Biology subjects

O'Neill, G. C.

Publications and source records attributed to O'Neill, G. C..

13 recordsLinked to original sources

bioRxiv2026

Measurement Equivalence of On-Scalp OPM-MEG and Cryogenic MEG for Auditory and Somatosensory Cortical Mapping Across Development

Wearable optically pumped magnetometer magnetoencephalography (OPM-MEG) reduces sensor-to-cortex distance compared with conventional cryogenic SQUID-MEG, but whether the two technologies yield equivalent neurophysiological conclusions remains unclear. We recorded auditory and somatosensory evoked fields in 18 participants (10-45 years) using a 128-sensor FieldLine HEDscan OPM-MEG system and a 275-channel CTF SQUID-MEG system within the same individuals. Equivalent current dipole source models were estimated using identical preprocessing and modeling procedures and compared using paired permutation testing. Both systems localized canonical auditory and somatosensory cortical generators with matched peak latencies and modest cross-system spatial differences. Auditory sources showed a consistent medial bias in SQUID-MEG localization, whereas somatosensory sources exhibited a small systematic offset ([~]4 mm), indicating stable coordinate differences rather than localization error. Dipole moments were larger for SQUID-MEG and goodness-of-fit higher for OPM-MEG; however, the increased moment was explained by a medial localization bias, demonstrating inverse-model effects rather than physiological disagreement. Auditory dipole moment increased with age in both systems, whereas somatosensory responses showed no age-related change. Together, these observations indicate preserved developmental physiology across platforms. These findings demonstrate that OPM-MEG and SQUID-MEG recover the same cortical generators and support equivalent biological interpretations despite predictable geometry-dependent coordinate differences. OPM-MEG therefore represents a measurement-equivalent implementation of MEG suitable for sensory functional mapping.

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bioRxiv2025

The Cerebellum Implements an Oscillatory Forward Model for Accurate Motor Timing

Voluntary movements are composed of small sub-movements generated by pulsatile bursts of muscle activity at 4-10 Hz. These motor intermittencies synchronize with rhythmic brain activity and vary with movement velocity and sensory delays, suggesting they are a signature of a central oscillatory motor control mechanism. We hypothesized that these pulsatile movements arise from a cerebellar clocking mechanism-a neuronal timing process that flexibly adjusts its dynamics to maintain motor precision under temporal uncertainty. If so, cerebellar rhythms should modulate their influence on movement depending on cue predictability. To test this, we used optically pumped magnetoencephalography (OP-MEG), which enables high-quality, movement-tolerant recordings of the brain with dense cerebellar coverage. Six participants performed an auditory-paced finger flexion-extension task at approximately 1 Hz with either regular or irregular cue timing to vary predictability. All participants exhibited clear 4-10 Hz intermittencies in their kinematics, synchronized to neural activity in the cerebellum and the posterior parietal cortex. Our connectivity analysis revealed for the first time, that cerebellar activity at this frequency, predominantly reflects sensory feedback, but during regular, predictable cueing, the cerebellum shifts to exert a greater feedforward influence on movement. Moreover, cerebellar oscillations were most persistently phase-aligned with motor intermittent rhythms during accurately timed actions, an effect that was absent under irregular cueing. These findings support the idea that the cerebellum implements an oscillatory forward model for motor timing and provide novel evidence for its ability to adjusting its role in coordinating sensorimotor integration according to sensory predictability. Motor intermittencies may thus represent the output of a cerebellar timing process that underpins precise voluntary action.

