately 200 ms after stimulus presentation. Moreover, attention influenced the spatial dimension as the regions showing the perspectival shape classification tendency propagated from the occipital lobe to the temporal lobe. As for the temporal dimension, attention led to a more robust and enduring classification tendency towards perspectival shapes. In summary, our study outlines a spatiotemporal neural profile for perspectival shapes that suggests a greater degree of perspectival representation than is often acknowledged.

Phase-dependent word perception emerges from region-specific sensitivity to the statistics of language.

Neural oscillations reflect fluctuations in excitability, which biases the percept of ambiguous sensory input. Why this bias occurs is still not fully understood. We hypothesized that neural populations representing likely events are more sensitive, and thereby become active on earlier oscillatory phases, when the ensemble itself is less excitable. Perception of ambiguous input presented during less-excitable phases should therefore be biased toward frequent or predictable stimuli that have lower activation thresholds. Here, we show such a frequency bias in spoken word recognition using psychophysics, magnetoencephalography (MEG), and computational modelling. With MEG, we found a double dissociation, where the phase of oscillations in the superior temporal gyrus and medial temporal gyrus biased word-identification behavior based on phoneme and lexical frequencies, respectively. This finding was reproduced in a computational model. These results demonstrate that oscillations provide a temporal ordering of neural activity based on the sensitivity of separable neural populations.

Adults with cerebral palsy exhibit uncharacteristic cortical oscillations during an adaptive sensorimotor control task.

Prior research has shown that the sensorimotor cortical oscillations are uncharacteristic in persons with cerebral palsy (CP); however, it is unknown if these altered cortical oscillations have an impact on adaptive sensorimotor control. This investigation evaluated the cortical dynamics when the motor action needs to be changed "on-the-fly". Adults with CP and neurotypical controls completed a sensorimotor task that required either proactive or reactive control while undergoing magnetoencephalography (MEG). When compared with the controls, the adults with CP had a weaker beta (18-24 Hz) event-related desynchronization (ERD), post-movement beta rebound (PMBR, 16-20 Hz) and theta (4-6 Hz) event-related synchronization (ERS) in the sensorimotor cortices. In agreement with normative work, the controls exhibited differences in the strength of the sensorimotor gamma (66-84 Hz) ERS during proactive compared to reactive trials, but similar condition-wise changes were not seen in adults with CP. Lastly, the adults with CP who had a stronger theta ERS tended to have better hand dexterity, as indicated by the Box and Blocks Test and Purdue Pegboard Test. These results may suggest that alterations in the theta and gamma cortical oscillations play a role in the altered hand dexterity and uncharacteristic adaptive sensorimotor control noted in adults with CP.

Finding structure during incremental speech comprehension.

A core aspect of human speech comprehension is the ability to incrementally integrate consecutive words into a structured and coherent interpretation, aligning with the speaker's intended meaning. This rapid process is subject to multidimensional probabilistic constraints, including both linguistic knowledge and non-linguistic information within specific contexts, and it is their interpretative coherence that drives successful comprehension. To study the neural substrates of this process, we extract word-by-word measures of sentential structure from BERT, a deep language model, which effectively approximates the coherent outcomes of the dynamic interplay among various types of constraints. Using representational similarity analysis, we tested BERT parse depths and relevant corpus-based measures against the spatiotemporally resolved brain activity recorded by electro-/magnetoencephalography when participants were listening to the same sentences. Our results provide a detailed picture of the neurobiological processes involved in the incremental construction of structured interpretations. These findings show when and where coherent interpretations emerge through the evaluation and integration of multifaceted constraints in the brain, which engages bilateral brain regions extending beyond the classical fronto-temporal language system. Furthermore, this study provides empirical evidence supporting the use of artificial neural networks as computational models for revealing the neural dynamics underpinning complex cognitive processes in the brain.