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bioRxiv2025

Assessing the digit organisation of focal hand dystonia using 7T functional MRI

IntroductionFocal hand dystonia (FHD) is typically treated with Botulinum Toxin (BTX/BoNT-A/Botox/ Onabotulinum Toxin Type A) injected into digit and wrist muscles to provide temporary symptomatic relief from muscle spasm. We use 7T functional MRI (fMRI) to study 1) differences in somatosensory and motor cortical digit maps between FHD patients and age and sex-matched healthy volunteers (HV), 2) changes in cortical digit maps of FHD patients after BTX treatment. MethodsFour FHD patients underwent behavioural measures and 7T fMRI at two timepoints: [~]30 days after BTX treatment at peak efficacy (Post-BTX), immediately prior to their next injection [~]100 days after treatment when therapeutic effects had declined (Pre-BTX). HVs were scanned at a single time point. Behavioural measures included temporal discrimination (TDT), amplitude thresholding (AMP) and spatial acuity grating orientation tasks. A somatosensory travelling wave (TW) digit-mapping fMRI task was performed on dominant/affected and non-dominant/un-affected hands, and a motor TW digit-mapping task on the dominant/affected hand. Fourier analysis derived digit maps which were compared to a probabilistic digit atlas, and population receptive field (pRF) mapping performed. Structural and resting state fMRI data were acquired. ResultsSpatial acuity was lowered in the dominant/affected hand in FHD compared to HVs, while TDT and AMP measures showed no significant differences. Somatosensory and motor TW cortical digit maps in FHD and HV showed clear digit ordering. Somatosensory and motor cortical digit maps were more disordered in the dominant/affected hand than the non-dominant hand for FHD Post and Pre-BTX compared to HVs (DICE coefficient/Figure of Merit). Compared to the atlas, HV maps were in-line for both hands, while in FHD central tendency (CT) was lower in the dominant/affected hand than non-dominant hand. pRF sizes were larger in the FHD Pre-BTX group compared to HV and Post-BTX for the dominant hand. ConclusionBehaviourally, FHD patients had lower spatial acuity than HVs. FHD digit maps had typical D1-D5 ordering, but DICE coefficients identified a disordered dominant hand in FHD patients compared to HVs at both timepoints. The FHD Pre-BTX group had larger pRF sizes than Post-BTX and HVs, suggesting BTX treatment coincides with more localised touch perception.

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bioRxiv2025

Wearable MEG data recorded during human stepping

Non-invasive spatiotemporal imaging of brain activity during large-scale, whole body movement is a significant methodological challenge for the field of movement neuroscience. Here, we present a dataset recorded using a new imaging modality - optically-pumped magnetoencephalography (OP-MEG) - to record brain activity during human stepping. Participants (n=3) performed a visually guided stepping task requiring precise foot placement while dual-axis and triaxial OP-MEG and leg muscle activity (electromyography, EMG) were recorded. The dataset also includes a structural MRI for each participant and foot kinematics. We validate the fidelity of the OPM data by showing movement-related beta band desynchronization source localised to the primary motor cortex. This multimodal dataset offers a resource for methodological development and testing for OPM data (e.g., movement-related interference rejection), within-subject analyses, and exploratory analyses to generate hypotheses for further work on the neural control of human stepping.

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bioRxiv2024

Volume conductor models for magnetospinography

The recent development of small, wearable, magnetic field sensors allow for the investigation of biomagnetic fields with a flexibility previously unavailable. We carry out forward computations to describe how current flow in the spinal cord and thorax gives rise to measurable magnetic fields outside the torso. We compare various open-access volume conductor models, in order to select the most parsimonious and accurate descriptor of the magnetic fields due to source current in the spinal cord. We find that fields produced due to current flow along the superior-inferior axis of the cord are relatively insensitive to the choice of volume conductor model. However, fields produced by current flow in predominantly left-right or anterior-posterior direction are significantly attenuated by the presence of bone in the forward model. Furthermore, volume conductors with bone demonstrate larger differences in field topographies for nearby sources compared to bone-free models. These findings suggest that precise modelling of spinal cord location and surrounding vertebrae will be important a-priori knowledge going forward.

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bioRxiv2024

Non-invasive evidence for rhythmic interactions between the human brain, spinal cord, and muscle

Voluntary human movement relies on interactions between the spinal cord, brain, and sensory afferents. The integrative function of the spinal cord has proven particularly difficult to study directly and non-invasively in humans due to challenges in measuring spinal cord activity. Investigations of sensorimotor integration often rely on cortico-muscular coupling, which can capture interactions between the brain and muscle, but cannot reveal how the spinal cord mediates this communication. Here, we introduce a system for direct, non-invasive imaging of concurrent brain and cervical spinal cord activity in humans using optically-pumped magnetometers (OPMs). We used this system to study endogenous interactions between the brain, spinal cord, and muscle involved in sensorimotor control during simple maintained contraction. Participants (n=3) performed a hand contraction with real-time visual feedback while we recorded brain and spinal cord activity using OPMs and muscle activity using EMG. We first identify the part of the spinal cord exhibiting a peak in estimated current flow in the cervical region during contraction. We then demonstrate that rhythmic activity in the spinal cord exhibits significant coupling with both brain and muscle activity in the 5-35 Hz frequency range. These findings evidence the possibility of concurrent spatio-temporal imaging along the entire neuro-axis.

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bioRxiv2023

Combining video telemetry and wearable MEG for naturalistic imaging

Neuroimaging studies have typically relied on rigorously controlled experimental paradigms to probe cognition, in which movement is restricted, primitive, an afterthought or merely used to indicate a subjects choice. Whilst powerful, these paradigms do not often resemble how we behave in everyday life, so a new generation of ecologically valid experiments are being developed. Magnetoencephalography (MEG) measures neural activity by sensing extracranial magnetic fields. It has recently been transformed from a large, static imaging modality to a wearable method where participants can move freely. This makes wearable MEG systems a prime candidate for naturalistic experiments going forward. However, these experiments will also require novel methods to capture and integrate information about complex behaviour executed during neuroimaging, and it is not yet clear how this could be achieved. Here we use video recordings of multi-limb dance moves, processed with open-source machine learning methods, to automatically identify analysis time windows of interest in concurrent wearable MEG data. In a first step, we compare a traditional, block-designed analysis of limb movements, where the times of interest are based on stimulus presentation, to an analysis pipeline based on hidden Markov model states derived from the video telemetry. Next, we show that it is possible to identify discrete modes of neuronal activity related to specific limbs and body posture by processing the participants choreographed movement in a dancing paradigm. This demonstrates the potential of combing video telemetry with mobile neuroimaging for future studies of complex and naturalistic behaviours.

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bioRxiv2023

Is high-frequency activity evidence of an anterior temporal lobe network or micro-saccades?

There is renewed interest in electrical activity that extends beyond the typical electrophysiological 100 Hz bandwidth. This activity, often in the anterior temporal lobe, has been attributed to processes ranging from memory consolidation to epileptiform activity. Here, using an open-access resting state magnetoencephalography (MEG) dataset (n = 89), and a second task-based MEG dataset, we could reliably localise high-frequency power to the temporal lobes across multiple bands up to 300-400 Hz. A functional connectivity analysis of this activity revealed a robust resting state bilateral network between the temporal lobes. However, we also found robust coherence in the 100-200 and 200-300 Hz bands between source reconstructed MEG data and the electrooculography (EOG) localised to within the temporal poles. Additional denoising schemes applied to the data could reduce power localisation to the temporal poles but the topography of the functional network did not drastically alter. Whilst it is clear that this network is biological and robust to established denoising methods, we cannot definitively rule yet on whether this is of neural or myogenic origin.

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bioRxiv2021

Spherical harmonic based noise rejection and neuronal sampling with multi-axis OPMs

In this study we explore the interference rejection and spatial sampling properties of multi-axis Optically Pumped Magnetometer (OPM) data. We use both vector spherical harmonics and eigenspectra to quantify how well an array can separate neuronal signal from environmental interference while adequately sampling the entire cortex. We found that triaxial OPMs have superb noise rejection properties allowing for very high orders of interference (L=6) to be accounted for while minimally affecting the neural space (2dB attenuation for a 60-sensor triaxial system). To adequately model the signals arising from the cortex, we show that at least 11th order (143 spatial degrees of freedom) irregular solid harmonics or 95 eigenvectors of the lead field are needed to model the neural space for OPM data (regardless of number of axes measured). This can be adequately sampled with 75-100 equidistant triaxial sensors (225-300 channels) or 200 equidistant radial channels. In other words, ordering the same number of channels in triaxial (rather than purely radial) configuration gives significant advantages not only in terms of external noise rejection but also minimizes cost, weight and cross-talk.

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bioRxiv2021

Using OPMs to measure neural activity in standing, mobile participants

Optically pumped magnetometer-based magnetoencephalography (OP-MEG) can be used to measure neuromagnetic fields while participants move in a magnetically shielded room. Head movements in previous OP-MEG studies have been up to 20 cm translation and [~]30{degrees} rotation in a sitting position. While this represents a step-change over stationary MEG systems, naturalistic head movement is likely to exceed these limits, particularly when participants are standing up. In this proof-of-concept study, we sought to push the movement limits of OP-MEG even further. Using a 90 channel (45-sensor) whole-head OP-MEG system and concurrent motion capture, we recorded auditory evoked fields while participants were: (i) sitting still, (ii) standing up and still, and (iii) standing up and making large natural head movements continuously throughout the recording - maximum translation 120 cm, maximum rotation 198{degrees}. Following pre-processing, movement artefacts were substantially reduced but not eliminated. However, upon utilisation of a beamformer, the M100 event-related field localised to primary auditory regions. Furthermore, the event-related fields from auditory cortex were remarkably consistent across the three conditions. These results suggest that a wide range of movement is possible with current OP-MEG systems. This in turn underscores the exciting potential of OP-MEG for recording neural activity during naturalistic paradigms that involve movement (e.g. navigation), and for scanning populations who are difficult to study with stationary MEG (e.g. young children).

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bioRxiv2021

Magnetic Field Mapping and Correction for Moving OP-MEG

BackgroundOptically pumped magnetometers (OPMs) have made moving, wearable magnetoencephalography (MEG) possible. The OPMs typically used for MEG require a low background magnetic field to operate, which is achieved using both passive and active magnetic shielding. However, the background magnetic field is never truly zero Tesla, and so the field at each of the OPMs changes as the participant moves. This leads to position and orientation dependent changes in the measurements, which manifest as low frequency artefacts in MEG data. ObjectiveWe modelled the spatial variation in the magnetic field and used the model to predict the movement artefact found in a dataset. MethodsWe demonstrate a method for modelling this field with a triaxial magnetometer, then showed that we can use the same technique to predict the movement artefact in a real OPM-based MEG (OP-MEG) dataset. ResultsUsing an 86-channel OP-MEG system, we found that this modelling method maximally reduced the power spectral density of the data by 26.2 {+/-} 0.6 dB at 0 Hz, when applied over 5 s non-overlapping windows. ConclusionThe magnetic field inside our state-of-the art magnetically shielded room can be well described by low-order spherical harmonic functions. We achieved a large reduction in movement noise when we applied this model to OP-MEG data. SignificanceReal-time implementation of this method could reduce passive shielding requirements for OP-MEG recording and allow the measurement of low-frequency brain activity during natural participant movement.

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bioRxiv2020

Modelling optically pumped magnetometerinterference as a mean (magnetic) field

Here we propose that much of the magnetic interference observed when using optically pumped magnetometers can be modeled spatially as a mean (magnetic) field. We show that this approximation reduces sensor level variability and substantially improves statistical power. This model does not require knowledge of the underlying neuroanatomy nor the sensor positions. It only needs information about the sensor orientation. Due to the models low rank there is little risk of removing substantial neural signal. However, we provide a framework to assess this risk for any sensor number, design or subject neuroanatomy. We find that the risk of unintentionally removing neural signal is reduced when multi-axis recordings are performed. We validated the method using a binaural auditory evoked response paradigm and demonstrated that the mean field correction increases reconstructed SNR in relevant brain regions in both the spatial and temporal domain. Considering the models simplicity and efficacy, we suggest that this mean field correction can be a powerful preprocessing step for arrays of optically pumped magnetometers.

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bioRxiv2018

Imaging human cortical responses to intraneural microstimulation using magnetoencephalography

The sensation of touch in the glabrous skin of the human hand is conveyed by thousands of fast-conducting mechanoreceptive afferents, which can be categorised into four distinct types. The spiking properties of these afferents in the periphery in response to varied tactile stimuli are well-characterised, but relatively little is known about the spatiotemporal properties of the neural representations of these different receptor types in the human cortex. Here, we use the novel methodological combination of single-unit intraneural microstimulation (INMS) with magnetoencephalography (MEG) to localise cortical representations of individual touch afferents in humans, by measuring the extracranial magnetic fields from neural currents. We found that by assessing the modulation of the beta (13-30 Hz) rhythm during single-unit INMS, significant changes in oscillatory amplitude occur in the contralateral primary somatosensory cortex within and across a group of fast adapting type I mechanoreceptive 20 afferents, which corresponded well to the induced response from matched vibrotactile stimulation. Combining the spatiotemporal specificity of MEG with the selective single-unit stimulation of INMS enables the interrogation of the central representations of different aspects of tactile afferent signalling within the human cortices. The fundamental finding that single-unit INMS ERD responses are robust and consistent with natural somatosensory stimuli will permit us to more dynamically probe the central nervous system responses in humans, to address questions about the processing of touch from the different classes of mechanoreceptive afferents and the effects of varying the stimulus frequency and patterning.

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